Feature

TOPLINE:

After the US Preventive Services Task Force (USPSTF) in May 2021 lowered from 50 to 45 the recommended age to begin colorectal cancer (CRC) screening for average-risk adults, there was a threefold increase in screening rates among individuals aged 45-49, but disparities by socioeconomic status and locality occurred.

METHODOLOGY:

• Researchers compared absolute and relative changes in screening uptake among average-risk adults 45-49 years between a 20-month period before and a 20-month period after the USPSTF recommendation was issued (May 1, 2018, to December 31, 2019, and May 1, 2021, to December 31, 2022). Data was evaluated bimonthly.
• They analyzed claims data from more than 10.2 million people with private Blue Cross Blue Shield (BCBS) coverage, with about three million eligible for screening during each bimonthly period, both pre- and post-recommendation.
• They used interrupted time-series analysis and autoregressive integrated moving average models to gauge changes in screening rates.

TAKEAWAY:

• Mean CRC screening uptake in average-risk adults 45-49 years increased from 0.50% in the pre-recommendation period to 1.51% post-recommendation, reflecting a significant absolute change of 1.01 percentage points but no significant relative change.
• Adults 45-49 years living in areas with the highest socioeconomic status (SES) had the largest absolute change in screening uptake compared with peers in the lowest SES areas (1.25 vs 0.75 percentage points). Relative changes were not significant.
• The absolute change in screening uptake was higher among individuals in metropolitan areas than individuals in nonmetropolitan areas (1.06 vs 0.73 percentage points). Again, relative changes were not significant.
• The screening uptake rate increased the fastest among those living in the highest SES and metropolitan areas (0.24 and 0.20 percentage points every 2 months, respectively).
• By December 2022 (the end of the post-recommendation period), CRC screening uptake among adults 45-49 years were on par with those seen in adults 50-75 years (2.37% vs 2.4%). Nonetheless, only 11.5% of average-risk adults aged 45-49 years received CRC screening during the post-recommendation period.

IN PRACTICE:

“The threefold increase in screening uptake among average-risk individuals aged 45-49 years reflects an accomplishment, yet evidence of widening disparities based on SDI [Social Deprivation Index] and locality indicate that population subgroups may not be benefiting equally from this change in CRC screening recommendation. Furthermore, given that only 11.5% of average-risk individuals aged 45-49 years during the post-recommendation period received CRC screening before the age of 50 years, targeted initiatives to improve screening in this age group are warranted to reach the national goal of screening 80% of the population in every community,” the researchers wrote.

SOURCE:

The study, with first author Sunny Siddique, MPH, with Yale School of Public Health, New Haven, Connecticut, was published online in JAMA Network Open. 

LIMITATIONS:

Data on race and ethnicity were incomplete, which may have impacted the analysis of disparities. The study cohort may not be fully representative of the general US population because BCBS beneficiaries tend to be younger and more socioeconomically advantaged with employer-based insurance. Specific information on the type of coverage provided by each beneficiary’s insurance plan was not available.

DISCLOSURES:

The study was funded by the National Cancer Institute. The authors declared no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE:

After the US Preventive Services Task Force (USPSTF) in May 2021 lowered from 50 to 45 the recommended age to begin colorectal cancer (CRC) screening for average-risk adults, there was a threefold increase in screening rates among individuals aged 45-49, but disparities by socioeconomic status and locality occurred.

METHODOLOGY:

• Researchers compared absolute and relative changes in screening uptake among average-risk adults 45-49 years between a 20-month period before and a 20-month period after the USPSTF recommendation was issued (May 1, 2018, to December 31, 2019, and May 1, 2021, to December 31, 2022). Data was evaluated bimonthly.
• They analyzed claims data from more than 10.2 million people with private Blue Cross Blue Shield (BCBS) coverage, with about three million eligible for screening during each bimonthly period, both pre- and post-recommendation.
• They used interrupted time-series analysis and autoregressive integrated moving average models to gauge changes in screening rates.

TAKEAWAY:

• Mean CRC screening uptake in average-risk adults 45-49 years increased from 0.50% in the pre-recommendation period to 1.51% post-recommendation, reflecting a significant absolute change of 1.01 percentage points but no significant relative change.
• Adults 45-49 years living in areas with the highest socioeconomic status (SES) had the largest absolute change in screening uptake compared with peers in the lowest SES areas (1.25 vs 0.75 percentage points). Relative changes were not significant.
• The absolute change in screening uptake was higher among individuals in metropolitan areas than individuals in nonmetropolitan areas (1.06 vs 0.73 percentage points). Again, relative changes were not significant.
• The screening uptake rate increased the fastest among those living in the highest SES and metropolitan areas (0.24 and 0.20 percentage points every 2 months, respectively).
• By December 2022 (the end of the post-recommendation period), CRC screening uptake among adults 45-49 years were on par with those seen in adults 50-75 years (2.37% vs 2.4%). Nonetheless, only 11.5% of average-risk adults aged 45-49 years received CRC screening during the post-recommendation period.

IN PRACTICE:

“The threefold increase in screening uptake among average-risk individuals aged 45-49 years reflects an accomplishment, yet evidence of widening disparities based on SDI [Social Deprivation Index] and locality indicate that population subgroups may not be benefiting equally from this change in CRC screening recommendation. Furthermore, given that only 11.5% of average-risk individuals aged 45-49 years during the post-recommendation period received CRC screening before the age of 50 years, targeted initiatives to improve screening in this age group are warranted to reach the national goal of screening 80% of the population in every community,” the researchers wrote.

SOURCE:

The study, with first author Sunny Siddique, MPH, with Yale School of Public Health, New Haven, Connecticut, was published online in JAMA Network Open. 

LIMITATIONS:

Data on race and ethnicity were incomplete, which may have impacted the analysis of disparities. The study cohort may not be fully representative of the general US population because BCBS beneficiaries tend to be younger and more socioeconomically advantaged with employer-based insurance. Specific information on the type of coverage provided by each beneficiary’s insurance plan was not available.

DISCLOSURES:

The study was funded by the National Cancer Institute. The authors declared no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE:

After the US Preventive Services Task Force (USPSTF) in May 2021 lowered from 50 to 45 the recommended age to begin colorectal cancer (CRC) screening for average-risk adults, there was a threefold increase in screening rates among individuals aged 45-49, but disparities by socioeconomic status and locality occurred.

METHODOLOGY:

• Researchers compared absolute and relative changes in screening uptake among average-risk adults 45-49 years between a 20-month period before and a 20-month period after the USPSTF recommendation was issued (May 1, 2018, to December 31, 2019, and May 1, 2021, to December 31, 2022). Data was evaluated bimonthly.
• They analyzed claims data from more than 10.2 million people with private Blue Cross Blue Shield (BCBS) coverage, with about three million eligible for screening during each bimonthly period, both pre- and post-recommendation.
• They used interrupted time-series analysis and autoregressive integrated moving average models to gauge changes in screening rates.

TAKEAWAY:

• Mean CRC screening uptake in average-risk adults 45-49 years increased from 0.50% in the pre-recommendation period to 1.51% post-recommendation, reflecting a significant absolute change of 1.01 percentage points but no significant relative change.
• Adults 45-49 years living in areas with the highest socioeconomic status (SES) had the largest absolute change in screening uptake compared with peers in the lowest SES areas (1.25 vs 0.75 percentage points). Relative changes were not significant.
• The absolute change in screening uptake was higher among individuals in metropolitan areas than individuals in nonmetropolitan areas (1.06 vs 0.73 percentage points). Again, relative changes were not significant.
• The screening uptake rate increased the fastest among those living in the highest SES and metropolitan areas (0.24 and 0.20 percentage points every 2 months, respectively).
• By December 2022 (the end of the post-recommendation period), CRC screening uptake among adults 45-49 years were on par with those seen in adults 50-75 years (2.37% vs 2.4%). Nonetheless, only 11.5% of average-risk adults aged 45-49 years received CRC screening during the post-recommendation period.

IN PRACTICE:

“The threefold increase in screening uptake among average-risk individuals aged 45-49 years reflects an accomplishment, yet evidence of widening disparities based on SDI [Social Deprivation Index] and locality indicate that population subgroups may not be benefiting equally from this change in CRC screening recommendation. Furthermore, given that only 11.5% of average-risk individuals aged 45-49 years during the post-recommendation period received CRC screening before the age of 50 years, targeted initiatives to improve screening in this age group are warranted to reach the national goal of screening 80% of the population in every community,” the researchers wrote.

SOURCE:

The study, with first author Sunny Siddique, MPH, with Yale School of Public Health, New Haven, Connecticut, was published online in JAMA Network Open. 

LIMITATIONS:

Data on race and ethnicity were incomplete, which may have impacted the analysis of disparities. The study cohort may not be fully representative of the general US population because BCBS beneficiaries tend to be younger and more socioeconomically advantaged with employer-based insurance. Specific information on the type of coverage provided by each beneficiary’s insurance plan was not available.

DISCLOSURES:

The study was funded by the National Cancer Institute. The authors declared no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

Diet is increasingly seen as a modifiable risk factor in prostate cancer.

Recent studies have shown that ultralow-carbohydrate diets, weight loss diets, supplementation with omega-3 fatty acids, pro- and anti-inflammatory diets, fasting, and even tea drinking may affect prostate cancer risk or risk for progression.

In October, a cohort study involving about 900 men under active surveillance for early stage prostate cancers found that those who reported eating a diet that adhered closely to the US government’s recommendations as indicated by the Healthy Eating Index (HEI) saw a lower risk for progression at a median 6.5 months follow-up.

These findings follow results from an observational study, published in May, that followed about 2000 men with locally advanced prostate tumors. Men consuming a primarily plant-based diet (one closely adhering to the plant-based diet index) had less likelihood of progression over a median 6.5 years than those consuming diets low in plant-based foods.

“There is an increasing body of literature that says your diet matters,” said urologist Stephen J. Freedland, MD, of Cedars-Sinai Medical Center in Los Angeles, California, and director of its Center for Integrated Research in Cancer and Lifestyle. “At the same time, there are a lot of things that could explain these associations. People who can afford lots of plant-based foods tend to have higher socioeconomic status, for example.”

What’s needed, Freedland said, are more randomized trials to test the hypotheses emerging from the longitudinal cohort studies. “That’s where I’m going with my own research,” he said. “I’d like to look at a study like [one of these] and design a trial. Let’s say we get half of patients to eat according to the healthy eating index, while half eat whatever they want. Can dietary modification change which genes are turned on and off in a tumor, as a start?”

 

Oncologist and Nutritionist Collaborate on Multiple Studies

Nutritionist Pao-Hwa Lin, PhD, of Duke University in Durham, North Carolina, has been working for several years with Freedland on trials of nutrition interventions. A longtime researcher of chronic disease and diet, she first collaborated with Freedland on a study, published in 2019, that looked at whether insulin could be driven down with diet and exercise in men treated with androgen deprivation therapy.

Not only are high levels of insulin a known contributor to prostate cancer growth, Lin said, but “insulin resistance is a very common side effect of hormone therapy. And we saw that the low carb diet was very helpful for that.” The finding led Freedland and Lin to design further trials investigating carbohydrate restriction in people with prostate cancer.

Lin said randomized trials tend to be smaller and shorter in duration than the observational cohort studies because “interventions like these can be hard to maintain, and recruitment can be hard to sustain. A very well controlled and intensive nutrition intervention is not going to be super long.” Short trial durations also mean that prostate cancer progression can be difficult to capture. Risk for progression has to be measured using surrogate markers, such as the doubling time for prostate-specific antigen (PSA).

In 2020, Freedland and Lin published results from a pilot study of 57 men who had been treated with surgery or radiation for localized prostate cancer but had a PSA recurrence and were randomized to an ultralow-carbohydrate diet or no restrictions for 6 months. The investigators saw that PSA doubling times, an intermediate measure of tumor growth rate, were slower among those consuming the low-carb diet.

Currently they are wrapping up a trial that randomizes men who have been scheduled for radical prostatectomy to daily supplementation with walnuts, a natural source of polyphenols and omega-3 acids. This time, the aim is to determine whether gene expression in tumors changes in response to supplementation.

The researchers are also recruiting for a study in men being treated for metastatic prostate cancer. This study randomizes patients to a fasting-mimicking diet, which is a type of intermittent fasting, or no dietary restrictions for 6 months.

Developed by biologist Valter Longo, PhD, of the University of Southern California, Los Angeles, the fasting-mimicking diet has been shown to boost treatment effects in women with hormone receptor–positive breast cancer. In 2023, Longo and his colleagues published results from a small pilot study of the same diet in men with prostate cancer, reporting some positive metabolic findings.

Longo, who is consulting on Lin and Freedland’s trial, “has proven that the diet is helpful in treatment outcomes for breast cancer. So we connected and decided to test it and see if it’s helpful in prostate cancer as well.”

 

More Than One Approach Likely to Work

Though Lin and Freedland have focused most of their investigations on carbohydrate restriction, neither dismisses the potential for other dietary approaches to show benefit.

“There are two main schools of thought in terms of the relationship between diet and prostate cancer,” Lin said. “One is the insulin angle, and that’s what we hypothesized when we first tested the low-carb diet. The other is the inflammation angle.”

Studies have shown greater adherence to the HEI — a diet quality indicator that favors grains, fruits, dairy, vegetables, beans, and seafood — or the plant-based diet index to be associated with lower biomarkers of inflammation, she noted.

Insulin resistance, Lin explained, “is also highly related to inflammation.” (Several of the diets being investigated in prostate cancer were originally studied in diabetes.)

Moreover, weight loss caused by low-carb diets — or other healthy diets — can have a positive effect on insulin resistance independent of diet composition. “So it is a very complicated picture — and that doesn’t exclude other pathways that could also be contributing,” she said.

On the surface, a low-carb diet that is heavy in eggs, cheeses, and meats would seem to have little in common with the HEI or a plant-based diet. But Freedland noted that there are commonalities among the approaches being studied. “No one’s promoting eating a lot of simple sugars. No one’s saying eat a lot of processed foods. All of these diets emphasize whole, natural foods,” he said.

Lin hopes that she and Freedland will one day be able to test a diet that is both lower carb and anti-inflammatory in men with prostate cancer. “Why not combine the approaches, have all the good features together?” she asked.

But Freeland pointed out and explained why most clinicians don’t make dietary recommendations to their newly diagnosed patients.

“A new prostate cancer patient already gets easily an hour discussion of treatment options, of pros and cons. Patients often become overwhelmed. And then to extend it further to talk about diet, they’ll end up even more overwhelmed.” Moreover, he said, current evidence offers doctors few take-home messages to deliver besides avoiding sugar and processed foods.

Multiple dietary approaches are likely to prove helpful in prostate cancer, and when the evidence for them is better established, patients and their doctors will want to consider lifestyle factors in choosing one. The best diet will depend on a patient’s philosophy, tastes, and willingness to follow it, he concluded.

“At the end of the day I’m not rooting for one diet or another. I just want to get the answers.”

Lin disclosed no financial conflicts of interest. Freedland disclosed serving as a speaker for AstraZeneca, Astellas, and Pfizer and as a consultant for Astellas, AstraZeneca, Bayer, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi-Aventis, and Sumitomo.

A version of this article first appeared on Medscape.com.

Diet is increasingly seen as a modifiable risk factor in prostate cancer.

Recent studies have shown that ultralow-carbohydrate diets, weight loss diets, supplementation with omega-3 fatty acids, pro- and anti-inflammatory diets, fasting, and even tea drinking may affect prostate cancer risk or risk for progression.

In October, a cohort study involving about 900 men under active surveillance for early stage prostate cancers found that those who reported eating a diet that adhered closely to the US government’s recommendations as indicated by the Healthy Eating Index (HEI) saw a lower risk for progression at a median 6.5 months follow-up.

These findings follow results from an observational study, published in May, that followed about 2000 men with locally advanced prostate tumors. Men consuming a primarily plant-based diet (one closely adhering to the plant-based diet index) had less likelihood of progression over a median 6.5 years than those consuming diets low in plant-based foods.

“There is an increasing body of literature that says your diet matters,” said urologist Stephen J. Freedland, MD, of Cedars-Sinai Medical Center in Los Angeles, California, and director of its Center for Integrated Research in Cancer and Lifestyle. “At the same time, there are a lot of things that could explain these associations. People who can afford lots of plant-based foods tend to have higher socioeconomic status, for example.”

What’s needed, Freedland said, are more randomized trials to test the hypotheses emerging from the longitudinal cohort studies. “That’s where I’m going with my own research,” he said. “I’d like to look at a study like [one of these] and design a trial. Let’s say we get half of patients to eat according to the healthy eating index, while half eat whatever they want. Can dietary modification change which genes are turned on and off in a tumor, as a start?”

 

Oncologist and Nutritionist Collaborate on Multiple Studies

Nutritionist Pao-Hwa Lin, PhD, of Duke University in Durham, North Carolina, has been working for several years with Freedland on trials of nutrition interventions. A longtime researcher of chronic disease and diet, she first collaborated with Freedland on a study, published in 2019, that looked at whether insulin could be driven down with diet and exercise in men treated with androgen deprivation therapy.

Not only are high levels of insulin a known contributor to prostate cancer growth, Lin said, but “insulin resistance is a very common side effect of hormone therapy. And we saw that the low carb diet was very helpful for that.” The finding led Freedland and Lin to design further trials investigating carbohydrate restriction in people with prostate cancer.

Lin said randomized trials tend to be smaller and shorter in duration than the observational cohort studies because “interventions like these can be hard to maintain, and recruitment can be hard to sustain. A very well controlled and intensive nutrition intervention is not going to be super long.” Short trial durations also mean that prostate cancer progression can be difficult to capture. Risk for progression has to be measured using surrogate markers, such as the doubling time for prostate-specific antigen (PSA).

In 2020, Freedland and Lin published results from a pilot study of 57 men who had been treated with surgery or radiation for localized prostate cancer but had a PSA recurrence and were randomized to an ultralow-carbohydrate diet or no restrictions for 6 months. The investigators saw that PSA doubling times, an intermediate measure of tumor growth rate, were slower among those consuming the low-carb diet.

Currently they are wrapping up a trial that randomizes men who have been scheduled for radical prostatectomy to daily supplementation with walnuts, a natural source of polyphenols and omega-3 acids. This time, the aim is to determine whether gene expression in tumors changes in response to supplementation.

The researchers are also recruiting for a study in men being treated for metastatic prostate cancer. This study randomizes patients to a fasting-mimicking diet, which is a type of intermittent fasting, or no dietary restrictions for 6 months.

Developed by biologist Valter Longo, PhD, of the University of Southern California, Los Angeles, the fasting-mimicking diet has been shown to boost treatment effects in women with hormone receptor–positive breast cancer. In 2023, Longo and his colleagues published results from a small pilot study of the same diet in men with prostate cancer, reporting some positive metabolic findings.

Longo, who is consulting on Lin and Freedland’s trial, “has proven that the diet is helpful in treatment outcomes for breast cancer. So we connected and decided to test it and see if it’s helpful in prostate cancer as well.”

 

More Than One Approach Likely to Work

Though Lin and Freedland have focused most of their investigations on carbohydrate restriction, neither dismisses the potential for other dietary approaches to show benefit.

“There are two main schools of thought in terms of the relationship between diet and prostate cancer,” Lin said. “One is the insulin angle, and that’s what we hypothesized when we first tested the low-carb diet. The other is the inflammation angle.”

Studies have shown greater adherence to the HEI — a diet quality indicator that favors grains, fruits, dairy, vegetables, beans, and seafood — or the plant-based diet index to be associated with lower biomarkers of inflammation, she noted.

Insulin resistance, Lin explained, “is also highly related to inflammation.” (Several of the diets being investigated in prostate cancer were originally studied in diabetes.)

Moreover, weight loss caused by low-carb diets — or other healthy diets — can have a positive effect on insulin resistance independent of diet composition. “So it is a very complicated picture — and that doesn’t exclude other pathways that could also be contributing,” she said.

On the surface, a low-carb diet that is heavy in eggs, cheeses, and meats would seem to have little in common with the HEI or a plant-based diet. But Freedland noted that there are commonalities among the approaches being studied. “No one’s promoting eating a lot of simple sugars. No one’s saying eat a lot of processed foods. All of these diets emphasize whole, natural foods,” he said.

Lin hopes that she and Freedland will one day be able to test a diet that is both lower carb and anti-inflammatory in men with prostate cancer. “Why not combine the approaches, have all the good features together?” she asked.

But Freeland pointed out and explained why most clinicians don’t make dietary recommendations to their newly diagnosed patients.

“A new prostate cancer patient already gets easily an hour discussion of treatment options, of pros and cons. Patients often become overwhelmed. And then to extend it further to talk about diet, they’ll end up even more overwhelmed.” Moreover, he said, current evidence offers doctors few take-home messages to deliver besides avoiding sugar and processed foods.

Multiple dietary approaches are likely to prove helpful in prostate cancer, and when the evidence for them is better established, patients and their doctors will want to consider lifestyle factors in choosing one. The best diet will depend on a patient’s philosophy, tastes, and willingness to follow it, he concluded.

“At the end of the day I’m not rooting for one diet or another. I just want to get the answers.”

Lin disclosed no financial conflicts of interest. Freedland disclosed serving as a speaker for AstraZeneca, Astellas, and Pfizer and as a consultant for Astellas, AstraZeneca, Bayer, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi-Aventis, and Sumitomo.

A version of this article first appeared on Medscape.com.

Diet is increasingly seen as a modifiable risk factor in prostate cancer.

Recent studies have shown that ultralow-carbohydrate diets, weight loss diets, supplementation with omega-3 fatty acids, pro- and anti-inflammatory diets, fasting, and even tea drinking may affect prostate cancer risk or risk for progression.

In October, a cohort study involving about 900 men under active surveillance for early stage prostate cancers found that those who reported eating a diet that adhered closely to the US government’s recommendations as indicated by the Healthy Eating Index (HEI) saw a lower risk for progression at a median 6.5 months follow-up.

These findings follow results from an observational study, published in May, that followed about 2000 men with locally advanced prostate tumors. Men consuming a primarily plant-based diet (one closely adhering to the plant-based diet index) had less likelihood of progression over a median 6.5 years than those consuming diets low in plant-based foods.

“There is an increasing body of literature that says your diet matters,” said urologist Stephen J. Freedland, MD, of Cedars-Sinai Medical Center in Los Angeles, California, and director of its Center for Integrated Research in Cancer and Lifestyle. “At the same time, there are a lot of things that could explain these associations. People who can afford lots of plant-based foods tend to have higher socioeconomic status, for example.”

What’s needed, Freedland said, are more randomized trials to test the hypotheses emerging from the longitudinal cohort studies. “That’s where I’m going with my own research,” he said. “I’d like to look at a study like [one of these] and design a trial. Let’s say we get half of patients to eat according to the healthy eating index, while half eat whatever they want. Can dietary modification change which genes are turned on and off in a tumor, as a start?”

 

Oncologist and Nutritionist Collaborate on Multiple Studies

Nutritionist Pao-Hwa Lin, PhD, of Duke University in Durham, North Carolina, has been working for several years with Freedland on trials of nutrition interventions. A longtime researcher of chronic disease and diet, she first collaborated with Freedland on a study, published in 2019, that looked at whether insulin could be driven down with diet and exercise in men treated with androgen deprivation therapy.

Not only are high levels of insulin a known contributor to prostate cancer growth, Lin said, but “insulin resistance is a very common side effect of hormone therapy. And we saw that the low carb diet was very helpful for that.” The finding led Freedland and Lin to design further trials investigating carbohydrate restriction in people with prostate cancer.

Lin said randomized trials tend to be smaller and shorter in duration than the observational cohort studies because “interventions like these can be hard to maintain, and recruitment can be hard to sustain. A very well controlled and intensive nutrition intervention is not going to be super long.” Short trial durations also mean that prostate cancer progression can be difficult to capture. Risk for progression has to be measured using surrogate markers, such as the doubling time for prostate-specific antigen (PSA).

In 2020, Freedland and Lin published results from a pilot study of 57 men who had been treated with surgery or radiation for localized prostate cancer but had a PSA recurrence and were randomized to an ultralow-carbohydrate diet or no restrictions for 6 months. The investigators saw that PSA doubling times, an intermediate measure of tumor growth rate, were slower among those consuming the low-carb diet.

Currently they are wrapping up a trial that randomizes men who have been scheduled for radical prostatectomy to daily supplementation with walnuts, a natural source of polyphenols and omega-3 acids. This time, the aim is to determine whether gene expression in tumors changes in response to supplementation.

The researchers are also recruiting for a study in men being treated for metastatic prostate cancer. This study randomizes patients to a fasting-mimicking diet, which is a type of intermittent fasting, or no dietary restrictions for 6 months.

Developed by biologist Valter Longo, PhD, of the University of Southern California, Los Angeles, the fasting-mimicking diet has been shown to boost treatment effects in women with hormone receptor–positive breast cancer. In 2023, Longo and his colleagues published results from a small pilot study of the same diet in men with prostate cancer, reporting some positive metabolic findings.

Longo, who is consulting on Lin and Freedland’s trial, “has proven that the diet is helpful in treatment outcomes for breast cancer. So we connected and decided to test it and see if it’s helpful in prostate cancer as well.”

 

More Than One Approach Likely to Work

Though Lin and Freedland have focused most of their investigations on carbohydrate restriction, neither dismisses the potential for other dietary approaches to show benefit.

“There are two main schools of thought in terms of the relationship between diet and prostate cancer,” Lin said. “One is the insulin angle, and that’s what we hypothesized when we first tested the low-carb diet. The other is the inflammation angle.”

Studies have shown greater adherence to the HEI — a diet quality indicator that favors grains, fruits, dairy, vegetables, beans, and seafood — or the plant-based diet index to be associated with lower biomarkers of inflammation, she noted.

Insulin resistance, Lin explained, “is also highly related to inflammation.” (Several of the diets being investigated in prostate cancer were originally studied in diabetes.)

Moreover, weight loss caused by low-carb diets — or other healthy diets — can have a positive effect on insulin resistance independent of diet composition. “So it is a very complicated picture — and that doesn’t exclude other pathways that could also be contributing,” she said.

On the surface, a low-carb diet that is heavy in eggs, cheeses, and meats would seem to have little in common with the HEI or a plant-based diet. But Freedland noted that there are commonalities among the approaches being studied. “No one’s promoting eating a lot of simple sugars. No one’s saying eat a lot of processed foods. All of these diets emphasize whole, natural foods,” he said.

Lin hopes that she and Freedland will one day be able to test a diet that is both lower carb and anti-inflammatory in men with prostate cancer. “Why not combine the approaches, have all the good features together?” she asked.

But Freeland pointed out and explained why most clinicians don’t make dietary recommendations to their newly diagnosed patients.

“A new prostate cancer patient already gets easily an hour discussion of treatment options, of pros and cons. Patients often become overwhelmed. And then to extend it further to talk about diet, they’ll end up even more overwhelmed.” Moreover, he said, current evidence offers doctors few take-home messages to deliver besides avoiding sugar and processed foods.

