Preventive Care

A Lancet Commission has redefined obesity by classifying it as either “clinical obesity,” a disease, or “preclinical,” a health risk factor, with the distinction based on factors beyond body mass index (BMI).

“We propose a radical overhaul of the actual diagnosis of obesity to improve global healthcare and practices and policies. The specific aims were to facilitate individualized assessment and care of people living with obesity while preserving resources by reducing overdiagnosis and unnecessary or inadequate interventions,” Professor Louise Baur, chair of Child & Adolescent Health at the University of Sydney, Australia, said during a UK Science Media Centre (SMC) news briefing.

The report calls first for a diagnosis of obesity via confirmation of excess adiposity using measures such as waist circumference or waist-to-hip ratio in addition to BMI. Next, a clinical assessment of signs and symptoms of organ dysfunction due to obesity and/or functional limitations determines whether the individual has the disease “clinical obesity,” or “preclinical obesity,” a condition of health risk but not an illness itself.

Published on January 14, 2025, in The Lancet Diabetes & Endocrinology, the document also provides broad guidance on management for the two obesity conditions, emphasizing a personalized and stigma-free approach. The Lancet Commission on Obesity comprised 56 experts in relevant fields including endocrinology, surgery, nutrition, and public health, along with people living with obesity.

The report has been endorsed by more than 75 medical organizations, including the Association of British Clinical Diabetologists, the American Association of Clinical Endocrinologists, the American Diabetes Association, the American Heart Association, the Obesity Society, the World Obesity Federation, and obesity and endocrinology societies from countries in Europe, Latin America, Asia, and South Africa.

In recent years, many in the field have found fault with the current BMI-based definition of obesity (> 30 for people of European descent or other cutoffs for specific ethnic groups), primarily because BMI alone doesn’t reflect a person’s fat vs lean mass, fat distribution, or overall health. The new definition aims to overcome these limitations, as well as settle the debate about whether obesity is a “disease.”

“We now have a clinical diagnosis for obesity, which has been lacking. ... The traditional classification based on BMI ... reflects simply whether or not there is excess adiposity, and sometimes not even precise in that regard, either…It has never been a classification that was meant to diagnose a specific illness with its own clinical characteristics in the same way we diagnose any other illness,” Commission Chair Francesco Rubino, MD, professor and chair of Metabolic and Bariatric Surgery at King’s College London, England, said in an interview.

He added, “The fact that now we have a clinical diagnosis allows recognition of the nuance that obesity is generally a risk and for some can be an illness. There are some who have risk but don’t have the illness here and now. And it’s crucially important for clinical decision-making, but also for policies to have a distinction between those two things because the treatment strategy for one and the other are substantially different.”

Asked to comment, obesity specialist Michael A. Weintraub, MD, clinical assistant professor of endocrinology at New York University Langone Health, said in an interview, “I wholeheartedly agree with modifying the definition of obesity in this more accurate way. ... There has already been a lot of talk about the fallibility of BMI and that BMI over 30 does not equal obesity. ... So a major Commission article like this I think can really move those discussions even more into the forefront and start changing practice.” 

However, Weintraub added, “I think there needs to be another step here of more practical guidance on how to actually implement this ... including how to measure waist circumference and to put it into a patient flow.” 

Asked to comment, obesity expert Luca Busetto, MD, associate professor of internal medicine at the Department of Medicine of the University of Padova, Italy, said in an interview that he agrees with the general concept of moving beyond BMI in defining obesity. That view was expressed in a proposed “framework” from the European Association for the Study of Obesity (EASO), for which Busetto was the lead author.

Busetto also agrees with the emphasis on the need for a complete clinical evaluation of patients to define their health status. “The precise definition of the symptoms defining clinical obesity in adults and children is extremely important, emphasizing the fact that obesity is a severe and disabling disease by itself, even without or before the occurrence of obesity-related complications,” he said.

However, he takes issue with the Commission’s designation that “preclinical” obesity is not a disease. “The critical point of disagreement for me is the message that obesity is a disease only if it is clinical or only if it presents functional impairment or clinical symptoms. This remains, in my opinion, an oversimplification, not taking into account the fact that the pathophysiological mechanisms that lead to fat accumulation and ‘adipose tissue-based chronic disease’ usually start well before the occurrence of symptoms.”

Busetto pointed to examples such as type 2 diabetes and chronic kidney disease, both of which can be asymptomatic in their early phases yet are still considered diseases at those points. “I have no problem in accepting a distinction between preclinical and clinical stages of the disease, and I like the definition of clinical obesity, but why should this imply the fact that obesity is NOT a disease since its beginning?”

The Commission does state that preclinical obesity should be addressed, mostly with preventive approaches but in some cases with more intensive management. “This is highly relevant, but the risk of an undertreatment of obesity in its asymptomatic state remains in place. This could delay appropriate management for a progressive disease that certainly should not be treated only when presenting symptoms. It would be too late,” Busetto said.

And EASO framework coauthor Gijs Goossens, PhD, professor of cardiometabolic physiology of obesity at Maastricht University Medical Centre, the Netherlands, added a concern that those with excess adiposity but lower BMI might be missed entirely, noting “Since abdominal fat accumulation better predicts chronic cardiometabolic diseases and can also be accompanied by clinical manifestations in individuals with overweight as a consequence of compromised adipose tissue function, the proposed model may lead to underdiagnosis or undertreatment in individuals with BMI 25-30 who have excess abdominal fat.”

 

Diagnosis and Management Beyond BMI

The Commission advises the use of BMI solely as a marker to screen for potential obesity. Those with a BMI > 40 can be assumed to have excess body fat. For others with a BMI at or near the threshold for obesity in a specific country or ethnic group or for whom there is the clinical judgment of the potential for clinical obesity, confirmation of excess or abnormal adiposity is needed by one of the following:

• At least one measurement of body size and BMI
• At least two measures of body size, regardless of BMI
• Direct body fat measurement, such as a dual-energy x-ray absorptiometry (DEXA) scan

Measurement of body size can be assessed in three ways: 

• Waist circumference ≥ 102 cm for men and ≥ 88 cm for women
• Waist-to-hip ratio > 0.90 for men and > 0.50 for women
• Waist-to-height ratio > 0.50 for all.

Weintraub noted, “Telemedicine is a useful tool used by many patients and providers but may also make it challenging to accurately assess someone’s body size. Having technology like an iPhone app to measure body size would circumvent this challenge but this type of tool has not yet been validated.” 

If the person does not have excess adiposity, they don’t have obesity. Those with excess adiposity do have obesity. Further assessment is then needed to establish whether the person has an illness, that is, clinical obesity, indicated by signs/symptoms of organ dysfunction, and/or limitations of daily activities. If not, they have “preclinical” obesity.

The document provides a list of 18 obesity-related organ, tissue, and body system criteria for diagnosing “clinical” obesity in adults, including upper airways (eg, apneas/hypopneas), respiratory (breathlessness), cardiovascular (hypertension, heart failure), liver (fatty liver disease with hepatic fibrosis), reproductive (polycystic ovary syndrome, hypogonadism), and metabolism (hyperglycemia, hypertriglyceridemia, low high-density lipoprotein cholesterol). A list of 13 such criteria is also provided for children. “Limitations of day-to-day activities” are included on both lists.

 

Management Differs by Designation

For preclinical obesity, management should focus on risk reduction and prevention of progression to clinical obesity or other obesity-related diseases. Such approaches include health counseling for weight loss or prevention of weight gain, monitoring over time, and active weight loss interventions in people at higher risk of developing clinical obesity and other obesity-related diseases.

Management for clinical obesity focuses on improvements or reversal of the organ dysfunction. The type of evidence-based treatment and management should be informed by individual risk-benefit assessments and decided via “active discussion” with the patient. Success is determined by improvement in the signs and symptoms rather than measures of weight loss.

In response to a reporter’s question at the SMC briefing about the implications for the use of weight-loss medications, Rubino noted that this wasn’t the focus of the report, but nonetheless said that this new obesity definition could help with their targeted use. “The strategy and intent by which you use the drugs is different in clinical and preclinical obesity. ... Pharmacological interventions could be used for patients with high-risk preclinical obesity, with the intent of reducing risk, but we ... would use the same medication at a different intensity, dose, and maybe in combination therapies.”

As for clinical obesity, “It could be more or less severe and could affect more than one organ, and so clinical obesity might require drugs, might require surgery, or may require, in some cases, a combination of both of them, to achieve the best possible outcomes. ... We want to make sure that the person is restoring health ... with whatever it takes.”

Rubino believes this new definition will convince the remaining clinicians who haven’t yet accepted the concept of obesity as a disease. “When they see clinical obesity, I think it will be much harder to say that a biological process that is capable of causing a dysfunction in the heart or the lungs is less of a disease than another biological process that causes similar dysfunction in the heart of the lungs. ... It’s going to be objective. Obesity is a spectrum of different situations. ... When it’s an illness, clinical obesity, it’s not a matter of if or when. It’s a matter of fact.”

There were no industrial grants or other funding for this initiative. King’s Health Partners hosted the initiative and provided logistical and personnel support to facilitate administrative work and the Delphi-like consensus-development process. Rubino declared receiving research grants from Ethicon (Johnson & Johnson), Novo Nordisk, and Medtronic; consulting fees from Morphic Medical; speaking honoraria from Medtronic, Ethicon, Novo Nordisk, Eli Lilly, and Amgen. Rubino has served (unpaid) as a member of the scientific advisory board for Keyron and a member of the data safety and monitoring board for GI Metabolic Solutions; is president of the Metabolic Health Institute (non-profit); and is the sole director of Metabolic Health International and London Metabolic and Bariatric Surgery (private practice). Baur declared serving on the scientific advisory board for Novo Nordisk (for the ACTION Teens study) and Eli Lilly and receiving speaker fees (paid to the institution) from Novo Nordisk.

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

A Lancet Commission has redefined obesity by classifying it as either “clinical obesity,” a disease, or “preclinical,” a health risk factor, with the distinction based on factors beyond body mass index (BMI).

“We propose a radical overhaul of the actual diagnosis of obesity to improve global healthcare and practices and policies. The specific aims were to facilitate individualized assessment and care of people living with obesity while preserving resources by reducing overdiagnosis and unnecessary or inadequate interventions,” Professor Louise Baur, chair of Child & Adolescent Health at the University of Sydney, Australia, said during a UK Science Media Centre (SMC) news briefing.

The report calls first for a diagnosis of obesity via confirmation of excess adiposity using measures such as waist circumference or waist-to-hip ratio in addition to BMI. Next, a clinical assessment of signs and symptoms of organ dysfunction due to obesity and/or functional limitations determines whether the individual has the disease “clinical obesity,” or “preclinical obesity,” a condition of health risk but not an illness itself.

Published on January 14, 2025, in The Lancet Diabetes & Endocrinology, the document also provides broad guidance on management for the two obesity conditions, emphasizing a personalized and stigma-free approach. The Lancet Commission on Obesity comprised 56 experts in relevant fields including endocrinology, surgery, nutrition, and public health, along with people living with obesity.

The report has been endorsed by more than 75 medical organizations, including the Association of British Clinical Diabetologists, the American Association of Clinical Endocrinologists, the American Diabetes Association, the American Heart Association, the Obesity Society, the World Obesity Federation, and obesity and endocrinology societies from countries in Europe, Latin America, Asia, and South Africa.

In recent years, many in the field have found fault with the current BMI-based definition of obesity (> 30 for people of European descent or other cutoffs for specific ethnic groups), primarily because BMI alone doesn’t reflect a person’s fat vs lean mass, fat distribution, or overall health. The new definition aims to overcome these limitations, as well as settle the debate about whether obesity is a “disease.”

“We now have a clinical diagnosis for obesity, which has been lacking. ... The traditional classification based on BMI ... reflects simply whether or not there is excess adiposity, and sometimes not even precise in that regard, either…It has never been a classification that was meant to diagnose a specific illness with its own clinical characteristics in the same way we diagnose any other illness,” Commission Chair Francesco Rubino, MD, professor and chair of Metabolic and Bariatric Surgery at King’s College London, England, said in an interview.

He added, “The fact that now we have a clinical diagnosis allows recognition of the nuance that obesity is generally a risk and for some can be an illness. There are some who have risk but don’t have the illness here and now. And it’s crucially important for clinical decision-making, but also for policies to have a distinction between those two things because the treatment strategy for one and the other are substantially different.”

Asked to comment, obesity specialist Michael A. Weintraub, MD, clinical assistant professor of endocrinology at New York University Langone Health, said in an interview, “I wholeheartedly agree with modifying the definition of obesity in this more accurate way. ... There has already been a lot of talk about the fallibility of BMI and that BMI over 30 does not equal obesity. ... So a major Commission article like this I think can really move those discussions even more into the forefront and start changing practice.” 

However, Weintraub added, “I think there needs to be another step here of more practical guidance on how to actually implement this ... including how to measure waist circumference and to put it into a patient flow.” 

Asked to comment, obesity expert Luca Busetto, MD, associate professor of internal medicine at the Department of Medicine of the University of Padova, Italy, said in an interview that he agrees with the general concept of moving beyond BMI in defining obesity. That view was expressed in a proposed “framework” from the European Association for the Study of Obesity (EASO), for which Busetto was the lead author.

Busetto also agrees with the emphasis on the need for a complete clinical evaluation of patients to define their health status. “The precise definition of the symptoms defining clinical obesity in adults and children is extremely important, emphasizing the fact that obesity is a severe and disabling disease by itself, even without or before the occurrence of obesity-related complications,” he said.

However, he takes issue with the Commission’s designation that “preclinical” obesity is not a disease. “The critical point of disagreement for me is the message that obesity is a disease only if it is clinical or only if it presents functional impairment or clinical symptoms. This remains, in my opinion, an oversimplification, not taking into account the fact that the pathophysiological mechanisms that lead to fat accumulation and ‘adipose tissue-based chronic disease’ usually start well before the occurrence of symptoms.”

Busetto pointed to examples such as type 2 diabetes and chronic kidney disease, both of which can be asymptomatic in their early phases yet are still considered diseases at those points. “I have no problem in accepting a distinction between preclinical and clinical stages of the disease, and I like the definition of clinical obesity, but why should this imply the fact that obesity is NOT a disease since its beginning?”

The Commission does state that preclinical obesity should be addressed, mostly with preventive approaches but in some cases with more intensive management. “This is highly relevant, but the risk of an undertreatment of obesity in its asymptomatic state remains in place. This could delay appropriate management for a progressive disease that certainly should not be treated only when presenting symptoms. It would be too late,” Busetto said.

And EASO framework coauthor Gijs Goossens, PhD, professor of cardiometabolic physiology of obesity at Maastricht University Medical Centre, the Netherlands, added a concern that those with excess adiposity but lower BMI might be missed entirely, noting “Since abdominal fat accumulation better predicts chronic cardiometabolic diseases and can also be accompanied by clinical manifestations in individuals with overweight as a consequence of compromised adipose tissue function, the proposed model may lead to underdiagnosis or undertreatment in individuals with BMI 25-30 who have excess abdominal fat.”

 

Diagnosis and Management Beyond BMI

The Commission advises the use of BMI solely as a marker to screen for potential obesity. Those with a BMI > 40 can be assumed to have excess body fat. For others with a BMI at or near the threshold for obesity in a specific country or ethnic group or for whom there is the clinical judgment of the potential for clinical obesity, confirmation of excess or abnormal adiposity is needed by one of the following:

• At least one measurement of body size and BMI
• At least two measures of body size, regardless of BMI
• Direct body fat measurement, such as a dual-energy x-ray absorptiometry (DEXA) scan

Measurement of body size can be assessed in three ways: 

• Waist circumference ≥ 102 cm for men and ≥ 88 cm for women
• Waist-to-hip ratio > 0.90 for men and > 0.50 for women
• Waist-to-height ratio > 0.50 for all.

Weintraub noted, “Telemedicine is a useful tool used by many patients and providers but may also make it challenging to accurately assess someone’s body size. Having technology like an iPhone app to measure body size would circumvent this challenge but this type of tool has not yet been validated.” 

If the person does not have excess adiposity, they don’t have obesity. Those with excess adiposity do have obesity. Further assessment is then needed to establish whether the person has an illness, that is, clinical obesity, indicated by signs/symptoms of organ dysfunction, and/or limitations of daily activities. If not, they have “preclinical” obesity.

The document provides a list of 18 obesity-related organ, tissue, and body system criteria for diagnosing “clinical” obesity in adults, including upper airways (eg, apneas/hypopneas), respiratory (breathlessness), cardiovascular (hypertension, heart failure), liver (fatty liver disease with hepatic fibrosis), reproductive (polycystic ovary syndrome, hypogonadism), and metabolism (hyperglycemia, hypertriglyceridemia, low high-density lipoprotein cholesterol). A list of 13 such criteria is also provided for children. “Limitations of day-to-day activities” are included on both lists.

 

Management Differs by Designation

For preclinical obesity, management should focus on risk reduction and prevention of progression to clinical obesity or other obesity-related diseases. Such approaches include health counseling for weight loss or prevention of weight gain, monitoring over time, and active weight loss interventions in people at higher risk of developing clinical obesity and other obesity-related diseases.

Management for clinical obesity focuses on improvements or reversal of the organ dysfunction. The type of evidence-based treatment and management should be informed by individual risk-benefit assessments and decided via “active discussion” with the patient. Success is determined by improvement in the signs and symptoms rather than measures of weight loss.

In response to a reporter’s question at the SMC briefing about the implications for the use of weight-loss medications, Rubino noted that this wasn’t the focus of the report, but nonetheless said that this new obesity definition could help with their targeted use. “The strategy and intent by which you use the drugs is different in clinical and preclinical obesity. ... Pharmacological interventions could be used for patients with high-risk preclinical obesity, with the intent of reducing risk, but we ... would use the same medication at a different intensity, dose, and maybe in combination therapies.”

As for clinical obesity, “It could be more or less severe and could affect more than one organ, and so clinical obesity might require drugs, might require surgery, or may require, in some cases, a combination of both of them, to achieve the best possible outcomes. ... We want to make sure that the person is restoring health ... with whatever it takes.”

Rubino believes this new definition will convince the remaining clinicians who haven’t yet accepted the concept of obesity as a disease. “When they see clinical obesity, I think it will be much harder to say that a biological process that is capable of causing a dysfunction in the heart or the lungs is less of a disease than another biological process that causes similar dysfunction in the heart of the lungs. ... It’s going to be objective. Obesity is a spectrum of different situations. ... When it’s an illness, clinical obesity, it’s not a matter of if or when. It’s a matter of fact.”

There were no industrial grants or other funding for this initiative. King’s Health Partners hosted the initiative and provided logistical and personnel support to facilitate administrative work and the Delphi-like consensus-development process. Rubino declared receiving research grants from Ethicon (Johnson & Johnson), Novo Nordisk, and Medtronic; consulting fees from Morphic Medical; speaking honoraria from Medtronic, Ethicon, Novo Nordisk, Eli Lilly, and Amgen. Rubino has served (unpaid) as a member of the scientific advisory board for Keyron and a member of the data safety and monitoring board for GI Metabolic Solutions; is president of the Metabolic Health Institute (non-profit); and is the sole director of Metabolic Health International and London Metabolic and Bariatric Surgery (private practice). Baur declared serving on the scientific advisory board for Novo Nordisk (for the ACTION Teens study) and Eli Lilly and receiving speaker fees (paid to the institution) from Novo Nordisk.

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

A Lancet Commission has redefined obesity by classifying it as either “clinical obesity,” a disease, or “preclinical,” a health risk factor, with the distinction based on factors beyond body mass index (BMI).

“We propose a radical overhaul of the actual diagnosis of obesity to improve global healthcare and practices and policies. The specific aims were to facilitate individualized assessment and care of people living with obesity while preserving resources by reducing overdiagnosis and unnecessary or inadequate interventions,” Professor Louise Baur, chair of Child & Adolescent Health at the University of Sydney, Australia, said during a UK Science Media Centre (SMC) news briefing.

The report calls first for a diagnosis of obesity via confirmation of excess adiposity using measures such as waist circumference or waist-to-hip ratio in addition to BMI. Next, a clinical assessment of signs and symptoms of organ dysfunction due to obesity and/or functional limitations determines whether the individual has the disease “clinical obesity,” or “preclinical obesity,” a condition of health risk but not an illness itself.

Published on January 14, 2025, in The Lancet Diabetes & Endocrinology, the document also provides broad guidance on management for the two obesity conditions, emphasizing a personalized and stigma-free approach. The Lancet Commission on Obesity comprised 56 experts in relevant fields including endocrinology, surgery, nutrition, and public health, along with people living with obesity.

The report has been endorsed by more than 75 medical organizations, including the Association of British Clinical Diabetologists, the American Association of Clinical Endocrinologists, the American Diabetes Association, the American Heart Association, the Obesity Society, the World Obesity Federation, and obesity and endocrinology societies from countries in Europe, Latin America, Asia, and South Africa.

In recent years, many in the field have found fault with the current BMI-based definition of obesity (> 30 for people of European descent or other cutoffs for specific ethnic groups), primarily because BMI alone doesn’t reflect a person’s fat vs lean mass, fat distribution, or overall health. The new definition aims to overcome these limitations, as well as settle the debate about whether obesity is a “disease.”

“We now have a clinical diagnosis for obesity, which has been lacking. ... The traditional classification based on BMI ... reflects simply whether or not there is excess adiposity, and sometimes not even precise in that regard, either…It has never been a classification that was meant to diagnose a specific illness with its own clinical characteristics in the same way we diagnose any other illness,” Commission Chair Francesco Rubino, MD, professor and chair of Metabolic and Bariatric Surgery at King’s College London, England, said in an interview.

He added, “The fact that now we have a clinical diagnosis allows recognition of the nuance that obesity is generally a risk and for some can be an illness. There are some who have risk but don’t have the illness here and now. And it’s crucially important for clinical decision-making, but also for policies to have a distinction between those two things because the treatment strategy for one and the other are substantially different.”

Asked to comment, obesity specialist Michael A. Weintraub, MD, clinical assistant professor of endocrinology at New York University Langone Health, said in an interview, “I wholeheartedly agree with modifying the definition of obesity in this more accurate way. ... There has already been a lot of talk about the fallibility of BMI and that BMI over 30 does not equal obesity. ... So a major Commission article like this I think can really move those discussions even more into the forefront and start changing practice.” 

However, Weintraub added, “I think there needs to be another step here of more practical guidance on how to actually implement this ... including how to measure waist circumference and to put it into a patient flow.” 

Asked to comment, obesity expert Luca Busetto, MD, associate professor of internal medicine at the Department of Medicine of the University of Padova, Italy, said in an interview that he agrees with the general concept of moving beyond BMI in defining obesity. That view was expressed in a proposed “framework” from the European Association for the Study of Obesity (EASO), for which Busetto was the lead author.

Busetto also agrees with the emphasis on the need for a complete clinical evaluation of patients to define their health status. “The precise definition of the symptoms defining clinical obesity in adults and children is extremely important, emphasizing the fact that obesity is a severe and disabling disease by itself, even without or before the occurrence of obesity-related complications,” he said.

However, he takes issue with the Commission’s designation that “preclinical” obesity is not a disease. “The critical point of disagreement for me is the message that obesity is a disease only if it is clinical or only if it presents functional impairment or clinical symptoms. This remains, in my opinion, an oversimplification, not taking into account the fact that the pathophysiological mechanisms that lead to fat accumulation and ‘adipose tissue-based chronic disease’ usually start well before the occurrence of symptoms.”

Busetto pointed to examples such as type 2 diabetes and chronic kidney disease, both of which can be asymptomatic in their early phases yet are still considered diseases at those points. “I have no problem in accepting a distinction between preclinical and clinical stages of the disease, and I like the definition of clinical obesity, but why should this imply the fact that obesity is NOT a disease since its beginning?”

The Commission does state that preclinical obesity should be addressed, mostly with preventive approaches but in some cases with more intensive management. “This is highly relevant, but the risk of an undertreatment of obesity in its asymptomatic state remains in place. This could delay appropriate management for a progressive disease that certainly should not be treated only when presenting symptoms. It would be too late,” Busetto said.

