Clinical Endocrinology News

Vitamin E may be best known for boosting skin and eye health as well as immune function. In recent years, researchers have explored the potential benefits of vitamin E on bone loss, especially in women with menopause-related osteoporosis. While data are beginning to roll in from these studies, evidence supporting a positive impact of vitamin E on osteoporosis and hip fracture risk in perimenopausal women remains elusive.

For osteoporosis, the rationale for using vitamin E is based on its antioxidant activity, which can scavenge potentially damaging free radicals. Researchers have asked whether vitamin E can help maintain the integrity of bone matrix and stimulate bone formation while minimizing bone resorption, particularly in trabecular (spongy) bone, the bone compartment preferentially affected in perimenopausal bone loss. 

Vitamin E mostly consists of two isomers: alpha-tocopherol and gamma-tocopherol. Alpha-tocopherol has higher antioxidant activity and is found in nuts, seeds, vegetable oils, green leafy vegetables, fortified cereals, and vitamin E supplements. Gamma-tocopherol is known for its superior anti-inflammatory properties and accounts for about 70% of the total vitamin E intake in a typical American diet, largely sourced from soybean and other vegetable oils. 

 

Benefits and Risks in Bone Loss Studies

Perimenopausal bone loss is caused, to a great extent, by the decrease in sex hormones. Studies of vitamin E in ovariectomized rats have yielded mixed results. This animal model lacks sex hormones and has similar bone changes to those of postmenopausal women. Some animal studies have suggested a positive effect of vitamin E on bone while others have reported no effect. 

Studies in humans also have produced conflicting reports of positive, neutral, and negative associations of vitamin E with bone health. For example, the Women’s Health Initiative examined the relationship between vitamin and mineral antioxidants and bone health in postmenopausal women and found no significant association between antioxidants and bone mineral density. 

Another study examining data from children and adolescents enrolled in the National Health and Nutrition Examination Survey (NHANES) database found an inverse association between alpha-tocopherol and lumbar spine bone density, suggesting a deleterious effect on bone. Inverse associations also have been reported in certain studies of postmenopausal women.

High doses of alpha-tocopherol have been linked to a risk for impaired bone health through a variety of mechanisms, such as interference with vitamin K metabolism; competitive binding for alpha-tocopherol transfer protein, inhibiting the entry of beneficial vitamin E isomers, including gamma-tocopherol; and pro-oxidant effects that harm bone. Thus, postmenopausal women taking vitamin E supplements primarily as high doses of alpha-tocopherol might be hindering their bone health. 

Data for gamma-tocopherol are more promising. Some studies hypothesize that gamma-tocopherol might uncouple bone turnover, leading to increased bone formation without affecting bone resorption. Further, a randomized controlled study of mixed tocopherols (rather than alpha-tocopherol) vs placebo reported a protective effect of this preparation on bone outcomes by suppressing bone resorption. This raises the importance of considering the specific forms of vitamin E when evaluating its role in bone health.

 

Limitations of Current Studies

Researchers acknowledge several limitations in studies to date. For example, there are very few randomized controlled trials assessing the impact of vitamin E on bone health. Most studies are cross-sectional or observational, even when longitudinal. Cross-sectional and observational designs prevent us from establishing a causal relationship between vitamin E and bone endpoints. 

Such designs also run the risk of additional confounders that may affect associations between vitamin E and bone, or the lack thereof. These could include both known and unknown confounders. Of note, gamma-tocopherol intake data were not available for certain NHANES studies. 

Further, people often consume multiple nutrients and supplements, complicating the identification of specific nutrient-disease associations. Most human studies estimate tocopherol intake by dietary questionnaires or measure serum tocopherol levels, which reflect short-term dietary intake, while bone mineral density is probably influenced by long-term dietary patterns.

 

Too Soon to Prescribe Vitamin E for Bone Health

Some nutrition experts advocate for vitamin E supplements containing mixed tocopherols, specifically suggesting a ratio of 50-100 IU of gamma-tocopherol per 400 IU of D-alpha-tocopherol. Additional research is essential to confirm and further clarify the role of gamma-tocopherol in bone formation and resorption. In fact, it is also important to explore the influence of other compounds in the vitamin E family on skeletal health.

Until more data are available, we would recommend following the Institute of Medicine’s guidelines for the recommended daily allowance (RDA) of vitamin E. This is age dependent, ranging from 4 to 11 mg/d between the ages of 0 and 13 years, and 15 mg/d thereafter. 

Overall, evidence of vitamin E’s impact on osteoporosis and hip fracture risk in perimenopausal women remains inconclusive. Although some observational and interventional studies suggest potential benefits, more interventional studies, particularly randomized controlled trials, are necessary to explore the risks and benefits of vitamin E supplementation and serum vitamin E levels on bone density and fracture risk more thoroughly.

Dr. Pani, Assistant Professor, Department of Internal Medicine, UVA School of Medicine; Medical Director, Department of General Medicine, Same Day Care Clinic, both in Charlottesville, has disclosed no relevant financial relationships. Dr. Misra, Professor, Chair, Physician-in-Chief, Department of Pediatrics, University of Virginia, and UVA Health Children’s, Charlottesville, has disclosed being a key opinion leader for Lumos Pharma.

A version of this article appeared on Medscape.com.

Vitamin E may be best known for boosting skin and eye health as well as immune function. In recent years, researchers have explored the potential benefits of vitamin E on bone loss, especially in women with menopause-related osteoporosis. While data are beginning to roll in from these studies, evidence supporting a positive impact of vitamin E on osteoporosis and hip fracture risk in perimenopausal women remains elusive.

For osteoporosis, the rationale for using vitamin E is based on its antioxidant activity, which can scavenge potentially damaging free radicals. Researchers have asked whether vitamin E can help maintain the integrity of bone matrix and stimulate bone formation while minimizing bone resorption, particularly in trabecular (spongy) bone, the bone compartment preferentially affected in perimenopausal bone loss. 

Vitamin E mostly consists of two isomers: alpha-tocopherol and gamma-tocopherol. Alpha-tocopherol has higher antioxidant activity and is found in nuts, seeds, vegetable oils, green leafy vegetables, fortified cereals, and vitamin E supplements. Gamma-tocopherol is known for its superior anti-inflammatory properties and accounts for about 70% of the total vitamin E intake in a typical American diet, largely sourced from soybean and other vegetable oils. 

 

Benefits and Risks in Bone Loss Studies

Perimenopausal bone loss is caused, to a great extent, by the decrease in sex hormones. Studies of vitamin E in ovariectomized rats have yielded mixed results. This animal model lacks sex hormones and has similar bone changes to those of postmenopausal women. Some animal studies have suggested a positive effect of vitamin E on bone while others have reported no effect. 

Studies in humans also have produced conflicting reports of positive, neutral, and negative associations of vitamin E with bone health. For example, the Women’s Health Initiative examined the relationship between vitamin and mineral antioxidants and bone health in postmenopausal women and found no significant association between antioxidants and bone mineral density. 

Another study examining data from children and adolescents enrolled in the National Health and Nutrition Examination Survey (NHANES) database found an inverse association between alpha-tocopherol and lumbar spine bone density, suggesting a deleterious effect on bone. Inverse associations also have been reported in certain studies of postmenopausal women.

High doses of alpha-tocopherol have been linked to a risk for impaired bone health through a variety of mechanisms, such as interference with vitamin K metabolism; competitive binding for alpha-tocopherol transfer protein, inhibiting the entry of beneficial vitamin E isomers, including gamma-tocopherol; and pro-oxidant effects that harm bone. Thus, postmenopausal women taking vitamin E supplements primarily as high doses of alpha-tocopherol might be hindering their bone health. 

Data for gamma-tocopherol are more promising. Some studies hypothesize that gamma-tocopherol might uncouple bone turnover, leading to increased bone formation without affecting bone resorption. Further, a randomized controlled study of mixed tocopherols (rather than alpha-tocopherol) vs placebo reported a protective effect of this preparation on bone outcomes by suppressing bone resorption. This raises the importance of considering the specific forms of vitamin E when evaluating its role in bone health.

 

Limitations of Current Studies

Researchers acknowledge several limitations in studies to date. For example, there are very few randomized controlled trials assessing the impact of vitamin E on bone health. Most studies are cross-sectional or observational, even when longitudinal. Cross-sectional and observational designs prevent us from establishing a causal relationship between vitamin E and bone endpoints. 

Such designs also run the risk of additional confounders that may affect associations between vitamin E and bone, or the lack thereof. These could include both known and unknown confounders. Of note, gamma-tocopherol intake data were not available for certain NHANES studies. 

Further, people often consume multiple nutrients and supplements, complicating the identification of specific nutrient-disease associations. Most human studies estimate tocopherol intake by dietary questionnaires or measure serum tocopherol levels, which reflect short-term dietary intake, while bone mineral density is probably influenced by long-term dietary patterns.

 

Too Soon to Prescribe Vitamin E for Bone Health

Some nutrition experts advocate for vitamin E supplements containing mixed tocopherols, specifically suggesting a ratio of 50-100 IU of gamma-tocopherol per 400 IU of D-alpha-tocopherol. Additional research is essential to confirm and further clarify the role of gamma-tocopherol in bone formation and resorption. In fact, it is also important to explore the influence of other compounds in the vitamin E family on skeletal health.

Until more data are available, we would recommend following the Institute of Medicine’s guidelines for the recommended daily allowance (RDA) of vitamin E. This is age dependent, ranging from 4 to 11 mg/d between the ages of 0 and 13 years, and 15 mg/d thereafter. 

Overall, evidence of vitamin E’s impact on osteoporosis and hip fracture risk in perimenopausal women remains inconclusive. Although some observational and interventional studies suggest potential benefits, more interventional studies, particularly randomized controlled trials, are necessary to explore the risks and benefits of vitamin E supplementation and serum vitamin E levels on bone density and fracture risk more thoroughly.

Dr. Pani, Assistant Professor, Department of Internal Medicine, UVA School of Medicine; Medical Director, Department of General Medicine, Same Day Care Clinic, both in Charlottesville, has disclosed no relevant financial relationships. Dr. Misra, Professor, Chair, Physician-in-Chief, Department of Pediatrics, University of Virginia, and UVA Health Children’s, Charlottesville, has disclosed being a key opinion leader for Lumos Pharma.

A version of this article appeared on Medscape.com.

Vitamin E may be best known for boosting skin and eye health as well as immune function. In recent years, researchers have explored the potential benefits of vitamin E on bone loss, especially in women with menopause-related osteoporosis. While data are beginning to roll in from these studies, evidence supporting a positive impact of vitamin E on osteoporosis and hip fracture risk in perimenopausal women remains elusive.

For osteoporosis, the rationale for using vitamin E is based on its antioxidant activity, which can scavenge potentially damaging free radicals. Researchers have asked whether vitamin E can help maintain the integrity of bone matrix and stimulate bone formation while minimizing bone resorption, particularly in trabecular (spongy) bone, the bone compartment preferentially affected in perimenopausal bone loss. 

Vitamin E mostly consists of two isomers: alpha-tocopherol and gamma-tocopherol. Alpha-tocopherol has higher antioxidant activity and is found in nuts, seeds, vegetable oils, green leafy vegetables, fortified cereals, and vitamin E supplements. Gamma-tocopherol is known for its superior anti-inflammatory properties and accounts for about 70% of the total vitamin E intake in a typical American diet, largely sourced from soybean and other vegetable oils. 

 

Benefits and Risks in Bone Loss Studies

Perimenopausal bone loss is caused, to a great extent, by the decrease in sex hormones. Studies of vitamin E in ovariectomized rats have yielded mixed results. This animal model lacks sex hormones and has similar bone changes to those of postmenopausal women. Some animal studies have suggested a positive effect of vitamin E on bone while others have reported no effect. 

Studies in humans also have produced conflicting reports of positive, neutral, and negative associations of vitamin E with bone health. For example, the Women’s Health Initiative examined the relationship between vitamin and mineral antioxidants and bone health in postmenopausal women and found no significant association between antioxidants and bone mineral density. 

Another study examining data from children and adolescents enrolled in the National Health and Nutrition Examination Survey (NHANES) database found an inverse association between alpha-tocopherol and lumbar spine bone density, suggesting a deleterious effect on bone. Inverse associations also have been reported in certain studies of postmenopausal women.

High doses of alpha-tocopherol have been linked to a risk for impaired bone health through a variety of mechanisms, such as interference with vitamin K metabolism; competitive binding for alpha-tocopherol transfer protein, inhibiting the entry of beneficial vitamin E isomers, including gamma-tocopherol; and pro-oxidant effects that harm bone. Thus, postmenopausal women taking vitamin E supplements primarily as high doses of alpha-tocopherol might be hindering their bone health. 

Data for gamma-tocopherol are more promising. Some studies hypothesize that gamma-tocopherol might uncouple bone turnover, leading to increased bone formation without affecting bone resorption. Further, a randomized controlled study of mixed tocopherols (rather than alpha-tocopherol) vs placebo reported a protective effect of this preparation on bone outcomes by suppressing bone resorption. This raises the importance of considering the specific forms of vitamin E when evaluating its role in bone health.

 

Limitations of Current Studies

Researchers acknowledge several limitations in studies to date. For example, there are very few randomized controlled trials assessing the impact of vitamin E on bone health. Most studies are cross-sectional or observational, even when longitudinal. Cross-sectional and observational designs prevent us from establishing a causal relationship between vitamin E and bone endpoints. 

Such designs also run the risk of additional confounders that may affect associations between vitamin E and bone, or the lack thereof. These could include both known and unknown confounders. Of note, gamma-tocopherol intake data were not available for certain NHANES studies. 

Further, people often consume multiple nutrients and supplements, complicating the identification of specific nutrient-disease associations. Most human studies estimate tocopherol intake by dietary questionnaires or measure serum tocopherol levels, which reflect short-term dietary intake, while bone mineral density is probably influenced by long-term dietary patterns.

 

Too Soon to Prescribe Vitamin E for Bone Health

Some nutrition experts advocate for vitamin E supplements containing mixed tocopherols, specifically suggesting a ratio of 50-100 IU of gamma-tocopherol per 400 IU of D-alpha-tocopherol. Additional research is essential to confirm and further clarify the role of gamma-tocopherol in bone formation and resorption. In fact, it is also important to explore the influence of other compounds in the vitamin E family on skeletal health.

Until more data are available, we would recommend following the Institute of Medicine’s guidelines for the recommended daily allowance (RDA) of vitamin E. This is age dependent, ranging from 4 to 11 mg/d between the ages of 0 and 13 years, and 15 mg/d thereafter. 

Overall, evidence of vitamin E’s impact on osteoporosis and hip fracture risk in perimenopausal women remains inconclusive. Although some observational and interventional studies suggest potential benefits, more interventional studies, particularly randomized controlled trials, are necessary to explore the risks and benefits of vitamin E supplementation and serum vitamin E levels on bone density and fracture risk more thoroughly.