Multiple dietary approaches are likely to prove helpful in prostate cancer, and when the evidence for them is better established, patients and their doctors will want to consider lifestyle factors in choosing one. The best diet will depend on a patient’s philosophy, tastes, and willingness to follow it, he concluded.

“At the end of the day I’m not rooting for one diet or another. I just want to get the answers.”

Lin disclosed no financial conflicts of interest. Freedland disclosed serving as a speaker for AstraZeneca, Astellas, and Pfizer and as a consultant for Astellas, AstraZeneca, Bayer, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi-Aventis, and Sumitomo.

A version of this article first appeared on Medscape.com.

Microplastics have been found in the lungs, liver, blood, and heart. Now, researchers report they have found the first evidence of the substances in human brains.

In a recent case series study that examined olfactory bulb tissue from deceased individuals, 8 of the 15 decedent brains showed the presence of microplastics, most commonly polypropylene, a plastic typically used in food packaging and water bottles.

Measuring less than 5 mm in size, microplastics are formed over time as plastic materials break down but don’t biodegrade. Exposure to these substances can come through food, air, and skin absorption.

While scientists are learning more about how these substances are absorbed by the body, questions remain about how much exposure is safe, what effect — if any — microplastics could have on brain function, and what clinicians should tell their patients.

 

What Are the Major Health Concerns?

The Plastic Health Council estimates that more than 500 million metric tons of plastic are produced worldwide each year. In addition, it reports that plastic products can contain more than 16,000 chemicals, about a quarter of which have been found to be hazardous to human health and the environment. Microplastics and nanoplastics can enter the body through the air, in food, or absorption through the skin.

A study published in March showed that patients with carotid plaques and the presence of microplastics and nanoplastics were at an increased risk for death or major cardiovascular events.

Other studies have shown a link between these substances and placental inflammation and preterm births, reduced male fertility, and endocrine disruption — as well as accelerated spread of cancer cells in the gut.

There is also evidence suggesting that microplastics may facilitate the development of antibiotic resistance in bacteria and could contribute to the rise in food allergies.

And now, Thais Mauad, MD, PhD, and colleagues have found the substances in the brain.

 

How Is the Brain Affected?

The investigators examined olfactory bulb tissues from 15 deceased Sao Paulo, Brazil, residents ranging in age from 33 to 100 years who underwent routine coroner autopsies. All but three of the participants were men.

Exclusion criteria included having undergone previous neurosurgical interventions. The tissues were analyzed using micro–Fourier transform infrared spectroscopy (µFTIR).

In addition, the researchers practiced a “plastic-free approach” in their analysis, which included using filters and covering glassware and samples with aluminum foil.

Study findings showed microplastics in 8 of the 15 participants — including in the centenarian. In total, there were 16 synthetic polymer particles and fibers detected, with up to four microplastics detected per olfactory bulb. Polypropylene was the most common polymer found (44%), followed by polyamide, nylon, and polyethylene vinyl acetate. These substances are commonly used in a wide range of products, including food packaging, textiles, kitchen utensils, medical devices, and adhesives.

The microplastic particles ranged in length from 5.5 to 26 microns (one millionth of a meter), with a width that ranged from 3 to 25 microns. The mean fiber length and width was 21 and 4 microns, respectively. For comparison, the diameter of one human hair averages about 70 microns, according to the US Food and Drug Administration (FDA).

“To our knowledge, this is the first study in which the presence of microplastics in the human brain was identified and characterized using µFTIR,” the researchers wrote.

 

How Do Microplastics Reach the Brain?

Although the possibility of microplastics crossing the blood-brain barrier has been questioned, senior investigator Mauad, associate professor in the Department of Pathology, the University of Sao Paulo in Brazil, noted that the olfactory pathway could offer an entry route through inhalation of the particles.

This means that “breathing within indoor environments could be a major source of plastic pollution in the brain,” she said in a press release.

“With much smaller nanoplastics entering the body with greater ease, the total level of plastic particles may be much higher. What is worrying is the capacity of such particles to be internalized by cells and alter how our bodies function,” she added.

Mauad said that although questions remain regarding the health implications of their findings, some animal studies have shown that the presence of microplastics in the brain is linked to neurotoxic effects, including oxidative stress.

In addition, exposure to particulate matter has been linked previously to such neurologic conditions as dementia and neurodegenerative conditions such as Parkinson’s disease “seem to have a connection with nasal abnormalities as initial symptoms,” the investigators noted.

While the olfactory pathway appears to be a likely route of exposure the researchers noted that other potential entry routes, including through blood circulation, may also be involved.

The research suggests that inhaling microplastics while indoors may be unavoidable, Mauad said, making it unlikely individuals can eliminate exposure to these substances.

“Everything that surrounds us is plastic. So we can’t really get rid of it,” she said.

 

Are Microplastics Regulated?

The most effective solution would be stricter regulations, Mauad said.

“The industry has chosen to sell many things in plastic, and I think this has to change. We need more policies to decrease plastic production — especially single-use plastic,” she said.

Federal, state, and local regulations for microplastics are “virtually nonexistent,” reported the Interstate Technology and Regulatory Council (ITRC), a state-led coalition that produces documents and trainings related to regulatory issues.

In 2021, the ITRC sent a survey to all US states asking about microplastics regulations. Of the 26 states that responded, only 4 said they had conducted sampling for microplastics. None of the responders indicated they had established any criteria or standards for microplastics, although eight states indicated they had plans to pursue them in the future.

Although federal regulations include the Microbead-Free Waters Act of 2015 and the Save Our Seas Act 2.0, the rules don’t directly pertain to microplastics.

There are also no regulations currently in place regarding microplastics or nanoplastics in food. A report issued in July by the FDA claimed that “the overall scientific evidence does not demonstrate that levels of microplastics or nanoplastics found in foods pose a risk to human health.”

International efforts to regulate microplastics are much further along. First created in 2022, the treaty would forge an international, legally binding agreement.

While it is a step in the right direction, the Plastic Health Council has cautioned about “the omission of measures in draft provisions that fully address the impact of plastic pollution on human health.” The treaty should reduce plastic production, eliminate single-use plastic items, and call for testing of all chemicals in plastics, the council argues.

The final round of negotiations for the UN Global Plastic Treaty is set for completion before the end of the year.

 

What Should Clinicians Know?

Much remains unknown about the potential health effects of microplastic exposure. So how can clinicians respond to questions from concerned patients?

“We don’t yet have enough evidence about the plastic particle itself, like those highlighted in the current study — and even more so when it comes to nanoplastics, which are a thousand times smaller,” said Phoebe Stapleton, PhD, associated professor in the Department of Pharmacology and Toxicology at the Ernest Mario School of Pharmacy at Rutgers University, Piscataway, New Jersey.

“But we do have a lot of evidence about the chemicals that are used to make plastics, and we’ve already seen regulation there from the EPA. That’s one conversation that clinicians could have with patients: about those chemicals,” she added.

Stapleton recommended clinicians stay current on the latest research and be ready to respond should a patient raise the issue. She also noted the importance of exercising caution when interpreting these new findings.

While the study is important — especially because it highlights inhalation as a viable route of entry — exposure through the olfactory area is still just a theory and hasn’t yet been fully proven.

In addition, Stapleton wonders whether there are tissues where these substances are not found. A discovery like that “would be really exciting because that means that that tissue has mechanisms protecting it, and maybe, we could learn more about how to keep microplastics out,” she said.

She would also like to see more studies on specific adverse health effects from microplastics in the body.

Mauad agreed.

“That’s the next set of questions: What are the toxicities or lack thereof in those tissues? That will give us more information as it pertains to human health. It doesn’t feel good to know they’re in our tissues, but we still don’t have a real understanding of what they’re doing when they’re there,” she said.

The current study was funded by the Alexander von Humboldt Foundation and by grants from the Brazilian Research Council and the Soa State Research Agency. It was also funded by the Plastic Soup Foundation — which, together with A Plastic Planet, forms the Plastic Health Council. The investigators and Stapleton reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Microplastics have been found in the lungs, liver, blood, and heart. Now, researchers report they have found the first evidence of the substances in human brains.

In a recent case series study that examined olfactory bulb tissue from deceased individuals, 8 of the 15 decedent brains showed the presence of microplastics, most commonly polypropylene, a plastic typically used in food packaging and water bottles.

Measuring less than 5 mm in size, microplastics are formed over time as plastic materials break down but don’t biodegrade. Exposure to these substances can come through food, air, and skin absorption.

While scientists are learning more about how these substances are absorbed by the body, questions remain about how much exposure is safe, what effect — if any — microplastics could have on brain function, and what clinicians should tell their patients.

 

What Are the Major Health Concerns?

The Plastic Health Council estimates that more than 500 million metric tons of plastic are produced worldwide each year. In addition, it reports that plastic products can contain more than 16,000 chemicals, about a quarter of which have been found to be hazardous to human health and the environment. Microplastics and nanoplastics can enter the body through the air, in food, or absorption through the skin.

A study published in March showed that patients with carotid plaques and the presence of microplastics and nanoplastics were at an increased risk for death or major cardiovascular events.

Other studies have shown a link between these substances and placental inflammation and preterm births, reduced male fertility, and endocrine disruption — as well as accelerated spread of cancer cells in the gut.

There is also evidence suggesting that microplastics may facilitate the development of antibiotic resistance in bacteria and could contribute to the rise in food allergies.

And now, Thais Mauad, MD, PhD, and colleagues have found the substances in the brain.

 

How Is the Brain Affected?

The investigators examined olfactory bulb tissues from 15 deceased Sao Paulo, Brazil, residents ranging in age from 33 to 100 years who underwent routine coroner autopsies. All but three of the participants were men.

Exclusion criteria included having undergone previous neurosurgical interventions. The tissues were analyzed using micro–Fourier transform infrared spectroscopy (µFTIR).

In addition, the researchers practiced a “plastic-free approach” in their analysis, which included using filters and covering glassware and samples with aluminum foil.

Study findings showed microplastics in 8 of the 15 participants — including in the centenarian. In total, there were 16 synthetic polymer particles and fibers detected, with up to four microplastics detected per olfactory bulb. Polypropylene was the most common polymer found (44%), followed by polyamide, nylon, and polyethylene vinyl acetate. These substances are commonly used in a wide range of products, including food packaging, textiles, kitchen utensils, medical devices, and adhesives.

The microplastic particles ranged in length from 5.5 to 26 microns (one millionth of a meter), with a width that ranged from 3 to 25 microns. The mean fiber length and width was 21 and 4 microns, respectively. For comparison, the diameter of one human hair averages about 70 microns, according to the US Food and Drug Administration (FDA).

“To our knowledge, this is the first study in which the presence of microplastics in the human brain was identified and characterized using µFTIR,” the researchers wrote.

 

How Do Microplastics Reach the Brain?

Although the possibility of microplastics crossing the blood-brain barrier has been questioned, senior investigator Mauad, associate professor in the Department of Pathology, the University of Sao Paulo in Brazil, noted that the olfactory pathway could offer an entry route through inhalation of the particles.

This means that “breathing within indoor environments could be a major source of plastic pollution in the brain,” she said in a press release.

“With much smaller nanoplastics entering the body with greater ease, the total level of plastic particles may be much higher. What is worrying is the capacity of such particles to be internalized by cells and alter how our bodies function,” she added.

Mauad said that although questions remain regarding the health implications of their findings, some animal studies have shown that the presence of microplastics in the brain is linked to neurotoxic effects, including oxidative stress.

In addition, exposure to particulate matter has been linked previously to such neurologic conditions as dementia and neurodegenerative conditions such as Parkinson’s disease “seem to have a connection with nasal abnormalities as initial symptoms,” the investigators noted.

While the olfactory pathway appears to be a likely route of exposure the researchers noted that other potential entry routes, including through blood circulation, may also be involved.

The research suggests that inhaling microplastics while indoors may be unavoidable, Mauad said, making it unlikely individuals can eliminate exposure to these substances.

“Everything that surrounds us is plastic. So we can’t really get rid of it,” she said.

 

Are Microplastics Regulated?

The most effective solution would be stricter regulations, Mauad said.

“The industry has chosen to sell many things in plastic, and I think this has to change. We need more policies to decrease plastic production — especially single-use plastic,” she said.

Federal, state, and local regulations for microplastics are “virtually nonexistent,” reported the Interstate Technology and Regulatory Council (ITRC), a state-led coalition that produces documents and trainings related to regulatory issues.

In 2021, the ITRC sent a survey to all US states asking about microplastics regulations. Of the 26 states that responded, only 4 said they had conducted sampling for microplastics. None of the responders indicated they had established any criteria or standards for microplastics, although eight states indicated they had plans to pursue them in the future.

Although federal regulations include the Microbead-Free Waters Act of 2015 and the Save Our Seas Act 2.0, the rules don’t directly pertain to microplastics.

There are also no regulations currently in place regarding microplastics or nanoplastics in food. A report issued in July by the FDA claimed that “the overall scientific evidence does not demonstrate that levels of microplastics or nanoplastics found in foods pose a risk to human health.”

International efforts to regulate microplastics are much further along. First created in 2022, the treaty would forge an international, legally binding agreement.

While it is a step in the right direction, the Plastic Health Council has cautioned about “the omission of measures in draft provisions that fully address the impact of plastic pollution on human health.” The treaty should reduce plastic production, eliminate single-use plastic items, and call for testing of all chemicals in plastics, the council argues.

The final round of negotiations for the UN Global Plastic Treaty is set for completion before the end of the year.

 

What Should Clinicians Know?

Much remains unknown about the potential health effects of microplastic exposure. So how can clinicians respond to questions from concerned patients?

“We don’t yet have enough evidence about the plastic particle itself, like those highlighted in the current study — and even more so when it comes to nanoplastics, which are a thousand times smaller,” said Phoebe Stapleton, PhD, associated professor in the Department of Pharmacology and Toxicology at the Ernest Mario School of Pharmacy at Rutgers University, Piscataway, New Jersey.

“But we do have a lot of evidence about the chemicals that are used to make plastics, and we’ve already seen regulation there from the EPA. That’s one conversation that clinicians could have with patients: about those chemicals,” she added.

Stapleton recommended clinicians stay current on the latest research and be ready to respond should a patient raise the issue. She also noted the importance of exercising caution when interpreting these new findings.

While the study is important — especially because it highlights inhalation as a viable route of entry — exposure through the olfactory area is still just a theory and hasn’t yet been fully proven.

In addition, Stapleton wonders whether there are tissues where these substances are not found. A discovery like that “would be really exciting because that means that that tissue has mechanisms protecting it, and maybe, we could learn more about how to keep microplastics out,” she said.

She would also like to see more studies on specific adverse health effects from microplastics in the body.

Mauad agreed.

“That’s the next set of questions: What are the toxicities or lack thereof in those tissues? That will give us more information as it pertains to human health. It doesn’t feel good to know they’re in our tissues, but we still don’t have a real understanding of what they’re doing when they’re there,” she said.

The current study was funded by the Alexander von Humboldt Foundation and by grants from the Brazilian Research Council and the Soa State Research Agency. It was also funded by the Plastic Soup Foundation — which, together with A Plastic Planet, forms the Plastic Health Council. The investigators and Stapleton reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Microplastics have been found in the lungs, liver, blood, and heart. Now, researchers report they have found the first evidence of the substances in human brains.

In a recent case series study that examined olfactory bulb tissue from deceased individuals, 8 of the 15 decedent brains showed the presence of microplastics, most commonly polypropylene, a plastic typically used in food packaging and water bottles.

Measuring less than 5 mm in size, microplastics are formed over time as plastic materials break down but don’t biodegrade. Exposure to these substances can come through food, air, and skin absorption.

While scientists are learning more about how these substances are absorbed by the body, questions remain about how much exposure is safe, what effect — if any — microplastics could have on brain function, and what clinicians should tell their patients.

 

What Are the Major Health Concerns?

The Plastic Health Council estimates that more than 500 million metric tons of plastic are produced worldwide each year. In addition, it reports that plastic products can contain more than 16,000 chemicals, about a quarter of which have been found to be hazardous to human health and the environment. Microplastics and nanoplastics can enter the body through the air, in food, or absorption through the skin.

A study published in March showed that patients with carotid plaques and the presence of microplastics and nanoplastics were at an increased risk for death or major cardiovascular events.

Other studies have shown a link between these substances and placental inflammation and preterm births, reduced male fertility, and endocrine disruption — as well as accelerated spread of cancer cells in the gut.

There is also evidence suggesting that microplastics may facilitate the development of antibiotic resistance in bacteria and could contribute to the rise in food allergies.

And now, Thais Mauad, MD, PhD, and colleagues have found the substances in the brain.

 

How Is the Brain Affected?

The investigators examined olfactory bulb tissues from 15 deceased Sao Paulo, Brazil, residents ranging in age from 33 to 100 years who underwent routine coroner autopsies. All but three of the participants were men.

Exclusion criteria included having undergone previous neurosurgical interventions. The tissues were analyzed using micro–Fourier transform infrared spectroscopy (µFTIR).

In addition, the researchers practiced a “plastic-free approach” in their analysis, which included using filters and covering glassware and samples with aluminum foil.

Study findings showed microplastics in 8 of the 15 participants — including in the centenarian. In total, there were 16 synthetic polymer particles and fibers detected, with up to four microplastics detected per olfactory bulb. Polypropylene was the most common polymer found (44%), followed by polyamide, nylon, and polyethylene vinyl acetate. These substances are commonly used in a wide range of products, including food packaging, textiles, kitchen utensils, medical devices, and adhesives.

The microplastic particles ranged in length from 5.5 to 26 microns (one millionth of a meter), with a width that ranged from 3 to 25 microns. The mean fiber length and width was 21 and 4 microns, respectively. For comparison, the diameter of one human hair averages about 70 microns, according to the US Food and Drug Administration (FDA).

“To our knowledge, this is the first study in which the presence of microplastics in the human brain was identified and characterized using µFTIR,” the researchers wrote.

 

How Do Microplastics Reach the Brain?

Although the possibility of microplastics crossing the blood-brain barrier has been questioned, senior investigator Mauad, associate professor in the Department of Pathology, the University of Sao Paulo in Brazil, noted that the olfactory pathway could offer an entry route through inhalation of the particles.

This means that “breathing within indoor environments could be a major source of plastic pollution in the brain,” she said in a press release.

“With much smaller nanoplastics entering the body with greater ease, the total level of plastic particles may be much higher. What is worrying is the capacity of such particles to be internalized by cells and alter how our bodies function,” she added.

Mauad said that although questions remain regarding the health implications of their findings, some animal studies have shown that the presence of microplastics in the brain is linked to neurotoxic effects, including oxidative stress.

In addition, exposure to particulate matter has been linked previously to such neurologic conditions as dementia and neurodegenerative conditions such as Parkinson’s disease “seem to have a connection with nasal abnormalities as initial symptoms,” the investigators noted.

While the olfactory pathway appears to be a likely route of exposure the researchers noted that other potential entry routes, including through blood circulation, may also be involved.

The research suggests that inhaling microplastics while indoors may be unavoidable, Mauad said, making it unlikely individuals can eliminate exposure to these substances.

“Everything that surrounds us is plastic. So we can’t really get rid of it,” she said.

 

Are Microplastics Regulated?

The most effective solution would be stricter regulations, Mauad said.

“The industry has chosen to sell many things in plastic, and I think this has to change. We need more policies to decrease plastic production — especially single-use plastic,” she said.

Federal, state, and local regulations for microplastics are “virtually nonexistent,” reported the Interstate Technology and Regulatory Council (ITRC), a state-led coalition that produces documents and trainings related to regulatory issues.

In 2021, the ITRC sent a survey to all US states asking about microplastics regulations. Of the 26 states that responded, only 4 said they had conducted sampling for microplastics. None of the responders indicated they had established any criteria or standards for microplastics, although eight states indicated they had plans to pursue them in the future.

Although federal regulations include the Microbead-Free Waters Act of 2015 and the Save Our Seas Act 2.0, the rules don’t directly pertain to microplastics.

There are also no regulations currently in place regarding microplastics or nanoplastics in food. A report issued in July by the FDA claimed that “the overall scientific evidence does not demonstrate that levels of microplastics or nanoplastics found in foods pose a risk to human health.”

International efforts to regulate microplastics are much further along. First created in 2022, the treaty would forge an international, legally binding agreement.

While it is a step in the right direction, the Plastic Health Council has cautioned about “the omission of measures in draft provisions that fully address the impact of plastic pollution on human health.” The treaty should reduce plastic production, eliminate single-use plastic items, and call for testing of all chemicals in plastics, the council argues.

The final round of negotiations for the UN Global Plastic Treaty is set for completion before the end of the year.

 

What Should Clinicians Know?

Much remains unknown about the potential health effects of microplastic exposure. So how can clinicians respond to questions from concerned patients?

“We don’t yet have enough evidence about the plastic particle itself, like those highlighted in the current study — and even more so when it comes to nanoplastics, which are a thousand times smaller,” said Phoebe Stapleton, PhD, associated professor in the Department of Pharmacology and Toxicology at the Ernest Mario School of Pharmacy at Rutgers University, Piscataway, New Jersey.

“But we do have a lot of evidence about the chemicals that are used to make plastics, and we’ve already seen regulation there from the EPA. That’s one conversation that clinicians could have with patients: about those chemicals,” she added.

Stapleton recommended clinicians stay current on the latest research and be ready to respond should a patient raise the issue. She also noted the importance of exercising caution when interpreting these new findings.

While the study is important — especially because it highlights inhalation as a viable route of entry — exposure through the olfactory area is still just a theory and hasn’t yet been fully proven.

In addition, Stapleton wonders whether there are tissues where these substances are not found. A discovery like that “would be really exciting because that means that that tissue has mechanisms protecting it, and maybe, we could learn more about how to keep microplastics out,” she said.

She would also like to see more studies on specific adverse health effects from microplastics in the body.

Mauad agreed.

“That’s the next set of questions: What are the toxicities or lack thereof in those tissues? That will give us more information as it pertains to human health. It doesn’t feel good to know they’re in our tissues, but we still don’t have a real understanding of what they’re doing when they’re there,” she said.

The current study was funded by the Alexander von Humboldt Foundation and by grants from the Brazilian Research Council and the Soa State Research Agency. It was also funded by the Plastic Soup Foundation — which, together with A Plastic Planet, forms the Plastic Health Council. The investigators and Stapleton reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

For some medical students and trainees who go on to become hematologists, attraction to the field happens the first time they’re engrossed in figuring out what a blood smear is telling them. Others get drawn to hematology during a rotation in residency, when they encounter patients with hemophilia or sickle cell disease.

But when it comes to turning people on to the idea of a career in classical hematology (CH), there may be no more powerful influence than a mentor who loves their job. That’s why the field is focusing so much on supporting mentors and mentees amid a stark shortage of classical hematologists.

“Mentorship is key for maintaining trainee interest in the field and for providing role models for career growth,” said Rakhi P. Naik, MD, MHS, associate professor of medicine and director of the Hematology Fellowship Track at Johns Hopkins University, Baltimore, Maryland, in an interview. “This collaboration is especially critical because there are so few trainees and so few mentors currently in the field.”

Now there’s new research backing up the power of mentorship, even when it’s only provided virtually, and a brand-new program aims to unite more mentors and mentees.

Here’s a closer look at mentor-focused efforts to attract medical students to CH.

 

How Severe Is the Shortage in CH?

Patients with conditions treated by classical hematologists are waiting months for appointments at many outpatient centers, with some being forced to wait 6 months or more, said Srikanth Nagalla, MD, chief of benign hematology at Miami Cancer Institute, Florida, in an interview.

The shortage is creating dire problems in the inpatient setting too, Nagalla said. “Serious blood disorders like heparin-induced thrombocytopenia, acute chest syndrome [a complication of sickle cell disease], and thrombotic thrombocytopenic purpura have to be diagnosed and treated in a timely manner. If not, the morbidity and mortality are really high.”

If classical hematologists aren’t available, he said, oncologists and others not trained in hematology will need to cover these patients. 

Hematologist Ariela Marshall, MD, associate professor of medicine at the University of Minnesota in Minneapolis, noted in an interview that the CH shortage comes at a time when medical advances and an aging population are boosting the number of patients with noncancerous blood disorders. Older people are at greater risk for blood clots, she said. And lifespans for patients with bleeding and clotting disorders are rising thanks to effective new treatments.

“Because of our larger patient population in CH, we are going to need more classical hematologists to follow them for longer and longer periods of time,” she said. 

There’s no sign yet that newly minted physicians will take up the slack in CH. A 2019 study found that just 4.6% of 626 of hematology/oncology fellows said they planned to go into CH, also known as benign hematology, vs 67.1% who expected to treat patients with solid tumors, blood cancer, or both. The rest, 24.6%, planned to work in CH plus the two oncology fields.

 

Why Does a Shortage Exist?

“The reasons are complex, but one of the most important factors was the combining of the adult hematology and medical oncology training programs by the Accreditation Council for Graduate Medical Education in 1995,” Naik said. “After that time, the majority of fellowship training programs went from having separate programs for hematology and medical oncology to combining the training for the two specialties into one. Because most of these combined training programs resided within Cancer Centers, classical hematology training slowly became de-emphasized.”

As a result, fewer fellows ended up specializing in CH, she said. 

The field of CH also appears to suffer from a less than enticing reputation. According to a 2019 study coauthored by Marshall, surveys of thousands of hematology/oncology fellows found that “hematology, particularly benign hematology, was viewed as having poorer income potential, research funding, job availability, and job security than oncology.”

Regarding pay, Marshall said the good news is that many classical hematologists work in academia, where it’s common for pay to be “equitable across hematology/oncology divisions and based more on academic rank and other factors rather than subspecialty within hematology oncology.”

However, she noted, “this may differ at institutions where hematology and oncology are different departments. For example, centers where oncology is its own department, and hematology is part of the department of medicine.” 

As for job availability, Naik said that there’s plenty of demand. “In academics, it is clear that there are jobs available everywhere, but trainees are often worried about job prospects in private practice. While classical hematology jobs in private practice are not widely advertised, I can attest that there is no shortage of need,” she said. “Many private practices do not specifically advertise for classical hematologists because they assume that classical hematology experts are not available. But I assure you that every private practice my trainees have ever approached is always ecstatic to hire a classical hematologist.”

 

Why Are Mentors Important?

Mentorship is crucial to promoting the value of CH as a great career choice in a competitive environment, classical hematologists say. “We can motivate trainees by showing how the disease states themselves are so fascinating and how the treatments are showing great outcomes,” Nagalla said. “We can show positive results, how patient lives can be changed, and how well-respected across the system [we] are.”

As a selling point, classical hematologists like to emphasize that their field requires intensive detective work. “Let’s say a patient comes with anemia, which might have 15 different causes. You get some labs, and then you systemically rule in or rule out most of these on the differential diagnosis,” Nagalla said. “Then once you narrow it down, you get more labs. You keep going to the next step and next step, and so finally you come to a conclusion.”