And EASO framework coauthor Gijs Goossens, PhD, professor of cardiometabolic physiology of obesity at Maastricht University Medical Centre, the Netherlands, added a concern that those with excess adiposity but lower BMI might be missed entirely, noting “Since abdominal fat accumulation better predicts chronic cardiometabolic diseases and can also be accompanied by clinical manifestations in individuals with overweight as a consequence of compromised adipose tissue function, the proposed model may lead to underdiagnosis or undertreatment in individuals with BMI 25-30 who have excess abdominal fat.”

 

Diagnosis and Management Beyond BMI

The Commission advises the use of BMI solely as a marker to screen for potential obesity. Those with a BMI > 40 can be assumed to have excess body fat. For others with a BMI at or near the threshold for obesity in a specific country or ethnic group or for whom there is the clinical judgment of the potential for clinical obesity, confirmation of excess or abnormal adiposity is needed by one of the following:

• At least one measurement of body size and BMI
• At least two measures of body size, regardless of BMI
• Direct body fat measurement, such as a dual-energy x-ray absorptiometry (DEXA) scan

Measurement of body size can be assessed in three ways: 

• Waist circumference ≥ 102 cm for men and ≥ 88 cm for women
• Waist-to-hip ratio > 0.90 for men and > 0.50 for women
• Waist-to-height ratio > 0.50 for all.

Weintraub noted, “Telemedicine is a useful tool used by many patients and providers but may also make it challenging to accurately assess someone’s body size. Having technology like an iPhone app to measure body size would circumvent this challenge but this type of tool has not yet been validated.” 

If the person does not have excess adiposity, they don’t have obesity. Those with excess adiposity do have obesity. Further assessment is then needed to establish whether the person has an illness, that is, clinical obesity, indicated by signs/symptoms of organ dysfunction, and/or limitations of daily activities. If not, they have “preclinical” obesity.

The document provides a list of 18 obesity-related organ, tissue, and body system criteria for diagnosing “clinical” obesity in adults, including upper airways (eg, apneas/hypopneas), respiratory (breathlessness), cardiovascular (hypertension, heart failure), liver (fatty liver disease with hepatic fibrosis), reproductive (polycystic ovary syndrome, hypogonadism), and metabolism (hyperglycemia, hypertriglyceridemia, low high-density lipoprotein cholesterol). A list of 13 such criteria is also provided for children. “Limitations of day-to-day activities” are included on both lists.

 

Management Differs by Designation

For preclinical obesity, management should focus on risk reduction and prevention of progression to clinical obesity or other obesity-related diseases. Such approaches include health counseling for weight loss or prevention of weight gain, monitoring over time, and active weight loss interventions in people at higher risk of developing clinical obesity and other obesity-related diseases.

Management for clinical obesity focuses on improvements or reversal of the organ dysfunction. The type of evidence-based treatment and management should be informed by individual risk-benefit assessments and decided via “active discussion” with the patient. Success is determined by improvement in the signs and symptoms rather than measures of weight loss.

In response to a reporter’s question at the SMC briefing about the implications for the use of weight-loss medications, Rubino noted that this wasn’t the focus of the report, but nonetheless said that this new obesity definition could help with their targeted use. “The strategy and intent by which you use the drugs is different in clinical and preclinical obesity. ... Pharmacological interventions could be used for patients with high-risk preclinical obesity, with the intent of reducing risk, but we ... would use the same medication at a different intensity, dose, and maybe in combination therapies.”

As for clinical obesity, “It could be more or less severe and could affect more than one organ, and so clinical obesity might require drugs, might require surgery, or may require, in some cases, a combination of both of them, to achieve the best possible outcomes. ... We want to make sure that the person is restoring health ... with whatever it takes.”

Rubino believes this new definition will convince the remaining clinicians who haven’t yet accepted the concept of obesity as a disease. “When they see clinical obesity, I think it will be much harder to say that a biological process that is capable of causing a dysfunction in the heart or the lungs is less of a disease than another biological process that causes similar dysfunction in the heart of the lungs. ... It’s going to be objective. Obesity is a spectrum of different situations. ... When it’s an illness, clinical obesity, it’s not a matter of if or when. It’s a matter of fact.”

There were no industrial grants or other funding for this initiative. King’s Health Partners hosted the initiative and provided logistical and personnel support to facilitate administrative work and the Delphi-like consensus-development process. Rubino declared receiving research grants from Ethicon (Johnson & Johnson), Novo Nordisk, and Medtronic; consulting fees from Morphic Medical; speaking honoraria from Medtronic, Ethicon, Novo Nordisk, Eli Lilly, and Amgen. Rubino has served (unpaid) as a member of the scientific advisory board for Keyron and a member of the data safety and monitoring board for GI Metabolic Solutions; is president of the Metabolic Health Institute (non-profit); and is the sole director of Metabolic Health International and London Metabolic and Bariatric Surgery (private practice). Baur declared serving on the scientific advisory board for Novo Nordisk (for the ACTION Teens study) and Eli Lilly and receiving speaker fees (paid to the institution) from Novo Nordisk.

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

You could be forgiven if you are confused about how blood pressure (BP) affects dementia. First, you read an article extolling the benefits of BP lowering, then a study about how stopping antihypertensives slows cognitive decline in nursing home residents. It’s enough to make you lose your mind.

The Brain Benefits of BP Lowering

It should be stated unequivocally that you should absolutely treat high BP. It may have once been acceptable to state, “The greatest danger to a man with high blood pressure lies in its discovery, because then some fool is certain to try and reduce it.” But those dark days are long behind us.

In these divided times, at least we can agree that we should treat high BP. The cardiovascular (CV) benefits, in and of themselves, justify the decision. But BP’s relationship with dementia is more complex. There are different types of dementia even though we tend to lump them all into one category. Vascular dementia is driven by the same pathophysiology and risk factors as cardiac disease. It’s intuitive that treating hypertension, diabetes, hypercholesterolemia, and smoking will decrease the risk for stroke and limit the damage to the brain that we see with repeated vascular insults. For Alzheimer’s disease, high BP and other CV risk factors seem to increase the risk even if the mechanism is not fully elucidated.

Estimates suggest that if we could lower the prevalence of hypertension by 25%, there would be 160,000 fewer cases of Alzheimer’s disease. But the data are not as robust as one might hope. A 2021 Cochrane review found that hypertension treatment slowed cognitive decline, but the quality of the evidence was low. Short duration of follow-up, dropouts, crossovers, and other problems with the data precluded any certainty. What’s more, hypertension in midlife is associated with cognitive decline and dementia, but its impact in those over age 70 is less clear. Later in life, or once cognitive impairment has already developed, it may be too late for BP lowering to have any impact.

 

Potential Harms of Lowering BP

All this needs to be weighed against the potential harms of treating hypertension. I will reiterate that hypertension should be treated and treated aggressively for the prevention of CV events. But overtreatment, especially in older patients, is associated with hypotension, falls, and syncope. Older patients are also at risk for polypharmacy and drug-drug interactions. 

When it comes to dementia, there is also a concern that overtreating high BP could make things worse. Hypotension and decreased cerebral perfusion could hasten cognitive decline by depriving the brain of that all too necessary oxygen. 

A Korean nationwide survey showed a U-shaped association between BP and Alzheimer’s disease risk in adults (mean age, 67 years), with both high and low BPs associated with a higher risk for Alzheimer’s disease. Though not all studies agree. A post hoc analysis of SPRINT MIND did not find any negative impact of intensive BP lowering on cognitive outcomes or cerebral perfusion in older adults (mean age, 68 years). But it didn’t do much good either. Given the heterogeneity of the data, doubts remain on whether aggressive BP lowering might be detrimental in older patients with comorbidities and preexisting dementia. The obvious corollary then is whether deprescribing hypertensive medications could be beneficial.

A recent publication in JAMA Internal Medicine attempted to address this very question. The cohort study used data from Veterans Affairs nursing home residents (mean age, 78 years) to emulate a randomized trial on deprescribing antihypertensives and cognitive decline. Many of the residents’ cognitive scores worsened over the course of follow-up; however, the decline was less pronounced in the deprescribing group (10% vs 12%). The same group did a similar analysis looking at CV outcomes and found no increased risk for heart attack or stroke with deprescribing BP medications. Taken together, these nursing home data suggest that deprescribing may help slow cognitive decline without the expected trade-off of increased CV events.

 

Deprescribing, Yes or No? 

However, randomized data would obviously be preferable, and these are in short supply. One such trial, the DANTE study, found no benefit to deprescribing in terms of cognition in adults aged 75 years or older with mild cognitive impairment. The study follow-up was only 16 weeks, however, which is hardly enough time to demonstrate any effect, positive or negative. The most that can be said is that it didn’t cause many short-term adverse events.

Perhaps the best conclusion to draw from this somewhat underwhelming collection of data is that lowering high BP is important, but less important the closer we get to the end of life. Hypotension is obviously bad, and overly aggressive BP lowering is going to lead to negative outcomes in older adults because gravity is an unforgiving mistress. 

Deprescribing antihypertensives in older adults is probably not going to cause major negative outcomes, but whether it will do much good in nonhypotensive patients is debatable. The bigger problem is the millions of people with undiagnosed or undertreated hypertension. We would probably have less dementia if we treated hypertension when it does the most good: as a primary-prevention strategy in midlife.

Dr. Labos is a cardiologist at Hôpital Notre-Dame, Montreal, Quebec, Canada. He disclosed no relevant conflicts of interest.

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

You could be forgiven if you are confused about how blood pressure (BP) affects dementia. First, you read an article extolling the benefits of BP lowering, then a study about how stopping antihypertensives slows cognitive decline in nursing home residents. It’s enough to make you lose your mind.

The Brain Benefits of BP Lowering

It should be stated unequivocally that you should absolutely treat high BP. It may have once been acceptable to state, “The greatest danger to a man with high blood pressure lies in its discovery, because then some fool is certain to try and reduce it.” But those dark days are long behind us.

In these divided times, at least we can agree that we should treat high BP. The cardiovascular (CV) benefits, in and of themselves, justify the decision. But BP’s relationship with dementia is more complex. There are different types of dementia even though we tend to lump them all into one category. Vascular dementia is driven by the same pathophysiology and risk factors as cardiac disease. It’s intuitive that treating hypertension, diabetes, hypercholesterolemia, and smoking will decrease the risk for stroke and limit the damage to the brain that we see with repeated vascular insults. For Alzheimer’s disease, high BP and other CV risk factors seem to increase the risk even if the mechanism is not fully elucidated.

Estimates suggest that if we could lower the prevalence of hypertension by 25%, there would be 160,000 fewer cases of Alzheimer’s disease. But the data are not as robust as one might hope. A 2021 Cochrane review found that hypertension treatment slowed cognitive decline, but the quality of the evidence was low. Short duration of follow-up, dropouts, crossovers, and other problems with the data precluded any certainty. What’s more, hypertension in midlife is associated with cognitive decline and dementia, but its impact in those over age 70 is less clear. Later in life, or once cognitive impairment has already developed, it may be too late for BP lowering to have any impact.

 

Potential Harms of Lowering BP

All this needs to be weighed against the potential harms of treating hypertension. I will reiterate that hypertension should be treated and treated aggressively for the prevention of CV events. But overtreatment, especially in older patients, is associated with hypotension, falls, and syncope. Older patients are also at risk for polypharmacy and drug-drug interactions. 

When it comes to dementia, there is also a concern that overtreating high BP could make things worse. Hypotension and decreased cerebral perfusion could hasten cognitive decline by depriving the brain of that all too necessary oxygen. 

A Korean nationwide survey showed a U-shaped association between BP and Alzheimer’s disease risk in adults (mean age, 67 years), with both high and low BPs associated with a higher risk for Alzheimer’s disease. Though not all studies agree. A post hoc analysis of SPRINT MIND did not find any negative impact of intensive BP lowering on cognitive outcomes or cerebral perfusion in older adults (mean age, 68 years). But it didn’t do much good either. Given the heterogeneity of the data, doubts remain on whether aggressive BP lowering might be detrimental in older patients with comorbidities and preexisting dementia. The obvious corollary then is whether deprescribing hypertensive medications could be beneficial.

A recent publication in JAMA Internal Medicine attempted to address this very question. The cohort study used data from Veterans Affairs nursing home residents (mean age, 78 years) to emulate a randomized trial on deprescribing antihypertensives and cognitive decline. Many of the residents’ cognitive scores worsened over the course of follow-up; however, the decline was less pronounced in the deprescribing group (10% vs 12%). The same group did a similar analysis looking at CV outcomes and found no increased risk for heart attack or stroke with deprescribing BP medications. Taken together, these nursing home data suggest that deprescribing may help slow cognitive decline without the expected trade-off of increased CV events.

 

Deprescribing, Yes or No? 

However, randomized data would obviously be preferable, and these are in short supply. One such trial, the DANTE study, found no benefit to deprescribing in terms of cognition in adults aged 75 years or older with mild cognitive impairment. The study follow-up was only 16 weeks, however, which is hardly enough time to demonstrate any effect, positive or negative. The most that can be said is that it didn’t cause many short-term adverse events.

Perhaps the best conclusion to draw from this somewhat underwhelming collection of data is that lowering high BP is important, but less important the closer we get to the end of life. Hypotension is obviously bad, and overly aggressive BP lowering is going to lead to negative outcomes in older adults because gravity is an unforgiving mistress. 

Deprescribing antihypertensives in older adults is probably not going to cause major negative outcomes, but whether it will do much good in nonhypotensive patients is debatable. The bigger problem is the millions of people with undiagnosed or undertreated hypertension. We would probably have less dementia if we treated hypertension when it does the most good: as a primary-prevention strategy in midlife.

Dr. Labos is a cardiologist at Hôpital Notre-Dame, Montreal, Quebec, Canada. He disclosed no relevant conflicts of interest.

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

You could be forgiven if you are confused about how blood pressure (BP) affects dementia. First, you read an article extolling the benefits of BP lowering, then a study about how stopping antihypertensives slows cognitive decline in nursing home residents. It’s enough to make you lose your mind.

The Brain Benefits of BP Lowering

It should be stated unequivocally that you should absolutely treat high BP. It may have once been acceptable to state, “The greatest danger to a man with high blood pressure lies in its discovery, because then some fool is certain to try and reduce it.” But those dark days are long behind us.

In these divided times, at least we can agree that we should treat high BP. The cardiovascular (CV) benefits, in and of themselves, justify the decision. But BP’s relationship with dementia is more complex. There are different types of dementia even though we tend to lump them all into one category. Vascular dementia is driven by the same pathophysiology and risk factors as cardiac disease. It’s intuitive that treating hypertension, diabetes, hypercholesterolemia, and smoking will decrease the risk for stroke and limit the damage to the brain that we see with repeated vascular insults. For Alzheimer’s disease, high BP and other CV risk factors seem to increase the risk even if the mechanism is not fully elucidated.

Estimates suggest that if we could lower the prevalence of hypertension by 25%, there would be 160,000 fewer cases of Alzheimer’s disease. But the data are not as robust as one might hope. A 2021 Cochrane review found that hypertension treatment slowed cognitive decline, but the quality of the evidence was low. Short duration of follow-up, dropouts, crossovers, and other problems with the data precluded any certainty. What’s more, hypertension in midlife is associated with cognitive decline and dementia, but its impact in those over age 70 is less clear. Later in life, or once cognitive impairment has already developed, it may be too late for BP lowering to have any impact.

 

Potential Harms of Lowering BP

All this needs to be weighed against the potential harms of treating hypertension. I will reiterate that hypertension should be treated and treated aggressively for the prevention of CV events. But overtreatment, especially in older patients, is associated with hypotension, falls, and syncope. Older patients are also at risk for polypharmacy and drug-drug interactions. 

When it comes to dementia, there is also a concern that overtreating high BP could make things worse. Hypotension and decreased cerebral perfusion could hasten cognitive decline by depriving the brain of that all too necessary oxygen. 

A Korean nationwide survey showed a U-shaped association between BP and Alzheimer’s disease risk in adults (mean age, 67 years), with both high and low BPs associated with a higher risk for Alzheimer’s disease. Though not all studies agree. A post hoc analysis of SPRINT MIND did not find any negative impact of intensive BP lowering on cognitive outcomes or cerebral perfusion in older adults (mean age, 68 years). But it didn’t do much good either. Given the heterogeneity of the data, doubts remain on whether aggressive BP lowering might be detrimental in older patients with comorbidities and preexisting dementia. The obvious corollary then is whether deprescribing hypertensive medications could be beneficial.

A recent publication in JAMA Internal Medicine attempted to address this very question. The cohort study used data from Veterans Affairs nursing home residents (mean age, 78 years) to emulate a randomized trial on deprescribing antihypertensives and cognitive decline. Many of the residents’ cognitive scores worsened over the course of follow-up; however, the decline was less pronounced in the deprescribing group (10% vs 12%). The same group did a similar analysis looking at CV outcomes and found no increased risk for heart attack or stroke with deprescribing BP medications. Taken together, these nursing home data suggest that deprescribing may help slow cognitive decline without the expected trade-off of increased CV events.

 

Deprescribing, Yes or No? 

However, randomized data would obviously be preferable, and these are in short supply. One such trial, the DANTE study, found no benefit to deprescribing in terms of cognition in adults aged 75 years or older with mild cognitive impairment. The study follow-up was only 16 weeks, however, which is hardly enough time to demonstrate any effect, positive or negative. The most that can be said is that it didn’t cause many short-term adverse events.

Perhaps the best conclusion to draw from this somewhat underwhelming collection of data is that lowering high BP is important, but less important the closer we get to the end of life. Hypotension is obviously bad, and overly aggressive BP lowering is going to lead to negative outcomes in older adults because gravity is an unforgiving mistress. 

Deprescribing antihypertensives in older adults is probably not going to cause major negative outcomes, but whether it will do much good in nonhypotensive patients is debatable. The bigger problem is the millions of people with undiagnosed or undertreated hypertension. We would probably have less dementia if we treated hypertension when it does the most good: as a primary-prevention strategy in midlife.

Dr. Labos is a cardiologist at Hôpital Notre-Dame, Montreal, Quebec, Canada. He disclosed no relevant conflicts of interest.

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

The latest glucagon-like peptide 1 (GLP-1) receptor agonists have been heralded for their potential to not only boost weight loss and glucose control but also improve cardiovascular, gastric, hepatic, and renal values.

Throughout 2024, research has also indicated GLP-1 drugs may reduce risks for obesity-related cancer.

In a US study of more than 1.6 million patients with type 2 diabetes, cancer researchers found that patients who took a GLP-1 drug had significant risk reductions for 10 of 13 obesity-associated cancers, as compared with patients who only took insulin.

The research team found a reduction in esophageal, colorectal, endometrial, gallbladder, kidney, liver, ovarian, and pancreatic cancers, as well as meningioma and multiple myeloma. They also saw a declining risk for stomach cancer, though it wasn’t considered statistically significant, but not a reduced risk for postmenopausal breast cancer or thyroid cancer.

The associations make sense, particularly because GLP-1 drugs have unexpected effects on modulating immune functions linked to obesity-associated cancers.

“The protective effects of GLP-1s against obesity-associated cancers likely stem from multiple mechanisms,” said lead author Lindsey Wang, a medical student and research scholar at Case Western Reserve University in Cleveland.

“These drugs promote substantial weight loss, reducing obesity-related cancer risks,” she said. “They also enhance insulin sensitivity and lower insulin levels, decreasing cancer cell growth signals.”

 

Additional GLP-1 Studies

The Case Western team also published a study in December 2023 that found people with type 2 diabetes who took GLP-1s had a 44% lower risk for colorectal cancer than those who took insulin and a 25% lower risk than those who took metformin. The research suggested even greater risk reductions among those with overweight or obesity, with GLP-1 users having a 50% lower risk than those who took insulin and a 42% lower risk than those who took metformin.

In another recent Case Western study, both bariatric surgery and GLP-1 drugs reduced the risk for obesity-related cancers. While those who had bariatric surgery had a 22% risk reduction over 10 years, as compared with those who received no treatment, those taking GLP-1 had a 39% risk reduction.

Other studies worldwide have looked at GLP-1 drugs and tumor effects among various cancer cell lines. In a study using pancreatic cancer cell lines, GLP-1 liraglutide suppressed cancer cell growth and led to cell death. Similarly, a study using breast cancer cells found liraglutide reduced cancer cell viability and the ability for cells to migrate.

As researchers identify additional links between GLP-1s and improvements across organ systems, the knock-on effects could lead to lower cancer risks as well. For example, studies presented at The Liver Meeting in San Diego in November pointed to GLP-1s reducing fatty liver disease, which can slow the progression to liver cancer.

“Separate from obesity, having higher levels of body fat is associated with an increased risk of several forms of cancer,” said Neil Iyengar, MD, an oncologist at Memorial Sloan Kettering Cancer Center in New York City. Iyengar researches the relationship between obesity and cancer.

“I foresee that this class of drugs will revolutionize obesity and the cancer burden that comes with it, if people can get access,” he said. “This really is an exciting development.”

 

Ongoing GLP-1 Research

On the other hand, cancer researchers have also expressed concerns about potential associations between GLP-1s and increased cancer risks. In the obesity-associated cancer study by Case Western researchers, patients with type 2 diabetes taking a GLP-1 drug appeared to have a slightly higher risk for kidney cancer than those taking metformin.

In addition, GLP-1 studies in animals have indicated that the drugs may increase the risks for medullary thyroid cancer and pancreatic cancer. However, the data on increased risks in humans remain inconclusive, and more recent studies refute these findings.

For instance, cancer researchers in India conducted a systematic review and meta-analysis of semaglutide and cancer risks, finding that 37 randomized controlled trials and 19 real-world studies didn’t find increased risks for any cancer, including pancreatic and thyroid cancers.

In another systematic review by Brazilian researchers, 50 trials found GLP-1s didn’t increase the risk for breast cancer or benign breast neoplasms.

In 2025, new retrospective studies will show more nuanced data, especially as more patients — both with and without type 2 diabetes — take semaglutide, tirzepatide, and new GLP-1 drugs in the research pipeline.

“The holy grail has always been getting a medication to treat obesity,” said Anne McTiernan, MD, PhD, an epidemiologist and obesity researcher at the Fred Hutchinson Cancer Center in Seattle.

“There have been trials focused on these medications’ effects on diabetes and cardiovascular disease treatment, but no trials have tested their effects on cancer risk,” she said. “Usually, many years of follow-up of large numbers of patients are needed to see cancer effects of a carcinogen or cancer-preventing intervention.”

Those clinical trials are likely coming soon, she said. Researchers will need to conduct prospective clinical trials to examine the direct relationship between GLP-1 drugs and cancer risks, as well as the underlying mechanisms linked to cancer cell growth, activation of immune cells, and anti-inflammatory properties.

Because GLP-1 medications aren’t intended to be taken forever, researchers will also need to consider the associations with long-term cancer risks. Even so, weight loss and other obesity-related improvements could contribute to overall lower cancer risks in the end.

“If taking these drugs for a limited amount of time can help people lose weight and get on an exercise plan, then that’s helping lower cancer risk long-term,” said Sonali Thosani, MD, associate professor of endocrine neoplasia and hormonal disorders at the University of Texas MD Anderson Cancer Center in Houston.

“But it all comes back to someone making lifestyle changes and sticking to them, even after they stop taking the drugs,” she said. “If they can do that, then you’ll probably see a net positive for long-term cancer risks and other long-term health risks.”

 

A version of this article appeared on Medscape.com.

The latest glucagon-like peptide 1 (GLP-1) receptor agonists have been heralded for their potential to not only boost weight loss and glucose control but also improve cardiovascular, gastric, hepatic, and renal values.

Throughout 2024, research has also indicated GLP-1 drugs may reduce risks for obesity-related cancer.

In a US study of more than 1.6 million patients with type 2 diabetes, cancer researchers found that patients who took a GLP-1 drug had significant risk reductions for 10 of 13 obesity-associated cancers, as compared with patients who only took insulin.

The research team found a reduction in esophageal, colorectal, endometrial, gallbladder, kidney, liver, ovarian, and pancreatic cancers, as well as meningioma and multiple myeloma. They also saw a declining risk for stomach cancer, though it wasn’t considered statistically significant, but not a reduced risk for postmenopausal breast cancer or thyroid cancer.

The associations make sense, particularly because GLP-1 drugs have unexpected effects on modulating immune functions linked to obesity-associated cancers.

“The protective effects of GLP-1s against obesity-associated cancers likely stem from multiple mechanisms,” said lead author Lindsey Wang, a medical student and research scholar at Case Western Reserve University in Cleveland.