Dr. Pani, Assistant Professor, Department of Internal Medicine, UVA School of Medicine; Medical Director, Department of General Medicine, Same Day Care Clinic, both in Charlottesville, has disclosed no relevant financial relationships. Dr. Misra, Professor, Chair, Physician-in-Chief, Department of Pediatrics, University of Virginia, and UVA Health Children’s, Charlottesville, has disclosed being a key opinion leader for Lumos Pharma.

A version of this article appeared on Medscape.com.

TOPLINE:

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, lipid-lowering drugs, were associated with a 22% lower risk for nonmelanoma skin cancer (NMSC) in patients with atherosclerotic cardiovascular disease (ASCVD), an effect that was particularly significant among men, those older than 65 years, and those with immunosuppression.

METHODOLOGY:

• To evaluate the risk for NMSC — basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) — in patients with ASCVD on PCSK9 inhibitors, researchers analyzed data from the US Collaborative Network in the TriNetX database of adults aged ≥ 40 years with ASCVD who received statin therapy between 2016 and 2022.
• A total of 73,636 patients were included, divided equally between those receiving a PCSK9 inhibitor (evolocumab, alirocumab, or inclisiran) plus statin therapy and the control group (those on statin therapy only).
• The analysis used propensity score matching for head-to-head comparisons, with hazard ratios (HRs) estimated using Cox proportional hazard models.
• Stratified analyses examined outcomes by age, sex, Fitzpatrick skin type, and immune status. (Immunosuppressed patients were those treated with immunosuppressants for more than 90 days in the year before the index date — the date when exposed patients were first prescribed a PCSK9 inhibitor, which was also index date for matched patients in the statin-only group.)

TAKEAWAY:

• Patients with ASCVD in the PCSK9 group showed significantly lower risks for NMSC (HR, 0.78; 95% CI, 0.71-0.87), BCC (HR, 0.78; 95% CI, 0.69-0.89), and SCC (HR, 0.79; 95% CI, 0.67-0.93) than control individuals on a statin only (P < .001 for all three).
• Both evolocumab and alirocumab demonstrated similar protective effects against the development of NMSC.
• The reduced risk for NMSC was particularly notable among patients aged 65-79 years (HR, 0.75; 95% CI, 0.66-0.86) and those aged ≥ 80 years (HR, 0.74; 95% CI, 0.60-0.91).
• Men showed a more pronounced reduction in the risk for NMSC (HR, 0.73; 95% CI, 0.64-0.83) than women (HR, 0.93; 95% CI, 0.78-1.11). The effect on lowering NMSC risk was also evident among immunosuppressed patients in the PCSK9 group (HR, 0.68; 95% CI, 0.60-0.75).

IN PRACTICE:

“The findings suggest the promising pleiotropic effect of PCSK9 inhibitors on the chemoprevention of NMSC,” the study authors wrote. Referring to previous studies that “provided mechanistic clues to our findings,” they added that “further studies are required to investigate the underlying mechanisms and establish causality.”

SOURCE:

The study was led by Cheng-Yuan Li, Taipei Veterans General Hospital, Taipei, Taiwan, and was published online in The British Journal of Dermatology.

LIMITATIONS:

Electronic health records lack information on sun protection habits, family history of skin cancer, diet, body mass index, and air pollution exposure, risk factors for NMSC. The study also lacked detailed information on enrollees’ lipid profiles and was focused mostly on patients in the United States, limiting the generalizability of the findings to other regions.

DISCLOSURES:

The study was supported by grants from Taipei Veterans General Hospital and the Ministry of Science and Technology, Taiwan. 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 first appeared on Medscape.com.

TOPLINE:

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, lipid-lowering drugs, were associated with a 22% lower risk for nonmelanoma skin cancer (NMSC) in patients with atherosclerotic cardiovascular disease (ASCVD), an effect that was particularly significant among men, those older than 65 years, and those with immunosuppression.

METHODOLOGY:

• To evaluate the risk for NMSC — basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) — in patients with ASCVD on PCSK9 inhibitors, researchers analyzed data from the US Collaborative Network in the TriNetX database of adults aged ≥ 40 years with ASCVD who received statin therapy between 2016 and 2022.
• A total of 73,636 patients were included, divided equally between those receiving a PCSK9 inhibitor (evolocumab, alirocumab, or inclisiran) plus statin therapy and the control group (those on statin therapy only).
• The analysis used propensity score matching for head-to-head comparisons, with hazard ratios (HRs) estimated using Cox proportional hazard models.
• Stratified analyses examined outcomes by age, sex, Fitzpatrick skin type, and immune status. (Immunosuppressed patients were those treated with immunosuppressants for more than 90 days in the year before the index date — the date when exposed patients were first prescribed a PCSK9 inhibitor, which was also index date for matched patients in the statin-only group.)

TAKEAWAY:

• Patients with ASCVD in the PCSK9 group showed significantly lower risks for NMSC (HR, 0.78; 95% CI, 0.71-0.87), BCC (HR, 0.78; 95% CI, 0.69-0.89), and SCC (HR, 0.79; 95% CI, 0.67-0.93) than control individuals on a statin only (P < .001 for all three).
• Both evolocumab and alirocumab demonstrated similar protective effects against the development of NMSC.
• The reduced risk for NMSC was particularly notable among patients aged 65-79 years (HR, 0.75; 95% CI, 0.66-0.86) and those aged ≥ 80 years (HR, 0.74; 95% CI, 0.60-0.91).
• Men showed a more pronounced reduction in the risk for NMSC (HR, 0.73; 95% CI, 0.64-0.83) than women (HR, 0.93; 95% CI, 0.78-1.11). The effect on lowering NMSC risk was also evident among immunosuppressed patients in the PCSK9 group (HR, 0.68; 95% CI, 0.60-0.75).

IN PRACTICE:

“The findings suggest the promising pleiotropic effect of PCSK9 inhibitors on the chemoprevention of NMSC,” the study authors wrote. Referring to previous studies that “provided mechanistic clues to our findings,” they added that “further studies are required to investigate the underlying mechanisms and establish causality.”

SOURCE:

The study was led by Cheng-Yuan Li, Taipei Veterans General Hospital, Taipei, Taiwan, and was published online in The British Journal of Dermatology.

LIMITATIONS:

Electronic health records lack information on sun protection habits, family history of skin cancer, diet, body mass index, and air pollution exposure, risk factors for NMSC. The study also lacked detailed information on enrollees’ lipid profiles and was focused mostly on patients in the United States, limiting the generalizability of the findings to other regions.

DISCLOSURES:

The study was supported by grants from Taipei Veterans General Hospital and the Ministry of Science and Technology, Taiwan. 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 first appeared on Medscape.com.

TOPLINE:

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, lipid-lowering drugs, were associated with a 22% lower risk for nonmelanoma skin cancer (NMSC) in patients with atherosclerotic cardiovascular disease (ASCVD), an effect that was particularly significant among men, those older than 65 years, and those with immunosuppression.

METHODOLOGY:

• To evaluate the risk for NMSC — basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) — in patients with ASCVD on PCSK9 inhibitors, researchers analyzed data from the US Collaborative Network in the TriNetX database of adults aged ≥ 40 years with ASCVD who received statin therapy between 2016 and 2022.
• A total of 73,636 patients were included, divided equally between those receiving a PCSK9 inhibitor (evolocumab, alirocumab, or inclisiran) plus statin therapy and the control group (those on statin therapy only).
• The analysis used propensity score matching for head-to-head comparisons, with hazard ratios (HRs) estimated using Cox proportional hazard models.
• Stratified analyses examined outcomes by age, sex, Fitzpatrick skin type, and immune status. (Immunosuppressed patients were those treated with immunosuppressants for more than 90 days in the year before the index date — the date when exposed patients were first prescribed a PCSK9 inhibitor, which was also index date for matched patients in the statin-only group.)

TAKEAWAY:

• Patients with ASCVD in the PCSK9 group showed significantly lower risks for NMSC (HR, 0.78; 95% CI, 0.71-0.87), BCC (HR, 0.78; 95% CI, 0.69-0.89), and SCC (HR, 0.79; 95% CI, 0.67-0.93) than control individuals on a statin only (P < .001 for all three).
• Both evolocumab and alirocumab demonstrated similar protective effects against the development of NMSC.
• The reduced risk for NMSC was particularly notable among patients aged 65-79 years (HR, 0.75; 95% CI, 0.66-0.86) and those aged ≥ 80 years (HR, 0.74; 95% CI, 0.60-0.91).
• Men showed a more pronounced reduction in the risk for NMSC (HR, 0.73; 95% CI, 0.64-0.83) than women (HR, 0.93; 95% CI, 0.78-1.11). The effect on lowering NMSC risk was also evident among immunosuppressed patients in the PCSK9 group (HR, 0.68; 95% CI, 0.60-0.75).

IN PRACTICE:

“The findings suggest the promising pleiotropic effect of PCSK9 inhibitors on the chemoprevention of NMSC,” the study authors wrote. Referring to previous studies that “provided mechanistic clues to our findings,” they added that “further studies are required to investigate the underlying mechanisms and establish causality.”

SOURCE:

The study was led by Cheng-Yuan Li, Taipei Veterans General Hospital, Taipei, Taiwan, and was published online in The British Journal of Dermatology.

LIMITATIONS:

Electronic health records lack information on sun protection habits, family history of skin cancer, diet, body mass index, and air pollution exposure, risk factors for NMSC. The study also lacked detailed information on enrollees’ lipid profiles and was focused mostly on patients in the United States, limiting the generalizability of the findings to other regions.

DISCLOSURES:

The study was supported by grants from Taipei Veterans General Hospital and the Ministry of Science and Technology, Taiwan. 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 first appeared on Medscape.com.

They’re literally not better. Idealistically, sure, but literally not. And there’s really no debate. Meaning there’s never been a reproducible diet and exercise intervention that has led to anywhere near the average weight lost by those taking obesity medications. Furthermore, when it comes to the durability of weight lost, the gulf between outcomes with diet and exercise vs obesity medications is even more dramatic.

Looking to the literature, one of the most trotted out studies on lifestyle’s impact on weight over time is the Look AHEAD trial. Before useful obesity medications came on the scene, I trotted it out myself. Why? Because it was heartening when faced with the societal refrain that diet and exercise never worked to be able to show that yes, in fact they do. But how well?

Looking to Look AHEAD’s 4-year data (Obesity [Silver Spring]. 2011 Oct;19[10]:1987-1998), those randomized to the intensive lifestyle initiative arm averaged a 4.7% total body weight loss – an amount that remained the same at 8 years. But I chose 4 years because that’s a better comparison with the semaglutide SELECT trial that revealed at 4 years, the average sustained weight lost was more than double that of Look AHEAD’s, at 10.2%. Meanwhile the recently released SURMOUNT-4 study on tirzepatide reported that at 88 weeks, the average weight lost by participants was a near bariatric surgery level of 25.3% with no signs suggestive of pending regains.

Now maybe you want to cling to the notion that if you just try hard enough, your diet and exercise regime can beat our new meds. Well, it’s difficult to think of a more miserable, often actual vomit-inducing intervention, than the spectacle that used to air weekly on prime time called The Biggest Loser, where participants lived on a ranch and were berated and exercised all day long for the chance to lose the most and win a quarter of a million dollars. But even there, the meds prove to be superior. Although the short-term Biggest Loser data do look markedly better than meds (and than bariatric surgery), whereby the average participant lost 48.8% of their body weight during the grueling 7-month long, 24/7 competition, by postcompetition year 6, the average weight lost dropped to 12.7%.

Yet on November 26, when word came out that Medicare is likely to extend coverage to obesity medications for far more Americans, one of the most common refrains was something along the lines of yes, lifestyle modification is the best choice for dealing with obesity but it’s good that there will be medication options for those where that’s insufficient.

What?

The only reason that the world isn’t comfortable with the eminently provable truth that diet and exercise are inferior to obesity medications for weight management is weight bias. The message is that people simply aren’t trying hard enough. This despite our comfort in knowing that medications have more of an impact than lifestyle on pretty much every other chronic disease. Nor can I recall any other circumstance when coverage of a remarkably effective drug was qualified by the suggestion that known-to-be-inferior interventions are still the best or favored choice.

At this point, obesity medications are plainly the first-line choice of treatment. They provide not only dramatically greater and more durable weight loss than lifestyle interventions, they have also been shown to very significantly reduce the risk for an ever-growing list of other medical concerns including heart attacks, strokes, type 2 diabetes, hypertension, sleep apnea, fatty liver disease, and more, while carrying minimal risk.

Let it also be said that improvements to diet and exercise are worth striving for at any weight, though one should not lose sight of the fact that perpetual, dramatic, intentional, behavior change in the name of health requires vast amounts of wide-ranging privilege to enact — amounts far beyond the average person’s abilities or physiologies (as demonstrated with obesity by decades of disappointing long-term lifestyle outcome data). 

Let it also be said that some people will indeed find success solely through lifestyle and that not every person who meets the medical criteria for any medication’s prescription, including obesity medications, is required or encouraged to take it. The clinician’s job, however, at its most basic, is to inform patients who meet medical use criteria of their options, and if a medication is indicated, to inform them of that medication’s risks and benefits and expected outcomes, to help their patients come to their own treatment decisions.

It’s not a bad thing that we have medications that deliver better outcomes than lifestyle — in fact, it’s terrific, and thankfully that they do is true for pretty much every medical condition for which we have medication. That’s in fact why we have medications! And so this constant refrain of golly-gee wouldn’t it be better if we could just manage obesity with lifestyle changes needs to be put to rest — we literally know it wouldn’t be better, and it’s only weight bias that would lead this evidence-based statement to seem off-putting.

Dr. Freedhoff is Associate Professor, Department of Family Medicine, University of Ottawa, and Medical Director, Bariatric Medical Institute, Ottawa, Ontario, Canada. He reported conflicts of interest with the Bariatric Medical Institute, Constant Health, Novo Nordisk, and Weighty Matters.

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

They’re literally not better. Idealistically, sure, but literally not. And there’s really no debate. Meaning there’s never been a reproducible diet and exercise intervention that has led to anywhere near the average weight lost by those taking obesity medications. Furthermore, when it comes to the durability of weight lost, the gulf between outcomes with diet and exercise vs obesity medications is even more dramatic.

Looking to the literature, one of the most trotted out studies on lifestyle’s impact on weight over time is the Look AHEAD trial. Before useful obesity medications came on the scene, I trotted it out myself. Why? Because it was heartening when faced with the societal refrain that diet and exercise never worked to be able to show that yes, in fact they do. But how well?