As for therapy, Marshall said that “while for many cancers there are specific treatment recommendations for patients with a specific cancer type at a specific stage, there is not always a specific treatment recommendation (or a ‘right answer’) for our CH patients. Treatment planning depends strongly on a patient’s preferences, other medical conditions, and a discussion about risks [and] benefits of different treatment options such that two patients with the same condition may choose two different treatment options.”

Marshall also emphasizes to trainees that “CH is a broad field. Physicians and trainees are able to interact and collaborate with physicians in other specialties such as gastroenterology, cardiology, ob/gyn, and surgical specialties.” 

 

Does Research Support Mentorship in CH?

The 2019 study that revealed just 4.6% of fellows planned to go into CH found that “fellows who planned to enter hematology-only careers were significantly more likely to report having clinical training and mentorship experiences in hematology throughout their training relative to fellows with oncology-only or combined hematology/oncology career plans.”

Now there are more data to support mentorships. For a study published in Blood Advances in September 2024, Zoya Qureshy, MD, an internal medicine chief resident at the University of California at San Diego, and colleagues evaluated a year-long external membership program implemented by the American Society of Hematology (ASH) Medical Educators Institute. 

The program linked 35 US hematology/oncology fellows (80% female, 46% White, 35% Asian) who were interested in CH to 34 North American faculty members. The pairs were told to meet virtually once a month. 

Of 30 mentees and 23 mentors surveyed, 94% and 85%, respectively, said their pairings were good matches. Two thirds of the mentees accepted faculty positions in CH after their mentorships.

“Our study showed that external mentorship in a virtual format is feasible,” Qureshy said in an interview. “Additionally, external mentorship provided benefits such as different perspectives and the opportunity for mentorship for those who may not have it in their field of interest at their home institution.”

Qureshy added that “one strength of our mentorship program was that mentoring pairs were meticulously assigned based on shared interests and background. Many participants cited this common ground as a reason why they thought their mentoring pair was a good match.” 

There’s an important caveat: Most of the mentees weren’t new to CH. About 70% had previously worked with a mentor in the CH field, and 86% had previously conducted research in the field. 

 

What’s Next for Mentorship in CH?

The ASH Hematology-Focused Fellowship Training Program Consortium aims to mint 50 new academic hematologists by 2030 through programs at 12 institutions. “Mentorship is an exciting aspect of the program since it allows classical hematology trainees to form a network of peers nationally and also provides access to mentors across institutions,” Naik said. “And as the workforce grows, there will be more and more role models for future trainees to look up to.”

Moving forward, she said, “we hope to inspire even more institutions to adopt hematology training tracks throughout the country.”

Meanwhile, ASH’s new Classical Hematology Advancement Mentorship is taking applications for its debut 2025 program through January 9, 2025. Trainees will meet monthly with mentors both virtually and in person. Applicants must have been in their first or second year of hematology/oncology fellowship training at accredited programs in the United States as of July 15, 2024.

Naik, Marshall, Nagalla, and Qureshy have no relevant disclosures.

A version of this article appeared on Medscape.com.

For some medical students and trainees who go on to become hematologists, attraction to the field happens the first time they’re engrossed in figuring out what a blood smear is telling them. Others get drawn to hematology during a rotation in residency, when they encounter patients with hemophilia or sickle cell disease.

But when it comes to turning people on to the idea of a career in classical hematology (CH), there may be no more powerful influence than a mentor who loves their job. That’s why the field is focusing so much on supporting mentors and mentees amid a stark shortage of classical hematologists.

“Mentorship is key for maintaining trainee interest in the field and for providing role models for career growth,” said Rakhi P. Naik, MD, MHS, associate professor of medicine and director of the Hematology Fellowship Track at Johns Hopkins University, Baltimore, Maryland, in an interview. “This collaboration is especially critical because there are so few trainees and so few mentors currently in the field.”

Now there’s new research backing up the power of mentorship, even when it’s only provided virtually, and a brand-new program aims to unite more mentors and mentees.

Here’s a closer look at mentor-focused efforts to attract medical students to CH.

 

How Severe Is the Shortage in CH?

Patients with conditions treated by classical hematologists are waiting months for appointments at many outpatient centers, with some being forced to wait 6 months or more, said Srikanth Nagalla, MD, chief of benign hematology at Miami Cancer Institute, Florida, in an interview.

The shortage is creating dire problems in the inpatient setting too, Nagalla said. “Serious blood disorders like heparin-induced thrombocytopenia, acute chest syndrome [a complication of sickle cell disease], and thrombotic thrombocytopenic purpura have to be diagnosed and treated in a timely manner. If not, the morbidity and mortality are really high.”

If classical hematologists aren’t available, he said, oncologists and others not trained in hematology will need to cover these patients. 

Hematologist Ariela Marshall, MD, associate professor of medicine at the University of Minnesota in Minneapolis, noted in an interview that the CH shortage comes at a time when medical advances and an aging population are boosting the number of patients with noncancerous blood disorders. Older people are at greater risk for blood clots, she said. And lifespans for patients with bleeding and clotting disorders are rising thanks to effective new treatments.

“Because of our larger patient population in CH, we are going to need more classical hematologists to follow them for longer and longer periods of time,” she said. 

There’s no sign yet that newly minted physicians will take up the slack in CH. A 2019 study found that just 4.6% of 626 of hematology/oncology fellows said they planned to go into CH, also known as benign hematology, vs 67.1% who expected to treat patients with solid tumors, blood cancer, or both. The rest, 24.6%, planned to work in CH plus the two oncology fields.

 

Why Does a Shortage Exist?

“The reasons are complex, but one of the most important factors was the combining of the adult hematology and medical oncology training programs by the Accreditation Council for Graduate Medical Education in 1995,” Naik said. “After that time, the majority of fellowship training programs went from having separate programs for hematology and medical oncology to combining the training for the two specialties into one. Because most of these combined training programs resided within Cancer Centers, classical hematology training slowly became de-emphasized.”

As a result, fewer fellows ended up specializing in CH, she said. 

The field of CH also appears to suffer from a less than enticing reputation. According to a 2019 study coauthored by Marshall, surveys of thousands of hematology/oncology fellows found that “hematology, particularly benign hematology, was viewed as having poorer income potential, research funding, job availability, and job security than oncology.”

Regarding pay, Marshall said the good news is that many classical hematologists work in academia, where it’s common for pay to be “equitable across hematology/oncology divisions and based more on academic rank and other factors rather than subspecialty within hematology oncology.”

However, she noted, “this may differ at institutions where hematology and oncology are different departments. For example, centers where oncology is its own department, and hematology is part of the department of medicine.” 

As for job availability, Naik said that there’s plenty of demand. “In academics, it is clear that there are jobs available everywhere, but trainees are often worried about job prospects in private practice. While classical hematology jobs in private practice are not widely advertised, I can attest that there is no shortage of need,” she said. “Many private practices do not specifically advertise for classical hematologists because they assume that classical hematology experts are not available. But I assure you that every private practice my trainees have ever approached is always ecstatic to hire a classical hematologist.”

 

Why Are Mentors Important?

Mentorship is crucial to promoting the value of CH as a great career choice in a competitive environment, classical hematologists say. “We can motivate trainees by showing how the disease states themselves are so fascinating and how the treatments are showing great outcomes,” Nagalla said. “We can show positive results, how patient lives can be changed, and how well-respected across the system [we] are.”

As a selling point, classical hematologists like to emphasize that their field requires intensive detective work. “Let’s say a patient comes with anemia, which might have 15 different causes. You get some labs, and then you systemically rule in or rule out most of these on the differential diagnosis,” Nagalla said. “Then once you narrow it down, you get more labs. You keep going to the next step and next step, and so finally you come to a conclusion.”

As for therapy, Marshall said that “while for many cancers there are specific treatment recommendations for patients with a specific cancer type at a specific stage, there is not always a specific treatment recommendation (or a ‘right answer’) for our CH patients. Treatment planning depends strongly on a patient’s preferences, other medical conditions, and a discussion about risks [and] benefits of different treatment options such that two patients with the same condition may choose two different treatment options.”

Marshall also emphasizes to trainees that “CH is a broad field. Physicians and trainees are able to interact and collaborate with physicians in other specialties such as gastroenterology, cardiology, ob/gyn, and surgical specialties.” 

 

Does Research Support Mentorship in CH?

The 2019 study that revealed just 4.6% of fellows planned to go into CH found that “fellows who planned to enter hematology-only careers were significantly more likely to report having clinical training and mentorship experiences in hematology throughout their training relative to fellows with oncology-only or combined hematology/oncology career plans.”

Now there are more data to support mentorships. For a study published in Blood Advances in September 2024, Zoya Qureshy, MD, an internal medicine chief resident at the University of California at San Diego, and colleagues evaluated a year-long external membership program implemented by the American Society of Hematology (ASH) Medical Educators Institute. 

The program linked 35 US hematology/oncology fellows (80% female, 46% White, 35% Asian) who were interested in CH to 34 North American faculty members. The pairs were told to meet virtually once a month. 

Of 30 mentees and 23 mentors surveyed, 94% and 85%, respectively, said their pairings were good matches. Two thirds of the mentees accepted faculty positions in CH after their mentorships.

“Our study showed that external mentorship in a virtual format is feasible,” Qureshy said in an interview. “Additionally, external mentorship provided benefits such as different perspectives and the opportunity for mentorship for those who may not have it in their field of interest at their home institution.”

Qureshy added that “one strength of our mentorship program was that mentoring pairs were meticulously assigned based on shared interests and background. Many participants cited this common ground as a reason why they thought their mentoring pair was a good match.” 

There’s an important caveat: Most of the mentees weren’t new to CH. About 70% had previously worked with a mentor in the CH field, and 86% had previously conducted research in the field. 

 

What’s Next for Mentorship in CH?

The ASH Hematology-Focused Fellowship Training Program Consortium aims to mint 50 new academic hematologists by 2030 through programs at 12 institutions. “Mentorship is an exciting aspect of the program since it allows classical hematology trainees to form a network of peers nationally and also provides access to mentors across institutions,” Naik said. “And as the workforce grows, there will be more and more role models for future trainees to look up to.”

Moving forward, she said, “we hope to inspire even more institutions to adopt hematology training tracks throughout the country.”

Meanwhile, ASH’s new Classical Hematology Advancement Mentorship is taking applications for its debut 2025 program through January 9, 2025. Trainees will meet monthly with mentors both virtually and in person. Applicants must have been in their first or second year of hematology/oncology fellowship training at accredited programs in the United States as of July 15, 2024.

Naik, Marshall, Nagalla, and Qureshy have no relevant disclosures.

A version of this article appeared on Medscape.com.

For some medical students and trainees who go on to become hematologists, attraction to the field happens the first time they’re engrossed in figuring out what a blood smear is telling them. Others get drawn to hematology during a rotation in residency, when they encounter patients with hemophilia or sickle cell disease.

But when it comes to turning people on to the idea of a career in classical hematology (CH), there may be no more powerful influence than a mentor who loves their job. That’s why the field is focusing so much on supporting mentors and mentees amid a stark shortage of classical hematologists.

“Mentorship is key for maintaining trainee interest in the field and for providing role models for career growth,” said Rakhi P. Naik, MD, MHS, associate professor of medicine and director of the Hematology Fellowship Track at Johns Hopkins University, Baltimore, Maryland, in an interview. “This collaboration is especially critical because there are so few trainees and so few mentors currently in the field.”

Now there’s new research backing up the power of mentorship, even when it’s only provided virtually, and a brand-new program aims to unite more mentors and mentees.

Here’s a closer look at mentor-focused efforts to attract medical students to CH.

 

How Severe Is the Shortage in CH?

Patients with conditions treated by classical hematologists are waiting months for appointments at many outpatient centers, with some being forced to wait 6 months or more, said Srikanth Nagalla, MD, chief of benign hematology at Miami Cancer Institute, Florida, in an interview.

The shortage is creating dire problems in the inpatient setting too, Nagalla said. “Serious blood disorders like heparin-induced thrombocytopenia, acute chest syndrome [a complication of sickle cell disease], and thrombotic thrombocytopenic purpura have to be diagnosed and treated in a timely manner. If not, the morbidity and mortality are really high.”

If classical hematologists aren’t available, he said, oncologists and others not trained in hematology will need to cover these patients. 

Hematologist Ariela Marshall, MD, associate professor of medicine at the University of Minnesota in Minneapolis, noted in an interview that the CH shortage comes at a time when medical advances and an aging population are boosting the number of patients with noncancerous blood disorders. Older people are at greater risk for blood clots, she said. And lifespans for patients with bleeding and clotting disorders are rising thanks to effective new treatments.

“Because of our larger patient population in CH, we are going to need more classical hematologists to follow them for longer and longer periods of time,” she said. 

There’s no sign yet that newly minted physicians will take up the slack in CH. A 2019 study found that just 4.6% of 626 of hematology/oncology fellows said they planned to go into CH, also known as benign hematology, vs 67.1% who expected to treat patients with solid tumors, blood cancer, or both. The rest, 24.6%, planned to work in CH plus the two oncology fields.

 

Why Does a Shortage Exist?

“The reasons are complex, but one of the most important factors was the combining of the adult hematology and medical oncology training programs by the Accreditation Council for Graduate Medical Education in 1995,” Naik said. “After that time, the majority of fellowship training programs went from having separate programs for hematology and medical oncology to combining the training for the two specialties into one. Because most of these combined training programs resided within Cancer Centers, classical hematology training slowly became de-emphasized.”

As a result, fewer fellows ended up specializing in CH, she said. 

The field of CH also appears to suffer from a less than enticing reputation. According to a 2019 study coauthored by Marshall, surveys of thousands of hematology/oncology fellows found that “hematology, particularly benign hematology, was viewed as having poorer income potential, research funding, job availability, and job security than oncology.”

Regarding pay, Marshall said the good news is that many classical hematologists work in academia, where it’s common for pay to be “equitable across hematology/oncology divisions and based more on academic rank and other factors rather than subspecialty within hematology oncology.”

However, she noted, “this may differ at institutions where hematology and oncology are different departments. For example, centers where oncology is its own department, and hematology is part of the department of medicine.” 

As for job availability, Naik said that there’s plenty of demand. “In academics, it is clear that there are jobs available everywhere, but trainees are often worried about job prospects in private practice. While classical hematology jobs in private practice are not widely advertised, I can attest that there is no shortage of need,” she said. “Many private practices do not specifically advertise for classical hematologists because they assume that classical hematology experts are not available. But I assure you that every private practice my trainees have ever approached is always ecstatic to hire a classical hematologist.”

 

Why Are Mentors Important?

Mentorship is crucial to promoting the value of CH as a great career choice in a competitive environment, classical hematologists say. “We can motivate trainees by showing how the disease states themselves are so fascinating and how the treatments are showing great outcomes,” Nagalla said. “We can show positive results, how patient lives can be changed, and how well-respected across the system [we] are.”

As a selling point, classical hematologists like to emphasize that their field requires intensive detective work. “Let’s say a patient comes with anemia, which might have 15 different causes. You get some labs, and then you systemically rule in or rule out most of these on the differential diagnosis,” Nagalla said. “Then once you narrow it down, you get more labs. You keep going to the next step and next step, and so finally you come to a conclusion.”

As for therapy, Marshall said that “while for many cancers there are specific treatment recommendations for patients with a specific cancer type at a specific stage, there is not always a specific treatment recommendation (or a ‘right answer’) for our CH patients. Treatment planning depends strongly on a patient’s preferences, other medical conditions, and a discussion about risks [and] benefits of different treatment options such that two patients with the same condition may choose two different treatment options.”

Marshall also emphasizes to trainees that “CH is a broad field. Physicians and trainees are able to interact and collaborate with physicians in other specialties such as gastroenterology, cardiology, ob/gyn, and surgical specialties.” 

 

Does Research Support Mentorship in CH?

The 2019 study that revealed just 4.6% of fellows planned to go into CH found that “fellows who planned to enter hematology-only careers were significantly more likely to report having clinical training and mentorship experiences in hematology throughout their training relative to fellows with oncology-only or combined hematology/oncology career plans.”

Now there are more data to support mentorships. For a study published in Blood Advances in September 2024, Zoya Qureshy, MD, an internal medicine chief resident at the University of California at San Diego, and colleagues evaluated a year-long external membership program implemented by the American Society of Hematology (ASH) Medical Educators Institute. 

The program linked 35 US hematology/oncology fellows (80% female, 46% White, 35% Asian) who were interested in CH to 34 North American faculty members. The pairs were told to meet virtually once a month. 

Of 30 mentees and 23 mentors surveyed, 94% and 85%, respectively, said their pairings were good matches. Two thirds of the mentees accepted faculty positions in CH after their mentorships.

“Our study showed that external mentorship in a virtual format is feasible,” Qureshy said in an interview. “Additionally, external mentorship provided benefits such as different perspectives and the opportunity for mentorship for those who may not have it in their field of interest at their home institution.”

Qureshy added that “one strength of our mentorship program was that mentoring pairs were meticulously assigned based on shared interests and background. Many participants cited this common ground as a reason why they thought their mentoring pair was a good match.” 

There’s an important caveat: Most of the mentees weren’t new to CH. About 70% had previously worked with a mentor in the CH field, and 86% had previously conducted research in the field. 

 

What’s Next for Mentorship in CH?

The ASH Hematology-Focused Fellowship Training Program Consortium aims to mint 50 new academic hematologists by 2030 through programs at 12 institutions. “Mentorship is an exciting aspect of the program since it allows classical hematology trainees to form a network of peers nationally and also provides access to mentors across institutions,” Naik said. “And as the workforce grows, there will be more and more role models for future trainees to look up to.”

Moving forward, she said, “we hope to inspire even more institutions to adopt hematology training tracks throughout the country.”

Meanwhile, ASH’s new Classical Hematology Advancement Mentorship is taking applications for its debut 2025 program through January 9, 2025. Trainees will meet monthly with mentors both virtually and in person. Applicants must have been in their first or second year of hematology/oncology fellowship training at accredited programs in the United States as of July 15, 2024.

Naik, Marshall, Nagalla, and Qureshy have no relevant disclosures.

A version of this article appeared on Medscape.com.

’Tis the season for recognizing seasonal affective disorder (SAD). Just don’t expect to find SAD in diagnostic handbooks.

As a memorable term, SAD “stuck in the general public, and to some extent among health professionals,” said Scott Patten, MD, PhD, professor of psychiatry and epidemiology at the University of Calgary in Alberta, Canada. “But it’s important to emphasize that that’s not an officially recognized diagnosis by the major classifications.”

Researchers coined the term SAD 40 years ago to describe a pattern of depression that sets in during the fall or winter and remits in the spring or summer.

Clinicians are diagnosing the disorder, albeit without that exact moniker.

In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the condition is considered a subtype of major depression.

So, for patients who meet criteria for recurrent major depressive disorder, the specifier “with seasonal pattern” might be applied.

The subtype covers cases where depressive episodes have followed a seasonal pattern for at least 2 years. Typically, onset occurs in the fall or winter followed by remission in the spring or summer. The opposite pattern is possible but less common.

When stressors such as seasonal unemployment better explain the pattern, the seasonal specifier should not be used, according to the manual. Bipolar disorder can follow a seasonal pattern as well.

Researchers estimate SAD affects about 5% of adults in the United States. The diagnosis is more common in women than in men, and more prevalent farther from the equator.

 

One Hallmark Symptom?

DSM-5 highlights characteristic features of winter depression, including:

• Loss of energy
• Hypersomnia
• A craving for carbohydrates
• Overeating
• Weight gain

Kelly Rohan, PhD, a researcher at the University of Vermont, Burlington, who has studied SAD since the 1990s, sees one symptom as a possible hallmark for the disorder: fatigue.

“I’ve personally never met someone who met the full diagnostic criteria for the seasonal pattern that did not have fatigue as one of their symptoms,” Rohan said. “In theory, they could exist, but I have spoken to hundreds of people with seasonal depression, and I have never met them if, in fact, they do exist.”

That differs from nonseasonal depression, for which insomnia is a more common problem with sleep, Patten said.

Clinicians look for at least five symptoms of depression that cause substantial impairment and distress for at least 2 weeks, such as pervasive sadness, difficulty concentrating, low self-esteem, or loss of interest in hobbies.

An average episode of winter depression can last 5 months, however, Rohan said. “That’s a long time to be in a major depressive episode.”

 

Seeing Subsyndromal Cases

In people who do not meet criteria for major depression with a seasonal pattern, the change of seasons still can affect energy levels and mood. Some patients have “subsyndromal SAD” and may benefit from treatments that have been developed for SAD such as bright light therapy, said Paul Desan, MD, PhD, director of the Winter Depression Research Clinic at Yale School of Medicine in New Haven, Connecticut.

“Many people come to our clinic because they have seasonal changes that don’t meet the full criteria for depression, but nevertheless, they want help,” Desan said.

The 1984 paper that introduced the term SAD explored artificial bright light as a promising treatment for the condition. The researchers had heard from dozens of patients with “recurrent depressions that occur annually at the same time each year,” and bright light appeared to help alleviate their symptoms.

Subsequent trials have found the approach effective. Even in nonseasonal depression, bright light therapy may increase the likelihood of remission, a recent meta-analysis found. Light therapy also may bolster the effectiveness of antidepressant medication in nonseasonal major depressive disorder, a randomized trial has shown.

Other treatments for SAD include cognitive behavioral therapy (CBT) and bupropion XL, which is approved as a preventive medication. Other drugs for major depressive disorder may be used.

 

Quest for Biomarkers

To better understand SAD and how available treatments work, Rohan is conducting a study that examines potential biomarkers in patients treated with light therapy or CBT. She and her colleagues are examining circadian phase angle difference (how well internal clocks match daily routines) and post-illumination pupil response (how the pupil constricts after a light turns off). They also are measuring participants’ pupil responses and brain activity upon seeing words that are associated with winter or summer (like “blizzard,” “icy,” “sunshine,” and “picnics.”) 

Studies have shown treating patients to remission with CBT reduces the risk for recurrence in subsequent years, relative to other treatment approaches, Rohan said. That may be because CBT gives people tools to avoid slipping into another depressive episode.

 

Avoid Self-Diagnosis

Rohan cautions patients against self-diagnosis and treatment.

“Having a conversation with your doctor is a good starting point,” she said. “Just because you can walk into Costco and walk out with a light box doesn’t mean that you should.” 

Light therapy can have side effects, including headaches, eye strain, and making patients feel wired, and it can be a challenge to determine the right dose, Rohan said.

Desan’s clinic website provides information about available devices for light therapy for patients who are looking to try this approach, but Desan agrees clinicians — especially primary care clinicians — can play a crucial role in helping patients. In more serious cases, a mental health expert may be necessary.

To start light therapy, Desan’s clinic typically recommends patients try 30 minutes of 10,000 lux bright light — roughly the brightness of being outside on a sunny day — before 8 AM for a 4-week trial.

Still, other specific issues might explain why a patient is struggling during winter months, Patten said. For example, people might experience financial stress around the holidays or consume excessive amounts of alcohol during that time.

“It’s important for clinicians to think broadly about it,” Patten said. “It might not always be light therapy or a medication. It might be focusing on some other aspect of what is going on for them in the winter.” 

Rohan’s research is funded by the National Institute of Mental Health, and she receives royalties for a manual on treating SAD with CBT. Patten and Desan had no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

’Tis the season for recognizing seasonal affective disorder (SAD). Just don’t expect to find SAD in diagnostic handbooks.

As a memorable term, SAD “stuck in the general public, and to some extent among health professionals,” said Scott Patten, MD, PhD, professor of psychiatry and epidemiology at the University of Calgary in Alberta, Canada. “But it’s important to emphasize that that’s not an officially recognized diagnosis by the major classifications.”

Researchers coined the term SAD 40 years ago to describe a pattern of depression that sets in during the fall or winter and remits in the spring or summer.

Clinicians are diagnosing the disorder, albeit without that exact moniker.

In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the condition is considered a subtype of major depression.

So, for patients who meet criteria for recurrent major depressive disorder, the specifier “with seasonal pattern” might be applied.

The subtype covers cases where depressive episodes have followed a seasonal pattern for at least 2 years. Typically, onset occurs in the fall or winter followed by remission in the spring or summer. The opposite pattern is possible but less common.

When stressors such as seasonal unemployment better explain the pattern, the seasonal specifier should not be used, according to the manual. Bipolar disorder can follow a seasonal pattern as well.

Researchers estimate SAD affects about 5% of adults in the United States. The diagnosis is more common in women than in men, and more prevalent farther from the equator.

 

One Hallmark Symptom?

DSM-5 highlights characteristic features of winter depression, including:

• Loss of energy
• Hypersomnia
• A craving for carbohydrates
• Overeating
• Weight gain

Kelly Rohan, PhD, a researcher at the University of Vermont, Burlington, who has studied SAD since the 1990s, sees one symptom as a possible hallmark for the disorder: fatigue.

“I’ve personally never met someone who met the full diagnostic criteria for the seasonal pattern that did not have fatigue as one of their symptoms,” Rohan said. “In theory, they could exist, but I have spoken to hundreds of people with seasonal depression, and I have never met them if, in fact, they do exist.”

That differs from nonseasonal depression, for which insomnia is a more common problem with sleep, Patten said.

Clinicians look for at least five symptoms of depression that cause substantial impairment and distress for at least 2 weeks, such as pervasive sadness, difficulty concentrating, low self-esteem, or loss of interest in hobbies.

An average episode of winter depression can last 5 months, however, Rohan said. “That’s a long time to be in a major depressive episode.”

 

Seeing Subsyndromal Cases

In people who do not meet criteria for major depression with a seasonal pattern, the change of seasons still can affect energy levels and mood. Some patients have “subsyndromal SAD” and may benefit from treatments that have been developed for SAD such as bright light therapy, said Paul Desan, MD, PhD, director of the Winter Depression Research Clinic at Yale School of Medicine in New Haven, Connecticut.

“Many people come to our clinic because they have seasonal changes that don’t meet the full criteria for depression, but nevertheless, they want help,” Desan said.

The 1984 paper that introduced the term SAD explored artificial bright light as a promising treatment for the condition. The researchers had heard from dozens of patients with “recurrent depressions that occur annually at the same time each year,” and bright light appeared to help alleviate their symptoms.

Subsequent trials have found the approach effective. Even in nonseasonal depression, bright light therapy may increase the likelihood of remission, a recent meta-analysis found. Light therapy also may bolster the effectiveness of antidepressant medication in nonseasonal major depressive disorder, a randomized trial has shown.

Other treatments for SAD include cognitive behavioral therapy (CBT) and bupropion XL, which is approved as a preventive medication. Other drugs for major depressive disorder may be used.

