Clinician Reviews

Injectable weight loss drugs like Wegovy, Saxenda, and Zepbound have been getting all the glory lately, but they’re not for everyone. If the inconvenience or cost of weight-loss drugs isn’t for you, another approach may be boosting your gut microbiome.

So how does one do that, and how does it work?

“There are a lot of different factors naturally in weight gain and weight loss, so the gut microbiome is certainly not the only thing,” said Chris Damman, MD, a gastroenterologist at the University of Washington. He studies how food and the microbiome affect your health. “With that caveat, it probably is playing an important role.”
 

Trillions of Microbes

The idea that your gut is home to an enormous range of tiny organisms — microbes — has existed for more than 100 years, but only in the 21st century have scientists had the ability to delve into specifics. 

We now know you want a robust assortment of microbes in your gut, especially in the lower gut, your colon. They feast on fiber from the food you eat and turn it into substances your body needs. Those substances send signals all over your body.

If you don’t have enough microbes or have too many of the wrong kinds, it influences those signals, which can lead to health problems. Over the last 20 years, research has linked problems in the gut microbiome to a wide variety of conditions, including inflammatory bowel disease, autoimmune diseases like rheumatoid arthritis, metabolic ones like diabetes, and cardiovascular disease, asthma, and even autism.

Thanks to these efforts, we know a lot about the interactions between your gut and the rest of your body, but we don’t know exactly how many things happen — whether some teeny critters within your microbiome cause the issues or vice versa.

“That’s the problem with so much of the microbiome stuff,” said Elizabeth Hohmann, MD, a physician investigator at the Massachusetts General Research Institute. “Olympic athletes have a better gut microbiome than most people. Well, sure they do — because they’re paying attention to their diet, they’re getting enough rest. Correlation does not causation make.”
 

The American Diet Messes With Your Gut

If you’re a typical American, you eat a lot of ultra-processed foods — manufactured with a long ingredients list that includes additives or preservatives. According to one study, those foods make up 73% of our food supply. That can have a serious impact on gut health.

“When you process a food and mill it, it turns a whole food into tiny particles,” Dr. Damman said. “That makes the food highly digestible. But if you eat a stalk of broccoli, a large amount of that broccoli in the form of fiber and other things will make its way to your lower gut, where it will feed microbes.”

With heavily processed foods, on the other hand, most of it gets digested before it can reach your lower gut, which leaves your microbes without the energy they need to survive.

Rosa Krajmalnik-Brown, PhD, is director of the Biodesign Center for Health Through Microbiomes at Arizona State University. Her lab has done research into how microbes use the undigested food that reaches your gut. She describes the problem with processed foods this way:

“Think about a Coke. When you drink it, all the sugar goes to your bloodstream, and the microbes in your gut don’t even know you’ve had it. Instead of drinking a Coke, if you eat an apple or something with fiber, some will go to you and some to the microbes. You’re feeding them, giving them energy.”
 

Weight and Your Gut Microbiome

The link between gut health and body weight has received a lot of attention. Research has shown, for example, that people with obesity have less diversity in their gut microbiome, and certain specific bacteria have been linked to obesity. In animal studies, transplanting gut microbes from obese mice to “germ-free” mice led those GF mice to gain weight. This suggests excess weight is, in fact, caused by certain microbes, but to date there’s scant evidence that the same is true with humans.

Dr. Krajmalnik-Brown’s group did an experiment in which they had people follow two different diets for 23 days each, with a break in between. Both provided similar amounts of calories and macronutrients each day but via different foods. The study’s typical Western menu featured processed foods — think grape juice, sandwiches made with deli turkey and white bread, and spaghetti with jarred sauce and ground beef. The other menu, what researchers called a “microbiome enhancer diet,” included foods like whole fruit, veggie sandwiches on multigrain buns, and steak with a side of whole wheat spaghetti.

While the study wasn’t designed for weight loss, an interesting thing happened when researchers analyzed participants’ bowel movements.

“We found that when you feed subjects a diet designed to provide more energy to the microbes and not to the [body], our subjects lost a little weight,” Dr. Krajmalnik-Brown said. “It looks like by feeding your microbes, it seems to make people healthier and potentially even lose a little.”

Another possible mechanism involves the same hormone that powers those injectable weight loss drugs. The lower part of your gut makes hormones that tell the entire gut to slow down and also help orchestrate metabolism and appetite. Among them is GLP-1. The drugs use a synthetic version, semaglutide or tirzepatide, to trigger the same effect.

According to Dr. Damman, you can stimulate your gut to make those helpful hormones with the food you eat — by giving your microbes the right fuel.
 

Eat to Feed Your Microbes

The foods you eat can affect your gut microbiome and so your weight. But don’t go looking for that one perfect ingredient, experts warn.

“Oftentimes we get this micro-focus, is this a good food or a bad food?” warned Katie Chapmon, a registered dietitian whose practice focuses on gut health. “You just want to make sure your microbiome is robust and healthy, so it communicates that your body is running, you’ve got it.”

Instead, try to give your body more of the kinds of food research has shown can feed your microbiome, many of which are plant-based. “Those are the things that are largely taken out during processing,” Dr. Damman said. He calls them the “Four Fs”:

Fiber: When you eat fiber-rich foods like fruits, vegetables, whole grains, nuts, and beans, your body can’t digest the fiber while it’s in the upper parts of your GI tract. It passes through to your lower gut, where healthy bacteria ferment it. That produces short-chain fatty acids, which send signals throughout your body, including ones related to appetite and feeling full.

Phenols: Phenolic compounds are antioxidants that give plant-based foods their color — when you talk about eating the rainbow, you’re talking about phenols. The microbes in your gut feed on them, too. “My goal for a meal is five distinct colors on the plate,” Ms. Chapmon said. “That rounds out the bases for the different polyphenols.”