“These drugs promote substantial weight loss, reducing obesity-related cancer risks,” she said. “They also enhance insulin sensitivity and lower insulin levels, decreasing cancer cell growth signals.”

 

Additional GLP-1 Studies

The Case Western team also published a study in December 2023 that found people with type 2 diabetes who took GLP-1s had a 44% lower risk for colorectal cancer than those who took insulin and a 25% lower risk than those who took metformin. The research suggested even greater risk reductions among those with overweight or obesity, with GLP-1 users having a 50% lower risk than those who took insulin and a 42% lower risk than those who took metformin.

In another recent Case Western study, both bariatric surgery and GLP-1 drugs reduced the risk for obesity-related cancers. While those who had bariatric surgery had a 22% risk reduction over 10 years, as compared with those who received no treatment, those taking GLP-1 had a 39% risk reduction.

Other studies worldwide have looked at GLP-1 drugs and tumor effects among various cancer cell lines. In a study using pancreatic cancer cell lines, GLP-1 liraglutide suppressed cancer cell growth and led to cell death. Similarly, a study using breast cancer cells found liraglutide reduced cancer cell viability and the ability for cells to migrate.

As researchers identify additional links between GLP-1s and improvements across organ systems, the knock-on effects could lead to lower cancer risks as well. For example, studies presented at The Liver Meeting in San Diego in November pointed to GLP-1s reducing fatty liver disease, which can slow the progression to liver cancer.

“Separate from obesity, having higher levels of body fat is associated with an increased risk of several forms of cancer,” said Neil Iyengar, MD, an oncologist at Memorial Sloan Kettering Cancer Center in New York City. Iyengar researches the relationship between obesity and cancer.

“I foresee that this class of drugs will revolutionize obesity and the cancer burden that comes with it, if people can get access,” he said. “This really is an exciting development.”

 

Ongoing GLP-1 Research

On the other hand, cancer researchers have also expressed concerns about potential associations between GLP-1s and increased cancer risks. In the obesity-associated cancer study by Case Western researchers, patients with type 2 diabetes taking a GLP-1 drug appeared to have a slightly higher risk for kidney cancer than those taking metformin.

In addition, GLP-1 studies in animals have indicated that the drugs may increase the risks for medullary thyroid cancer and pancreatic cancer. However, the data on increased risks in humans remain inconclusive, and more recent studies refute these findings.

For instance, cancer researchers in India conducted a systematic review and meta-analysis of semaglutide and cancer risks, finding that 37 randomized controlled trials and 19 real-world studies didn’t find increased risks for any cancer, including pancreatic and thyroid cancers.

In another systematic review by Brazilian researchers, 50 trials found GLP-1s didn’t increase the risk for breast cancer or benign breast neoplasms.

In 2025, new retrospective studies will show more nuanced data, especially as more patients — both with and without type 2 diabetes — take semaglutide, tirzepatide, and new GLP-1 drugs in the research pipeline.

“The holy grail has always been getting a medication to treat obesity,” said Anne McTiernan, MD, PhD, an epidemiologist and obesity researcher at the Fred Hutchinson Cancer Center in Seattle.

“There have been trials focused on these medications’ effects on diabetes and cardiovascular disease treatment, but no trials have tested their effects on cancer risk,” she said. “Usually, many years of follow-up of large numbers of patients are needed to see cancer effects of a carcinogen or cancer-preventing intervention.”

Those clinical trials are likely coming soon, she said. Researchers will need to conduct prospective clinical trials to examine the direct relationship between GLP-1 drugs and cancer risks, as well as the underlying mechanisms linked to cancer cell growth, activation of immune cells, and anti-inflammatory properties.

Because GLP-1 medications aren’t intended to be taken forever, researchers will also need to consider the associations with long-term cancer risks. Even so, weight loss and other obesity-related improvements could contribute to overall lower cancer risks in the end.

“If taking these drugs for a limited amount of time can help people lose weight and get on an exercise plan, then that’s helping lower cancer risk long-term,” said Sonali Thosani, MD, associate professor of endocrine neoplasia and hormonal disorders at the University of Texas MD Anderson Cancer Center in Houston.

“But it all comes back to someone making lifestyle changes and sticking to them, even after they stop taking the drugs,” she said. “If they can do that, then you’ll probably see a net positive for long-term cancer risks and other long-term health risks.”

 

A version of this article appeared on Medscape.com.

The latest glucagon-like peptide 1 (GLP-1) receptor agonists have been heralded for their potential to not only boost weight loss and glucose control but also improve cardiovascular, gastric, hepatic, and renal values.

Throughout 2024, research has also indicated GLP-1 drugs may reduce risks for obesity-related cancer.

In a US study of more than 1.6 million patients with type 2 diabetes, cancer researchers found that patients who took a GLP-1 drug had significant risk reductions for 10 of 13 obesity-associated cancers, as compared with patients who only took insulin.

The research team found a reduction in esophageal, colorectal, endometrial, gallbladder, kidney, liver, ovarian, and pancreatic cancers, as well as meningioma and multiple myeloma. They also saw a declining risk for stomach cancer, though it wasn’t considered statistically significant, but not a reduced risk for postmenopausal breast cancer or thyroid cancer.

The associations make sense, particularly because GLP-1 drugs have unexpected effects on modulating immune functions linked to obesity-associated cancers.

“The protective effects of GLP-1s against obesity-associated cancers likely stem from multiple mechanisms,” said lead author Lindsey Wang, a medical student and research scholar at Case Western Reserve University in Cleveland.

“These drugs promote substantial weight loss, reducing obesity-related cancer risks,” she said. “They also enhance insulin sensitivity and lower insulin levels, decreasing cancer cell growth signals.”

 

Additional GLP-1 Studies

The Case Western team also published a study in December 2023 that found people with type 2 diabetes who took GLP-1s had a 44% lower risk for colorectal cancer than those who took insulin and a 25% lower risk than those who took metformin. The research suggested even greater risk reductions among those with overweight or obesity, with GLP-1 users having a 50% lower risk than those who took insulin and a 42% lower risk than those who took metformin.

In another recent Case Western study, both bariatric surgery and GLP-1 drugs reduced the risk for obesity-related cancers. While those who had bariatric surgery had a 22% risk reduction over 10 years, as compared with those who received no treatment, those taking GLP-1 had a 39% risk reduction.

Other studies worldwide have looked at GLP-1 drugs and tumor effects among various cancer cell lines. In a study using pancreatic cancer cell lines, GLP-1 liraglutide suppressed cancer cell growth and led to cell death. Similarly, a study using breast cancer cells found liraglutide reduced cancer cell viability and the ability for cells to migrate.

As researchers identify additional links between GLP-1s and improvements across organ systems, the knock-on effects could lead to lower cancer risks as well. For example, studies presented at The Liver Meeting in San Diego in November pointed to GLP-1s reducing fatty liver disease, which can slow the progression to liver cancer.

“Separate from obesity, having higher levels of body fat is associated with an increased risk of several forms of cancer,” said Neil Iyengar, MD, an oncologist at Memorial Sloan Kettering Cancer Center in New York City. Iyengar researches the relationship between obesity and cancer.

“I foresee that this class of drugs will revolutionize obesity and the cancer burden that comes with it, if people can get access,” he said. “This really is an exciting development.”

 

Ongoing GLP-1 Research

On the other hand, cancer researchers have also expressed concerns about potential associations between GLP-1s and increased cancer risks. In the obesity-associated cancer study by Case Western researchers, patients with type 2 diabetes taking a GLP-1 drug appeared to have a slightly higher risk for kidney cancer than those taking metformin.

In addition, GLP-1 studies in animals have indicated that the drugs may increase the risks for medullary thyroid cancer and pancreatic cancer. However, the data on increased risks in humans remain inconclusive, and more recent studies refute these findings.

For instance, cancer researchers in India conducted a systematic review and meta-analysis of semaglutide and cancer risks, finding that 37 randomized controlled trials and 19 real-world studies didn’t find increased risks for any cancer, including pancreatic and thyroid cancers.

In another systematic review by Brazilian researchers, 50 trials found GLP-1s didn’t increase the risk for breast cancer or benign breast neoplasms.

In 2025, new retrospective studies will show more nuanced data, especially as more patients — both with and without type 2 diabetes — take semaglutide, tirzepatide, and new GLP-1 drugs in the research pipeline.

“The holy grail has always been getting a medication to treat obesity,” said Anne McTiernan, MD, PhD, an epidemiologist and obesity researcher at the Fred Hutchinson Cancer Center in Seattle.

“There have been trials focused on these medications’ effects on diabetes and cardiovascular disease treatment, but no trials have tested their effects on cancer risk,” she said. “Usually, many years of follow-up of large numbers of patients are needed to see cancer effects of a carcinogen or cancer-preventing intervention.”

Those clinical trials are likely coming soon, she said. Researchers will need to conduct prospective clinical trials to examine the direct relationship between GLP-1 drugs and cancer risks, as well as the underlying mechanisms linked to cancer cell growth, activation of immune cells, and anti-inflammatory properties.

Because GLP-1 medications aren’t intended to be taken forever, researchers will also need to consider the associations with long-term cancer risks. Even so, weight loss and other obesity-related improvements could contribute to overall lower cancer risks in the end.

“If taking these drugs for a limited amount of time can help people lose weight and get on an exercise plan, then that’s helping lower cancer risk long-term,” said Sonali Thosani, MD, associate professor of endocrine neoplasia and hormonal disorders at the University of Texas MD Anderson Cancer Center in Houston.

“But it all comes back to someone making lifestyle changes and sticking to them, even after they stop taking the drugs,” she said. “If they can do that, then you’ll probably see a net positive for long-term cancer risks and other long-term health risks.”

 

A version of this article appeared on Medscape.com.

TOPLINE:

Both low and high levels of high-density lipoprotein (HDL) are associated with an increased risk for age-related macular degeneration (AMD). This study also identified a potential novel single-nucleotide polymorphism linked to an elevated risk for the retina condition.

METHODOLOGY:

• Researchers conducted a cross-sectional retrospective analysis using data from the All of Us research program to assess the association between lipoprotein and the risk for AMD.
• They analyzed data from 2328 patients with AMD (mean age, 75.5 years; 46.7% women; 84.2% White individuals) and 5028 matched controls (mean age, 75.6 years; 52.5% women; 82.9% White individuals).
• Data were extracted for smoking status, history of hyperlipidemia, use of statins (categorized as hepatically and non-hepatically metabolized), and laboratory values for total triglyceride, low-density lipoprotein (LDL), and HDL levels.
• Data for single-nucleotide polymorphisms associated with the dysregulation of LDL and HDL metabolism were extracted using the PLINK toolkit.

TAKEAWAY:

• Both high and low HDL levels were associated with an increased risk for AMD (adjusted odds ratio [aOR], 1.28 for both; both P < .001), whereas low and high levels of triglyceride and LDL did not demonstrate a statistically significant association with the risk for AMD.
• A history of smoking and statin use showed significant associations with an increased risk for AMD (aOR, 1.30 and 1.36, respectively; both P < .001).
• Single-nucleotide polymorphisms in the genes associated with HDL metabolism, ABCA1 and LIPC, were negatively associated with the risk for AMD (aOR, 0.88; P = .04 and aOR, 0.86; P = .001, respectively).
• Lipoprotein(a) or Lp(a) was identified as a novel single nucleotide polymorphism linked to an increased risk for AMD (aOR, 1.37; P = .007).

IN PRACTICE:

“Despite conflicting evidence regarding the relationship with elevated HDL and AMD risk, this is to our knowledge the first time a U-shaped relationship with low and high HDL and AMD has been described. In fact, the presence of a U-shaped relationship may explain inconsistency in prior analyses comparing mean HDL levels in AMD and control populations,” the study authors wrote. 

SOURCE:

The study was led by Jimmy S. Chen, MD, of the Viterbi Family Department of Ophthalmology and Shiley Eye Institute at the University of California, San Diego. It was published online on January 3, 2025, in Ophthalmology.

LIMITATIONS:

The study was limited by the retrospective collection and analysis of data. The use of billing codes for diagnosis extraction may have introduced documentation inaccuracies. The subgroup analysis by severity of AMD was not performed.

DISCLOSURES:

One of the authors was funded by grants from the National Eye Institute (NEI), Research to Prevent Blindness Career Development Award, Robert Machemer MD and International Retinal Research Foundation, and the UC San Diego Academic Senate. Another author reported receiving a grant from the National Heart, Lung, and Blood Institute, while a third author received funding from the National Institutes of Health (NIH), NEI, and Research to Prevent Blindness. The All of Us Research Program was supported by grants from the NIH and other sources. The authors reported no conflicts of interest.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Both low and high levels of high-density lipoprotein (HDL) are associated with an increased risk for age-related macular degeneration (AMD). This study also identified a potential novel single-nucleotide polymorphism linked to an elevated risk for the retina condition.

METHODOLOGY:

• Researchers conducted a cross-sectional retrospective analysis using data from the All of Us research program to assess the association between lipoprotein and the risk for AMD.
• They analyzed data from 2328 patients with AMD (mean age, 75.5 years; 46.7% women; 84.2% White individuals) and 5028 matched controls (mean age, 75.6 years; 52.5% women; 82.9% White individuals).
• Data were extracted for smoking status, history of hyperlipidemia, use of statins (categorized as hepatically and non-hepatically metabolized), and laboratory values for total triglyceride, low-density lipoprotein (LDL), and HDL levels.
• Data for single-nucleotide polymorphisms associated with the dysregulation of LDL and HDL metabolism were extracted using the PLINK toolkit.

TAKEAWAY:

• Both high and low HDL levels were associated with an increased risk for AMD (adjusted odds ratio [aOR], 1.28 for both; both P < .001), whereas low and high levels of triglyceride and LDL did not demonstrate a statistically significant association with the risk for AMD.
• A history of smoking and statin use showed significant associations with an increased risk for AMD (aOR, 1.30 and 1.36, respectively; both P < .001).
• Single-nucleotide polymorphisms in the genes associated with HDL metabolism, ABCA1 and LIPC, were negatively associated with the risk for AMD (aOR, 0.88; P = .04 and aOR, 0.86; P = .001, respectively).
• Lipoprotein(a) or Lp(a) was identified as a novel single nucleotide polymorphism linked to an increased risk for AMD (aOR, 1.37; P = .007).

IN PRACTICE:

“Despite conflicting evidence regarding the relationship with elevated HDL and AMD risk, this is to our knowledge the first time a U-shaped relationship with low and high HDL and AMD has been described. In fact, the presence of a U-shaped relationship may explain inconsistency in prior analyses comparing mean HDL levels in AMD and control populations,” the study authors wrote. 

SOURCE:

The study was led by Jimmy S. Chen, MD, of the Viterbi Family Department of Ophthalmology and Shiley Eye Institute at the University of California, San Diego. It was published online on January 3, 2025, in Ophthalmology.

LIMITATIONS:

The study was limited by the retrospective collection and analysis of data. The use of billing codes for diagnosis extraction may have introduced documentation inaccuracies. The subgroup analysis by severity of AMD was not performed.

DISCLOSURES:

One of the authors was funded by grants from the National Eye Institute (NEI), Research to Prevent Blindness Career Development Award, Robert Machemer MD and International Retinal Research Foundation, and the UC San Diego Academic Senate. Another author reported receiving a grant from the National Heart, Lung, and Blood Institute, while a third author received funding from the National Institutes of Health (NIH), NEI, and Research to Prevent Blindness. The All of Us Research Program was supported by grants from the NIH and other sources. The authors reported no conflicts of interest.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Both low and high levels of high-density lipoprotein (HDL) are associated with an increased risk for age-related macular degeneration (AMD). This study also identified a potential novel single-nucleotide polymorphism linked to an elevated risk for the retina condition.

METHODOLOGY:

• Researchers conducted a cross-sectional retrospective analysis using data from the All of Us research program to assess the association between lipoprotein and the risk for AMD.
• They analyzed data from 2328 patients with AMD (mean age, 75.5 years; 46.7% women; 84.2% White individuals) and 5028 matched controls (mean age, 75.6 years; 52.5% women; 82.9% White individuals).
• Data were extracted for smoking status, history of hyperlipidemia, use of statins (categorized as hepatically and non-hepatically metabolized), and laboratory values for total triglyceride, low-density lipoprotein (LDL), and HDL levels.
• Data for single-nucleotide polymorphisms associated with the dysregulation of LDL and HDL metabolism were extracted using the PLINK toolkit.

TAKEAWAY:

• Both high and low HDL levels were associated with an increased risk for AMD (adjusted odds ratio [aOR], 1.28 for both; both P < .001), whereas low and high levels of triglyceride and LDL did not demonstrate a statistically significant association with the risk for AMD.
• A history of smoking and statin use showed significant associations with an increased risk for AMD (aOR, 1.30 and 1.36, respectively; both P < .001).
• Single-nucleotide polymorphisms in the genes associated with HDL metabolism, ABCA1 and LIPC, were negatively associated with the risk for AMD (aOR, 0.88; P = .04 and aOR, 0.86; P = .001, respectively).
• Lipoprotein(a) or Lp(a) was identified as a novel single nucleotide polymorphism linked to an increased risk for AMD (aOR, 1.37; P = .007).

IN PRACTICE:

“Despite conflicting evidence regarding the relationship with elevated HDL and AMD risk, this is to our knowledge the first time a U-shaped relationship with low and high HDL and AMD has been described. In fact, the presence of a U-shaped relationship may explain inconsistency in prior analyses comparing mean HDL levels in AMD and control populations,” the study authors wrote. 

SOURCE:

The study was led by Jimmy S. Chen, MD, of the Viterbi Family Department of Ophthalmology and Shiley Eye Institute at the University of California, San Diego. It was published online on January 3, 2025, in Ophthalmology.

LIMITATIONS:

The study was limited by the retrospective collection and analysis of data. The use of billing codes for diagnosis extraction may have introduced documentation inaccuracies. The subgroup analysis by severity of AMD was not performed.

DISCLOSURES:

One of the authors was funded by grants from the National Eye Institute (NEI), Research to Prevent Blindness Career Development Award, Robert Machemer MD and International Retinal Research Foundation, and the UC San Diego Academic Senate. Another author reported receiving a grant from the National Heart, Lung, and Blood Institute, while a third author received funding from the National Institutes of Health (NIH), NEI, and Research to Prevent Blindness. The All of Us Research Program was supported by grants from the NIH and other sources. The authors reported no conflicts of interest.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The evidence is clear: Alcohol can cause cancer.

Earlier this month, US surgeon general Vivek Murthy, MD, issued an advisory, calling for alcoholic beverages to carry a warning label about cancer risk. The advisory flagged alcohol as the third leading preventable cause of cancer in the United States, after tobacco and obesity, and highlighted people’s limited awareness about the relationship between alcohol and cancer risk.

But, when it comes to cancer risk, are all types of alcohol created equal?

For many years, red wine seemed to be an outlier, with studies indicating that, in moderation, it might even be good for you. Red wine has anti-inflammatory and antioxidant properties — most notably, it contains the antioxidant resveratrol. Starting in the 1990s, research began to hint that the compound might protect against heart disease, aging, and cancer, though much of this work was done in animals or test tubes.

The idea that red wine carries health benefits, however, has been called into question more recently. A recent meta-analysis, for instance, suggests that many previous studies touting the health benefits of more moderate drinking were likely biased, potentially leading to “misleading positive health associations.” And one recent study found that alcohol consumption, largely red wine and beer, at all levels was linked to an increased risk for cardiovascular disease.

Although wine’s health halo is dwindling, there might be an exception: Cancer risk.

Overall, research shows that even light to moderate drinking increases the risk for at least seven types of cancer, but when focusing on red wine, in particular, that risk calculus can look different.

“It’s very complicated and nuanced,” said Timothy Rebbeck, PhD, professor of cancer prevention, Harvard T.H. Chan School of Public Health, Boston. “And ‘complicated and nuanced’ doesn’t work very well in public health messages.”

The Knowns About Alcohol and Cancer Risk

Some things about the relationship between alcohol and cancer risk are crystal clear. “There’s no question that alcohol is a group 1 carcinogen,” Rebbeck said. “Alcohol can cause cancer.”

Groups including the International Agency for Research on Cancer (IARC) and American Cancer Society agree that alcohol use is an established cause of seven types of cancer: Those of the oral cavity, larynx, pharynx, esophagus (squamous cell carcinoma), liver (hepatocellular carcinoma), breast, and colon/rectum. Heavy drinking — at least 8 standard drinks a week for women and 15 for men — and binge drinking — 4 or more drinks in 2 hours for women and 5 or more for men — only amplify that risk. (A “standard” drink has 14 g of alcohol, which translates to a 5-oz glass of wine.)

“We’re most concerned about high-risk drinking — more than 2 drinks a day — and/or binge drinking,” said Noelle LoConte, MD, of the Division of Hematology, Medical Oncology and Palliative Care, University of Wisconsin School of Medicine and Public Health, Madison, who authored a 2018 statement on alcohol and cancer risk from the American Society of Clinical Oncology (ASCO).

Compared with not drinking, heavy drinking is linked with a roughly fivefold increase in the risk for oral cavity, pharyngeal, and esophageal cancers, and a 61% increase in the risk for breast cancer, according to LoConte and colleagues.

Things get murkier when it comes to moderate drinking — defined as up to 1 standard drink per day for women and 2 per day for men. There is evidence, LoConte said, that moderate drinking is associated with increased cancer risks, though the magnitude is generally much less than heavier drinking.

Cancer type also matters. One analysis found that the risk for breast cancer increased with even light to moderate alcohol consumption. Compared with no drinking, light to moderate drinking has also been linked to increased risks for oral cavity, pharynx, larynx, and esophageal cancers.

As for whether the type of alcoholic beverage matters, LoConte said, there’s no clear physiological reason that wine would be less risky than beer or liquor. Research indicates that ethanol is the problematic ingredient: Once ingested, it’s metabolized into acetaldehyde, a DNA-damaging substance that’s considered a probable human carcinogen. Ethanol can also alter circulating levels of estrogens and androgens, LoConte said, which is thought to drive its association with breast cancer risk.

“It likely doesn’t matter how you choose to get your ethanol,” she said. “It’s a question of volume.”

Hints That Wine Is an Outlier

Still, some studies suggest that how people ingest ethanol could make a difference.

A study published in August in JAMA Network Open is a case in point. The study found that, among older adults, light to heavy drinkers had an increased risk of dying from cancer, compared with occasional drinkers (though the increased risk among light to moderate drinkers occurred only among people who also had chronic health conditions, such as diabetes or high blood pressure, or were of lower socioeconomic status).

Wine drinkers fared differently. Most notably, drinkers who “preferred” wine — consuming over 80% of total ethanol from wine — or those who drank only with meals showed a small reduction in their risk for cancer mortality and all-cause mortality (hazard ratio [HR], 0.94 for both). The small protective association was somewhat stronger among people who reported both patterns (HR, 0.88), especially if they were of lower socioeconomic status (HR, 0.79).

The findings are in line with other research suggesting that wine drinkers may be outliers when it comes to cancer risk. A 2023 meta-analysis of 26 observational studies, for instance, found no association between wine consumption and any cancer type, with the caveat that there was «substantial» heterogeneity among the studies.

This heterogeneity caveat speaks to the inherent limitations of observational research, said Tim Stockwell, PhD, of the Canadian Institute for Substance Use Research, University of Victoria in British Columbia, Canada.

“Individual studies of alcohol and cancer risk do find differences by type of drink, or patterns of drinking,” Stockwell said. “But it’s so hard to unpack the confounding that goes along with the type of person who’s a wine drinker or a beer drinker or a spirit drinker. The beverage of choice seems to come with a lot of baggage.”

Compared with people who favor beer or liquor, he noted, wine aficionados are typically higher-income, exercise more often, smoke less, and have different diets, for example. The “best” studies, Rebbeck said, try to adjust for those differences, but it’s challenging.

The authors of the 2023 meta-analysis noted that “many components in wine could have anticarcinogenic effects” that theoretically could counter the ill effects of ethanol. Besides resveratrol, which is mainly found in red wine, the list includes anthocyanins, quercetin, and tannins. However, the authors also acknowledged that they couldn’t account for whether other lifestyle habits might explain why wine drinkers, overall, showed no increased cancer risks and sometimes lower risks.