 

Quest for Biomarkers

To better understand SAD and how available treatments work, Rohan is conducting a study that examines potential biomarkers in patients treated with light therapy or CBT. She and her colleagues are examining circadian phase angle difference (how well internal clocks match daily routines) and post-illumination pupil response (how the pupil constricts after a light turns off). They also are measuring participants’ pupil responses and brain activity upon seeing words that are associated with winter or summer (like “blizzard,” “icy,” “sunshine,” and “picnics.”) 

Studies have shown treating patients to remission with CBT reduces the risk for recurrence in subsequent years, relative to other treatment approaches, Rohan said. That may be because CBT gives people tools to avoid slipping into another depressive episode.

 

Avoid Self-Diagnosis

Rohan cautions patients against self-diagnosis and treatment.

“Having a conversation with your doctor is a good starting point,” she said. “Just because you can walk into Costco and walk out with a light box doesn’t mean that you should.” 

Light therapy can have side effects, including headaches, eye strain, and making patients feel wired, and it can be a challenge to determine the right dose, Rohan said.

Desan’s clinic website provides information about available devices for light therapy for patients who are looking to try this approach, but Desan agrees clinicians — especially primary care clinicians — can play a crucial role in helping patients. In more serious cases, a mental health expert may be necessary.

To start light therapy, Desan’s clinic typically recommends patients try 30 minutes of 10,000 lux bright light — roughly the brightness of being outside on a sunny day — before 8 AM for a 4-week trial.

Still, other specific issues might explain why a patient is struggling during winter months, Patten said. For example, people might experience financial stress around the holidays or consume excessive amounts of alcohol during that time.

“It’s important for clinicians to think broadly about it,” Patten said. “It might not always be light therapy or a medication. It might be focusing on some other aspect of what is going on for them in the winter.” 

Rohan’s research is funded by the National Institute of Mental Health, and she receives royalties for a manual on treating SAD with CBT. Patten and Desan had no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

’Tis the season for recognizing seasonal affective disorder (SAD). Just don’t expect to find SAD in diagnostic handbooks.

As a memorable term, SAD “stuck in the general public, and to some extent among health professionals,” said Scott Patten, MD, PhD, professor of psychiatry and epidemiology at the University of Calgary in Alberta, Canada. “But it’s important to emphasize that that’s not an officially recognized diagnosis by the major classifications.”

Researchers coined the term SAD 40 years ago to describe a pattern of depression that sets in during the fall or winter and remits in the spring or summer.

Clinicians are diagnosing the disorder, albeit without that exact moniker.

In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the condition is considered a subtype of major depression.

So, for patients who meet criteria for recurrent major depressive disorder, the specifier “with seasonal pattern” might be applied.

The subtype covers cases where depressive episodes have followed a seasonal pattern for at least 2 years. Typically, onset occurs in the fall or winter followed by remission in the spring or summer. The opposite pattern is possible but less common.

When stressors such as seasonal unemployment better explain the pattern, the seasonal specifier should not be used, according to the manual. Bipolar disorder can follow a seasonal pattern as well.

Researchers estimate SAD affects about 5% of adults in the United States. The diagnosis is more common in women than in men, and more prevalent farther from the equator.

 

One Hallmark Symptom?

DSM-5 highlights characteristic features of winter depression, including:

• Loss of energy
• Hypersomnia
• A craving for carbohydrates
• Overeating
• Weight gain

Kelly Rohan, PhD, a researcher at the University of Vermont, Burlington, who has studied SAD since the 1990s, sees one symptom as a possible hallmark for the disorder: fatigue.

“I’ve personally never met someone who met the full diagnostic criteria for the seasonal pattern that did not have fatigue as one of their symptoms,” Rohan said. “In theory, they could exist, but I have spoken to hundreds of people with seasonal depression, and I have never met them if, in fact, they do exist.”

That differs from nonseasonal depression, for which insomnia is a more common problem with sleep, Patten said.

Clinicians look for at least five symptoms of depression that cause substantial impairment and distress for at least 2 weeks, such as pervasive sadness, difficulty concentrating, low self-esteem, or loss of interest in hobbies.

An average episode of winter depression can last 5 months, however, Rohan said. “That’s a long time to be in a major depressive episode.”

 

Seeing Subsyndromal Cases

In people who do not meet criteria for major depression with a seasonal pattern, the change of seasons still can affect energy levels and mood. Some patients have “subsyndromal SAD” and may benefit from treatments that have been developed for SAD such as bright light therapy, said Paul Desan, MD, PhD, director of the Winter Depression Research Clinic at Yale School of Medicine in New Haven, Connecticut.

“Many people come to our clinic because they have seasonal changes that don’t meet the full criteria for depression, but nevertheless, they want help,” Desan said.

The 1984 paper that introduced the term SAD explored artificial bright light as a promising treatment for the condition. The researchers had heard from dozens of patients with “recurrent depressions that occur annually at the same time each year,” and bright light appeared to help alleviate their symptoms.

Subsequent trials have found the approach effective. Even in nonseasonal depression, bright light therapy may increase the likelihood of remission, a recent meta-analysis found. Light therapy also may bolster the effectiveness of antidepressant medication in nonseasonal major depressive disorder, a randomized trial has shown.

Other treatments for SAD include cognitive behavioral therapy (CBT) and bupropion XL, which is approved as a preventive medication. Other drugs for major depressive disorder may be used.

 

Quest for Biomarkers

To better understand SAD and how available treatments work, Rohan is conducting a study that examines potential biomarkers in patients treated with light therapy or CBT. She and her colleagues are examining circadian phase angle difference (how well internal clocks match daily routines) and post-illumination pupil response (how the pupil constricts after a light turns off). They also are measuring participants’ pupil responses and brain activity upon seeing words that are associated with winter or summer (like “blizzard,” “icy,” “sunshine,” and “picnics.”) 

Studies have shown treating patients to remission with CBT reduces the risk for recurrence in subsequent years, relative to other treatment approaches, Rohan said. That may be because CBT gives people tools to avoid slipping into another depressive episode.

 

Avoid Self-Diagnosis

Rohan cautions patients against self-diagnosis and treatment.

“Having a conversation with your doctor is a good starting point,” she said. “Just because you can walk into Costco and walk out with a light box doesn’t mean that you should.” 

Light therapy can have side effects, including headaches, eye strain, and making patients feel wired, and it can be a challenge to determine the right dose, Rohan said.

Desan’s clinic website provides information about available devices for light therapy for patients who are looking to try this approach, but Desan agrees clinicians — especially primary care clinicians — can play a crucial role in helping patients. In more serious cases, a mental health expert may be necessary.

To start light therapy, Desan’s clinic typically recommends patients try 30 minutes of 10,000 lux bright light — roughly the brightness of being outside on a sunny day — before 8 AM for a 4-week trial.

Still, other specific issues might explain why a patient is struggling during winter months, Patten said. For example, people might experience financial stress around the holidays or consume excessive amounts of alcohol during that time.

“It’s important for clinicians to think broadly about it,” Patten said. “It might not always be light therapy or a medication. It might be focusing on some other aspect of what is going on for them in the winter.” 

Rohan’s research is funded by the National Institute of Mental Health, and she receives royalties for a manual on treating SAD with CBT. Patten and Desan had no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

President-elect Donald Trump’s vision for the nation’s top health agencies is coming into focus with three nominations announced Nov. 22 that drew both criticism and praise:

• Surgeon and health researcher Martin A. Makary, MD, MPH, to lead the US Food and Drug Administration (FDA).
• Former Republican congressman and physician David J. Weldon, MD, for director of the US Centers for Disease Control and Prevention (CDC).
• Fox News contributor Janette Nesheiwat, MD, for surgeon general.

Earlier in November, Trump nominated vaccine skeptic and former presidential candidate Robert F. Kennedy Jr. to lead the US Department of Health and Human Services (HHS). 

Here’s what to know about the latest nominees, who, like Kennedy, must be confirmed by the US Senate.

 

Martin A. Makary

Currently a professor at the Johns Hopkins School of Medicine and chief of islet transplant surgery at Johns Hopkins Hospital, Makary co-invented in 2006 a surgery checklist that became a widely-used patient safety tool. 

As a US FDA commissioner, Makary would preside over a $6.5 billion agency with more than 18,000 employees. The agency, part of HHS, oversees human and animal drugs and vaccines, medical devices, food, tobacco and other products. Some of Makary’s views align closely with those of HHS nominee Kennedy. 

Makary is also chief medical officer of telehealth platform Sesame.

Makary was primarily known as a health researcher and author of books about price transparency and the cost of health care until the COVID-19 pandemic, when he became an outspoken critic of the federal response, lambasting restrictions and mandates advocated by the CDC and other public health officials. 

In 2023, Makary told the House Select Subcommittee on the COVID Pandemic that federal officials had ignored what he called “natural immunity.” Studies have shown that natural immunity is “at least as effective as vaccinated immunity, and probably better,” testified Makary.

Makary called for an overhaul of the US FDA in a 2021 Fox News opinion, saying that its culture was “defined by counterproductive rigidity and a refusal to adapt.”

Blind Spots, his most recent book, takes on what he calls “medical dogma” and challenges conventional views on subjects ranging from the microbiome to marijuana to cancer prevention, hormone replacement therapy, antibiotics and peanut allergies.

In an interview he posted to X, Makary blames inappropriate use of antibiotics for a variety of childhood illnesses. He cites increases in obesity, learning disabilities, attention deficit disorder, asthma, celiac disease, ulcerative colitis and Crohn’s disease as all potentially causally related to antibiotics given in childhood.

Makary is an advisor to two conservative think tanks, the Foundation for Research on Equal Opportunity, and to Paragon Health Institute, begun in 2021 by two former top officials in the previous Trump administration.

Makary would “cut the bureaucratic red tape at the agency to make sure Americans get the medical cures and treatments they deserve,” Trump said on his social media platform, Truth Social, and in a press release.

While Los Angeles Times owner and physician-entrepreneur Patrick Soon-Shiong, MBBCh, MSc, praised the nomination of Makary (and the two other nominees) as “inspired,” other physicians criticized Makary for his anti-COVID mandate views and “fear-mongering” over COVID vaccine side effects.

 

Janette Nesheiwat

As surgeon general, Nesheiwat would serve as the top “health communicator in chief” and oversee the 6000 member US Public Health Service Commissioned Corps.

She is a frequent medical contributor to Fox News and serves as a medical director for a group of urgent care clinics in New York. She received her medical degree from the American University of the Caribbean School of Medicine and completed a family medicine residency at the University of Arkansas for Medical Sciences. She is board-certified in family medicine.

Nesheiwat sells vitamin supplements on her website and in December will publish a book on “miracles in medicine” and her Christian faith. 

Trump said in a statement that Nesheiwat “is a fierce advocate and strong communicator for preventive medicine and public health. She is committed to ensuring that Americans have access to affordable, quality healthcare, and believes in empowering individuals to take charge of their health to live longer, healthier lives.”

While Nesheiwat was critical of COVID mandates, she voiced more support for COVID vaccines and mask-wearing during the pandemic than her fellow nominees, leading some Trump supporters to criticize her nomination. 

“A good appointment, happy about this: I got to know @DoctorJanette during the pandemic, exchanging information. She is very smart, thoughtful, interested in learning, and a compassionate doctor, and…a truly nice person,” noted vaccine researcher Peter Hotez, MD, PhD, said on X.

 

David J. Weldon

If confirmed, former congressman Weldon would oversee the sprawling CDC, an agency with a roughly $17 billion budget, 15,000 employees or contractors, and numerous centers covering everything from health statistics to vaccines to epidemiology.

After earning his medical degree from the University at Buffalo School of Medicine, Weldon served in the US Army and US Army reserve. The Republican later served for 14 years in Congress representing Florida’s 15th district, which covers the Tampa region.

He now practices as an internist in Brevard County, Florida.

In Congress, Weldon raised concerns about the safety of some vaccines and promoted the false narrative that a former vaccine ingredient, thimerosal, caused autism, the Washington Post reported. Thimerosal has not been used in child vaccines for more than two decades. He also introduced a bill to move vaccine safety oversight from the CDC to an independent agency within HHS.

Trump said in a statement that Weldon “will proudly restore the CDC to its true purpose, and will work to end the Chronic Disease Epidemic.” 

But some physicians criticized Weldon for what they called his anti-vaccine views.

A version of this article first appeared on Medscape.com.

President-elect Donald Trump’s vision for the nation’s top health agencies is coming into focus with three nominations announced Nov. 22 that drew both criticism and praise:

• Surgeon and health researcher Martin A. Makary, MD, MPH, to lead the US Food and Drug Administration (FDA).
• Former Republican congressman and physician David J. Weldon, MD, for director of the US Centers for Disease Control and Prevention (CDC).
• Fox News contributor Janette Nesheiwat, MD, for surgeon general.

Earlier in November, Trump nominated vaccine skeptic and former presidential candidate Robert F. Kennedy Jr. to lead the US Department of Health and Human Services (HHS). 

Here’s what to know about the latest nominees, who, like Kennedy, must be confirmed by the US Senate.

 

Martin A. Makary

Currently a professor at the Johns Hopkins School of Medicine and chief of islet transplant surgery at Johns Hopkins Hospital, Makary co-invented in 2006 a surgery checklist that became a widely-used patient safety tool. 

As a US FDA commissioner, Makary would preside over a $6.5 billion agency with more than 18,000 employees. The agency, part of HHS, oversees human and animal drugs and vaccines, medical devices, food, tobacco and other products. Some of Makary’s views align closely with those of HHS nominee Kennedy. 

Makary is also chief medical officer of telehealth platform Sesame.

Makary was primarily known as a health researcher and author of books about price transparency and the cost of health care until the COVID-19 pandemic, when he became an outspoken critic of the federal response, lambasting restrictions and mandates advocated by the CDC and other public health officials. 

In 2023, Makary told the House Select Subcommittee on the COVID Pandemic that federal officials had ignored what he called “natural immunity.” Studies have shown that natural immunity is “at least as effective as vaccinated immunity, and probably better,” testified Makary.

Makary called for an overhaul of the US FDA in a 2021 Fox News opinion, saying that its culture was “defined by counterproductive rigidity and a refusal to adapt.”

Blind Spots, his most recent book, takes on what he calls “medical dogma” and challenges conventional views on subjects ranging from the microbiome to marijuana to cancer prevention, hormone replacement therapy, antibiotics and peanut allergies.

In an interview he posted to X, Makary blames inappropriate use of antibiotics for a variety of childhood illnesses. He cites increases in obesity, learning disabilities, attention deficit disorder, asthma, celiac disease, ulcerative colitis and Crohn’s disease as all potentially causally related to antibiotics given in childhood.

Makary is an advisor to two conservative think tanks, the Foundation for Research on Equal Opportunity, and to Paragon Health Institute, begun in 2021 by two former top officials in the previous Trump administration.

Makary would “cut the bureaucratic red tape at the agency to make sure Americans get the medical cures and treatments they deserve,” Trump said on his social media platform, Truth Social, and in a press release.

While Los Angeles Times owner and physician-entrepreneur Patrick Soon-Shiong, MBBCh, MSc, praised the nomination of Makary (and the two other nominees) as “inspired,” other physicians criticized Makary for his anti-COVID mandate views and “fear-mongering” over COVID vaccine side effects.

 

Janette Nesheiwat

As surgeon general, Nesheiwat would serve as the top “health communicator in chief” and oversee the 6000 member US Public Health Service Commissioned Corps.

She is a frequent medical contributor to Fox News and serves as a medical director for a group of urgent care clinics in New York. She received her medical degree from the American University of the Caribbean School of Medicine and completed a family medicine residency at the University of Arkansas for Medical Sciences. She is board-certified in family medicine.

Nesheiwat sells vitamin supplements on her website and in December will publish a book on “miracles in medicine” and her Christian faith. 

Trump said in a statement that Nesheiwat “is a fierce advocate and strong communicator for preventive medicine and public health. She is committed to ensuring that Americans have access to affordable, quality healthcare, and believes in empowering individuals to take charge of their health to live longer, healthier lives.”

While Nesheiwat was critical of COVID mandates, she voiced more support for COVID vaccines and mask-wearing during the pandemic than her fellow nominees, leading some Trump supporters to criticize her nomination. 

“A good appointment, happy about this: I got to know @DoctorJanette during the pandemic, exchanging information. She is very smart, thoughtful, interested in learning, and a compassionate doctor, and…a truly nice person,” noted vaccine researcher Peter Hotez, MD, PhD, said on X.

 

David J. Weldon

If confirmed, former congressman Weldon would oversee the sprawling CDC, an agency with a roughly $17 billion budget, 15,000 employees or contractors, and numerous centers covering everything from health statistics to vaccines to epidemiology.

After earning his medical degree from the University at Buffalo School of Medicine, Weldon served in the US Army and US Army reserve. The Republican later served for 14 years in Congress representing Florida’s 15th district, which covers the Tampa region.

He now practices as an internist in Brevard County, Florida.

In Congress, Weldon raised concerns about the safety of some vaccines and promoted the false narrative that a former vaccine ingredient, thimerosal, caused autism, the Washington Post reported. Thimerosal has not been used in child vaccines for more than two decades. He also introduced a bill to move vaccine safety oversight from the CDC to an independent agency within HHS.

Trump said in a statement that Weldon “will proudly restore the CDC to its true purpose, and will work to end the Chronic Disease Epidemic.” 

But some physicians criticized Weldon for what they called his anti-vaccine views.

A version of this article first appeared on Medscape.com.

President-elect Donald Trump’s vision for the nation’s top health agencies is coming into focus with three nominations announced Nov. 22 that drew both criticism and praise:

• Surgeon and health researcher Martin A. Makary, MD, MPH, to lead the US Food and Drug Administration (FDA).
• Former Republican congressman and physician David J. Weldon, MD, for director of the US Centers for Disease Control and Prevention (CDC).
• Fox News contributor Janette Nesheiwat, MD, for surgeon general.

Earlier in November, Trump nominated vaccine skeptic and former presidential candidate Robert F. Kennedy Jr. to lead the US Department of Health and Human Services (HHS). 

Here’s what to know about the latest nominees, who, like Kennedy, must be confirmed by the US Senate.

 

Martin A. Makary

Currently a professor at the Johns Hopkins School of Medicine and chief of islet transplant surgery at Johns Hopkins Hospital, Makary co-invented in 2006 a surgery checklist that became a widely-used patient safety tool. 

As a US FDA commissioner, Makary would preside over a $6.5 billion agency with more than 18,000 employees. The agency, part of HHS, oversees human and animal drugs and vaccines, medical devices, food, tobacco and other products. Some of Makary’s views align closely with those of HHS nominee Kennedy. 

Makary is also chief medical officer of telehealth platform Sesame.

Makary was primarily known as a health researcher and author of books about price transparency and the cost of health care until the COVID-19 pandemic, when he became an outspoken critic of the federal response, lambasting restrictions and mandates advocated by the CDC and other public health officials. 

In 2023, Makary told the House Select Subcommittee on the COVID Pandemic that federal officials had ignored what he called “natural immunity.” Studies have shown that natural immunity is “at least as effective as vaccinated immunity, and probably better,” testified Makary.

Makary called for an overhaul of the US FDA in a 2021 Fox News opinion, saying that its culture was “defined by counterproductive rigidity and a refusal to adapt.”

Blind Spots, his most recent book, takes on what he calls “medical dogma” and challenges conventional views on subjects ranging from the microbiome to marijuana to cancer prevention, hormone replacement therapy, antibiotics and peanut allergies.

In an interview he posted to X, Makary blames inappropriate use of antibiotics for a variety of childhood illnesses. He cites increases in obesity, learning disabilities, attention deficit disorder, asthma, celiac disease, ulcerative colitis and Crohn’s disease as all potentially causally related to antibiotics given in childhood.

Makary is an advisor to two conservative think tanks, the Foundation for Research on Equal Opportunity, and to Paragon Health Institute, begun in 2021 by two former top officials in the previous Trump administration.

Makary would “cut the bureaucratic red tape at the agency to make sure Americans get the medical cures and treatments they deserve,” Trump said on his social media platform, Truth Social, and in a press release.

While Los Angeles Times owner and physician-entrepreneur Patrick Soon-Shiong, MBBCh, MSc, praised the nomination of Makary (and the two other nominees) as “inspired,” other physicians criticized Makary for his anti-COVID mandate views and “fear-mongering” over COVID vaccine side effects.

 

Janette Nesheiwat

As surgeon general, Nesheiwat would serve as the top “health communicator in chief” and oversee the 6000 member US Public Health Service Commissioned Corps.

She is a frequent medical contributor to Fox News and serves as a medical director for a group of urgent care clinics in New York. She received her medical degree from the American University of the Caribbean School of Medicine and completed a family medicine residency at the University of Arkansas for Medical Sciences. She is board-certified in family medicine.

Nesheiwat sells vitamin supplements on her website and in December will publish a book on “miracles in medicine” and her Christian faith. 

Trump said in a statement that Nesheiwat “is a fierce advocate and strong communicator for preventive medicine and public health. She is committed to ensuring that Americans have access to affordable, quality healthcare, and believes in empowering individuals to take charge of their health to live longer, healthier lives.”

While Nesheiwat was critical of COVID mandates, she voiced more support for COVID vaccines and mask-wearing during the pandemic than her fellow nominees, leading some Trump supporters to criticize her nomination. 

“A good appointment, happy about this: I got to know @DoctorJanette during the pandemic, exchanging information. She is very smart, thoughtful, interested in learning, and a compassionate doctor, and…a truly nice person,” noted vaccine researcher Peter Hotez, MD, PhD, said on X.

 

David J. Weldon

If confirmed, former congressman Weldon would oversee the sprawling CDC, an agency with a roughly $17 billion budget, 15,000 employees or contractors, and numerous centers covering everything from health statistics to vaccines to epidemiology.

After earning his medical degree from the University at Buffalo School of Medicine, Weldon served in the US Army and US Army reserve. The Republican later served for 14 years in Congress representing Florida’s 15th district, which covers the Tampa region.

He now practices as an internist in Brevard County, Florida.

In Congress, Weldon raised concerns about the safety of some vaccines and promoted the false narrative that a former vaccine ingredient, thimerosal, caused autism, the Washington Post reported. Thimerosal has not been used in child vaccines for more than two decades. He also introduced a bill to move vaccine safety oversight from the CDC to an independent agency within HHS.

Trump said in a statement that Weldon “will proudly restore the CDC to its true purpose, and will work to end the Chronic Disease Epidemic.” 

But some physicians criticized Weldon for what they called his anti-vaccine views.

A version of this article first appeared on Medscape.com.

Suicide and self-harm continue to be serious concerns in Europe, despite decreasing rates over the past two decades. In 2021 alone, 47,346 people died by suicide in the European Union, close to 1% of all deaths reported that year. Measures have been taken at population, subpopulation, and individual levels to prevent suicide and suicide attempts. But can more be done? Yes, according to experts.

Researchers are investigating factors that contribute to suicide at the individual level, as well as environmental and societal pressures that may increase risk. New predictive tools show promise in identifying individuals at high risk, and ongoing programs offer hope for early and ongoing interventions. Successful preventive strategies are multimodal, emphasizing the need for trained primary care and mental health professionals to work together to identify and support individuals at risk at every age and in all settings.

 

‘Radical Change’ Needed

The medical community’s approach to suicide prevention is all wrong, according to Igor Galynker, MD, PhD, clinical professor of psychiatry and director of the Mount Sinai Suicide Prevention Research Lab in New York City. 

Galynker is collaborating with colleagues in various parts of the world, including Europe, to validate the use of suicide crisis syndrome (SCS) as a diagnosis to help imminent suicide risk evaluation and treatment.

SCS is a negative cognitive-affective state associated with imminent suicidal behavior in those who are already at high risk for suicide. Galynker and his colleagues want to see SCS recognized and accepted as a suicide-specific diagnosis in the Diagnostic and Statistical Manual of Mental Disorders and the World Health Organization’s International Classification of Diseases. 

Currently, he explained to this news organization, clinicians depend on a person at risk for suicide telling them that this is what they are feeling. This is “absurd,” he said, because people in this situation are in acute pain and distress and cannot answer accurately.

“It is the most lethal psychiatric condition, because people die from it ... yet we rely on people at the worst moment of their lives to tell us accurately when and how they are going to kill themselves. We don’t ask people with serious mental illness to diagnose their own mental illness and rely on that diagnosis.”

Data show that most people who attempt or die by suicide deny suicidal thoughts when assessed by healthcare providers using current questionnaires and scales. Thus, there needs to be “a radical change” in how patients at acute risk are assessed and treated to help “prevent suicides and avoid lost opportunities to intervene,” he said.

Galynker explained that SCS is the final and most acute stage of the “ narrative crisis model” of suicide, which reflects the progression of suicidal risk from chronic risk factors to imminent suicidal risk. “The narrative crisis model has four distinct and successive stages, with specific guidance and applicable interventions that enable patients to receive a stage-specific treatment.”

“Suicide crisis syndrome is a very treatable syndrome that rapidly resolves” with appropriate interventions, he said. “Once it is treated, the patient can engage with psychotherapy and other treatments.”

Galynker said he and his colleagues have had encouraging results with their studies so far on the subjective and objective views of clinicians using the risk assessment tools they are developing to assess suicidal ideation. Further studies are ongoing. 

 

Improving Prediction

There is definitely room for improvement in current approaches to suicide prevention, said Raffaella Calati, PhD, assistant professor of clinical psychology at the University of Milano-Bicocca, Italy, who has had research collaborations with Galynker.

Calati advocates for a more integrated approach across disciplines, institutions, and the community to provide an effective support network for those at risk. 

Accurately predicting suicide risk is challenging, she told this news organization. She and colleagues are working to develop more precise predictive tools for identifying individuals at risk, often by leveraging artificial intelligence and data analytics. They have designed and implemented app-based interventions for psychiatric patients at risk for suicide and university students with psychological distress. The interventions are personalized and based on multiple approaches, such as cognitive-behavioral therapy (CBT) and third-wave CBT. 

The results of current studies are preliminary, she acknowledged, “but even if apps are extremely complex, our projects received high interest from participants and the scientific community,” she said. The aim now is to integrate these tools into healthcare systems so that monitoring high-risk patients becomes part of regular care. 

Another area of focus is the identification of specific subtypes of individuals at risk for suicide, particularly by examining factors such as pain, dissociation, and interoception — the ability to sense and interpret internal signals from the body. 

“By understanding how these experiences intersect and contribute to suicide risk, I aim to identify distinct profiles within at-risk populations, which could ultimately enable more tailored and effective prevention efforts,” she said.

Her work also involves meta-research to build large, comprehensive datasets that increase statistical power for exploring suicide risk factors, such as physical health conditions and symptoms associated with borderline personality disorder. By creating these datasets, she aims to “improve understanding of how various factors contribute to suicide risk, ultimately supporting more effective prevention strategies.”

 

Country-Level Efforts

Preventive work is underway in other countries as well. In Nordic countries such as Denmark, Finland, and Sweden, large-scale national registries that track people’s medical histories, prescriptions, and demographic information are being used to develop predictive algorithms that identify those at high risk for suicide. The predictions are based on known risk factors like previous mental health diagnoses, substance abuse, and social determinants of health.