Fermented foods: You can get a different kind of health benefit by eating food that’s already fermented — like sauerkraut, kimchi, kefir, yogurt, miso, tempeh, and kombucha. Fermentation can make the phenols in foods more accessible to your body. Plus, each mouthful introduces good bacteria into your body, some of which make it down to your gut. The bacteria that are already there feed on these new strains, which helps to increase the diversity of your microbiome.

Healthy fats: Here, it’s not so much about feeding the good bacteria in your microbiome. Dr. Damman says that omega-3 fatty acids, found in fatty fish, canola oil, some nuts, and other foods, decrease inflammation in the lining of your gut. Plus, healthy fat sources like extra-virgin olive oil and avocados are full of phenols.

Eating for gut health isn’t a magic bullet in terms of weight loss. But the benefits of a healthy gut go far beyond shedding a few pounds.

“I think we need to strive for health, not weight loss.” Dr. Krajmalnik-Brown said. “Keep your gut healthy and your microbes healthy, and that should eventually lead to a healthy weight. You’ll make your microbes happy, and your microbes do a lot for your health.”

A version of this article appeared on WebMD.com.

Injectable weight loss drugs like Wegovy, Saxenda, and Zepbound have been getting all the glory lately, but they’re not for everyone. If the inconvenience or cost of weight-loss drugs isn’t for you, another approach may be boosting your gut microbiome.

So how does one do that, and how does it work?

“There are a lot of different factors naturally in weight gain and weight loss, so the gut microbiome is certainly not the only thing,” said Chris Damman, MD, a gastroenterologist at the University of Washington. He studies how food and the microbiome affect your health. “With that caveat, it probably is playing an important role.”
 

Trillions of Microbes

The idea that your gut is home to an enormous range of tiny organisms — microbes — has existed for more than 100 years, but only in the 21st century have scientists had the ability to delve into specifics. 

We now know you want a robust assortment of microbes in your gut, especially in the lower gut, your colon. They feast on fiber from the food you eat and turn it into substances your body needs. Those substances send signals all over your body.

If you don’t have enough microbes or have too many of the wrong kinds, it influences those signals, which can lead to health problems. Over the last 20 years, research has linked problems in the gut microbiome to a wide variety of conditions, including inflammatory bowel disease, autoimmune diseases like rheumatoid arthritis, metabolic ones like diabetes, and cardiovascular disease, asthma, and even autism.

Thanks to these efforts, we know a lot about the interactions between your gut and the rest of your body, but we don’t know exactly how many things happen — whether some teeny critters within your microbiome cause the issues or vice versa.

“That’s the problem with so much of the microbiome stuff,” said Elizabeth Hohmann, MD, a physician investigator at the Massachusetts General Research Institute. “Olympic athletes have a better gut microbiome than most people. Well, sure they do — because they’re paying attention to their diet, they’re getting enough rest. Correlation does not causation make.”
 

The American Diet Messes With Your Gut

If you’re a typical American, you eat a lot of ultra-processed foods — manufactured with a long ingredients list that includes additives or preservatives. According to one study, those foods make up 73% of our food supply. That can have a serious impact on gut health.

“When you process a food and mill it, it turns a whole food into tiny particles,” Dr. Damman said. “That makes the food highly digestible. But if you eat a stalk of broccoli, a large amount of that broccoli in the form of fiber and other things will make its way to your lower gut, where it will feed microbes.”

With heavily processed foods, on the other hand, most of it gets digested before it can reach your lower gut, which leaves your microbes without the energy they need to survive.

Rosa Krajmalnik-Brown, PhD, is director of the Biodesign Center for Health Through Microbiomes at Arizona State University. Her lab has done research into how microbes use the undigested food that reaches your gut. She describes the problem with processed foods this way:

“Think about a Coke. When you drink it, all the sugar goes to your bloodstream, and the microbes in your gut don’t even know you’ve had it. Instead of drinking a Coke, if you eat an apple or something with fiber, some will go to you and some to the microbes. You’re feeding them, giving them energy.”
 

Weight and Your Gut Microbiome

The link between gut health and body weight has received a lot of attention. Research has shown, for example, that people with obesity have less diversity in their gut microbiome, and certain specific bacteria have been linked to obesity. In animal studies, transplanting gut microbes from obese mice to “germ-free” mice led those GF mice to gain weight. This suggests excess weight is, in fact, caused by certain microbes, but to date there’s scant evidence that the same is true with humans.

Dr. Krajmalnik-Brown’s group did an experiment in which they had people follow two different diets for 23 days each, with a break in between. Both provided similar amounts of calories and macronutrients each day but via different foods. The study’s typical Western menu featured processed foods — think grape juice, sandwiches made with deli turkey and white bread, and spaghetti with jarred sauce and ground beef. The other menu, what researchers called a “microbiome enhancer diet,” included foods like whole fruit, veggie sandwiches on multigrain buns, and steak with a side of whole wheat spaghetti.

While the study wasn’t designed for weight loss, an interesting thing happened when researchers analyzed participants’ bowel movements.

“We found that when you feed subjects a diet designed to provide more energy to the microbes and not to the [body], our subjects lost a little weight,” Dr. Krajmalnik-Brown said. “It looks like by feeding your microbes, it seems to make people healthier and potentially even lose a little.”

Another possible mechanism involves the same hormone that powers those injectable weight loss drugs. The lower part of your gut makes hormones that tell the entire gut to slow down and also help orchestrate metabolism and appetite. Among them is GLP-1. The drugs use a synthetic version, semaglutide or tirzepatide, to trigger the same effect.

According to Dr. Damman, you can stimulate your gut to make those helpful hormones with the food you eat — by giving your microbes the right fuel.
 

