MDedge Endocrinology

Internal medicine primarily affords us the skill to cope with disorders of chronicity that rarely disappear. For every pneumococcal pneumonia we eradicate, we have multiple patients with HIV who will be treated indefinitely. Diabetes, once a lethal disease, is now a chronic condition for most patients, and even with treatment the trajectory is usually one of progression.

One gratifying exception in my professional lifetime has been the introduction of gastric surgeries that reduce morbidity and seem to extend the life span of those who successfully undergo these procedures. The Roux-en-Y gastric bypass and sleeve gastrectomy have kept thousands of patients in better health for many years, giving them a second chance. For a subset, however, this second chance comes with a stumbling block of substance use – most notably alcohol – that exceeds their preoperative use.
 

Increased alcohol use after surgery

A group affiliated with the Department of Veterans Affairs (VA) recently reviewed the large central database to identify changes in alcohol consumption among patients who had undergone successful bariatric surgery. The VA regularly administers the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), a survey validated as a reliable estimate of individual alcohol consumption. It is inserted into the VA electronic health record where it can be readily retrieved. By matching these survey results with individuals who underwent bariatric surgery at the VA and survived at least 8 years post op, the authors were able to follow trends in alcohol consumption, beginning 2 years before surgery through 8 years after.

Using the same database, the authors identified a larger number of nonoperative control patients with slightly less obesity but otherwise matched for several elements of comorbidity, such as hypertension, certain psychiatric disorders, and personal habits, including alcohol consumption.

Alcohol use was categorized as none, minor social use, and “unhealthy” use. Among those with no or minor social use preoperatively, 4% converted to unhealthy use at 3 years and about 5% at 8 years, significantly more than in the nonoperative control group. Those who had gastric bypass had somewhat more conversion than did those who had sleeve gastrectomy, though not significantly so.

Patients with an alcohol concern preoperatively took an interesting course. Consumption declined from 2 years pre op to the year of surgery, suggesting that curtailing its use may have been a surgical precondition. Postoperatively, they returned to unhealthy drinking levels. Those who underwent the sleeve gastrectomy consumed about the same amount of alcohol as did their matched nonoperative controls, but those who underwent bypass increased their baseline unhealthy use beyond that of the controls.

Because total abstinence is often the recommendation for treating alcoholism, the research group assessed how adherent the excessive drinkers were to abstinence. In anticipation of surgery, the rates of abstinence increased until the year of surgery, but by 3 years post op, consumption was often up to unhealthy levels, though no more than that of control participants with preexisting drinking problems.
 

Smoking and illicit drug use

Although increased alcohol consumption has generated the most studies, some attention has been given to smoking and illicit drug use, which may also increase over time.

One small study looked at composite tobacco, alcohol, and drug use pre- and postoperatively over 2 years, using population data. The authors found a parallel pattern of users voluntarily reducing their substance use in anticipation of surgery but relapsing as the procedure made them more functional and perhaps more independent. Of the substances people resumed, alcohol by far involved the largest increase in use from the preoperative baseline.

These studies, as important as they are, reveal what happened more effectively than they disclose why it happened. The latter requires some clinical experience. Curtailing cigarettes and alcohol use preoperatively may have been done to stay in the good graces of the surgeon. Many patients may have seen this as their path to a second chance that they intended to maintain.

The incentive to proceed to surgical weight loss, which incurs a measure of risk and forces changes in long ingrained eating habits, involves avoiding future morbidity and promoting longevity. Thus, the postoperative behaviors that threaten the long-term goal need to become a component of ongoing follow-up.

The acquisition of adverse behaviors not present preoperatively seems more difficult to sort out, and obligates those of us following these patients to ask about changes in alcohol use and provide resources for them should they need intervention.

Dr. Plotzker is a retired endocrinologist with 40 years of experience treating patients in both private practice and hospital settings.

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

Internal medicine primarily affords us the skill to cope with disorders of chronicity that rarely disappear. For every pneumococcal pneumonia we eradicate, we have multiple patients with HIV who will be treated indefinitely. Diabetes, once a lethal disease, is now a chronic condition for most patients, and even with treatment the trajectory is usually one of progression.

One gratifying exception in my professional lifetime has been the introduction of gastric surgeries that reduce morbidity and seem to extend the life span of those who successfully undergo these procedures. The Roux-en-Y gastric bypass and sleeve gastrectomy have kept thousands of patients in better health for many years, giving them a second chance. For a subset, however, this second chance comes with a stumbling block of substance use – most notably alcohol – that exceeds their preoperative use.
 

Increased alcohol use after surgery

A group affiliated with the Department of Veterans Affairs (VA) recently reviewed the large central database to identify changes in alcohol consumption among patients who had undergone successful bariatric surgery. The VA regularly administers the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), a survey validated as a reliable estimate of individual alcohol consumption. It is inserted into the VA electronic health record where it can be readily retrieved. By matching these survey results with individuals who underwent bariatric surgery at the VA and survived at least 8 years post op, the authors were able to follow trends in alcohol consumption, beginning 2 years before surgery through 8 years after.

Using the same database, the authors identified a larger number of nonoperative control patients with slightly less obesity but otherwise matched for several elements of comorbidity, such as hypertension, certain psychiatric disorders, and personal habits, including alcohol consumption.

Alcohol use was categorized as none, minor social use, and “unhealthy” use. Among those with no or minor social use preoperatively, 4% converted to unhealthy use at 3 years and about 5% at 8 years, significantly more than in the nonoperative control group. Those who had gastric bypass had somewhat more conversion than did those who had sleeve gastrectomy, though not significantly so.

Patients with an alcohol concern preoperatively took an interesting course. Consumption declined from 2 years pre op to the year of surgery, suggesting that curtailing its use may have been a surgical precondition. Postoperatively, they returned to unhealthy drinking levels. Those who underwent the sleeve gastrectomy consumed about the same amount of alcohol as did their matched nonoperative controls, but those who underwent bypass increased their baseline unhealthy use beyond that of the controls.

Because total abstinence is often the recommendation for treating alcoholism, the research group assessed how adherent the excessive drinkers were to abstinence. In anticipation of surgery, the rates of abstinence increased until the year of surgery, but by 3 years post op, consumption was often up to unhealthy levels, though no more than that of control participants with preexisting drinking problems.
 

Smoking and illicit drug use

Although increased alcohol consumption has generated the most studies, some attention has been given to smoking and illicit drug use, which may also increase over time.

One small study looked at composite tobacco, alcohol, and drug use pre- and postoperatively over 2 years, using population data. The authors found a parallel pattern of users voluntarily reducing their substance use in anticipation of surgery but relapsing as the procedure made them more functional and perhaps more independent. Of the substances people resumed, alcohol by far involved the largest increase in use from the preoperative baseline.

These studies, as important as they are, reveal what happened more effectively than they disclose why it happened. The latter requires some clinical experience. Curtailing cigarettes and alcohol use preoperatively may have been done to stay in the good graces of the surgeon. Many patients may have seen this as their path to a second chance that they intended to maintain.

The incentive to proceed to surgical weight loss, which incurs a measure of risk and forces changes in long ingrained eating habits, involves avoiding future morbidity and promoting longevity. Thus, the postoperative behaviors that threaten the long-term goal need to become a component of ongoing follow-up.

The acquisition of adverse behaviors not present preoperatively seems more difficult to sort out, and obligates those of us following these patients to ask about changes in alcohol use and provide resources for them should they need intervention.

Dr. Plotzker is a retired endocrinologist with 40 years of experience treating patients in both private practice and hospital settings.

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

Internal medicine primarily affords us the skill to cope with disorders of chronicity that rarely disappear. For every pneumococcal pneumonia we eradicate, we have multiple patients with HIV who will be treated indefinitely. Diabetes, once a lethal disease, is now a chronic condition for most patients, and even with treatment the trajectory is usually one of progression.

One gratifying exception in my professional lifetime has been the introduction of gastric surgeries that reduce morbidity and seem to extend the life span of those who successfully undergo these procedures. The Roux-en-Y gastric bypass and sleeve gastrectomy have kept thousands of patients in better health for many years, giving them a second chance. For a subset, however, this second chance comes with a stumbling block of substance use – most notably alcohol – that exceeds their preoperative use.
 

Increased alcohol use after surgery

A group affiliated with the Department of Veterans Affairs (VA) recently reviewed the large central database to identify changes in alcohol consumption among patients who had undergone successful bariatric surgery. The VA regularly administers the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), a survey validated as a reliable estimate of individual alcohol consumption. It is inserted into the VA electronic health record where it can be readily retrieved. By matching these survey results with individuals who underwent bariatric surgery at the VA and survived at least 8 years post op, the authors were able to follow trends in alcohol consumption, beginning 2 years before surgery through 8 years after.

Using the same database, the authors identified a larger number of nonoperative control patients with slightly less obesity but otherwise matched for several elements of comorbidity, such as hypertension, certain psychiatric disorders, and personal habits, including alcohol consumption.

Alcohol use was categorized as none, minor social use, and “unhealthy” use. Among those with no or minor social use preoperatively, 4% converted to unhealthy use at 3 years and about 5% at 8 years, significantly more than in the nonoperative control group. Those who had gastric bypass had somewhat more conversion than did those who had sleeve gastrectomy, though not significantly so.

Patients with an alcohol concern preoperatively took an interesting course. Consumption declined from 2 years pre op to the year of surgery, suggesting that curtailing its use may have been a surgical precondition. Postoperatively, they returned to unhealthy drinking levels. Those who underwent the sleeve gastrectomy consumed about the same amount of alcohol as did their matched nonoperative controls, but those who underwent bypass increased their baseline unhealthy use beyond that of the controls.

Because total abstinence is often the recommendation for treating alcoholism, the research group assessed how adherent the excessive drinkers were to abstinence. In anticipation of surgery, the rates of abstinence increased until the year of surgery, but by 3 years post op, consumption was often up to unhealthy levels, though no more than that of control participants with preexisting drinking problems.
 

Smoking and illicit drug use

Although increased alcohol consumption has generated the most studies, some attention has been given to smoking and illicit drug use, which may also increase over time.

One small study looked at composite tobacco, alcohol, and drug use pre- and postoperatively over 2 years, using population data. The authors found a parallel pattern of users voluntarily reducing their substance use in anticipation of surgery but relapsing as the procedure made them more functional and perhaps more independent. Of the substances people resumed, alcohol by far involved the largest increase in use from the preoperative baseline.

These studies, as important as they are, reveal what happened more effectively than they disclose why it happened. The latter requires some clinical experience. Curtailing cigarettes and alcohol use preoperatively may have been done to stay in the good graces of the surgeon. Many patients may have seen this as their path to a second chance that they intended to maintain.

The incentive to proceed to surgical weight loss, which incurs a measure of risk and forces changes in long ingrained eating habits, involves avoiding future morbidity and promoting longevity. Thus, the postoperative behaviors that threaten the long-term goal need to become a component of ongoing follow-up.

The acquisition of adverse behaviors not present preoperatively seems more difficult to sort out, and obligates those of us following these patients to ask about changes in alcohol use and provide resources for them should they need intervention.

Dr. Plotzker is a retired endocrinologist with 40 years of experience treating patients in both private practice and hospital settings.

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

A peripherally-acting substance that boosts energy expenditure and reduces fat mass has the potential to become an obesity treatment that doesn’t produce cardiovascular or psychiatric side effects, scientists say.

The agent, BIBO3304, is a selective antagonist of the neuropeptide Y1 receptor, which is elevated in the fat tissue of individuals with obesity, resulting in reduced fat accumulation. It was originally developed more than 25 years ago by scientists at Boehringer Ingelheim, who had thought that it would reduce appetite by targeting Y1 receptors in the brain. But when it didn’t cross the blood-brain barrier as an oral drug, the company abandoned it.

Now a series of experiments by Chenxu Yan, of the Garvan Institute of Medical Research, St. Vincent’s Hospital, Sydney, and colleagues have shown that “BIBO” works directly on Y1 receptors in the periphery to turn fat-storing white fat cells into heat-generating brown-like fat tissue, thereby enhancing energy expenditure.

The data were published online May 11 in Nature Communications.
 

Drug’s lack of effect on the brain turns out to be a positive

“Rather than just having the cells store fat, we change their characteristics so that most of the excess energy gets burned and produces heat instead of being stored as fat. BIBO programs the cell toward a more heat-producing cell rather than a fat-storing cell,” study coauthor Herbert Herzog, PhD, of the Garvan Institute, said in an interview.

Importantly, he said, the lack of effect on the brain that caused the drug’s initial developer to abandon it turns out to be a positive.

“As we looked at fat specifically, and we didn’t want to have any interference with the brain, this seems to work out as a real advantage … It has the desired effect of blocking fat accumulation but has the enormous benefit of not interfering with any brain function. That’s why so many of the obesity drugs that were on the market were taken off, because of the side effects they caused in the brain on mood and cardiovascular control. It’s a completely different ball game.”

The problem now, he said, is that because BIBO is off-patent, no pharmaceutical company is currently willing to invest in its development as a peripherally acting weight-loss drug, despite its potential advantages.

“We’re trying to find some interested party to help us get this to the clinical setting. We’re basic scientists. We need big money. We can do small-scale studies to get proof of principle. Hopefully, if that’s interesting, some bigger company will come along,” said Dr. Herzog.
 

Experiments in mice, human tissues demonstrate principle

In the series of studies, investigators fed genetically inbred mice a high-fat, high-sugar diet while giving BIBO to half of them. Over 8 weeks, the mice given BIBO had 40% less gain in fat mass compared to those overfed without the drug, despite them all eating the same amount.

Using a noninvasive infrared camera to measure skin surface temperature above brown adipose tissue, they found that the temperature was significantly increased with BIBO, independent of the weight of the brown fat.

This suggests that the thermogenesis of the brown fat is significantly contributing to whole-body energy expenditure. “With the drug, the mice have far greater energy expenditure measured by heat production,” Dr. Herzog explained.

In vitro experiments showed that Y1R blockade by BIBO induced “beigeing” of white fat deposits into more heat-producing brown fat. The body temperature increase is about 0.1-0.2ºC. “That’s a tiny amount, but it actually requires quite a lot of energy,” he said.

Experiments using fat tissue taken from obese and normal-weight humans showed the same thermogenesis with BIBO. “It’s such a fundamental process [that] you wouldn’t expect it to differ. The same mechanism is even found in flies and primitive worms,” he noted.
 

Neuropeptide Y receptor blockage: A treatment for many ills?

Previously, Dr. Herzog and colleagues found that blockade of the neuropeptide Y1 receptor also increases bone mass in mice.

“It’s a modest effect, but there’s nothing out there at the moment that really improves bone mass. If you can stop osteoporosis, that’s a benefit on its own,” he said.

Now they hope to study BIBO’s vasodilatory properties as a potential treatment for hypertension, if they get the funding.

Dr. Herzog is hopeful, as obesity, osteoporosis, and hypertension are all chronic conditions. “Having one drug that benefits them all would surely be of interest to clinicians and drug companies,” he observed.  

Dr. Yan and Dr. Herzog have reported no relevant financial relationships.

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

A peripherally-acting substance that boosts energy expenditure and reduces fat mass has the potential to become an obesity treatment that doesn’t produce cardiovascular or psychiatric side effects, scientists say.

The agent, BIBO3304, is a selective antagonist of the neuropeptide Y1 receptor, which is elevated in the fat tissue of individuals with obesity, resulting in reduced fat accumulation. It was originally developed more than 25 years ago by scientists at Boehringer Ingelheim, who had thought that it would reduce appetite by targeting Y1 receptors in the brain. But when it didn’t cross the blood-brain barrier as an oral drug, the company abandoned it.

Now a series of experiments by Chenxu Yan, of the Garvan Institute of Medical Research, St. Vincent’s Hospital, Sydney, and colleagues have shown that “BIBO” works directly on Y1 receptors in the periphery to turn fat-storing white fat cells into heat-generating brown-like fat tissue, thereby enhancing energy expenditure.

The data were published online May 11 in Nature Communications.
 

Drug’s lack of effect on the brain turns out to be a positive

“Rather than just having the cells store fat, we change their characteristics so that most of the excess energy gets burned and produces heat instead of being stored as fat. BIBO programs the cell toward a more heat-producing cell rather than a fat-storing cell,” study coauthor Herbert Herzog, PhD, of the Garvan Institute, said in an interview.

Importantly, he said, the lack of effect on the brain that caused the drug’s initial developer to abandon it turns out to be a positive.

“As we looked at fat specifically, and we didn’t want to have any interference with the brain, this seems to work out as a real advantage … It has the desired effect of blocking fat accumulation but has the enormous benefit of not interfering with any brain function. That’s why so many of the obesity drugs that were on the market were taken off, because of the side effects they caused in the brain on mood and cardiovascular control. It’s a completely different ball game.”

The problem now, he said, is that because BIBO is off-patent, no pharmaceutical company is currently willing to invest in its development as a peripherally acting weight-loss drug, despite its potential advantages.

“We’re trying to find some interested party to help us get this to the clinical setting. We’re basic scientists. We need big money. We can do small-scale studies to get proof of principle. Hopefully, if that’s interesting, some bigger company will come along,” said Dr. Herzog.
 

Experiments in mice, human tissues demonstrate principle

In the series of studies, investigators fed genetically inbred mice a high-fat, high-sugar diet while giving BIBO to half of them. Over 8 weeks, the mice given BIBO had 40% less gain in fat mass compared to those overfed without the drug, despite them all eating the same amount.