A recent Norwegian study found that a novel assessment tool used at admission to an acute inpatient unit was a powerful predictor of suicide within 3 years post-discharge.

Researchers in the Netherlands have also recently co-designed a digital integrated suicide prevention program, which has led to a significant reduction in suicide mortality. 

SUPREMOCOL (suicide prevention by monitoring and collaborative care) was implemented in Noord-Brabant, a province in the Netherlands that historically had high suicide rates. It combines technology and personal care, allowing healthcare providers to track a person’s mental health, including by phone calls, text messages, and mobile apps that help people express their feelings and report any changes in their mental state. By staying connected, the program aims to identify warning signs early and provide timely interventions.

The results from the 5-year project showed that rates dropped by 21.5%, from 14.4 per 100,000 to 11.8 per 100,000, and remained low, with a rate of 11.3 per 100,000 by 2021.

Finland used to have one of the highest suicide rates in the world. Now it is implementing its suicide prevention program for 2020-2030, with 36 proposed measures to prevent suicide mortality. 

The program includes measures such as increasing public awareness, early intervention, supporting at-risk groups, developing new treatment options, and enhancing research efforts. Earlier successful interventions included limiting access to firearms and poison, and increasing use of antidepressants and other targeted interventions.

“A key is to ensure that the individuals at risk of suicide have access to adequate, timely, and evidence-based care,” said Timo Partonen, MD, research professor at the Finnish Institute for Health and Welfare and associate professor of psychiatry at the University of Helsinki.

“Emergency and frontline professionals, as well as general practitioners and occupational health physicians, have a key role in identifying people at risk of suicide,” he noted. “High-quality competencies will be developed for healthcare professionals, including access to evidence-based suicide prevention models for addressing and assessing suicide risk.” 

 

Global Strategies

Policymakers across Europe are increasingly recognizing the importance of enhanced public health approaches to suicide prevention. 

The recently adopted EU Action Plan on Mental Health emphasizes the need for comprehensive suicide prevention strategies across Europe, including the promotion of mental health literacy and the provision of accessible mental health services.

The plan was informed by initiatives such as the European Alliance Against Depression (EAAD)-Best project, which ran from 2021 until March 2024. The collaborative project brought together researchers, healthcare providers, and community organizations to improve care for patients with depression and to prevent suicidal behavior in Europe. 

The multimodal approach included community engagement and training for healthcare professionals, as well as promoting the international uptake of the iFightDepression tool, an internet-based self-management approach for patients with depression. It has shown promise in reducing suicide rates in participating regions, including Europe, Australia, South America, and Africa.

“What we now know is that multiple interventions produce a synergic effect with a tendency to reduce suicidal behavior,” said EAAD founding member Ricardo Gusmão, MD, PhD, professor of public mental health at the University of Porto, Portugal. Current approaches to suicide prevention globally vary widely, with “many, fragmentary, atomized interventions, and we know that none of them, in isolation, produces spectacular results.” 

Gusmão explained that promising national suicide prevention strategies are based on multicomponent community interventions. On the clinical side, they encompass training primary health and specialized mental health professionals, and have a guaranteed chain of care and functioning pathways for access. They also involve educational programs in schools, universities, prisons, work settings, and geriatric care centers. Additionally, they have well-developed good standards for media communication and health marketing campaigns on well-being and mental health literacy.

Relevant and cohesive themes for successful strategies include the promotion of positive mental health, the identification and available treatments for depression and common mental disorders, and the management of suicidal crisis stigma. 

“We are now focusing on workplace settings and vulnerable groups such as youth, the elderly, unemployed, migrants and, of course, people affected by mental disorders,” he said. “Suicide prevention is like a web that must be weaved by long-lasting efforts and intersectoral collaboration.”

“Even one suicide is one too many,” Brendan Kelly, MD, PhD, professor of psychiatry, Trinity College Dublin, and author of The Modern Psychiatrist’s Guide to Contemporary Practice, told this news organization. “Nobody is born wanting to die by suicide. And every suicide is an individual tragedy, not a statistic. We need to work ever more intensively to reduce rates of suicide. All contributions to research and fresh thinking are welcome.”

Galynker, Calati, Partonen, and Kelly have disclosed no relevant financial relationships.  Gusmão has been involved in organizing Janssen-funded trainings for registrars on suicidal crisis management. 

 

A version of this article first appeared on Medscape.com.

Suicide and self-harm continue to be serious concerns in Europe, despite decreasing rates over the past two decades. In 2021 alone, 47,346 people died by suicide in the European Union, close to 1% of all deaths reported that year. Measures have been taken at population, subpopulation, and individual levels to prevent suicide and suicide attempts. But can more be done? Yes, according to experts.

Researchers are investigating factors that contribute to suicide at the individual level, as well as environmental and societal pressures that may increase risk. New predictive tools show promise in identifying individuals at high risk, and ongoing programs offer hope for early and ongoing interventions. Successful preventive strategies are multimodal, emphasizing the need for trained primary care and mental health professionals to work together to identify and support individuals at risk at every age and in all settings.

 

‘Radical Change’ Needed

The medical community’s approach to suicide prevention is all wrong, according to Igor Galynker, MD, PhD, clinical professor of psychiatry and director of the Mount Sinai Suicide Prevention Research Lab in New York City. 

Galynker is collaborating with colleagues in various parts of the world, including Europe, to validate the use of suicide crisis syndrome (SCS) as a diagnosis to help imminent suicide risk evaluation and treatment.

SCS is a negative cognitive-affective state associated with imminent suicidal behavior in those who are already at high risk for suicide. Galynker and his colleagues want to see SCS recognized and accepted as a suicide-specific diagnosis in the Diagnostic and Statistical Manual of Mental Disorders and the World Health Organization’s International Classification of Diseases. 

Currently, he explained to this news organization, clinicians depend on a person at risk for suicide telling them that this is what they are feeling. This is “absurd,” he said, because people in this situation are in acute pain and distress and cannot answer accurately.

“It is the most lethal psychiatric condition, because people die from it ... yet we rely on people at the worst moment of their lives to tell us accurately when and how they are going to kill themselves. We don’t ask people with serious mental illness to diagnose their own mental illness and rely on that diagnosis.”

Data show that most people who attempt or die by suicide deny suicidal thoughts when assessed by healthcare providers using current questionnaires and scales. Thus, there needs to be “a radical change” in how patients at acute risk are assessed and treated to help “prevent suicides and avoid lost opportunities to intervene,” he said.

Galynker explained that SCS is the final and most acute stage of the “ narrative crisis model” of suicide, which reflects the progression of suicidal risk from chronic risk factors to imminent suicidal risk. “The narrative crisis model has four distinct and successive stages, with specific guidance and applicable interventions that enable patients to receive a stage-specific treatment.”

“Suicide crisis syndrome is a very treatable syndrome that rapidly resolves” with appropriate interventions, he said. “Once it is treated, the patient can engage with psychotherapy and other treatments.”

Galynker said he and his colleagues have had encouraging results with their studies so far on the subjective and objective views of clinicians using the risk assessment tools they are developing to assess suicidal ideation. Further studies are ongoing. 

 

Improving Prediction

There is definitely room for improvement in current approaches to suicide prevention, said Raffaella Calati, PhD, assistant professor of clinical psychology at the University of Milano-Bicocca, Italy, who has had research collaborations with Galynker.

Calati advocates for a more integrated approach across disciplines, institutions, and the community to provide an effective support network for those at risk. 

Accurately predicting suicide risk is challenging, she told this news organization. She and colleagues are working to develop more precise predictive tools for identifying individuals at risk, often by leveraging artificial intelligence and data analytics. They have designed and implemented app-based interventions for psychiatric patients at risk for suicide and university students with psychological distress. The interventions are personalized and based on multiple approaches, such as cognitive-behavioral therapy (CBT) and third-wave CBT. 

The results of current studies are preliminary, she acknowledged, “but even if apps are extremely complex, our projects received high interest from participants and the scientific community,” she said. The aim now is to integrate these tools into healthcare systems so that monitoring high-risk patients becomes part of regular care. 

Another area of focus is the identification of specific subtypes of individuals at risk for suicide, particularly by examining factors such as pain, dissociation, and interoception — the ability to sense and interpret internal signals from the body. 

“By understanding how these experiences intersect and contribute to suicide risk, I aim to identify distinct profiles within at-risk populations, which could ultimately enable more tailored and effective prevention efforts,” she said.

Her work also involves meta-research to build large, comprehensive datasets that increase statistical power for exploring suicide risk factors, such as physical health conditions and symptoms associated with borderline personality disorder. By creating these datasets, she aims to “improve understanding of how various factors contribute to suicide risk, ultimately supporting more effective prevention strategies.”

 

Country-Level Efforts

Preventive work is underway in other countries as well. In Nordic countries such as Denmark, Finland, and Sweden, large-scale national registries that track people’s medical histories, prescriptions, and demographic information are being used to develop predictive algorithms that identify those at high risk for suicide. The predictions are based on known risk factors like previous mental health diagnoses, substance abuse, and social determinants of health.

A recent Norwegian study found that a novel assessment tool used at admission to an acute inpatient unit was a powerful predictor of suicide within 3 years post-discharge.

Researchers in the Netherlands have also recently co-designed a digital integrated suicide prevention program, which has led to a significant reduction in suicide mortality. 

SUPREMOCOL (suicide prevention by monitoring and collaborative care) was implemented in Noord-Brabant, a province in the Netherlands that historically had high suicide rates. It combines technology and personal care, allowing healthcare providers to track a person’s mental health, including by phone calls, text messages, and mobile apps that help people express their feelings and report any changes in their mental state. By staying connected, the program aims to identify warning signs early and provide timely interventions.

The results from the 5-year project showed that rates dropped by 21.5%, from 14.4 per 100,000 to 11.8 per 100,000, and remained low, with a rate of 11.3 per 100,000 by 2021.

Finland used to have one of the highest suicide rates in the world. Now it is implementing its suicide prevention program for 2020-2030, with 36 proposed measures to prevent suicide mortality. 

The program includes measures such as increasing public awareness, early intervention, supporting at-risk groups, developing new treatment options, and enhancing research efforts. Earlier successful interventions included limiting access to firearms and poison, and increasing use of antidepressants and other targeted interventions.

“A key is to ensure that the individuals at risk of suicide have access to adequate, timely, and evidence-based care,” said Timo Partonen, MD, research professor at the Finnish Institute for Health and Welfare and associate professor of psychiatry at the University of Helsinki.

“Emergency and frontline professionals, as well as general practitioners and occupational health physicians, have a key role in identifying people at risk of suicide,” he noted. “High-quality competencies will be developed for healthcare professionals, including access to evidence-based suicide prevention models for addressing and assessing suicide risk.” 

 

Global Strategies

Policymakers across Europe are increasingly recognizing the importance of enhanced public health approaches to suicide prevention. 

The recently adopted EU Action Plan on Mental Health emphasizes the need for comprehensive suicide prevention strategies across Europe, including the promotion of mental health literacy and the provision of accessible mental health services.

The plan was informed by initiatives such as the European Alliance Against Depression (EAAD)-Best project, which ran from 2021 until March 2024. The collaborative project brought together researchers, healthcare providers, and community organizations to improve care for patients with depression and to prevent suicidal behavior in Europe. 

The multimodal approach included community engagement and training for healthcare professionals, as well as promoting the international uptake of the iFightDepression tool, an internet-based self-management approach for patients with depression. It has shown promise in reducing suicide rates in participating regions, including Europe, Australia, South America, and Africa.

“What we now know is that multiple interventions produce a synergic effect with a tendency to reduce suicidal behavior,” said EAAD founding member Ricardo Gusmão, MD, PhD, professor of public mental health at the University of Porto, Portugal. Current approaches to suicide prevention globally vary widely, with “many, fragmentary, atomized interventions, and we know that none of them, in isolation, produces spectacular results.” 

Gusmão explained that promising national suicide prevention strategies are based on multicomponent community interventions. On the clinical side, they encompass training primary health and specialized mental health professionals, and have a guaranteed chain of care and functioning pathways for access. They also involve educational programs in schools, universities, prisons, work settings, and geriatric care centers. Additionally, they have well-developed good standards for media communication and health marketing campaigns on well-being and mental health literacy.

Relevant and cohesive themes for successful strategies include the promotion of positive mental health, the identification and available treatments for depression and common mental disorders, and the management of suicidal crisis stigma. 

“We are now focusing on workplace settings and vulnerable groups such as youth, the elderly, unemployed, migrants and, of course, people affected by mental disorders,” he said. “Suicide prevention is like a web that must be weaved by long-lasting efforts and intersectoral collaboration.”

“Even one suicide is one too many,” Brendan Kelly, MD, PhD, professor of psychiatry, Trinity College Dublin, and author of The Modern Psychiatrist’s Guide to Contemporary Practice, told this news organization. “Nobody is born wanting to die by suicide. And every suicide is an individual tragedy, not a statistic. We need to work ever more intensively to reduce rates of suicide. All contributions to research and fresh thinking are welcome.”

Galynker, Calati, Partonen, and Kelly have disclosed no relevant financial relationships.  Gusmão has been involved in organizing Janssen-funded trainings for registrars on suicidal crisis management. 

 

A version of this article first appeared on Medscape.com.

Suicide and self-harm continue to be serious concerns in Europe, despite decreasing rates over the past two decades. In 2021 alone, 47,346 people died by suicide in the European Union, close to 1% of all deaths reported that year. Measures have been taken at population, subpopulation, and individual levels to prevent suicide and suicide attempts. But can more be done? Yes, according to experts.

Researchers are investigating factors that contribute to suicide at the individual level, as well as environmental and societal pressures that may increase risk. New predictive tools show promise in identifying individuals at high risk, and ongoing programs offer hope for early and ongoing interventions. Successful preventive strategies are multimodal, emphasizing the need for trained primary care and mental health professionals to work together to identify and support individuals at risk at every age and in all settings.

 

‘Radical Change’ Needed

The medical community’s approach to suicide prevention is all wrong, according to Igor Galynker, MD, PhD, clinical professor of psychiatry and director of the Mount Sinai Suicide Prevention Research Lab in New York City. 

Galynker is collaborating with colleagues in various parts of the world, including Europe, to validate the use of suicide crisis syndrome (SCS) as a diagnosis to help imminent suicide risk evaluation and treatment.

SCS is a negative cognitive-affective state associated with imminent suicidal behavior in those who are already at high risk for suicide. Galynker and his colleagues want to see SCS recognized and accepted as a suicide-specific diagnosis in the Diagnostic and Statistical Manual of Mental Disorders and the World Health Organization’s International Classification of Diseases. 

Currently, he explained to this news organization, clinicians depend on a person at risk for suicide telling them that this is what they are feeling. This is “absurd,” he said, because people in this situation are in acute pain and distress and cannot answer accurately.

“It is the most lethal psychiatric condition, because people die from it ... yet we rely on people at the worst moment of their lives to tell us accurately when and how they are going to kill themselves. We don’t ask people with serious mental illness to diagnose their own mental illness and rely on that diagnosis.”

Data show that most people who attempt or die by suicide deny suicidal thoughts when assessed by healthcare providers using current questionnaires and scales. Thus, there needs to be “a radical change” in how patients at acute risk are assessed and treated to help “prevent suicides and avoid lost opportunities to intervene,” he said.

Galynker explained that SCS is the final and most acute stage of the “ narrative crisis model” of suicide, which reflects the progression of suicidal risk from chronic risk factors to imminent suicidal risk. “The narrative crisis model has four distinct and successive stages, with specific guidance and applicable interventions that enable patients to receive a stage-specific treatment.”

“Suicide crisis syndrome is a very treatable syndrome that rapidly resolves” with appropriate interventions, he said. “Once it is treated, the patient can engage with psychotherapy and other treatments.”

Galynker said he and his colleagues have had encouraging results with their studies so far on the subjective and objective views of clinicians using the risk assessment tools they are developing to assess suicidal ideation. Further studies are ongoing. 

 

Improving Prediction

There is definitely room for improvement in current approaches to suicide prevention, said Raffaella Calati, PhD, assistant professor of clinical psychology at the University of Milano-Bicocca, Italy, who has had research collaborations with Galynker.

Calati advocates for a more integrated approach across disciplines, institutions, and the community to provide an effective support network for those at risk. 

Accurately predicting suicide risk is challenging, she told this news organization. She and colleagues are working to develop more precise predictive tools for identifying individuals at risk, often by leveraging artificial intelligence and data analytics. They have designed and implemented app-based interventions for psychiatric patients at risk for suicide and university students with psychological distress. The interventions are personalized and based on multiple approaches, such as cognitive-behavioral therapy (CBT) and third-wave CBT. 

The results of current studies are preliminary, she acknowledged, “but even if apps are extremely complex, our projects received high interest from participants and the scientific community,” she said. The aim now is to integrate these tools into healthcare systems so that monitoring high-risk patients becomes part of regular care. 

Another area of focus is the identification of specific subtypes of individuals at risk for suicide, particularly by examining factors such as pain, dissociation, and interoception — the ability to sense and interpret internal signals from the body. 

“By understanding how these experiences intersect and contribute to suicide risk, I aim to identify distinct profiles within at-risk populations, which could ultimately enable more tailored and effective prevention efforts,” she said.

Her work also involves meta-research to build large, comprehensive datasets that increase statistical power for exploring suicide risk factors, such as physical health conditions and symptoms associated with borderline personality disorder. By creating these datasets, she aims to “improve understanding of how various factors contribute to suicide risk, ultimately supporting more effective prevention strategies.”

 

Country-Level Efforts

Preventive work is underway in other countries as well. In Nordic countries such as Denmark, Finland, and Sweden, large-scale national registries that track people’s medical histories, prescriptions, and demographic information are being used to develop predictive algorithms that identify those at high risk for suicide. The predictions are based on known risk factors like previous mental health diagnoses, substance abuse, and social determinants of health.

A recent Norwegian study found that a novel assessment tool used at admission to an acute inpatient unit was a powerful predictor of suicide within 3 years post-discharge.

Researchers in the Netherlands have also recently co-designed a digital integrated suicide prevention program, which has led to a significant reduction in suicide mortality. 

SUPREMOCOL (suicide prevention by monitoring and collaborative care) was implemented in Noord-Brabant, a province in the Netherlands that historically had high suicide rates. It combines technology and personal care, allowing healthcare providers to track a person’s mental health, including by phone calls, text messages, and mobile apps that help people express their feelings and report any changes in their mental state. By staying connected, the program aims to identify warning signs early and provide timely interventions.

The results from the 5-year project showed that rates dropped by 21.5%, from 14.4 per 100,000 to 11.8 per 100,000, and remained low, with a rate of 11.3 per 100,000 by 2021.

Finland used to have one of the highest suicide rates in the world. Now it is implementing its suicide prevention program for 2020-2030, with 36 proposed measures to prevent suicide mortality. 

The program includes measures such as increasing public awareness, early intervention, supporting at-risk groups, developing new treatment options, and enhancing research efforts. Earlier successful interventions included limiting access to firearms and poison, and increasing use of antidepressants and other targeted interventions.

“A key is to ensure that the individuals at risk of suicide have access to adequate, timely, and evidence-based care,” said Timo Partonen, MD, research professor at the Finnish Institute for Health and Welfare and associate professor of psychiatry at the University of Helsinki.

“Emergency and frontline professionals, as well as general practitioners and occupational health physicians, have a key role in identifying people at risk of suicide,” he noted. “High-quality competencies will be developed for healthcare professionals, including access to evidence-based suicide prevention models for addressing and assessing suicide risk.” 

 

Global Strategies

Policymakers across Europe are increasingly recognizing the importance of enhanced public health approaches to suicide prevention. 

The recently adopted EU Action Plan on Mental Health emphasizes the need for comprehensive suicide prevention strategies across Europe, including the promotion of mental health literacy and the provision of accessible mental health services.

The plan was informed by initiatives such as the European Alliance Against Depression (EAAD)-Best project, which ran from 2021 until March 2024. The collaborative project brought together researchers, healthcare providers, and community organizations to improve care for patients with depression and to prevent suicidal behavior in Europe. 

The multimodal approach included community engagement and training for healthcare professionals, as well as promoting the international uptake of the iFightDepression tool, an internet-based self-management approach for patients with depression. It has shown promise in reducing suicide rates in participating regions, including Europe, Australia, South America, and Africa.

“What we now know is that multiple interventions produce a synergic effect with a tendency to reduce suicidal behavior,” said EAAD founding member Ricardo Gusmão, MD, PhD, professor of public mental health at the University of Porto, Portugal. Current approaches to suicide prevention globally vary widely, with “many, fragmentary, atomized interventions, and we know that none of them, in isolation, produces spectacular results.” 

Gusmão explained that promising national suicide prevention strategies are based on multicomponent community interventions. On the clinical side, they encompass training primary health and specialized mental health professionals, and have a guaranteed chain of care and functioning pathways for access. They also involve educational programs in schools, universities, prisons, work settings, and geriatric care centers. Additionally, they have well-developed good standards for media communication and health marketing campaigns on well-being and mental health literacy.

Relevant and cohesive themes for successful strategies include the promotion of positive mental health, the identification and available treatments for depression and common mental disorders, and the management of suicidal crisis stigma. 

“We are now focusing on workplace settings and vulnerable groups such as youth, the elderly, unemployed, migrants and, of course, people affected by mental disorders,” he said. “Suicide prevention is like a web that must be weaved by long-lasting efforts and intersectoral collaboration.”

“Even one suicide is one too many,” Brendan Kelly, MD, PhD, professor of psychiatry, Trinity College Dublin, and author of The Modern Psychiatrist’s Guide to Contemporary Practice, told this news organization. “Nobody is born wanting to die by suicide. And every suicide is an individual tragedy, not a statistic. We need to work ever more intensively to reduce rates of suicide. All contributions to research and fresh thinking are welcome.”

Galynker, Calati, Partonen, and Kelly have disclosed no relevant financial relationships.  Gusmão has been involved in organizing Janssen-funded trainings for registrars on suicidal crisis management. 

 

A version of this article first appeared on Medscape.com.

Interest is growing in the role of nutrition as means of slowing, or even preventing, neurodegeneration in patients with Parkinson’s disease.

For 15 years, John Duda, MD, national director of the VA Parkinson’s Disease Research, Education and Clinical Centers, has urged his patients to “keep waiting” for effective treatments to manage both motor and nonmotor symptoms of Parkinson’s disease.

However, Duda, who also serves as director of the Brain Wellness Clinic at the Corporal Michael J. Crescenz VA Medical Center in Philadelphia, Pennsylvania, recognized the persistent lack of effective drugs to address these symptoms. This prompted him to consider what other evidence-based strategies he could use to support his patients. 

“I recognized that nutritional approaches within a broader program that includes medication review, stress management, social connections, adequate sleep, and physical exercise could make a real difference,” he said.

Observational studies have shown an inverse association between dietary patterns and Parkinson’s disease risk, age of onset, symptom severity, and mortality rates — particularly with the Mediterranean diet (MeDi) and the MIND diet, which combines elements of MeDi and the Dietary Approaches to Stop Hypertension (DASH) diet. Although randomized controlled trials are still limited, the epidemiologic evidence supporting dietary interventions is “compelling,” said Duda. 

For example, a cross-sectional study comparing 167 participants with Parkinson’s disease vs 119 controls showed that later age of Parkinson’s disease onset correlated with adherence to the MIND diet in women, with a difference of up to 17.4 years (P < .001) between low and high dietary tertiles. 

The MeDi was correlated with later onset in men, with differences of up to 8.4 years (P = .002). As previously reported, a healthy diet emphasizing vegetables, fruits, nuts, and grains was inversely associated with prodromal features of Parkinson’s disease, including constipation, excessive daytime sleepiness, and depression. In addition, lower rates of Parkinson’s disease have been shown in populations following vegetarian and vegan dietary patterns. 

 

Does Parkinson’s disease Start in the Gut?

Parkinson’s disease is characterized by decreased short-chain fatty acid–producing bacteria and increased pro-inflammatory species linked to intestinal inflammation and alpha-synuclein aggregation. “There are reasons to believe that a-synuclein accumulation may start in the gut,” Duda noted.

Numerous studies implicate gut microbiome dysbiosis as a pathogenic mechanism in Parkinson’s disease, with gastrointestinal symptoms often predating motor symptoms. Dysbiosis might result in a pro-inflammatory state potentially linked to the recurrent gastrointestinal symptoms. Fecal microbiota transplant may restore a healthier gut environment and beneficially affect Parkinson’s disease symptoms, he said.

Some of the benefits conferred by the MeDi and other healthy diets may be mediated by improving the gut microbiome. Duda cited a study that showed that a 14-day ovo-lacto vegetarian diet intervention and a daily fecal enema for 8 days improved not only the microbiome but also Movement Disorder Society Unified Parkinson’s Disease Rating Scale—part III scores. 

Duda also reviewed the role of dietary interventions in addressing common Parkinson’s disease symptoms, such as orthostatic hypotension. He recommended that Parkinson’s disease patients with this condition should avoid eating large meals, increase dietary salt intake, increase fluid intake, and decrease alcohol intake.

Malnutrition affects close to 25% of those with Parkinson’s disease, which is partially attributable to diminished olfaction. Because the experience of taste is largely driven by a sense of smell, patients may be less interested in eating. Duda recommended increasing herbs, spices, and other flavors in food. High caloric–density foods, including nuts, nut butters, and seeds, can boost weight, he said. However, he added, any patient with significant weight loss should consult a nutritionist.

Constipation is one of the most debilitating symptoms of Parkinson’s disease, affecting up to 66% of patients. Duda advised increasing fluid intake, exercise, and dietary fiber and use of stool softeners and laxatives. The MeDi may reduce symptoms of constipation and have a beneficial effect on gut microbiota. 

Coffee may be helpful for sleepiness in Parkinson’s disease and may also confer neuroprotective, motor, and cognitive benefits. As an adjuvant treatment, caffeine may alter levodopa pharmacokinetics, reduce dyskinesia, improve gait in patients with freezing and may even reduce the risk of developing Parkinson’s disease, with a maximum benefit reached at approximately three cups of coffee daily.

 

Problematic Foods

There is also a growing body of evidence regarding the deleterious effects of ultraprocessed foods (UPFs), Duda said. He noted that a recent systematic review and meta-analysis of 28 studies showed that higher UPF intake was significantly associated with an enhanced risk for Parkinson’s disease (relative risk, 1.56; 95% CI, 1.21-2.02). As previously reported, UPFs have been tied to a host of adverse neurologic outcomes, including cognitive decline and stroke. 

Although protein is a necessary nutrient, incorporating it into the diet of Parkinson’s disease patients taking levodopa is complicated. Levodopa, a large neutral amino acid (LNAA), competes with other LNAAs for transport to the brain from the small intestine, Duda explained. 

“Some people notice that carbidopa-levodopa doesn’t work as well if taken with a high-protein meal.” He recommended taking carbidopa-levodopa 30 minutes before or 60 minutes after meals.