Eat to Feed Your Microbes

The foods you eat can affect your gut microbiome and so your weight. But don’t go looking for that one perfect ingredient, experts warn.

“Oftentimes we get this micro-focus, is this a good food or a bad food?” warned Katie Chapmon, a registered dietitian whose practice focuses on gut health. “You just want to make sure your microbiome is robust and healthy, so it communicates that your body is running, you’ve got it.”

Instead, try to give your body more of the kinds of food research has shown can feed your microbiome, many of which are plant-based. “Those are the things that are largely taken out during processing,” Dr. Damman said. He calls them the “Four Fs”:

Fiber: When you eat fiber-rich foods like fruits, vegetables, whole grains, nuts, and beans, your body can’t digest the fiber while it’s in the upper parts of your GI tract. It passes through to your lower gut, where healthy bacteria ferment it. That produces short-chain fatty acids, which send signals throughout your body, including ones related to appetite and feeling full.

Phenols: Phenolic compounds are antioxidants that give plant-based foods their color — when you talk about eating the rainbow, you’re talking about phenols. The microbes in your gut feed on them, too. “My goal for a meal is five distinct colors on the plate,” Ms. Chapmon said. “That rounds out the bases for the different polyphenols.”

Fermented foods: You can get a different kind of health benefit by eating food that’s already fermented — like sauerkraut, kimchi, kefir, yogurt, miso, tempeh, and kombucha. Fermentation can make the phenols in foods more accessible to your body. Plus, each mouthful introduces good bacteria into your body, some of which make it down to your gut. The bacteria that are already there feed on these new strains, which helps to increase the diversity of your microbiome.

Healthy fats: Here, it’s not so much about feeding the good bacteria in your microbiome. Dr. Damman says that omega-3 fatty acids, found in fatty fish, canola oil, some nuts, and other foods, decrease inflammation in the lining of your gut. Plus, healthy fat sources like extra-virgin olive oil and avocados are full of phenols.

Eating for gut health isn’t a magic bullet in terms of weight loss. But the benefits of a healthy gut go far beyond shedding a few pounds.

“I think we need to strive for health, not weight loss.” Dr. Krajmalnik-Brown said. “Keep your gut healthy and your microbes healthy, and that should eventually lead to a healthy weight. You’ll make your microbes happy, and your microbes do a lot for your health.”

A version of this article appeared on WebMD.com.

Injectable weight loss drugs like Wegovy, Saxenda, and Zepbound have been getting all the glory lately, but they’re not for everyone. If the inconvenience or cost of weight-loss drugs isn’t for you, another approach may be boosting your gut microbiome.

So how does one do that, and how does it work?

“There are a lot of different factors naturally in weight gain and weight loss, so the gut microbiome is certainly not the only thing,” said Chris Damman, MD, a gastroenterologist at the University of Washington. He studies how food and the microbiome affect your health. “With that caveat, it probably is playing an important role.”
 

Trillions of Microbes

The idea that your gut is home to an enormous range of tiny organisms — microbes — has existed for more than 100 years, but only in the 21st century have scientists had the ability to delve into specifics. 

We now know you want a robust assortment of microbes in your gut, especially in the lower gut, your colon. They feast on fiber from the food you eat and turn it into substances your body needs. Those substances send signals all over your body.

If you don’t have enough microbes or have too many of the wrong kinds, it influences those signals, which can lead to health problems. Over the last 20 years, research has linked problems in the gut microbiome to a wide variety of conditions, including inflammatory bowel disease, autoimmune diseases like rheumatoid arthritis, metabolic ones like diabetes, and cardiovascular disease, asthma, and even autism.

Thanks to these efforts, we know a lot about the interactions between your gut and the rest of your body, but we don’t know exactly how many things happen — whether some teeny critters within your microbiome cause the issues or vice versa.

“That’s the problem with so much of the microbiome stuff,” said Elizabeth Hohmann, MD, a physician investigator at the Massachusetts General Research Institute. “Olympic athletes have a better gut microbiome than most people. Well, sure they do — because they’re paying attention to their diet, they’re getting enough rest. Correlation does not causation make.”
 

The American Diet Messes With Your Gut

If you’re a typical American, you eat a lot of ultra-processed foods — manufactured with a long ingredients list that includes additives or preservatives. According to one study, those foods make up 73% of our food supply. That can have a serious impact on gut health.

“When you process a food and mill it, it turns a whole food into tiny particles,” Dr. Damman said. “That makes the food highly digestible. But if you eat a stalk of broccoli, a large amount of that broccoli in the form of fiber and other things will make its way to your lower gut, where it will feed microbes.”

With heavily processed foods, on the other hand, most of it gets digested before it can reach your lower gut, which leaves your microbes without the energy they need to survive.

Rosa Krajmalnik-Brown, PhD, is director of the Biodesign Center for Health Through Microbiomes at Arizona State University. Her lab has done research into how microbes use the undigested food that reaches your gut. She describes the problem with processed foods this way:

“Think about a Coke. When you drink it, all the sugar goes to your bloodstream, and the microbes in your gut don’t even know you’ve had it. Instead of drinking a Coke, if you eat an apple or something with fiber, some will go to you and some to the microbes. You’re feeding them, giving them energy.”
 

Weight and Your Gut Microbiome

The link between gut health and body weight has received a lot of attention. Research has shown, for example, that people with obesity have less diversity in their gut microbiome, and certain specific bacteria have been linked to obesity. In animal studies, transplanting gut microbes from obese mice to “germ-free” mice led those GF mice to gain weight. This suggests excess weight is, in fact, caused by certain microbes, but to date there’s scant evidence that the same is true with humans.