Still, groups such as the IARC and ASCO hold that there is no known “safe” level, or type, of alcohol when it comes to cancer.

In the latest Canadian guidelines on alcohol use, the scientific panel calculated that people who have 6 drinks a week throughout adulthood (whatever the source of the alcohol) could shave 11 weeks from their life expectancy, on average, said Stockwell, who was on the guideline panel. Compare that with heavy drinking, where 4 drinks a day could rob the average person of 2 or 3 years. “If you’re drinking a lot, you could get huge benefits from cutting down,” Stockwell explained. “If you’re a moderate drinker, the benefits would obviously be less.”

Stockwell said that choices around drinking and breast cancer risk, specifically, can be “tough.” Unlike many of the other alcohol-associated cancers, he noted, breast cancer is common — so even small relative risk increases may be concerning. Based on a 2020 meta-analysis of 22 cohort studies, the risk for breast cancer rises by about 10%, on average, for every 10 g of alcohol a woman drinks per day. This study also found no evidence that wine is any different from other types of alcohol.

In real life, the calculus around wine consumption and cancer risk will probably vary widely from person to person, Rebbeck said. One woman with a family history of breast cancer might decide that having wine with dinner isn’t worth it. Another with the same family history might see that glass of wine as a stress reliever and opt to focus on other ways to reduce her breast cancer risk — by exercising and maintaining a healthy weight, for example.

“The bottom line is, in human studies, the data on light to moderate drinking and cancer are limited and messy, and you can’t draw firm conclusions from them,” Rebbeck said. “It probably raises risk in some people, but we don’t know who those people are. And the risk increases are relatively small.”

A Conversation Few Are Having

Even with many studies highlighting the connection between alcohol consumption and cancer risk, most people remain unaware about this risk.

A 2023 study by the National Cancer Institute found that only a minority of US adults knew that drinking alcohol is linked to increased cancer risk, and they were much less likely to say that was true of wine: Only 20% did, vs 31% who said that liquor can boost cancer risk. Meanwhile, 10% believed that wine helps prevent cancer. Other studies show that even among cancer survivors and patients undergoing active cancer treatment, many drink — often heavily.

“What we know right now is, physicians almost never talk about this,” LoConte said.

That could be due to time constraints, according to Rebbeck, or clinicians’ perceptions that the subject is too complicated and/or their own confusion about the data. There could also be some “cognitive dissonance” at play, LoConte noted, because many doctors drink alcohol.

It’s critical, she said, that conversations about drinking habits become “normalized,” and that should include informing patients that alcohol use is associated with certain cancers. Again, LoConte said, it’s high-risk drinking that’s most concerning and where reducing intake could have the biggest impact on cancer risk and other health outcomes.

“From a cancer prevention standpoint, it’s probably best not to drink,” she said. “But people don’t make choices based solely on cancer risk. We don’t want to come out with recommendations saying no one should drink. I don’t think the data support that, and people would buck against that advice.”

Rebbeck made a similar point. Even if there’s uncertainty about the risks for a daily glass of wine, he said, people can use that information to make decisions. “Everybody’s preferences and choices are going to be different,” Rebbeck said. “And that’s all we can really do.”

A version of this article appeared on Medscape.com.

The evidence is clear: Alcohol can cause cancer.

Earlier this month, US surgeon general Vivek Murthy, MD, issued an advisory, calling for alcoholic beverages to carry a warning label about cancer risk. The advisory flagged alcohol as the third leading preventable cause of cancer in the United States, after tobacco and obesity, and highlighted people’s limited awareness about the relationship between alcohol and cancer risk.

But, when it comes to cancer risk, are all types of alcohol created equal?

For many years, red wine seemed to be an outlier, with studies indicating that, in moderation, it might even be good for you. Red wine has anti-inflammatory and antioxidant properties — most notably, it contains the antioxidant resveratrol. Starting in the 1990s, research began to hint that the compound might protect against heart disease, aging, and cancer, though much of this work was done in animals or test tubes.

The idea that red wine carries health benefits, however, has been called into question more recently. A recent meta-analysis, for instance, suggests that many previous studies touting the health benefits of more moderate drinking were likely biased, potentially leading to “misleading positive health associations.” And one recent study found that alcohol consumption, largely red wine and beer, at all levels was linked to an increased risk for cardiovascular disease.

Although wine’s health halo is dwindling, there might be an exception: Cancer risk.

Overall, research shows that even light to moderate drinking increases the risk for at least seven types of cancer, but when focusing on red wine, in particular, that risk calculus can look different.

“It’s very complicated and nuanced,” said Timothy Rebbeck, PhD, professor of cancer prevention, Harvard T.H. Chan School of Public Health, Boston. “And ‘complicated and nuanced’ doesn’t work very well in public health messages.”

The Knowns About Alcohol and Cancer Risk

Some things about the relationship between alcohol and cancer risk are crystal clear. “There’s no question that alcohol is a group 1 carcinogen,” Rebbeck said. “Alcohol can cause cancer.”

Groups including the International Agency for Research on Cancer (IARC) and American Cancer Society agree that alcohol use is an established cause of seven types of cancer: Those of the oral cavity, larynx, pharynx, esophagus (squamous cell carcinoma), liver (hepatocellular carcinoma), breast, and colon/rectum. Heavy drinking — at least 8 standard drinks a week for women and 15 for men — and binge drinking — 4 or more drinks in 2 hours for women and 5 or more for men — only amplify that risk. (A “standard” drink has 14 g of alcohol, which translates to a 5-oz glass of wine.)

“We’re most concerned about high-risk drinking — more than 2 drinks a day — and/or binge drinking,” said Noelle LoConte, MD, of the Division of Hematology, Medical Oncology and Palliative Care, University of Wisconsin School of Medicine and Public Health, Madison, who authored a 2018 statement on alcohol and cancer risk from the American Society of Clinical Oncology (ASCO).

Compared with not drinking, heavy drinking is linked with a roughly fivefold increase in the risk for oral cavity, pharyngeal, and esophageal cancers, and a 61% increase in the risk for breast cancer, according to LoConte and colleagues.

Things get murkier when it comes to moderate drinking — defined as up to 1 standard drink per day for women and 2 per day for men. There is evidence, LoConte said, that moderate drinking is associated with increased cancer risks, though the magnitude is generally much less than heavier drinking.

Cancer type also matters. One analysis found that the risk for breast cancer increased with even light to moderate alcohol consumption. Compared with no drinking, light to moderate drinking has also been linked to increased risks for oral cavity, pharynx, larynx, and esophageal cancers.

As for whether the type of alcoholic beverage matters, LoConte said, there’s no clear physiological reason that wine would be less risky than beer or liquor. Research indicates that ethanol is the problematic ingredient: Once ingested, it’s metabolized into acetaldehyde, a DNA-damaging substance that’s considered a probable human carcinogen. Ethanol can also alter circulating levels of estrogens and androgens, LoConte said, which is thought to drive its association with breast cancer risk.

“It likely doesn’t matter how you choose to get your ethanol,” she said. “It’s a question of volume.”

Hints That Wine Is an Outlier

Still, some studies suggest that how people ingest ethanol could make a difference.

A study published in August in JAMA Network Open is a case in point. The study found that, among older adults, light to heavy drinkers had an increased risk of dying from cancer, compared with occasional drinkers (though the increased risk among light to moderate drinkers occurred only among people who also had chronic health conditions, such as diabetes or high blood pressure, or were of lower socioeconomic status).

Wine drinkers fared differently. Most notably, drinkers who “preferred” wine — consuming over 80% of total ethanol from wine — or those who drank only with meals showed a small reduction in their risk for cancer mortality and all-cause mortality (hazard ratio [HR], 0.94 for both). The small protective association was somewhat stronger among people who reported both patterns (HR, 0.88), especially if they were of lower socioeconomic status (HR, 0.79).

The findings are in line with other research suggesting that wine drinkers may be outliers when it comes to cancer risk. A 2023 meta-analysis of 26 observational studies, for instance, found no association between wine consumption and any cancer type, with the caveat that there was «substantial» heterogeneity among the studies.

This heterogeneity caveat speaks to the inherent limitations of observational research, said Tim Stockwell, PhD, of the Canadian Institute for Substance Use Research, University of Victoria in British Columbia, Canada.

“Individual studies of alcohol and cancer risk do find differences by type of drink, or patterns of drinking,” Stockwell said. “But it’s so hard to unpack the confounding that goes along with the type of person who’s a wine drinker or a beer drinker or a spirit drinker. The beverage of choice seems to come with a lot of baggage.”

Compared with people who favor beer or liquor, he noted, wine aficionados are typically higher-income, exercise more often, smoke less, and have different diets, for example. The “best” studies, Rebbeck said, try to adjust for those differences, but it’s challenging.

The authors of the 2023 meta-analysis noted that “many components in wine could have anticarcinogenic effects” that theoretically could counter the ill effects of ethanol. Besides resveratrol, which is mainly found in red wine, the list includes anthocyanins, quercetin, and tannins. However, the authors also acknowledged that they couldn’t account for whether other lifestyle habits might explain why wine drinkers, overall, showed no increased cancer risks and sometimes lower risks.

Still, groups such as the IARC and ASCO hold that there is no known “safe” level, or type, of alcohol when it comes to cancer.

In the latest Canadian guidelines on alcohol use, the scientific panel calculated that people who have 6 drinks a week throughout adulthood (whatever the source of the alcohol) could shave 11 weeks from their life expectancy, on average, said Stockwell, who was on the guideline panel. Compare that with heavy drinking, where 4 drinks a day could rob the average person of 2 or 3 years. “If you’re drinking a lot, you could get huge benefits from cutting down,” Stockwell explained. “If you’re a moderate drinker, the benefits would obviously be less.”

Stockwell said that choices around drinking and breast cancer risk, specifically, can be “tough.” Unlike many of the other alcohol-associated cancers, he noted, breast cancer is common — so even small relative risk increases may be concerning. Based on a 2020 meta-analysis of 22 cohort studies, the risk for breast cancer rises by about 10%, on average, for every 10 g of alcohol a woman drinks per day. This study also found no evidence that wine is any different from other types of alcohol.

In real life, the calculus around wine consumption and cancer risk will probably vary widely from person to person, Rebbeck said. One woman with a family history of breast cancer might decide that having wine with dinner isn’t worth it. Another with the same family history might see that glass of wine as a stress reliever and opt to focus on other ways to reduce her breast cancer risk — by exercising and maintaining a healthy weight, for example.

“The bottom line is, in human studies, the data on light to moderate drinking and cancer are limited and messy, and you can’t draw firm conclusions from them,” Rebbeck said. “It probably raises risk in some people, but we don’t know who those people are. And the risk increases are relatively small.”

A Conversation Few Are Having

Even with many studies highlighting the connection between alcohol consumption and cancer risk, most people remain unaware about this risk.

A 2023 study by the National Cancer Institute found that only a minority of US adults knew that drinking alcohol is linked to increased cancer risk, and they were much less likely to say that was true of wine: Only 20% did, vs 31% who said that liquor can boost cancer risk. Meanwhile, 10% believed that wine helps prevent cancer. Other studies show that even among cancer survivors and patients undergoing active cancer treatment, many drink — often heavily.

“What we know right now is, physicians almost never talk about this,” LoConte said.

That could be due to time constraints, according to Rebbeck, or clinicians’ perceptions that the subject is too complicated and/or their own confusion about the data. There could also be some “cognitive dissonance” at play, LoConte noted, because many doctors drink alcohol.

It’s critical, she said, that conversations about drinking habits become “normalized,” and that should include informing patients that alcohol use is associated with certain cancers. Again, LoConte said, it’s high-risk drinking that’s most concerning and where reducing intake could have the biggest impact on cancer risk and other health outcomes.

“From a cancer prevention standpoint, it’s probably best not to drink,” she said. “But people don’t make choices based solely on cancer risk. We don’t want to come out with recommendations saying no one should drink. I don’t think the data support that, and people would buck against that advice.”

Rebbeck made a similar point. Even if there’s uncertainty about the risks for a daily glass of wine, he said, people can use that information to make decisions. “Everybody’s preferences and choices are going to be different,” Rebbeck said. “And that’s all we can really do.”

A version of this article appeared on Medscape.com.

The evidence is clear: Alcohol can cause cancer.

Earlier this month, US surgeon general Vivek Murthy, MD, issued an advisory, calling for alcoholic beverages to carry a warning label about cancer risk. The advisory flagged alcohol as the third leading preventable cause of cancer in the United States, after tobacco and obesity, and highlighted people’s limited awareness about the relationship between alcohol and cancer risk.

But, when it comes to cancer risk, are all types of alcohol created equal?

For many years, red wine seemed to be an outlier, with studies indicating that, in moderation, it might even be good for you. Red wine has anti-inflammatory and antioxidant properties — most notably, it contains the antioxidant resveratrol. Starting in the 1990s, research began to hint that the compound might protect against heart disease, aging, and cancer, though much of this work was done in animals or test tubes.

The idea that red wine carries health benefits, however, has been called into question more recently. A recent meta-analysis, for instance, suggests that many previous studies touting the health benefits of more moderate drinking were likely biased, potentially leading to “misleading positive health associations.” And one recent study found that alcohol consumption, largely red wine and beer, at all levels was linked to an increased risk for cardiovascular disease.

Although wine’s health halo is dwindling, there might be an exception: Cancer risk.

Overall, research shows that even light to moderate drinking increases the risk for at least seven types of cancer, but when focusing on red wine, in particular, that risk calculus can look different.

“It’s very complicated and nuanced,” said Timothy Rebbeck, PhD, professor of cancer prevention, Harvard T.H. Chan School of Public Health, Boston. “And ‘complicated and nuanced’ doesn’t work very well in public health messages.”

The Knowns About Alcohol and Cancer Risk

Some things about the relationship between alcohol and cancer risk are crystal clear. “There’s no question that alcohol is a group 1 carcinogen,” Rebbeck said. “Alcohol can cause cancer.”

Groups including the International Agency for Research on Cancer (IARC) and American Cancer Society agree that alcohol use is an established cause of seven types of cancer: Those of the oral cavity, larynx, pharynx, esophagus (squamous cell carcinoma), liver (hepatocellular carcinoma), breast, and colon/rectum. Heavy drinking — at least 8 standard drinks a week for women and 15 for men — and binge drinking — 4 or more drinks in 2 hours for women and 5 or more for men — only amplify that risk. (A “standard” drink has 14 g of alcohol, which translates to a 5-oz glass of wine.)

“We’re most concerned about high-risk drinking — more than 2 drinks a day — and/or binge drinking,” said Noelle LoConte, MD, of the Division of Hematology, Medical Oncology and Palliative Care, University of Wisconsin School of Medicine and Public Health, Madison, who authored a 2018 statement on alcohol and cancer risk from the American Society of Clinical Oncology (ASCO).

Compared with not drinking, heavy drinking is linked with a roughly fivefold increase in the risk for oral cavity, pharyngeal, and esophageal cancers, and a 61% increase in the risk for breast cancer, according to LoConte and colleagues.

Things get murkier when it comes to moderate drinking — defined as up to 1 standard drink per day for women and 2 per day for men. There is evidence, LoConte said, that moderate drinking is associated with increased cancer risks, though the magnitude is generally much less than heavier drinking.

Cancer type also matters. One analysis found that the risk for breast cancer increased with even light to moderate alcohol consumption. Compared with no drinking, light to moderate drinking has also been linked to increased risks for oral cavity, pharynx, larynx, and esophageal cancers.

As for whether the type of alcoholic beverage matters, LoConte said, there’s no clear physiological reason that wine would be less risky than beer or liquor. Research indicates that ethanol is the problematic ingredient: Once ingested, it’s metabolized into acetaldehyde, a DNA-damaging substance that’s considered a probable human carcinogen. Ethanol can also alter circulating levels of estrogens and androgens, LoConte said, which is thought to drive its association with breast cancer risk.

“It likely doesn’t matter how you choose to get your ethanol,” she said. “It’s a question of volume.”

Hints That Wine Is an Outlier

Still, some studies suggest that how people ingest ethanol could make a difference.

A study published in August in JAMA Network Open is a case in point. The study found that, among older adults, light to heavy drinkers had an increased risk of dying from cancer, compared with occasional drinkers (though the increased risk among light to moderate drinkers occurred only among people who also had chronic health conditions, such as diabetes or high blood pressure, or were of lower socioeconomic status).

Wine drinkers fared differently. Most notably, drinkers who “preferred” wine — consuming over 80% of total ethanol from wine — or those who drank only with meals showed a small reduction in their risk for cancer mortality and all-cause mortality (hazard ratio [HR], 0.94 for both). The small protective association was somewhat stronger among people who reported both patterns (HR, 0.88), especially if they were of lower socioeconomic status (HR, 0.79).

The findings are in line with other research suggesting that wine drinkers may be outliers when it comes to cancer risk. A 2023 meta-analysis of 26 observational studies, for instance, found no association between wine consumption and any cancer type, with the caveat that there was «substantial» heterogeneity among the studies.

This heterogeneity caveat speaks to the inherent limitations of observational research, said Tim Stockwell, PhD, of the Canadian Institute for Substance Use Research, University of Victoria in British Columbia, Canada.

“Individual studies of alcohol and cancer risk do find differences by type of drink, or patterns of drinking,” Stockwell said. “But it’s so hard to unpack the confounding that goes along with the type of person who’s a wine drinker or a beer drinker or a spirit drinker. The beverage of choice seems to come with a lot of baggage.”

Compared with people who favor beer or liquor, he noted, wine aficionados are typically higher-income, exercise more often, smoke less, and have different diets, for example. The “best” studies, Rebbeck said, try to adjust for those differences, but it’s challenging.

The authors of the 2023 meta-analysis noted that “many components in wine could have anticarcinogenic effects” that theoretically could counter the ill effects of ethanol. Besides resveratrol, which is mainly found in red wine, the list includes anthocyanins, quercetin, and tannins. However, the authors also acknowledged that they couldn’t account for whether other lifestyle habits might explain why wine drinkers, overall, showed no increased cancer risks and sometimes lower risks.

Still, groups such as the IARC and ASCO hold that there is no known “safe” level, or type, of alcohol when it comes to cancer.

In the latest Canadian guidelines on alcohol use, the scientific panel calculated that people who have 6 drinks a week throughout adulthood (whatever the source of the alcohol) could shave 11 weeks from their life expectancy, on average, said Stockwell, who was on the guideline panel. Compare that with heavy drinking, where 4 drinks a day could rob the average person of 2 or 3 years. “If you’re drinking a lot, you could get huge benefits from cutting down,” Stockwell explained. “If you’re a moderate drinker, the benefits would obviously be less.”

Stockwell said that choices around drinking and breast cancer risk, specifically, can be “tough.” Unlike many of the other alcohol-associated cancers, he noted, breast cancer is common — so even small relative risk increases may be concerning. Based on a 2020 meta-analysis of 22 cohort studies, the risk for breast cancer rises by about 10%, on average, for every 10 g of alcohol a woman drinks per day. This study also found no evidence that wine is any different from other types of alcohol.

In real life, the calculus around wine consumption and cancer risk will probably vary widely from person to person, Rebbeck said. One woman with a family history of breast cancer might decide that having wine with dinner isn’t worth it. Another with the same family history might see that glass of wine as a stress reliever and opt to focus on other ways to reduce her breast cancer risk — by exercising and maintaining a healthy weight, for example.

“The bottom line is, in human studies, the data on light to moderate drinking and cancer are limited and messy, and you can’t draw firm conclusions from them,” Rebbeck said. “It probably raises risk in some people, but we don’t know who those people are. And the risk increases are relatively small.”

A Conversation Few Are Having

Even with many studies highlighting the connection between alcohol consumption and cancer risk, most people remain unaware about this risk.

A 2023 study by the National Cancer Institute found that only a minority of US adults knew that drinking alcohol is linked to increased cancer risk, and they were much less likely to say that was true of wine: Only 20% did, vs 31% who said that liquor can boost cancer risk. Meanwhile, 10% believed that wine helps prevent cancer. Other studies show that even among cancer survivors and patients undergoing active cancer treatment, many drink — often heavily.

“What we know right now is, physicians almost never talk about this,” LoConte said.

That could be due to time constraints, according to Rebbeck, or clinicians’ perceptions that the subject is too complicated and/or their own confusion about the data. There could also be some “cognitive dissonance” at play, LoConte noted, because many doctors drink alcohol.

It’s critical, she said, that conversations about drinking habits become “normalized,” and that should include informing patients that alcohol use is associated with certain cancers. Again, LoConte said, it’s high-risk drinking that’s most concerning and where reducing intake could have the biggest impact on cancer risk and other health outcomes.

“From a cancer prevention standpoint, it’s probably best not to drink,” she said. “But people don’t make choices based solely on cancer risk. We don’t want to come out with recommendations saying no one should drink. I don’t think the data support that, and people would buck against that advice.”

Rebbeck made a similar point. Even if there’s uncertainty about the risks for a daily glass of wine, he said, people can use that information to make decisions. “Everybody’s preferences and choices are going to be different,” Rebbeck said. “And that’s all we can really do.”

A version of this article appeared on Medscape.com.

New data link higher county-level radon exposure to gestational diabetes (GD) in women who haven’t previously given birth, emphasizing the need to consider environmental risks in maternal and fetal healthcare.

Yijia Zhang, PhD, with the Department of Obstetrics and Gynecology, Vagelos College of Physicians and Surgeons at Columbia University Irving Medical Center in New York, and colleagues found in a study of 9107 nulliparous pregnant women that those living in US counties with higher radon levels (2 picocuries [pCi]/L) had higher odds of developing GD than those in counties with lower (< 1 pCi/L) radon levels (odds ratio [OR], 1.37; 95% CI, 1.02-1.84.) The researchers used three radon categories, and the middle level was 1 to < 2 pCi/L.

Findings were published online on January 10 in JAMA Network Open. The researchers used data from The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b), a multicenter, prospective cohort study that examines factors associated with pregnancy-related outcomes.

“To our knowledge, this is the first study to examine the association between radon exposure and the risk of GD,” the authors wrote.

The researchers also found higher odds of GD in women who had ever smoked who lived in counties with a higher (2 pCi/L) radon level (OR, 2.09; 95% CI, 1.41-3.11) and women living in counties with both higher radon and fine particulate matter air pollutants (PM2.5) levels (OR, 1.93; 95% CI, 1.31-2.83), though no statistically significant interactions were observed. 

 

GD Affects 10% of Pregnancies

GD affects about 10% of pregnancies every year in the United States, according to the Centers for Disease Control and Prevention, and can affect women and offspring long term as it raises mothers’ risk of type 2 diabetes and cardiovascular disease and raises the risk for childhood obesity. Radon exposure’s link with lung cancer risk has been well established, but its link to other health risks is uncertain, the authors note.

The authors said their findings are hypothesis-generating and said, “It is vital to conduct studies that incorporate individual-level indoor radon exposure data,” to get closer to understanding the underlying mechanisms.

 

Individual-Level Exposure Measures Needed

They note that the average radon level in a county might not reflect an individual’s exposure and individual-level residential factors involved with radon exposure, such as household mitigation, and whether a dwelling has a basement, for instance, “are crucial for enhancing the precision of exposure assessment.”

In an invited commentary, Alberto Ruano-Ravina, PhD, and Lucía Martín-Gisbert, MSc, both with the Department of Preventive Medicine and Public Health at the University of Santiago de Compostela in Galicia, Spain, also urged that individual-level studies be conducted to further investigate radon’s link to health risks, noting that “[r]adon is possibly the most prevalent indoor carcinogen to which human beings are exposed.”

“There is no reason for not having these studies once we have some evidence of an association from ecological studies,” they wrote. They point out that reliable radon assessments are easy and inexpensive.

“The potential association of radon exposure with gestational diabetes or any other disease should be better analyzed using exclusively radon-prone areas. An observance of a dose-response effect may be indicative of a causal relationship, and it could be easily evidenced in radon-prone areas should such a relationship exist,” the commenters wrote.

Such areas have low, medium, high, and extremely high concentration levels, the commenters wrote. Zhang’s team, they point out, had to use only three exposure levels because the number of residents in high-exposure areas (exceeding 3 pCi/L) was too small.

“It is time now to move forward and really understand the full implications of radon exposure for health,” they concluded.