Rebecca Gilbert, MD, PhD, chief mission officer of the American Parkinson’s Disease Association, said that patients with Parkinson’s disease might want to avoid eating protein during the day, concentrating instead on carbohydrates and vegetables and saving the protein for the evening, which is closer to bedtime. Some evidence also supports the use of protein redistribution diets to enhance the clinical response to levodopa and reduce motor fluctuations. 

 

What About Supplements? 

It’s “hard to prove that one specific supplement can be protective against Parkinson’s disease because diet consists of many different components and the whole diet may be worth more than the sum of its parts,” Gilbert said. The evidence for individual supplements “isn’t robust enough to say they prevent or treat Parkinson’s disease.”

Research on the role of specific nutrients in Parkinson’s disease is conflicting, with no clear evidence supporting or refuting their benefits. For example, a study that followed participants for about 30 years showed no link between reduced Parkinson’s disease risk and vitamin B or folate intake. 

On the other hand, there is research suggesting that certain vitamins may help reduce Parkinson’s disease risk, although these nutrients do not operate in isolation. For instance, one recent study showed a connection between vitamins C and E and reduced Parkinson’s disease risk, but factors such as body mass index and coffee consumption appeared to influence the strength of this association.

Consuming polyunsaturated fatty acids along with reducing saturated fatty acid intake has been tied to a reduced risk for Parkinson’s disease. 

Additionally, certain foods may offer protective effects, including green and black tea, with consumption of three or more cups per day associated with a delay in motor symptom onset by 7.7 years. Foods high in nicotine content, such as those from the Solanaceae family — including peppers, tomatoes, tomato juice, and potatoes — have also been linked to potential protective benefits.

Diets rich in antioxidants, including carotenoids, lutein, and vitamins E and C, have been robustly linked to a reduced risk for parkinsonism and progression of parkinsonian symptoms in older adults.

Increasing the intake of dietary flavonoids, particularly tea, berry fruits, apples, red wine, and oranges or orange juice, can reduce Parkinson’s disease risk. One study showed that male participants in the highest quintile of total flavonoid consumption had a 40% lower Parkinson’s disease risk compared with those in the lowest quintile. Another study showed that flavonoid-rich foods were also associated with a lower risk for death in patients with Parkinson’s disease. 

 

Food as Medicine 

Although recent research shows that the drug development pipeline for Parkinson’s disease is robust, with a wide variety of approaches being developed and evaluated in phase 1 and 2, investigators note that only a limited number of disease-modifying treatments are transitioning to phase 3.

Duda noted that phytochemicals incorporated into the diet might target some of the same mechanisms that are targets of these drugs in development. 

“Flavonoids have been shown to stabilize alpha-synuclein in vitro,” he said. “Caffeine, curcumin, resveratrol, and eliminating meat and dairy inhibit mTOR [mammalian target of rapamycin], and mTOR inhibition results in increased autophagy that may help clear alpha-synuclein. Genestein, an isoflavone in soybeans, protects dopaminergic neurons by inhibiting microglia activation. Flavonoids inhibit inflammation by inhibiting release of NO [nitric oxide] and pro-inflammatory cytokines,” he noted. 

Ongoing studies of dietary interventions for Parkinson’s disease are exploring various areas, including the potential role of the ketogenic diet in protecting the gut microbiome, optimizing protein intake for muscle preservation and sleep, the effects of psyllium and wheat bran on weight and constipation, and the impact of a gluten-free diet.

 

Practical Tips for Healthy Eating 

Gilbert emphasized that there are no medications or interventions currently available that can delay a Parkinson’s disease diagnosis by up to 17 years, as some dietary patterns have been shown to do, and she noted that it’s not possible to replicate the MeDi diet in a pill. However, she recommended a practical approach to eating that includes a diet low in ultraprocessed foods and high in beneficial nutrients. She encouraged people to shop for “real food” and enjoy a variety of colorful fruits and vegetables.

Duda acknowledged that motivating patients to follow a healthy diet can be difficult. As a result, the focus often shifts to making small adjustments and modifications. For example, he suggested that instead of pairing meat with French fries, people could opt for vegetables or add greens to their meals. Similarly, instead of having eggs and bacon for breakfast, they might choose oatmeal.

Preparing whole-food, plant-based meals may take more time than patients are accustomed to, so Duda suggests that, if possible, patients involve loved ones in both the meal preparation and the meal itself. He explained that a healthy meal can become an opportunity for bonding and that the key is educating them about new meal-related concepts. 

Duda reported no relevant financial relationships with the pharmaceutical or food industries. He has received compensation from the Physicians Committee for Responsible Medicine for his lecture delivered at the conference and research grant support from the VA, the National Institutes of Health, the Michael J. Fox Foundation, and the Department of Defense unrelated to this topic. Gilbert reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Interest is growing in the role of nutrition as means of slowing, or even preventing, neurodegeneration in patients with Parkinson’s disease.

For 15 years, John Duda, MD, national director of the VA Parkinson’s Disease Research, Education and Clinical Centers, has urged his patients to “keep waiting” for effective treatments to manage both motor and nonmotor symptoms of Parkinson’s disease.

However, Duda, who also serves as director of the Brain Wellness Clinic at the Corporal Michael J. Crescenz VA Medical Center in Philadelphia, Pennsylvania, recognized the persistent lack of effective drugs to address these symptoms. This prompted him to consider what other evidence-based strategies he could use to support his patients. 

“I recognized that nutritional approaches within a broader program that includes medication review, stress management, social connections, adequate sleep, and physical exercise could make a real difference,” he said.

Observational studies have shown an inverse association between dietary patterns and Parkinson’s disease risk, age of onset, symptom severity, and mortality rates — particularly with the Mediterranean diet (MeDi) and the MIND diet, which combines elements of MeDi and the Dietary Approaches to Stop Hypertension (DASH) diet. Although randomized controlled trials are still limited, the epidemiologic evidence supporting dietary interventions is “compelling,” said Duda. 

For example, a cross-sectional study comparing 167 participants with Parkinson’s disease vs 119 controls showed that later age of Parkinson’s disease onset correlated with adherence to the MIND diet in women, with a difference of up to 17.4 years (P < .001) between low and high dietary tertiles. 

The MeDi was correlated with later onset in men, with differences of up to 8.4 years (P = .002). As previously reported, a healthy diet emphasizing vegetables, fruits, nuts, and grains was inversely associated with prodromal features of Parkinson’s disease, including constipation, excessive daytime sleepiness, and depression. In addition, lower rates of Parkinson’s disease have been shown in populations following vegetarian and vegan dietary patterns. 

 

Does Parkinson’s disease Start in the Gut?

Parkinson’s disease is characterized by decreased short-chain fatty acid–producing bacteria and increased pro-inflammatory species linked to intestinal inflammation and alpha-synuclein aggregation. “There are reasons to believe that a-synuclein accumulation may start in the gut,” Duda noted.

Numerous studies implicate gut microbiome dysbiosis as a pathogenic mechanism in Parkinson’s disease, with gastrointestinal symptoms often predating motor symptoms. Dysbiosis might result in a pro-inflammatory state potentially linked to the recurrent gastrointestinal symptoms. Fecal microbiota transplant may restore a healthier gut environment and beneficially affect Parkinson’s disease symptoms, he said.

Some of the benefits conferred by the MeDi and other healthy diets may be mediated by improving the gut microbiome. Duda cited a study that showed that a 14-day ovo-lacto vegetarian diet intervention and a daily fecal enema for 8 days improved not only the microbiome but also Movement Disorder Society Unified Parkinson’s Disease Rating Scale—part III scores. 

Duda also reviewed the role of dietary interventions in addressing common Parkinson’s disease symptoms, such as orthostatic hypotension. He recommended that Parkinson’s disease patients with this condition should avoid eating large meals, increase dietary salt intake, increase fluid intake, and decrease alcohol intake.

Malnutrition affects close to 25% of those with Parkinson’s disease, which is partially attributable to diminished olfaction. Because the experience of taste is largely driven by a sense of smell, patients may be less interested in eating. Duda recommended increasing herbs, spices, and other flavors in food. High caloric–density foods, including nuts, nut butters, and seeds, can boost weight, he said. However, he added, any patient with significant weight loss should consult a nutritionist.

Constipation is one of the most debilitating symptoms of Parkinson’s disease, affecting up to 66% of patients. Duda advised increasing fluid intake, exercise, and dietary fiber and use of stool softeners and laxatives. The MeDi may reduce symptoms of constipation and have a beneficial effect on gut microbiota. 

Coffee may be helpful for sleepiness in Parkinson’s disease and may also confer neuroprotective, motor, and cognitive benefits. As an adjuvant treatment, caffeine may alter levodopa pharmacokinetics, reduce dyskinesia, improve gait in patients with freezing and may even reduce the risk of developing Parkinson’s disease, with a maximum benefit reached at approximately three cups of coffee daily.

 

Problematic Foods

There is also a growing body of evidence regarding the deleterious effects of ultraprocessed foods (UPFs), Duda said. He noted that a recent systematic review and meta-analysis of 28 studies showed that higher UPF intake was significantly associated with an enhanced risk for Parkinson’s disease (relative risk, 1.56; 95% CI, 1.21-2.02). As previously reported, UPFs have been tied to a host of adverse neurologic outcomes, including cognitive decline and stroke. 

Although protein is a necessary nutrient, incorporating it into the diet of Parkinson’s disease patients taking levodopa is complicated. Levodopa, a large neutral amino acid (LNAA), competes with other LNAAs for transport to the brain from the small intestine, Duda explained. 

“Some people notice that carbidopa-levodopa doesn’t work as well if taken with a high-protein meal.” He recommended taking carbidopa-levodopa 30 minutes before or 60 minutes after meals.

Rebecca Gilbert, MD, PhD, chief mission officer of the American Parkinson’s Disease Association, said that patients with Parkinson’s disease might want to avoid eating protein during the day, concentrating instead on carbohydrates and vegetables and saving the protein for the evening, which is closer to bedtime. Some evidence also supports the use of protein redistribution diets to enhance the clinical response to levodopa and reduce motor fluctuations. 

 

What About Supplements? 

It’s “hard to prove that one specific supplement can be protective against Parkinson’s disease because diet consists of many different components and the whole diet may be worth more than the sum of its parts,” Gilbert said. The evidence for individual supplements “isn’t robust enough to say they prevent or treat Parkinson’s disease.”

Research on the role of specific nutrients in Parkinson’s disease is conflicting, with no clear evidence supporting or refuting their benefits. For example, a study that followed participants for about 30 years showed no link between reduced Parkinson’s disease risk and vitamin B or folate intake. 

On the other hand, there is research suggesting that certain vitamins may help reduce Parkinson’s disease risk, although these nutrients do not operate in isolation. For instance, one recent study showed a connection between vitamins C and E and reduced Parkinson’s disease risk, but factors such as body mass index and coffee consumption appeared to influence the strength of this association.

Consuming polyunsaturated fatty acids along with reducing saturated fatty acid intake has been tied to a reduced risk for Parkinson’s disease. 

Additionally, certain foods may offer protective effects, including green and black tea, with consumption of three or more cups per day associated with a delay in motor symptom onset by 7.7 years. Foods high in nicotine content, such as those from the Solanaceae family — including peppers, tomatoes, tomato juice, and potatoes — have also been linked to potential protective benefits.

Diets rich in antioxidants, including carotenoids, lutein, and vitamins E and C, have been robustly linked to a reduced risk for parkinsonism and progression of parkinsonian symptoms in older adults.

Increasing the intake of dietary flavonoids, particularly tea, berry fruits, apples, red wine, and oranges or orange juice, can reduce Parkinson’s disease risk. One study showed that male participants in the highest quintile of total flavonoid consumption had a 40% lower Parkinson’s disease risk compared with those in the lowest quintile. Another study showed that flavonoid-rich foods were also associated with a lower risk for death in patients with Parkinson’s disease. 

 

Food as Medicine 

Although recent research shows that the drug development pipeline for Parkinson’s disease is robust, with a wide variety of approaches being developed and evaluated in phase 1 and 2, investigators note that only a limited number of disease-modifying treatments are transitioning to phase 3.

Duda noted that phytochemicals incorporated into the diet might target some of the same mechanisms that are targets of these drugs in development. 

“Flavonoids have been shown to stabilize alpha-synuclein in vitro,” he said. “Caffeine, curcumin, resveratrol, and eliminating meat and dairy inhibit mTOR [mammalian target of rapamycin], and mTOR inhibition results in increased autophagy that may help clear alpha-synuclein. Genestein, an isoflavone in soybeans, protects dopaminergic neurons by inhibiting microglia activation. Flavonoids inhibit inflammation by inhibiting release of NO [nitric oxide] and pro-inflammatory cytokines,” he noted. 

Ongoing studies of dietary interventions for Parkinson’s disease are exploring various areas, including the potential role of the ketogenic diet in protecting the gut microbiome, optimizing protein intake for muscle preservation and sleep, the effects of psyllium and wheat bran on weight and constipation, and the impact of a gluten-free diet.

 

Practical Tips for Healthy Eating 

Gilbert emphasized that there are no medications or interventions currently available that can delay a Parkinson’s disease diagnosis by up to 17 years, as some dietary patterns have been shown to do, and she noted that it’s not possible to replicate the MeDi diet in a pill. However, she recommended a practical approach to eating that includes a diet low in ultraprocessed foods and high in beneficial nutrients. She encouraged people to shop for “real food” and enjoy a variety of colorful fruits and vegetables.

Duda acknowledged that motivating patients to follow a healthy diet can be difficult. As a result, the focus often shifts to making small adjustments and modifications. For example, he suggested that instead of pairing meat with French fries, people could opt for vegetables or add greens to their meals. Similarly, instead of having eggs and bacon for breakfast, they might choose oatmeal.

Preparing whole-food, plant-based meals may take more time than patients are accustomed to, so Duda suggests that, if possible, patients involve loved ones in both the meal preparation and the meal itself. He explained that a healthy meal can become an opportunity for bonding and that the key is educating them about new meal-related concepts. 

Duda reported no relevant financial relationships with the pharmaceutical or food industries. He has received compensation from the Physicians Committee for Responsible Medicine for his lecture delivered at the conference and research grant support from the VA, the National Institutes of Health, the Michael J. Fox Foundation, and the Department of Defense unrelated to this topic. Gilbert reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Interest is growing in the role of nutrition as means of slowing, or even preventing, neurodegeneration in patients with Parkinson’s disease.

For 15 years, John Duda, MD, national director of the VA Parkinson’s Disease Research, Education and Clinical Centers, has urged his patients to “keep waiting” for effective treatments to manage both motor and nonmotor symptoms of Parkinson’s disease.

However, Duda, who also serves as director of the Brain Wellness Clinic at the Corporal Michael J. Crescenz VA Medical Center in Philadelphia, Pennsylvania, recognized the persistent lack of effective drugs to address these symptoms. This prompted him to consider what other evidence-based strategies he could use to support his patients. 

“I recognized that nutritional approaches within a broader program that includes medication review, stress management, social connections, adequate sleep, and physical exercise could make a real difference,” he said.

Observational studies have shown an inverse association between dietary patterns and Parkinson’s disease risk, age of onset, symptom severity, and mortality rates — particularly with the Mediterranean diet (MeDi) and the MIND diet, which combines elements of MeDi and the Dietary Approaches to Stop Hypertension (DASH) diet. Although randomized controlled trials are still limited, the epidemiologic evidence supporting dietary interventions is “compelling,” said Duda. 

For example, a cross-sectional study comparing 167 participants with Parkinson’s disease vs 119 controls showed that later age of Parkinson’s disease onset correlated with adherence to the MIND diet in women, with a difference of up to 17.4 years (P < .001) between low and high dietary tertiles. 

The MeDi was correlated with later onset in men, with differences of up to 8.4 years (P = .002). As previously reported, a healthy diet emphasizing vegetables, fruits, nuts, and grains was inversely associated with prodromal features of Parkinson’s disease, including constipation, excessive daytime sleepiness, and depression. In addition, lower rates of Parkinson’s disease have been shown in populations following vegetarian and vegan dietary patterns. 

 

Does Parkinson’s disease Start in the Gut?

Parkinson’s disease is characterized by decreased short-chain fatty acid–producing bacteria and increased pro-inflammatory species linked to intestinal inflammation and alpha-synuclein aggregation. “There are reasons to believe that a-synuclein accumulation may start in the gut,” Duda noted.

Numerous studies implicate gut microbiome dysbiosis as a pathogenic mechanism in Parkinson’s disease, with gastrointestinal symptoms often predating motor symptoms. Dysbiosis might result in a pro-inflammatory state potentially linked to the recurrent gastrointestinal symptoms. Fecal microbiota transplant may restore a healthier gut environment and beneficially affect Parkinson’s disease symptoms, he said.

Some of the benefits conferred by the MeDi and other healthy diets may be mediated by improving the gut microbiome. Duda cited a study that showed that a 14-day ovo-lacto vegetarian diet intervention and a daily fecal enema for 8 days improved not only the microbiome but also Movement Disorder Society Unified Parkinson’s Disease Rating Scale—part III scores. 

Duda also reviewed the role of dietary interventions in addressing common Parkinson’s disease symptoms, such as orthostatic hypotension. He recommended that Parkinson’s disease patients with this condition should avoid eating large meals, increase dietary salt intake, increase fluid intake, and decrease alcohol intake.

Malnutrition affects close to 25% of those with Parkinson’s disease, which is partially attributable to diminished olfaction. Because the experience of taste is largely driven by a sense of smell, patients may be less interested in eating. Duda recommended increasing herbs, spices, and other flavors in food. High caloric–density foods, including nuts, nut butters, and seeds, can boost weight, he said. However, he added, any patient with significant weight loss should consult a nutritionist.

Constipation is one of the most debilitating symptoms of Parkinson’s disease, affecting up to 66% of patients. Duda advised increasing fluid intake, exercise, and dietary fiber and use of stool softeners and laxatives. The MeDi may reduce symptoms of constipation and have a beneficial effect on gut microbiota. 

Coffee may be helpful for sleepiness in Parkinson’s disease and may also confer neuroprotective, motor, and cognitive benefits. As an adjuvant treatment, caffeine may alter levodopa pharmacokinetics, reduce dyskinesia, improve gait in patients with freezing and may even reduce the risk of developing Parkinson’s disease, with a maximum benefit reached at approximately three cups of coffee daily.

 

Problematic Foods

There is also a growing body of evidence regarding the deleterious effects of ultraprocessed foods (UPFs), Duda said. He noted that a recent systematic review and meta-analysis of 28 studies showed that higher UPF intake was significantly associated with an enhanced risk for Parkinson’s disease (relative risk, 1.56; 95% CI, 1.21-2.02). As previously reported, UPFs have been tied to a host of adverse neurologic outcomes, including cognitive decline and stroke. 

Although protein is a necessary nutrient, incorporating it into the diet of Parkinson’s disease patients taking levodopa is complicated. Levodopa, a large neutral amino acid (LNAA), competes with other LNAAs for transport to the brain from the small intestine, Duda explained. 

“Some people notice that carbidopa-levodopa doesn’t work as well if taken with a high-protein meal.” He recommended taking carbidopa-levodopa 30 minutes before or 60 minutes after meals.

Rebecca Gilbert, MD, PhD, chief mission officer of the American Parkinson’s Disease Association, said that patients with Parkinson’s disease might want to avoid eating protein during the day, concentrating instead on carbohydrates and vegetables and saving the protein for the evening, which is closer to bedtime. Some evidence also supports the use of protein redistribution diets to enhance the clinical response to levodopa and reduce motor fluctuations. 

 

What About Supplements? 

It’s “hard to prove that one specific supplement can be protective against Parkinson’s disease because diet consists of many different components and the whole diet may be worth more than the sum of its parts,” Gilbert said. The evidence for individual supplements “isn’t robust enough to say they prevent or treat Parkinson’s disease.”

Research on the role of specific nutrients in Parkinson’s disease is conflicting, with no clear evidence supporting or refuting their benefits. For example, a study that followed participants for about 30 years showed no link between reduced Parkinson’s disease risk and vitamin B or folate intake. 

On the other hand, there is research suggesting that certain vitamins may help reduce Parkinson’s disease risk, although these nutrients do not operate in isolation. For instance, one recent study showed a connection between vitamins C and E and reduced Parkinson’s disease risk, but factors such as body mass index and coffee consumption appeared to influence the strength of this association.

Consuming polyunsaturated fatty acids along with reducing saturated fatty acid intake has been tied to a reduced risk for Parkinson’s disease. 

Additionally, certain foods may offer protective effects, including green and black tea, with consumption of three or more cups per day associated with a delay in motor symptom onset by 7.7 years. Foods high in nicotine content, such as those from the Solanaceae family — including peppers, tomatoes, tomato juice, and potatoes — have also been linked to potential protective benefits.

Diets rich in antioxidants, including carotenoids, lutein, and vitamins E and C, have been robustly linked to a reduced risk for parkinsonism and progression of parkinsonian symptoms in older adults.

Increasing the intake of dietary flavonoids, particularly tea, berry fruits, apples, red wine, and oranges or orange juice, can reduce Parkinson’s disease risk. One study showed that male participants in the highest quintile of total flavonoid consumption had a 40% lower Parkinson’s disease risk compared with those in the lowest quintile. Another study showed that flavonoid-rich foods were also associated with a lower risk for death in patients with Parkinson’s disease. 

 

Food as Medicine 

Although recent research shows that the drug development pipeline for Parkinson’s disease is robust, with a wide variety of approaches being developed and evaluated in phase 1 and 2, investigators note that only a limited number of disease-modifying treatments are transitioning to phase 3.

Duda noted that phytochemicals incorporated into the diet might target some of the same mechanisms that are targets of these drugs in development. 

“Flavonoids have been shown to stabilize alpha-synuclein in vitro,” he said. “Caffeine, curcumin, resveratrol, and eliminating meat and dairy inhibit mTOR [mammalian target of rapamycin], and mTOR inhibition results in increased autophagy that may help clear alpha-synuclein. Genestein, an isoflavone in soybeans, protects dopaminergic neurons by inhibiting microglia activation. Flavonoids inhibit inflammation by inhibiting release of NO [nitric oxide] and pro-inflammatory cytokines,” he noted. 

Ongoing studies of dietary interventions for Parkinson’s disease are exploring various areas, including the potential role of the ketogenic diet in protecting the gut microbiome, optimizing protein intake for muscle preservation and sleep, the effects of psyllium and wheat bran on weight and constipation, and the impact of a gluten-free diet.

 

Practical Tips for Healthy Eating 

Gilbert emphasized that there are no medications or interventions currently available that can delay a Parkinson’s disease diagnosis by up to 17 years, as some dietary patterns have been shown to do, and she noted that it’s not possible to replicate the MeDi diet in a pill. However, she recommended a practical approach to eating that includes a diet low in ultraprocessed foods and high in beneficial nutrients. She encouraged people to shop for “real food” and enjoy a variety of colorful fruits and vegetables.

Duda acknowledged that motivating patients to follow a healthy diet can be difficult. As a result, the focus often shifts to making small adjustments and modifications. For example, he suggested that instead of pairing meat with French fries, people could opt for vegetables or add greens to their meals. Similarly, instead of having eggs and bacon for breakfast, they might choose oatmeal.

Preparing whole-food, plant-based meals may take more time than patients are accustomed to, so Duda suggests that, if possible, patients involve loved ones in both the meal preparation and the meal itself. He explained that a healthy meal can become an opportunity for bonding and that the key is educating them about new meal-related concepts. 

Duda reported no relevant financial relationships with the pharmaceutical or food industries. He has received compensation from the Physicians Committee for Responsible Medicine for his lecture delivered at the conference and research grant support from the VA, the National Institutes of Health, the Michael J. Fox Foundation, and the Department of Defense unrelated to this topic. Gilbert reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Just a few years after some TikTok videos spiked the demand, one in eight US adults has tried Ozempic (semaglutide) or another drug in its class. Glucagon-like peptide 1 (GLP-1) receptor agonist medications have revolutionized obesity medicine.

But they’re not without problems. In the early days of the social media craze, news reports often featured patients whose gastrointestinal side effects sent them to the emergency room (ER).

“It happened a lot then. Patients didn’t want to complain because they were losing weight, and they wound up in the ER with extreme constipation or a small bowel obstruction,” said Caroline Apovian, MD, co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.

“But that’s not really happening now,” she added.

Research backs up her assertion: A recent clinical review of studies found that many patients still experience side effects, but only at a mild to moderate level, while the dosage increases — and the unpleasantness tapers with time. Roughly 7% of patients discontinue the medications due to these symptoms.

Here’s what the latest research shows about GLP-1s’ side effects.

 

Most Common: Gastrointestinal Issues

Depending on the symptom and the specific drug, anywhere from one third to one half of patients will experience some kind of stomach trouble.

• In that clinical review, which looked at studies of three GLP-1 medications — semaglutide (Ozempic, Wegovy, Rybelsus), liraglutide (Saxenda, Victoza), and tirzepatide (Mounjaro, Zepbound) — semaglutide users fared comparatively worse.
• Nausea was reported most frequently — 44.2% of semaglutide users dealt with it, compared with 40.2% for liraglutide and 31% for tirzepatide. Diarrhea, constipation, and vomiting also struck one quarter to one third of semaglutide patients, and slightly fewer for the other two medications.

Apovian finds that careful dosage helps her patients avoid the worst effects.

“We don’t know who’s going to do well and who’s not,” she said. “We start slowly, and usually things go OK.”

If a patient does react poorly, she’ll hold off on increasing the dosage until they acclimate and advise using over-the-counter meds like MiraLAX to address the symptoms.

Few documented severe adverse gastro events appeared in the data, affecting less than 1% of liraglutide and tirzepatide patients and 2.6% of semaglutide users. The majority of these events were gallbladder-related.

 

Questions About Causation: Depression and Suicidality

About a year ago, a study used 18 years’ worth of data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to examine how often patients reported suicidal ideation and/or depression while using GLP-1 medications. Compared with metformin and insulin, researchers found disproportionate reporting by patients using semaglutide and liraglutide. Other GLP-1 medications didn’t show this effect. The researchers pointed out: These statistics don’t show causation — there’s no clear reason why those two medications were linked to more reports.

Further research has been more reassuring:

• Another study also used FAERS but looked only at data from 2018 to 2022, when usage of these drugs was ramping up, and found no link between suicidal or self-injurious behaviors and GLP-1.
• A recent cohort study, which looked at data from nearly 300,000 people, found that GLP-1 users aren’t at increased risk for death by suicide.
• Both the FDA and the European Medicines Agency have issued statements that the evidence doesn’t support a causal association.

There are several factors at play here. People with obesity and diabetes are more likely to have depression to begin with. And more importantly, even if there is a link, causality remains unclear. For instance, patients who lose weight via bariatric surgery are at increased risk for depression, substance abuse, and self-harm. These symptoms may be related to the weight loss itself, not the medications.