Dr. Krajmalnik-Brown’s group did an experiment in which they had people follow two different diets for 23 days each, with a break in between. Both provided similar amounts of calories and macronutrients each day but via different foods. The study’s typical Western menu featured processed foods — think grape juice, sandwiches made with deli turkey and white bread, and spaghetti with jarred sauce and ground beef. The other menu, what researchers called a “microbiome enhancer diet,” included foods like whole fruit, veggie sandwiches on multigrain buns, and steak with a side of whole wheat spaghetti.

While the study wasn’t designed for weight loss, an interesting thing happened when researchers analyzed participants’ bowel movements.

“We found that when you feed subjects a diet designed to provide more energy to the microbes and not to the [body], our subjects lost a little weight,” Dr. Krajmalnik-Brown said. “It looks like by feeding your microbes, it seems to make people healthier and potentially even lose a little.”

Another possible mechanism involves the same hormone that powers those injectable weight loss drugs. The lower part of your gut makes hormones that tell the entire gut to slow down and also help orchestrate metabolism and appetite. Among them is GLP-1. The drugs use a synthetic version, semaglutide or tirzepatide, to trigger the same effect.

According to Dr. Damman, you can stimulate your gut to make those helpful hormones with the food you eat — by giving your microbes the right fuel.
 

Eat to Feed Your Microbes

The foods you eat can affect your gut microbiome and so your weight. But don’t go looking for that one perfect ingredient, experts warn.

“Oftentimes we get this micro-focus, is this a good food or a bad food?” warned Katie Chapmon, a registered dietitian whose practice focuses on gut health. “You just want to make sure your microbiome is robust and healthy, so it communicates that your body is running, you’ve got it.”

Instead, try to give your body more of the kinds of food research has shown can feed your microbiome, many of which are plant-based. “Those are the things that are largely taken out during processing,” Dr. Damman said. He calls them the “Four Fs”:

Fiber: When you eat fiber-rich foods like fruits, vegetables, whole grains, nuts, and beans, your body can’t digest the fiber while it’s in the upper parts of your GI tract. It passes through to your lower gut, where healthy bacteria ferment it. That produces short-chain fatty acids, which send signals throughout your body, including ones related to appetite and feeling full.

Phenols: Phenolic compounds are antioxidants that give plant-based foods their color — when you talk about eating the rainbow, you’re talking about phenols. The microbes in your gut feed on them, too. “My goal for a meal is five distinct colors on the plate,” Ms. Chapmon said. “That rounds out the bases for the different polyphenols.”

Fermented foods: You can get a different kind of health benefit by eating food that’s already fermented — like sauerkraut, kimchi, kefir, yogurt, miso, tempeh, and kombucha. Fermentation can make the phenols in foods more accessible to your body. Plus, each mouthful introduces good bacteria into your body, some of which make it down to your gut. The bacteria that are already there feed on these new strains, which helps to increase the diversity of your microbiome.

Healthy fats: Here, it’s not so much about feeding the good bacteria in your microbiome. Dr. Damman says that omega-3 fatty acids, found in fatty fish, canola oil, some nuts, and other foods, decrease inflammation in the lining of your gut. Plus, healthy fat sources like extra-virgin olive oil and avocados are full of phenols.

Eating for gut health isn’t a magic bullet in terms of weight loss. But the benefits of a healthy gut go far beyond shedding a few pounds.

“I think we need to strive for health, not weight loss.” Dr. Krajmalnik-Brown said. “Keep your gut healthy and your microbes healthy, and that should eventually lead to a healthy weight. You’ll make your microbes happy, and your microbes do a lot for your health.”

A version of this article appeared on WebMD.com.

TOPLINE: 

Accelerometer-measured physical activity (PA), whether light, moderate, or vigorous, is associated with lower risk for heart failure (HF) in older women while more sedentary time is associated with higher HF risk in these women, results of a new study suggest. 

METHODOLOGY:

• The analysis included 5951 women aged 63-99 years (mean age, 78.6 years), including 33.7% Black, 17.2% Hispanic, and 49.2% White individuals without HF from the Objective Physical Activity and Cardiovascular Health (OPACH) study, an ancillary to the Women’s Health Initiative Long-Life Study.
• Participants wore an accelerometer on their hip 24 hours a day for up to 7 consecutive days except when in water, kept nightly sleep logs, completed questionnaires to provide information on medical history and sociodemographic and lifestyle factors, and self-rated their general health status.
• Researchers recorded their use of assistive walking devices; determined body mass index as well as blood pressure; obtained fasting serum glucose, total and high-density lipoprotein cholesterol, triglyceride, and high-sensitivity C-reactive protein concentrations; and scored participants’ multimorbidity.
• They determined intensity-specific PA using vector magnitude acceleration cut points (light PA, 19-518 counts/15 s; moderate to vigorous PA [MVPA], > 518) and steps per day using dedicated software, and they quantified sedentary time (total and mean bout duration).
• The primary outcome was overall self-reported HF later adjudicated by physicians using medical record reviews; secondary endpoints were heart failure with reduced ejection fraction (HFrEF) and preserved EF (HFpEF), classified by an EF of < 45% or 45% or > 45%, respectively, after cardiac imaging.