Looking to Look AHEAD’s 4-year data (Obesity [Silver Spring]. 2011 Oct;19[10]:1987-1998), those randomized to the intensive lifestyle initiative arm averaged a 4.7% total body weight loss – an amount that remained the same at 8 years. But I chose 4 years because that’s a better comparison with the semaglutide SELECT trial that revealed at 4 years, the average sustained weight lost was more than double that of Look AHEAD’s, at 10.2%. Meanwhile the recently released SURMOUNT-4 study on tirzepatide reported that at 88 weeks, the average weight lost by participants was a near bariatric surgery level of 25.3% with no signs suggestive of pending regains.

Now maybe you want to cling to the notion that if you just try hard enough, your diet and exercise regime can beat our new meds. Well, it’s difficult to think of a more miserable, often actual vomit-inducing intervention, than the spectacle that used to air weekly on prime time called The Biggest Loser, where participants lived on a ranch and were berated and exercised all day long for the chance to lose the most and win a quarter of a million dollars. But even there, the meds prove to be superior. Although the short-term Biggest Loser data do look markedly better than meds (and than bariatric surgery), whereby the average participant lost 48.8% of their body weight during the grueling 7-month long, 24/7 competition, by postcompetition year 6, the average weight lost dropped to 12.7%.

Yet on November 26, when word came out that Medicare is likely to extend coverage to obesity medications for far more Americans, one of the most common refrains was something along the lines of yes, lifestyle modification is the best choice for dealing with obesity but it’s good that there will be medication options for those where that’s insufficient.

What?

The only reason that the world isn’t comfortable with the eminently provable truth that diet and exercise are inferior to obesity medications for weight management is weight bias. The message is that people simply aren’t trying hard enough. This despite our comfort in knowing that medications have more of an impact than lifestyle on pretty much every other chronic disease. Nor can I recall any other circumstance when coverage of a remarkably effective drug was qualified by the suggestion that known-to-be-inferior interventions are still the best or favored choice.

At this point, obesity medications are plainly the first-line choice of treatment. They provide not only dramatically greater and more durable weight loss than lifestyle interventions, they have also been shown to very significantly reduce the risk for an ever-growing list of other medical concerns including heart attacks, strokes, type 2 diabetes, hypertension, sleep apnea, fatty liver disease, and more, while carrying minimal risk.

Let it also be said that improvements to diet and exercise are worth striving for at any weight, though one should not lose sight of the fact that perpetual, dramatic, intentional, behavior change in the name of health requires vast amounts of wide-ranging privilege to enact — amounts far beyond the average person’s abilities or physiologies (as demonstrated with obesity by decades of disappointing long-term lifestyle outcome data). 

Let it also be said that some people will indeed find success solely through lifestyle and that not every person who meets the medical criteria for any medication’s prescription, including obesity medications, is required or encouraged to take it. The clinician’s job, however, at its most basic, is to inform patients who meet medical use criteria of their options, and if a medication is indicated, to inform them of that medication’s risks and benefits and expected outcomes, to help their patients come to their own treatment decisions.

It’s not a bad thing that we have medications that deliver better outcomes than lifestyle — in fact, it’s terrific, and thankfully that they do is true for pretty much every medical condition for which we have medication. That’s in fact why we have medications! And so this constant refrain of golly-gee wouldn’t it be better if we could just manage obesity with lifestyle changes needs to be put to rest — we literally know it wouldn’t be better, and it’s only weight bias that would lead this evidence-based statement to seem off-putting.

Dr. Freedhoff is Associate Professor, Department of Family Medicine, University of Ottawa, and Medical Director, Bariatric Medical Institute, Ottawa, Ontario, Canada. He reported conflicts of interest with the Bariatric Medical Institute, Constant Health, Novo Nordisk, and Weighty Matters.

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

They’re literally not better. Idealistically, sure, but literally not. And there’s really no debate. Meaning there’s never been a reproducible diet and exercise intervention that has led to anywhere near the average weight lost by those taking obesity medications. Furthermore, when it comes to the durability of weight lost, the gulf between outcomes with diet and exercise vs obesity medications is even more dramatic.

Looking to the literature, one of the most trotted out studies on lifestyle’s impact on weight over time is the Look AHEAD trial. Before useful obesity medications came on the scene, I trotted it out myself. Why? Because it was heartening when faced with the societal refrain that diet and exercise never worked to be able to show that yes, in fact they do. But how well?

Looking to Look AHEAD’s 4-year data (Obesity [Silver Spring]. 2011 Oct;19[10]:1987-1998), those randomized to the intensive lifestyle initiative arm averaged a 4.7% total body weight loss – an amount that remained the same at 8 years. But I chose 4 years because that’s a better comparison with the semaglutide SELECT trial that revealed at 4 years, the average sustained weight lost was more than double that of Look AHEAD’s, at 10.2%. Meanwhile the recently released SURMOUNT-4 study on tirzepatide reported that at 88 weeks, the average weight lost by participants was a near bariatric surgery level of 25.3% with no signs suggestive of pending regains.

Now maybe you want to cling to the notion that if you just try hard enough, your diet and exercise regime can beat our new meds. Well, it’s difficult to think of a more miserable, often actual vomit-inducing intervention, than the spectacle that used to air weekly on prime time called The Biggest Loser, where participants lived on a ranch and were berated and exercised all day long for the chance to lose the most and win a quarter of a million dollars. But even there, the meds prove to be superior. Although the short-term Biggest Loser data do look markedly better than meds (and than bariatric surgery), whereby the average participant lost 48.8% of their body weight during the grueling 7-month long, 24/7 competition, by postcompetition year 6, the average weight lost dropped to 12.7%.

Yet on November 26, when word came out that Medicare is likely to extend coverage to obesity medications for far more Americans, one of the most common refrains was something along the lines of yes, lifestyle modification is the best choice for dealing with obesity but it’s good that there will be medication options for those where that’s insufficient.

What?

The only reason that the world isn’t comfortable with the eminently provable truth that diet and exercise are inferior to obesity medications for weight management is weight bias. The message is that people simply aren’t trying hard enough. This despite our comfort in knowing that medications have more of an impact than lifestyle on pretty much every other chronic disease. Nor can I recall any other circumstance when coverage of a remarkably effective drug was qualified by the suggestion that known-to-be-inferior interventions are still the best or favored choice.

At this point, obesity medications are plainly the first-line choice of treatment. They provide not only dramatically greater and more durable weight loss than lifestyle interventions, they have also been shown to very significantly reduce the risk for an ever-growing list of other medical concerns including heart attacks, strokes, type 2 diabetes, hypertension, sleep apnea, fatty liver disease, and more, while carrying minimal risk.

Let it also be said that improvements to diet and exercise are worth striving for at any weight, though one should not lose sight of the fact that perpetual, dramatic, intentional, behavior change in the name of health requires vast amounts of wide-ranging privilege to enact — amounts far beyond the average person’s abilities or physiologies (as demonstrated with obesity by decades of disappointing long-term lifestyle outcome data). 

Let it also be said that some people will indeed find success solely through lifestyle and that not every person who meets the medical criteria for any medication’s prescription, including obesity medications, is required or encouraged to take it. The clinician’s job, however, at its most basic, is to inform patients who meet medical use criteria of their options, and if a medication is indicated, to inform them of that medication’s risks and benefits and expected outcomes, to help their patients come to their own treatment decisions.

It’s not a bad thing that we have medications that deliver better outcomes than lifestyle — in fact, it’s terrific, and thankfully that they do is true for pretty much every medical condition for which we have medication. That’s in fact why we have medications! And so this constant refrain of golly-gee wouldn’t it be better if we could just manage obesity with lifestyle changes needs to be put to rest — we literally know it wouldn’t be better, and it’s only weight bias that would lead this evidence-based statement to seem off-putting.

Dr. Freedhoff is Associate Professor, Department of Family Medicine, University of Ottawa, and Medical Director, Bariatric Medical Institute, Ottawa, Ontario, Canada. He reported conflicts of interest with the Bariatric Medical Institute, Constant Health, Novo Nordisk, and Weighty Matters.

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

TOPLINE:

Consuming five or more servings per week of dark chocolate is associated with a lower risk for type 2 diabetes (T2D), compared with infrequent or no consumption. Conversely, a higher consumption of milk chocolate does not significantly affect the risk for diabetes and may contribute to greater weight gain.

METHODOLOGY:

• Chocolate is rich in flavanols, natural compounds known to support heart health and lower the risk for T2D. However, the link between chocolate consumption and the risk for T2D is uncertain, with inconsistent research findings that don’t distinguish between dark or milk chocolate.
• Researchers conducted a prospective cohort study to investigate the associations between dark, milk, and total chocolate consumption and the risk for T2D in three long-term US studies of female nurses and male healthcare professionals with no history of diabetes, cardiovascular disease, or cancer at baseline.
• The relationship between total chocolate consumption and the risk for diabetes was investigated in 192,208 individuals who reported their chocolate consumption using validated food frequency questionnaires every 4 years from 1986 onward.
• Information on chocolate subtypes was assessed from 2006/2007 onward in 111,654 participants.
• Participants self-reported T2D through biennial questionnaires, which was confirmed via supplementary questionnaires collecting data on glucose levels, hemoglobin A1c concentration, symptoms, and treatments; they also self-reported their body weight at baseline and during follow-ups.

TAKEAWAY:

• During 4,829,175 person-years of follow-up, researchers identified 18,862 individuals with incident T2D in the total chocolate analysis cohort.
• In the chocolate subtype cohort, 4771 incident T2D cases were identified during 1,270,348 person-years of follow-up. Having at least five servings per week of dark chocolate was associated with a 21% lower risk for T2D (adjusted hazard ratio, 0.79; P for trend = .006), while milk chocolate consumption showed no significant link (P for trend = .75).
• The risk for T2D decreased by 3% for each additional serving of dark chocolate consumed weekly, indicating a dose-response effect.
• Compared with individuals who did not change their chocolate intake, those who had an increased milk chocolate intake had greater weight gain over 4-year periods (mean difference, 0.35 kg; 95% CI, 0.27-0.43); dark chocolate showed no significant association with weight change.

IN PRACTICE:

“Even though dark and milk chocolate have similar levels of calories and saturated fat, it appears that the rich polyphenols in dark chocolate might offset the effects of saturated fat and sugar on weight gain and diabetes. It’s an intriguing difference that’s worth exploring more,” corresponding author Qi Sun from the Departments of Nutrition and Epidemiology, Harvard TH Chan School of Public Health, Boston, Massachusetts, said in a press release.

SOURCE:

This study was led by Binkai Liu, Harvard TH Chan School of Public Health. It was published online in The BMJ.

LIMITATIONS:

The relatively limited number of participants in the higher chocolate consumption groups may have reduced the statistical power for detecting modest associations between dark chocolate consumption and the risk for T2D. Additionally, the study population primarily consisted of non-Hispanic White adults older than 50 years at baseline, which, along with their professional backgrounds, may have limited the generalizability of the study findings to other populations with different socioeconomic or personal characteristics. Chocolate consumption in this study was lower than the national average of three servings per week, which may have limited the ability to assess the dose-response relationship at higher intake levels.

DISCLOSURES:

This study was supported by grants from the National Institutes of Health. Some authors reported receiving investigator-initiated grants, being on scientific advisory boards, and receiving research funding from certain institutions.

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:

Consuming five or more servings per week of dark chocolate is associated with a lower risk for type 2 diabetes (T2D), compared with infrequent or no consumption. Conversely, a higher consumption of milk chocolate does not significantly affect the risk for diabetes and may contribute to greater weight gain.

METHODOLOGY:

• Chocolate is rich in flavanols, natural compounds known to support heart health and lower the risk for T2D. However, the link between chocolate consumption and the risk for T2D is uncertain, with inconsistent research findings that don’t distinguish between dark or milk chocolate.
• Researchers conducted a prospective cohort study to investigate the associations between dark, milk, and total chocolate consumption and the risk for T2D in three long-term US studies of female nurses and male healthcare professionals with no history of diabetes, cardiovascular disease, or cancer at baseline.
• The relationship between total chocolate consumption and the risk for diabetes was investigated in 192,208 individuals who reported their chocolate consumption using validated food frequency questionnaires every 4 years from 1986 onward.
• Information on chocolate subtypes was assessed from 2006/2007 onward in 111,654 participants.
• Participants self-reported T2D through biennial questionnaires, which was confirmed via supplementary questionnaires collecting data on glucose levels, hemoglobin A1c concentration, symptoms, and treatments; they also self-reported their body weight at baseline and during follow-ups.

TAKEAWAY:

• During 4,829,175 person-years of follow-up, researchers identified 18,862 individuals with incident T2D in the total chocolate analysis cohort.
• In the chocolate subtype cohort, 4771 incident T2D cases were identified during 1,270,348 person-years of follow-up. Having at least five servings per week of dark chocolate was associated with a 21% lower risk for T2D (adjusted hazard ratio, 0.79; P for trend = .006), while milk chocolate consumption showed no significant link (P for trend = .75).
• The risk for T2D decreased by 3% for each additional serving of dark chocolate consumed weekly, indicating a dose-response effect.
• Compared with individuals who did not change their chocolate intake, those who had an increased milk chocolate intake had greater weight gain over 4-year periods (mean difference, 0.35 kg; 95% CI, 0.27-0.43); dark chocolate showed no significant association with weight change.

IN PRACTICE:

“Even though dark and milk chocolate have similar levels of calories and saturated fat, it appears that the rich polyphenols in dark chocolate might offset the effects of saturated fat and sugar on weight gain and diabetes. It’s an intriguing difference that’s worth exploring more,” corresponding author Qi Sun from the Departments of Nutrition and Epidemiology, Harvard TH Chan School of Public Health, Boston, Massachusetts, said in a press release.

SOURCE:

This study was led by Binkai Liu, Harvard TH Chan School of Public Health. It was published online in The BMJ.

LIMITATIONS:

The relatively limited number of participants in the higher chocolate consumption groups may have reduced the statistical power for detecting modest associations between dark chocolate consumption and the risk for T2D. Additionally, the study population primarily consisted of non-Hispanic White adults older than 50 years at baseline, which, along with their professional backgrounds, may have limited the generalizability of the study findings to other populations with different socioeconomic or personal characteristics. Chocolate consumption in this study was lower than the national average of three servings per week, which may have limited the ability to assess the dose-response relationship at higher intake levels.

DISCLOSURES:

This study was supported by grants from the National Institutes of Health. Some authors reported receiving investigator-initiated grants, being on scientific advisory boards, and receiving research funding from certain institutions.

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:

Consuming five or more servings per week of dark chocolate is associated with a lower risk for type 2 diabetes (T2D), compared with infrequent or no consumption. Conversely, a higher consumption of milk chocolate does not significantly affect the risk for diabetes and may contribute to greater weight gain.