Using a noninvasive infrared camera to measure skin surface temperature above brown adipose tissue, they found that the temperature was significantly increased with BIBO, independent of the weight of the brown fat.

This suggests that the thermogenesis of the brown fat is significantly contributing to whole-body energy expenditure. “With the drug, the mice have far greater energy expenditure measured by heat production,” Dr. Herzog explained.

In vitro experiments showed that Y1R blockade by BIBO induced “beigeing” of white fat deposits into more heat-producing brown fat. The body temperature increase is about 0.1-0.2ºC. “That’s a tiny amount, but it actually requires quite a lot of energy,” he said.

Experiments using fat tissue taken from obese and normal-weight humans showed the same thermogenesis with BIBO. “It’s such a fundamental process [that] you wouldn’t expect it to differ. The same mechanism is even found in flies and primitive worms,” he noted.
 

Neuropeptide Y receptor blockage: A treatment for many ills?

Previously, Dr. Herzog and colleagues found that blockade of the neuropeptide Y1 receptor also increases bone mass in mice.

“It’s a modest effect, but there’s nothing out there at the moment that really improves bone mass. If you can stop osteoporosis, that’s a benefit on its own,” he said.

Now they hope to study BIBO’s vasodilatory properties as a potential treatment for hypertension, if they get the funding.

Dr. Herzog is hopeful, as obesity, osteoporosis, and hypertension are all chronic conditions. “Having one drug that benefits them all would surely be of interest to clinicians and drug companies,” he observed.  

Dr. Yan and Dr. Herzog have reported no relevant financial relationships.

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

A peripherally-acting substance that boosts energy expenditure and reduces fat mass has the potential to become an obesity treatment that doesn’t produce cardiovascular or psychiatric side effects, scientists say.

The agent, BIBO3304, is a selective antagonist of the neuropeptide Y1 receptor, which is elevated in the fat tissue of individuals with obesity, resulting in reduced fat accumulation. It was originally developed more than 25 years ago by scientists at Boehringer Ingelheim, who had thought that it would reduce appetite by targeting Y1 receptors in the brain. But when it didn’t cross the blood-brain barrier as an oral drug, the company abandoned it.

Now a series of experiments by Chenxu Yan, of the Garvan Institute of Medical Research, St. Vincent’s Hospital, Sydney, and colleagues have shown that “BIBO” works directly on Y1 receptors in the periphery to turn fat-storing white fat cells into heat-generating brown-like fat tissue, thereby enhancing energy expenditure.

The data were published online May 11 in Nature Communications.
 

Drug’s lack of effect on the brain turns out to be a positive

“Rather than just having the cells store fat, we change their characteristics so that most of the excess energy gets burned and produces heat instead of being stored as fat. BIBO programs the cell toward a more heat-producing cell rather than a fat-storing cell,” study coauthor Herbert Herzog, PhD, of the Garvan Institute, said in an interview.

Importantly, he said, the lack of effect on the brain that caused the drug’s initial developer to abandon it turns out to be a positive.

“As we looked at fat specifically, and we didn’t want to have any interference with the brain, this seems to work out as a real advantage … It has the desired effect of blocking fat accumulation but has the enormous benefit of not interfering with any brain function. That’s why so many of the obesity drugs that were on the market were taken off, because of the side effects they caused in the brain on mood and cardiovascular control. It’s a completely different ball game.”

The problem now, he said, is that because BIBO is off-patent, no pharmaceutical company is currently willing to invest in its development as a peripherally acting weight-loss drug, despite its potential advantages.

“We’re trying to find some interested party to help us get this to the clinical setting. We’re basic scientists. We need big money. We can do small-scale studies to get proof of principle. Hopefully, if that’s interesting, some bigger company will come along,” said Dr. Herzog.
 

Experiments in mice, human tissues demonstrate principle

In the series of studies, investigators fed genetically inbred mice a high-fat, high-sugar diet while giving BIBO to half of them. Over 8 weeks, the mice given BIBO had 40% less gain in fat mass compared to those overfed without the drug, despite them all eating the same amount.

Using a noninvasive infrared camera to measure skin surface temperature above brown adipose tissue, they found that the temperature was significantly increased with BIBO, independent of the weight of the brown fat.

This suggests that the thermogenesis of the brown fat is significantly contributing to whole-body energy expenditure. “With the drug, the mice have far greater energy expenditure measured by heat production,” Dr. Herzog explained.

In vitro experiments showed that Y1R blockade by BIBO induced “beigeing” of white fat deposits into more heat-producing brown fat. The body temperature increase is about 0.1-0.2ºC. “That’s a tiny amount, but it actually requires quite a lot of energy,” he said.

Experiments using fat tissue taken from obese and normal-weight humans showed the same thermogenesis with BIBO. “It’s such a fundamental process [that] you wouldn’t expect it to differ. The same mechanism is even found in flies and primitive worms,” he noted.
 

Neuropeptide Y receptor blockage: A treatment for many ills?

Previously, Dr. Herzog and colleagues found that blockade of the neuropeptide Y1 receptor also increases bone mass in mice.

“It’s a modest effect, but there’s nothing out there at the moment that really improves bone mass. If you can stop osteoporosis, that’s a benefit on its own,” he said.

Now they hope to study BIBO’s vasodilatory properties as a potential treatment for hypertension, if they get the funding.

Dr. Herzog is hopeful, as obesity, osteoporosis, and hypertension are all chronic conditions. “Having one drug that benefits them all would surely be of interest to clinicians and drug companies,” he observed.  

Dr. Yan and Dr. Herzog have reported no relevant financial relationships.

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

It’s now official: The investigational sodium-glucose cotransporter (SGLT) 1/2 inhibitor sotagliflozin is the first agent clearly shown in a prespecified analysis of randomized trials to improve clinical outcomes in patients with heart failure with reduced ejection fraction (HFpEF).

Researchers who ran the SCORED and SOLOIST-WHF pivotal trials for sotagliflozin first made that claim in November 2020 when reporting top-line results from a prespecified meta-analysis of the two trials during the American Heart Association annual scientific sessions. A follow-up report during the annual scientific sessions of the American College of Cardiology fleshed out the evidence and firmed up their landmark conclusion.

The meta-analysis (Abstract 410-08) included 4,500 patients with type 2 diabetes and diagnosed heart failure at entry; its primary endpoint, which was the same in both trials, was the combined incidence of cardiovascular death and the total number of either hospitalization for heart failure or urgent outpatient visits for heart failure.

Compared with placebo, treatment with sotagliflozin for a median of about 15 months dropped this composite endpoint by a relative 33% among the 1,931 who began the study with a left ventricular ejection fraction (LVEF) of at least 50% (HFpEF), by a relative 22% in the 1,758 patients who entered with an LVEF of less than 40% (patients with heart failure with reduced ejection fraction), and by a relative 43% among the 811 patients who began with an LVEF of 40%-49% (patients with heart failure with mid-range ejection fraction). The relative risk reductions were significant for all three subgroups, Deepak L. Bhatt, MD, reported at the meeting.
 

Equally effective ‘across the full range of LVEFs.’

Perhaps as notable and unprecedented was the further finding that the clinical benefits seen with treatment of patients with type 2 diabetes with sotagliflozin was consistent regardless of the ejection fraction they had at entry. Enrolled patients with baseline LVEFs in the range of 25% received a relative benefit from sotagliflozin treatment that was statistically no different from the benefit seen in patients who entered with an LVEF in the neighborhood of 45%, 65%, or at any other level across the LVEF spectrum, a finding that Dr. Bhatt called “remarkable” during a press briefing. “The results show the benefit of sotagliflozin across the full range of LVEFs.”

“We are very excited in the heart failure world by the SGLT2 inhibitors; we’ve been impressed by their reduction in heart failure hospitalizations, but we wonder about the patients with HFpEF, where we haven’t had a blockbuster drug to give,” said Ileana L. Piña, MD, a heart failure specialist and medical officer with the Food and Drug Administration.

The new findings “look like they could pose a regulatory indication [for sotagliflozin] for patients with type 2 diabetes and heart failure across the entire spectrum of heart failure,” said Christopher M. O’Connor, MD, a heart failure specialist and president of the Inova Heart & Vascular institute in Falls Church, Va., and designated discussant for Dr. Bhatt’s report.

A significant on-treatment reduction in CV death

Other new, notable findings from the meta-analysis included the observation that while treatment with sotagliflozin failed to produce a significant reduction in cardiovascular death, compared with placebo, in the intent-to-treat analysis of all patients and of those with heart failure at baseline (it produced nonsignificant point-estimate reductions of 11% compared with placebo for all patients, and of 23% for patients who began the study with heart failure), it did result in a significant 23% relative risk reduction when the researchers focused on patients while they remained adherent to their sotagliflozin regimen (the on-treatment analysis). This 23% relative reduction appeared among all enrolled patients, as well as in the subgroup that started with diagnosed heart failure.

“Given the totality of data from the SGLT2 inhibitors, I think this is a real finding,” Dr. Bhatt said.

Additional analyses also showed that, among women, treatment with sotagliflozin was linked with significant relative reductions in the primary endpoint of roughly 30% compared with placebo among all patients, and also among those with heart failure at baseline. “HFpEF is a problem particularly in older women, and we showed that the benefit was consistent in men and women,” Dr. Bhatt said.

He acknowledged that results are expected soon from two pivotal trials that are examining two different SGLT2 inhibitors, dapagliflozin and empagliflozin, in patients with HFpEF. “I think there will be a class effect for both SGLT2 inhibitors and sotagliflozin for reducing heart failure events in patients with HFpEF, and I predict that the dapagliflozin and empagliflozin trials will have positive results,” Dr. Bhatt said.

Sotagliflozin differs from the SGLT2 inhibitors by also inhibiting SGLT1, an enzyme found in the gastrointestinal system that, when inhibited, results in increased glucose excretion from the gut and a cut in bloodstream levels of postprandial glucose levels. The Food and Drug Administration accepted data from SCORED and SOLOIST-WHF as part of the evidence the agency is now considering for granting a new drug approval to sotagliflozin.

SCORED and SOLOIST-WHF were initially sponsored by Sanofi, and later by Lexicon Pharmaceuticals. Dr. Bhatt’s institution, Brigham and Women’s Hospital, has received funding from Sanofi and Lexicon Pharmaceuticals. He has been a consultant to and received honoraria from K₂P, Level Ex, and MJH Life Sciences; he has been an adviser to Cardax, Cereno Scientific, Myokardia, Novo Nordisk, Phase Bio, and PLx Pharma; and he has received research funding from numerous companies. Dr. Piña has no relevant disclosures. Dr. O’Connor has been a consultant to Arena, Bayer, Bristol-Myers Squibb, Merck, and Windtree, and he has an ownership interest in Biscardia.

[email protected]

It’s now official: The investigational sodium-glucose cotransporter (SGLT) 1/2 inhibitor sotagliflozin is the first agent clearly shown in a prespecified analysis of randomized trials to improve clinical outcomes in patients with heart failure with reduced ejection fraction (HFpEF).

Researchers who ran the SCORED and SOLOIST-WHF pivotal trials for sotagliflozin first made that claim in November 2020 when reporting top-line results from a prespecified meta-analysis of the two trials during the American Heart Association annual scientific sessions. A follow-up report during the annual scientific sessions of the American College of Cardiology fleshed out the evidence and firmed up their landmark conclusion.

The meta-analysis (Abstract 410-08) included 4,500 patients with type 2 diabetes and diagnosed heart failure at entry; its primary endpoint, which was the same in both trials, was the combined incidence of cardiovascular death and the total number of either hospitalization for heart failure or urgent outpatient visits for heart failure.

Compared with placebo, treatment with sotagliflozin for a median of about 15 months dropped this composite endpoint by a relative 33% among the 1,931 who began the study with a left ventricular ejection fraction (LVEF) of at least 50% (HFpEF), by a relative 22% in the 1,758 patients who entered with an LVEF of less than 40% (patients with heart failure with reduced ejection fraction), and by a relative 43% among the 811 patients who began with an LVEF of 40%-49% (patients with heart failure with mid-range ejection fraction). The relative risk reductions were significant for all three subgroups, Deepak L. Bhatt, MD, reported at the meeting.
 

Equally effective ‘across the full range of LVEFs.’

Perhaps as notable and unprecedented was the further finding that the clinical benefits seen with treatment of patients with type 2 diabetes with sotagliflozin was consistent regardless of the ejection fraction they had at entry. Enrolled patients with baseline LVEFs in the range of 25% received a relative benefit from sotagliflozin treatment that was statistically no different from the benefit seen in patients who entered with an LVEF in the neighborhood of 45%, 65%, or at any other level across the LVEF spectrum, a finding that Dr. Bhatt called “remarkable” during a press briefing. “The results show the benefit of sotagliflozin across the full range of LVEFs.”

“We are very excited in the heart failure world by the SGLT2 inhibitors; we’ve been impressed by their reduction in heart failure hospitalizations, but we wonder about the patients with HFpEF, where we haven’t had a blockbuster drug to give,” said Ileana L. Piña, MD, a heart failure specialist and medical officer with the Food and Drug Administration.

The new findings “look like they could pose a regulatory indication [for sotagliflozin] for patients with type 2 diabetes and heart failure across the entire spectrum of heart failure,” said Christopher M. O’Connor, MD, a heart failure specialist and president of the Inova Heart & Vascular institute in Falls Church, Va., and designated discussant for Dr. Bhatt’s report.

A significant on-treatment reduction in CV death

Other new, notable findings from the meta-analysis included the observation that while treatment with sotagliflozin failed to produce a significant reduction in cardiovascular death, compared with placebo, in the intent-to-treat analysis of all patients and of those with heart failure at baseline (it produced nonsignificant point-estimate reductions of 11% compared with placebo for all patients, and of 23% for patients who began the study with heart failure), it did result in a significant 23% relative risk reduction when the researchers focused on patients while they remained adherent to their sotagliflozin regimen (the on-treatment analysis). This 23% relative reduction appeared among all enrolled patients, as well as in the subgroup that started with diagnosed heart failure.

“Given the totality of data from the SGLT2 inhibitors, I think this is a real finding,” Dr. Bhatt said.

Additional analyses also showed that, among women, treatment with sotagliflozin was linked with significant relative reductions in the primary endpoint of roughly 30% compared with placebo among all patients, and also among those with heart failure at baseline. “HFpEF is a problem particularly in older women, and we showed that the benefit was consistent in men and women,” Dr. Bhatt said.

He acknowledged that results are expected soon from two pivotal trials that are examining two different SGLT2 inhibitors, dapagliflozin and empagliflozin, in patients with HFpEF. “I think there will be a class effect for both SGLT2 inhibitors and sotagliflozin for reducing heart failure events in patients with HFpEF, and I predict that the dapagliflozin and empagliflozin trials will have positive results,” Dr. Bhatt said.

Sotagliflozin differs from the SGLT2 inhibitors by also inhibiting SGLT1, an enzyme found in the gastrointestinal system that, when inhibited, results in increased glucose excretion from the gut and a cut in bloodstream levels of postprandial glucose levels. The Food and Drug Administration accepted data from SCORED and SOLOIST-WHF as part of the evidence the agency is now considering for granting a new drug approval to sotagliflozin.

SCORED and SOLOIST-WHF were initially sponsored by Sanofi, and later by Lexicon Pharmaceuticals. Dr. Bhatt’s institution, Brigham and Women’s Hospital, has received funding from Sanofi and Lexicon Pharmaceuticals. He has been a consultant to and received honoraria from K₂P, Level Ex, and MJH Life Sciences; he has been an adviser to Cardax, Cereno Scientific, Myokardia, Novo Nordisk, Phase Bio, and PLx Pharma; and he has received research funding from numerous companies. Dr. Piña has no relevant disclosures. Dr. O’Connor has been a consultant to Arena, Bayer, Bristol-Myers Squibb, Merck, and Windtree, and he has an ownership interest in Biscardia.

[email protected]

It’s now official: The investigational sodium-glucose cotransporter (SGLT) 1/2 inhibitor sotagliflozin is the first agent clearly shown in a prespecified analysis of randomized trials to improve clinical outcomes in patients with heart failure with reduced ejection fraction (HFpEF).

Researchers who ran the SCORED and SOLOIST-WHF pivotal trials for sotagliflozin first made that claim in November 2020 when reporting top-line results from a prespecified meta-analysis of the two trials during the American Heart Association annual scientific sessions. A follow-up report during the annual scientific sessions of the American College of Cardiology fleshed out the evidence and firmed up their landmark conclusion.

The meta-analysis (Abstract 410-08) included 4,500 patients with type 2 diabetes and diagnosed heart failure at entry; its primary endpoint, which was the same in both trials, was the combined incidence of cardiovascular death and the total number of either hospitalization for heart failure or urgent outpatient visits for heart failure.

Compared with placebo, treatment with sotagliflozin for a median of about 15 months dropped this composite endpoint by a relative 33% among the 1,931 who began the study with a left ventricular ejection fraction (LVEF) of at least 50% (HFpEF), by a relative 22% in the 1,758 patients who entered with an LVEF of less than 40% (patients with heart failure with reduced ejection fraction), and by a relative 43% among the 811 patients who began with an LVEF of 40%-49% (patients with heart failure with mid-range ejection fraction). The relative risk reductions were significant for all three subgroups, Deepak L. Bhatt, MD, reported at the meeting.
 

Equally effective ‘across the full range of LVEFs.’