TAKEAWAY:

• A total of 407 HF cases (including 257 HFpEF and 110 HFrEF) were identified during a mean of 7.5 years of follow-up.
• HFrEF was not associated with PA measures in the fully adjusted model (which controlled extensively for health and physical functioning status), but overall HF and HFpEF were inversely associated with total PA (per 1-standard deviation [SD] increment: hazard ratio [HR] 0.85; 95% CI, 0.75-0.95 and HR, 0.78; 95% CI, 0.67-0.91, respectively), light PA (HR, 0.88; 95% CI, 0.78-0.98 and HR, 0.80; 95% CI, 0.70-0.93, respectively) and MVPA (HR, 0.84; 95% CI, 0.73-0.97 and HR, 0.85; 95% CI, 0.72-1.01, respectively).
• With regard to daily steps, each 1-SD increment was associated with a significant 26% lower risk for overall HF (HR 0.74; 95% CI, 0.63-0.88) and 29% lower risk for HFpEF (HR, 0.71; 95% CI, 0.57-0.88), with these inverse risks becoming significant at about 2000 steps/d, “far less than the often touted 10,000 steps/d for promoting health benefits,” noted the authors.
• Total sedentary time was positively associated (per 1 SD in the fully adjusted model) with risks of overall HF (HR, 1.17; 95% CI, 1.04-1.33) and HFpEF (HR, 1.29; 95% CI, 1.10-1.51) but not HFrEF; mean sedentary bout duration was significantly inversely associated with HFrEF (per 1 SD: HR, 0.76; 95% CI, 0.61-0.97), although the relatively small number of cases at the extremes of bout duration may contribute to this unexpected inverse association, said the authors.

IN PRACTICE:

The implications of promoting PA, regardless of intensity, for primary HFpEF prevention in later life, “has profound public health and clinical relevance,” the authors concluded. They noted that HFpEF is a “burgeoning epidemic” that disproportionately affects women and minorities with limited available therapies.

STUDY DETAILS:

The study, led by Michael J. LaMonte, PhD, MPH, University at Buffalo-SUNY, Buffalo, New York, was published online on February 21, 2024, in JAMA Cardiology.

LIMITATIONS:

There was only a single accelerometer assessment of PA and sedentary exposures and relatively small numbers of HFrEF cases, which restricted analytic precision. Although researchers controlled for several established vascular biomarkers, they did not have HF-specific measures such as cardiac troponin or N-terminal pro–brain natriuretic peptide. It’s unknown if the findings can be generalized to men and populations dissimilar to women in OPACH.

DISCLOSURES:

The study was funded in part by the National Heart, Lung, and Blood Institute, National Institutes of Health, and US Department of Health and Human Services. LaMonte reported receiving grants from the National Institutes of Health during the conduct of the study; see paper for disclosures of the other authors.
 

A version of this article appeared on Medscape.com.

TOPLINE: 

Accelerometer-measured physical activity (PA), whether light, moderate, or vigorous, is associated with lower risk for heart failure (HF) in older women while more sedentary time is associated with higher HF risk in these women, results of a new study suggest. 

METHODOLOGY:

• The analysis included 5951 women aged 63-99 years (mean age, 78.6 years), including 33.7% Black, 17.2% Hispanic, and 49.2% White individuals without HF from the Objective Physical Activity and Cardiovascular Health (OPACH) study, an ancillary to the Women’s Health Initiative Long-Life Study.
• Participants wore an accelerometer on their hip 24 hours a day for up to 7 consecutive days except when in water, kept nightly sleep logs, completed questionnaires to provide information on medical history and sociodemographic and lifestyle factors, and self-rated their general health status.
• Researchers recorded their use of assistive walking devices; determined body mass index as well as blood pressure; obtained fasting serum glucose, total and high-density lipoprotein cholesterol, triglyceride, and high-sensitivity C-reactive protein concentrations; and scored participants’ multimorbidity.
• They determined intensity-specific PA using vector magnitude acceleration cut points (light PA, 19-518 counts/15 s; moderate to vigorous PA [MVPA], > 518) and steps per day using dedicated software, and they quantified sedentary time (total and mean bout duration).
• The primary outcome was overall self-reported HF later adjudicated by physicians using medical record reviews; secondary endpoints were heart failure with reduced ejection fraction (HFrEF) and preserved EF (HFpEF), classified by an EF of < 45% or 45% or > 45%, respectively, after cardiac imaging.

TAKEAWAY:

• A total of 407 HF cases (including 257 HFpEF and 110 HFrEF) were identified during a mean of 7.5 years of follow-up.
• HFrEF was not associated with PA measures in the fully adjusted model (which controlled extensively for health and physical functioning status), but overall HF and HFpEF were inversely associated with total PA (per 1-standard deviation [SD] increment: hazard ratio [HR] 0.85; 95% CI, 0.75-0.95 and HR, 0.78; 95% CI, 0.67-0.91, respectively), light PA (HR, 0.88; 95% CI, 0.78-0.98 and HR, 0.80; 95% CI, 0.70-0.93, respectively) and MVPA (HR, 0.84; 95% CI, 0.73-0.97 and HR, 0.85; 95% CI, 0.72-1.01, respectively).
• With regard to daily steps, each 1-SD increment was associated with a significant 26% lower risk for overall HF (HR 0.74; 95% CI, 0.63-0.88) and 29% lower risk for HFpEF (HR, 0.71; 95% CI, 0.57-0.88), with these inverse risks becoming significant at about 2000 steps/d, “far less than the often touted 10,000 steps/d for promoting health benefits,” noted the authors.
• Total sedentary time was positively associated (per 1 SD in the fully adjusted model) with risks of overall HF (HR, 1.17; 95% CI, 1.04-1.33) and HFpEF (HR, 1.29; 95% CI, 1.10-1.51) but not HFrEF; mean sedentary bout duration was significantly inversely associated with HFrEF (per 1 SD: HR, 0.76; 95% CI, 0.61-0.97), although the relatively small number of cases at the extremes of bout duration may contribute to this unexpected inverse association, said the authors.

IN PRACTICE:

The implications of promoting PA, regardless of intensity, for primary HFpEF prevention in later life, “has profound public health and clinical relevance,” the authors concluded. They noted that HFpEF is a “burgeoning epidemic” that disproportionately affects women and minorities with limited available therapies.

STUDY DETAILS:

The study, led by Michael J. LaMonte, PhD, MPH, University at Buffalo-SUNY, Buffalo, New York, was published online on February 21, 2024, in JAMA Cardiology.