METHODOLOGY:

• Chocolate is rich in flavanols, natural compounds known to support heart health and lower the risk for T2D. However, the link between chocolate consumption and the risk for T2D is uncertain, with inconsistent research findings that don’t distinguish between dark or milk chocolate.
• Researchers conducted a prospective cohort study to investigate the associations between dark, milk, and total chocolate consumption and the risk for T2D in three long-term US studies of female nurses and male healthcare professionals with no history of diabetes, cardiovascular disease, or cancer at baseline.
• The relationship between total chocolate consumption and the risk for diabetes was investigated in 192,208 individuals who reported their chocolate consumption using validated food frequency questionnaires every 4 years from 1986 onward.
• Information on chocolate subtypes was assessed from 2006/2007 onward in 111,654 participants.
• Participants self-reported T2D through biennial questionnaires, which was confirmed via supplementary questionnaires collecting data on glucose levels, hemoglobin A1c concentration, symptoms, and treatments; they also self-reported their body weight at baseline and during follow-ups.

TAKEAWAY:

• During 4,829,175 person-years of follow-up, researchers identified 18,862 individuals with incident T2D in the total chocolate analysis cohort.
• In the chocolate subtype cohort, 4771 incident T2D cases were identified during 1,270,348 person-years of follow-up. Having at least five servings per week of dark chocolate was associated with a 21% lower risk for T2D (adjusted hazard ratio, 0.79; P for trend = .006), while milk chocolate consumption showed no significant link (P for trend = .75).
• The risk for T2D decreased by 3% for each additional serving of dark chocolate consumed weekly, indicating a dose-response effect.
• Compared with individuals who did not change their chocolate intake, those who had an increased milk chocolate intake had greater weight gain over 4-year periods (mean difference, 0.35 kg; 95% CI, 0.27-0.43); dark chocolate showed no significant association with weight change.

IN PRACTICE:

“Even though dark and milk chocolate have similar levels of calories and saturated fat, it appears that the rich polyphenols in dark chocolate might offset the effects of saturated fat and sugar on weight gain and diabetes. It’s an intriguing difference that’s worth exploring more,” corresponding author Qi Sun from the Departments of Nutrition and Epidemiology, Harvard TH Chan School of Public Health, Boston, Massachusetts, said in a press release.

SOURCE:

This study was led by Binkai Liu, Harvard TH Chan School of Public Health. It was published online in The BMJ.

LIMITATIONS:

The relatively limited number of participants in the higher chocolate consumption groups may have reduced the statistical power for detecting modest associations between dark chocolate consumption and the risk for T2D. Additionally, the study population primarily consisted of non-Hispanic White adults older than 50 years at baseline, which, along with their professional backgrounds, may have limited the generalizability of the study findings to other populations with different socioeconomic or personal characteristics. Chocolate consumption in this study was lower than the national average of three servings per week, which may have limited the ability to assess the dose-response relationship at higher intake levels.

DISCLOSURES:

This study was supported by grants from the National Institutes of Health. Some authors reported receiving investigator-initiated grants, being on scientific advisory boards, and receiving research funding from certain institutions.

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 results of the SUMMIT trial of the long-acting agonist of glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors, tirzepatide, in patients with heart failure with preserved ejection fraction (HFpEF) and obesity are positive. But the trial design leaves clinicians and regulators with big doses of uncertainty.

Known Facts About HFpEF

HFpEF has exceeded heart failure with reduced ejection fraction (HFrEF) as the most common form of heart failure. HFpEF differs from HFrEF in that patients with preserved ejection fraction often present later in life with more comorbidities.

Some of these comorbidities are on the causal pathway of heart failure. Obesity, for instance, both associates with HFpEF and surely causes the diastolic dysfunction central to the condition. This may be a direct effect via high excess adipose tissue or an indirect effect via pro-inflammatory pathways.

GLP-1 agonists and the dual-acting GIP/GLP1 agonist tirzepatide have proven efficacy for weight loss. Semaglutide has previously been shown to improve quality of life and physical functioning in two small trials of patients with HFpEF and obesity. Semaglutide also reduced hard clinical outcomes in patients with obesity and these other conditions: chronic kidney disease, diabetes, and established atherosclerotic vascular disease.

This class of drugs is costly. The combination of both high drug costs and highly prevalent conditions such as obesity and HFpEF forces clinicians to make both value and clinical judgments when translating evidence.

 

The SUMMIT Trial

The SUMMIT trial aimed to evaluate tirzepatide’s effect on typical heart failure events, health status and functional capacity in patients with obesity and HFpEF. A total of 731 patients were randomly assigned to receive to tirzepatide or placebo.

Investigators chose two co-primary endpoints. The first was a composite of cardiovascular (CV) death and worsening heart failure events—the latter could be a hospitalization for heart failure, a visit for intravenous diuretics, or intensification of oral diuretics. The idea behind this rather unique composite was to capture all heart failure events. The second co-primary endpoint was a change in baseline Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) at 1 year.

Characteristics of the patients included an average age of 65 years, 55% were female, the average body mass index was 38, and the mean left ventricular ejection fraction was 61% (the minimum for trial entry was 50%). Just under half had been hospitalized for heart failure in the year before trial entry.

 

Tirzepatide Results

The primary outcome of CV death and first heart failure event occurred in 36 patients (9.9%) in the tirzepatide group and 56 patients (15.3%) in the placebo group, for a hazard ratio of 0.62 (95% CI, 0.41-0.95; P =.026).

The 5.4% absolute risk reduction in the primary endpoint was completely driven by lower rates of heart failure events (8% vs 14.2%). CV death was actually higher in the tirzepatide arm, but the number of deaths was low in both arms (8 vs 5).

The rate of hospitalizations due to heart failure was lower with tirzepatide (3.3% vs 7.1%), as was intensification of oral diuretics (4.7% vs 5.7%).

The second co-primary endpoint of change from baseline in KCCQ-CSS favored tirzepatide.

Other secondary endpoints also favored tirzepatide: longer 6-minute walk distance, greater change in body weight (-11.6%), and lower high-sensitivity C-reactive protein levels and systolic blood pressure (-4.7 mm Hg).

 

Authors’ Conclusions and Expert Comments

At the American Heart Association Scientific Sessions, the primary investigator Milton Packer, MD, said SUMMIT was the first trial of patients with obesity and HFpEF that had major heart failure outcomes as the primary endpoint. And that tirzepatide changed the clinical trajectory of the disease.

Jennifer Ho, MD, associate professor of medicine at Harvard Medical School, Boston, Massachusetts, said, “This really is a practice-changing trial and cements this type of therapy as one of the cornerstones of obesity and HFpEF treatment.”

Other experts cited a recently published pooled analysis of semaglutide trials looking specifically at patients with HFpEF and found lower rates of HF events with the GLP-1 agonist.

The SUMMIT trial results were covered in 53 news outlets— nearly all with glowing headlines.

 

My Six Concerns With SUMMIT

The trial delivered statistically positive findings. What’s more, patients lost weight, and a greater than 11% weight loss difference is meaningful. Patients with a baseline weight of more than 100 kg who lose this much weight are bound to feel and function better.

The first problem comes when we ask whether the results are disease-modifying. There was no difference in CV death. And the number of hospitalizations for heart failure — the more standard endpoint — was low, at only 12 and 26, respectively. Contrast this with the DELIVER trial of the sodium-glucose cotransporter 2 inhibitor dapagliflozin in HFpEF where there were nearly 750 hospitalizations for heart failure and PARAGON-HF of sacubitril-valsartan vs valsartan in HFpEF, where there were nearly 1500. SUMMIT simply had too few events to make conclusions — a point Packer has made regarding AF ablation trials in patients with heart failure.

I have previously called GLP-1 drugs disease-modifying in patients with obesity and atherosclerotic disease. This is because the SELECT trial of semaglutide randomized more than 17,000 patients and recorded a 20% reduction in hard outcomes. And there were more than 1200 primary outcome events. SUMMIT does not come close to this measure.

The second issue is short follow-up. These were 65-year-old patients and with only 2 years of follow-up, it is hard to make conclusions regarding whether or not these drugs can provide long-term benefit.

The third issue is that SUMMIT authors don’t tell us the number of all-cause hospitalizations. I was part of a recently published meta-analysis of more than 100 heart failure trials that raised questions regarding the value of hospitalizations for heart failure as a surrogate for heart failure outcomes.

For instance, we found that in large trials there was great variability in the ability of a reduction in HF hospitalizations to predict a reduction in all-cause hospitalization. In small trials, such as SUMMIT, it would likely be impossible to predict how the reduction in HF hospitalization would predict all-cause hospitalization. I believe all-cause hospitalization is a more inclusive endpoint because it is bias free; it captures benefits and potential harms of the therapy; and it is patient-centered, because patients probably do not care what type of hospitalization they avoid.

The fourth issue with SUMMIT is the difficulty in maintaining blinding, which reduces confidence in outcomes that require clinical decisions or patient judgments. Owing to gastrointestinal symptoms, decreased appetite, and weight loss, patients on this class of drugs are very likely to know their treatment assignment. This is a criticism of not only SUMMIT but all GLP-1 agonist trials. The fact that blinding is difficult to maintain argues for choosing endpoints less susceptible to bias, such as CV death or all-cause hospitalization.

Proponents of tirzepatide for this indication might argue that unblinding is less of an issue because of objective endpoints such as biomarkers. And they have a point, but nearly all other endpoints, especially the co-primary endpoint of KCCQ-CSS, are largely susceptible to bias.

The fifth and main problem comes in translating this evidence in the clinic. Should doctors give up on nondrug means of weight loss? All of the positive outcome trials in this class of drugs have also shown weight loss. I believe we should take these data and use them to re-invigorate our advocacy for weight loss without medication. I know the standard answer to this proposal is nihilism: It just will not work. And I cannot deny that we have failed previously in our efforts to help patients lose weight. But perhaps now, with the vast amount of data, we can be more persuasive. Imagine a world where key opinion leaders made weight loss the message rather than prescription of a drug.

Finally, if you approach SUMMIT from the view of a regulator, with its small numbers of outcome events and bias-susceptible endpoints, you cannot allow a disease-modifying claim. For that we would need a properly powered trial that shows that the drug reduces both CV death and all-cause hospitalization.

In the end, SUMMIT is not close to changing treatment norms in patients with HFpEF. As evidence-based clinicians, we should demand more from our partners in industry and academia.

Dr. Mandrola practices cardiac electrophysiology in Baptist Medical Associates, Louisville, Kentucky, and is a writer and podcaster for Medscape. He espouses a conservative approach to medical practice. He participates in clinical research and writes often about the state of medical evidence. He has disclosed no relevant financial relationships.

 

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

The results of the SUMMIT trial of the long-acting agonist of glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors, tirzepatide, in patients with heart failure with preserved ejection fraction (HFpEF) and obesity are positive. But the trial design leaves clinicians and regulators with big doses of uncertainty.

Known Facts About HFpEF

HFpEF has exceeded heart failure with reduced ejection fraction (HFrEF) as the most common form of heart failure. HFpEF differs from HFrEF in that patients with preserved ejection fraction often present later in life with more comorbidities.

Some of these comorbidities are on the causal pathway of heart failure. Obesity, for instance, both associates with HFpEF and surely causes the diastolic dysfunction central to the condition. This may be a direct effect via high excess adipose tissue or an indirect effect via pro-inflammatory pathways.

GLP-1 agonists and the dual-acting GIP/GLP1 agonist tirzepatide have proven efficacy for weight loss. Semaglutide has previously been shown to improve quality of life and physical functioning in two small trials of patients with HFpEF and obesity. Semaglutide also reduced hard clinical outcomes in patients with obesity and these other conditions: chronic kidney disease, diabetes, and established atherosclerotic vascular disease.

This class of drugs is costly. The combination of both high drug costs and highly prevalent conditions such as obesity and HFpEF forces clinicians to make both value and clinical judgments when translating evidence.

 

The SUMMIT Trial

The SUMMIT trial aimed to evaluate tirzepatide’s effect on typical heart failure events, health status and functional capacity in patients with obesity and HFpEF. A total of 731 patients were randomly assigned to receive to tirzepatide or placebo.

Investigators chose two co-primary endpoints. The first was a composite of cardiovascular (CV) death and worsening heart failure events—the latter could be a hospitalization for heart failure, a visit for intravenous diuretics, or intensification of oral diuretics. The idea behind this rather unique composite was to capture all heart failure events. The second co-primary endpoint was a change in baseline Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) at 1 year.

Characteristics of the patients included an average age of 65 years, 55% were female, the average body mass index was 38, and the mean left ventricular ejection fraction was 61% (the minimum for trial entry was 50%). Just under half had been hospitalized for heart failure in the year before trial entry.

 

Tirzepatide Results

The primary outcome of CV death and first heart failure event occurred in 36 patients (9.9%) in the tirzepatide group and 56 patients (15.3%) in the placebo group, for a hazard ratio of 0.62 (95% CI, 0.41-0.95; P =.026).

The 5.4% absolute risk reduction in the primary endpoint was completely driven by lower rates of heart failure events (8% vs 14.2%). CV death was actually higher in the tirzepatide arm, but the number of deaths was low in both arms (8 vs 5).

The rate of hospitalizations due to heart failure was lower with tirzepatide (3.3% vs 7.1%), as was intensification of oral diuretics (4.7% vs 5.7%).

The second co-primary endpoint of change from baseline in KCCQ-CSS favored tirzepatide.

Other secondary endpoints also favored tirzepatide: longer 6-minute walk distance, greater change in body weight (-11.6%), and lower high-sensitivity C-reactive protein levels and systolic blood pressure (-4.7 mm Hg).

 

Authors’ Conclusions and Expert Comments

At the American Heart Association Scientific Sessions, the primary investigator Milton Packer, MD, said SUMMIT was the first trial of patients with obesity and HFpEF that had major heart failure outcomes as the primary endpoint. And that tirzepatide changed the clinical trajectory of the disease.

Jennifer Ho, MD, associate professor of medicine at Harvard Medical School, Boston, Massachusetts, said, “This really is a practice-changing trial and cements this type of therapy as one of the cornerstones of obesity and HFpEF treatment.”

Other experts cited a recently published pooled analysis of semaglutide trials looking specifically at patients with HFpEF and found lower rates of HF events with the GLP-1 agonist.

The SUMMIT trial results were covered in 53 news outlets— nearly all with glowing headlines.

 

My Six Concerns With SUMMIT

The trial delivered statistically positive findings. What’s more, patients lost weight, and a greater than 11% weight loss difference is meaningful. Patients with a baseline weight of more than 100 kg who lose this much weight are bound to feel and function better.