Perhaps as notable and unprecedented was the further finding that the clinical benefits seen with treatment of patients with type 2 diabetes with sotagliflozin was consistent regardless of the ejection fraction they had at entry. Enrolled patients with baseline LVEFs in the range of 25% received a relative benefit from sotagliflozin treatment that was statistically no different from the benefit seen in patients who entered with an LVEF in the neighborhood of 45%, 65%, or at any other level across the LVEF spectrum, a finding that Dr. Bhatt called “remarkable” during a press briefing. “The results show the benefit of sotagliflozin across the full range of LVEFs.”

“We are very excited in the heart failure world by the SGLT2 inhibitors; we’ve been impressed by their reduction in heart failure hospitalizations, but we wonder about the patients with HFpEF, where we haven’t had a blockbuster drug to give,” said Ileana L. Piña, MD, a heart failure specialist and medical officer with the Food and Drug Administration.

The new findings “look like they could pose a regulatory indication [for sotagliflozin] for patients with type 2 diabetes and heart failure across the entire spectrum of heart failure,” said Christopher M. O’Connor, MD, a heart failure specialist and president of the Inova Heart & Vascular institute in Falls Church, Va., and designated discussant for Dr. Bhatt’s report.

A significant on-treatment reduction in CV death

Other new, notable findings from the meta-analysis included the observation that while treatment with sotagliflozin failed to produce a significant reduction in cardiovascular death, compared with placebo, in the intent-to-treat analysis of all patients and of those with heart failure at baseline (it produced nonsignificant point-estimate reductions of 11% compared with placebo for all patients, and of 23% for patients who began the study with heart failure), it did result in a significant 23% relative risk reduction when the researchers focused on patients while they remained adherent to their sotagliflozin regimen (the on-treatment analysis). This 23% relative reduction appeared among all enrolled patients, as well as in the subgroup that started with diagnosed heart failure.

“Given the totality of data from the SGLT2 inhibitors, I think this is a real finding,” Dr. Bhatt said.

Additional analyses also showed that, among women, treatment with sotagliflozin was linked with significant relative reductions in the primary endpoint of roughly 30% compared with placebo among all patients, and also among those with heart failure at baseline. “HFpEF is a problem particularly in older women, and we showed that the benefit was consistent in men and women,” Dr. Bhatt said.

He acknowledged that results are expected soon from two pivotal trials that are examining two different SGLT2 inhibitors, dapagliflozin and empagliflozin, in patients with HFpEF. “I think there will be a class effect for both SGLT2 inhibitors and sotagliflozin for reducing heart failure events in patients with HFpEF, and I predict that the dapagliflozin and empagliflozin trials will have positive results,” Dr. Bhatt said.

Sotagliflozin differs from the SGLT2 inhibitors by also inhibiting SGLT1, an enzyme found in the gastrointestinal system that, when inhibited, results in increased glucose excretion from the gut and a cut in bloodstream levels of postprandial glucose levels. The Food and Drug Administration accepted data from SCORED and SOLOIST-WHF as part of the evidence the agency is now considering for granting a new drug approval to sotagliflozin.

SCORED and SOLOIST-WHF were initially sponsored by Sanofi, and later by Lexicon Pharmaceuticals. Dr. Bhatt’s institution, Brigham and Women’s Hospital, has received funding from Sanofi and Lexicon Pharmaceuticals. He has been a consultant to and received honoraria from K₂P, Level Ex, and MJH Life Sciences; he has been an adviser to Cardax, Cereno Scientific, Myokardia, Novo Nordisk, Phase Bio, and PLx Pharma; and he has received research funding from numerous companies. Dr. Piña has no relevant disclosures. Dr. O’Connor has been a consultant to Arena, Bayer, Bristol-Myers Squibb, Merck, and Windtree, and he has an ownership interest in Biscardia.

[email protected]

Individuals at increased risk for dementia because of family history can reduce that risk by adopting healthy lifestyle behaviors, data from more than 300,000 adults aged 50-73 years suggest.

Having a parent or sibling with dementia can increase a person’s risk of developing dementia themselves by nearly 75%, compared with someone with no first-degree family history of dementia, according to Angelique Brellenthin, PhD, of Iowa State University, Ames, and colleagues.

In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting sponsored by the American Heart Association, the researchers reviewed information for 302,239 men and women who were enrolled in the U.K. Biobank, a population-based study of more than 500,000 individuals in the United Kingdom, between 2006 and 2010.

The study participants had no evidence of dementia at baseline, and completed questionnaires about family history and lifestyle. The questions included details about six healthy lifestyle behaviors: eating a healthy diet, engaging in at least 150 minutes of moderate to vigorous physical activity per week, sleeping 6-9 hours each night, drinking alcohol in moderation, not smoking, and maintaining a body mass index below the obese level (less than 30 kg/m²).

The researchers identified 1,698 participants (0.6%) who developed dementia over an average follow-up period of 8 years. Those with a family history (first-degree relative) of dementia had a 70% increased risk of dementia, compared with those who had no such family history.

Overall, individuals who engaged in all six healthy behaviors reduced their risk of dementia by about half, compared with those who engaged in two or fewer healthy behaviors. Engaging in three healthy behaviors reduced the risk of dementia by 30%, compared with engaging in two or fewer healthy behaviors, and this association held after controlling not only for family history of dementia, but also for other dementia risk factors such as age, sex, race, and education level, as well as high blood pressure, high cholesterol, and the presence of type 2 diabetes.

Similarly, among participants with a family history of dementia, those who engaged in three healthy lifestyle behaviors showed a 25%-35% reduction in dementia risk, compared with those who engaged in two or fewer healthy behaviors.

The study findings were limited by several factors including the inability to prove that lifestyle can cause or prevent dementia, only to show an association, the researchers noted. Also, the findings were limited by the reliance on self-reports, rather than genetic data, to confirm familial dementia.

However, the findings were strengthened by the large sample size, and the results suggest that a healthy lifestyle can impact cognitive health, and support the value of encouraging healthy behaviors in general, and especially among individuals with a family history of dementia, they said.
 

Small changes may promote prevention

The study is important now because, as the population ages, many individuals have a family member who has had dementia, said lead author Dr. Brellenthin, in an interview. “It’s important to understand how lifestyle behaviors affect the risk of dementia when it runs in families,” she said.

Dr. Brellenthin said she was surprised by some of the findings. “It was surprising to see that the risk of dementia was reduced with just three healthy behaviors [but was further reduced as you added more behaviors] compared to two or fewer behaviors. However, it was not surprising to see that these same lifestyle behaviors that tend to be good for the heart and body are also good for the brain.”

The evidence that following just three healthy behaviors can reduce the risk of dementia by 25%-35% for individuals with a familial history of dementia has clinical implications, Dr. Brellenthin said. “Many people are already following some of these behaviors like not smoking, so it might be possible to focus on adding just one more behavior, like getting enough sleep, and going from there.”

Commenting on the study, AHA President Mitchell S. V. Elkind, MD, said that the study “tells us that, yes, family history is important [in determining the risk of dementia], and much of that may be driven by genetic factors, but some of that impact can be mitigated or decreased by engaging in those important behaviors that we know are good to maintain brain health.

“The tricky thing, of course, is getting people to engage in these behaviors. That’s where a lot of work in the future will be: changing people’s behavior to become more healthy, and figuring out exactly which behaviors may be the easiest to engage in and be most likely to have public health impact,” added Dr. Elkind, professor of neurology and epidemiology at Columbia University and attending neurologist at New York–Presbyterian/Columbia University Irving Medical Center, New York.

The study received no outside funding, but the was research was conducted using the U.K. Biobank resources. The researchers had no financial conflicts to disclose.

Individuals at increased risk for dementia because of family history can reduce that risk by adopting healthy lifestyle behaviors, data from more than 300,000 adults aged 50-73 years suggest.

Having a parent or sibling with dementia can increase a person’s risk of developing dementia themselves by nearly 75%, compared with someone with no first-degree family history of dementia, according to Angelique Brellenthin, PhD, of Iowa State University, Ames, and colleagues.

In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting sponsored by the American Heart Association, the researchers reviewed information for 302,239 men and women who were enrolled in the U.K. Biobank, a population-based study of more than 500,000 individuals in the United Kingdom, between 2006 and 2010.

The study participants had no evidence of dementia at baseline, and completed questionnaires about family history and lifestyle. The questions included details about six healthy lifestyle behaviors: eating a healthy diet, engaging in at least 150 minutes of moderate to vigorous physical activity per week, sleeping 6-9 hours each night, drinking alcohol in moderation, not smoking, and maintaining a body mass index below the obese level (less than 30 kg/m²).

The researchers identified 1,698 participants (0.6%) who developed dementia over an average follow-up period of 8 years. Those with a family history (first-degree relative) of dementia had a 70% increased risk of dementia, compared with those who had no such family history.

Overall, individuals who engaged in all six healthy behaviors reduced their risk of dementia by about half, compared with those who engaged in two or fewer healthy behaviors. Engaging in three healthy behaviors reduced the risk of dementia by 30%, compared with engaging in two or fewer healthy behaviors, and this association held after controlling not only for family history of dementia, but also for other dementia risk factors such as age, sex, race, and education level, as well as high blood pressure, high cholesterol, and the presence of type 2 diabetes.

Similarly, among participants with a family history of dementia, those who engaged in three healthy lifestyle behaviors showed a 25%-35% reduction in dementia risk, compared with those who engaged in two or fewer healthy behaviors.

The study findings were limited by several factors including the inability to prove that lifestyle can cause or prevent dementia, only to show an association, the researchers noted. Also, the findings were limited by the reliance on self-reports, rather than genetic data, to confirm familial dementia.

However, the findings were strengthened by the large sample size, and the results suggest that a healthy lifestyle can impact cognitive health, and support the value of encouraging healthy behaviors in general, and especially among individuals with a family history of dementia, they said.
 

Small changes may promote prevention

The study is important now because, as the population ages, many individuals have a family member who has had dementia, said lead author Dr. Brellenthin, in an interview. “It’s important to understand how lifestyle behaviors affect the risk of dementia when it runs in families,” she said.

Dr. Brellenthin said she was surprised by some of the findings. “It was surprising to see that the risk of dementia was reduced with just three healthy behaviors [but was further reduced as you added more behaviors] compared to two or fewer behaviors. However, it was not surprising to see that these same lifestyle behaviors that tend to be good for the heart and body are also good for the brain.”

The evidence that following just three healthy behaviors can reduce the risk of dementia by 25%-35% for individuals with a familial history of dementia has clinical implications, Dr. Brellenthin said. “Many people are already following some of these behaviors like not smoking, so it might be possible to focus on adding just one more behavior, like getting enough sleep, and going from there.”

Commenting on the study, AHA President Mitchell S. V. Elkind, MD, said that the study “tells us that, yes, family history is important [in determining the risk of dementia], and much of that may be driven by genetic factors, but some of that impact can be mitigated or decreased by engaging in those important behaviors that we know are good to maintain brain health.

“The tricky thing, of course, is getting people to engage in these behaviors. That’s where a lot of work in the future will be: changing people’s behavior to become more healthy, and figuring out exactly which behaviors may be the easiest to engage in and be most likely to have public health impact,” added Dr. Elkind, professor of neurology and epidemiology at Columbia University and attending neurologist at New York–Presbyterian/Columbia University Irving Medical Center, New York.

The study received no outside funding, but the was research was conducted using the U.K. Biobank resources. The researchers had no financial conflicts to disclose.

Individuals at increased risk for dementia because of family history can reduce that risk by adopting healthy lifestyle behaviors, data from more than 300,000 adults aged 50-73 years suggest.

Having a parent or sibling with dementia can increase a person’s risk of developing dementia themselves by nearly 75%, compared with someone with no first-degree family history of dementia, according to Angelique Brellenthin, PhD, of Iowa State University, Ames, and colleagues.

In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting sponsored by the American Heart Association, the researchers reviewed information for 302,239 men and women who were enrolled in the U.K. Biobank, a population-based study of more than 500,000 individuals in the United Kingdom, between 2006 and 2010.

The study participants had no evidence of dementia at baseline, and completed questionnaires about family history and lifestyle. The questions included details about six healthy lifestyle behaviors: eating a healthy diet, engaging in at least 150 minutes of moderate to vigorous physical activity per week, sleeping 6-9 hours each night, drinking alcohol in moderation, not smoking, and maintaining a body mass index below the obese level (less than 30 kg/m²).

The researchers identified 1,698 participants (0.6%) who developed dementia over an average follow-up period of 8 years. Those with a family history (first-degree relative) of dementia had a 70% increased risk of dementia, compared with those who had no such family history.

Overall, individuals who engaged in all six healthy behaviors reduced their risk of dementia by about half, compared with those who engaged in two or fewer healthy behaviors. Engaging in three healthy behaviors reduced the risk of dementia by 30%, compared with engaging in two or fewer healthy behaviors, and this association held after controlling not only for family history of dementia, but also for other dementia risk factors such as age, sex, race, and education level, as well as high blood pressure, high cholesterol, and the presence of type 2 diabetes.

Similarly, among participants with a family history of dementia, those who engaged in three healthy lifestyle behaviors showed a 25%-35% reduction in dementia risk, compared with those who engaged in two or fewer healthy behaviors.

The study findings were limited by several factors including the inability to prove that lifestyle can cause or prevent dementia, only to show an association, the researchers noted. Also, the findings were limited by the reliance on self-reports, rather than genetic data, to confirm familial dementia.

However, the findings were strengthened by the large sample size, and the results suggest that a healthy lifestyle can impact cognitive health, and support the value of encouraging healthy behaviors in general, and especially among individuals with a family history of dementia, they said.
 

Small changes may promote prevention

The study is important now because, as the population ages, many individuals have a family member who has had dementia, said lead author Dr. Brellenthin, in an interview. “It’s important to understand how lifestyle behaviors affect the risk of dementia when it runs in families,” she said.

Dr. Brellenthin said she was surprised by some of the findings. “It was surprising to see that the risk of dementia was reduced with just three healthy behaviors [but was further reduced as you added more behaviors] compared to two or fewer behaviors. However, it was not surprising to see that these same lifestyle behaviors that tend to be good for the heart and body are also good for the brain.”

The evidence that following just three healthy behaviors can reduce the risk of dementia by 25%-35% for individuals with a familial history of dementia has clinical implications, Dr. Brellenthin said. “Many people are already following some of these behaviors like not smoking, so it might be possible to focus on adding just one more behavior, like getting enough sleep, and going from there.”

Commenting on the study, AHA President Mitchell S. V. Elkind, MD, said that the study “tells us that, yes, family history is important [in determining the risk of dementia], and much of that may be driven by genetic factors, but some of that impact can be mitigated or decreased by engaging in those important behaviors that we know are good to maintain brain health.

“The tricky thing, of course, is getting people to engage in these behaviors. That’s where a lot of work in the future will be: changing people’s behavior to become more healthy, and figuring out exactly which behaviors may be the easiest to engage in and be most likely to have public health impact,” added Dr. Elkind, professor of neurology and epidemiology at Columbia University and attending neurologist at New York–Presbyterian/Columbia University Irving Medical Center, New York.

The study received no outside funding, but the was research was conducted using the U.K. Biobank resources. The researchers had no financial conflicts to disclose.

The Centers for Disease Control and Prevention’s latest guidance on what fully vaccinated people can do safely – including not socially distancing and not wearing a mask indoors or outdoors unless other regulations require it – has been widely misinterpreted and caused confusion, two infectious disease experts said at a briefing on May 20 hosted by the Infectious Diseases Society of America (IDSA).

The CDC did not ‘’lift” the mask mandate, but rather supplied guidance for those who are fully vaccinated. However, many questions and gray areas remain, and the experts addressed those. ‘’The CDC guidance is really directed at people who are fully vaccinated and who we know are likely to have a really solid response to the vaccine,” said Jeanne Marrazzo, MD, MPH, director of infectious diseases at the University of Alabama at Birmingham and an IDSA board member.

That message was largely lost, said Dr. Marrazzo and Jeffrey Duchin, MD, health officer of public health for Seattle and King County, Washington, and also an IDSA board member. Dr. Duchin said many people mistakenly regarded the new guidance as a message that the pandemic is over.

Among their practical tips on how to interpret the guidance:
 

To mask or not?

To make the decision, people need to think about not only the numbers of vaccinated versus unvaccinated individuals in their community but the local rates of disease, the experts said.  And they need to know that the CDC guidance doesn’t apply if regulations by federal or state authorities or businesses and workplace are in conflict.

Deciding on mask use sometimes depends on where you are going. What about going into grocery stores or large bin stores without a mask? “If you are fully vaccinated and have no other conditions that compromise your immune system, and the rates of COVID are relatively low where you live, and the vaccination rates are high, I would be 100% fine” without a mask, Dr. Marrazzo said. But it’s important to think of all these factors in calculating your risk.

“I’m still wearing a mask when I go anywhere in public,” she said, citing vaccination rates that have not yet reached 50% in her area.

If that rate reached 80%, the typical percentage talked about for herd immunity, and new cases were low, Dr. Marrazzo said she might shed the mask.

The CDC also continues to recommend masks on mass transit for all.

One population that also must be considered, and who must evaluate their risk, even if vaccinated, are the immunocompromised, Dr. Marrazzo said. While people think of the immunocompromised as those with HIV or organ transplants, the numbers are actually much larger.