LIMITATIONS:

There was only a single accelerometer assessment of PA and sedentary exposures and relatively small numbers of HFrEF cases, which restricted analytic precision. Although researchers controlled for several established vascular biomarkers, they did not have HF-specific measures such as cardiac troponin or N-terminal pro–brain natriuretic peptide. It’s unknown if the findings can be generalized to men and populations dissimilar to women in OPACH.

DISCLOSURES:

The study was funded in part by the National Heart, Lung, and Blood Institute, National Institutes of Health, and US Department of Health and Human Services. LaMonte reported receiving grants from the National Institutes of Health during the conduct of the study; see paper for disclosures of the other authors.
 

A version of this article appeared on Medscape.com.

TOPLINE: 

Accelerometer-measured physical activity (PA), whether light, moderate, or vigorous, is associated with lower risk for heart failure (HF) in older women while more sedentary time is associated with higher HF risk in these women, results of a new study suggest. 

METHODOLOGY:

• The analysis included 5951 women aged 63-99 years (mean age, 78.6 years), including 33.7% Black, 17.2% Hispanic, and 49.2% White individuals without HF from the Objective Physical Activity and Cardiovascular Health (OPACH) study, an ancillary to the Women’s Health Initiative Long-Life Study.
• Participants wore an accelerometer on their hip 24 hours a day for up to 7 consecutive days except when in water, kept nightly sleep logs, completed questionnaires to provide information on medical history and sociodemographic and lifestyle factors, and self-rated their general health status.
• Researchers recorded their use of assistive walking devices; determined body mass index as well as blood pressure; obtained fasting serum glucose, total and high-density lipoprotein cholesterol, triglyceride, and high-sensitivity C-reactive protein concentrations; and scored participants’ multimorbidity.
• They determined intensity-specific PA using vector magnitude acceleration cut points (light PA, 19-518 counts/15 s; moderate to vigorous PA [MVPA], > 518) and steps per day using dedicated software, and they quantified sedentary time (total and mean bout duration).
• The primary outcome was overall self-reported HF later adjudicated by physicians using medical record reviews; secondary endpoints were heart failure with reduced ejection fraction (HFrEF) and preserved EF (HFpEF), classified by an EF of < 45% or 45% or > 45%, respectively, after cardiac imaging.

TAKEAWAY:

• A total of 407 HF cases (including 257 HFpEF and 110 HFrEF) were identified during a mean of 7.5 years of follow-up.
• HFrEF was not associated with PA measures in the fully adjusted model (which controlled extensively for health and physical functioning status), but overall HF and HFpEF were inversely associated with total PA (per 1-standard deviation [SD] increment: hazard ratio [HR] 0.85; 95% CI, 0.75-0.95 and HR, 0.78; 95% CI, 0.67-0.91, respectively), light PA (HR, 0.88; 95% CI, 0.78-0.98 and HR, 0.80; 95% CI, 0.70-0.93, respectively) and MVPA (HR, 0.84; 95% CI, 0.73-0.97 and HR, 0.85; 95% CI, 0.72-1.01, respectively).
• With regard to daily steps, each 1-SD increment was associated with a significant 26% lower risk for overall HF (HR 0.74; 95% CI, 0.63-0.88) and 29% lower risk for HFpEF (HR, 0.71; 95% CI, 0.57-0.88), with these inverse risks becoming significant at about 2000 steps/d, “far less than the often touted 10,000 steps/d for promoting health benefits,” noted the authors.
• Total sedentary time was positively associated (per 1 SD in the fully adjusted model) with risks of overall HF (HR, 1.17; 95% CI, 1.04-1.33) and HFpEF (HR, 1.29; 95% CI, 1.10-1.51) but not HFrEF; mean sedentary bout duration was significantly inversely associated with HFrEF (per 1 SD: HR, 0.76; 95% CI, 0.61-0.97), although the relatively small number of cases at the extremes of bout duration may contribute to this unexpected inverse association, said the authors.

IN PRACTICE:

The implications of promoting PA, regardless of intensity, for primary HFpEF prevention in later life, “has profound public health and clinical relevance,” the authors concluded. They noted that HFpEF is a “burgeoning epidemic” that disproportionately affects women and minorities with limited available therapies.

STUDY DETAILS:

The study, led by Michael J. LaMonte, PhD, MPH, University at Buffalo-SUNY, Buffalo, New York, was published online on February 21, 2024, in JAMA Cardiology.

LIMITATIONS:

There was only a single accelerometer assessment of PA and sedentary exposures and relatively small numbers of HFrEF cases, which restricted analytic precision. Although researchers controlled for several established vascular biomarkers, they did not have HF-specific measures such as cardiac troponin or N-terminal pro–brain natriuretic peptide. It’s unknown if the findings can be generalized to men and populations dissimilar to women in OPACH.

DISCLOSURES:

The study was funded in part by the National Heart, Lung, and Blood Institute, National Institutes of Health, and US Department of Health and Human Services. LaMonte reported receiving grants from the National Institutes of Health during the conduct of the study; see paper for disclosures of the other authors.
 

A version of this article appeared on Medscape.com.

The risk of being hospitalized because of COVID-19 was reduced by 84% among people who used Paxlovid, reports a new study.

This medicine has been approved for use in the United States for people over 12 years old who are at risk of having a severe COVID-19 infection. 

The study was published in the Journal of Antimicrobial Chemotherapy.

Study authors examined the health records of almost 45,000 outpatients who tested positive for COVID-19 from January to August 2022. This sample period was when the Omicron strain was dominant.

The average patient age was 47. Sixty-two percent were White, 24% were Black, 6% were Hispanic, and 8% had an unknown ethnicity. A slight majority, 51%, had received two or more vaccine doses before the study period.