The first problem comes when we ask whether the results are disease-modifying. There was no difference in CV death. And the number of hospitalizations for heart failure — the more standard endpoint — was low, at only 12 and 26, respectively. Contrast this with the DELIVER trial of the sodium-glucose cotransporter 2 inhibitor dapagliflozin in HFpEF where there were nearly 750 hospitalizations for heart failure and PARAGON-HF of sacubitril-valsartan vs valsartan in HFpEF, where there were nearly 1500. SUMMIT simply had too few events to make conclusions — a point Packer has made regarding AF ablation trials in patients with heart failure.

I have previously called GLP-1 drugs disease-modifying in patients with obesity and atherosclerotic disease. This is because the SELECT trial of semaglutide randomized more than 17,000 patients and recorded a 20% reduction in hard outcomes. And there were more than 1200 primary outcome events. SUMMIT does not come close to this measure.

The second issue is short follow-up. These were 65-year-old patients and with only 2 years of follow-up, it is hard to make conclusions regarding whether or not these drugs can provide long-term benefit.

The third issue is that SUMMIT authors don’t tell us the number of all-cause hospitalizations. I was part of a recently published meta-analysis of more than 100 heart failure trials that raised questions regarding the value of hospitalizations for heart failure as a surrogate for heart failure outcomes.

For instance, we found that in large trials there was great variability in the ability of a reduction in HF hospitalizations to predict a reduction in all-cause hospitalization. In small trials, such as SUMMIT, it would likely be impossible to predict how the reduction in HF hospitalization would predict all-cause hospitalization. I believe all-cause hospitalization is a more inclusive endpoint because it is bias free; it captures benefits and potential harms of the therapy; and it is patient-centered, because patients probably do not care what type of hospitalization they avoid.

The fourth issue with SUMMIT is the difficulty in maintaining blinding, which reduces confidence in outcomes that require clinical decisions or patient judgments. Owing to gastrointestinal symptoms, decreased appetite, and weight loss, patients on this class of drugs are very likely to know their treatment assignment. This is a criticism of not only SUMMIT but all GLP-1 agonist trials. The fact that blinding is difficult to maintain argues for choosing endpoints less susceptible to bias, such as CV death or all-cause hospitalization.

Proponents of tirzepatide for this indication might argue that unblinding is less of an issue because of objective endpoints such as biomarkers. And they have a point, but nearly all other endpoints, especially the co-primary endpoint of KCCQ-CSS, are largely susceptible to bias.

The fifth and main problem comes in translating this evidence in the clinic. Should doctors give up on nondrug means of weight loss? All of the positive outcome trials in this class of drugs have also shown weight loss. I believe we should take these data and use them to re-invigorate our advocacy for weight loss without medication. I know the standard answer to this proposal is nihilism: It just will not work. And I cannot deny that we have failed previously in our efforts to help patients lose weight. But perhaps now, with the vast amount of data, we can be more persuasive. Imagine a world where key opinion leaders made weight loss the message rather than prescription of a drug.

Finally, if you approach SUMMIT from the view of a regulator, with its small numbers of outcome events and bias-susceptible endpoints, you cannot allow a disease-modifying claim. For that we would need a properly powered trial that shows that the drug reduces both CV death and all-cause hospitalization.

In the end, SUMMIT is not close to changing treatment norms in patients with HFpEF. As evidence-based clinicians, we should demand more from our partners in industry and academia.

Dr. Mandrola practices cardiac electrophysiology in Baptist Medical Associates, Louisville, Kentucky, and is a writer and podcaster for Medscape. He espouses a conservative approach to medical practice. He participates in clinical research and writes often about the state of medical evidence. He has disclosed no relevant financial relationships.

 

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

The results of the SUMMIT trial of the long-acting agonist of glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors, tirzepatide, in patients with heart failure with preserved ejection fraction (HFpEF) and obesity are positive. But the trial design leaves clinicians and regulators with big doses of uncertainty.

Known Facts About HFpEF

HFpEF has exceeded heart failure with reduced ejection fraction (HFrEF) as the most common form of heart failure. HFpEF differs from HFrEF in that patients with preserved ejection fraction often present later in life with more comorbidities.

Some of these comorbidities are on the causal pathway of heart failure. Obesity, for instance, both associates with HFpEF and surely causes the diastolic dysfunction central to the condition. This may be a direct effect via high excess adipose tissue or an indirect effect via pro-inflammatory pathways.

GLP-1 agonists and the dual-acting GIP/GLP1 agonist tirzepatide have proven efficacy for weight loss. Semaglutide has previously been shown to improve quality of life and physical functioning in two small trials of patients with HFpEF and obesity. Semaglutide also reduced hard clinical outcomes in patients with obesity and these other conditions: chronic kidney disease, diabetes, and established atherosclerotic vascular disease.

This class of drugs is costly. The combination of both high drug costs and highly prevalent conditions such as obesity and HFpEF forces clinicians to make both value and clinical judgments when translating evidence.

 

The SUMMIT Trial

The SUMMIT trial aimed to evaluate tirzepatide’s effect on typical heart failure events, health status and functional capacity in patients with obesity and HFpEF. A total of 731 patients were randomly assigned to receive to tirzepatide or placebo.

Investigators chose two co-primary endpoints. The first was a composite of cardiovascular (CV) death and worsening heart failure events—the latter could be a hospitalization for heart failure, a visit for intravenous diuretics, or intensification of oral diuretics. The idea behind this rather unique composite was to capture all heart failure events. The second co-primary endpoint was a change in baseline Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) at 1 year.

Characteristics of the patients included an average age of 65 years, 55% were female, the average body mass index was 38, and the mean left ventricular ejection fraction was 61% (the minimum for trial entry was 50%). Just under half had been hospitalized for heart failure in the year before trial entry.

 

Tirzepatide Results

The primary outcome of CV death and first heart failure event occurred in 36 patients (9.9%) in the tirzepatide group and 56 patients (15.3%) in the placebo group, for a hazard ratio of 0.62 (95% CI, 0.41-0.95; P =.026).

The 5.4% absolute risk reduction in the primary endpoint was completely driven by lower rates of heart failure events (8% vs 14.2%). CV death was actually higher in the tirzepatide arm, but the number of deaths was low in both arms (8 vs 5).

The rate of hospitalizations due to heart failure was lower with tirzepatide (3.3% vs 7.1%), as was intensification of oral diuretics (4.7% vs 5.7%).

The second co-primary endpoint of change from baseline in KCCQ-CSS favored tirzepatide.

Other secondary endpoints also favored tirzepatide: longer 6-minute walk distance, greater change in body weight (-11.6%), and lower high-sensitivity C-reactive protein levels and systolic blood pressure (-4.7 mm Hg).

 

Authors’ Conclusions and Expert Comments

At the American Heart Association Scientific Sessions, the primary investigator Milton Packer, MD, said SUMMIT was the first trial of patients with obesity and HFpEF that had major heart failure outcomes as the primary endpoint. And that tirzepatide changed the clinical trajectory of the disease.

Jennifer Ho, MD, associate professor of medicine at Harvard Medical School, Boston, Massachusetts, said, “This really is a practice-changing trial and cements this type of therapy as one of the cornerstones of obesity and HFpEF treatment.”

Other experts cited a recently published pooled analysis of semaglutide trials looking specifically at patients with HFpEF and found lower rates of HF events with the GLP-1 agonist.

The SUMMIT trial results were covered in 53 news outlets— nearly all with glowing headlines.

 

My Six Concerns With SUMMIT

The trial delivered statistically positive findings. What’s more, patients lost weight, and a greater than 11% weight loss difference is meaningful. Patients with a baseline weight of more than 100 kg who lose this much weight are bound to feel and function better.

The first problem comes when we ask whether the results are disease-modifying. There was no difference in CV death. And the number of hospitalizations for heart failure — the more standard endpoint — was low, at only 12 and 26, respectively. Contrast this with the DELIVER trial of the sodium-glucose cotransporter 2 inhibitor dapagliflozin in HFpEF where there were nearly 750 hospitalizations for heart failure and PARAGON-HF of sacubitril-valsartan vs valsartan in HFpEF, where there were nearly 1500. SUMMIT simply had too few events to make conclusions — a point Packer has made regarding AF ablation trials in patients with heart failure.

I have previously called GLP-1 drugs disease-modifying in patients with obesity and atherosclerotic disease. This is because the SELECT trial of semaglutide randomized more than 17,000 patients and recorded a 20% reduction in hard outcomes. And there were more than 1200 primary outcome events. SUMMIT does not come close to this measure.

The second issue is short follow-up. These were 65-year-old patients and with only 2 years of follow-up, it is hard to make conclusions regarding whether or not these drugs can provide long-term benefit.

The third issue is that SUMMIT authors don’t tell us the number of all-cause hospitalizations. I was part of a recently published meta-analysis of more than 100 heart failure trials that raised questions regarding the value of hospitalizations for heart failure as a surrogate for heart failure outcomes.

For instance, we found that in large trials there was great variability in the ability of a reduction in HF hospitalizations to predict a reduction in all-cause hospitalization. In small trials, such as SUMMIT, it would likely be impossible to predict how the reduction in HF hospitalization would predict all-cause hospitalization. I believe all-cause hospitalization is a more inclusive endpoint because it is bias free; it captures benefits and potential harms of the therapy; and it is patient-centered, because patients probably do not care what type of hospitalization they avoid.

The fourth issue with SUMMIT is the difficulty in maintaining blinding, which reduces confidence in outcomes that require clinical decisions or patient judgments. Owing to gastrointestinal symptoms, decreased appetite, and weight loss, patients on this class of drugs are very likely to know their treatment assignment. This is a criticism of not only SUMMIT but all GLP-1 agonist trials. The fact that blinding is difficult to maintain argues for choosing endpoints less susceptible to bias, such as CV death or all-cause hospitalization.

Proponents of tirzepatide for this indication might argue that unblinding is less of an issue because of objective endpoints such as biomarkers. And they have a point, but nearly all other endpoints, especially the co-primary endpoint of KCCQ-CSS, are largely susceptible to bias.

The fifth and main problem comes in translating this evidence in the clinic. Should doctors give up on nondrug means of weight loss? All of the positive outcome trials in this class of drugs have also shown weight loss. I believe we should take these data and use them to re-invigorate our advocacy for weight loss without medication. I know the standard answer to this proposal is nihilism: It just will not work. And I cannot deny that we have failed previously in our efforts to help patients lose weight. But perhaps now, with the vast amount of data, we can be more persuasive. Imagine a world where key opinion leaders made weight loss the message rather than prescription of a drug.

Finally, if you approach SUMMIT from the view of a regulator, with its small numbers of outcome events and bias-susceptible endpoints, you cannot allow a disease-modifying claim. For that we would need a properly powered trial that shows that the drug reduces both CV death and all-cause hospitalization.

In the end, SUMMIT is not close to changing treatment norms in patients with HFpEF. As evidence-based clinicians, we should demand more from our partners in industry and academia.

Dr. Mandrola practices cardiac electrophysiology in Baptist Medical Associates, Louisville, Kentucky, and is a writer and podcaster for Medscape. He espouses a conservative approach to medical practice. He participates in clinical research and writes often about the state of medical evidence. He has disclosed no relevant financial relationships.

 

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

Endocrine disruptors (EDs) — chemicals in the environment that could affect human endocrine function — are increasingly becoming a prominent concern for the public as well as professionals. At its 40th congress, the French Society of Endocrinology hosted a public lecture on the subject, given by Nicolas Chevalier, MD, PhD, professor of endocrinology at the University Hospital of Nice in France.

Environmental EDs

Chevalier began by asking the audience to remember one number: 906. This is the number of substances identified by the French Agency for Food, Environmental and Occupational Health & Safety for which there are sufficient scientific data to confirm or at least suspect endocrine-disrupting activity. In reality, the number is likely closer to 10,000, he said.

These chemicals include bisphenol A and its substitutes, parabens, phthalates, and pesticides. Additionally, lithium (mainly found in batteries), polychlorinated biphenyls, per- and polyfluoroalkyl substances, and polybromodiphenyl ethers, or brominated flame retardants, are included. These products are found throughout our environment, so much so that Chevalier said: “We are swimming in a soup of endocrine disruptors.”

The main source of human contamination is food, responsible for an estimated 80%-90% of those encountered. They may enter the food supply during production or preservation, and pesticides are not the only culprits. For example, fatty fish contain heavy metals. Water is also a significant source of contamination. It is worth noting that tap water is the cleanest and most monitored type when it comes to EDs. However, plastic bottles leach not only EDs but also microplastics, which are a major environmental pollution source.

Many other features in our daily environment contain EDs: Clothing (especially shoes), nonstick cookware, plastic containers (especially those heated in the microwave), plastic toys (which young children often put in their mouths), and cosmetic products (makeup, which is increasingly used by young girls). The placenta is not the barrier it was once thought to be: Amniotic fluid has been found to contain about 35 molecules that are toxic for the fetus, with at least 11 or 12 exceeding safety thresholds.

 

Multiple Linked Diseases

An incomplete list of ED-related diseases would include cancer, infertility, obesity, and diabetes, Chevalier said. Are these data alarmist? he asked. After all, life expectancy has increased globally by more than 10 years since the 1970s, and this has occurred alongside the increased use of EDs. However, he suggested remembering a second number: 157. This represents the billions of euros in European healthcare costs primarily caused by neurologic disorders linked to pesticides. They have a half-life estimated at least 10 years, and banning them will not stop them from persisting in the environment for up to 40 years. US studies have shown that their presence in the environment contributes to cognitive delays in young children.

Another area of concern is the rising infertility rates among couples, now affecting around one in five in France. This trend has been linked to the toxicity of EDs on the genital tract, especially in men, and is not only related to increased use of birth control. For example, in sub-Saharan Africa, rates of contraceptive use have increased only marginally, but birth rates have significantly decreased in areas contaminated by waste that is inadequately managed by Western standards.

EDs have also been implicated in the rising incidence of several cancers, including breast cancer in women and prostate cancer in men, and may have contributed to increases in both childhood obesity and adult diabetes.

 

A Difficult Battle

Chevalier asked: Is the increase in ED contamination inevitable? No, he said, but it is extremely difficult to counter. Governments are reluctant to legislate, particularly when jobs are at stake, even though certain workers are particularly exposed. The ideal situation would be for the public to take matters into their own hands by eliminating EDs from their environment through daily actions that pressure policymakers to act. For example:

• Eliminate plastics (especially for food products) and nonstick coatings
• Reject most cleaning products in favor of traditional solutions (eg, white vinegar and baking soda)
• Avoid imported toys (as producer countries often fail to comply with European health standards)

Environmental charters have been created by several local authorities and regional health agencies. Chevalier urged the public to rely on their recommendations and resources to help drive change.

 

This story was translated from Univadis France 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.