One coauthor reported serving on the board of directors for Merck for Mothers and as a board member for March for Moms outside the submitted work. One coauthor reported grants from the National Heart, Lung, and Blood Institute and the National Institutes of Health (NIH) during the conduct of the study. Four coauthors reported grants from the NIH during the conduct of the study. One coauthor reported grants from the NIH during the conduct of the study and being a cofounder of Naima Health and receiving personal fees from Organon outside the submitted work. Both commenters reported no relevant financial disclosures.

A version of this article appeared on Medscape.com.

New data link higher county-level radon exposure to gestational diabetes (GD) in women who haven’t previously given birth, emphasizing the need to consider environmental risks in maternal and fetal healthcare.

Yijia Zhang, PhD, with the Department of Obstetrics and Gynecology, Vagelos College of Physicians and Surgeons at Columbia University Irving Medical Center in New York, and colleagues found in a study of 9107 nulliparous pregnant women that those living in US counties with higher radon levels (2 picocuries [pCi]/L) had higher odds of developing GD than those in counties with lower (< 1 pCi/L) radon levels (odds ratio [OR], 1.37; 95% CI, 1.02-1.84.) The researchers used three radon categories, and the middle level was 1 to < 2 pCi/L.

Findings were published online on January 10 in JAMA Network Open. The researchers used data from The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b), a multicenter, prospective cohort study that examines factors associated with pregnancy-related outcomes.

“To our knowledge, this is the first study to examine the association between radon exposure and the risk of GD,” the authors wrote.

The researchers also found higher odds of GD in women who had ever smoked who lived in counties with a higher (2 pCi/L) radon level (OR, 2.09; 95% CI, 1.41-3.11) and women living in counties with both higher radon and fine particulate matter air pollutants (PM2.5) levels (OR, 1.93; 95% CI, 1.31-2.83), though no statistically significant interactions were observed. 

 

GD Affects 10% of Pregnancies

GD affects about 10% of pregnancies every year in the United States, according to the Centers for Disease Control and Prevention, and can affect women and offspring long term as it raises mothers’ risk of type 2 diabetes and cardiovascular disease and raises the risk for childhood obesity. Radon exposure’s link with lung cancer risk has been well established, but its link to other health risks is uncertain, the authors note.

The authors said their findings are hypothesis-generating and said, “It is vital to conduct studies that incorporate individual-level indoor radon exposure data,” to get closer to understanding the underlying mechanisms.

 

Individual-Level Exposure Measures Needed

They note that the average radon level in a county might not reflect an individual’s exposure and individual-level residential factors involved with radon exposure, such as household mitigation, and whether a dwelling has a basement, for instance, “are crucial for enhancing the precision of exposure assessment.”

In an invited commentary, Alberto Ruano-Ravina, PhD, and Lucía Martín-Gisbert, MSc, both with the Department of Preventive Medicine and Public Health at the University of Santiago de Compostela in Galicia, Spain, also urged that individual-level studies be conducted to further investigate radon’s link to health risks, noting that “[r]adon is possibly the most prevalent indoor carcinogen to which human beings are exposed.”

“There is no reason for not having these studies once we have some evidence of an association from ecological studies,” they wrote. They point out that reliable radon assessments are easy and inexpensive.

“The potential association of radon exposure with gestational diabetes or any other disease should be better analyzed using exclusively radon-prone areas. An observance of a dose-response effect may be indicative of a causal relationship, and it could be easily evidenced in radon-prone areas should such a relationship exist,” the commenters wrote.

Such areas have low, medium, high, and extremely high concentration levels, the commenters wrote. Zhang’s team, they point out, had to use only three exposure levels because the number of residents in high-exposure areas (exceeding 3 pCi/L) was too small.

“It is time now to move forward and really understand the full implications of radon exposure for health,” they concluded.

One coauthor reported serving on the board of directors for Merck for Mothers and as a board member for March for Moms outside the submitted work. One coauthor reported grants from the National Heart, Lung, and Blood Institute and the National Institutes of Health (NIH) during the conduct of the study. Four coauthors reported grants from the NIH during the conduct of the study. One coauthor reported grants from the NIH during the conduct of the study and being a cofounder of Naima Health and receiving personal fees from Organon outside the submitted work. Both commenters reported no relevant financial disclosures.

A version of this article appeared on Medscape.com.

New data link higher county-level radon exposure to gestational diabetes (GD) in women who haven’t previously given birth, emphasizing the need to consider environmental risks in maternal and fetal healthcare.

Yijia Zhang, PhD, with the Department of Obstetrics and Gynecology, Vagelos College of Physicians and Surgeons at Columbia University Irving Medical Center in New York, and colleagues found in a study of 9107 nulliparous pregnant women that those living in US counties with higher radon levels (2 picocuries [pCi]/L) had higher odds of developing GD than those in counties with lower (< 1 pCi/L) radon levels (odds ratio [OR], 1.37; 95% CI, 1.02-1.84.) The researchers used three radon categories, and the middle level was 1 to < 2 pCi/L.

Findings were published online on January 10 in JAMA Network Open. The researchers used data from The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b), a multicenter, prospective cohort study that examines factors associated with pregnancy-related outcomes.

“To our knowledge, this is the first study to examine the association between radon exposure and the risk of GD,” the authors wrote.

The researchers also found higher odds of GD in women who had ever smoked who lived in counties with a higher (2 pCi/L) radon level (OR, 2.09; 95% CI, 1.41-3.11) and women living in counties with both higher radon and fine particulate matter air pollutants (PM2.5) levels (OR, 1.93; 95% CI, 1.31-2.83), though no statistically significant interactions were observed. 

 

GD Affects 10% of Pregnancies

GD affects about 10% of pregnancies every year in the United States, according to the Centers for Disease Control and Prevention, and can affect women and offspring long term as it raises mothers’ risk of type 2 diabetes and cardiovascular disease and raises the risk for childhood obesity. Radon exposure’s link with lung cancer risk has been well established, but its link to other health risks is uncertain, the authors note.

The authors said their findings are hypothesis-generating and said, “It is vital to conduct studies that incorporate individual-level indoor radon exposure data,” to get closer to understanding the underlying mechanisms.

 

Individual-Level Exposure Measures Needed

They note that the average radon level in a county might not reflect an individual’s exposure and individual-level residential factors involved with radon exposure, such as household mitigation, and whether a dwelling has a basement, for instance, “are crucial for enhancing the precision of exposure assessment.”

In an invited commentary, Alberto Ruano-Ravina, PhD, and Lucía Martín-Gisbert, MSc, both with the Department of Preventive Medicine and Public Health at the University of Santiago de Compostela in Galicia, Spain, also urged that individual-level studies be conducted to further investigate radon’s link to health risks, noting that “[r]adon is possibly the most prevalent indoor carcinogen to which human beings are exposed.”

“There is no reason for not having these studies once we have some evidence of an association from ecological studies,” they wrote. They point out that reliable radon assessments are easy and inexpensive.

“The potential association of radon exposure with gestational diabetes or any other disease should be better analyzed using exclusively radon-prone areas. An observance of a dose-response effect may be indicative of a causal relationship, and it could be easily evidenced in radon-prone areas should such a relationship exist,” the commenters wrote.

Such areas have low, medium, high, and extremely high concentration levels, the commenters wrote. Zhang’s team, they point out, had to use only three exposure levels because the number of residents in high-exposure areas (exceeding 3 pCi/L) was too small.

“It is time now to move forward and really understand the full implications of radon exposure for health,” they concluded.

One coauthor reported serving on the board of directors for Merck for Mothers and as a board member for March for Moms outside the submitted work. One coauthor reported grants from the National Heart, Lung, and Blood Institute and the National Institutes of Health (NIH) during the conduct of the study. Four coauthors reported grants from the NIH during the conduct of the study. One coauthor reported grants from the NIH during the conduct of the study and being a cofounder of Naima Health and receiving personal fees from Organon outside the submitted work. Both commenters reported no relevant financial disclosures.

A version of this article appeared on Medscape.com.

Given that more than 100 million US adults have obesity, including 22 million with severe obesity, physicians regularly see patients with the condition in their practices.

Fortunately, doctors have more tools than ever to help their patients. But the question remains: Which method is the safest and most effective? Is it diet and lifestyle changes, one of the recently approved anti-obesity medications (AOMs), bariatric surgery, or a combination approach?

There are no head-to-head trials comparing these three approaches, said Vanita Rahman, MD, clinic director of the Barnard Medical Center, Washington, DC, at the International Conference on Nutrition in Medicine, sponsored by the Physicians Committee for Responsible Medicine.

Instead, doctors must evaluate the merits and drawbacks of each intervention and decide with their patients which treatment is best for them, she told Medscape Medical News. When she sees patients, Rahman shares the pertinent research with them, so they are able to make an informed choice.

 

Looking at the Options

In her presentation at the conference, Rahman summarized the guidelines issued by the American Heart Association/American College of Cardiology/The Obesity Society for Management of Overweight and Obesity in Adults and the American Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines For Medical Care of Patients with Obesity, including lifestyle changes, AOMs, and bariatric surgery (Table 1).

As shown, the current clinical guidelines offer recommendations that consider such factors as the patient’s BMI and presence of one or more comorbidities. Generally, they begin with lifestyle changes for people with overweight, the possibility of an AOM for those with obesity, and bariatric surgery as an option for those with severe obesity-related complications.

“In obesity, we traditionally thought the process was ‘either-or’ — either lifestyle or surgery or medication — and somehow lifestyle is better,” Sheethal Reddy, PhD, a psychologist at the Bariatric Center at Emory University Hospital Midtown, Atlanta, told Medscape Medical News.

Now physicians often use a combination of methods, but lifestyle is foundational to all of them, she said.

“If you don’t make lifestyle changes, none of the approaches will ultimately be effective,” said Reddy, who also is an assistant professor in the Division of General and GI Surgery at Emory School of Medicine, Atlanta.

Lifestyle changes don’t just involve diet and nutrition but include physical exercise.

“Being sedentary affects everything — sleep quality, appetite regulation, and metabolism. Without sufficient exercise, the body isn’t functioning well enough to have a healthy metabolism,” Reddy said.

 

How Durable Are the Interventions?

Although bariatric surgery has demonstrated effectiveness in helping patients lose weight, many of them regain some or most of it, Rahman said.

A systematic review and meta-analysis found weight regain in 49% of patients who underwent bariatric surgery patients, with the highest prevalence after Roux-en-Y gastric bypass.

Another study of approximately 45,000 patients who underwent bariatric surgery found differences not only in the percentage of total weight loss among Roux-en-Y gastric bypass, sleeve gastrectomy, and adjustable gastric band procedures but also in how much of that weight stayed off between 1 and 5 years following the procedure (Table 2).

 

Weight regain also is a risk with AOMs, if they’re discontinued.

The STEP 1 trial tested the effectiveness of semaglutide — a glucagon-like peptide 1 (GLP-1) receptor agonist — as an adjunct to lifestyle intervention for weight loss in patients with obesity or with overweight and at least one comorbidity but not diabetes. Mean weight loss with semaglutide was 17.3% but that figure dropped 11.6 percentage points after treatment was discontinued.

Other studies also have found that patients regain weight after GLP-1 discontinuation.

Tirzepatide, a GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) combination, has shown efficacy with weight reduction, but patients experienced some weight regain upon discontinuation. In one study, patients experienced a mean weight loss of 20.9% after 36 weeks of tirzepatide. In the study’s subsequent 52-week double-blind, placebo-controlled period, patients who stopped taking the medication experienced a weight regain of 14%, whereas those who remained on the medication lost an additional 5.5% of weight.

GLP-1 and GLP-1/GIP medications do not address the factors that contribute to overweight and obesity, Rahman said. “They simply suppress the appetite; therefore, weight gain occurs after stopping them.”

Patients may stop taking anti-obesity drugs for a variety of reasons, including side effects. Rahman noted that the common side effects include nausea, vomiting, and constipation, whereas rare side effects include gastroparesis, gallbladder and biliary disease, thyroid cancer, and suicidal thoughts. GLP-1 and GLP-1/GIP medications also carry a risk for non-arteritic anterior ischemic optic neuropathy, she said.

Moreover, health insurance does not always cover these medications, which likely affects patient access to the drugs and compliance rates.

“Given the side effects and frequent lack of insurance coverage, significant questions remain about long-term safety and feasibility of these agents,” Rahman said.

 

What About Nutritional Approaches?

The lifestyle interventions in the semaglutide and tirzepatide studies included 500 kcal/d deficit diets, which is difficult for people to maintain, noted Rahman, who is the author of the book Simply Plant Based: Fabulous Food for a Healthy Life.

Additionally, bariatric surgery has been associated with long-term micronutrient deficiencies, including deficiencies in vitamins A, D, E, K, B1, and B12, as well as folate, iron, zinc, copper, selenium, and calcium, she said.

The best approach to food from a patient compliance standpoint and to avoid nutrient deficiencies is a whole-food, plant-based diet, Rahman said. She advocates this nutritional approach, along with physical activity, for patients regardless of whether they’ve selected lifestyle intervention alone or combined with an AOM or bariatric surgery to address obesity.

Rahman cited a 5-year heart disease study comparing an intensive lifestyle program involving a vegetarian diet, aerobic exercise, stress management training, smoking cessation, and group psychosocial support to treatment as usual. Patients in the lifestyle group lost 10.9 kg at 1 year and sustained weight loss of 5.8 kg at 5 years, whereas weight in the control group remained relatively unchanged from baseline.

She also pointed to the findings of a study of patients with obesity or with overweight and at least one comorbidity that compared standard care with a low-fat, whole-food, plant-based diet with vitamin B12 supplementation. At 6 months, mean BMI reduction was greater in the intervention group than the standard care group (−4.4 vs −0.4).

In her practice, Rahman has seen the benefits of a whole-food, plant-based diet for patients with obesity.

If people are committed to this type of dietary approach and are given the tools and resources to do it effectively, “their thinking changes, their taste buds change, and they grow to enjoy this new way of eating,” she said. “They see results, and it’s a lifestyle that can be sustained long-term.”

 

Addressing Drivers of Weight Gain

Patients also need help addressing the various factors that may contribute to overweight and obesity, including overconsumption of ultra-processed foods, substandard nutritional quality of restaurant foods, increasing portion sizes, distraction during eating, emotional eating, late-night eating, and cultural/traditional values surrounding food, Rahman noted.

Supatra Tovar, PsyD, RD, a clinical psychologist with a practice in Pasadena, California, agreed that identifying the reasons for weight gain is critical for treatment.

“If you’re not addressing underlying issues, such as a person’s relationship with food, behaviors around food, the tendency to mindlessly eat or emotionally eat or eat to seek comfort, the person’s weight problems won’t ultimately be fully solved by any of the three approaches — dieting, medications, or bariatric surgery,” she said.

Some of her patients “engage in extreme dieting and deprivation, and many who use medications or have had bariatric surgery hardly eat and often develop nutritional deficiencies,” said Tovar, author of the book Deprogram Diet Culture: Rethink Your Relationship with Food, Heal Your Mind, and Live a Diet-Free Life.

The key to healthy and sustained weight loss is to “become attuned to the body’s signals, learn how to honor hunger, stop eating when satisfied, and eat more healthful foods, such as fruits and vegetables, whole grains, lean proteins — especially plant-based proteins — and the body gives signals that this is what it wants,” she said.

Tovar doesn’t give her clients a specific diet or set of portions.

“I teach them to listen to their bodies,” she said. “They’ve lost significant amounts of weight and continued to keep it off because they’ve done this kind of work.”

 

When Lifestyle Changes Aren’t Enough

For many patients, lifestyle interventions are insufficient to address the degree of overweight and obesity and common comorbidities, said W. Timothy Garvey, MD, associate director and professor, Department of Nutrition Sciences, School of Health Professions, University of Alabama at Birmingham.

“Of course, nutritional approaches are very important, not only for weight but also for general health-related reasons,” said Garvey, lead author of the 2016 American Association of Clinical Endocrinologists obesity guidelines. “We’ve seen that the Mediterranean and some plant-based diets can prevent progression from prediabetes to diabetes and improve other parameters that reflect metabolic health.”

However, it’s “not common that patients can follow these diets, lose weight, and keep it off,” Garvey cautioned. Up to 50% of weight that’s lost through lifestyle changes is typically regained by 1-year follow-up, with almost all remaining lost weight subsequently regained in the majority of individuals because the person “has to fight against pathophysiological process that drive weight regain,” he noted.

Weight-loss medications can address these pathophysiologic processes by “addressing interactions of satiety hormones with feeding centers in the brain, suppressing the appetite, and making it easier for patients to adhere to a reduced-calorie diet.”

Garvey views the weight-loss medications in the same light as drugs for diabetes and hypertension, in that people need to keep taking them to sustain the benefit.

There’s still a role for bariatric surgery because not everyone can tolerate the AOMs or achieve sufficient weight loss.

“Patients with very high BMI who have trouble ambulating might benefit from a combination of bariatric surgery and medication,” Garvey said.

While some side effects are associated with AOMs, being an “alarmist” about them can be detrimental to patients, he warned.

“We’re treating obesity, which is a serious disease, and we need to employ all the tools that we can,” Garvey said.

Rahman and Tovar are authors of books about weight loss. Reddy reported no relevant financial relationships. Garvey is a consultant on advisory boards for Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Pfizer, Fractyl Health, Alnylam Pharmaceuticals, Inogen, Zealand, Allurion, Carmot/Roche, Terns Pharmaceuticals, Neurocrine, Keros Therapeutics, and Regeneron. He is the site principal investigator for multi-centered clinical trials sponsored by his university and funded by Novo Nordisk, Eli Lilly, Epitomee, Neurovalens, and Pfizer. He serves as a consultant on the advisory board for the nonprofit Milken Foundation and is a member of the Data Monitoring Committee for phase 3 clinical trials conducted by Boehringer-Ingelheim and Eli Lilly.

 

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

Given that more than 100 million US adults have obesity, including 22 million with severe obesity, physicians regularly see patients with the condition in their practices.

Fortunately, doctors have more tools than ever to help their patients. But the question remains: Which method is the safest and most effective? Is it diet and lifestyle changes, one of the recently approved anti-obesity medications (AOMs), bariatric surgery, or a combination approach?

There are no head-to-head trials comparing these three approaches, said Vanita Rahman, MD, clinic director of the Barnard Medical Center, Washington, DC, at the International Conference on Nutrition in Medicine, sponsored by the Physicians Committee for Responsible Medicine.

Instead, doctors must evaluate the merits and drawbacks of each intervention and decide with their patients which treatment is best for them, she told Medscape Medical News. When she sees patients, Rahman shares the pertinent research with them, so they are able to make an informed choice.

 

Looking at the Options

In her presentation at the conference, Rahman summarized the guidelines issued by the American Heart Association/American College of Cardiology/The Obesity Society for Management of Overweight and Obesity in Adults and the American Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines For Medical Care of Patients with Obesity, including lifestyle changes, AOMs, and bariatric surgery (Table 1).

As shown, the current clinical guidelines offer recommendations that consider such factors as the patient’s BMI and presence of one or more comorbidities. Generally, they begin with lifestyle changes for people with overweight, the possibility of an AOM for those with obesity, and bariatric surgery as an option for those with severe obesity-related complications.

“In obesity, we traditionally thought the process was ‘either-or’ — either lifestyle or surgery or medication — and somehow lifestyle is better,” Sheethal Reddy, PhD, a psychologist at the Bariatric Center at Emory University Hospital Midtown, Atlanta, told Medscape Medical News.

Now physicians often use a combination of methods, but lifestyle is foundational to all of them, she said.

“If you don’t make lifestyle changes, none of the approaches will ultimately be effective,” said Reddy, who also is an assistant professor in the Division of General and GI Surgery at Emory School of Medicine, Atlanta.

Lifestyle changes don’t just involve diet and nutrition but include physical exercise.

“Being sedentary affects everything — sleep quality, appetite regulation, and metabolism. Without sufficient exercise, the body isn’t functioning well enough to have a healthy metabolism,” Reddy said.

 

How Durable Are the Interventions?

Although bariatric surgery has demonstrated effectiveness in helping patients lose weight, many of them regain some or most of it, Rahman said.

A systematic review and meta-analysis found weight regain in 49% of patients who underwent bariatric surgery patients, with the highest prevalence after Roux-en-Y gastric bypass.

Another study of approximately 45,000 patients who underwent bariatric surgery found differences not only in the percentage of total weight loss among Roux-en-Y gastric bypass, sleeve gastrectomy, and adjustable gastric band procedures but also in how much of that weight stayed off between 1 and 5 years following the procedure (Table 2).

 

Weight regain also is a risk with AOMs, if they’re discontinued.

The STEP 1 trial tested the effectiveness of semaglutide — a glucagon-like peptide 1 (GLP-1) receptor agonist — as an adjunct to lifestyle intervention for weight loss in patients with obesity or with overweight and at least one comorbidity but not diabetes. Mean weight loss with semaglutide was 17.3% but that figure dropped 11.6 percentage points after treatment was discontinued.

Other studies also have found that patients regain weight after GLP-1 discontinuation.

Tirzepatide, a GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) combination, has shown efficacy with weight reduction, but patients experienced some weight regain upon discontinuation. In one study, patients experienced a mean weight loss of 20.9% after 36 weeks of tirzepatide. In the study’s subsequent 52-week double-blind, placebo-controlled period, patients who stopped taking the medication experienced a weight regain of 14%, whereas those who remained on the medication lost an additional 5.5% of weight.

GLP-1 and GLP-1/GIP medications do not address the factors that contribute to overweight and obesity, Rahman said. “They simply suppress the appetite; therefore, weight gain occurs after stopping them.”

Patients may stop taking anti-obesity drugs for a variety of reasons, including side effects. Rahman noted that the common side effects include nausea, vomiting, and constipation, whereas rare side effects include gastroparesis, gallbladder and biliary disease, thyroid cancer, and suicidal thoughts. GLP-1 and GLP-1/GIP medications also carry a risk for non-arteritic anterior ischemic optic neuropathy, she said.

Moreover, health insurance does not always cover these medications, which likely affects patient access to the drugs and compliance rates.

“Given the side effects and frequent lack of insurance coverage, significant questions remain about long-term safety and feasibility of these agents,” Rahman said.

 

What About Nutritional Approaches?

The lifestyle interventions in the semaglutide and tirzepatide studies included 500 kcal/d deficit diets, which is difficult for people to maintain, noted Rahman, who is the author of the book Simply Plant Based: Fabulous Food for a Healthy Life.

Additionally, bariatric surgery has been associated with long-term micronutrient deficiencies, including deficiencies in vitamins A, D, E, K, B1, and B12, as well as folate, iron, zinc, copper, selenium, and calcium, she said.

The best approach to food from a patient compliance standpoint and to avoid nutrient deficiencies is a whole-food, plant-based diet, Rahman said. She advocates this nutritional approach, along with physical activity, for patients regardless of whether they’ve selected lifestyle intervention alone or combined with an AOM or bariatric surgery to address obesity.

Rahman cited a 5-year heart disease study comparing an intensive lifestyle program involving a vegetarian diet, aerobic exercise, stress management training, smoking cessation, and group psychosocial support to treatment as usual. Patients in the lifestyle group lost 10.9 kg at 1 year and sustained weight loss of 5.8 kg at 5 years, whereas weight in the control group remained relatively unchanged from baseline.

She also pointed to the findings of a study of patients with obesity or with overweight and at least one comorbidity that compared standard care with a low-fat, whole-food, plant-based diet with vitamin B12 supplementation. At 6 months, mean BMI reduction was greater in the intervention group than the standard care group (−4.4 vs −0.4).

In her practice, Rahman has seen the benefits of a whole-food, plant-based diet for patients with obesity.

If people are committed to this type of dietary approach and are given the tools and resources to do it effectively, “their thinking changes, their taste buds change, and they grow to enjoy this new way of eating,” she said. “They see results, and it’s a lifestyle that can be sustained long-term.”

 

Addressing Drivers of Weight Gain

Patients also need help addressing the various factors that may contribute to overweight and obesity, including overconsumption of ultra-processed foods, substandard nutritional quality of restaurant foods, increasing portion sizes, distraction during eating, emotional eating, late-night eating, and cultural/traditional values surrounding food, Rahman noted.

Supatra Tovar, PsyD, RD, a clinical psychologist with a practice in Pasadena, California, agreed that identifying the reasons for weight gain is critical for treatment.