From the study group, 201 people were hospitalized within 28 days of their positive COVID test.

Almost 5,000 people in the study group received Paxlovid. The use of Paxlovid was the best indicator of avoiding hospitalization, with three of those people being hospitalized.

“Patients who were treated with Paxlovid were twice as likely to have received at least two doses of COVID-19 vaccine,” the University of Minnesota’s CIDRAP reported. “They were also more likely to be 70 years or older.”

People taking Paxlovid were more likely to be White and to live in middle- or upper-income areas.

“COVID-19 hospitalization risk was reduced by 84% among [Paxlovid] recipients in a large, diverse healthcare system during the Omicron wave,” the study’s authors wrote. “These results suggest that [Paxlovid] remained highly effective in a setting substantially different than the original clinical trials.”
 

A version of this article appeared on WebMD.com.

The risk of being hospitalized because of COVID-19 was reduced by 84% among people who used Paxlovid, reports a new study.

This medicine has been approved for use in the United States for people over 12 years old who are at risk of having a severe COVID-19 infection. 

The study was published in the Journal of Antimicrobial Chemotherapy.

Study authors examined the health records of almost 45,000 outpatients who tested positive for COVID-19 from January to August 2022. This sample period was when the Omicron strain was dominant.

The average patient age was 47. Sixty-two percent were White, 24% were Black, 6% were Hispanic, and 8% had an unknown ethnicity. A slight majority, 51%, had received two or more vaccine doses before the study period.

From the study group, 201 people were hospitalized within 28 days of their positive COVID test.

Almost 5,000 people in the study group received Paxlovid. The use of Paxlovid was the best indicator of avoiding hospitalization, with three of those people being hospitalized.

“Patients who were treated with Paxlovid were twice as likely to have received at least two doses of COVID-19 vaccine,” the University of Minnesota’s CIDRAP reported. “They were also more likely to be 70 years or older.”

People taking Paxlovid were more likely to be White and to live in middle- or upper-income areas.

“COVID-19 hospitalization risk was reduced by 84% among [Paxlovid] recipients in a large, diverse healthcare system during the Omicron wave,” the study’s authors wrote. “These results suggest that [Paxlovid] remained highly effective in a setting substantially different than the original clinical trials.”
 

A version of this article appeared on WebMD.com.

The risk of being hospitalized because of COVID-19 was reduced by 84% among people who used Paxlovid, reports a new study.

This medicine has been approved for use in the United States for people over 12 years old who are at risk of having a severe COVID-19 infection. 

The study was published in the Journal of Antimicrobial Chemotherapy.

Study authors examined the health records of almost 45,000 outpatients who tested positive for COVID-19 from January to August 2022. This sample period was when the Omicron strain was dominant.

The average patient age was 47. Sixty-two percent were White, 24% were Black, 6% were Hispanic, and 8% had an unknown ethnicity. A slight majority, 51%, had received two or more vaccine doses before the study period.

From the study group, 201 people were hospitalized within 28 days of their positive COVID test.

Almost 5,000 people in the study group received Paxlovid. The use of Paxlovid was the best indicator of avoiding hospitalization, with three of those people being hospitalized.

“Patients who were treated with Paxlovid were twice as likely to have received at least two doses of COVID-19 vaccine,” the University of Minnesota’s CIDRAP reported. “They were also more likely to be 70 years or older.”

People taking Paxlovid were more likely to be White and to live in middle- or upper-income areas.

“COVID-19 hospitalization risk was reduced by 84% among [Paxlovid] recipients in a large, diverse healthcare system during the Omicron wave,” the study’s authors wrote. “These results suggest that [Paxlovid] remained highly effective in a setting substantially different than the original clinical trials.”
 

A version of this article appeared on WebMD.com.

Many patients with obesity blame weight gain on their metabolism. The reality is that metabolism can be blamed for weight regain after people try to lose weight! As we age, our metabolism does slow down; sometimes we think it stops working.

Metabolism, or resting energy expenditure, is directly related to how much muscle mass we have. As we age, we lose muscle, which is called sarcopenia.

What happens to our metabolism when we try to lose weight? Let’s first discuss what metabolism is.
 

What Is Metabolism?

Metabolism refers to the chemical reactions in the body’s cells that convert food into energy for sustaining life, cellular processes, and as storage for a rainy day.

Total energy expenditure (TEE) is broken down into resting energy expenditure (REE), thermic effect of food (TEF), and nonresting expenditure (NREE) or physical activity, and is made up of: TEE = 60% REE + 10% TEF + 30% NREE.

An elegant study performed by Dr. Rudy Leibel explored the effects of weight loss or weight gain on metabolism in 23 lean and 18 patients with obesity who were placed in a metabolic chamber. Weight loss of 10% or 20% body weight led to a decrease in TEE roughly equal to about 300 kcal/d, and an increase in body weight of 10% caused an increase in TEE of about 500 kcal/d. These changes led to the patient reverting to the prior weight (before weight loss or gain). In other words, Dr. Leibel postulated a feedback mechanism for the effect of fat mass decrease or increase on energy metabolism. The feedback mechanism or signal from fat was subsequently found to be leptin.

In a later study, Dr. Leibel and colleagues investigated the effects of body fat mass change on TEE and found that a 10% reduction in weight caused a decrease of TEE by 21%, comprising a decrease in NREE of 37.5% and a decrease in REE of 11.6%.

Therefore, the biggest change in TEE comes from NREE or exercise energy expenditure. The 35% variance in NEE change was accounted for by a decrease in muscle work efficiency in generating 10 watts or low levels of work such as walking.

In other words, when persons with obesity or lean persons lose weight, the efficiency of muscle at low levels of work increases such that one burns less energy when walking than one normally would. This helps conserve energy and tends to cause the body to go back to the higher weight.
 