Endocrine disruptors (EDs) — chemicals in the environment that could affect human endocrine function — are increasingly becoming a prominent concern for the public as well as professionals. At its 40th congress, the French Society of Endocrinology hosted a public lecture on the subject, given by Nicolas Chevalier, MD, PhD, professor of endocrinology at the University Hospital of Nice in France.

Environmental EDs

Chevalier began by asking the audience to remember one number: 906. This is the number of substances identified by the French Agency for Food, Environmental and Occupational Health & Safety for which there are sufficient scientific data to confirm or at least suspect endocrine-disrupting activity. In reality, the number is likely closer to 10,000, he said.

These chemicals include bisphenol A and its substitutes, parabens, phthalates, and pesticides. Additionally, lithium (mainly found in batteries), polychlorinated biphenyls, per- and polyfluoroalkyl substances, and polybromodiphenyl ethers, or brominated flame retardants, are included. These products are found throughout our environment, so much so that Chevalier said: “We are swimming in a soup of endocrine disruptors.”

The main source of human contamination is food, responsible for an estimated 80%-90% of those encountered. They may enter the food supply during production or preservation, and pesticides are not the only culprits. For example, fatty fish contain heavy metals. Water is also a significant source of contamination. It is worth noting that tap water is the cleanest and most monitored type when it comes to EDs. However, plastic bottles leach not only EDs but also microplastics, which are a major environmental pollution source.

Many other features in our daily environment contain EDs: Clothing (especially shoes), nonstick cookware, plastic containers (especially those heated in the microwave), plastic toys (which young children often put in their mouths), and cosmetic products (makeup, which is increasingly used by young girls). The placenta is not the barrier it was once thought to be: Amniotic fluid has been found to contain about 35 molecules that are toxic for the fetus, with at least 11 or 12 exceeding safety thresholds.

 

Multiple Linked Diseases

An incomplete list of ED-related diseases would include cancer, infertility, obesity, and diabetes, Chevalier said. Are these data alarmist? he asked. After all, life expectancy has increased globally by more than 10 years since the 1970s, and this has occurred alongside the increased use of EDs. However, he suggested remembering a second number: 157. This represents the billions of euros in European healthcare costs primarily caused by neurologic disorders linked to pesticides. They have a half-life estimated at least 10 years, and banning them will not stop them from persisting in the environment for up to 40 years. US studies have shown that their presence in the environment contributes to cognitive delays in young children.

Another area of concern is the rising infertility rates among couples, now affecting around one in five in France. This trend has been linked to the toxicity of EDs on the genital tract, especially in men, and is not only related to increased use of birth control. For example, in sub-Saharan Africa, rates of contraceptive use have increased only marginally, but birth rates have significantly decreased in areas contaminated by waste that is inadequately managed by Western standards.

EDs have also been implicated in the rising incidence of several cancers, including breast cancer in women and prostate cancer in men, and may have contributed to increases in both childhood obesity and adult diabetes.

 

A Difficult Battle

Chevalier asked: Is the increase in ED contamination inevitable? No, he said, but it is extremely difficult to counter. Governments are reluctant to legislate, particularly when jobs are at stake, even though certain workers are particularly exposed. The ideal situation would be for the public to take matters into their own hands by eliminating EDs from their environment through daily actions that pressure policymakers to act. For example:

• Eliminate plastics (especially for food products) and nonstick coatings
• Reject most cleaning products in favor of traditional solutions (eg, white vinegar and baking soda)
• Avoid imported toys (as producer countries often fail to comply with European health standards)

Environmental charters have been created by several local authorities and regional health agencies. Chevalier urged the public to rely on their recommendations and resources to help drive change.

 

This story was translated from Univadis France 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.

Endocrine disruptors (EDs) — chemicals in the environment that could affect human endocrine function — are increasingly becoming a prominent concern for the public as well as professionals. At its 40th congress, the French Society of Endocrinology hosted a public lecture on the subject, given by Nicolas Chevalier, MD, PhD, professor of endocrinology at the University Hospital of Nice in France.

Environmental EDs

Chevalier began by asking the audience to remember one number: 906. This is the number of substances identified by the French Agency for Food, Environmental and Occupational Health & Safety for which there are sufficient scientific data to confirm or at least suspect endocrine-disrupting activity. In reality, the number is likely closer to 10,000, he said.

These chemicals include bisphenol A and its substitutes, parabens, phthalates, and pesticides. Additionally, lithium (mainly found in batteries), polychlorinated biphenyls, per- and polyfluoroalkyl substances, and polybromodiphenyl ethers, or brominated flame retardants, are included. These products are found throughout our environment, so much so that Chevalier said: “We are swimming in a soup of endocrine disruptors.”

The main source of human contamination is food, responsible for an estimated 80%-90% of those encountered. They may enter the food supply during production or preservation, and pesticides are not the only culprits. For example, fatty fish contain heavy metals. Water is also a significant source of contamination. It is worth noting that tap water is the cleanest and most monitored type when it comes to EDs. However, plastic bottles leach not only EDs but also microplastics, which are a major environmental pollution source.

Many other features in our daily environment contain EDs: Clothing (especially shoes), nonstick cookware, plastic containers (especially those heated in the microwave), plastic toys (which young children often put in their mouths), and cosmetic products (makeup, which is increasingly used by young girls). The placenta is not the barrier it was once thought to be: Amniotic fluid has been found to contain about 35 molecules that are toxic for the fetus, with at least 11 or 12 exceeding safety thresholds.

 

Multiple Linked Diseases

An incomplete list of ED-related diseases would include cancer, infertility, obesity, and diabetes, Chevalier said. Are these data alarmist? he asked. After all, life expectancy has increased globally by more than 10 years since the 1970s, and this has occurred alongside the increased use of EDs. However, he suggested remembering a second number: 157. This represents the billions of euros in European healthcare costs primarily caused by neurologic disorders linked to pesticides. They have a half-life estimated at least 10 years, and banning them will not stop them from persisting in the environment for up to 40 years. US studies have shown that their presence in the environment contributes to cognitive delays in young children.

Another area of concern is the rising infertility rates among couples, now affecting around one in five in France. This trend has been linked to the toxicity of EDs on the genital tract, especially in men, and is not only related to increased use of birth control. For example, in sub-Saharan Africa, rates of contraceptive use have increased only marginally, but birth rates have significantly decreased in areas contaminated by waste that is inadequately managed by Western standards.

EDs have also been implicated in the rising incidence of several cancers, including breast cancer in women and prostate cancer in men, and may have contributed to increases in both childhood obesity and adult diabetes.

 

A Difficult Battle

Chevalier asked: Is the increase in ED contamination inevitable? No, he said, but it is extremely difficult to counter. Governments are reluctant to legislate, particularly when jobs are at stake, even though certain workers are particularly exposed. The ideal situation would be for the public to take matters into their own hands by eliminating EDs from their environment through daily actions that pressure policymakers to act. For example:

• Eliminate plastics (especially for food products) and nonstick coatings
• Reject most cleaning products in favor of traditional solutions (eg, white vinegar and baking soda)
• Avoid imported toys (as producer countries often fail to comply with European health standards)

Environmental charters have been created by several local authorities and regional health agencies. Chevalier urged the public to rely on their recommendations and resources to help drive change.

 

This story was translated from Univadis France 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.

Three basic truths about ultraprocessed foods: Junk food, available pretty much everywhere, tastes great. Advertising works. And most of us don’t crave green leafy salads when we’re hungry.

Of those three truths, the one that tends to get more public health attention is advertising. More specifically, advertising junk food to kids. 

Back in the days when cable television was king of all free time, study after study tried to quantify junk- and fast-food advertising to kids and speculated about its impact on childhood obesity rates. But as broadcast television use began fading, advertisers — and, of course, studies about advertising — turned their attention first to gaming and now to social media.

The social media numbers are quite staggering. According to a study published — probably not coincidentally — on Halloween, looking at the 40 top brands of junk- and fast food sold in Canada, those 40 brands alone were mentioned over 16 million times by social media users, reaching an estimated 42 billion total users within a 1-year period. 

And unique to the challenge of junk- and fast-food advertising on social media is that it also includes “earned” advertising, the kind not paid for by manufacturers but rather the kind where friends, family, and influencers post about junk food. Occasionally, though, these lines are blurred by initiatives from fast-food manufacturers explicitly encouraging social sharing. Consequently, even were there a desire, there isn’t likely to be a regulatory mechanism to markedly reduce it. 

For years, here in North America, excepting Quebec, the desire has been mainly to just talk about how concerned we are about junk-food advertising to kids. Elsewhere, however, some countries tried to do more, including both Mexico and Chile, which put kid-targeted TV food advertising bans in place in 2014 and 2016, respectively. 

Did they work? It depends on what outcome you’re considering. If the question is, did they work in regard to obesity? — which is how everyone tends to frame the question — by themselves, probably not. No one sandbag stops a flood, and though junk-food advertising is certainly a sandbag, we’re still facing a torrential downpour of obesity contributors. No doubt they did work to reduce kids’ exposure to junk-food advertising on television, but what remains to be seen is whether there is a means to now tackle social media’s generous servings of the same. Moreover, the obesity lens is the wrong one. Ultraprocessed food consumption isn’t good for anyone, regardless of weight, and its reduced marketing and consumption is a worthy goal of its own.

But Chile and Mexico are filling more than single sandbags, as both countries have rolled out a suite of interventions they are hoping will help improve nutrition: from front-of–package labeling reforms and warnings, to the banning of advertising geared specifically to appeal to children (like sugary cereal cartoon mascots), to implementing sugar-sweetened-beverage taxes, to having blanket overall bans on food advertising during the daytime.

Mexico is even taking first steps to start addressing junk food’s ubiquity by banning its sale in schools altogether. Schools found to be selling common Mexican junk food fare, such as sugary fruit drinks; chips; artificial pork rinds; and soy-encased, salty peanuts with chili, will see their administrators facing heavy fines. 

Because therein lies the biggest rub. Going back to those three simple truths, junk food is hyperpalatable and consequently tends to be what we crave when we’re hungry. So even if we miraculously one day do more than just talk about advertising reforms, and especially given that we won’t be able to do anything about social media’s earned product placements, junk food’s ubiquitous availability within arms’ reach or on our Uber Eats apps will see us be likely to continue its excessive consumption. 

That’s not to say we shouldn’t emulate Mexico and Chile’s initiatives, nor that they shouldn’t continue to build upon them, but one thing is certain: Human nature and inconvenient truths around food are incredibly powerful forces that we haven’t yet figured out how to tame.

Dr. Freedhoff, Associate Professor, Department of Family Medicine, University of Ottawa; Medical Director, Bariatric Medical Institute, Ottawa, Ontario, Canada, has disclosed relevant financial relationships with Bariatric Medical Institute, Constant Health, Novo Nordisk, and Weighty Matters.

A version of this article appeared on Medscape.com.

Three basic truths about ultraprocessed foods: Junk food, available pretty much everywhere, tastes great. Advertising works. And most of us don’t crave green leafy salads when we’re hungry.

Of those three truths, the one that tends to get more public health attention is advertising. More specifically, advertising junk food to kids. 

Back in the days when cable television was king of all free time, study after study tried to quantify junk- and fast-food advertising to kids and speculated about its impact on childhood obesity rates. But as broadcast television use began fading, advertisers — and, of course, studies about advertising — turned their attention first to gaming and now to social media.

The social media numbers are quite staggering. According to a study published — probably not coincidentally — on Halloween, looking at the 40 top brands of junk- and fast food sold in Canada, those 40 brands alone were mentioned over 16 million times by social media users, reaching an estimated 42 billion total users within a 1-year period. 

And unique to the challenge of junk- and fast-food advertising on social media is that it also includes “earned” advertising, the kind not paid for by manufacturers but rather the kind where friends, family, and influencers post about junk food. Occasionally, though, these lines are blurred by initiatives from fast-food manufacturers explicitly encouraging social sharing. Consequently, even were there a desire, there isn’t likely to be a regulatory mechanism to markedly reduce it. 

For years, here in North America, excepting Quebec, the desire has been mainly to just talk about how concerned we are about junk-food advertising to kids. Elsewhere, however, some countries tried to do more, including both Mexico and Chile, which put kid-targeted TV food advertising bans in place in 2014 and 2016, respectively. 

Did they work? It depends on what outcome you’re considering. If the question is, did they work in regard to obesity? — which is how everyone tends to frame the question — by themselves, probably not. No one sandbag stops a flood, and though junk-food advertising is certainly a sandbag, we’re still facing a torrential downpour of obesity contributors. No doubt they did work to reduce kids’ exposure to junk-food advertising on television, but what remains to be seen is whether there is a means to now tackle social media’s generous servings of the same. Moreover, the obesity lens is the wrong one. Ultraprocessed food consumption isn’t good for anyone, regardless of weight, and its reduced marketing and consumption is a worthy goal of its own.

But Chile and Mexico are filling more than single sandbags, as both countries have rolled out a suite of interventions they are hoping will help improve nutrition: from front-of–package labeling reforms and warnings, to the banning of advertising geared specifically to appeal to children (like sugary cereal cartoon mascots), to implementing sugar-sweetened-beverage taxes, to having blanket overall bans on food advertising during the daytime.

Mexico is even taking first steps to start addressing junk food’s ubiquity by banning its sale in schools altogether. Schools found to be selling common Mexican junk food fare, such as sugary fruit drinks; chips; artificial pork rinds; and soy-encased, salty peanuts with chili, will see their administrators facing heavy fines. 

Because therein lies the biggest rub. Going back to those three simple truths, junk food is hyperpalatable and consequently tends to be what we crave when we’re hungry. So even if we miraculously one day do more than just talk about advertising reforms, and especially given that we won’t be able to do anything about social media’s earned product placements, junk food’s ubiquitous availability within arms’ reach or on our Uber Eats apps will see us be likely to continue its excessive consumption. 

That’s not to say we shouldn’t emulate Mexico and Chile’s initiatives, nor that they shouldn’t continue to build upon them, but one thing is certain: Human nature and inconvenient truths around food are incredibly powerful forces that we haven’t yet figured out how to tame.

Dr. Freedhoff, Associate Professor, Department of Family Medicine, University of Ottawa; Medical Director, Bariatric Medical Institute, Ottawa, Ontario, Canada, has disclosed relevant financial relationships with Bariatric Medical Institute, Constant Health, Novo Nordisk, and Weighty Matters.

A version of this article appeared on Medscape.com.

Three basic truths about ultraprocessed foods: Junk food, available pretty much everywhere, tastes great. Advertising works. And most of us don’t crave green leafy salads when we’re hungry.

Of those three truths, the one that tends to get more public health attention is advertising. More specifically, advertising junk food to kids. 