“A study a couple of years ago indicated up to 3% of Americans may actually have been told by their physician they have some of level of being immunocompromised,” she said. Among the examples are those who are on dialysis, on chemotherapy, or those taking any of the medications that modify the immune system.

“Millions of people fit this bill, and we have [very] little data on whether the vaccine works in them. We think it does,” Dr. Marrazzo said.

Still, she said, it’s a reason for these people to be cautious. For some other vaccines, the dose is modified for those who are immunocompromised. What’s not known yet is whether additional doses of the COVID vaccines might boost protection for those who are immunocompromised.

Many people, even after vaccination, may choose to keep wearing a mask especially in indoor, crowded settings, Dr. Duchin said. “We need to expect, accept, and respect continued mask wearing by anyone at any time.”

In most outdoor settings, he said, “I think masks are probably not necessary, vaccinated or not, regardless of age.” One exception: close face-to-face contact, such as in certain sports.
 

How to protect toddlers and infants

With masks not practical or recommended for infants and toddlers under 2 years old, Dr. Marrazzo said adults should remember that ‘’those very little kids don’t do poorly at all [even if infected], although there is not a ton of data.”

Adults should still treat young children as vulnerable, especially newborns. Adults not yet vaccinated should wear a mask when around them, she said.
 

J & J vaccine recipients

With less ‘’real world” data on the Johnson & Johnson vaccine, should those who got it think of themselves in a different risk group than those who got Moderna or Pfizer and adjust their behavior accordingly? 

“The J&J vaccine, based on everything we know, does provide a great deal of protection,” Dr. Marrazzo said. ‘’We don’t know as much about prevention of transmission in the asymptomatic cases in the J&J.”

Most of that data, she said, is from the mRNA vaccines Pfizer and Moderna. “I think it’s an important area to study and learn about.” But all three vaccines, overall, provide a high level of protection, she said.

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

The Centers for Disease Control and Prevention’s latest guidance on what fully vaccinated people can do safely – including not socially distancing and not wearing a mask indoors or outdoors unless other regulations require it – has been widely misinterpreted and caused confusion, two infectious disease experts said at a briefing on May 20 hosted by the Infectious Diseases Society of America (IDSA).

The CDC did not ‘’lift” the mask mandate, but rather supplied guidance for those who are fully vaccinated. However, many questions and gray areas remain, and the experts addressed those. ‘’The CDC guidance is really directed at people who are fully vaccinated and who we know are likely to have a really solid response to the vaccine,” said Jeanne Marrazzo, MD, MPH, director of infectious diseases at the University of Alabama at Birmingham and an IDSA board member.

That message was largely lost, said Dr. Marrazzo and Jeffrey Duchin, MD, health officer of public health for Seattle and King County, Washington, and also an IDSA board member. Dr. Duchin said many people mistakenly regarded the new guidance as a message that the pandemic is over.

Among their practical tips on how to interpret the guidance:
 

To mask or not?

To make the decision, people need to think about not only the numbers of vaccinated versus unvaccinated individuals in their community but the local rates of disease, the experts said.  And they need to know that the CDC guidance doesn’t apply if regulations by federal or state authorities or businesses and workplace are in conflict.

Deciding on mask use sometimes depends on where you are going. What about going into grocery stores or large bin stores without a mask? “If you are fully vaccinated and have no other conditions that compromise your immune system, and the rates of COVID are relatively low where you live, and the vaccination rates are high, I would be 100% fine” without a mask, Dr. Marrazzo said. But it’s important to think of all these factors in calculating your risk.

“I’m still wearing a mask when I go anywhere in public,” she said, citing vaccination rates that have not yet reached 50% in her area.

If that rate reached 80%, the typical percentage talked about for herd immunity, and new cases were low, Dr. Marrazzo said she might shed the mask.

The CDC also continues to recommend masks on mass transit for all.

One population that also must be considered, and who must evaluate their risk, even if vaccinated, are the immunocompromised, Dr. Marrazzo said. While people think of the immunocompromised as those with HIV or organ transplants, the numbers are actually much larger.

“A study a couple of years ago indicated up to 3% of Americans may actually have been told by their physician they have some of level of being immunocompromised,” she said. Among the examples are those who are on dialysis, on chemotherapy, or those taking any of the medications that modify the immune system.

“Millions of people fit this bill, and we have [very] little data on whether the vaccine works in them. We think it does,” Dr. Marrazzo said.

Still, she said, it’s a reason for these people to be cautious. For some other vaccines, the dose is modified for those who are immunocompromised. What’s not known yet is whether additional doses of the COVID vaccines might boost protection for those who are immunocompromised.

Many people, even after vaccination, may choose to keep wearing a mask especially in indoor, crowded settings, Dr. Duchin said. “We need to expect, accept, and respect continued mask wearing by anyone at any time.”

In most outdoor settings, he said, “I think masks are probably not necessary, vaccinated or not, regardless of age.” One exception: close face-to-face contact, such as in certain sports.
 

How to protect toddlers and infants

With masks not practical or recommended for infants and toddlers under 2 years old, Dr. Marrazzo said adults should remember that ‘’those very little kids don’t do poorly at all [even if infected], although there is not a ton of data.”

Adults should still treat young children as vulnerable, especially newborns. Adults not yet vaccinated should wear a mask when around them, she said.
 

J & J vaccine recipients

With less ‘’real world” data on the Johnson & Johnson vaccine, should those who got it think of themselves in a different risk group than those who got Moderna or Pfizer and adjust their behavior accordingly? 

“The J&J vaccine, based on everything we know, does provide a great deal of protection,” Dr. Marrazzo said. ‘’We don’t know as much about prevention of transmission in the asymptomatic cases in the J&J.”

Most of that data, she said, is from the mRNA vaccines Pfizer and Moderna. “I think it’s an important area to study and learn about.” But all three vaccines, overall, provide a high level of protection, she said.

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

The Centers for Disease Control and Prevention’s latest guidance on what fully vaccinated people can do safely – including not socially distancing and not wearing a mask indoors or outdoors unless other regulations require it – has been widely misinterpreted and caused confusion, two infectious disease experts said at a briefing on May 20 hosted by the Infectious Diseases Society of America (IDSA).

The CDC did not ‘’lift” the mask mandate, but rather supplied guidance for those who are fully vaccinated. However, many questions and gray areas remain, and the experts addressed those. ‘’The CDC guidance is really directed at people who are fully vaccinated and who we know are likely to have a really solid response to the vaccine,” said Jeanne Marrazzo, MD, MPH, director of infectious diseases at the University of Alabama at Birmingham and an IDSA board member.

That message was largely lost, said Dr. Marrazzo and Jeffrey Duchin, MD, health officer of public health for Seattle and King County, Washington, and also an IDSA board member. Dr. Duchin said many people mistakenly regarded the new guidance as a message that the pandemic is over.

Among their practical tips on how to interpret the guidance:
 

To mask or not?

To make the decision, people need to think about not only the numbers of vaccinated versus unvaccinated individuals in their community but the local rates of disease, the experts said.  And they need to know that the CDC guidance doesn’t apply if regulations by federal or state authorities or businesses and workplace are in conflict.

Deciding on mask use sometimes depends on where you are going. What about going into grocery stores or large bin stores without a mask? “If you are fully vaccinated and have no other conditions that compromise your immune system, and the rates of COVID are relatively low where you live, and the vaccination rates are high, I would be 100% fine” without a mask, Dr. Marrazzo said. But it’s important to think of all these factors in calculating your risk.

“I’m still wearing a mask when I go anywhere in public,” she said, citing vaccination rates that have not yet reached 50% in her area.

If that rate reached 80%, the typical percentage talked about for herd immunity, and new cases were low, Dr. Marrazzo said she might shed the mask.

The CDC also continues to recommend masks on mass transit for all.

One population that also must be considered, and who must evaluate their risk, even if vaccinated, are the immunocompromised, Dr. Marrazzo said. While people think of the immunocompromised as those with HIV or organ transplants, the numbers are actually much larger.

“A study a couple of years ago indicated up to 3% of Americans may actually have been told by their physician they have some of level of being immunocompromised,” she said. Among the examples are those who are on dialysis, on chemotherapy, or those taking any of the medications that modify the immune system.

“Millions of people fit this bill, and we have [very] little data on whether the vaccine works in them. We think it does,” Dr. Marrazzo said.

Still, she said, it’s a reason for these people to be cautious. For some other vaccines, the dose is modified for those who are immunocompromised. What’s not known yet is whether additional doses of the COVID vaccines might boost protection for those who are immunocompromised.

Many people, even after vaccination, may choose to keep wearing a mask especially in indoor, crowded settings, Dr. Duchin said. “We need to expect, accept, and respect continued mask wearing by anyone at any time.”

In most outdoor settings, he said, “I think masks are probably not necessary, vaccinated or not, regardless of age.” One exception: close face-to-face contact, such as in certain sports.
 

How to protect toddlers and infants

With masks not practical or recommended for infants and toddlers under 2 years old, Dr. Marrazzo said adults should remember that ‘’those very little kids don’t do poorly at all [even if infected], although there is not a ton of data.”

Adults should still treat young children as vulnerable, especially newborns. Adults not yet vaccinated should wear a mask when around them, she said.
 

J & J vaccine recipients

With less ‘’real world” data on the Johnson & Johnson vaccine, should those who got it think of themselves in a different risk group than those who got Moderna or Pfizer and adjust their behavior accordingly? 

“The J&J vaccine, based on everything we know, does provide a great deal of protection,” Dr. Marrazzo said. ‘’We don’t know as much about prevention of transmission in the asymptomatic cases in the J&J.”

Most of that data, she said, is from the mRNA vaccines Pfizer and Moderna. “I think it’s an important area to study and learn about.” But all three vaccines, overall, provide a high level of protection, she said.

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

Older people with prediabetes who followed a diet rich in sardines for 1 year show significant reductions in risk of developing type 2 diabetes compared with those placed on a similarly healthy diet but without the sardines, results from a new randomized trial show. 

“A 1-year, sardine-enriched type 2 diabetes-preventive diet in an elderly population with prediabetes exerts a greater protective effect against developing type 2 diabetes and cardiovascular events, by improving anthropometric parameters, blood chemistry profile, lipid composition in erythrocytes membranes, and metabolomics data,” report the authors in research published in Clinical Nutrition by Diana Díaz-Rizzolo, PhD, of the Hospital Clinic of Barcelona, Spain, and colleagues.

While cardiovascular and other health benefits of unsaturated fats in oily fish are well-established and are a key component in diets such as the highly recommended Mediterranean diet, the authors note that the consumption of sardines for the prevention of type 2 diabetes has not previously been studied.

In addition to being rich in healthy omega-3 fatty acids, sardines have high concentrations of taurine – approximately 147 mg per 100 g serving – which, depending on the sardine species, is believed to have hypoglycemic, antioxidant, and anti-inflammatory benefits, the authors note.
 

Participants advised to consume the whole sardine, bones and all

To evaluate the effects, researchers enrolled 152 patients aged 65 and older who had been diagnosed with prediabetes (blood glucose levels between 100-124 mg/dL) and placed them all on a nutritional program to reduce the risk of diabetes for 1 year.

In addition, about half (n = 75) were also instructed to consume 200 g of canned sardines in olive oil per week, in 100 g servings consumed twice per week.

Those participants were recommended to consume the entire sardine, without removal of bones, due to their rich content of calcium and vitamin D. They were also provided with recipes that used canned sardines.

At 1 year, the percentage of participants classified as being at a very high risk of type 2 diabetes, assessed by the Finnish Diabetes Risk Score (FINDRISC), compared with baseline, had declined to a much greater degree in the sardine consumption group (37% at baseline vs. 8% at 1 year) compared with those in the control group, who only consumed the nutritional diet (27% vs. 22%) (P = .021).

In addition, those in the sardine group had greater increases in healthy HDL cholesterol and the glucose-regulating protein hormone adiponectin, with decreases in triglycerides compared with the nonsardine group (all P < .005).

Furthermore, the sardine consumption group had a greater decrease in insulin resistance, assessed by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR; P = .032).
 

Sardines are cheap and reduce blood pressure too

“Not only are sardines reasonably priced and easy to find, but they are safe and help to prevent the onset of type 2 diabetes,” said Dr. Díaz-Rizzolo in a press statement.

Those in the sardine group also showed significant decreases in systolic blood pressure (P = .014) and diastolic blood pressure (P = .020) versus baseline, while no significant changes were observed in the control group. The authors suggest that sardines’ rich taurine concentrations could play a role in those effects.

“Previously, only lean fish consumption had demonstrated an improvement in blood pressure, not fatty fish consumption, perhaps because the species studied excluded those with a higher taurine content such as sardines,” they speculate.

In addition to showing improvements in levels of taurine, those in the sardine group also showed increases in nutrients that have been linked to health benefits, including omega-3 EPA and DHA, vitamin D, and fluorine (all P < .05).

The authors note that the increases could be attributed to sardines’ rich concentration of those nutrients, as well as to the olive oil that is present in the sardine can.
 

Some benefits seen in both groups

The patients in the study were a mean age of 71 and had been in a prediabetic state for an average of 4.8 years at the beginning of the study. They were 55% male and there were no other significant differences in characteristics between the groups.

While the conversion from being prediabetic to type 2 diabetes in the adult population has been reported to be about 10.6%, and the risk has been observed to be even higher in the 65 and older population, rates were lower than that in both groups.

“At the end of our 1-year study, we observed a [rate of] new-onset type 2 diabetes of 2.7% and 5.2% in the sardine group and control group, respectively,” the authors note. They add the differences were not statistically significant.

Both the sardine consumption and control groups showed significant reductions in A1c versus baseline (P = .011 and P = .010, respectively), as well as significant reductions in glucose fasting concentrations (P = .020 and P = .040, respectively).

And while the sardine group showed greater improvements in HDL versus the control group (P = .045), only the control group showed a significant decrease in total cholesterol versus baseline (P = .032).

Both groups showed improvements in the management of body weight, body mass index, and waist and hip circumference, in addition to improvement in body composition – despite no physical activity components in the programs, the authors note.

“This is probably because both groups followed the same base type 2 diabetes-preventive diet, with the one exception of sardine supplementation, and, although they did not modify their physical activity, both groups reduced their daily caloric intake through food,” the authors note.

The possibility of reducing diabetes risk through dietary changes as opposed to weight loss is especially important in the older population, the authors note, as some studies suggest a link between weight loss in the elderly and an increased risk of mortality.

In a second phase of the study, the researchers say they are evaluating the effect of sardines on the intestinal microbiota, “since it affects the regulation of many biological processes, and we need to understand if they have played a part in this protective effect against type 2 diabetes,” Dr. Díaz-Rizzolo concluded.

The study was funded by RecerCaixa 2013. The authors report that “no industry sponsorship was received for this work that could have influenced its outcome.”

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

Older people with prediabetes who followed a diet rich in sardines for 1 year show significant reductions in risk of developing type 2 diabetes compared with those placed on a similarly healthy diet but without the sardines, results from a new randomized trial show. 

“A 1-year, sardine-enriched type 2 diabetes-preventive diet in an elderly population with prediabetes exerts a greater protective effect against developing type 2 diabetes and cardiovascular events, by improving anthropometric parameters, blood chemistry profile, lipid composition in erythrocytes membranes, and metabolomics data,” report the authors in research published in Clinical Nutrition by Diana Díaz-Rizzolo, PhD, of the Hospital Clinic of Barcelona, Spain, and colleagues.

While cardiovascular and other health benefits of unsaturated fats in oily fish are well-established and are a key component in diets such as the highly recommended Mediterranean diet, the authors note that the consumption of sardines for the prevention of type 2 diabetes has not previously been studied.

In addition to being rich in healthy omega-3 fatty acids, sardines have high concentrations of taurine – approximately 147 mg per 100 g serving – which, depending on the sardine species, is believed to have hypoglycemic, antioxidant, and anti-inflammatory benefits, the authors note.
 

Participants advised to consume the whole sardine, bones and all

To evaluate the effects, researchers enrolled 152 patients aged 65 and older who had been diagnosed with prediabetes (blood glucose levels between 100-124 mg/dL) and placed them all on a nutritional program to reduce the risk of diabetes for 1 year.

In addition, about half (n = 75) were also instructed to consume 200 g of canned sardines in olive oil per week, in 100 g servings consumed twice per week.

Those participants were recommended to consume the entire sardine, without removal of bones, due to their rich content of calcium and vitamin D. They were also provided with recipes that used canned sardines.

At 1 year, the percentage of participants classified as being at a very high risk of type 2 diabetes, assessed by the Finnish Diabetes Risk Score (FINDRISC), compared with baseline, had declined to a much greater degree in the sardine consumption group (37% at baseline vs. 8% at 1 year) compared with those in the control group, who only consumed the nutritional diet (27% vs. 22%) (P = .021).

In addition, those in the sardine group had greater increases in healthy HDL cholesterol and the glucose-regulating protein hormone adiponectin, with decreases in triglycerides compared with the nonsardine group (all P < .005).

Furthermore, the sardine consumption group had a greater decrease in insulin resistance, assessed by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR; P = .032).
 

Sardines are cheap and reduce blood pressure too

“Not only are sardines reasonably priced and easy to find, but they are safe and help to prevent the onset of type 2 diabetes,” said Dr. Díaz-Rizzolo in a press statement.

Those in the sardine group also showed significant decreases in systolic blood pressure (P = .014) and diastolic blood pressure (P = .020) versus baseline, while no significant changes were observed in the control group. The authors suggest that sardines’ rich taurine concentrations could play a role in those effects.