“If you’re not addressing underlying issues, such as a person’s relationship with food, behaviors around food, the tendency to mindlessly eat or emotionally eat or eat to seek comfort, the person’s weight problems won’t ultimately be fully solved by any of the three approaches — dieting, medications, or bariatric surgery,” she said.

Some of her patients “engage in extreme dieting and deprivation, and many who use medications or have had bariatric surgery hardly eat and often develop nutritional deficiencies,” said Tovar, author of the book Deprogram Diet Culture: Rethink Your Relationship with Food, Heal Your Mind, and Live a Diet-Free Life.

The key to healthy and sustained weight loss is to “become attuned to the body’s signals, learn how to honor hunger, stop eating when satisfied, and eat more healthful foods, such as fruits and vegetables, whole grains, lean proteins — especially plant-based proteins — and the body gives signals that this is what it wants,” she said.

Tovar doesn’t give her clients a specific diet or set of portions.

“I teach them to listen to their bodies,” she said. “They’ve lost significant amounts of weight and continued to keep it off because they’ve done this kind of work.”

 

When Lifestyle Changes Aren’t Enough

For many patients, lifestyle interventions are insufficient to address the degree of overweight and obesity and common comorbidities, said W. Timothy Garvey, MD, associate director and professor, Department of Nutrition Sciences, School of Health Professions, University of Alabama at Birmingham.

“Of course, nutritional approaches are very important, not only for weight but also for general health-related reasons,” said Garvey, lead author of the 2016 American Association of Clinical Endocrinologists obesity guidelines. “We’ve seen that the Mediterranean and some plant-based diets can prevent progression from prediabetes to diabetes and improve other parameters that reflect metabolic health.”

However, it’s “not common that patients can follow these diets, lose weight, and keep it off,” Garvey cautioned. Up to 50% of weight that’s lost through lifestyle changes is typically regained by 1-year follow-up, with almost all remaining lost weight subsequently regained in the majority of individuals because the person “has to fight against pathophysiological process that drive weight regain,” he noted.

Weight-loss medications can address these pathophysiologic processes by “addressing interactions of satiety hormones with feeding centers in the brain, suppressing the appetite, and making it easier for patients to adhere to a reduced-calorie diet.”

Garvey views the weight-loss medications in the same light as drugs for diabetes and hypertension, in that people need to keep taking them to sustain the benefit.

There’s still a role for bariatric surgery because not everyone can tolerate the AOMs or achieve sufficient weight loss.

“Patients with very high BMI who have trouble ambulating might benefit from a combination of bariatric surgery and medication,” Garvey said.

While some side effects are associated with AOMs, being an “alarmist” about them can be detrimental to patients, he warned.

“We’re treating obesity, which is a serious disease, and we need to employ all the tools that we can,” Garvey said.

Rahman and Tovar are authors of books about weight loss. Reddy reported no relevant financial relationships. Garvey is a consultant on advisory boards for Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Pfizer, Fractyl Health, Alnylam Pharmaceuticals, Inogen, Zealand, Allurion, Carmot/Roche, Terns Pharmaceuticals, Neurocrine, Keros Therapeutics, and Regeneron. He is the site principal investigator for multi-centered clinical trials sponsored by his university and funded by Novo Nordisk, Eli Lilly, Epitomee, Neurovalens, and Pfizer. He serves as a consultant on the advisory board for the nonprofit Milken Foundation and is a member of the Data Monitoring Committee for phase 3 clinical trials conducted by Boehringer-Ingelheim and Eli Lilly.

 

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

Given that more than 100 million US adults have obesity, including 22 million with severe obesity, physicians regularly see patients with the condition in their practices.

Fortunately, doctors have more tools than ever to help their patients. But the question remains: Which method is the safest and most effective? Is it diet and lifestyle changes, one of the recently approved anti-obesity medications (AOMs), bariatric surgery, or a combination approach?

There are no head-to-head trials comparing these three approaches, said Vanita Rahman, MD, clinic director of the Barnard Medical Center, Washington, DC, at the International Conference on Nutrition in Medicine, sponsored by the Physicians Committee for Responsible Medicine.

Instead, doctors must evaluate the merits and drawbacks of each intervention and decide with their patients which treatment is best for them, she told Medscape Medical News. When she sees patients, Rahman shares the pertinent research with them, so they are able to make an informed choice.

 

Looking at the Options

In her presentation at the conference, Rahman summarized the guidelines issued by the American Heart Association/American College of Cardiology/The Obesity Society for Management of Overweight and Obesity in Adults and the American Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines For Medical Care of Patients with Obesity, including lifestyle changes, AOMs, and bariatric surgery (Table 1).

As shown, the current clinical guidelines offer recommendations that consider such factors as the patient’s BMI and presence of one or more comorbidities. Generally, they begin with lifestyle changes for people with overweight, the possibility of an AOM for those with obesity, and bariatric surgery as an option for those with severe obesity-related complications.

“In obesity, we traditionally thought the process was ‘either-or’ — either lifestyle or surgery or medication — and somehow lifestyle is better,” Sheethal Reddy, PhD, a psychologist at the Bariatric Center at Emory University Hospital Midtown, Atlanta, told Medscape Medical News.

Now physicians often use a combination of methods, but lifestyle is foundational to all of them, she said.

“If you don’t make lifestyle changes, none of the approaches will ultimately be effective,” said Reddy, who also is an assistant professor in the Division of General and GI Surgery at Emory School of Medicine, Atlanta.

Lifestyle changes don’t just involve diet and nutrition but include physical exercise.

“Being sedentary affects everything — sleep quality, appetite regulation, and metabolism. Without sufficient exercise, the body isn’t functioning well enough to have a healthy metabolism,” Reddy said.

 

How Durable Are the Interventions?

Although bariatric surgery has demonstrated effectiveness in helping patients lose weight, many of them regain some or most of it, Rahman said.

A systematic review and meta-analysis found weight regain in 49% of patients who underwent bariatric surgery patients, with the highest prevalence after Roux-en-Y gastric bypass.

Another study of approximately 45,000 patients who underwent bariatric surgery found differences not only in the percentage of total weight loss among Roux-en-Y gastric bypass, sleeve gastrectomy, and adjustable gastric band procedures but also in how much of that weight stayed off between 1 and 5 years following the procedure (Table 2).

 

Weight regain also is a risk with AOMs, if they’re discontinued.

The STEP 1 trial tested the effectiveness of semaglutide — a glucagon-like peptide 1 (GLP-1) receptor agonist — as an adjunct to lifestyle intervention for weight loss in patients with obesity or with overweight and at least one comorbidity but not diabetes. Mean weight loss with semaglutide was 17.3% but that figure dropped 11.6 percentage points after treatment was discontinued.

Other studies also have found that patients regain weight after GLP-1 discontinuation.

Tirzepatide, a GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) combination, has shown efficacy with weight reduction, but patients experienced some weight regain upon discontinuation. In one study, patients experienced a mean weight loss of 20.9% after 36 weeks of tirzepatide. In the study’s subsequent 52-week double-blind, placebo-controlled period, patients who stopped taking the medication experienced a weight regain of 14%, whereas those who remained on the medication lost an additional 5.5% of weight.

GLP-1 and GLP-1/GIP medications do not address the factors that contribute to overweight and obesity, Rahman said. “They simply suppress the appetite; therefore, weight gain occurs after stopping them.”

Patients may stop taking anti-obesity drugs for a variety of reasons, including side effects. Rahman noted that the common side effects include nausea, vomiting, and constipation, whereas rare side effects include gastroparesis, gallbladder and biliary disease, thyroid cancer, and suicidal thoughts. GLP-1 and GLP-1/GIP medications also carry a risk for non-arteritic anterior ischemic optic neuropathy, she said.

Moreover, health insurance does not always cover these medications, which likely affects patient access to the drugs and compliance rates.

“Given the side effects and frequent lack of insurance coverage, significant questions remain about long-term safety and feasibility of these agents,” Rahman said.

 

What About Nutritional Approaches?

The lifestyle interventions in the semaglutide and tirzepatide studies included 500 kcal/d deficit diets, which is difficult for people to maintain, noted Rahman, who is the author of the book Simply Plant Based: Fabulous Food for a Healthy Life.

Additionally, bariatric surgery has been associated with long-term micronutrient deficiencies, including deficiencies in vitamins A, D, E, K, B1, and B12, as well as folate, iron, zinc, copper, selenium, and calcium, she said.

The best approach to food from a patient compliance standpoint and to avoid nutrient deficiencies is a whole-food, plant-based diet, Rahman said. She advocates this nutritional approach, along with physical activity, for patients regardless of whether they’ve selected lifestyle intervention alone or combined with an AOM or bariatric surgery to address obesity.

Rahman cited a 5-year heart disease study comparing an intensive lifestyle program involving a vegetarian diet, aerobic exercise, stress management training, smoking cessation, and group psychosocial support to treatment as usual. Patients in the lifestyle group lost 10.9 kg at 1 year and sustained weight loss of 5.8 kg at 5 years, whereas weight in the control group remained relatively unchanged from baseline.

She also pointed to the findings of a study of patients with obesity or with overweight and at least one comorbidity that compared standard care with a low-fat, whole-food, plant-based diet with vitamin B12 supplementation. At 6 months, mean BMI reduction was greater in the intervention group than the standard care group (−4.4 vs −0.4).

In her practice, Rahman has seen the benefits of a whole-food, plant-based diet for patients with obesity.

If people are committed to this type of dietary approach and are given the tools and resources to do it effectively, “their thinking changes, their taste buds change, and they grow to enjoy this new way of eating,” she said. “They see results, and it’s a lifestyle that can be sustained long-term.”

 

Addressing Drivers of Weight Gain

Patients also need help addressing the various factors that may contribute to overweight and obesity, including overconsumption of ultra-processed foods, substandard nutritional quality of restaurant foods, increasing portion sizes, distraction during eating, emotional eating, late-night eating, and cultural/traditional values surrounding food, Rahman noted.

Supatra Tovar, PsyD, RD, a clinical psychologist with a practice in Pasadena, California, agreed that identifying the reasons for weight gain is critical for treatment.

“If you’re not addressing underlying issues, such as a person’s relationship with food, behaviors around food, the tendency to mindlessly eat or emotionally eat or eat to seek comfort, the person’s weight problems won’t ultimately be fully solved by any of the three approaches — dieting, medications, or bariatric surgery,” she said.

Some of her patients “engage in extreme dieting and deprivation, and many who use medications or have had bariatric surgery hardly eat and often develop nutritional deficiencies,” said Tovar, author of the book Deprogram Diet Culture: Rethink Your Relationship with Food, Heal Your Mind, and Live a Diet-Free Life.

The key to healthy and sustained weight loss is to “become attuned to the body’s signals, learn how to honor hunger, stop eating when satisfied, and eat more healthful foods, such as fruits and vegetables, whole grains, lean proteins — especially plant-based proteins — and the body gives signals that this is what it wants,” she said.

Tovar doesn’t give her clients a specific diet or set of portions.

“I teach them to listen to their bodies,” she said. “They’ve lost significant amounts of weight and continued to keep it off because they’ve done this kind of work.”

 

When Lifestyle Changes Aren’t Enough

For many patients, lifestyle interventions are insufficient to address the degree of overweight and obesity and common comorbidities, said W. Timothy Garvey, MD, associate director and professor, Department of Nutrition Sciences, School of Health Professions, University of Alabama at Birmingham.

“Of course, nutritional approaches are very important, not only for weight but also for general health-related reasons,” said Garvey, lead author of the 2016 American Association of Clinical Endocrinologists obesity guidelines. “We’ve seen that the Mediterranean and some plant-based diets can prevent progression from prediabetes to diabetes and improve other parameters that reflect metabolic health.”

However, it’s “not common that patients can follow these diets, lose weight, and keep it off,” Garvey cautioned. Up to 50% of weight that’s lost through lifestyle changes is typically regained by 1-year follow-up, with almost all remaining lost weight subsequently regained in the majority of individuals because the person “has to fight against pathophysiological process that drive weight regain,” he noted.

Weight-loss medications can address these pathophysiologic processes by “addressing interactions of satiety hormones with feeding centers in the brain, suppressing the appetite, and making it easier for patients to adhere to a reduced-calorie diet.”

Garvey views the weight-loss medications in the same light as drugs for diabetes and hypertension, in that people need to keep taking them to sustain the benefit.

There’s still a role for bariatric surgery because not everyone can tolerate the AOMs or achieve sufficient weight loss.

“Patients with very high BMI who have trouble ambulating might benefit from a combination of bariatric surgery and medication,” Garvey said.

While some side effects are associated with AOMs, being an “alarmist” about them can be detrimental to patients, he warned.

“We’re treating obesity, which is a serious disease, and we need to employ all the tools that we can,” Garvey said.

Rahman and Tovar are authors of books about weight loss. Reddy reported no relevant financial relationships. Garvey is a consultant on advisory boards for Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Pfizer, Fractyl Health, Alnylam Pharmaceuticals, Inogen, Zealand, Allurion, Carmot/Roche, Terns Pharmaceuticals, Neurocrine, Keros Therapeutics, and Regeneron. He is the site principal investigator for multi-centered clinical trials sponsored by his university and funded by Novo Nordisk, Eli Lilly, Epitomee, Neurovalens, and Pfizer. He serves as a consultant on the advisory board for the nonprofit Milken Foundation and is a member of the Data Monitoring Committee for phase 3 clinical trials conducted by Boehringer-Ingelheim and Eli Lilly.

 

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

As the use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) continues to exponentially expand obesity treatment, concerns have arisen regarding their impact on nutrition in people who take them.

While the medications’ dampening effects on appetite result in an average weight reduction ≥ 15%, they also pose a risk for malnutrition.

“It’s important to eat a balanced diet when taking these medications,” Deena Adimoolam, MD, an endocrinologist based in New York City and a member of the national advisory committees for the Endocrine Society and the American Diabetes Association, said in an interview. “If someone’s diet is minimal, it’s important they’re keeping up with their need for macronutrients — protein, fat, carbohydrates — as well as micronutrients — vitamins and minerals.” 

The decreased caloric intake resulting from the use of GLP-1 RAs makes it essential for patients to consume nutrient-dense foods. Clinicians can help patients achieve a healthy diet by anticipating nutrition problems, advising them on recommended target ranges of nutrient intake, and referring them for appropriate counseling.

 

Where to Begin

The task begins with “setting the right expectations before the patient starts treatment,” said Scott Isaacs, MD, president-elect of the American Association of Clinical Endocrinology.

To that end, it’s important to explain to patients how the medications affect appetite and how to adapt. GLP-1 RAs don’t completely turn off the appetite, and the effect at the beginning will likely be very mild, Isaacs said in an interview.

Some patients don’t notice a change for 2-3 months, although others see an effect sooner.

“Typically, people will notice that the main impact is on satiation, meaning they’ll fill up more quickly,” said Isaacs, who is an adjunct associate professor at Emory University School of Medicine, Atlanta, Georgia. “It’s important to tell them to stop eating when they feel full because eating when full can increase the side effects, such as nausea, vomiting, diarrhea, and constipation.”

A review article, written by lead author Jaime Almandoz, MD, University of Texas Southwestern Medical Center, Dallas, in Obesity offers a “5 A’s model” as a guide on how to begin discussing overweight or obesity with patients. This involves asking for permission to discuss weight and asking about food and vitamin/supplement intake; assessing the patient’s medical history and root causes of obesity, and conducting a physical examination; advising the patient regarding treatment options and reasonable expectations; agreeing on treatment and lifestyle goals; and assisting the patient to address challenges, referring them as needed to for additional support (eg, a dietitian), as well as arranging for follow-up.

 

Impact of GLP-1 RAs on Food Preferences

Besides reducing hunger and increasing satiety, GLP-1 RAs may affect food preferences, according to a research review published in The International Journal of Obesity. It cites a 2014 study that found that people taking GLP-1 RAs displayed decreased neuronal responses to images of food measured by functional magnetic resonance imaging in the areas of brain associated with appetite and reward. This might affect taste preferences and food intake.

Additionally, a 2023 study suggested that during the weight-loss phase of treatment (as opposed to the maintenance phase), patients may experience reduced cravings for dairy and starchy food, less desire to eat salty or spicy foods, and less difficulty controlling eating and resisting cravings.

“Altered food preferences, decreased food cravings, and reduced food intake may contribute to long-term weight loss,” according to the research review. Tailored treatments focusing on the weight maintenance phase are needed, the authors wrote.

 

Are Patients Vulnerable to Malnutrition?

A recent review found that total caloric intake was reduced by 16%-39% in patients taking a GLP-1 RA or dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA, but few studies evaluated the composition of these patients’ diets. Research that examines the qualitative changes in macronutrient and micronutrient intake of patients on these medications is needed, the authors wrote.

They outlined several nutritional concerns, including whether GLP-1 RA or GIP/ GLP-1 RA use could result in protein intake insufficient for maintaining muscle strength, mass, and function or in inadequate dietary quality (ie, poor intake of micronutrients, fiber, and fluid).

“Although we don’t necessarily see ‘malnutrition’ in our practice, we do see patients who lose too much weight after months and months of treatment, patients who aren’t hungry and don’t eat all day and have one big meal at the end of the day because they don’t feel like eating, and people who continue to eat unhealthy foods,” Isaacs said.

Some patients, however, have medical histories placing them at a greater risk for malnutrition. “Identification of these individuals may help prevent more serious nutritional and medical complications that might occur with decreased food intake associated with AOMs [anti-obesity medications],” Almandoz and colleagues noted in their review.

 

What Should Patients Eat?

Nutritional needs vary based on the patient’s age, sex, body weight, physical activity, and other factors, Almandoz and colleagues wrote. For this reason, energy intake during weight loss should be “personalized.”

The authors also recommended specific sources of the various dietary components and noted red flags signaling potential deficiencies 

Nutritional needs vary based on the degree of appetite suppression in the patient, Adimoolam said. “I recommend at least two servings of fruits and vegetables daily, and drinking plenty of water throughout the day,” she added.

Protein in particular is a “key macronutrient,” and insufficient intake can lead to a variety of adverse effects, including sarcopenia — which is already a concern in individuals being treated with GLP-1 RAs. Meal replacement products (eg, shakes or bars) can supplement diets to help meet protein needs, especially if appetite is significantly reduced.

“There are definitely concerns for sarcopenia, so we have our patients taking these drugs try to eat healthy lean proteins – 100 g/d — and exercise,” Isaacs said. Exercise, including resistance training, not only improves muscle mass but also potentiates the effects of the GLP-1 RAs in patients with obesity and type 2 diabetes.

Adequate hydration is essential for patients taking GLP-1 RAs. “One of the commonly described side effects is fatigue, but there’s no biological reason why these medications should cause fatigue. My opinion is that these patients are dehydrated, and that may be causing the fatigue,” Isaacs said.

Some patients taking GLP-1 RAs lose interest in food. Isaacs regarded this as an “adverse reaction to the medication, which necessitates either stopping it altogether, changing the dose, or adjusting the diet.” There are “many different solutions, and one size doesn’t fit all,” he said.

 

Dietary and Behavioral Counseling

The drugs don’t necessarily motivate a person to eat healthier food, only to eat less food, Isaacs noted.

“The person might be eating low-volume but high-calorie food, such as bag of chips or a cookie instead of an apple,” Isaacs said. Patients who are losing weight “may not realize that weight loss isn’t the only important outcome. Because they’re losing weight, they think it’s okay to eat junk food.”

Patients need education and guidance about how to eat while on these medications. Most patients find counseling about meal planning helpful, he said.

Isaacs gives nutritional guidance to his patients when he prescribes a weight loss medication. “But most physicians don’t have time to offer that type of specific counseling on an ongoing basis,” he said. Isaacs refers patients requiring more detailed and long-term guidance to a dietitian.

Patients with monotonous diets of poor quality are at increased risk for nutrition deficiencies, and counseling by a registered dietitian could help improve their dietary quality.

Registered dietitians can develop a multifaceted approach not only focusing on medication management but also on customizing the patient’s diet, assisting with lifestyle adjustments, and addressing the mental health issues surrounding obesity and its management.

People seeking obesity treatment often have psychiatric conditions, psychological distress, or disordered eating patterns, and questions and concerns have emerged about how GLP-1 RA use might affect existing mental health problems. For example, if the medication suppresses the feeling of gratification a person once got from eating high-energy dense foods, that individual may “seek rewards or pleasure elsewhere, and possibly from unhealthy sources.”

Psychological issues also may emerge as a result of weight loss, so it’s helpful to take a multidisciplinary approach that includes mental health practitioners to support patients who are being treated with GLP-1 RAs. Patients taking these agents should be monitored for the emergence or worsening of psychiatric conditions, such as depression and suicidal ideation.

Achieving significant weight loss may lead to “unexpected changes” in the dynamics of patients’ relationship with others, “which can be distressing.” Clinicians should be “sensitive to patients’ social and emotional needs” and provide support or refer patients for help with coping strategies.

GLP-1 RAs have enormous potential to improve health outcomes in patients with obesity. Careful patient selection, close monitoring, and support for patients with nutrition and other lifestyle issues can increase the chances that these agents will fulfill their potential.

Isaacs declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

As the use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) continues to exponentially expand obesity treatment, concerns have arisen regarding their impact on nutrition in people who take them.

While the medications’ dampening effects on appetite result in an average weight reduction ≥ 15%, they also pose a risk for malnutrition.

“It’s important to eat a balanced diet when taking these medications,” Deena Adimoolam, MD, an endocrinologist based in New York City and a member of the national advisory committees for the Endocrine Society and the American Diabetes Association, said in an interview. “If someone’s diet is minimal, it’s important they’re keeping up with their need for macronutrients — protein, fat, carbohydrates — as well as micronutrients — vitamins and minerals.” 

The decreased caloric intake resulting from the use of GLP-1 RAs makes it essential for patients to consume nutrient-dense foods. Clinicians can help patients achieve a healthy diet by anticipating nutrition problems, advising them on recommended target ranges of nutrient intake, and referring them for appropriate counseling.

 

Where to Begin

The task begins with “setting the right expectations before the patient starts treatment,” said Scott Isaacs, MD, president-elect of the American Association of Clinical Endocrinology.

To that end, it’s important to explain to patients how the medications affect appetite and how to adapt. GLP-1 RAs don’t completely turn off the appetite, and the effect at the beginning will likely be very mild, Isaacs said in an interview.

Some patients don’t notice a change for 2-3 months, although others see an effect sooner.

“Typically, people will notice that the main impact is on satiation, meaning they’ll fill up more quickly,” said Isaacs, who is an adjunct associate professor at Emory University School of Medicine, Atlanta, Georgia. “It’s important to tell them to stop eating when they feel full because eating when full can increase the side effects, such as nausea, vomiting, diarrhea, and constipation.”

A review article, written by lead author Jaime Almandoz, MD, University of Texas Southwestern Medical Center, Dallas, in Obesity offers a “5 A’s model” as a guide on how to begin discussing overweight or obesity with patients. This involves asking for permission to discuss weight and asking about food and vitamin/supplement intake; assessing the patient’s medical history and root causes of obesity, and conducting a physical examination; advising the patient regarding treatment options and reasonable expectations; agreeing on treatment and lifestyle goals; and assisting the patient to address challenges, referring them as needed to for additional support (eg, a dietitian), as well as arranging for follow-up.

 

Impact of GLP-1 RAs on Food Preferences

Besides reducing hunger and increasing satiety, GLP-1 RAs may affect food preferences, according to a research review published in The International Journal of Obesity. It cites a 2014 study that found that people taking GLP-1 RAs displayed decreased neuronal responses to images of food measured by functional magnetic resonance imaging in the areas of brain associated with appetite and reward. This might affect taste preferences and food intake.

Additionally, a 2023 study suggested that during the weight-loss phase of treatment (as opposed to the maintenance phase), patients may experience reduced cravings for dairy and starchy food, less desire to eat salty or spicy foods, and less difficulty controlling eating and resisting cravings.

“Altered food preferences, decreased food cravings, and reduced food intake may contribute to long-term weight loss,” according to the research review. Tailored treatments focusing on the weight maintenance phase are needed, the authors wrote.

 

Are Patients Vulnerable to Malnutrition?

A recent review found that total caloric intake was reduced by 16%-39% in patients taking a GLP-1 RA or dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA, but few studies evaluated the composition of these patients’ diets. Research that examines the qualitative changes in macronutrient and micronutrient intake of patients on these medications is needed, the authors wrote.