“Some people use food as something other than nutrition. They use food to soothe other psychological issues,” Apovian said. “When that’s taken away, the psychological issues are still there.”

In her practice, she’s seen the risk for mental health issues rise with more substantial weight loss — 50-100 pounds.

This lack of clarity regarding causation means it’s important to perform a detailed patient history before prescribing, so you can monitor more closely with preexisting psychiatric disorders.

 

Possible Link: Ocular Symptoms

Here, too, the research isn’t definitive but leans toward no clear association. Several studies have looked for a link between GLP-1 and vision-related issues:

• One examined FAERS data and network pharmacology and found semaglutide and lixisenatide were significantly associated with adverse events like blurred vision, visual impairment, and diabetic retinopathy.
• This summer, a cohort study of almost 17,000 people with diabetes or overweight/obesity suggested a link between semaglutide and nonarteritic anterior ischemic optic neuropathy (NAION), a common cause of blindness due to optic nerve damage. The study found “a substantially increased risk of NAION among individuals prescribed semaglutide relative to those prescribed other medications to treat type 2 diabetes and obesity or overweight.”
• But this month, another cohort study with 135,000 participants looked at NAION in people with type 2 diabetes, obesity, or both. It compared results with common non-GLP-1 medications and found just the opposite: No increased risk for NAION.

One drawback with all these studies is that they’re based on large databases rather than randomized controlled trials (RCTs). When researchers focused on RCTs in a 2023 meta-analysis, they found a significant association with only one form of GLP-1, albiglutide — which was withdrawn from the market in 2017. The other six FDA-approved drugs didn’t show a statistically significant link.

 

Possible Trouble: Pulmonary Aspiration Under Sedation

Earlier this month, the FDA updated labeling for semaglutide, liraglutide, and tirzepatide to include a warning about the risk for aspiration during surgery. While there are no published studies, several case reports have appeared.

GLP-1 medications delay gastric emptying, so even though a patient may have fasted before surgery as usual, some food or liquid may remain. In response to this possibility, a group of professional medical societies issued guidelines for using these medications during the perioperative period. They include:

• Consideration of dosage, symptoms, and other medical conditions: The risk is higher during the escalation phase, and in general, higher doses mean higher risk.
• Potential discontinuation of GLP-1 usage when assessment shows an elevated risk.
• Assessment on the day of the procedure for possible delayed gastric emptying.
• Preoperative dietary modifications, which might include switching to a liquid diet.

Rare: Serious Effects

And then there are the outliers, the frightening issues that make headlines. On their own, none of these are common enough to affect consideration of GLP-1 use:

• Studies in rats suggested an increased risk for thyroid cancer, but subsequent research has found no evidence.
• Colonic ischemia in association with tirzepatide.
• Acute pancreatitis leading to death in association with semaglutide.
• Speaking of pancreatitis, that clinical review of studies did find that both liraglutide and semaglutide led to an elevated risk for pancreatitis, bowel obstruction, and gastroparesis. But the numbers were so small as to be insignificant — for instance, just 0.2% of patients experienced pancreatitis.

Benefits Outweigh Risks

When you lay out these side effects against the countless known benefits of weight loss and blood sugar management — the lower risk for high blood pressure, heart disease, stroke, metabolic syndrome, fatty liver disease, several cancers, and more — the advantages of GLP-1 drugs seem clear. Ultimately, of course, it’s the patient’s decision whether to begin and continue taking any medication for a chronic disease.

Apovian recommends having in-depth conversations before you write that first prescription – she compares the situation to using an antihypertensive drug. If your patient understands potential side effects, they’re more likely to maintain long-term compliance.

“We educate our patients how to use these drugs, indefinitely, if you want to maintain a lower, healthier body weight,” she said. “I don’t see patients who stop using them, but they’re out there. These are people desperate to lose weight, who aren’t given the education to understand we’re treating a disease. It’s not a matter of willpower.”

And once a patient starts taking a GLP-1, monitor them closely, with in-person visits rather than telehealth, while increasing the dosage. If they experience side effects, stay at that level until they ease. And if the patient has a good weight-loss response at a lower dose, stay there. Just because you can go higher, it doesn’t mean you should.

 

A version of this article first appeared on Medscape.com.

Just a few years after some TikTok videos spiked the demand, one in eight US adults has tried Ozempic (semaglutide) or another drug in its class. Glucagon-like peptide 1 (GLP-1) receptor agonist medications have revolutionized obesity medicine.

But they’re not without problems. In the early days of the social media craze, news reports often featured patients whose gastrointestinal side effects sent them to the emergency room (ER).

“It happened a lot then. Patients didn’t want to complain because they were losing weight, and they wound up in the ER with extreme constipation or a small bowel obstruction,” said Caroline Apovian, MD, co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.

“But that’s not really happening now,” she added.

Research backs up her assertion: A recent clinical review of studies found that many patients still experience side effects, but only at a mild to moderate level, while the dosage increases — and the unpleasantness tapers with time. Roughly 7% of patients discontinue the medications due to these symptoms.

Here’s what the latest research shows about GLP-1s’ side effects.

 

Most Common: Gastrointestinal Issues

Depending on the symptom and the specific drug, anywhere from one third to one half of patients will experience some kind of stomach trouble.

• In that clinical review, which looked at studies of three GLP-1 medications — semaglutide (Ozempic, Wegovy, Rybelsus), liraglutide (Saxenda, Victoza), and tirzepatide (Mounjaro, Zepbound) — semaglutide users fared comparatively worse.
• Nausea was reported most frequently — 44.2% of semaglutide users dealt with it, compared with 40.2% for liraglutide and 31% for tirzepatide. Diarrhea, constipation, and vomiting also struck one quarter to one third of semaglutide patients, and slightly fewer for the other two medications.

Apovian finds that careful dosage helps her patients avoid the worst effects.

“We don’t know who’s going to do well and who’s not,” she said. “We start slowly, and usually things go OK.”

If a patient does react poorly, she’ll hold off on increasing the dosage until they acclimate and advise using over-the-counter meds like MiraLAX to address the symptoms.

Few documented severe adverse gastro events appeared in the data, affecting less than 1% of liraglutide and tirzepatide patients and 2.6% of semaglutide users. The majority of these events were gallbladder-related.

 

Questions About Causation: Depression and Suicidality

About a year ago, a study used 18 years’ worth of data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to examine how often patients reported suicidal ideation and/or depression while using GLP-1 medications. Compared with metformin and insulin, researchers found disproportionate reporting by patients using semaglutide and liraglutide. Other GLP-1 medications didn’t show this effect. The researchers pointed out: These statistics don’t show causation — there’s no clear reason why those two medications were linked to more reports.

Further research has been more reassuring:

• Another study also used FAERS but looked only at data from 2018 to 2022, when usage of these drugs was ramping up, and found no link between suicidal or self-injurious behaviors and GLP-1.
• A recent cohort study, which looked at data from nearly 300,000 people, found that GLP-1 users aren’t at increased risk for death by suicide.
• Both the FDA and the European Medicines Agency have issued statements that the evidence doesn’t support a causal association.

There are several factors at play here. People with obesity and diabetes are more likely to have depression to begin with. And more importantly, even if there is a link, causality remains unclear. For instance, patients who lose weight via bariatric surgery are at increased risk for depression, substance abuse, and self-harm. These symptoms may be related to the weight loss itself, not the medications.

“Some people use food as something other than nutrition. They use food to soothe other psychological issues,” Apovian said. “When that’s taken away, the psychological issues are still there.”

In her practice, she’s seen the risk for mental health issues rise with more substantial weight loss — 50-100 pounds.

This lack of clarity regarding causation means it’s important to perform a detailed patient history before prescribing, so you can monitor more closely with preexisting psychiatric disorders.

 

Possible Link: Ocular Symptoms

Here, too, the research isn’t definitive but leans toward no clear association. Several studies have looked for a link between GLP-1 and vision-related issues:

• One examined FAERS data and network pharmacology and found semaglutide and lixisenatide were significantly associated with adverse events like blurred vision, visual impairment, and diabetic retinopathy.
• This summer, a cohort study of almost 17,000 people with diabetes or overweight/obesity suggested a link between semaglutide and nonarteritic anterior ischemic optic neuropathy (NAION), a common cause of blindness due to optic nerve damage. The study found “a substantially increased risk of NAION among individuals prescribed semaglutide relative to those prescribed other medications to treat type 2 diabetes and obesity or overweight.”
• But this month, another cohort study with 135,000 participants looked at NAION in people with type 2 diabetes, obesity, or both. It compared results with common non-GLP-1 medications and found just the opposite: No increased risk for NAION.

One drawback with all these studies is that they’re based on large databases rather than randomized controlled trials (RCTs). When researchers focused on RCTs in a 2023 meta-analysis, they found a significant association with only one form of GLP-1, albiglutide — which was withdrawn from the market in 2017. The other six FDA-approved drugs didn’t show a statistically significant link.

 

Possible Trouble: Pulmonary Aspiration Under Sedation

Earlier this month, the FDA updated labeling for semaglutide, liraglutide, and tirzepatide to include a warning about the risk for aspiration during surgery. While there are no published studies, several case reports have appeared.

GLP-1 medications delay gastric emptying, so even though a patient may have fasted before surgery as usual, some food or liquid may remain. In response to this possibility, a group of professional medical societies issued guidelines for using these medications during the perioperative period. They include:

• Consideration of dosage, symptoms, and other medical conditions: The risk is higher during the escalation phase, and in general, higher doses mean higher risk.
• Potential discontinuation of GLP-1 usage when assessment shows an elevated risk.
• Assessment on the day of the procedure for possible delayed gastric emptying.
• Preoperative dietary modifications, which might include switching to a liquid diet.

Rare: Serious Effects

And then there are the outliers, the frightening issues that make headlines. On their own, none of these are common enough to affect consideration of GLP-1 use:

• Studies in rats suggested an increased risk for thyroid cancer, but subsequent research has found no evidence.
• Colonic ischemia in association with tirzepatide.
• Acute pancreatitis leading to death in association with semaglutide.
• Speaking of pancreatitis, that clinical review of studies did find that both liraglutide and semaglutide led to an elevated risk for pancreatitis, bowel obstruction, and gastroparesis. But the numbers were so small as to be insignificant — for instance, just 0.2% of patients experienced pancreatitis.

Benefits Outweigh Risks

When you lay out these side effects against the countless known benefits of weight loss and blood sugar management — the lower risk for high blood pressure, heart disease, stroke, metabolic syndrome, fatty liver disease, several cancers, and more — the advantages of GLP-1 drugs seem clear. Ultimately, of course, it’s the patient’s decision whether to begin and continue taking any medication for a chronic disease.

Apovian recommends having in-depth conversations before you write that first prescription – she compares the situation to using an antihypertensive drug. If your patient understands potential side effects, they’re more likely to maintain long-term compliance.

“We educate our patients how to use these drugs, indefinitely, if you want to maintain a lower, healthier body weight,” she said. “I don’t see patients who stop using them, but they’re out there. These are people desperate to lose weight, who aren’t given the education to understand we’re treating a disease. It’s not a matter of willpower.”

And once a patient starts taking a GLP-1, monitor them closely, with in-person visits rather than telehealth, while increasing the dosage. If they experience side effects, stay at that level until they ease. And if the patient has a good weight-loss response at a lower dose, stay there. Just because you can go higher, it doesn’t mean you should.

 

A version of this article first appeared on Medscape.com.

Just a few years after some TikTok videos spiked the demand, one in eight US adults has tried Ozempic (semaglutide) or another drug in its class. Glucagon-like peptide 1 (GLP-1) receptor agonist medications have revolutionized obesity medicine.

But they’re not without problems. In the early days of the social media craze, news reports often featured patients whose gastrointestinal side effects sent them to the emergency room (ER).

“It happened a lot then. Patients didn’t want to complain because they were losing weight, and they wound up in the ER with extreme constipation or a small bowel obstruction,” said Caroline Apovian, MD, co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.

“But that’s not really happening now,” she added.

Research backs up her assertion: A recent clinical review of studies found that many patients still experience side effects, but only at a mild to moderate level, while the dosage increases — and the unpleasantness tapers with time. Roughly 7% of patients discontinue the medications due to these symptoms.

Here’s what the latest research shows about GLP-1s’ side effects.

 

Most Common: Gastrointestinal Issues

Depending on the symptom and the specific drug, anywhere from one third to one half of patients will experience some kind of stomach trouble.

• In that clinical review, which looked at studies of three GLP-1 medications — semaglutide (Ozempic, Wegovy, Rybelsus), liraglutide (Saxenda, Victoza), and tirzepatide (Mounjaro, Zepbound) — semaglutide users fared comparatively worse.
• Nausea was reported most frequently — 44.2% of semaglutide users dealt with it, compared with 40.2% for liraglutide and 31% for tirzepatide. Diarrhea, constipation, and vomiting also struck one quarter to one third of semaglutide patients, and slightly fewer for the other two medications.

Apovian finds that careful dosage helps her patients avoid the worst effects.

“We don’t know who’s going to do well and who’s not,” she said. “We start slowly, and usually things go OK.”

If a patient does react poorly, she’ll hold off on increasing the dosage until they acclimate and advise using over-the-counter meds like MiraLAX to address the symptoms.

Few documented severe adverse gastro events appeared in the data, affecting less than 1% of liraglutide and tirzepatide patients and 2.6% of semaglutide users. The majority of these events were gallbladder-related.

 

Questions About Causation: Depression and Suicidality

About a year ago, a study used 18 years’ worth of data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to examine how often patients reported suicidal ideation and/or depression while using GLP-1 medications. Compared with metformin and insulin, researchers found disproportionate reporting by patients using semaglutide and liraglutide. Other GLP-1 medications didn’t show this effect. The researchers pointed out: These statistics don’t show causation — there’s no clear reason why those two medications were linked to more reports.

Further research has been more reassuring:

• Another study also used FAERS but looked only at data from 2018 to 2022, when usage of these drugs was ramping up, and found no link between suicidal or self-injurious behaviors and GLP-1.
• A recent cohort study, which looked at data from nearly 300,000 people, found that GLP-1 users aren’t at increased risk for death by suicide.
• Both the FDA and the European Medicines Agency have issued statements that the evidence doesn’t support a causal association.

There are several factors at play here. People with obesity and diabetes are more likely to have depression to begin with. And more importantly, even if there is a link, causality remains unclear. For instance, patients who lose weight via bariatric surgery are at increased risk for depression, substance abuse, and self-harm. These symptoms may be related to the weight loss itself, not the medications.

“Some people use food as something other than nutrition. They use food to soothe other psychological issues,” Apovian said. “When that’s taken away, the psychological issues are still there.”

In her practice, she’s seen the risk for mental health issues rise with more substantial weight loss — 50-100 pounds.

This lack of clarity regarding causation means it’s important to perform a detailed patient history before prescribing, so you can monitor more closely with preexisting psychiatric disorders.

 

Possible Link: Ocular Symptoms

Here, too, the research isn’t definitive but leans toward no clear association. Several studies have looked for a link between GLP-1 and vision-related issues:

• One examined FAERS data and network pharmacology and found semaglutide and lixisenatide were significantly associated with adverse events like blurred vision, visual impairment, and diabetic retinopathy.
• This summer, a cohort study of almost 17,000 people with diabetes or overweight/obesity suggested a link between semaglutide and nonarteritic anterior ischemic optic neuropathy (NAION), a common cause of blindness due to optic nerve damage. The study found “a substantially increased risk of NAION among individuals prescribed semaglutide relative to those prescribed other medications to treat type 2 diabetes and obesity or overweight.”
• But this month, another cohort study with 135,000 participants looked at NAION in people with type 2 diabetes, obesity, or both. It compared results with common non-GLP-1 medications and found just the opposite: No increased risk for NAION.

One drawback with all these studies is that they’re based on large databases rather than randomized controlled trials (RCTs). When researchers focused on RCTs in a 2023 meta-analysis, they found a significant association with only one form of GLP-1, albiglutide — which was withdrawn from the market in 2017. The other six FDA-approved drugs didn’t show a statistically significant link.

 

Possible Trouble: Pulmonary Aspiration Under Sedation

Earlier this month, the FDA updated labeling for semaglutide, liraglutide, and tirzepatide to include a warning about the risk for aspiration during surgery. While there are no published studies, several case reports have appeared.

GLP-1 medications delay gastric emptying, so even though a patient may have fasted before surgery as usual, some food or liquid may remain. In response to this possibility, a group of professional medical societies issued guidelines for using these medications during the perioperative period. They include:

• Consideration of dosage, symptoms, and other medical conditions: The risk is higher during the escalation phase, and in general, higher doses mean higher risk.
• Potential discontinuation of GLP-1 usage when assessment shows an elevated risk.
• Assessment on the day of the procedure for possible delayed gastric emptying.
• Preoperative dietary modifications, which might include switching to a liquid diet.

Rare: Serious Effects

And then there are the outliers, the frightening issues that make headlines. On their own, none of these are common enough to affect consideration of GLP-1 use:

• Studies in rats suggested an increased risk for thyroid cancer, but subsequent research has found no evidence.
• Colonic ischemia in association with tirzepatide.
• Acute pancreatitis leading to death in association with semaglutide.
• Speaking of pancreatitis, that clinical review of studies did find that both liraglutide and semaglutide led to an elevated risk for pancreatitis, bowel obstruction, and gastroparesis. But the numbers were so small as to be insignificant — for instance, just 0.2% of patients experienced pancreatitis.

Benefits Outweigh Risks

When you lay out these side effects against the countless known benefits of weight loss and blood sugar management — the lower risk for high blood pressure, heart disease, stroke, metabolic syndrome, fatty liver disease, several cancers, and more — the advantages of GLP-1 drugs seem clear. Ultimately, of course, it’s the patient’s decision whether to begin and continue taking any medication for a chronic disease.

Apovian recommends having in-depth conversations before you write that first prescription – she compares the situation to using an antihypertensive drug. If your patient understands potential side effects, they’re more likely to maintain long-term compliance.

“We educate our patients how to use these drugs, indefinitely, if you want to maintain a lower, healthier body weight,” she said. “I don’t see patients who stop using them, but they’re out there. These are people desperate to lose weight, who aren’t given the education to understand we’re treating a disease. It’s not a matter of willpower.”

And once a patient starts taking a GLP-1, monitor them closely, with in-person visits rather than telehealth, while increasing the dosage. If they experience side effects, stay at that level until they ease. And if the patient has a good weight-loss response at a lower dose, stay there. Just because you can go higher, it doesn’t mean you should.

 

A version of this article first appeared on Medscape.com.

Rates of overweight and obesity have more than doubled in the United States during the last three decades, according to a new analysis. By 2050, it’s anticipated that 213 million adults (age, > 25 years) and 43 million children and adolescents will have overweight or obesity. The results led authors of a study to describe obesity as having reached a “crisis point” requiring urgent action and interventions.

Are glucagon-like peptide 1 receptor agonists (GLP-1 RAs), originally developed and prescribed for diabetes and now approved for weight loss, the answer? 

Their popularity is certainly surging. Between the last 6 months of 2022 vs the last 6 months of 2024, the number of patients prescribed GLP-1 RAs increased by 132.6%. This is also reflected in a shift in public awareness, with a recent survey of US adults finding that 32% of respondents had heard “a lot” about these drugs, up from 19% in 2023.

GLP-1 RAs (including tirzepatide, which targets not only the GLP-1 receptor but also the glucose-dependent insulinotropic polypeptide receptor) have shown efficacy in weight loss. A 2022 review and meta-analysis of 22 trials (17,183 patients) found that 50.2% and 17.5% of those treated with GLP-1 RAs had a ≥ 5% and ≥ 10% weight loss, respectively, compared with placebo. A 2023 review of 41 trials (15,135 patients) found that compared with controls, GLP-1 RAs significantly reduced body weight, body mass index, waist circumference, and waist-to-hip ratio.

“GLP-1 RAs are great medications,” Andres Acosta, MD, PhD, director of the Precision Medicine for Obesity Laboratory, Mayo Clinic, Rochester, Minnesota, told Medscape Medical News. “We’ve been using them for almost two decades. But now there’s excitement about their utility in treating obesity.”

 

Treating the Four Categories of Obesity 

Daniel Drucker, MD, senior investigator at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, is a pioneer in diabetes treatment and particularly in the development of GLP-1 RAs. Drucker told Medscape Medical News that despite the efficacy and enormous potential of GLP-1 RAs, “we know some people don’t lose much weight when taking these medicines and others don’t feel well and can’t take them.”

The number of individuals who don’t respond to or aren’t able to tolerate GLP-1 RAs “might be small — less than 10% of people who try to take them — but we don’t fully understand the differences in response across different individuals,” Drucker said.

Acosta agreed, adding that it’s “essential for us to identify who will be the best responders, as we do with medications for other conditions, such as cancer and cardiovascular disease.”

Acosta’s group has spent more than a decade engaged in efforts to identify unique characteristics among patients with obesity and has succeeded in identifying four obesity phenotypes.

“What matters in the space of GLP-1 is that using this classification, we can identify the best responders and those who don’t respond.” 

The first phenotype, described as “Hungry Gut” (HG), includes patients with abnormal postprandial satiety. “Although they may be satiated at the end of a meal, they have accelerated gastric emptying and therefore feel hungry between meals and want to keep eating,” he said.

There are also patients who experience abnormal satiety during meals. According to Acosta, these are the patients who will return to the table for second and third helpings. “They don’t feel full and continue to eat more and more in a single sitting” — a phenomenon referred to as “Hungry Brain.”

The third phenotype — “Emotional Hunger” — consists of people who are “hedonic” about food or engage in emotional eating behavior, whereas in the fourth group, people have “an abnormal metabolism in which they don’t burn enough calories. They have an inefficient metabolic rate.” This latter phenomenon is called “Slow Burn.”

Acosta and colleagues randomized 312 patients attending a weight management center to phenotype-guided or non–phenotype-guided treatment with anti-obesity medications (phentermine, phentermine/topiramate, bupropion/naltrexone, lorcaserin, and liraglutide). The phenotype-guided approach was associated with a 1.75-fold greater weight loss after 1 year than the non–phenotype-guided approach (mean weight loss, 15.9% vs 9.0%, respectively).

 

GLP-1 RAs: Not One-Size-Fits-All

Acosta’s group has developed a genetic test that uses patients’ saliva to identify their obesity phenotype, with the aim of predicting the best responders to GLP-1 RAs. The test, MyPhenome genetic obesity test, is licensed by Acosta’s lab and available through Phenomix Sciences.

Acosta and colleagues presented their findings at the American Gastroenterological Association’s 2024 annual meeting regarding a machine-learning gene risk score (ML-GRS) they developed to predict HG, based on saliva and blood samples. Their genetic studies generated a ML-GRS that classified participants with obesity along a continuum from “HG Positive” (HG+) to “HG Negative” (HG−). Compared with the HG− participants, those who were HG+ had superior total body weight loss with semaglutide at 9 and 12 months. When used to predict response, the ML-GRS had an area under the curve of 0.76 (P = .04) and a positive predictive value of 0.95.

According to Acosta, HG+ patients are “the best responders to the GLP-1 RAs, although we don’t yet understand the mechanism of why they have the phenomenon of abnormal postprandial satiety. It may be an abnormal genetic pathway or abnormal secretion of GLP-1. More studies are needed.”

He noted that GLP-1 RAs “might also be helpful with the second [Hungry Brain] category, but these patients do better with phentermine-topiramate,” as demonstrated in a 2023 study conducted by Acosta and colleagues.

His group has also studied which lifestyle interventions are most effective for each phenotype. “When a unique lifestyle intervention targeting each phenotype was applied, patients lost more weight and had greater metabolic improvement,” he reported.

“Treating obesity no longer needs to be trial-and-error, but should be done using precision medicine because one size doesn’t fit all,” Acosta said.

 

Concerning Side Effects

The popular media has featured stories about individuals who took GLP-1 RAs for weight loss and experienced serious side effects, including a recent account of a British nurse who died after taking tirzepatide. As reported by the BBC, the nurse’s death certificate listed multiple organ failure, septic shock, and pancreatitis as the immediate causes of death, with the “use of prescribed tirzepatide” recorded as a contributing factor. The report went on to note that there were 23 suspected deaths in the United Kingdom tied to semaglutide since 2019.

Beyond brand-name products, there are also risks associated with GLP-1 RAs manufactured by compounding pharmacies. In early November, CNN reported that compounded semaglutide has been linked to at least 10 deaths. Because of a prior shortage of tirzepatide, the US Food and Drug Administration (FDA) had allowed compounding pharmacies to manufacture the drug. In October, the FDA clarified that it won’t take legal action against compounders, even now that the shortage has been resolved.

A pharmacovigilance study using the FDA Adverse Event Reporting System identified “potential safety signals of increased mortality and serious adverse event reporting” associated with certain GLP-1 RAs — especially in younger patients and women (P < .0001 for both groups).

The most common side effects reported with GLP-1 RAs are gastrointestinal events, such as nausea, diarrhea, constipation, and vomiting. Most occur during dose initiation and escalation and wane over the following weeks. However, studies have also reported severe side effects, including a higher risk for pancreatitis, bowel obstruction, and gastroparesis, as well as a significantly higher risk for gallbladder and biliary diseases. In fact, according to one study, patients with diabetes taking GLP-1 RAs reported gastrointestinal-related issues as a “prominent factor” in their decision to discontinue taking these medications.

Several types of cancer are potentially associated with GLP-1 RAs, but findings regarding this potential link have been inconsistent. In a recent review article, Drucker noted there were only inconsistent data linking GLP-1 RAs with thyroid cancer and medullary thyroid cancer and that their potential association with pancreatic has “not been supported by results from randomized controlled trials or real-world data.” 

Concerns have been raised about loss of lean mass and muscle strength and function, especially in older individuals with obesity and advanced liver, cardiovascular, or kidney disease. However, as Drucker pointed out in his review article, muscle function may not correlate with the loss of lean mass. In fact, there are “consistent reductions” in lean mass after bariatric surgery, but “little evidence to date for impairment of muscle function.” He added that newer GLP-1 agents under development for obesity treatment are focusing on “developing complementary therapies that preferentially reduce adipose tissue, while sparing lean mass.”

As covered by Medscape Medical News, there have been reports of potential suicidal ideation associated with GLP-1 RAs. This triggered a 2023 review from the European Medicines Agency. However, recent results from a cohort study and a post hoc analysis of randomized controlled trials concluded that there is no evidence that these drugs increase suicidal ideation or behavior.

In early November, the FDA updated the labels for the GLP-1 RAs to include a warning regarding pulmonary aspiration during general anesthesia or deep sedation. Guidance from a group of societies, led by the American Society of Anesthesiologists, contains recommendations regarding nuances of addressing this concern in surgical patients taking these agents.

 

Not a Standalone Treatment

Marc-Andre Cornier, MD, professor of medicine, James A. Keating Endowed Chair in Diabetes, and director of the Division of Endocrinology, Diabetes and Metabolic Diseases, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, told Medscape Medical News that GLP-1 RAs should not be viewed as cosmetic interventions but rather as medical treatments, “not only for weight loss but to reverse obesity-associated complications.” 