“Previously, only lean fish consumption had demonstrated an improvement in blood pressure, not fatty fish consumption, perhaps because the species studied excluded those with a higher taurine content such as sardines,” they speculate.

In addition to showing improvements in levels of taurine, those in the sardine group also showed increases in nutrients that have been linked to health benefits, including omega-3 EPA and DHA, vitamin D, and fluorine (all P < .05).

The authors note that the increases could be attributed to sardines’ rich concentration of those nutrients, as well as to the olive oil that is present in the sardine can.
 

Some benefits seen in both groups

The patients in the study were a mean age of 71 and had been in a prediabetic state for an average of 4.8 years at the beginning of the study. They were 55% male and there were no other significant differences in characteristics between the groups.

While the conversion from being prediabetic to type 2 diabetes in the adult population has been reported to be about 10.6%, and the risk has been observed to be even higher in the 65 and older population, rates were lower than that in both groups.

“At the end of our 1-year study, we observed a [rate of] new-onset type 2 diabetes of 2.7% and 5.2% in the sardine group and control group, respectively,” the authors note. They add the differences were not statistically significant.

Both the sardine consumption and control groups showed significant reductions in A1c versus baseline (P = .011 and P = .010, respectively), as well as significant reductions in glucose fasting concentrations (P = .020 and P = .040, respectively).

And while the sardine group showed greater improvements in HDL versus the control group (P = .045), only the control group showed a significant decrease in total cholesterol versus baseline (P = .032).

Both groups showed improvements in the management of body weight, body mass index, and waist and hip circumference, in addition to improvement in body composition – despite no physical activity components in the programs, the authors note.

“This is probably because both groups followed the same base type 2 diabetes-preventive diet, with the one exception of sardine supplementation, and, although they did not modify their physical activity, both groups reduced their daily caloric intake through food,” the authors note.

The possibility of reducing diabetes risk through dietary changes as opposed to weight loss is especially important in the older population, the authors note, as some studies suggest a link between weight loss in the elderly and an increased risk of mortality.

In a second phase of the study, the researchers say they are evaluating the effect of sardines on the intestinal microbiota, “since it affects the regulation of many biological processes, and we need to understand if they have played a part in this protective effect against type 2 diabetes,” Dr. Díaz-Rizzolo concluded.

The study was funded by RecerCaixa 2013. The authors report that “no industry sponsorship was received for this work that could have influenced its outcome.”

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

Older people with prediabetes who followed a diet rich in sardines for 1 year show significant reductions in risk of developing type 2 diabetes compared with those placed on a similarly healthy diet but without the sardines, results from a new randomized trial show. 

“A 1-year, sardine-enriched type 2 diabetes-preventive diet in an elderly population with prediabetes exerts a greater protective effect against developing type 2 diabetes and cardiovascular events, by improving anthropometric parameters, blood chemistry profile, lipid composition in erythrocytes membranes, and metabolomics data,” report the authors in research published in Clinical Nutrition by Diana Díaz-Rizzolo, PhD, of the Hospital Clinic of Barcelona, Spain, and colleagues.

While cardiovascular and other health benefits of unsaturated fats in oily fish are well-established and are a key component in diets such as the highly recommended Mediterranean diet, the authors note that the consumption of sardines for the prevention of type 2 diabetes has not previously been studied.

In addition to being rich in healthy omega-3 fatty acids, sardines have high concentrations of taurine – approximately 147 mg per 100 g serving – which, depending on the sardine species, is believed to have hypoglycemic, antioxidant, and anti-inflammatory benefits, the authors note.
 

Participants advised to consume the whole sardine, bones and all

To evaluate the effects, researchers enrolled 152 patients aged 65 and older who had been diagnosed with prediabetes (blood glucose levels between 100-124 mg/dL) and placed them all on a nutritional program to reduce the risk of diabetes for 1 year.

In addition, about half (n = 75) were also instructed to consume 200 g of canned sardines in olive oil per week, in 100 g servings consumed twice per week.

Those participants were recommended to consume the entire sardine, without removal of bones, due to their rich content of calcium and vitamin D. They were also provided with recipes that used canned sardines.

At 1 year, the percentage of participants classified as being at a very high risk of type 2 diabetes, assessed by the Finnish Diabetes Risk Score (FINDRISC), compared with baseline, had declined to a much greater degree in the sardine consumption group (37% at baseline vs. 8% at 1 year) compared with those in the control group, who only consumed the nutritional diet (27% vs. 22%) (P = .021).

In addition, those in the sardine group had greater increases in healthy HDL cholesterol and the glucose-regulating protein hormone adiponectin, with decreases in triglycerides compared with the nonsardine group (all P < .005).

Furthermore, the sardine consumption group had a greater decrease in insulin resistance, assessed by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR; P = .032).
 

Sardines are cheap and reduce blood pressure too

“Not only are sardines reasonably priced and easy to find, but they are safe and help to prevent the onset of type 2 diabetes,” said Dr. Díaz-Rizzolo in a press statement.

Those in the sardine group also showed significant decreases in systolic blood pressure (P = .014) and diastolic blood pressure (P = .020) versus baseline, while no significant changes were observed in the control group. The authors suggest that sardines’ rich taurine concentrations could play a role in those effects.

“Previously, only lean fish consumption had demonstrated an improvement in blood pressure, not fatty fish consumption, perhaps because the species studied excluded those with a higher taurine content such as sardines,” they speculate.

In addition to showing improvements in levels of taurine, those in the sardine group also showed increases in nutrients that have been linked to health benefits, including omega-3 EPA and DHA, vitamin D, and fluorine (all P < .05).

The authors note that the increases could be attributed to sardines’ rich concentration of those nutrients, as well as to the olive oil that is present in the sardine can.
 

Some benefits seen in both groups

The patients in the study were a mean age of 71 and had been in a prediabetic state for an average of 4.8 years at the beginning of the study. They were 55% male and there were no other significant differences in characteristics between the groups.

While the conversion from being prediabetic to type 2 diabetes in the adult population has been reported to be about 10.6%, and the risk has been observed to be even higher in the 65 and older population, rates were lower than that in both groups.

“At the end of our 1-year study, we observed a [rate of] new-onset type 2 diabetes of 2.7% and 5.2% in the sardine group and control group, respectively,” the authors note. They add the differences were not statistically significant.

Both the sardine consumption and control groups showed significant reductions in A1c versus baseline (P = .011 and P = .010, respectively), as well as significant reductions in glucose fasting concentrations (P = .020 and P = .040, respectively).

And while the sardine group showed greater improvements in HDL versus the control group (P = .045), only the control group showed a significant decrease in total cholesterol versus baseline (P = .032).

Both groups showed improvements in the management of body weight, body mass index, and waist and hip circumference, in addition to improvement in body composition – despite no physical activity components in the programs, the authors note.

“This is probably because both groups followed the same base type 2 diabetes-preventive diet, with the one exception of sardine supplementation, and, although they did not modify their physical activity, both groups reduced their daily caloric intake through food,” the authors note.

The possibility of reducing diabetes risk through dietary changes as opposed to weight loss is especially important in the older population, the authors note, as some studies suggest a link between weight loss in the elderly and an increased risk of mortality.

In a second phase of the study, the researchers say they are evaluating the effect of sardines on the intestinal microbiota, “since it affects the regulation of many biological processes, and we need to understand if they have played a part in this protective effect against type 2 diabetes,” Dr. Díaz-Rizzolo concluded.

The study was funded by RecerCaixa 2013. The authors report that “no industry sponsorship was received for this work that could have influenced its outcome.”

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

Polycystic ovary syndrome, the most common endocrinopathy and most common cause of female infertility, affects 8%-13% of reproductive-aged women. PCOS has a profound impact on a woman’s life yet its diagnosis and management remain confusing despite being first described nearly a century ago by Stein and Leventhal.

To illustrate, in a global survey of 1,385 women with PCOS, one-third or more reported a delay of greater than 2 years and nearly half required evaluation by at least three health professionals before a diagnosis was established (J Clin Endocrinol Metab. 2017;102[2]:604-12). A vital health problem that urgently requires a gap analysis and needs assessment, PCOS is not “just about fertility” but has extensive gynecologic and metabolic consequences that require a personalized approach to care coordinated among the fields of internal medicine, pediatrics, dermatology, and, of course, gynecology.
 

Diagnosis in adults and adolescence

Normal menstrual intervals do not always equate with ovulation. Up to 40% of hirsute women with monthly cycles may not ovulate regularly. The Rotterdam criteria are used to confirm PCOS and require two of the following three: 1) ovulation dysfunction (cycle interval > 35 d or < 8 cycles/year); 2) hyperandrogenism (i.e., elevated total or free testosterone, DHEAS, or signs of hirsutism or acne with Ferriman-Gallwey score greater than 6); 3) polycystic ovaries on ultrasound (20 or more 2- to 9-mm follicles on at least one ovary, and/or increased ovarian volume (> 10 mL) – all at the exclusion of other etiologies including hyperprolactinemia, thyroid dysfunction, androgen-secreting tumors including Cushing’s syndrome, and nonclassic adrenal hyperplasia mostly easily screened by obtaining 17-hydroxyprogesterone.

For adolescents, by age 14 most will have adult androgen levels. Ovarian ultrasound should not be used as a criterion in this age group given the frequency of this appearance. Due to frequent menstrual irregularity, it is recommended to wait at least 2 years post menarche before consideration of a diagnosis.

Antimüllerian hormone is two- to threefold higher in women with PCOS but this hormone level has not yet been accepted as a diagnostic criterion.
 

The metabolic connection

A multisystem disorder whose name misdirects its morbidity, PCOS affects the metabolic, reproductive, and psychological system through vicious cycles of distorted feedback signals. Without a consensus of its origin, there appears to be a hypersensitivity of pituitary luteinizing hormone (LH) to hypothalamic gonadotrophin-releasing hormone. Consequently, elevated LH stimulates ovarian theca cells to increase androgens with resultant hyperandrogenic consequences. Parenthetically, the tonic elevation in LH explains the false-positive surges PCOS women experience when testing their urine during ovulation induction.

Elevations in insulin from unexplained damage to the insulin receptor acts synergistically with LH to increase ovarian androgens and inhibit ovulation. Hyperinsulinemia and abdominal fat deposition contribute to impaired glucose tolerance which is threefold higher with PCOS.

The metabolic syndrome, an association of disorders including hypertension, impaired glucose tolerance, dyslipidemia, and obesity, occurs at an increased overall prevalence rate of 43%-47% in women with PCOS, which is twice as high as in women without PCOS. PCOS is associated with low-grade chronic inflammation, which places these women at increased risk of nonalcoholic fatty liver disease. Dyslipidemia is the most common metabolic disorder in PCOS. These metabolic consequences, including obstructive sleep apnea, are worsened by hyperandrogenemia and an elevated BMI.
 

A genetic link

Multigenetic in origin, PCOS has a fivefold higher risk of inheritance from mothers with PCOS to daughters influenced by prenatal androgen exposure in utero. Genetic studies suggest a causal relationship between PCOS with body mass index, insulin resistance, onset of menopause, depression, and male-pattern balding (PLoS Genet 2018;14[12]:e10007813).

Fifteen genetic risk areas in the human genome seem to predispose to PCOS. New results suggest that altering the gut microbiome via prebiotic or probiotic therapies may be a potential treatment option.
 

Reproductive and gynecologic management

Due to chronic anovulation, unopposed estrogen can result in abnormal endometrial bleeding, endometrial hyperplasia, and a fourfold risk of endometrial cancer. This underscores the importance of regular progestin withdrawal, combined oral contraception (COC), or a progestin intrauterine device.

PCOS is a leading cause of infertility and is associated with abnormal bleeding, miscarriage, gestational diabetes, and gestational hypertension, all of which are higher based on a hyperandrogenic phenotype.

The rate of infertility in women with PCOS is 70%-80%, with ovulation dysfunction being the dominant cause. For years, the mainstay for ovulation induction was clomiphene citrate; however, letrozole has shown higher pregnancy success rates, particularly in women who have a BMI greater than 30 kg/m². (N Engl J Med. 2014;371:119-29). Despite multiple studies demonstrating its efficacy and safety, letrozole remains without Food and Drug Administration approval for ovulation induction.

Metformin has been recommended in women with prediabetes or a BMI above 30, and it may improve menstrual regularity but has not been shown to improve live birth rates nor reduce the pregnancy complications of miscarriage or gestational diabetes. Inositol, the ubiquitous endogenous carbohydrate, has not demonstrated clear improvement in reproduction.

Laparoscopic ovarian diathermy (LOD) is a second-line treatment option, as is the use of gonadotropins, to overcome unsuccessful conservative attempts at ovulation induction. LOD is more invasive but outcomes are equivalent to gonadotropin usage while providing a dramatic reduction in multiple gestation, ovarian hyperstimulation syndrome, and cost (not including the surgical procedure). Ultimately, in vitro fertilization is an option for continued infertility in women with PCOS.
 

Metabolic/gynecologic management

Given the multisystem effect of PCOS, health care providers caring for these women should be vigilant and aggressive at ensuring appropriate monitoring and management. For women with PCOS with an elevated BMI, lifestyle modification is the first line of management. Weight loss alone of only 2%-5% may restore ovulation function.

The combination of dyslipidemia, elevated BMI, and impaired glucose tolerance would presumably predict the risk of cardiovascular events, yet the impact is not proven. Despite an increase in carotid intima media thickness, there are data that suggest only an increase in stroke or myocardial infarction (J Clin Endocrinol Metab. 2019;104[4]:1221-31).

Hyperandrogenism is cosmetically and psychologically disrupting to PCOS patients. The topical application of eflornithine hydrochloride may be of value for mild to moderate facial hair growth. Spironolactone is the preferred first-line agent. (Caution: effective contraception is necessary to avoid feminization of a male fetus). Women with PCOS have a higher risk of disordered eating and body image distress as well as a fivefold higher rate of mental distress such as anxiety and depression.

No specific diet has been determined as part of treatment, yet healthy food selection and caloric intake combined with exercise has been shown to improve metabolic and psychological well-being.
 

Conclusion

PCOS is a ubiquitous, frustrating, and life-altering disease. Health care providers, particularly those in women’s health, must ensure appropriate counseling and education with evidence-based medicine to empower patients toward improved health.

Dr. Trolice is director of Fertility CARE - The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. He has no conflicts of interest. Please contact him at [email protected].

Polycystic ovary syndrome, the most common endocrinopathy and most common cause of female infertility, affects 8%-13% of reproductive-aged women. PCOS has a profound impact on a woman’s life yet its diagnosis and management remain confusing despite being first described nearly a century ago by Stein and Leventhal.

To illustrate, in a global survey of 1,385 women with PCOS, one-third or more reported a delay of greater than 2 years and nearly half required evaluation by at least three health professionals before a diagnosis was established (J Clin Endocrinol Metab. 2017;102[2]:604-12). A vital health problem that urgently requires a gap analysis and needs assessment, PCOS is not “just about fertility” but has extensive gynecologic and metabolic consequences that require a personalized approach to care coordinated among the fields of internal medicine, pediatrics, dermatology, and, of course, gynecology.
 

Diagnosis in adults and adolescence

Normal menstrual intervals do not always equate with ovulation. Up to 40% of hirsute women with monthly cycles may not ovulate regularly. The Rotterdam criteria are used to confirm PCOS and require two of the following three: 1) ovulation dysfunction (cycle interval > 35 d or < 8 cycles/year); 2) hyperandrogenism (i.e., elevated total or free testosterone, DHEAS, or signs of hirsutism or acne with Ferriman-Gallwey score greater than 6); 3) polycystic ovaries on ultrasound (20 or more 2- to 9-mm follicles on at least one ovary, and/or increased ovarian volume (> 10 mL) – all at the exclusion of other etiologies including hyperprolactinemia, thyroid dysfunction, androgen-secreting tumors including Cushing’s syndrome, and nonclassic adrenal hyperplasia mostly easily screened by obtaining 17-hydroxyprogesterone.

For adolescents, by age 14 most will have adult androgen levels. Ovarian ultrasound should not be used as a criterion in this age group given the frequency of this appearance. Due to frequent menstrual irregularity, it is recommended to wait at least 2 years post menarche before consideration of a diagnosis.

Antimüllerian hormone is two- to threefold higher in women with PCOS but this hormone level has not yet been accepted as a diagnostic criterion.
 

The metabolic connection

A multisystem disorder whose name misdirects its morbidity, PCOS affects the metabolic, reproductive, and psychological system through vicious cycles of distorted feedback signals. Without a consensus of its origin, there appears to be a hypersensitivity of pituitary luteinizing hormone (LH) to hypothalamic gonadotrophin-releasing hormone. Consequently, elevated LH stimulates ovarian theca cells to increase androgens with resultant hyperandrogenic consequences. Parenthetically, the tonic elevation in LH explains the false-positive surges PCOS women experience when testing their urine during ovulation induction.

Elevations in insulin from unexplained damage to the insulin receptor acts synergistically with LH to increase ovarian androgens and inhibit ovulation. Hyperinsulinemia and abdominal fat deposition contribute to impaired glucose tolerance which is threefold higher with PCOS.