They outlined several nutritional concerns, including whether GLP-1 RA or GIP/ GLP-1 RA use could result in protein intake insufficient for maintaining muscle strength, mass, and function or in inadequate dietary quality (ie, poor intake of micronutrients, fiber, and fluid).

“Although we don’t necessarily see ‘malnutrition’ in our practice, we do see patients who lose too much weight after months and months of treatment, patients who aren’t hungry and don’t eat all day and have one big meal at the end of the day because they don’t feel like eating, and people who continue to eat unhealthy foods,” Isaacs said.

Some patients, however, have medical histories placing them at a greater risk for malnutrition. “Identification of these individuals may help prevent more serious nutritional and medical complications that might occur with decreased food intake associated with AOMs [anti-obesity medications],” Almandoz and colleagues noted in their review.

 

What Should Patients Eat?

Nutritional needs vary based on the patient’s age, sex, body weight, physical activity, and other factors, Almandoz and colleagues wrote. For this reason, energy intake during weight loss should be “personalized.”

The authors also recommended specific sources of the various dietary components and noted red flags signaling potential deficiencies 

Nutritional needs vary based on the degree of appetite suppression in the patient, Adimoolam said. “I recommend at least two servings of fruits and vegetables daily, and drinking plenty of water throughout the day,” she added.

Protein in particular is a “key macronutrient,” and insufficient intake can lead to a variety of adverse effects, including sarcopenia — which is already a concern in individuals being treated with GLP-1 RAs. Meal replacement products (eg, shakes or bars) can supplement diets to help meet protein needs, especially if appetite is significantly reduced.

“There are definitely concerns for sarcopenia, so we have our patients taking these drugs try to eat healthy lean proteins – 100 g/d — and exercise,” Isaacs said. Exercise, including resistance training, not only improves muscle mass but also potentiates the effects of the GLP-1 RAs in patients with obesity and type 2 diabetes.

Adequate hydration is essential for patients taking GLP-1 RAs. “One of the commonly described side effects is fatigue, but there’s no biological reason why these medications should cause fatigue. My opinion is that these patients are dehydrated, and that may be causing the fatigue,” Isaacs said.

Some patients taking GLP-1 RAs lose interest in food. Isaacs regarded this as an “adverse reaction to the medication, which necessitates either stopping it altogether, changing the dose, or adjusting the diet.” There are “many different solutions, and one size doesn’t fit all,” he said.

 

Dietary and Behavioral Counseling

The drugs don’t necessarily motivate a person to eat healthier food, only to eat less food, Isaacs noted.

“The person might be eating low-volume but high-calorie food, such as bag of chips or a cookie instead of an apple,” Isaacs said. Patients who are losing weight “may not realize that weight loss isn’t the only important outcome. Because they’re losing weight, they think it’s okay to eat junk food.”

Patients need education and guidance about how to eat while on these medications. Most patients find counseling about meal planning helpful, he said.

Isaacs gives nutritional guidance to his patients when he prescribes a weight loss medication. “But most physicians don’t have time to offer that type of specific counseling on an ongoing basis,” he said. Isaacs refers patients requiring more detailed and long-term guidance to a dietitian.

Patients with monotonous diets of poor quality are at increased risk for nutrition deficiencies, and counseling by a registered dietitian could help improve their dietary quality.

Registered dietitians can develop a multifaceted approach not only focusing on medication management but also on customizing the patient’s diet, assisting with lifestyle adjustments, and addressing the mental health issues surrounding obesity and its management.

People seeking obesity treatment often have psychiatric conditions, psychological distress, or disordered eating patterns, and questions and concerns have emerged about how GLP-1 RA use might affect existing mental health problems. For example, if the medication suppresses the feeling of gratification a person once got from eating high-energy dense foods, that individual may “seek rewards or pleasure elsewhere, and possibly from unhealthy sources.”

Psychological issues also may emerge as a result of weight loss, so it’s helpful to take a multidisciplinary approach that includes mental health practitioners to support patients who are being treated with GLP-1 RAs. Patients taking these agents should be monitored for the emergence or worsening of psychiatric conditions, such as depression and suicidal ideation.

Achieving significant weight loss may lead to “unexpected changes” in the dynamics of patients’ relationship with others, “which can be distressing.” Clinicians should be “sensitive to patients’ social and emotional needs” and provide support or refer patients for help with coping strategies.

GLP-1 RAs have enormous potential to improve health outcomes in patients with obesity. Careful patient selection, close monitoring, and support for patients with nutrition and other lifestyle issues can increase the chances that these agents will fulfill their potential.

Isaacs declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

As the use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) continues to exponentially expand obesity treatment, concerns have arisen regarding their impact on nutrition in people who take them.

While the medications’ dampening effects on appetite result in an average weight reduction ≥ 15%, they also pose a risk for malnutrition.

“It’s important to eat a balanced diet when taking these medications,” Deena Adimoolam, MD, an endocrinologist based in New York City and a member of the national advisory committees for the Endocrine Society and the American Diabetes Association, said in an interview. “If someone’s diet is minimal, it’s important they’re keeping up with their need for macronutrients — protein, fat, carbohydrates — as well as micronutrients — vitamins and minerals.” 

The decreased caloric intake resulting from the use of GLP-1 RAs makes it essential for patients to consume nutrient-dense foods. Clinicians can help patients achieve a healthy diet by anticipating nutrition problems, advising them on recommended target ranges of nutrient intake, and referring them for appropriate counseling.

 

Where to Begin

The task begins with “setting the right expectations before the patient starts treatment,” said Scott Isaacs, MD, president-elect of the American Association of Clinical Endocrinology.

To that end, it’s important to explain to patients how the medications affect appetite and how to adapt. GLP-1 RAs don’t completely turn off the appetite, and the effect at the beginning will likely be very mild, Isaacs said in an interview.

Some patients don’t notice a change for 2-3 months, although others see an effect sooner.

“Typically, people will notice that the main impact is on satiation, meaning they’ll fill up more quickly,” said Isaacs, who is an adjunct associate professor at Emory University School of Medicine, Atlanta, Georgia. “It’s important to tell them to stop eating when they feel full because eating when full can increase the side effects, such as nausea, vomiting, diarrhea, and constipation.”

A review article, written by lead author Jaime Almandoz, MD, University of Texas Southwestern Medical Center, Dallas, in Obesity offers a “5 A’s model” as a guide on how to begin discussing overweight or obesity with patients. This involves asking for permission to discuss weight and asking about food and vitamin/supplement intake; assessing the patient’s medical history and root causes of obesity, and conducting a physical examination; advising the patient regarding treatment options and reasonable expectations; agreeing on treatment and lifestyle goals; and assisting the patient to address challenges, referring them as needed to for additional support (eg, a dietitian), as well as arranging for follow-up.

 

Impact of GLP-1 RAs on Food Preferences

Besides reducing hunger and increasing satiety, GLP-1 RAs may affect food preferences, according to a research review published in The International Journal of Obesity. It cites a 2014 study that found that people taking GLP-1 RAs displayed decreased neuronal responses to images of food measured by functional magnetic resonance imaging in the areas of brain associated with appetite and reward. This might affect taste preferences and food intake.

Additionally, a 2023 study suggested that during the weight-loss phase of treatment (as opposed to the maintenance phase), patients may experience reduced cravings for dairy and starchy food, less desire to eat salty or spicy foods, and less difficulty controlling eating and resisting cravings.

“Altered food preferences, decreased food cravings, and reduced food intake may contribute to long-term weight loss,” according to the research review. Tailored treatments focusing on the weight maintenance phase are needed, the authors wrote.

 

Are Patients Vulnerable to Malnutrition?

A recent review found that total caloric intake was reduced by 16%-39% in patients taking a GLP-1 RA or dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA, but few studies evaluated the composition of these patients’ diets. Research that examines the qualitative changes in macronutrient and micronutrient intake of patients on these medications is needed, the authors wrote.

They outlined several nutritional concerns, including whether GLP-1 RA or GIP/ GLP-1 RA use could result in protein intake insufficient for maintaining muscle strength, mass, and function or in inadequate dietary quality (ie, poor intake of micronutrients, fiber, and fluid).

“Although we don’t necessarily see ‘malnutrition’ in our practice, we do see patients who lose too much weight after months and months of treatment, patients who aren’t hungry and don’t eat all day and have one big meal at the end of the day because they don’t feel like eating, and people who continue to eat unhealthy foods,” Isaacs said.

Some patients, however, have medical histories placing them at a greater risk for malnutrition. “Identification of these individuals may help prevent more serious nutritional and medical complications that might occur with decreased food intake associated with AOMs [anti-obesity medications],” Almandoz and colleagues noted in their review.

 

What Should Patients Eat?

Nutritional needs vary based on the patient’s age, sex, body weight, physical activity, and other factors, Almandoz and colleagues wrote. For this reason, energy intake during weight loss should be “personalized.”

The authors also recommended specific sources of the various dietary components and noted red flags signaling potential deficiencies 

Nutritional needs vary based on the degree of appetite suppression in the patient, Adimoolam said. “I recommend at least two servings of fruits and vegetables daily, and drinking plenty of water throughout the day,” she added.

Protein in particular is a “key macronutrient,” and insufficient intake can lead to a variety of adverse effects, including sarcopenia — which is already a concern in individuals being treated with GLP-1 RAs. Meal replacement products (eg, shakes or bars) can supplement diets to help meet protein needs, especially if appetite is significantly reduced.

“There are definitely concerns for sarcopenia, so we have our patients taking these drugs try to eat healthy lean proteins – 100 g/d — and exercise,” Isaacs said. Exercise, including resistance training, not only improves muscle mass but also potentiates the effects of the GLP-1 RAs in patients with obesity and type 2 diabetes.

Adequate hydration is essential for patients taking GLP-1 RAs. “One of the commonly described side effects is fatigue, but there’s no biological reason why these medications should cause fatigue. My opinion is that these patients are dehydrated, and that may be causing the fatigue,” Isaacs said.

Some patients taking GLP-1 RAs lose interest in food. Isaacs regarded this as an “adverse reaction to the medication, which necessitates either stopping it altogether, changing the dose, or adjusting the diet.” There are “many different solutions, and one size doesn’t fit all,” he said.

 

Dietary and Behavioral Counseling

The drugs don’t necessarily motivate a person to eat healthier food, only to eat less food, Isaacs noted.

“The person might be eating low-volume but high-calorie food, such as bag of chips or a cookie instead of an apple,” Isaacs said. Patients who are losing weight “may not realize that weight loss isn’t the only important outcome. Because they’re losing weight, they think it’s okay to eat junk food.”

Patients need education and guidance about how to eat while on these medications. Most patients find counseling about meal planning helpful, he said.

Isaacs gives nutritional guidance to his patients when he prescribes a weight loss medication. “But most physicians don’t have time to offer that type of specific counseling on an ongoing basis,” he said. Isaacs refers patients requiring more detailed and long-term guidance to a dietitian.

Patients with monotonous diets of poor quality are at increased risk for nutrition deficiencies, and counseling by a registered dietitian could help improve their dietary quality.

Registered dietitians can develop a multifaceted approach not only focusing on medication management but also on customizing the patient’s diet, assisting with lifestyle adjustments, and addressing the mental health issues surrounding obesity and its management.

People seeking obesity treatment often have psychiatric conditions, psychological distress, or disordered eating patterns, and questions and concerns have emerged about how GLP-1 RA use might affect existing mental health problems. For example, if the medication suppresses the feeling of gratification a person once got from eating high-energy dense foods, that individual may “seek rewards or pleasure elsewhere, and possibly from unhealthy sources.”

Psychological issues also may emerge as a result of weight loss, so it’s helpful to take a multidisciplinary approach that includes mental health practitioners to support patients who are being treated with GLP-1 RAs. Patients taking these agents should be monitored for the emergence or worsening of psychiatric conditions, such as depression and suicidal ideation.

Achieving significant weight loss may lead to “unexpected changes” in the dynamics of patients’ relationship with others, “which can be distressing.” Clinicians should be “sensitive to patients’ social and emotional needs” and provide support or refer patients for help with coping strategies.

GLP-1 RAs have enormous potential to improve health outcomes in patients with obesity. Careful patient selection, close monitoring, and support for patients with nutrition and other lifestyle issues can increase the chances that these agents will fulfill their potential.

Isaacs declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

Results published from a systematic review and meta-analysis find an inverse association and a dose-response link between fluoride exposure and children’s IQ scores.

Kyla W. Taylor, PhD, with the Division of Translational Toxicology at the National Institutes of Health, Morrisville, North Carolina, led the multicountry study published online in JAMA Pediatrics.

Two accompanying editorials offer two very different perspectives on how to interpret the researchers’ conclusions.
 

Study Results

The authors noted that, of the 74 studies included in the review (64 cross-sectional and 10 cohort studies), most (45) were conducted in China. Other countries included were Canada (3), Denmark (1), India (12), Iran (4), Mexico (4), New Zealand (1), Pakistan (2), Spain (1), and Taiwan (1). “Fifty-two studies were rated high risk of bias, and 22 were rated low risk of bias,” the authors stated.

Researchers found that 64 of the 74 studies reported inverse associations between fluoride exposure measures and children’s IQ scores. Their analysis of 59 studies with group-level measures of fluoride in drinking water, dental fluorosis, or other measures of fluoride exposure showed an inverse relationship between fluoride exposure and IQ (pooled standardized mean difference [SMD], −0.45; 95% CI, −0.57 to −0.33; P < .001). Of those 59 studies, encompassing 20,932 children, 47 had high risk for bias and 12 had low risk for bias.

In 31 studies that reported fluoride measurements in drinking water, a dose-response relationship was found between exposed and reference groups (SMD, –0.15; 95% CI, –0.20 to –0.11; P < .001). That relationship remained inverse when exposed groups were limited to less than 4 mg fluoride/L and less than 2 mg/L. However, the association was not seen at less than 1.5 mg/L.

In 20 studies reporting fluoride measured in urine, there was an inverse dose-response association (SMD, –0.15; 95% CI, –0.23 to –0.07; P < .001). Those inverse relationships held at levels less than 4 mg/L, less than 2 mg/L, and less than 1.5 mg/L fluoride in urine.

For perspective, in the United States, the US Public Health Service in 2015 lowered the recommended concentration of fluoride in drinking water from a range of 0.7-1.2 mg/L to 0.7 mg/L to reduce the risk for dental fluorosis while keeping its protective effect against dental caries. 

When Taylor’s team analyzed 13 studies with individual-level measures, they found an IQ score decrease of 1.63 points (95% CI, –2.33 to –0.93; P < .001) per 1-mg/L increase in urinary fluoride. Among studies with a low risk for bias, they observed an IQ score decrease of 1.14 points (95% CI, –1.68 to –0.61; P < .001). The inverse relationship remained when stratified by factors including risk for bias, sex, age, country, outcome assessment type, exposure timing (prenatal or postnatal), and exposure matrix (urinary fluoride, intake and water fluoride), the authors wrote.

The authors conclude both that inverse relationships and a dose-response association between fluoride measured in urine and drinking water and children’s IQs were found across the literature examined but also that “there were limited data and uncertainty in the dose-response association between fluoride exposure and children’s IQ when fluoride exposure was estimated by drinking water alone at concentrations less than 1.5 mg/L.”

The authors point out that, “To our knowledge, no studies of fluoride exposure and children’s IQ have been performed in the United States and no nationally representative urinary fluoride levels are available, hindering application of these findings to the US population.”
 

Editorial: Time to Reassess Systemic Fluoride

Bruce P. Lanphear, MD, MPH, with Simon Fraser University, Vancouver, British Columbia, Canada, is the lead author on an editorial that suggests these data point to the need to reassess systemic fluoride exposure.

“Their study is the largest and includes the most rigorous series of meta-analyses of fluoride ever conducted,” Lanphear and colleagues wrote. “It is time for health organizations and regulatory bodies to reassess the risks and benefits of fluoride, particularly for pregnant women and infants.”

Lanphear’s team says distinguishing between water fluoride and urinary fluoride levels is important in these results “because regulatory and public health agencies must consider total fluoride intake when assessing risks.”

Taylor and colleagues’ finding that there was no statistically significant association between water fluoride les than 1.5 mg/L and children’s IQ scores in the dose-response meta-analysis doesn’t mean fluoride is not a potential risk for lower IQ scores in fluoridated communities, they wrote. “Water fluoride concentration does not capture the amount of water ingested or other sources of ingested fluoride. In contrast, urinary fluoride is a biological measure of total fluoride exposure, including the dynamic interface between bone fluoride stores and blood fluoride.”
 

Editorial: Be Cautious About the Conclusions

Steven M. Levy, DDS, MPH, cites “major areas of concern” in the meta-analysis in his editorial.

He points to the large majority of studies in the meta-analysis that were at “high risk of bias” (47 high risk vs 12 that were low risk). He also cited information from a further look at the low-risk-of-bias studies included in the supplement.

“The studies with lower risk of bias showed a negligible effect (standardized mean difference [SMD], −0.19; 95% CI, −0.35 to −0.04) with very high heterogeneity (I2 = 87%), and a majority of publications (8 of 12) did not show a negative association between fluoride and childhood IQ,” Levy wrote. 

“Taylor et al do not adequately justify selection or omission of studies or explain or justify the calculated individual effect sizes presented in the main analysis. Also, readers are not told which studies with lower risk of bias are included in the subanalyses for water fluoride levels less than 1.5 mg/L, less than 2.0 mg/L, and less than 4.0 mg/L; therefore, readers cannot independently consider important differences across these studies.”

Levy also states that the magnitudes of the possible IQ differences are unfairly inflated. For the United Staes and most of the world, he points out, the recommended community water fluoridation level is 0.7 mg/L. Therefore, the difference between a community with low fluoride levels (about 0.2 mg/L) and one with optimal levels is about 0.5 mg/L. 

“However, Taylor and colleagues use a difference of 1.0 mg/L in their calculations, artificially doubling the estimated impact on IQ,” Levy wrote.

The meta-analysis should not affect public policy on adding fluoride to community water systems “and the widespread use of fluoride for caries prevention should continue,” Levy concluded.
 

Concerns About Quality of Studies Included

Charlotte Lewis, MD, MPH, associate professor of pediatrics at the University of Washington School of Medicine and part of Seattle Children’s Multidisciplinary Infant Nutrition and Feeding Team, Seattle, who was not involved in the meta-analysis or editorials, said that systemic fluoridation should not change based on these results, citing what she said are problems with methodology.

“There are many concerns about the quality of studies included in this meta-analysis,” Lewis said. “Although the authors claim to have separated out low-bias studies, it is important to note that many of these same studies have substantial methodological flaws.”

She said studies deemed low-bias and included in the meta-analysis “relied on multiple examiners for cognitive testing without consideration for inter-rater variation or reliability measures.” She added that “a number of the studies failed to account for maternal IQ scores, breastfeeding, lead exposure, or other factors that could affect cognitive development, further contributing to biased conclusions.”

Importantly, she said, many of the studies, including one by Rivka Green and colleagues published in JAMA Pediatrics, relied on maternal spot urinary fluoride to assess fetal exposure to fluoride. “This is not a valid way to assess fetal exposure to fluoride and including such studies in this meta-analysis has led to inappropriate conclusions because they are based on studies using a flawed exposure measure.” 

She pointed to recent longitudinal, population-based studies, including one by Jayant V Kumar and colleagues that have found no adverse impact on IQ, or other cognitive tests, of drinking water with low levels of fluoride present, comparable to US community water fluoridation standards. 

“Relative to the small convenience-sample, cross-sectional studies included in this meta-analysis, longitudinal, population-based studies are considered significantly more reliable for establishing cause and effect,” she said.
 

Fluoride Levels Different Globally

Lewis said in some parts of the world fluoride is present in the environment in much higher levels than in fluoridated water in the United States.

“There are known adverse health effects of high fluoride ingestion in these endemic regions found primarily in China, India, and Iran. This points to the importance of dose response. What is beneficial at low levels can be toxic at high levels and that appears to be the case, not surprisingly, for fluoride as well. However, at 0.7 ppm, the level of fluoride in community water fluoridation, we experience fluoride’s beneficial effects when we regularly drink optimally fluoridated water.”

“Water fluoridation is an important public health approach available and beneficial to all, even those unable to afford or access dental care,” she said. “Water fluoridation diminishes oral health disparities, and its removal threatens to worsen disparities and increased suffering from dental disease. I remain confident in the benefits and safety of community water fluoridation.”

Taylor and colleagues reported no relevant financial relationships. Lanphear reported grants from the National Institute of Environmental Health Sciences and the Canadian Institute for Health Research and having served as a nonretained and unpaid expert witness in a federal fluoride suit against the US EPA. Levy reported past grants from the National Institute of Dental and Craniofacial Research related to fluoride, dental caries, dental fluorosis, and bone development. He reported small grant funding from the Centers for Disease Control and Prevention related to fluoride, dental caries, and fluorosis. He consults for the Centers for Disease Control and Prevention and the National Institute of Dental and Craniofacial Research and serves on the National Fluoride Advisory Committee for the American Dental Association.

A version of this article appeared on Medscape.com.

Results published from a systematic review and meta-analysis find an inverse association and a dose-response link between fluoride exposure and children’s IQ scores.

Kyla W. Taylor, PhD, with the Division of Translational Toxicology at the National Institutes of Health, Morrisville, North Carolina, led the multicountry study published online in JAMA Pediatrics.

Two accompanying editorials offer two very different perspectives on how to interpret the researchers’ conclusions.
 

Study Results

The authors noted that, of the 74 studies included in the review (64 cross-sectional and 10 cohort studies), most (45) were conducted in China. Other countries included were Canada (3), Denmark (1), India (12), Iran (4), Mexico (4), New Zealand (1), Pakistan (2), Spain (1), and Taiwan (1). “Fifty-two studies were rated high risk of bias, and 22 were rated low risk of bias,” the authors stated.

Researchers found that 64 of the 74 studies reported inverse associations between fluoride exposure measures and children’s IQ scores. Their analysis of 59 studies with group-level measures of fluoride in drinking water, dental fluorosis, or other measures of fluoride exposure showed an inverse relationship between fluoride exposure and IQ (pooled standardized mean difference [SMD], −0.45; 95% CI, −0.57 to −0.33; P < .001). Of those 59 studies, encompassing 20,932 children, 47 had high risk for bias and 12 had low risk for bias.

In 31 studies that reported fluoride measurements in drinking water, a dose-response relationship was found between exposed and reference groups (SMD, –0.15; 95% CI, –0.20 to –0.11; P < .001). That relationship remained inverse when exposed groups were limited to less than 4 mg fluoride/L and less than 2 mg/L. However, the association was not seen at less than 1.5 mg/L.

In 20 studies reporting fluoride measured in urine, there was an inverse dose-response association (SMD, –0.15; 95% CI, –0.23 to –0.07; P < .001). Those inverse relationships held at levels less than 4 mg/L, less than 2 mg/L, and less than 1.5 mg/L fluoride in urine.

For perspective, in the United States, the US Public Health Service in 2015 lowered the recommended concentration of fluoride in drinking water from a range of 0.7-1.2 mg/L to 0.7 mg/L to reduce the risk for dental fluorosis while keeping its protective effect against dental caries. 

When Taylor’s team analyzed 13 studies with individual-level measures, they found an IQ score decrease of 1.63 points (95% CI, –2.33 to –0.93; P < .001) per 1-mg/L increase in urinary fluoride. Among studies with a low risk for bias, they observed an IQ score decrease of 1.14 points (95% CI, –1.68 to –0.61; P < .001). The inverse relationship remained when stratified by factors including risk for bias, sex, age, country, outcome assessment type, exposure timing (prenatal or postnatal), and exposure matrix (urinary fluoride, intake and water fluoride), the authors wrote.

The authors conclude both that inverse relationships and a dose-response association between fluoride measured in urine and drinking water and children’s IQs were found across the literature examined but also that “there were limited data and uncertainty in the dose-response association between fluoride exposure and children’s IQ when fluoride exposure was estimated by drinking water alone at concentrations less than 1.5 mg/L.”

The authors point out that, “To our knowledge, no studies of fluoride exposure and children’s IQ have been performed in the United States and no nationally representative urinary fluoride levels are available, hindering application of these findings to the US population.”
 

Editorial: Time to Reassess Systemic Fluoride

Bruce P. Lanphear, MD, MPH, with Simon Fraser University, Vancouver, British Columbia, Canada, is the lead author on an editorial that suggests these data point to the need to reassess systemic fluoride exposure.