Back in the days when cable television was king of all free time, study after study tried to quantify junk- and fast-food advertising to kids and speculated about its impact on childhood obesity rates. But as broadcast television use began fading, advertisers — and, of course, studies about advertising — turned their attention first to gaming and now to social media.

The social media numbers are quite staggering. According to a study published — probably not coincidentally — on Halloween, looking at the 40 top brands of junk- and fast food sold in Canada, those 40 brands alone were mentioned over 16 million times by social media users, reaching an estimated 42 billion total users within a 1-year period. 

And unique to the challenge of junk- and fast-food advertising on social media is that it also includes “earned” advertising, the kind not paid for by manufacturers but rather the kind where friends, family, and influencers post about junk food. Occasionally, though, these lines are blurred by initiatives from fast-food manufacturers explicitly encouraging social sharing. Consequently, even were there a desire, there isn’t likely to be a regulatory mechanism to markedly reduce it. 

For years, here in North America, excepting Quebec, the desire has been mainly to just talk about how concerned we are about junk-food advertising to kids. Elsewhere, however, some countries tried to do more, including both Mexico and Chile, which put kid-targeted TV food advertising bans in place in 2014 and 2016, respectively. 

Did they work? It depends on what outcome you’re considering. If the question is, did they work in regard to obesity? — which is how everyone tends to frame the question — by themselves, probably not. No one sandbag stops a flood, and though junk-food advertising is certainly a sandbag, we’re still facing a torrential downpour of obesity contributors. No doubt they did work to reduce kids’ exposure to junk-food advertising on television, but what remains to be seen is whether there is a means to now tackle social media’s generous servings of the same. Moreover, the obesity lens is the wrong one. Ultraprocessed food consumption isn’t good for anyone, regardless of weight, and its reduced marketing and consumption is a worthy goal of its own.

But Chile and Mexico are filling more than single sandbags, as both countries have rolled out a suite of interventions they are hoping will help improve nutrition: from front-of–package labeling reforms and warnings, to the banning of advertising geared specifically to appeal to children (like sugary cereal cartoon mascots), to implementing sugar-sweetened-beverage taxes, to having blanket overall bans on food advertising during the daytime.

Mexico is even taking first steps to start addressing junk food’s ubiquity by banning its sale in schools altogether. Schools found to be selling common Mexican junk food fare, such as sugary fruit drinks; chips; artificial pork rinds; and soy-encased, salty peanuts with chili, will see their administrators facing heavy fines. 

Because therein lies the biggest rub. Going back to those three simple truths, junk food is hyperpalatable and consequently tends to be what we crave when we’re hungry. So even if we miraculously one day do more than just talk about advertising reforms, and especially given that we won’t be able to do anything about social media’s earned product placements, junk food’s ubiquitous availability within arms’ reach or on our Uber Eats apps will see us be likely to continue its excessive consumption. 

That’s not to say we shouldn’t emulate Mexico and Chile’s initiatives, nor that they shouldn’t continue to build upon them, but one thing is certain: Human nature and inconvenient truths around food are incredibly powerful forces that we haven’t yet figured out how to tame.

Dr. Freedhoff, Associate Professor, Department of Family Medicine, University of Ottawa; Medical Director, Bariatric Medical Institute, Ottawa, Ontario, Canada, has disclosed relevant financial relationships with Bariatric Medical Institute, Constant Health, Novo Nordisk, and Weighty Matters.

A version of this article appeared on Medscape.com.

In a new statement, the American Diabetes Association (ADA) has advised against the use of compounded glucagon-like peptide 1 receptor agonist (GLP-1 RA) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA medication classes.

The ADA recommends GLP-1 RA and GIP/GLP-1 RA medications approved by the Food and Drug Administration (FDA) for the treatment of type 2 diabetes, cardiovascular and kidney disease risk reduction, and weight management. The new ADA statement pertains to the unapproved, unregulated versions that have emerged as the demand for these medications for weight loss increases. These are often marketed directly to consumers.

“Compounded GLP-1 RA and dual GIP/GLP-1 RA products have been associated with clinically important dosing errors and adverse events. More concerning to individuals’ safety are counterfeit products that have made their way into the US drug supply chain and those advertised online and by unregulated sources,” the ADA said in the statement, published online on December 2, 2024, in Diabetes Care.

The statement, authored by Joshua J. Neumiller, PharmD, CDCES, of the Department of Pharmacotherapy, Washington State University, Spokane, and colleagues, states the following:

• Non–FDA-approved compounded incretin products are not recommended for use due to uncertainty about their content and resulting concerns about safety, quality, and effectiveness.
• If an incretin medication is unavailable (eg, in shortage), switching to a different FDA-approved medication is recommended as clinically appropriate to achieve and maintain individualized glucose-lowering, weight management, and/or cardiovascular and kidney risk reduction goals.
• Upon resolution of incretin product unavailability, reassess the appropriateness of resuming the original FDA-approved incretin medication.

The document points out that compounded products are not identical to the FDA-approved versions, may be distributed in nonstandard dosing devices, and may not provide sufficient user instructions.

However, “the ADA also recognizes that individuals and clinicians may still elect to use or recommend compounded products for financial or other reasons,” and therefore offers additional advice for the public, including the following:

• Discuss product use with their usual healthcare providers.
• Only use products that include dosing guidance.
• Verify that the compounding pharmacy is registered with FDA.

In addition, report any adverse events or medication errors to the FDA’s Medwatch.

A version of this article appeared on Medscape.com.

In a new statement, the American Diabetes Association (ADA) has advised against the use of compounded glucagon-like peptide 1 receptor agonist (GLP-1 RA) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA medication classes.

The ADA recommends GLP-1 RA and GIP/GLP-1 RA medications approved by the Food and Drug Administration (FDA) for the treatment of type 2 diabetes, cardiovascular and kidney disease risk reduction, and weight management. The new ADA statement pertains to the unapproved, unregulated versions that have emerged as the demand for these medications for weight loss increases. These are often marketed directly to consumers.

“Compounded GLP-1 RA and dual GIP/GLP-1 RA products have been associated with clinically important dosing errors and adverse events. More concerning to individuals’ safety are counterfeit products that have made their way into the US drug supply chain and those advertised online and by unregulated sources,” the ADA said in the statement, published online on December 2, 2024, in Diabetes Care.

The statement, authored by Joshua J. Neumiller, PharmD, CDCES, of the Department of Pharmacotherapy, Washington State University, Spokane, and colleagues, states the following:

• Non–FDA-approved compounded incretin products are not recommended for use due to uncertainty about their content and resulting concerns about safety, quality, and effectiveness.
• If an incretin medication is unavailable (eg, in shortage), switching to a different FDA-approved medication is recommended as clinically appropriate to achieve and maintain individualized glucose-lowering, weight management, and/or cardiovascular and kidney risk reduction goals.
• Upon resolution of incretin product unavailability, reassess the appropriateness of resuming the original FDA-approved incretin medication.

The document points out that compounded products are not identical to the FDA-approved versions, may be distributed in nonstandard dosing devices, and may not provide sufficient user instructions.

However, “the ADA also recognizes that individuals and clinicians may still elect to use or recommend compounded products for financial or other reasons,” and therefore offers additional advice for the public, including the following:

• Discuss product use with their usual healthcare providers.
• Only use products that include dosing guidance.
• Verify that the compounding pharmacy is registered with FDA.

In addition, report any adverse events or medication errors to the FDA’s Medwatch.

A version of this article appeared on Medscape.com.

In a new statement, the American Diabetes Association (ADA) has advised against the use of compounded glucagon-like peptide 1 receptor agonist (GLP-1 RA) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA medication classes.

The ADA recommends GLP-1 RA and GIP/GLP-1 RA medications approved by the Food and Drug Administration (FDA) for the treatment of type 2 diabetes, cardiovascular and kidney disease risk reduction, and weight management. The new ADA statement pertains to the unapproved, unregulated versions that have emerged as the demand for these medications for weight loss increases. These are often marketed directly to consumers.

“Compounded GLP-1 RA and dual GIP/GLP-1 RA products have been associated with clinically important dosing errors and adverse events. More concerning to individuals’ safety are counterfeit products that have made their way into the US drug supply chain and those advertised online and by unregulated sources,” the ADA said in the statement, published online on December 2, 2024, in Diabetes Care.

The statement, authored by Joshua J. Neumiller, PharmD, CDCES, of the Department of Pharmacotherapy, Washington State University, Spokane, and colleagues, states the following:

• Non–FDA-approved compounded incretin products are not recommended for use due to uncertainty about their content and resulting concerns about safety, quality, and effectiveness.
• If an incretin medication is unavailable (eg, in shortage), switching to a different FDA-approved medication is recommended as clinically appropriate to achieve and maintain individualized glucose-lowering, weight management, and/or cardiovascular and kidney risk reduction goals.
• Upon resolution of incretin product unavailability, reassess the appropriateness of resuming the original FDA-approved incretin medication.

The document points out that compounded products are not identical to the FDA-approved versions, may be distributed in nonstandard dosing devices, and may not provide sufficient user instructions.

However, “the ADA also recognizes that individuals and clinicians may still elect to use or recommend compounded products for financial or other reasons,” and therefore offers additional advice for the public, including the following:

• Discuss product use with their usual healthcare providers.
• Only use products that include dosing guidance.
• Verify that the compounding pharmacy is registered with FDA.

In addition, report any adverse events or medication errors to the FDA’s Medwatch.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with serum ferritin levels higher than 1000 μg/L show a 91% increased risk for any fracture, with a doubled risk for vertebral and humerus fractures compared with those without iron overload.

 

METHODOLOGY:

• Iron overload’s association with decreased bone mineral density is established, but its relationship to osteoporotic fracture risk has remained understudied and inconsistent across fracture sites.
• Researchers conducted a population-based cohort study using a UK general practice database to evaluate the fracture risk in 20,264 patients with iron overload and 192,956 matched controls without elevated ferritin (mean age, 57 years; about 40% women).
• Patients with iron overload were identified as those with laboratory-confirmed iron overload (serum ferritin levels > 1000 μg/L; n = 13,510) or a diagnosis of an iron overloading disorder, such as thalassemia major, sickle cell disease, or hemochromatosis (n = 6754).
• The primary outcome of interest was the first occurrence of an osteoporotic fracture after the diagnosis of iron overload or first record of high ferritin.
• A sensitivity analysis was conducted to check the impact of laboratory-confirmed iron overload on the risk for osteoporotic fracture compared with a diagnosis code without elevated ferritin.

TAKEAWAY:

• In the overall cohort, patients with iron overload had a 55% higher risk for any osteoporotic fracture than control individuals (adjusted hazard ratio [aHR], 1.55; 95% CI, 1.42-1.68), with the highest risk observed for vertebral fractures (aHR, 1.97; 95% CI, 1.63-2.37) and humerus fractures (aHR, 1.91; 95% CI, 1.61-2.26).
• Patients with laboratory-confirmed iron overload showed a 91% increased risk for any fracture (aHR, 1.91; 95% CI, 1.73-2.10), with a 2.5-fold higher risk observed for vertebral fractures (aHR, 2.51; 95% CI, 2.01-3.12), followed by humerus fractures (aHR, 2.41; 95% CI, 1.96-2.95).
• There was no increased risk for fracture at any site in patients with a diagnosis of an iron overloading disorder but no laboratory-confirmed iron overload.
• No sex-specific differences were identified in the association between iron overload and fracture risk.

IN PRACTICE:

“The main clinical message from our findings is that clinicians should consider iron overloading as a risk factor for fracture. Importantly, among high-risk patients presenting with serum ferritin values exceeding 1000 μg/L, osteoporosis screening and treatment strategies should be initiated in accordance with the guidelines for patients with hepatic disease,” the authors wrote.

 

SOURCE:

The study was led by Andrea Michelle Burden, PhD, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich in Switzerland, and was published online in The Journal of Clinical Endocrinology & Metabolism.

 

LIMITATIONS:

The study could not assess the duration of iron overload on fracture risk, and thus, patients could enter the cohort with a single elevated serum ferritin value that may not have reflected systemic iron overload. The authors also acknowledged potential exposure misclassification among matched control individuals because only 2.9% had a serum ferritin value available at baseline. Also, researchers were unable to adjust for inflammation status due to the limited availability of C-reactive protein measurements and the lack of leukocyte count data in primary care settings.

 

DISCLOSURES:

This study received support through grants from the German Research Foundation. The authors declared 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:

Patients with serum ferritin levels higher than 1000 μg/L show a 91% increased risk for any fracture, with a doubled risk for vertebral and humerus fractures compared with those without iron overload.

 

METHODOLOGY:

• Iron overload’s association with decreased bone mineral density is established, but its relationship to osteoporotic fracture risk has remained understudied and inconsistent across fracture sites.
• Researchers conducted a population-based cohort study using a UK general practice database to evaluate the fracture risk in 20,264 patients with iron overload and 192,956 matched controls without elevated ferritin (mean age, 57 years; about 40% women).
• Patients with iron overload were identified as those with laboratory-confirmed iron overload (serum ferritin levels > 1000 μg/L; n = 13,510) or a diagnosis of an iron overloading disorder, such as thalassemia major, sickle cell disease, or hemochromatosis (n = 6754).
• The primary outcome of interest was the first occurrence of an osteoporotic fracture after the diagnosis of iron overload or first record of high ferritin.
• A sensitivity analysis was conducted to check the impact of laboratory-confirmed iron overload on the risk for osteoporotic fracture compared with a diagnosis code without elevated ferritin.

TAKEAWAY:

• In the overall cohort, patients with iron overload had a 55% higher risk for any osteoporotic fracture than control individuals (adjusted hazard ratio [aHR], 1.55; 95% CI, 1.42-1.68), with the highest risk observed for vertebral fractures (aHR, 1.97; 95% CI, 1.63-2.37) and humerus fractures (aHR, 1.91; 95% CI, 1.61-2.26).
• Patients with laboratory-confirmed iron overload showed a 91% increased risk for any fracture (aHR, 1.91; 95% CI, 1.73-2.10), with a 2.5-fold higher risk observed for vertebral fractures (aHR, 2.51; 95% CI, 2.01-3.12), followed by humerus fractures (aHR, 2.41; 95% CI, 1.96-2.95).
• There was no increased risk for fracture at any site in patients with a diagnosis of an iron overloading disorder but no laboratory-confirmed iron overload.
• No sex-specific differences were identified in the association between iron overload and fracture risk.

IN PRACTICE:

“The main clinical message from our findings is that clinicians should consider iron overloading as a risk factor for fracture. Importantly, among high-risk patients presenting with serum ferritin values exceeding 1000 μg/L, osteoporosis screening and treatment strategies should be initiated in accordance with the guidelines for patients with hepatic disease,” the authors wrote.

 

SOURCE:

The study was led by Andrea Michelle Burden, PhD, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich in Switzerland, and was published online in The Journal of Clinical Endocrinology & Metabolism.