The metabolic syndrome, an association of disorders including hypertension, impaired glucose tolerance, dyslipidemia, and obesity, occurs at an increased overall prevalence rate of 43%-47% in women with PCOS, which is twice as high as in women without PCOS. PCOS is associated with low-grade chronic inflammation, which places these women at increased risk of nonalcoholic fatty liver disease. Dyslipidemia is the most common metabolic disorder in PCOS. These metabolic consequences, including obstructive sleep apnea, are worsened by hyperandrogenemia and an elevated BMI.
 

A genetic link

Multigenetic in origin, PCOS has a fivefold higher risk of inheritance from mothers with PCOS to daughters influenced by prenatal androgen exposure in utero. Genetic studies suggest a causal relationship between PCOS with body mass index, insulin resistance, onset of menopause, depression, and male-pattern balding (PLoS Genet 2018;14[12]:e10007813).

Fifteen genetic risk areas in the human genome seem to predispose to PCOS. New results suggest that altering the gut microbiome via prebiotic or probiotic therapies may be a potential treatment option.
 

Reproductive and gynecologic management

Due to chronic anovulation, unopposed estrogen can result in abnormal endometrial bleeding, endometrial hyperplasia, and a fourfold risk of endometrial cancer. This underscores the importance of regular progestin withdrawal, combined oral contraception (COC), or a progestin intrauterine device.

PCOS is a leading cause of infertility and is associated with abnormal bleeding, miscarriage, gestational diabetes, and gestational hypertension, all of which are higher based on a hyperandrogenic phenotype.

The rate of infertility in women with PCOS is 70%-80%, with ovulation dysfunction being the dominant cause. For years, the mainstay for ovulation induction was clomiphene citrate; however, letrozole has shown higher pregnancy success rates, particularly in women who have a BMI greater than 30 kg/m². (N Engl J Med. 2014;371:119-29). Despite multiple studies demonstrating its efficacy and safety, letrozole remains without Food and Drug Administration approval for ovulation induction.

Metformin has been recommended in women with prediabetes or a BMI above 30, and it may improve menstrual regularity but has not been shown to improve live birth rates nor reduce the pregnancy complications of miscarriage or gestational diabetes. Inositol, the ubiquitous endogenous carbohydrate, has not demonstrated clear improvement in reproduction.

Laparoscopic ovarian diathermy (LOD) is a second-line treatment option, as is the use of gonadotropins, to overcome unsuccessful conservative attempts at ovulation induction. LOD is more invasive but outcomes are equivalent to gonadotropin usage while providing a dramatic reduction in multiple gestation, ovarian hyperstimulation syndrome, and cost (not including the surgical procedure). Ultimately, in vitro fertilization is an option for continued infertility in women with PCOS.
 

Metabolic/gynecologic management

Given the multisystem effect of PCOS, health care providers caring for these women should be vigilant and aggressive at ensuring appropriate monitoring and management. For women with PCOS with an elevated BMI, lifestyle modification is the first line of management. Weight loss alone of only 2%-5% may restore ovulation function.

The combination of dyslipidemia, elevated BMI, and impaired glucose tolerance would presumably predict the risk of cardiovascular events, yet the impact is not proven. Despite an increase in carotid intima media thickness, there are data that suggest only an increase in stroke or myocardial infarction (J Clin Endocrinol Metab. 2019;104[4]:1221-31).

Hyperandrogenism is cosmetically and psychologically disrupting to PCOS patients. The topical application of eflornithine hydrochloride may be of value for mild to moderate facial hair growth. Spironolactone is the preferred first-line agent. (Caution: effective contraception is necessary to avoid feminization of a male fetus). Women with PCOS have a higher risk of disordered eating and body image distress as well as a fivefold higher rate of mental distress such as anxiety and depression.

No specific diet has been determined as part of treatment, yet healthy food selection and caloric intake combined with exercise has been shown to improve metabolic and psychological well-being.
 

Conclusion

PCOS is a ubiquitous, frustrating, and life-altering disease. Health care providers, particularly those in women’s health, must ensure appropriate counseling and education with evidence-based medicine to empower patients toward improved health.

Dr. Trolice is director of Fertility CARE - The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. He has no conflicts of interest. Please contact him at [email protected].

Polycystic ovary syndrome, the most common endocrinopathy and most common cause of female infertility, affects 8%-13% of reproductive-aged women. PCOS has a profound impact on a woman’s life yet its diagnosis and management remain confusing despite being first described nearly a century ago by Stein and Leventhal.

To illustrate, in a global survey of 1,385 women with PCOS, one-third or more reported a delay of greater than 2 years and nearly half required evaluation by at least three health professionals before a diagnosis was established (J Clin Endocrinol Metab. 2017;102[2]:604-12). A vital health problem that urgently requires a gap analysis and needs assessment, PCOS is not “just about fertility” but has extensive gynecologic and metabolic consequences that require a personalized approach to care coordinated among the fields of internal medicine, pediatrics, dermatology, and, of course, gynecology.
 

Diagnosis in adults and adolescence

Normal menstrual intervals do not always equate with ovulation. Up to 40% of hirsute women with monthly cycles may not ovulate regularly. The Rotterdam criteria are used to confirm PCOS and require two of the following three: 1) ovulation dysfunction (cycle interval > 35 d or < 8 cycles/year); 2) hyperandrogenism (i.e., elevated total or free testosterone, DHEAS, or signs of hirsutism or acne with Ferriman-Gallwey score greater than 6); 3) polycystic ovaries on ultrasound (20 or more 2- to 9-mm follicles on at least one ovary, and/or increased ovarian volume (> 10 mL) – all at the exclusion of other etiologies including hyperprolactinemia, thyroid dysfunction, androgen-secreting tumors including Cushing’s syndrome, and nonclassic adrenal hyperplasia mostly easily screened by obtaining 17-hydroxyprogesterone.

For adolescents, by age 14 most will have adult androgen levels. Ovarian ultrasound should not be used as a criterion in this age group given the frequency of this appearance. Due to frequent menstrual irregularity, it is recommended to wait at least 2 years post menarche before consideration of a diagnosis.

Antimüllerian hormone is two- to threefold higher in women with PCOS but this hormone level has not yet been accepted as a diagnostic criterion.
 

The metabolic connection

A multisystem disorder whose name misdirects its morbidity, PCOS affects the metabolic, reproductive, and psychological system through vicious cycles of distorted feedback signals. Without a consensus of its origin, there appears to be a hypersensitivity of pituitary luteinizing hormone (LH) to hypothalamic gonadotrophin-releasing hormone. Consequently, elevated LH stimulates ovarian theca cells to increase androgens with resultant hyperandrogenic consequences. Parenthetically, the tonic elevation in LH explains the false-positive surges PCOS women experience when testing their urine during ovulation induction.

Elevations in insulin from unexplained damage to the insulin receptor acts synergistically with LH to increase ovarian androgens and inhibit ovulation. Hyperinsulinemia and abdominal fat deposition contribute to impaired glucose tolerance which is threefold higher with PCOS.

The metabolic syndrome, an association of disorders including hypertension, impaired glucose tolerance, dyslipidemia, and obesity, occurs at an increased overall prevalence rate of 43%-47% in women with PCOS, which is twice as high as in women without PCOS. PCOS is associated with low-grade chronic inflammation, which places these women at increased risk of nonalcoholic fatty liver disease. Dyslipidemia is the most common metabolic disorder in PCOS. These metabolic consequences, including obstructive sleep apnea, are worsened by hyperandrogenemia and an elevated BMI.
 

A genetic link

Multigenetic in origin, PCOS has a fivefold higher risk of inheritance from mothers with PCOS to daughters influenced by prenatal androgen exposure in utero. Genetic studies suggest a causal relationship between PCOS with body mass index, insulin resistance, onset of menopause, depression, and male-pattern balding (PLoS Genet 2018;14[12]:e10007813).

Fifteen genetic risk areas in the human genome seem to predispose to PCOS. New results suggest that altering the gut microbiome via prebiotic or probiotic therapies may be a potential treatment option.
 

Reproductive and gynecologic management

Due to chronic anovulation, unopposed estrogen can result in abnormal endometrial bleeding, endometrial hyperplasia, and a fourfold risk of endometrial cancer. This underscores the importance of regular progestin withdrawal, combined oral contraception (COC), or a progestin intrauterine device.

PCOS is a leading cause of infertility and is associated with abnormal bleeding, miscarriage, gestational diabetes, and gestational hypertension, all of which are higher based on a hyperandrogenic phenotype.

The rate of infertility in women with PCOS is 70%-80%, with ovulation dysfunction being the dominant cause. For years, the mainstay for ovulation induction was clomiphene citrate; however, letrozole has shown higher pregnancy success rates, particularly in women who have a BMI greater than 30 kg/m². (N Engl J Med. 2014;371:119-29). Despite multiple studies demonstrating its efficacy and safety, letrozole remains without Food and Drug Administration approval for ovulation induction.

Metformin has been recommended in women with prediabetes or a BMI above 30, and it may improve menstrual regularity but has not been shown to improve live birth rates nor reduce the pregnancy complications of miscarriage or gestational diabetes. Inositol, the ubiquitous endogenous carbohydrate, has not demonstrated clear improvement in reproduction.

Laparoscopic ovarian diathermy (LOD) is a second-line treatment option, as is the use of gonadotropins, to overcome unsuccessful conservative attempts at ovulation induction. LOD is more invasive but outcomes are equivalent to gonadotropin usage while providing a dramatic reduction in multiple gestation, ovarian hyperstimulation syndrome, and cost (not including the surgical procedure). Ultimately, in vitro fertilization is an option for continued infertility in women with PCOS.
 

Metabolic/gynecologic management

Given the multisystem effect of PCOS, health care providers caring for these women should be vigilant and aggressive at ensuring appropriate monitoring and management. For women with PCOS with an elevated BMI, lifestyle modification is the first line of management. Weight loss alone of only 2%-5% may restore ovulation function.

The combination of dyslipidemia, elevated BMI, and impaired glucose tolerance would presumably predict the risk of cardiovascular events, yet the impact is not proven. Despite an increase in carotid intima media thickness, there are data that suggest only an increase in stroke or myocardial infarction (J Clin Endocrinol Metab. 2019;104[4]:1221-31).

Hyperandrogenism is cosmetically and psychologically disrupting to PCOS patients. The topical application of eflornithine hydrochloride may be of value for mild to moderate facial hair growth. Spironolactone is the preferred first-line agent. (Caution: effective contraception is necessary to avoid feminization of a male fetus). Women with PCOS have a higher risk of disordered eating and body image distress as well as a fivefold higher rate of mental distress such as anxiety and depression.

No specific diet has been determined as part of treatment, yet healthy food selection and caloric intake combined with exercise has been shown to improve metabolic and psychological well-being.
 

Conclusion

PCOS is a ubiquitous, frustrating, and life-altering disease. Health care providers, particularly those in women’s health, must ensure appropriate counseling and education with evidence-based medicine to empower patients toward improved health.

Dr. Trolice is director of Fertility CARE - The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. He has no conflicts of interest. Please contact him at [email protected].

No ifs, ands, or butt ventilators

Breathing, on most days, is a pretty simple task. You inhale, the oxygen goes in, fills your lungs, becomes carbon dioxide, and is exhaled. But as certain recent events have made very clear, some diseases make this task difficult, which is where ventilators come in. The issue is, some patients can’t really use ventilators.

Enter a new study from Japan, which tested the ability of mice and pigs to absorb oxygen through the rectum. Yes, breathing through the butt. It’s not actually such a far-fetched idea; several aquatic animals such as sea cucumbers and catfish absorb oxygen through their intestines, and as any drunken frat boy can tell you after a good butt chug, other chemicals can absolutely be absorbed by human intestines.

After an initial successful experiment where a group of mice had their intestines scrubbed, had pure oxygen inserted enterally, and were exposed to a hypoxic environment, the researchers decided to step up their game and avoid the exhaustive act of digestive scrubbing by enlisting the aid of something out of science fiction: perfluorocarbon. If you haven’t seen “The Abyss,” this liquid can absorb massive amounts of oxygen, so you can actually breathe it in the same way you do with air.

Robert Jones/Pixabay

Better, stronger, faster … pinker

Many people, most of whom aren’t even athletes, commit huge amounts of time, effort, and expense to improve their athletic performance. But what if there’s an easier way?

Research conducted at the University of Westminster (England) showed that participants could, with one fairly simple intervention, get on a treadmill and run 212 meters further in 30 minutes, increasing their speed by an average of 4.4%. Not only that, but “feelings of pleasure were also enhanced, meaning participants found running more enjoyable,” according to a statement from the university.

Is this amazing intervention a new wonder drug? No. Is it a super special nutritional supplement? Negatory. An energy drink that “gives you wiiings”? Nope. The latest designer steroid? Nyet.

Kristan Hutchison (Property of National Science Foundation)

Hey … I’m singing here!

Noise pollution has been linked to plenty of negative outcomes, but the latest target is the poor baby zebra finch.

Researchers at the Max Planck Institute of Ornithology in Germany say traffic noise disrupts the timing of vocal development and impairs learning in the flying finches. The noise was also shown to suppress their immune systems, because of lingering stress.

pixel2013/pixabay

Slimy soap

Remember at the beginning of the pandemic when it was almost impossible to find sufficient hand-washing supplies? Just when you thought you’d tried everything, there is soap made from snail slime.

Snail slime, surprisingly, has many beneficial properties for humans. The slime has antiaging and skin healing properties and is actually used in some Korean beauty supplies. The snails even use the slime to help fix their shells if they become damaged.

Petra Göschel/Pixabay

No ifs, ands, or butt ventilators

Breathing, on most days, is a pretty simple task. You inhale, the oxygen goes in, fills your lungs, becomes carbon dioxide, and is exhaled. But as certain recent events have made very clear, some diseases make this task difficult, which is where ventilators come in. The issue is, some patients can’t really use ventilators.

Enter a new study from Japan, which tested the ability of mice and pigs to absorb oxygen through the rectum. Yes, breathing through the butt. It’s not actually such a far-fetched idea; several aquatic animals such as sea cucumbers and catfish absorb oxygen through their intestines, and as any drunken frat boy can tell you after a good butt chug, other chemicals can absolutely be absorbed by human intestines.

After an initial successful experiment where a group of mice had their intestines scrubbed, had pure oxygen inserted enterally, and were exposed to a hypoxic environment, the researchers decided to step up their game and avoid the exhaustive act of digestive scrubbing by enlisting the aid of something out of science fiction: perfluorocarbon. If you haven’t seen “The Abyss,” this liquid can absorb massive amounts of oxygen, so you can actually breathe it in the same way you do with air.

Robert Jones/Pixabay

Better, stronger, faster … pinker

Many people, most of whom aren’t even athletes, commit huge amounts of time, effort, and expense to improve their athletic performance. But what if there’s an easier way?

Research conducted at the University of Westminster (England) showed that participants could, with one fairly simple intervention, get on a treadmill and run 212 meters further in 30 minutes, increasing their speed by an average of 4.4%. Not only that, but “feelings of pleasure were also enhanced, meaning participants found running more enjoyable,” according to a statement from the university.

Is this amazing intervention a new wonder drug? No. Is it a super special nutritional supplement? Negatory. An energy drink that “gives you wiiings”? Nope. The latest designer steroid? Nyet.

Kristan Hutchison (Property of National Science Foundation)

Hey … I’m singing here!

Noise pollution has been linked to plenty of negative outcomes, but the latest target is the poor baby zebra finch.

Researchers at the Max Planck Institute of Ornithology in Germany say traffic noise disrupts the timing of vocal development and impairs learning in the flying finches. The noise was also shown to suppress their immune systems, because of lingering stress.

pixel2013/pixabay

Slimy soap

Remember at the beginning of the pandemic when it was almost impossible to find sufficient hand-washing supplies? Just when you thought you’d tried everything, there is soap made from snail slime.

Snail slime, surprisingly, has many beneficial properties for humans. The slime has antiaging and skin healing properties and is actually used in some Korean beauty supplies. The snails even use the slime to help fix their shells if they become damaged.

Petra Göschel/Pixabay

No ifs, ands, or butt ventilators

Breathing, on most days, is a pretty simple task. You inhale, the oxygen goes in, fills your lungs, becomes carbon dioxide, and is exhaled. But as certain recent events have made very clear, some diseases make this task difficult, which is where ventilators come in. The issue is, some patients can’t really use ventilators.

Enter a new study from Japan, which tested the ability of mice and pigs to absorb oxygen through the rectum. Yes, breathing through the butt. It’s not actually such a far-fetched idea; several aquatic animals such as sea cucumbers and catfish absorb oxygen through their intestines, and as any drunken frat boy can tell you after a good butt chug, other chemicals can absolutely be absorbed by human intestines.

After an initial successful experiment where a group of mice had their intestines scrubbed, had pure oxygen inserted enterally, and were exposed to a hypoxic environment, the researchers decided to step up their game and avoid the exhaustive act of digestive scrubbing by enlisting the aid of something out of science fiction: perfluorocarbon. If you haven’t seen “The Abyss,” this liquid can absorb massive amounts of oxygen, so you can actually breathe it in the same way you do with air.

Robert Jones/Pixabay

Better, stronger, faster … pinker

Many people, most of whom aren’t even athletes, commit huge amounts of time, effort, and expense to improve their athletic performance. But what if there’s an easier way?

Research conducted at the University of Westminster (England) showed that participants could, with one fairly simple intervention, get on a treadmill and run 212 meters further in 30 minutes, increasing their speed by an average of 4.4%. Not only that, but “feelings of pleasure were also enhanced, meaning participants found running more enjoyable,” according to a statement from the university.