“Their study is the largest and includes the most rigorous series of meta-analyses of fluoride ever conducted,” Lanphear and colleagues wrote. “It is time for health organizations and regulatory bodies to reassess the risks and benefits of fluoride, particularly for pregnant women and infants.”

Lanphear’s team says distinguishing between water fluoride and urinary fluoride levels is important in these results “because regulatory and public health agencies must consider total fluoride intake when assessing risks.”

Taylor and colleagues’ finding that there was no statistically significant association between water fluoride les than 1.5 mg/L and children’s IQ scores in the dose-response meta-analysis doesn’t mean fluoride is not a potential risk for lower IQ scores in fluoridated communities, they wrote. “Water fluoride concentration does not capture the amount of water ingested or other sources of ingested fluoride. In contrast, urinary fluoride is a biological measure of total fluoride exposure, including the dynamic interface between bone fluoride stores and blood fluoride.”
 

Editorial: Be Cautious About the Conclusions

Steven M. Levy, DDS, MPH, cites “major areas of concern” in the meta-analysis in his editorial.

He points to the large majority of studies in the meta-analysis that were at “high risk of bias” (47 high risk vs 12 that were low risk). He also cited information from a further look at the low-risk-of-bias studies included in the supplement.

“The studies with lower risk of bias showed a negligible effect (standardized mean difference [SMD], −0.19; 95% CI, −0.35 to −0.04) with very high heterogeneity (I2 = 87%), and a majority of publications (8 of 12) did not show a negative association between fluoride and childhood IQ,” Levy wrote. 

“Taylor et al do not adequately justify selection or omission of studies or explain or justify the calculated individual effect sizes presented in the main analysis. Also, readers are not told which studies with lower risk of bias are included in the subanalyses for water fluoride levels less than 1.5 mg/L, less than 2.0 mg/L, and less than 4.0 mg/L; therefore, readers cannot independently consider important differences across these studies.”

Levy also states that the magnitudes of the possible IQ differences are unfairly inflated. For the United Staes and most of the world, he points out, the recommended community water fluoridation level is 0.7 mg/L. Therefore, the difference between a community with low fluoride levels (about 0.2 mg/L) and one with optimal levels is about 0.5 mg/L. 

“However, Taylor and colleagues use a difference of 1.0 mg/L in their calculations, artificially doubling the estimated impact on IQ,” Levy wrote.

The meta-analysis should not affect public policy on adding fluoride to community water systems “and the widespread use of fluoride for caries prevention should continue,” Levy concluded.
 

Concerns About Quality of Studies Included

Charlotte Lewis, MD, MPH, associate professor of pediatrics at the University of Washington School of Medicine and part of Seattle Children’s Multidisciplinary Infant Nutrition and Feeding Team, Seattle, who was not involved in the meta-analysis or editorials, said that systemic fluoridation should not change based on these results, citing what she said are problems with methodology.

“There are many concerns about the quality of studies included in this meta-analysis,” Lewis said. “Although the authors claim to have separated out low-bias studies, it is important to note that many of these same studies have substantial methodological flaws.”

She said studies deemed low-bias and included in the meta-analysis “relied on multiple examiners for cognitive testing without consideration for inter-rater variation or reliability measures.” She added that “a number of the studies failed to account for maternal IQ scores, breastfeeding, lead exposure, or other factors that could affect cognitive development, further contributing to biased conclusions.”

Importantly, she said, many of the studies, including one by Rivka Green and colleagues published in JAMA Pediatrics, relied on maternal spot urinary fluoride to assess fetal exposure to fluoride. “This is not a valid way to assess fetal exposure to fluoride and including such studies in this meta-analysis has led to inappropriate conclusions because they are based on studies using a flawed exposure measure.” 

She pointed to recent longitudinal, population-based studies, including one by Jayant V Kumar and colleagues that have found no adverse impact on IQ, or other cognitive tests, of drinking water with low levels of fluoride present, comparable to US community water fluoridation standards. 

“Relative to the small convenience-sample, cross-sectional studies included in this meta-analysis, longitudinal, population-based studies are considered significantly more reliable for establishing cause and effect,” she said.
 

Fluoride Levels Different Globally

Lewis said in some parts of the world fluoride is present in the environment in much higher levels than in fluoridated water in the United States.

“There are known adverse health effects of high fluoride ingestion in these endemic regions found primarily in China, India, and Iran. This points to the importance of dose response. What is beneficial at low levels can be toxic at high levels and that appears to be the case, not surprisingly, for fluoride as well. However, at 0.7 ppm, the level of fluoride in community water fluoridation, we experience fluoride’s beneficial effects when we regularly drink optimally fluoridated water.”

“Water fluoridation is an important public health approach available and beneficial to all, even those unable to afford or access dental care,” she said. “Water fluoridation diminishes oral health disparities, and its removal threatens to worsen disparities and increased suffering from dental disease. I remain confident in the benefits and safety of community water fluoridation.”

Taylor and colleagues reported no relevant financial relationships. Lanphear reported grants from the National Institute of Environmental Health Sciences and the Canadian Institute for Health Research and having served as a nonretained and unpaid expert witness in a federal fluoride suit against the US EPA. Levy reported past grants from the National Institute of Dental and Craniofacial Research related to fluoride, dental caries, dental fluorosis, and bone development. He reported small grant funding from the Centers for Disease Control and Prevention related to fluoride, dental caries, and fluorosis. He consults for the Centers for Disease Control and Prevention and the National Institute of Dental and Craniofacial Research and serves on the National Fluoride Advisory Committee for the American Dental Association.

A version of this article appeared on Medscape.com.

Results published from a systematic review and meta-analysis find an inverse association and a dose-response link between fluoride exposure and children’s IQ scores.

Kyla W. Taylor, PhD, with the Division of Translational Toxicology at the National Institutes of Health, Morrisville, North Carolina, led the multicountry study published online in JAMA Pediatrics.

Two accompanying editorials offer two very different perspectives on how to interpret the researchers’ conclusions.
 

Study Results

The authors noted that, of the 74 studies included in the review (64 cross-sectional and 10 cohort studies), most (45) were conducted in China. Other countries included were Canada (3), Denmark (1), India (12), Iran (4), Mexico (4), New Zealand (1), Pakistan (2), Spain (1), and Taiwan (1). “Fifty-two studies were rated high risk of bias, and 22 were rated low risk of bias,” the authors stated.

Researchers found that 64 of the 74 studies reported inverse associations between fluoride exposure measures and children’s IQ scores. Their analysis of 59 studies with group-level measures of fluoride in drinking water, dental fluorosis, or other measures of fluoride exposure showed an inverse relationship between fluoride exposure and IQ (pooled standardized mean difference [SMD], −0.45; 95% CI, −0.57 to −0.33; P < .001). Of those 59 studies, encompassing 20,932 children, 47 had high risk for bias and 12 had low risk for bias.

In 31 studies that reported fluoride measurements in drinking water, a dose-response relationship was found between exposed and reference groups (SMD, –0.15; 95% CI, –0.20 to –0.11; P < .001). That relationship remained inverse when exposed groups were limited to less than 4 mg fluoride/L and less than 2 mg/L. However, the association was not seen at less than 1.5 mg/L.

In 20 studies reporting fluoride measured in urine, there was an inverse dose-response association (SMD, –0.15; 95% CI, –0.23 to –0.07; P < .001). Those inverse relationships held at levels less than 4 mg/L, less than 2 mg/L, and less than 1.5 mg/L fluoride in urine.

For perspective, in the United States, the US Public Health Service in 2015 lowered the recommended concentration of fluoride in drinking water from a range of 0.7-1.2 mg/L to 0.7 mg/L to reduce the risk for dental fluorosis while keeping its protective effect against dental caries. 

When Taylor’s team analyzed 13 studies with individual-level measures, they found an IQ score decrease of 1.63 points (95% CI, –2.33 to –0.93; P < .001) per 1-mg/L increase in urinary fluoride. Among studies with a low risk for bias, they observed an IQ score decrease of 1.14 points (95% CI, –1.68 to –0.61; P < .001). The inverse relationship remained when stratified by factors including risk for bias, sex, age, country, outcome assessment type, exposure timing (prenatal or postnatal), and exposure matrix (urinary fluoride, intake and water fluoride), the authors wrote.

The authors conclude both that inverse relationships and a dose-response association between fluoride measured in urine and drinking water and children’s IQs were found across the literature examined but also that “there were limited data and uncertainty in the dose-response association between fluoride exposure and children’s IQ when fluoride exposure was estimated by drinking water alone at concentrations less than 1.5 mg/L.”

The authors point out that, “To our knowledge, no studies of fluoride exposure and children’s IQ have been performed in the United States and no nationally representative urinary fluoride levels are available, hindering application of these findings to the US population.”
 

Editorial: Time to Reassess Systemic Fluoride

Bruce P. Lanphear, MD, MPH, with Simon Fraser University, Vancouver, British Columbia, Canada, is the lead author on an editorial that suggests these data point to the need to reassess systemic fluoride exposure.

“Their study is the largest and includes the most rigorous series of meta-analyses of fluoride ever conducted,” Lanphear and colleagues wrote. “It is time for health organizations and regulatory bodies to reassess the risks and benefits of fluoride, particularly for pregnant women and infants.”

Lanphear’s team says distinguishing between water fluoride and urinary fluoride levels is important in these results “because regulatory and public health agencies must consider total fluoride intake when assessing risks.”

Taylor and colleagues’ finding that there was no statistically significant association between water fluoride les than 1.5 mg/L and children’s IQ scores in the dose-response meta-analysis doesn’t mean fluoride is not a potential risk for lower IQ scores in fluoridated communities, they wrote. “Water fluoride concentration does not capture the amount of water ingested or other sources of ingested fluoride. In contrast, urinary fluoride is a biological measure of total fluoride exposure, including the dynamic interface between bone fluoride stores and blood fluoride.”
 

Editorial: Be Cautious About the Conclusions

Steven M. Levy, DDS, MPH, cites “major areas of concern” in the meta-analysis in his editorial.

He points to the large majority of studies in the meta-analysis that were at “high risk of bias” (47 high risk vs 12 that were low risk). He also cited information from a further look at the low-risk-of-bias studies included in the supplement.

“The studies with lower risk of bias showed a negligible effect (standardized mean difference [SMD], −0.19; 95% CI, −0.35 to −0.04) with very high heterogeneity (I2 = 87%), and a majority of publications (8 of 12) did not show a negative association between fluoride and childhood IQ,” Levy wrote. 

“Taylor et al do not adequately justify selection or omission of studies or explain or justify the calculated individual effect sizes presented in the main analysis. Also, readers are not told which studies with lower risk of bias are included in the subanalyses for water fluoride levels less than 1.5 mg/L, less than 2.0 mg/L, and less than 4.0 mg/L; therefore, readers cannot independently consider important differences across these studies.”

Levy also states that the magnitudes of the possible IQ differences are unfairly inflated. For the United Staes and most of the world, he points out, the recommended community water fluoridation level is 0.7 mg/L. Therefore, the difference between a community with low fluoride levels (about 0.2 mg/L) and one with optimal levels is about 0.5 mg/L. 

“However, Taylor and colleagues use a difference of 1.0 mg/L in their calculations, artificially doubling the estimated impact on IQ,” Levy wrote.

The meta-analysis should not affect public policy on adding fluoride to community water systems “and the widespread use of fluoride for caries prevention should continue,” Levy concluded.
 

Concerns About Quality of Studies Included

Charlotte Lewis, MD, MPH, associate professor of pediatrics at the University of Washington School of Medicine and part of Seattle Children’s Multidisciplinary Infant Nutrition and Feeding Team, Seattle, who was not involved in the meta-analysis or editorials, said that systemic fluoridation should not change based on these results, citing what she said are problems with methodology.

“There are many concerns about the quality of studies included in this meta-analysis,” Lewis said. “Although the authors claim to have separated out low-bias studies, it is important to note that many of these same studies have substantial methodological flaws.”

She said studies deemed low-bias and included in the meta-analysis “relied on multiple examiners for cognitive testing without consideration for inter-rater variation or reliability measures.” She added that “a number of the studies failed to account for maternal IQ scores, breastfeeding, lead exposure, or other factors that could affect cognitive development, further contributing to biased conclusions.”

Importantly, she said, many of the studies, including one by Rivka Green and colleagues published in JAMA Pediatrics, relied on maternal spot urinary fluoride to assess fetal exposure to fluoride. “This is not a valid way to assess fetal exposure to fluoride and including such studies in this meta-analysis has led to inappropriate conclusions because they are based on studies using a flawed exposure measure.” 

She pointed to recent longitudinal, population-based studies, including one by Jayant V Kumar and colleagues that have found no adverse impact on IQ, or other cognitive tests, of drinking water with low levels of fluoride present, comparable to US community water fluoridation standards. 

“Relative to the small convenience-sample, cross-sectional studies included in this meta-analysis, longitudinal, population-based studies are considered significantly more reliable for establishing cause and effect,” she said.
 

Fluoride Levels Different Globally

Lewis said in some parts of the world fluoride is present in the environment in much higher levels than in fluoridated water in the United States.

“There are known adverse health effects of high fluoride ingestion in these endemic regions found primarily in China, India, and Iran. This points to the importance of dose response. What is beneficial at low levels can be toxic at high levels and that appears to be the case, not surprisingly, for fluoride as well. However, at 0.7 ppm, the level of fluoride in community water fluoridation, we experience fluoride’s beneficial effects when we regularly drink optimally fluoridated water.”

“Water fluoridation is an important public health approach available and beneficial to all, even those unable to afford or access dental care,” she said. “Water fluoridation diminishes oral health disparities, and its removal threatens to worsen disparities and increased suffering from dental disease. I remain confident in the benefits and safety of community water fluoridation.”

Taylor and colleagues reported no relevant financial relationships. Lanphear reported grants from the National Institute of Environmental Health Sciences and the Canadian Institute for Health Research and having served as a nonretained and unpaid expert witness in a federal fluoride suit against the US EPA. Levy reported past grants from the National Institute of Dental and Craniofacial Research related to fluoride, dental caries, dental fluorosis, and bone development. He reported small grant funding from the Centers for Disease Control and Prevention related to fluoride, dental caries, and fluorosis. He consults for the Centers for Disease Control and Prevention and the National Institute of Dental and Craniofacial Research and serves on the National Fluoride Advisory Committee for the American Dental Association.

A version of this article appeared on Medscape.com.

A major prospective study of more than half a million UK women conducted over almost 17 years has confirmed an association between dietary calcium intake and decreased risk of colorectal cancer. 

Cancer Research UK (CRUK), which funded the study, said that it demonstrated the benefits of a healthy, balanced diet for lowering cancer risk.

Colorectal cancer is the third most common cancer worldwide. Incidence rates vary markedly, with higher rates observed in high-income countries. The risk increases for individuals who migrate from low- to high-incidence areas, suggesting that lifestyle and environmental factors contribute to its development.

While alcohol and processed meats are established carcinogens, and red meat is classified as probably carcinogenic, there is a lack of consensus regarding the relationships between other dietary factors and colorectal cancer risk. This uncertainty may be due, at least in part, to relatively few studies giving comprehensive results on all food types, as well as dietary measurement errors, and/or small sample sizes.

 

Study Tracked 97 Dietary Factors

To address these gaps, the research team, led by the University of Oxford in England, tracked the intake of 97 dietary factors in 542,778 women from 2001 for an average of 16.6 years. During this period 12,251 participants developed colorectal cancer. The women completed detailed dietary questionnaires at baseline, with 7% participating in at least one subsequent 24-hour online dietary assessment.

Women diagnosed with colorectal cancer were generally older, taller, more likely to have a family history of bowel cancer, and have more adverse health behaviors, compared with participants overall.

 

Calcium Intake Showed the Strongest Protective Association

Relative risks (RR) for colorectal cancer were calculated for intakes of all 97 dietary factors, with significant associations found for 17 of them. Calcium intake showed the strongest protective effect, with each additional 300 mg per day – equivalent to a large glass of milk – associated with a 17% reduced RR. 

Six dairy-related factors associated with calcium – dairy milk, yogurt, riboflavin, magnesium, phosphorus, and potassium intakes – also demonstrated inverse associations with colorectal cancer risk. Weaker protective effects were noted for breakfast cereal, fruit, wholegrains, carbohydrates, fibre, total sugars, folate, and vitamin C. However, the team commented that these inverse associations might reflect residual confounding from other lifestyle or other dietary factors.

Calcium’s protective role was independent of dairy milk intake. The study, published in Nature Communications, concluded that, while “dairy products help protect against colorectal cancer,” that protection is “driven largely or wholly by calcium.”

 

Alcohol and Processed Meat Confirmed as Risk Factors

As expected, alcohol showed the reverse association, with each additional 20 g daily – equivalent to one large glass of wine – associated with a 15% RR increase. Weaker associations were seen for the combined category of red and processed meat, with each additional 30 g per day associated with an 8% increased RR for colorectal cancer. This association was minimally affected by diet and lifestyle factors.

Commenting to the Science Media Centre (SMC), Tom Sanders, professor emeritus of nutrition and dietetics at King’s College London, England, said: “One theory is that the calcium may bind to free bile acids in the gut, preventing the harmful effects of free bile acids on gut mucosa.” However, the lactose content in milk also has effects on large bowel microflora, which may in turn affect risk.

Also commenting to the SMC, David Nunan, senior research fellow at the University of Oxford’s Centre for Evidence Based Medicine, who was not involved in the study, cautioned that the findings were subject to the bias inherent in observational studies. “These biases often inflate the estimated associations compared to controlled experiments,” he said. Nunan advised caution in interpreting the findings, as more robust research, such as randomized controlled trials, would be needed to establish causation.

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

A major prospective study of more than half a million UK women conducted over almost 17 years has confirmed an association between dietary calcium intake and decreased risk of colorectal cancer. 

Cancer Research UK (CRUK), which funded the study, said that it demonstrated the benefits of a healthy, balanced diet for lowering cancer risk.

Colorectal cancer is the third most common cancer worldwide. Incidence rates vary markedly, with higher rates observed in high-income countries. The risk increases for individuals who migrate from low- to high-incidence areas, suggesting that lifestyle and environmental factors contribute to its development.

While alcohol and processed meats are established carcinogens, and red meat is classified as probably carcinogenic, there is a lack of consensus regarding the relationships between other dietary factors and colorectal cancer risk. This uncertainty may be due, at least in part, to relatively few studies giving comprehensive results on all food types, as well as dietary measurement errors, and/or small sample sizes.

 

Study Tracked 97 Dietary Factors

To address these gaps, the research team, led by the University of Oxford in England, tracked the intake of 97 dietary factors in 542,778 women from 2001 for an average of 16.6 years. During this period 12,251 participants developed colorectal cancer. The women completed detailed dietary questionnaires at baseline, with 7% participating in at least one subsequent 24-hour online dietary assessment.

Women diagnosed with colorectal cancer were generally older, taller, more likely to have a family history of bowel cancer, and have more adverse health behaviors, compared with participants overall.

 

Calcium Intake Showed the Strongest Protective Association

Relative risks (RR) for colorectal cancer were calculated for intakes of all 97 dietary factors, with significant associations found for 17 of them. Calcium intake showed the strongest protective effect, with each additional 300 mg per day – equivalent to a large glass of milk – associated with a 17% reduced RR. 

Six dairy-related factors associated with calcium – dairy milk, yogurt, riboflavin, magnesium, phosphorus, and potassium intakes – also demonstrated inverse associations with colorectal cancer risk. Weaker protective effects were noted for breakfast cereal, fruit, wholegrains, carbohydrates, fibre, total sugars, folate, and vitamin C. However, the team commented that these inverse associations might reflect residual confounding from other lifestyle or other dietary factors.

Calcium’s protective role was independent of dairy milk intake. The study, published in Nature Communications, concluded that, while “dairy products help protect against colorectal cancer,” that protection is “driven largely or wholly by calcium.”

 

Alcohol and Processed Meat Confirmed as Risk Factors

As expected, alcohol showed the reverse association, with each additional 20 g daily – equivalent to one large glass of wine – associated with a 15% RR increase. Weaker associations were seen for the combined category of red and processed meat, with each additional 30 g per day associated with an 8% increased RR for colorectal cancer. This association was minimally affected by diet and lifestyle factors.

Commenting to the Science Media Centre (SMC), Tom Sanders, professor emeritus of nutrition and dietetics at King’s College London, England, said: “One theory is that the calcium may bind to free bile acids in the gut, preventing the harmful effects of free bile acids on gut mucosa.” However, the lactose content in milk also has effects on large bowel microflora, which may in turn affect risk.

Also commenting to the SMC, David Nunan, senior research fellow at the University of Oxford’s Centre for Evidence Based Medicine, who was not involved in the study, cautioned that the findings were subject to the bias inherent in observational studies. “These biases often inflate the estimated associations compared to controlled experiments,” he said. Nunan advised caution in interpreting the findings, as more robust research, such as randomized controlled trials, would be needed to establish causation.

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

A major prospective study of more than half a million UK women conducted over almost 17 years has confirmed an association between dietary calcium intake and decreased risk of colorectal cancer. 

Cancer Research UK (CRUK), which funded the study, said that it demonstrated the benefits of a healthy, balanced diet for lowering cancer risk.

Colorectal cancer is the third most common cancer worldwide. Incidence rates vary markedly, with higher rates observed in high-income countries. The risk increases for individuals who migrate from low- to high-incidence areas, suggesting that lifestyle and environmental factors contribute to its development.

While alcohol and processed meats are established carcinogens, and red meat is classified as probably carcinogenic, there is a lack of consensus regarding the relationships between other dietary factors and colorectal cancer risk. This uncertainty may be due, at least in part, to relatively few studies giving comprehensive results on all food types, as well as dietary measurement errors, and/or small sample sizes.

 

Study Tracked 97 Dietary Factors

To address these gaps, the research team, led by the University of Oxford in England, tracked the intake of 97 dietary factors in 542,778 women from 2001 for an average of 16.6 years. During this period 12,251 participants developed colorectal cancer. The women completed detailed dietary questionnaires at baseline, with 7% participating in at least one subsequent 24-hour online dietary assessment.

Women diagnosed with colorectal cancer were generally older, taller, more likely to have a family history of bowel cancer, and have more adverse health behaviors, compared with participants overall.

 

Calcium Intake Showed the Strongest Protective Association

Relative risks (RR) for colorectal cancer were calculated for intakes of all 97 dietary factors, with significant associations found for 17 of them. Calcium intake showed the strongest protective effect, with each additional 300 mg per day – equivalent to a large glass of milk – associated with a 17% reduced RR. 

Six dairy-related factors associated with calcium – dairy milk, yogurt, riboflavin, magnesium, phosphorus, and potassium intakes – also demonstrated inverse associations with colorectal cancer risk. Weaker protective effects were noted for breakfast cereal, fruit, wholegrains, carbohydrates, fibre, total sugars, folate, and vitamin C. However, the team commented that these inverse associations might reflect residual confounding from other lifestyle or other dietary factors.

Calcium’s protective role was independent of dairy milk intake. The study, published in Nature Communications, concluded that, while “dairy products help protect against colorectal cancer,” that protection is “driven largely or wholly by calcium.”

 

Alcohol and Processed Meat Confirmed as Risk Factors

As expected, alcohol showed the reverse association, with each additional 20 g daily – equivalent to one large glass of wine – associated with a 15% RR increase. Weaker associations were seen for the combined category of red and processed meat, with each additional 30 g per day associated with an 8% increased RR for colorectal cancer. This association was minimally affected by diet and lifestyle factors.

Commenting to the Science Media Centre (SMC), Tom Sanders, professor emeritus of nutrition and dietetics at King’s College London, England, said: “One theory is that the calcium may bind to free bile acids in the gut, preventing the harmful effects of free bile acids on gut mucosa.” However, the lactose content in milk also has effects on large bowel microflora, which may in turn affect risk.

Also commenting to the SMC, David Nunan, senior research fellow at the University of Oxford’s Centre for Evidence Based Medicine, who was not involved in the study, cautioned that the findings were subject to the bias inherent in observational studies. “These biases often inflate the estimated associations compared to controlled experiments,” he said. Nunan advised caution in interpreting the findings, as more robust research, such as randomized controlled trials, would be needed to establish causation.

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