Moreover, they should be used “as an adjunct to lifestyle changes,” emphasized Cornier. “We want our patients to have a high-quality diet with high protein content, fluid, vitamins, and minerals, and we want them to exercise.” Especially with the concern of potential loss of muscle mass with these agents, “resistance exercise might help mitigate that concern.”

Recently published recommendations can assist clinicians in guiding patients taking GLP-1 RAs to optimize nutrition. The recommendations note that patients should be referred to a registered dietitian to “complement and support” treatment with anti-obesity medications.

 

What Do Patients Want?

Despite the ever-rising popularity of GLP-1 RAs, a new national survey of over 2200 US adults conducted by the Physicians Committee for Responsible Medicine suggests that most Americans don’t want to use them. Among those who wanted to lose weight, almost three-quarters “disagreed” or “strongly disagreed” with the idea of taking a weight-loss injectable, and 68% of those who wanted to lose weight “agreed” or “strongly agreed” that they would be willing to try a plant-based diet, if it could lead to significant weight loss.

Moreover, many individuals treated with GLP-1 RAs discontinue their use, despite the probability of regaining the weight, according to a report that found only 46.3% of GLP-1 users were still taking the medications at 6 months and only 32.3% at 1 year. The authors commented that their real-world findings show a “substantially lower” 1-year persistence rate, compared with the rate reported in clinical trials. They suggest that the financial burden (> $12,000/year) may contribute to discontinuation.

Discontinuation of GLP-1 RAs can lead to worsening cardiometabolic parameters, with a potential increased risk for adverse outcomes; moreover, weight cycling (“yo-yo dieting”) carries its own risks. In light of these concerns, it’s particularly important to select appropriate patients and to determine whether potential short-term therapy has any enduring benefit.

Acosta agreed. “It’s exciting when looking at the data on how to find the best responders and who should make the effort to take these medications — not only in terms of side effects but also in terms of cost and which patients will receive maximum benefits and should be covered by insurance.” 

Drucker has served as a consultant or speaker for Altimmune, Amgen, AstraZeneca, Arrowhead, Boehringer Ingelheim, Kallyope, Merck Research Laboratories, Novo Nordisk, Pfizer, and Zealand Pharma. He holds nonexercised options in Kallyope. Mount Sinai Hospital receives research support for investigator-initiated studies in the Drucker laboratory from Amgen, Novo Nordisk, Pfizer, and Zealand Pharma. Gila Therapeutics and Phenomix Sciences have licensed Acosta’s research technologies from University of Florida and Mayo Clinic. Acosta received consultant fees in the last 5 years from Rhythm Pharmaceuticals, Gila Therapeutics, Amgen, General Mills, Regeneron Pharmaceuticals, Boehringer Ingelheim, Novo Nordisk, Currax, Nestlé, Phenomix Sciences, Bausch Health, and Rare Disease. He received funding support from the National Institutes of Health, Vivus Pharmaceuticals, Novo Nordisk, Apollo Endosurgery, Satiogen Pharmaceuticals, Spatz Medical, Rhythm Pharmaceuticals, Regeneron Pharmaceuticals, Boehringer Ingelheim, and Novo Nordisk. In the past, Cornier has served as a consultant for Novo Nordisk.

 

A version of this article first appeared on Medscape.com.

Rates of overweight and obesity have more than doubled in the United States during the last three decades, according to a new analysis. By 2050, it’s anticipated that 213 million adults (age, > 25 years) and 43 million children and adolescents will have overweight or obesity. The results led authors of a study to describe obesity as having reached a “crisis point” requiring urgent action and interventions.

Are glucagon-like peptide 1 receptor agonists (GLP-1 RAs), originally developed and prescribed for diabetes and now approved for weight loss, the answer? 

Their popularity is certainly surging. Between the last 6 months of 2022 vs the last 6 months of 2024, the number of patients prescribed GLP-1 RAs increased by 132.6%. This is also reflected in a shift in public awareness, with a recent survey of US adults finding that 32% of respondents had heard “a lot” about these drugs, up from 19% in 2023.

GLP-1 RAs (including tirzepatide, which targets not only the GLP-1 receptor but also the glucose-dependent insulinotropic polypeptide receptor) have shown efficacy in weight loss. A 2022 review and meta-analysis of 22 trials (17,183 patients) found that 50.2% and 17.5% of those treated with GLP-1 RAs had a ≥ 5% and ≥ 10% weight loss, respectively, compared with placebo. A 2023 review of 41 trials (15,135 patients) found that compared with controls, GLP-1 RAs significantly reduced body weight, body mass index, waist circumference, and waist-to-hip ratio.

“GLP-1 RAs are great medications,” Andres Acosta, MD, PhD, director of the Precision Medicine for Obesity Laboratory, Mayo Clinic, Rochester, Minnesota, told Medscape Medical News. “We’ve been using them for almost two decades. But now there’s excitement about their utility in treating obesity.”

 

Treating the Four Categories of Obesity 

Daniel Drucker, MD, senior investigator at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, is a pioneer in diabetes treatment and particularly in the development of GLP-1 RAs. Drucker told Medscape Medical News that despite the efficacy and enormous potential of GLP-1 RAs, “we know some people don’t lose much weight when taking these medicines and others don’t feel well and can’t take them.”

The number of individuals who don’t respond to or aren’t able to tolerate GLP-1 RAs “might be small — less than 10% of people who try to take them — but we don’t fully understand the differences in response across different individuals,” Drucker said.

Acosta agreed, adding that it’s “essential for us to identify who will be the best responders, as we do with medications for other conditions, such as cancer and cardiovascular disease.”

Acosta’s group has spent more than a decade engaged in efforts to identify unique characteristics among patients with obesity and has succeeded in identifying four obesity phenotypes.

“What matters in the space of GLP-1 is that using this classification, we can identify the best responders and those who don’t respond.” 

The first phenotype, described as “Hungry Gut” (HG), includes patients with abnormal postprandial satiety. “Although they may be satiated at the end of a meal, they have accelerated gastric emptying and therefore feel hungry between meals and want to keep eating,” he said.

There are also patients who experience abnormal satiety during meals. According to Acosta, these are the patients who will return to the table for second and third helpings. “They don’t feel full and continue to eat more and more in a single sitting” — a phenomenon referred to as “Hungry Brain.”

The third phenotype — “Emotional Hunger” — consists of people who are “hedonic” about food or engage in emotional eating behavior, whereas in the fourth group, people have “an abnormal metabolism in which they don’t burn enough calories. They have an inefficient metabolic rate.” This latter phenomenon is called “Slow Burn.”

Acosta and colleagues randomized 312 patients attending a weight management center to phenotype-guided or non–phenotype-guided treatment with anti-obesity medications (phentermine, phentermine/topiramate, bupropion/naltrexone, lorcaserin, and liraglutide). The phenotype-guided approach was associated with a 1.75-fold greater weight loss after 1 year than the non–phenotype-guided approach (mean weight loss, 15.9% vs 9.0%, respectively).

 

GLP-1 RAs: Not One-Size-Fits-All

Acosta’s group has developed a genetic test that uses patients’ saliva to identify their obesity phenotype, with the aim of predicting the best responders to GLP-1 RAs. The test, MyPhenome genetic obesity test, is licensed by Acosta’s lab and available through Phenomix Sciences.

Acosta and colleagues presented their findings at the American Gastroenterological Association’s 2024 annual meeting regarding a machine-learning gene risk score (ML-GRS) they developed to predict HG, based on saliva and blood samples. Their genetic studies generated a ML-GRS that classified participants with obesity along a continuum from “HG Positive” (HG+) to “HG Negative” (HG−). Compared with the HG− participants, those who were HG+ had superior total body weight loss with semaglutide at 9 and 12 months. When used to predict response, the ML-GRS had an area under the curve of 0.76 (P = .04) and a positive predictive value of 0.95.

According to Acosta, HG+ patients are “the best responders to the GLP-1 RAs, although we don’t yet understand the mechanism of why they have the phenomenon of abnormal postprandial satiety. It may be an abnormal genetic pathway or abnormal secretion of GLP-1. More studies are needed.”

He noted that GLP-1 RAs “might also be helpful with the second [Hungry Brain] category, but these patients do better with phentermine-topiramate,” as demonstrated in a 2023 study conducted by Acosta and colleagues.

His group has also studied which lifestyle interventions are most effective for each phenotype. “When a unique lifestyle intervention targeting each phenotype was applied, patients lost more weight and had greater metabolic improvement,” he reported.

“Treating obesity no longer needs to be trial-and-error, but should be done using precision medicine because one size doesn’t fit all,” Acosta said.

 

Concerning Side Effects

The popular media has featured stories about individuals who took GLP-1 RAs for weight loss and experienced serious side effects, including a recent account of a British nurse who died after taking tirzepatide. As reported by the BBC, the nurse’s death certificate listed multiple organ failure, septic shock, and pancreatitis as the immediate causes of death, with the “use of prescribed tirzepatide” recorded as a contributing factor. The report went on to note that there were 23 suspected deaths in the United Kingdom tied to semaglutide since 2019.

Beyond brand-name products, there are also risks associated with GLP-1 RAs manufactured by compounding pharmacies. In early November, CNN reported that compounded semaglutide has been linked to at least 10 deaths. Because of a prior shortage of tirzepatide, the US Food and Drug Administration (FDA) had allowed compounding pharmacies to manufacture the drug. In October, the FDA clarified that it won’t take legal action against compounders, even now that the shortage has been resolved.

A pharmacovigilance study using the FDA Adverse Event Reporting System identified “potential safety signals of increased mortality and serious adverse event reporting” associated with certain GLP-1 RAs — especially in younger patients and women (P < .0001 for both groups).

The most common side effects reported with GLP-1 RAs are gastrointestinal events, such as nausea, diarrhea, constipation, and vomiting. Most occur during dose initiation and escalation and wane over the following weeks. However, studies have also reported severe side effects, including a higher risk for pancreatitis, bowel obstruction, and gastroparesis, as well as a significantly higher risk for gallbladder and biliary diseases. In fact, according to one study, patients with diabetes taking GLP-1 RAs reported gastrointestinal-related issues as a “prominent factor” in their decision to discontinue taking these medications.

Several types of cancer are potentially associated with GLP-1 RAs, but findings regarding this potential link have been inconsistent. In a recent review article, Drucker noted there were only inconsistent data linking GLP-1 RAs with thyroid cancer and medullary thyroid cancer and that their potential association with pancreatic has “not been supported by results from randomized controlled trials or real-world data.” 

Concerns have been raised about loss of lean mass and muscle strength and function, especially in older individuals with obesity and advanced liver, cardiovascular, or kidney disease. However, as Drucker pointed out in his review article, muscle function may not correlate with the loss of lean mass. In fact, there are “consistent reductions” in lean mass after bariatric surgery, but “little evidence to date for impairment of muscle function.” He added that newer GLP-1 agents under development for obesity treatment are focusing on “developing complementary therapies that preferentially reduce adipose tissue, while sparing lean mass.”

As covered by Medscape Medical News, there have been reports of potential suicidal ideation associated with GLP-1 RAs. This triggered a 2023 review from the European Medicines Agency. However, recent results from a cohort study and a post hoc analysis of randomized controlled trials concluded that there is no evidence that these drugs increase suicidal ideation or behavior.

In early November, the FDA updated the labels for the GLP-1 RAs to include a warning regarding pulmonary aspiration during general anesthesia or deep sedation. Guidance from a group of societies, led by the American Society of Anesthesiologists, contains recommendations regarding nuances of addressing this concern in surgical patients taking these agents.

 

Not a Standalone Treatment

Marc-Andre Cornier, MD, professor of medicine, James A. Keating Endowed Chair in Diabetes, and director of the Division of Endocrinology, Diabetes and Metabolic Diseases, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, told Medscape Medical News that GLP-1 RAs should not be viewed as cosmetic interventions but rather as medical treatments, “not only for weight loss but to reverse obesity-associated complications.” 

Moreover, they should be used “as an adjunct to lifestyle changes,” emphasized Cornier. “We want our patients to have a high-quality diet with high protein content, fluid, vitamins, and minerals, and we want them to exercise.” Especially with the concern of potential loss of muscle mass with these agents, “resistance exercise might help mitigate that concern.”

Recently published recommendations can assist clinicians in guiding patients taking GLP-1 RAs to optimize nutrition. The recommendations note that patients should be referred to a registered dietitian to “complement and support” treatment with anti-obesity medications.

 

What Do Patients Want?

Despite the ever-rising popularity of GLP-1 RAs, a new national survey of over 2200 US adults conducted by the Physicians Committee for Responsible Medicine suggests that most Americans don’t want to use them. Among those who wanted to lose weight, almost three-quarters “disagreed” or “strongly disagreed” with the idea of taking a weight-loss injectable, and 68% of those who wanted to lose weight “agreed” or “strongly agreed” that they would be willing to try a plant-based diet, if it could lead to significant weight loss.

Moreover, many individuals treated with GLP-1 RAs discontinue their use, despite the probability of regaining the weight, according to a report that found only 46.3% of GLP-1 users were still taking the medications at 6 months and only 32.3% at 1 year. The authors commented that their real-world findings show a “substantially lower” 1-year persistence rate, compared with the rate reported in clinical trials. They suggest that the financial burden (> $12,000/year) may contribute to discontinuation.

Discontinuation of GLP-1 RAs can lead to worsening cardiometabolic parameters, with a potential increased risk for adverse outcomes; moreover, weight cycling (“yo-yo dieting”) carries its own risks. In light of these concerns, it’s particularly important to select appropriate patients and to determine whether potential short-term therapy has any enduring benefit.

Acosta agreed. “It’s exciting when looking at the data on how to find the best responders and who should make the effort to take these medications — not only in terms of side effects but also in terms of cost and which patients will receive maximum benefits and should be covered by insurance.” 

Drucker has served as a consultant or speaker for Altimmune, Amgen, AstraZeneca, Arrowhead, Boehringer Ingelheim, Kallyope, Merck Research Laboratories, Novo Nordisk, Pfizer, and Zealand Pharma. He holds nonexercised options in Kallyope. Mount Sinai Hospital receives research support for investigator-initiated studies in the Drucker laboratory from Amgen, Novo Nordisk, Pfizer, and Zealand Pharma. Gila Therapeutics and Phenomix Sciences have licensed Acosta’s research technologies from University of Florida and Mayo Clinic. Acosta received consultant fees in the last 5 years from Rhythm Pharmaceuticals, Gila Therapeutics, Amgen, General Mills, Regeneron Pharmaceuticals, Boehringer Ingelheim, Novo Nordisk, Currax, Nestlé, Phenomix Sciences, Bausch Health, and Rare Disease. He received funding support from the National Institutes of Health, Vivus Pharmaceuticals, Novo Nordisk, Apollo Endosurgery, Satiogen Pharmaceuticals, Spatz Medical, Rhythm Pharmaceuticals, Regeneron Pharmaceuticals, Boehringer Ingelheim, and Novo Nordisk. In the past, Cornier has served as a consultant for Novo Nordisk.

 

A version of this article first appeared on Medscape.com.

Rates of overweight and obesity have more than doubled in the United States during the last three decades, according to a new analysis. By 2050, it’s anticipated that 213 million adults (age, > 25 years) and 43 million children and adolescents will have overweight or obesity. The results led authors of a study to describe obesity as having reached a “crisis point” requiring urgent action and interventions.

Are glucagon-like peptide 1 receptor agonists (GLP-1 RAs), originally developed and prescribed for diabetes and now approved for weight loss, the answer? 

Their popularity is certainly surging. Between the last 6 months of 2022 vs the last 6 months of 2024, the number of patients prescribed GLP-1 RAs increased by 132.6%. This is also reflected in a shift in public awareness, with a recent survey of US adults finding that 32% of respondents had heard “a lot” about these drugs, up from 19% in 2023.

GLP-1 RAs (including tirzepatide, which targets not only the GLP-1 receptor but also the glucose-dependent insulinotropic polypeptide receptor) have shown efficacy in weight loss. A 2022 review and meta-analysis of 22 trials (17,183 patients) found that 50.2% and 17.5% of those treated with GLP-1 RAs had a ≥ 5% and ≥ 10% weight loss, respectively, compared with placebo. A 2023 review of 41 trials (15,135 patients) found that compared with controls, GLP-1 RAs significantly reduced body weight, body mass index, waist circumference, and waist-to-hip ratio.

“GLP-1 RAs are great medications,” Andres Acosta, MD, PhD, director of the Precision Medicine for Obesity Laboratory, Mayo Clinic, Rochester, Minnesota, told Medscape Medical News. “We’ve been using them for almost two decades. But now there’s excitement about their utility in treating obesity.”

 

Treating the Four Categories of Obesity 

Daniel Drucker, MD, senior investigator at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, is a pioneer in diabetes treatment and particularly in the development of GLP-1 RAs. Drucker told Medscape Medical News that despite the efficacy and enormous potential of GLP-1 RAs, “we know some people don’t lose much weight when taking these medicines and others don’t feel well and can’t take them.”

The number of individuals who don’t respond to or aren’t able to tolerate GLP-1 RAs “might be small — less than 10% of people who try to take them — but we don’t fully understand the differences in response across different individuals,” Drucker said.

Acosta agreed, adding that it’s “essential for us to identify who will be the best responders, as we do with medications for other conditions, such as cancer and cardiovascular disease.”

Acosta’s group has spent more than a decade engaged in efforts to identify unique characteristics among patients with obesity and has succeeded in identifying four obesity phenotypes.

“What matters in the space of GLP-1 is that using this classification, we can identify the best responders and those who don’t respond.” 

The first phenotype, described as “Hungry Gut” (HG), includes patients with abnormal postprandial satiety. “Although they may be satiated at the end of a meal, they have accelerated gastric emptying and therefore feel hungry between meals and want to keep eating,” he said.

There are also patients who experience abnormal satiety during meals. According to Acosta, these are the patients who will return to the table for second and third helpings. “They don’t feel full and continue to eat more and more in a single sitting” — a phenomenon referred to as “Hungry Brain.”

The third phenotype — “Emotional Hunger” — consists of people who are “hedonic” about food or engage in emotional eating behavior, whereas in the fourth group, people have “an abnormal metabolism in which they don’t burn enough calories. They have an inefficient metabolic rate.” This latter phenomenon is called “Slow Burn.”

Acosta and colleagues randomized 312 patients attending a weight management center to phenotype-guided or non–phenotype-guided treatment with anti-obesity medications (phentermine, phentermine/topiramate, bupropion/naltrexone, lorcaserin, and liraglutide). The phenotype-guided approach was associated with a 1.75-fold greater weight loss after 1 year than the non–phenotype-guided approach (mean weight loss, 15.9% vs 9.0%, respectively).

 

GLP-1 RAs: Not One-Size-Fits-All

Acosta’s group has developed a genetic test that uses patients’ saliva to identify their obesity phenotype, with the aim of predicting the best responders to GLP-1 RAs. The test, MyPhenome genetic obesity test, is licensed by Acosta’s lab and available through Phenomix Sciences.

Acosta and colleagues presented their findings at the American Gastroenterological Association’s 2024 annual meeting regarding a machine-learning gene risk score (ML-GRS) they developed to predict HG, based on saliva and blood samples. Their genetic studies generated a ML-GRS that classified participants with obesity along a continuum from “HG Positive” (HG+) to “HG Negative” (HG−). Compared with the HG− participants, those who were HG+ had superior total body weight loss with semaglutide at 9 and 12 months. When used to predict response, the ML-GRS had an area under the curve of 0.76 (P = .04) and a positive predictive value of 0.95.

According to Acosta, HG+ patients are “the best responders to the GLP-1 RAs, although we don’t yet understand the mechanism of why they have the phenomenon of abnormal postprandial satiety. It may be an abnormal genetic pathway or abnormal secretion of GLP-1. More studies are needed.”

He noted that GLP-1 RAs “might also be helpful with the second [Hungry Brain] category, but these patients do better with phentermine-topiramate,” as demonstrated in a 2023 study conducted by Acosta and colleagues.

His group has also studied which lifestyle interventions are most effective for each phenotype. “When a unique lifestyle intervention targeting each phenotype was applied, patients lost more weight and had greater metabolic improvement,” he reported.

“Treating obesity no longer needs to be trial-and-error, but should be done using precision medicine because one size doesn’t fit all,” Acosta said.

 

Concerning Side Effects

The popular media has featured stories about individuals who took GLP-1 RAs for weight loss and experienced serious side effects, including a recent account of a British nurse who died after taking tirzepatide. As reported by the BBC, the nurse’s death certificate listed multiple organ failure, septic shock, and pancreatitis as the immediate causes of death, with the “use of prescribed tirzepatide” recorded as a contributing factor. The report went on to note that there were 23 suspected deaths in the United Kingdom tied to semaglutide since 2019.

Beyond brand-name products, there are also risks associated with GLP-1 RAs manufactured by compounding pharmacies. In early November, CNN reported that compounded semaglutide has been linked to at least 10 deaths. Because of a prior shortage of tirzepatide, the US Food and Drug Administration (FDA) had allowed compounding pharmacies to manufacture the drug. In October, the FDA clarified that it won’t take legal action against compounders, even now that the shortage has been resolved.

A pharmacovigilance study using the FDA Adverse Event Reporting System identified “potential safety signals of increased mortality and serious adverse event reporting” associated with certain GLP-1 RAs — especially in younger patients and women (P < .0001 for both groups).

The most common side effects reported with GLP-1 RAs are gastrointestinal events, such as nausea, diarrhea, constipation, and vomiting. Most occur during dose initiation and escalation and wane over the following weeks. However, studies have also reported severe side effects, including a higher risk for pancreatitis, bowel obstruction, and gastroparesis, as well as a significantly higher risk for gallbladder and biliary diseases. In fact, according to one study, patients with diabetes taking GLP-1 RAs reported gastrointestinal-related issues as a “prominent factor” in their decision to discontinue taking these medications.

Several types of cancer are potentially associated with GLP-1 RAs, but findings regarding this potential link have been inconsistent. In a recent review article, Drucker noted there were only inconsistent data linking GLP-1 RAs with thyroid cancer and medullary thyroid cancer and that their potential association with pancreatic has “not been supported by results from randomized controlled trials or real-world data.” 

Concerns have been raised about loss of lean mass and muscle strength and function, especially in older individuals with obesity and advanced liver, cardiovascular, or kidney disease. However, as Drucker pointed out in his review article, muscle function may not correlate with the loss of lean mass. In fact, there are “consistent reductions” in lean mass after bariatric surgery, but “little evidence to date for impairment of muscle function.” He added that newer GLP-1 agents under development for obesity treatment are focusing on “developing complementary therapies that preferentially reduce adipose tissue, while sparing lean mass.”

As covered by Medscape Medical News, there have been reports of potential suicidal ideation associated with GLP-1 RAs. This triggered a 2023 review from the European Medicines Agency. However, recent results from a cohort study and a post hoc analysis of randomized controlled trials concluded that there is no evidence that these drugs increase suicidal ideation or behavior.

In early November, the FDA updated the labels for the GLP-1 RAs to include a warning regarding pulmonary aspiration during general anesthesia or deep sedation. Guidance from a group of societies, led by the American Society of Anesthesiologists, contains recommendations regarding nuances of addressing this concern in surgical patients taking these agents.

 

Not a Standalone Treatment

Marc-Andre Cornier, MD, professor of medicine, James A. Keating Endowed Chair in Diabetes, and director of the Division of Endocrinology, Diabetes and Metabolic Diseases, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, told Medscape Medical News that GLP-1 RAs should not be viewed as cosmetic interventions but rather as medical treatments, “not only for weight loss but to reverse obesity-associated complications.” 

Moreover, they should be used “as an adjunct to lifestyle changes,” emphasized Cornier. “We want our patients to have a high-quality diet with high protein content, fluid, vitamins, and minerals, and we want them to exercise.” Especially with the concern of potential loss of muscle mass with these agents, “resistance exercise might help mitigate that concern.”

Recently published recommendations can assist clinicians in guiding patients taking GLP-1 RAs to optimize nutrition. The recommendations note that patients should be referred to a registered dietitian to “complement and support” treatment with anti-obesity medications.

 

What Do Patients Want?

Despite the ever-rising popularity of GLP-1 RAs, a new national survey of over 2200 US adults conducted by the Physicians Committee for Responsible Medicine suggests that most Americans don’t want to use them. Among those who wanted to lose weight, almost three-quarters “disagreed” or “strongly disagreed” with the idea of taking a weight-loss injectable, and 68% of those who wanted to lose weight “agreed” or “strongly agreed” that they would be willing to try a plant-based diet, if it could lead to significant weight loss.

Moreover, many individuals treated with GLP-1 RAs discontinue their use, despite the probability of regaining the weight, according to a report that found only 46.3% of GLP-1 users were still taking the medications at 6 months and only 32.3% at 1 year. The authors commented that their real-world findings show a “substantially lower” 1-year persistence rate, compared with the rate reported in clinical trials. They suggest that the financial burden (> $12,000/year) may contribute to discontinuation.

Discontinuation of GLP-1 RAs can lead to worsening cardiometabolic parameters, with a potential increased risk for adverse outcomes; moreover, weight cycling (“yo-yo dieting”) carries its own risks. In light of these concerns, it’s particularly important to select appropriate patients and to determine whether potential short-term therapy has any enduring benefit.

Acosta agreed. “It’s exciting when looking at the data on how to find the best responders and who should make the effort to take these medications — not only in terms of side effects but also in terms of cost and which patients will receive maximum benefits and should be covered by insurance.” 

Drucker has served as a consultant or speaker for Altimmune, Amgen, AstraZeneca, Arrowhead, Boehringer Ingelheim, Kallyope, Merck Research Laboratories, Novo Nordisk, Pfizer, and Zealand Pharma. He holds nonexercised options in Kallyope. Mount Sinai Hospital receives research support for investigator-initiated studies in the Drucker laboratory from Amgen, Novo Nordisk, Pfizer, and Zealand Pharma. Gila Therapeutics and Phenomix Sciences have licensed Acosta’s research technologies from University of Florida and Mayo Clinic. Acosta received consultant fees in the last 5 years from Rhythm Pharmaceuticals, Gila Therapeutics, Amgen, General Mills, Regeneron Pharmaceuticals, Boehringer Ingelheim, Novo Nordisk, Currax, Nestlé, Phenomix Sciences, Bausch Health, and Rare Disease. He received funding support from the National Institutes of Health, Vivus Pharmaceuticals, Novo Nordisk, Apollo Endosurgery, Satiogen Pharmaceuticals, Spatz Medical, Rhythm Pharmaceuticals, Regeneron Pharmaceuticals, Boehringer Ingelheim, and Novo Nordisk. In the past, Cornier has served as a consultant for Novo Nordisk.

 

A version of this article first appeared on Medscape.com.