Is this amazing intervention a new wonder drug? No. Is it a super special nutritional supplement? Negatory. An energy drink that “gives you wiiings”? Nope. The latest designer steroid? Nyet.

Kristan Hutchison (Property of National Science Foundation)

Hey … I’m singing here!

Noise pollution has been linked to plenty of negative outcomes, but the latest target is the poor baby zebra finch.

Researchers at the Max Planck Institute of Ornithology in Germany say traffic noise disrupts the timing of vocal development and impairs learning in the flying finches. The noise was also shown to suppress their immune systems, because of lingering stress.

pixel2013/pixabay

Slimy soap

Remember at the beginning of the pandemic when it was almost impossible to find sufficient hand-washing supplies? Just when you thought you’d tried everything, there is soap made from snail slime.

Snail slime, surprisingly, has many beneficial properties for humans. The slime has antiaging and skin healing properties and is actually used in some Korean beauty supplies. The snails even use the slime to help fix their shells if they become damaged.

Petra Göschel/Pixabay

Although use of some herbal and dietary supplements show statistically greater weight loss compared with placebo, it is not sufficient to benefit health, according to the joint findings of two systematic reviews, which are the first to comprehensively include all available herbal and dietary supplements for weight loss for over 15 years.

Sally Kubetin/MDedge News

“There is currently insufficient evidence to recommend any of the supplements we included in our reviews for weight loss,” stressed lead author Erica Bessell, a PhD candidate from the University of Sydney.

She added that some products with promising results warrant further investigation in well-conducted randomized controlled trials (RCTs) to determine their efficacy and safety.

But, overall, she would like to see a reduction in the number of products on the market without evidence to support their efficacy, “because, as we found, many of the products currently marketed for weight loss just do not work.

“Herbal and dietary supplements might seem like a quick-fix solution to weight problems, but people need to be aware of how little we actually know about them,” she said in an interview. “We would recommend that people trying to lose weight should save their money and seek out evidence-based care instead,” she emphasized.

The research was presented as two posters at this year’s online European Congress on Obesity (ECO). The meeting was presented by the European Association for the Study of Obesity.
 

Herbal and dietary supplement industry booming

Supplements for weight loss are growing in popularity, sustaining a rapidly expanding business sector globally. In the United States, the herbal and dietary supplements industry was estimated to be worth USD $41 billion in 2020, with 15% of Americans having tried a weight loss supplement in their efforts to shed pounds.

In light of this, Ms. Bessell said it is increasingly important to ensure supplements are efficacious and safe: “The popularity of these products underscores the urgency of conducting larger, more rigorous studies to have reasonable assurance of their safety and effectiveness for weight loss.”

Commenting on the study and the wider issues related to the surge in uptake of herbal and dietary supplements, Susan Arentz, PhD, said the evidence is similar to that for other complex interventions that people attempt for weight loss, including for example exercise, in that it is heterogeneous and low quality.

“One outstanding limitation for herbal medicine was the failure of trialists to validate the contents of interventions. Given the chemical variability of plants grown and harvested in different conditions, and the presence of pharmaceuticals and heavy metals found in some supplements ... future investigations of standardized herbal supplements and RCTs of higher methodological quality are needed,” remarked Dr. Arentz, a board member of the Australasian Integrative Medicine Association and researcher at Western Sydney University.

“Also, further RCTs are warranted due to the consumer preferences for natural treatments, especially in health settings with predominant use of traditional medicines and practices,” said Dr. Arentz.   
 

One review for herbal supplements, one for organic compounds

To accommodate the large number of trials investigating supplements for weight loss, the researchers conducted two systematic reviews, together representing 121 randomized placebo-controlled trials. One of the reviews investigated herbal supplements, and the other examined supplements with isolated organic compounds for example, specific fibers or lipids.  

Many of the included trials had been published in the last decade and had not been previously included in an up-to-date systematic review.

Ms. Bessell added that many studies often had a small sample size or were poorly designed, with insufficient information on the composition of supplements, and often featured little data on long-term effectiveness.

The two reviews primarily analyzed efficacy, not safety, because many of the studies did not report adverse effects.

The first review, published last year in Diabetes, Obesity and Metabolism, looked at 54 placebo-controlled randomized trials up to August 2018 on the effect of herbal supplements on weight loss . The study included 4,331 individuals aged 16 years or older who were overweight or obese. To be clinically meaningful, a weight loss of at least 2.5 kg was required over a period of, most often, 12 weeks or less.

Herbal supplements included in the analysis included green tea, Garcinia cambogia and mangosteen (tropical fruits), white kidney bean, ephedra (a stimulant that increases metabolism), African mango, yerba mate (herbal tea made from the leaves and twigs of the Ilex paraguariensis plant), veld grape (commonly used in Indian traditional medicine), licorice root, and East Indian Globe Thistle (used in Ayurvedic medicine).

The second review analyzed 67 randomized trials up to December 2019 that compared the effect of dietary supplements containing naturally occurring isolated organic compounds to placebo for weight loss in 5,194 individuals aged 16 years or older who were overweight or obese.

Meta-analyses were conducted for chitosan, glucomannan, conjugated linoleic acid, and fructans comparing the mean weight difference post intervention between participants receiving the dietary supplement and those on placebo.
 

No clinically significant results

Commenting on the overall results, Ms. Bessell said: “Though most supplements were safe for use in the short term, very few were found to produce clinically meaningful weight loss. Those that were found to result in clinically meaningful weight loss had only been investigated in one or two trials, so we need more research.”

The first review on herbal supplements found that only Phaseolus vulgaris (white kidney bean) resulted in significant weight loss compared with placebo, with an average weight difference of 1.61 kg (3.5 pounds). The result was not clinically meaningful, however.

For isolated organic compounds, significant weight differences compared with placebo were seen for chitosan, with a mean difference of 1.84 kg (4 pounds), glucomannan at 1.27 kg (2.8 pounds), and conjugated linoleic acid at 1.08 kg (2.4 pounds).

Again, none of these findings met the criteria for clinical significance (weight loss of 2.5 kg [5.5 pounds] or more).

In addition, some combination preparations containing African mango, veld grape, East Indian Globe Thistle, and mangosteen showed promising results with a mean weight difference of 1.85 kg (4 pounds), but were investigated in three or fewer trials, often with poor research methodology or reporting, and the findings should be interpreted with caution, the researchers noted.

Other dietary supplements, including modified cellulose – a plant fiber that expands in the stomach to induce a feeling of fullness – and blood orange juice extract, also showed encouraging results but were investigated in one trial and need more evidence before they can be recommended for weight loss, Ms. Bessell added.

She pointed out that some supplements are banned in some countries, such as ephedra (an extract from the plant Ephedra sinica). “This supplement is already banned in many countries because of the risk of serious adverse effects. The possibility of drug interactions may also be present with some other supplements, so health professionals and consumers should be aware of this.”

The isolated organic compounds supplements review was published in the International Journal of Obesity to coincide with the ECO 2021 conference.

Ms. Bessell has declared no relevant conflicts of interests. Dr. Arentz reviewed the systematic review of RCTs of herbal medicine supplements for weight loss published in Diabetes, Obesity and Metabolism.
 

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

Although use of some herbal and dietary supplements show statistically greater weight loss compared with placebo, it is not sufficient to benefit health, according to the joint findings of two systematic reviews, which are the first to comprehensively include all available herbal and dietary supplements for weight loss for over 15 years.

Sally Kubetin/MDedge News

“There is currently insufficient evidence to recommend any of the supplements we included in our reviews for weight loss,” stressed lead author Erica Bessell, a PhD candidate from the University of Sydney.

She added that some products with promising results warrant further investigation in well-conducted randomized controlled trials (RCTs) to determine their efficacy and safety.

But, overall, she would like to see a reduction in the number of products on the market without evidence to support their efficacy, “because, as we found, many of the products currently marketed for weight loss just do not work.

“Herbal and dietary supplements might seem like a quick-fix solution to weight problems, but people need to be aware of how little we actually know about them,” she said in an interview. “We would recommend that people trying to lose weight should save their money and seek out evidence-based care instead,” she emphasized.

The research was presented as two posters at this year’s online European Congress on Obesity (ECO). The meeting was presented by the European Association for the Study of Obesity.
 

Herbal and dietary supplement industry booming

Supplements for weight loss are growing in popularity, sustaining a rapidly expanding business sector globally. In the United States, the herbal and dietary supplements industry was estimated to be worth USD $41 billion in 2020, with 15% of Americans having tried a weight loss supplement in their efforts to shed pounds.

In light of this, Ms. Bessell said it is increasingly important to ensure supplements are efficacious and safe: “The popularity of these products underscores the urgency of conducting larger, more rigorous studies to have reasonable assurance of their safety and effectiveness for weight loss.”

Commenting on the study and the wider issues related to the surge in uptake of herbal and dietary supplements, Susan Arentz, PhD, said the evidence is similar to that for other complex interventions that people attempt for weight loss, including for example exercise, in that it is heterogeneous and low quality.

“One outstanding limitation for herbal medicine was the failure of trialists to validate the contents of interventions. Given the chemical variability of plants grown and harvested in different conditions, and the presence of pharmaceuticals and heavy metals found in some supplements ... future investigations of standardized herbal supplements and RCTs of higher methodological quality are needed,” remarked Dr. Arentz, a board member of the Australasian Integrative Medicine Association and researcher at Western Sydney University.

“Also, further RCTs are warranted due to the consumer preferences for natural treatments, especially in health settings with predominant use of traditional medicines and practices,” said Dr. Arentz.   
 

One review for herbal supplements, one for organic compounds

To accommodate the large number of trials investigating supplements for weight loss, the researchers conducted two systematic reviews, together representing 121 randomized placebo-controlled trials. One of the reviews investigated herbal supplements, and the other examined supplements with isolated organic compounds for example, specific fibers or lipids.  

Many of the included trials had been published in the last decade and had not been previously included in an up-to-date systematic review.

Ms. Bessell added that many studies often had a small sample size or were poorly designed, with insufficient information on the composition of supplements, and often featured little data on long-term effectiveness.

The two reviews primarily analyzed efficacy, not safety, because many of the studies did not report adverse effects.

The first review, published last year in Diabetes, Obesity and Metabolism, looked at 54 placebo-controlled randomized trials up to August 2018 on the effect of herbal supplements on weight loss . The study included 4,331 individuals aged 16 years or older who were overweight or obese. To be clinically meaningful, a weight loss of at least 2.5 kg was required over a period of, most often, 12 weeks or less.

Herbal supplements included in the analysis included green tea, Garcinia cambogia and mangosteen (tropical fruits), white kidney bean, ephedra (a stimulant that increases metabolism), African mango, yerba mate (herbal tea made from the leaves and twigs of the Ilex paraguariensis plant), veld grape (commonly used in Indian traditional medicine), licorice root, and East Indian Globe Thistle (used in Ayurvedic medicine).

The second review analyzed 67 randomized trials up to December 2019 that compared the effect of dietary supplements containing naturally occurring isolated organic compounds to placebo for weight loss in 5,194 individuals aged 16 years or older who were overweight or obese.

Meta-analyses were conducted for chitosan, glucomannan, conjugated linoleic acid, and fructans comparing the mean weight difference post intervention between participants receiving the dietary supplement and those on placebo.
 

No clinically significant results

Commenting on the overall results, Ms. Bessell said: “Though most supplements were safe for use in the short term, very few were found to produce clinically meaningful weight loss. Those that were found to result in clinically meaningful weight loss had only been investigated in one or two trials, so we need more research.”

The first review on herbal supplements found that only Phaseolus vulgaris (white kidney bean) resulted in significant weight loss compared with placebo, with an average weight difference of 1.61 kg (3.5 pounds). The result was not clinically meaningful, however.

For isolated organic compounds, significant weight differences compared with placebo were seen for chitosan, with a mean difference of 1.84 kg (4 pounds), glucomannan at 1.27 kg (2.8 pounds), and conjugated linoleic acid at 1.08 kg (2.4 pounds).

Again, none of these findings met the criteria for clinical significance (weight loss of 2.5 kg [5.5 pounds] or more).

In addition, some combination preparations containing African mango, veld grape, East Indian Globe Thistle, and mangosteen showed promising results with a mean weight difference of 1.85 kg (4 pounds), but were investigated in three or fewer trials, often with poor research methodology or reporting, and the findings should be interpreted with caution, the researchers noted.

Other dietary supplements, including modified cellulose – a plant fiber that expands in the stomach to induce a feeling of fullness – and blood orange juice extract, also showed encouraging results but were investigated in one trial and need more evidence before they can be recommended for weight loss, Ms. Bessell added.

She pointed out that some supplements are banned in some countries, such as ephedra (an extract from the plant Ephedra sinica). “This supplement is already banned in many countries because of the risk of serious adverse effects. The possibility of drug interactions may also be present with some other supplements, so health professionals and consumers should be aware of this.”

The isolated organic compounds supplements review was published in the International Journal of Obesity to coincide with the ECO 2021 conference.

Ms. Bessell has declared no relevant conflicts of interests. Dr. Arentz reviewed the systematic review of RCTs of herbal medicine supplements for weight loss published in Diabetes, Obesity and Metabolism.
 

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

Although use of some herbal and dietary supplements show statistically greater weight loss compared with placebo, it is not sufficient to benefit health, according to the joint findings of two systematic reviews, which are the first to comprehensively include all available herbal and dietary supplements for weight loss for over 15 years.

Sally Kubetin/MDedge News

“There is currently insufficient evidence to recommend any of the supplements we included in our reviews for weight loss,” stressed lead author Erica Bessell, a PhD candidate from the University of Sydney.

She added that some products with promising results warrant further investigation in well-conducted randomized controlled trials (RCTs) to determine their efficacy and safety.

But, overall, she would like to see a reduction in the number of products on the market without evidence to support their efficacy, “because, as we found, many of the products currently marketed for weight loss just do not work.

“Herbal and dietary supplements might seem like a quick-fix solution to weight problems, but people need to be aware of how little we actually know about them,” she said in an interview. “We would recommend that people trying to lose weight should save their money and seek out evidence-based care instead,” she emphasized.

The research was presented as two posters at this year’s online European Congress on Obesity (ECO). The meeting was presented by the European Association for the Study of Obesity.
 

Herbal and dietary supplement industry booming

Supplements for weight loss are growing in popularity, sustaining a rapidly expanding business sector globally. In the United States, the herbal and dietary supplements industry was estimated to be worth USD $41 billion in 2020, with 15% of Americans having tried a weight loss supplement in their efforts to shed pounds.

In light of this, Ms. Bessell said it is increasingly important to ensure supplements are efficacious and safe: “The popularity of these products underscores the urgency of conducting larger, more rigorous studies to have reasonable assurance of their safety and effectiveness for weight loss.”

Commenting on the study and the wider issues related to the surge in uptake of herbal and dietary supplements, Susan Arentz, PhD, said the evidence is similar to that for other complex interventions that people attempt for weight loss, including for example exercise, in that it is heterogeneous and low quality.

“One outstanding limitation for herbal medicine was the failure of trialists to validate the contents of interventions. Given the chemical variability of plants grown and harvested in different conditions, and the presence of pharmaceuticals and heavy metals found in some supplements ... future investigations of standardized herbal supplements and RCTs of higher methodological quality are needed,” remarked Dr. Arentz, a board member of the Australasian Integrative Medicine Association and researcher at Western Sydney University.

“Also, further RCTs are warranted due to the consumer preferences for natural treatments, especially in health settings with predominant use of traditional medicines and practices,” said Dr. Arentz.   
 

One review for herbal supplements, one for organic compounds

To accommodate the large number of trials investigating supplements for weight loss, the researchers conducted two systematic reviews, together representing 121 randomized placebo-controlled trials. One of the reviews investigated herbal supplements, and the other examined supplements with isolated organic compounds for example, specific fibers or lipids.  

Many of the included trials had been published in the last decade and had not been previously included in an up-to-date systematic review.

Ms. Bessell added that many studies often had a small sample size or were poorly designed, with insufficient information on the composition of supplements, and often featured little data on long-term effectiveness.

The two reviews primarily analyzed efficacy, not safety, because many of the studies did not report adverse effects.

The first review, published last year in Diabetes, Obesity and Metabolism, looked at 54 placebo-controlled randomized trials up to August 2018 on the effect of herbal supplements on weight loss . The study included 4,331 individuals aged 16 years or older who were overweight or obese. To be clinically meaningful, a weight loss of at least 2.5 kg was required over a period of, most often, 12 weeks or less.

Herbal supplements included in the analysis included green tea, Garcinia cambogia and mangosteen (tropical fruits), white kidney bean, ephedra (a stimulant that increases metabolism), African mango, yerba mate (herbal tea made from the leaves and twigs of the Ilex paraguariensis plant), veld grape (commonly used in Indian traditional medicine), licorice root, and East Indian Globe Thistle (used in Ayurvedic medicine).

The second review analyzed 67 randomized trials up to December 2019 that compared the effect of dietary supplements containing naturally occurring isolated organic compounds to placebo for weight loss in 5,194 individuals aged 16 years or older who were overweight or obese.

Meta-analyses were conducted for chitosan, glucomannan, conjugated linoleic acid, and fructans comparing the mean weight difference post intervention between participants receiving the dietary supplement and those on placebo.
 

No clinically significant results

Commenting on the overall results, Ms. Bessell said: “Though most supplements were safe for use in the short term, very few were found to produce clinically meaningful weight loss. Those that were found to result in clinically meaningful weight loss had only been investigated in one or two trials, so we need more research.”