 

LIMITATIONS:

The study could not assess the duration of iron overload on fracture risk, and thus, patients could enter the cohort with a single elevated serum ferritin value that may not have reflected systemic iron overload. The authors also acknowledged potential exposure misclassification among matched control individuals because only 2.9% had a serum ferritin value available at baseline. Also, researchers were unable to adjust for inflammation status due to the limited availability of C-reactive protein measurements and the lack of leukocyte count data in primary care settings.

 

DISCLOSURES:

This study received support through grants from the German Research Foundation. The authors declared 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:

Patients with serum ferritin levels higher than 1000 μg/L show a 91% increased risk for any fracture, with a doubled risk for vertebral and humerus fractures compared with those without iron overload.

 

METHODOLOGY:

• Iron overload’s association with decreased bone mineral density is established, but its relationship to osteoporotic fracture risk has remained understudied and inconsistent across fracture sites.
• Researchers conducted a population-based cohort study using a UK general practice database to evaluate the fracture risk in 20,264 patients with iron overload and 192,956 matched controls without elevated ferritin (mean age, 57 years; about 40% women).
• Patients with iron overload were identified as those with laboratory-confirmed iron overload (serum ferritin levels > 1000 μg/L; n = 13,510) or a diagnosis of an iron overloading disorder, such as thalassemia major, sickle cell disease, or hemochromatosis (n = 6754).
• The primary outcome of interest was the first occurrence of an osteoporotic fracture after the diagnosis of iron overload or first record of high ferritin.
• A sensitivity analysis was conducted to check the impact of laboratory-confirmed iron overload on the risk for osteoporotic fracture compared with a diagnosis code without elevated ferritin.

TAKEAWAY:

• In the overall cohort, patients with iron overload had a 55% higher risk for any osteoporotic fracture than control individuals (adjusted hazard ratio [aHR], 1.55; 95% CI, 1.42-1.68), with the highest risk observed for vertebral fractures (aHR, 1.97; 95% CI, 1.63-2.37) and humerus fractures (aHR, 1.91; 95% CI, 1.61-2.26).
• Patients with laboratory-confirmed iron overload showed a 91% increased risk for any fracture (aHR, 1.91; 95% CI, 1.73-2.10), with a 2.5-fold higher risk observed for vertebral fractures (aHR, 2.51; 95% CI, 2.01-3.12), followed by humerus fractures (aHR, 2.41; 95% CI, 1.96-2.95).
• There was no increased risk for fracture at any site in patients with a diagnosis of an iron overloading disorder but no laboratory-confirmed iron overload.
• No sex-specific differences were identified in the association between iron overload and fracture risk.

IN PRACTICE:

“The main clinical message from our findings is that clinicians should consider iron overloading as a risk factor for fracture. Importantly, among high-risk patients presenting with serum ferritin values exceeding 1000 μg/L, osteoporosis screening and treatment strategies should be initiated in accordance with the guidelines for patients with hepatic disease,” the authors wrote.

 

SOURCE:

The study was led by Andrea Michelle Burden, PhD, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich in Switzerland, and was published online in The Journal of Clinical Endocrinology & Metabolism.

 

LIMITATIONS:

The study could not assess the duration of iron overload on fracture risk, and thus, patients could enter the cohort with a single elevated serum ferritin value that may not have reflected systemic iron overload. The authors also acknowledged potential exposure misclassification among matched control individuals because only 2.9% had a serum ferritin value available at baseline. Also, researchers were unable to adjust for inflammation status due to the limited availability of C-reactive protein measurements and the lack of leukocyte count data in primary care settings.

 

DISCLOSURES:

This study received support through grants from the German Research Foundation. The authors declared 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 word “malnutrition” probably brings to mind images of very thin patients with catabolic illness. But it really just means “poor nutrition,” which can — and often does — apply to patients with overweight or obesity.

That’s because malnutrition doesn’t occur simply because of a lack of calories, but rather because there is a gap in the nutrition the body requires and the nutrition it receives.

Each day, clinicians see patients with chronic conditions related to malnutrition. That list includes diabetes and hypertension, which can be promoted by excess intake of certain nutrients (carbohydrates and sodium) or inadequate intake of others (fiber, protein, potassium, magnesium, and calcium).

 

Diet Education Is Vital in Chronic Disease Management

Diet education is without a doubt a core pillar of chronic disease management. Nutrition therapy is recommended in treatment guidelines for the management of some of the most commonly seen chronic conditions such as hypertension, diabetes, and kidney disease. But in one study, only 58% of physicians, nurses and other health professionals surveyed had received formal nutrition education and only 40% were confident in their ability to provide nutrition education to patients.

As a registered dietitian, I welcome referrals for both prevention and management of chronic diseases with open arms. But medical nutrition therapy with a registered dietitian may not be realistic for all patients owing to financial, geographic, or other constraints. So, their best option may be the few minutes that a physician or physician extender has to spare at the end of their appointment.

But time constraints may result in clinicians turning to short, easy-to-remember messages such as “Don’t eat anything white” or “Only shop the edges of the grocery store.” Although catchy, this type of advice can inadvertently encourage patients to skip over foods that are actually very nutrient dense. For example, white foods such as onions, turnips, mushrooms, cauliflower, and even popcorn are low in calories and high in nutritional value. The center aisles of the grocery store may harbor high-carbohydrate breakfast cereals and potato chips, but they are also home to legumes, nuts, and canned and frozen fruits and vegetables.

What may be more effective is educating the patient on the importance of focusing on the nutrient density of foods, rather than simply limiting certain food groups or colors.

 

How to Work Nutrient Density into the Conversation

Nutrient density is a concept that refers to the proportion of nutrients to calories in a food item: essentially, a food’s qualitative nutritional value. It provides more depth than simply referring to foods as being high or low in calories, healthy or unhealthy, or good or bad.

Educating patients about nutrition density and encouraging a focus on foods that are low in calories and high in vitamins and minerals can help address micronutrient deficiencies, which may be more common than previously thought and linked to the chronic diseases that we see daily. It is worth noting that some foods that are not low in calories are still nutrient dense. Avocados, liver, and nuts come to mind as foods that are high in calories, but they have additional nutrients such as fiber, potassium, antioxidants, vitamin A, iron, and selenium that can still make them an excellent choice if they are part of a well-balanced diet.

I fear that we often underestimate our patients. We worry that not providing them with a list of acceptable foods will set them up for failure. But, in my experience, that list of “good” and “bad” foods may be useful for a week or so but will eventually become lost on the fridge under children’s artwork and save-the-dates.

Patients know that potato chips offer little more than fat, carbs, and salt and that they’re a poor choice for long-term health. What they might not know is that cocktail peanuts can also satisfy the craving for a salty snack, with more than four times the protein, twice the fiber, and just over half of the sodium found in the same serving size of regular salted potato chips. Peanuts have the added bonus of being high in heart-healthy monounsaturated fatty acids.

The best thing that clinicians can do with just a few minutes of time for diet education is to talk to patients about the nutrient density of whole foods and caution patients against highly processed foods, because processing can decrease nutritional content. Our most effective option is to explain why a varied diet with focus on fruits, vegetables, lean protein, nuts, legumes, and healthy fats is beneficial for cardiovascular and metabolic health. After that, all that is left is to trust the patient to make the right choices for their health.

Brandy Winfree Root, a renal dietitian in private practice in Mary Esther, Florida, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

The word “malnutrition” probably brings to mind images of very thin patients with catabolic illness. But it really just means “poor nutrition,” which can — and often does — apply to patients with overweight or obesity.

That’s because malnutrition doesn’t occur simply because of a lack of calories, but rather because there is a gap in the nutrition the body requires and the nutrition it receives.

Each day, clinicians see patients with chronic conditions related to malnutrition. That list includes diabetes and hypertension, which can be promoted by excess intake of certain nutrients (carbohydrates and sodium) or inadequate intake of others (fiber, protein, potassium, magnesium, and calcium).

 

Diet Education Is Vital in Chronic Disease Management

Diet education is without a doubt a core pillar of chronic disease management. Nutrition therapy is recommended in treatment guidelines for the management of some of the most commonly seen chronic conditions such as hypertension, diabetes, and kidney disease. But in one study, only 58% of physicians, nurses and other health professionals surveyed had received formal nutrition education and only 40% were confident in their ability to provide nutrition education to patients.

As a registered dietitian, I welcome referrals for both prevention and management of chronic diseases with open arms. But medical nutrition therapy with a registered dietitian may not be realistic for all patients owing to financial, geographic, or other constraints. So, their best option may be the few minutes that a physician or physician extender has to spare at the end of their appointment.

But time constraints may result in clinicians turning to short, easy-to-remember messages such as “Don’t eat anything white” or “Only shop the edges of the grocery store.” Although catchy, this type of advice can inadvertently encourage patients to skip over foods that are actually very nutrient dense. For example, white foods such as onions, turnips, mushrooms, cauliflower, and even popcorn are low in calories and high in nutritional value. The center aisles of the grocery store may harbor high-carbohydrate breakfast cereals and potato chips, but they are also home to legumes, nuts, and canned and frozen fruits and vegetables.

What may be more effective is educating the patient on the importance of focusing on the nutrient density of foods, rather than simply limiting certain food groups or colors.

 

How to Work Nutrient Density into the Conversation

Nutrient density is a concept that refers to the proportion of nutrients to calories in a food item: essentially, a food’s qualitative nutritional value. It provides more depth than simply referring to foods as being high or low in calories, healthy or unhealthy, or good or bad.

Educating patients about nutrition density and encouraging a focus on foods that are low in calories and high in vitamins and minerals can help address micronutrient deficiencies, which may be more common than previously thought and linked to the chronic diseases that we see daily. It is worth noting that some foods that are not low in calories are still nutrient dense. Avocados, liver, and nuts come to mind as foods that are high in calories, but they have additional nutrients such as fiber, potassium, antioxidants, vitamin A, iron, and selenium that can still make them an excellent choice if they are part of a well-balanced diet.

I fear that we often underestimate our patients. We worry that not providing them with a list of acceptable foods will set them up for failure. But, in my experience, that list of “good” and “bad” foods may be useful for a week or so but will eventually become lost on the fridge under children’s artwork and save-the-dates.

Patients know that potato chips offer little more than fat, carbs, and salt and that they’re a poor choice for long-term health. What they might not know is that cocktail peanuts can also satisfy the craving for a salty snack, with more than four times the protein, twice the fiber, and just over half of the sodium found in the same serving size of regular salted potato chips. Peanuts have the added bonus of being high in heart-healthy monounsaturated fatty acids.

The best thing that clinicians can do with just a few minutes of time for diet education is to talk to patients about the nutrient density of whole foods and caution patients against highly processed foods, because processing can decrease nutritional content. Our most effective option is to explain why a varied diet with focus on fruits, vegetables, lean protein, nuts, legumes, and healthy fats is beneficial for cardiovascular and metabolic health. After that, all that is left is to trust the patient to make the right choices for their health.

Brandy Winfree Root, a renal dietitian in private practice in Mary Esther, Florida, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

The word “malnutrition” probably brings to mind images of very thin patients with catabolic illness. But it really just means “poor nutrition,” which can — and often does — apply to patients with overweight or obesity.

That’s because malnutrition doesn’t occur simply because of a lack of calories, but rather because there is a gap in the nutrition the body requires and the nutrition it receives.

Each day, clinicians see patients with chronic conditions related to malnutrition. That list includes diabetes and hypertension, which can be promoted by excess intake of certain nutrients (carbohydrates and sodium) or inadequate intake of others (fiber, protein, potassium, magnesium, and calcium).

 

Diet Education Is Vital in Chronic Disease Management

Diet education is without a doubt a core pillar of chronic disease management. Nutrition therapy is recommended in treatment guidelines for the management of some of the most commonly seen chronic conditions such as hypertension, diabetes, and kidney disease. But in one study, only 58% of physicians, nurses and other health professionals surveyed had received formal nutrition education and only 40% were confident in their ability to provide nutrition education to patients.

As a registered dietitian, I welcome referrals for both prevention and management of chronic diseases with open arms. But medical nutrition therapy with a registered dietitian may not be realistic for all patients owing to financial, geographic, or other constraints. So, their best option may be the few minutes that a physician or physician extender has to spare at the end of their appointment.

But time constraints may result in clinicians turning to short, easy-to-remember messages such as “Don’t eat anything white” or “Only shop the edges of the grocery store.” Although catchy, this type of advice can inadvertently encourage patients to skip over foods that are actually very nutrient dense. For example, white foods such as onions, turnips, mushrooms, cauliflower, and even popcorn are low in calories and high in nutritional value. The center aisles of the grocery store may harbor high-carbohydrate breakfast cereals and potato chips, but they are also home to legumes, nuts, and canned and frozen fruits and vegetables.

What may be more effective is educating the patient on the importance of focusing on the nutrient density of foods, rather than simply limiting certain food groups or colors.

 

How to Work Nutrient Density into the Conversation

Nutrient density is a concept that refers to the proportion of nutrients to calories in a food item: essentially, a food’s qualitative nutritional value. It provides more depth than simply referring to foods as being high or low in calories, healthy or unhealthy, or good or bad.

Educating patients about nutrition density and encouraging a focus on foods that are low in calories and high in vitamins and minerals can help address micronutrient deficiencies, which may be more common than previously thought and linked to the chronic diseases that we see daily. It is worth noting that some foods that are not low in calories are still nutrient dense. Avocados, liver, and nuts come to mind as foods that are high in calories, but they have additional nutrients such as fiber, potassium, antioxidants, vitamin A, iron, and selenium that can still make them an excellent choice if they are part of a well-balanced diet.

I fear that we often underestimate our patients. We worry that not providing them with a list of acceptable foods will set them up for failure. But, in my experience, that list of “good” and “bad” foods may be useful for a week or so but will eventually become lost on the fridge under children’s artwork and save-the-dates.

Patients know that potato chips offer little more than fat, carbs, and salt and that they’re a poor choice for long-term health. What they might not know is that cocktail peanuts can also satisfy the craving for a salty snack, with more than four times the protein, twice the fiber, and just over half of the sodium found in the same serving size of regular salted potato chips. Peanuts have the added bonus of being high in heart-healthy monounsaturated fatty acids.

The best thing that clinicians can do with just a few minutes of time for diet education is to talk to patients about the nutrient density of whole foods and caution patients against highly processed foods, because processing can decrease nutritional content. Our most effective option is to explain why a varied diet with focus on fruits, vegetables, lean protein, nuts, legumes, and healthy fats is beneficial for cardiovascular and metabolic health. After that, all that is left is to trust the patient to make the right choices for their health.

Brandy Winfree Root, a renal dietitian in private practice in Mary Esther, Florida, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.