The first review on herbal supplements found that only Phaseolus vulgaris (white kidney bean) resulted in significant weight loss compared with placebo, with an average weight difference of 1.61 kg (3.5 pounds). The result was not clinically meaningful, however.

For isolated organic compounds, significant weight differences compared with placebo were seen for chitosan, with a mean difference of 1.84 kg (4 pounds), glucomannan at 1.27 kg (2.8 pounds), and conjugated linoleic acid at 1.08 kg (2.4 pounds).

Again, none of these findings met the criteria for clinical significance (weight loss of 2.5 kg [5.5 pounds] or more).

In addition, some combination preparations containing African mango, veld grape, East Indian Globe Thistle, and mangosteen showed promising results with a mean weight difference of 1.85 kg (4 pounds), but were investigated in three or fewer trials, often with poor research methodology or reporting, and the findings should be interpreted with caution, the researchers noted.

Other dietary supplements, including modified cellulose – a plant fiber that expands in the stomach to induce a feeling of fullness – and blood orange juice extract, also showed encouraging results but were investigated in one trial and need more evidence before they can be recommended for weight loss, Ms. Bessell added.

She pointed out that some supplements are banned in some countries, such as ephedra (an extract from the plant Ephedra sinica). “This supplement is already banned in many countries because of the risk of serious adverse effects. The possibility of drug interactions may also be present with some other supplements, so health professionals and consumers should be aware of this.”

The isolated organic compounds supplements review was published in the International Journal of Obesity to coincide with the ECO 2021 conference.

Ms. Bessell has declared no relevant conflicts of interests. Dr. Arentz reviewed the systematic review of RCTs of herbal medicine supplements for weight loss published in Diabetes, Obesity and Metabolism.
 

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

Those of us treating nonalcoholic fatty liver disease (NAFLD) often find ourselves having similar conversations with our patients. After diagnosis, our next step is usually describing to them how they can improve their outcomes through a healthy diet and exercise.

Westend61/Getty Images

We can point to the latest data espousing the benefits of moderate weight reduction. The recently released American Gastroenterological Association (AGA) Clinical Practice Update gives us compelling evidence of what can be achieved with specific thresholds of total body weight loss: >5% can decrease hepatic steatosis, >7% potentially leads to resolution of nonalcoholic steatohepatitis, and >10% possibly allows for regression or stability of fibrosis.

More often than not, our patients then ask us, “What diet do you recommend?”

The AGA’s Clinical Practice Update recommends that people with NAFLD follow the Mediterranean diet, minimize saturated fatty acid intake (specifically red and processed meat), and limit or eliminate consumption of commercially produced fructose.

It’s a tried-and-true, evidence-based recommendation. Yet, recent data suggest that modifying the Mediterranean diet so that it’s further enriched with specific green polyphenols may yield even more benefits to at-risk patients.
 

The upside of a greener Mediterranean diet

In a recently published study, investigators behind the DIRECT-PLUS clinical trial randomly assigned 294 participants with abdominal obesity/dyslipidemia into three diet groups (all accompanied by physical activity): standard healthy dietary guidelines (HDG), standard Mediterranean, and the so-called green Mediterranean diet.

Both Mediterranean diet groups were calorie restricted and called for 28 g/day of walnuts (+440 mg/day polyphenols provided). However, the green Mediterranean diet was further supplemented with 3-4 cups/day of green tea and 100 g/day of Mankai (a Wolffia globosa aquatic plant strain) in the form of frozen cubes turned into a green shake that replaced dinner (+1,240 mg/day total polyphenols provided). The percent change in intrahepatic fat content was quantified continuously by proton magnetic resonance spectroscopy. NAFLD was defined as an intrahepatic fat content of >5%.

After 18 months, the prevalence of NAFLD declined to 54.8% in the HDG group, 47.9% in the standard Mediterranean group, and 31.5% in the green Mediterranean group. Both Mediterranean groups achieved similar moderate weight loss and had significantly higher total plasma polyphenol levels versus the HDG group. However, the green Mediterranean group achieved significantly greater proportional intrahepatic fat content loss (-38.9%) than both the standard Mediterranean (-19.6; P = .023) and HDG (-12.2%; P < .001) groups.

In isolating the individual components of the diets, researchers determined that the degree of intrahepatic fat content loss was significantly associated with increased Mankai and walnut intake, decreased red/processed meat consumption, improved serum folate and adipokines/lipids biomarkers, and changes in microbiome composition and specific bacteria.

The authors suggest that the mechanisms by which polyphenols reduced steatosis and prevented liver injury may include reduced de novo lipogenesis, increased fatty acid oxidation, and reduced oxidative stress.

In an additional analysis, DIRECT-PLUS investigators also revealed the beneficial effects of the green Mediterranean diet on cardiometabolic health. Although both Mediterranean diets achieved similar weight loss (-6.2 kg for green Mediterranean and -5.4 kg for standard Mediterranean), which was superior to that observed in the HDG group (-1.5 kg; P < .001), the green Mediterranean group had a greater reduction in waist circumference than the standard Mediterranean group (-8.6 vs. -6.8 cm, respectively; P = .033). Within 6 months, the green Mediterranean group also achieved a greater decrease in low-density lipoprotein cholesterol levels, diastolic blood pressure, and insulin resistance.
 

A new dietary tool for combating obesity

The rising global incidence of NAFLD has made it even more urgent to identify new and improved ways of preventing the onset of obesity-related complications. To aid those efforts, we’ve been equipped with useful tools for educating our patients and their families, such as the 2020-2025 Dietary Guidelines for Americans from the U.S. Department of Agriculture (USDA), which makes a clear case for the disease-combating effects of healthy eating patterns.

This message does not appear to be making the impact it should, however, particularly among teens and young adults. It was recently reported that in 2017, only 7% of U.S. high school students consumed recommended amounts of fruits and only 2% consumed enough vegetables to meet USDA recommendations.

Novel approaches, including enhanced school and community programs, will be required to address this issue, but so will presenting patients with satisfactory dietary alternatives. Compellingly, DIRECT-PLUS investigators reported an 89.8% retention rate at 18 months among volunteers, who were able to comply with the dietary regimen with no significant complaints regarding taste. This signals that even though the “green” modification is more stringent than the typical Mediterranean regimen, it is one to which participants can adhere.

Although the real-world applicability of this diet remains to be seen, DIRECT-PLUS gives us encouraging evidence that a Mediterranean diet amplified with green plant-based proteins/polyphenols can lead to twice the intrahepatic fat loss, as compared to other nutritional strategies, and reduce the rate of NAFLD.

And as we know, having another dietary option to offer our patients is always a welcome addition to the menu.

Dr. Balistreri is with the department of hepatology & nutrition at Cincinnati Children’s Hospital Medical Center. He has disclosed no relevant financial relationships.

Iris Shai, PhD, one of the authors of the study, “Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial,” is an adviser to Hinoman, which markets Mankai. Ilan Youngster, MD, another author of that study, is medical adviser for MyBiotics.

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

This article was updated May 21, 2021.

Those of us treating nonalcoholic fatty liver disease (NAFLD) often find ourselves having similar conversations with our patients. After diagnosis, our next step is usually describing to them how they can improve their outcomes through a healthy diet and exercise.

Westend61/Getty Images

We can point to the latest data espousing the benefits of moderate weight reduction. The recently released American Gastroenterological Association (AGA) Clinical Practice Update gives us compelling evidence of what can be achieved with specific thresholds of total body weight loss: >5% can decrease hepatic steatosis, >7% potentially leads to resolution of nonalcoholic steatohepatitis, and >10% possibly allows for regression or stability of fibrosis.

More often than not, our patients then ask us, “What diet do you recommend?”

The AGA’s Clinical Practice Update recommends that people with NAFLD follow the Mediterranean diet, minimize saturated fatty acid intake (specifically red and processed meat), and limit or eliminate consumption of commercially produced fructose.

It’s a tried-and-true, evidence-based recommendation. Yet, recent data suggest that modifying the Mediterranean diet so that it’s further enriched with specific green polyphenols may yield even more benefits to at-risk patients.
 

The upside of a greener Mediterranean diet

In a recently published study, investigators behind the DIRECT-PLUS clinical trial randomly assigned 294 participants with abdominal obesity/dyslipidemia into three diet groups (all accompanied by physical activity): standard healthy dietary guidelines (HDG), standard Mediterranean, and the so-called green Mediterranean diet.

Both Mediterranean diet groups were calorie restricted and called for 28 g/day of walnuts (+440 mg/day polyphenols provided). However, the green Mediterranean diet was further supplemented with 3-4 cups/day of green tea and 100 g/day of Mankai (a Wolffia globosa aquatic plant strain) in the form of frozen cubes turned into a green shake that replaced dinner (+1,240 mg/day total polyphenols provided). The percent change in intrahepatic fat content was quantified continuously by proton magnetic resonance spectroscopy. NAFLD was defined as an intrahepatic fat content of >5%.

After 18 months, the prevalence of NAFLD declined to 54.8% in the HDG group, 47.9% in the standard Mediterranean group, and 31.5% in the green Mediterranean group. Both Mediterranean groups achieved similar moderate weight loss and had significantly higher total plasma polyphenol levels versus the HDG group. However, the green Mediterranean group achieved significantly greater proportional intrahepatic fat content loss (-38.9%) than both the standard Mediterranean (-19.6; P = .023) and HDG (-12.2%; P < .001) groups.

In isolating the individual components of the diets, researchers determined that the degree of intrahepatic fat content loss was significantly associated with increased Mankai and walnut intake, decreased red/processed meat consumption, improved serum folate and adipokines/lipids biomarkers, and changes in microbiome composition and specific bacteria.

The authors suggest that the mechanisms by which polyphenols reduced steatosis and prevented liver injury may include reduced de novo lipogenesis, increased fatty acid oxidation, and reduced oxidative stress.

In an additional analysis, DIRECT-PLUS investigators also revealed the beneficial effects of the green Mediterranean diet on cardiometabolic health. Although both Mediterranean diets achieved similar weight loss (-6.2 kg for green Mediterranean and -5.4 kg for standard Mediterranean), which was superior to that observed in the HDG group (-1.5 kg; P < .001), the green Mediterranean group had a greater reduction in waist circumference than the standard Mediterranean group (-8.6 vs. -6.8 cm, respectively; P = .033). Within 6 months, the green Mediterranean group also achieved a greater decrease in low-density lipoprotein cholesterol levels, diastolic blood pressure, and insulin resistance.
 

A new dietary tool for combating obesity

The rising global incidence of NAFLD has made it even more urgent to identify new and improved ways of preventing the onset of obesity-related complications. To aid those efforts, we’ve been equipped with useful tools for educating our patients and their families, such as the 2020-2025 Dietary Guidelines for Americans from the U.S. Department of Agriculture (USDA), which makes a clear case for the disease-combating effects of healthy eating patterns.

This message does not appear to be making the impact it should, however, particularly among teens and young adults. It was recently reported that in 2017, only 7% of U.S. high school students consumed recommended amounts of fruits and only 2% consumed enough vegetables to meet USDA recommendations.

Novel approaches, including enhanced school and community programs, will be required to address this issue, but so will presenting patients with satisfactory dietary alternatives. Compellingly, DIRECT-PLUS investigators reported an 89.8% retention rate at 18 months among volunteers, who were able to comply with the dietary regimen with no significant complaints regarding taste. This signals that even though the “green” modification is more stringent than the typical Mediterranean regimen, it is one to which participants can adhere.

Although the real-world applicability of this diet remains to be seen, DIRECT-PLUS gives us encouraging evidence that a Mediterranean diet amplified with green plant-based proteins/polyphenols can lead to twice the intrahepatic fat loss, as compared to other nutritional strategies, and reduce the rate of NAFLD.

And as we know, having another dietary option to offer our patients is always a welcome addition to the menu.

Dr. Balistreri is with the department of hepatology & nutrition at Cincinnati Children’s Hospital Medical Center. He has disclosed no relevant financial relationships.

Iris Shai, PhD, one of the authors of the study, “Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial,” is an adviser to Hinoman, which markets Mankai. Ilan Youngster, MD, another author of that study, is medical adviser for MyBiotics.

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

This article was updated May 21, 2021.

Those of us treating nonalcoholic fatty liver disease (NAFLD) often find ourselves having similar conversations with our patients. After diagnosis, our next step is usually describing to them how they can improve their outcomes through a healthy diet and exercise.

Westend61/Getty Images

We can point to the latest data espousing the benefits of moderate weight reduction. The recently released American Gastroenterological Association (AGA) Clinical Practice Update gives us compelling evidence of what can be achieved with specific thresholds of total body weight loss: >5% can decrease hepatic steatosis, >7% potentially leads to resolution of nonalcoholic steatohepatitis, and >10% possibly allows for regression or stability of fibrosis.

More often than not, our patients then ask us, “What diet do you recommend?”

The AGA’s Clinical Practice Update recommends that people with NAFLD follow the Mediterranean diet, minimize saturated fatty acid intake (specifically red and processed meat), and limit or eliminate consumption of commercially produced fructose.

It’s a tried-and-true, evidence-based recommendation. Yet, recent data suggest that modifying the Mediterranean diet so that it’s further enriched with specific green polyphenols may yield even more benefits to at-risk patients.
 

The upside of a greener Mediterranean diet

In a recently published study, investigators behind the DIRECT-PLUS clinical trial randomly assigned 294 participants with abdominal obesity/dyslipidemia into three diet groups (all accompanied by physical activity): standard healthy dietary guidelines (HDG), standard Mediterranean, and the so-called green Mediterranean diet.

Both Mediterranean diet groups were calorie restricted and called for 28 g/day of walnuts (+440 mg/day polyphenols provided). However, the green Mediterranean diet was further supplemented with 3-4 cups/day of green tea and 100 g/day of Mankai (a Wolffia globosa aquatic plant strain) in the form of frozen cubes turned into a green shake that replaced dinner (+1,240 mg/day total polyphenols provided). The percent change in intrahepatic fat content was quantified continuously by proton magnetic resonance spectroscopy. NAFLD was defined as an intrahepatic fat content of >5%.

After 18 months, the prevalence of NAFLD declined to 54.8% in the HDG group, 47.9% in the standard Mediterranean group, and 31.5% in the green Mediterranean group. Both Mediterranean groups achieved similar moderate weight loss and had significantly higher total plasma polyphenol levels versus the HDG group. However, the green Mediterranean group achieved significantly greater proportional intrahepatic fat content loss (-38.9%) than both the standard Mediterranean (-19.6; P = .023) and HDG (-12.2%; P < .001) groups.

In isolating the individual components of the diets, researchers determined that the degree of intrahepatic fat content loss was significantly associated with increased Mankai and walnut intake, decreased red/processed meat consumption, improved serum folate and adipokines/lipids biomarkers, and changes in microbiome composition and specific bacteria.

The authors suggest that the mechanisms by which polyphenols reduced steatosis and prevented liver injury may include reduced de novo lipogenesis, increased fatty acid oxidation, and reduced oxidative stress.

In an additional analysis, DIRECT-PLUS investigators also revealed the beneficial effects of the green Mediterranean diet on cardiometabolic health. Although both Mediterranean diets achieved similar weight loss (-6.2 kg for green Mediterranean and -5.4 kg for standard Mediterranean), which was superior to that observed in the HDG group (-1.5 kg; P < .001), the green Mediterranean group had a greater reduction in waist circumference than the standard Mediterranean group (-8.6 vs. -6.8 cm, respectively; P = .033). Within 6 months, the green Mediterranean group also achieved a greater decrease in low-density lipoprotein cholesterol levels, diastolic blood pressure, and insulin resistance.
 

A new dietary tool for combating obesity

The rising global incidence of NAFLD has made it even more urgent to identify new and improved ways of preventing the onset of obesity-related complications. To aid those efforts, we’ve been equipped with useful tools for educating our patients and their families, such as the 2020-2025 Dietary Guidelines for Americans from the U.S. Department of Agriculture (USDA), which makes a clear case for the disease-combating effects of healthy eating patterns.

This message does not appear to be making the impact it should, however, particularly among teens and young adults. It was recently reported that in 2017, only 7% of U.S. high school students consumed recommended amounts of fruits and only 2% consumed enough vegetables to meet USDA recommendations.

Novel approaches, including enhanced school and community programs, will be required to address this issue, but so will presenting patients with satisfactory dietary alternatives. Compellingly, DIRECT-PLUS investigators reported an 89.8% retention rate at 18 months among volunteers, who were able to comply with the dietary regimen with no significant complaints regarding taste. This signals that even though the “green” modification is more stringent than the typical Mediterranean regimen, it is one to which participants can adhere.

Although the real-world applicability of this diet remains to be seen, DIRECT-PLUS gives us encouraging evidence that a Mediterranean diet amplified with green plant-based proteins/polyphenols can lead to twice the intrahepatic fat loss, as compared to other nutritional strategies, and reduce the rate of NAFLD.

And as we know, having another dietary option to offer our patients is always a welcome addition to the menu.

Dr. Balistreri is with the department of hepatology & nutrition at Cincinnati Children’s Hospital Medical Center. He has disclosed no relevant financial relationships.

Iris Shai, PhD, one of the authors of the study, “Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial,” is an adviser to Hinoman, which markets Mankai. Ilan Youngster, MD, another author of that study, is medical adviser for MyBiotics.

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

This article was updated May 21, 2021.