So, How Can One Change Metabolism?

Let’s say one did lose weight and wants to counteract this TEE loss and increased muscle efficiency at low levels of work.

To counteract this effect, one should increase muscle work beyond low level so that more energy is expended. Another way would be to increase muscle mass so that there is more muscle that can do work.

This is exactly how metabolism can be altered or increased. What can be changed most readily, and what we have the most power over in our bodies, is the NREE.

To do this, muscles need anabolic power — the power to heal and build muscle mass. Anabolic power comes from eating healthy protein sources such as lean chicken, fish, beef, and eggs as well as dry beans, tofu, and dairy products.. It seems that older adults (> 60 years) need more protein than younger adults to build muscle mass, due to the body’s natural aging process which leads to sarcopenia. How much more? Studies show between 1.2 and 1.5 g/kg of body weight per day, whereas younger persons need 0.80 g/kg.

Developing sarcopenia with age involves muscle losing the ability to use protein and amino acids to rebuild injured tissue.

Let’s put this in perspective for treating obesity.

Obesity is brought on by the body’s defense of a higher body weight by interaction with the environment of highly processed foods that work on the reward pathway, leading to weight gain and resistance to satiety. Weight loss via diet, exercise, and medications works, but this weight loss is also accompanied by a decrease in TEE.

Weight loss is primarily fat mass loss, but depending on the degree of protein intake and muscle resistance training, 20%-50% of the total weight loss is muscle mass loss. Therefore, higher-protein diets and resistance exercise can be useful in preserving muscle mass and counteracting the decrease in TEE, maintaining energy expenditure. In older patients, an additional factor is the muscle’s lack of ability to use protein as an anabolic agent to protect muscle mass and thus the need for higher protein loads to do this.

All in all, can doctors help patients boost their metabolism, especially as they lose weight and maintain that loss? Yes — through protein intake and resistance exercise training.

Here are some tips to help your patients get cardio and resistance exercise into their routine.

First find out whether your patient prefers a social exercise interaction or solo training. If social, then the gym or classes such as cycling or boot camps at those gyms may work for them, especially if they can go with a friend. If solo is better, than a gym in the home might work. Peloton bikes are expensive but the interaction is all on the website!

A personal trainer may help motivate the patient if they know someone is waiting for them.

Let’s hit the gym!

Another note: There are agents in the obesity treatment pipeline that purport to change body composition while helping patients lose weight. Some of these agents are myostatin antagonists and antibodies that inhibit the activity of myostatin to break down muscle. These agents have been found to build muscle mass, but whether the quality of the muscle mass leads to an increase in muscle strength or functionality remains controversial. The next frontier in obesity treatment will be about decreasing fat mass and increasing muscle mass while making sure that increased muscle mass leads to improved functionality.

In the meantime, aside from new agents on the horizon, the best and healthiest way to keep metabolism on the up and up is to eat healthy lean proteins and exercise. How much exercise? The recommendation is 30-60 minutes of moderate to vigorous physical activity at least 5 days per week; plus 20 minutes of resistance exercise training 2-3 days per week for upper- and lower-extremity and core strength.

Again, let’s hit the gym!
 

Dr. Apovian is in the department of medicine, and codirector, Center for Weight Management and Wellness, Section of Endocrinology, Diabetes, and Hypertension, at Brigham and Women’s Hospital, Harvard Medical School, Boston. She disclosed ties with Altimmune, Cowen and Company, Currax Pharmaceuticals, EPG Communication Holdings, Gelesis, Srl, L-Nutra, and NeuroBo Pharmaceuticals, and Novo Nordisk. She received research grant from the National Institutes of Health, Patient-Centered Outcomes Research Institute, and GI Dynamics.

A version of this article appeared on Medscape.com.

Many patients with obesity blame weight gain on their metabolism. The reality is that metabolism can be blamed for weight regain after people try to lose weight! As we age, our metabolism does slow down; sometimes we think it stops working.

Metabolism, or resting energy expenditure, is directly related to how much muscle mass we have. As we age, we lose muscle, which is called sarcopenia.

What happens to our metabolism when we try to lose weight? Let’s first discuss what metabolism is.
 

What Is Metabolism?

Metabolism refers to the chemical reactions in the body’s cells that convert food into energy for sustaining life, cellular processes, and as storage for a rainy day.

Total energy expenditure (TEE) is broken down into resting energy expenditure (REE), thermic effect of food (TEF), and nonresting expenditure (NREE) or physical activity, and is made up of: TEE = 60% REE + 10% TEF + 30% NREE.

An elegant study performed by Dr. Rudy Leibel explored the effects of weight loss or weight gain on metabolism in 23 lean and 18 patients with obesity who were placed in a metabolic chamber. Weight loss of 10% or 20% body weight led to a decrease in TEE roughly equal to about 300 kcal/d, and an increase in body weight of 10% caused an increase in TEE of about 500 kcal/d. These changes led to the patient reverting to the prior weight (before weight loss or gain). In other words, Dr. Leibel postulated a feedback mechanism for the effect of fat mass decrease or increase on energy metabolism. The feedback mechanism or signal from fat was subsequently found to be leptin.

In a later study, Dr. Leibel and colleagues investigated the effects of body fat mass change on TEE and found that a 10% reduction in weight caused a decrease of TEE by 21%, comprising a decrease in NREE of 37.5% and a decrease in REE of 11.6%.

Therefore, the biggest change in TEE comes from NREE or exercise energy expenditure. The 35% variance in NEE change was accounted for by a decrease in muscle work efficiency in generating 10 watts or low levels of work such as walking.

In other words, when persons with obesity or lean persons lose weight, the efficiency of muscle at low levels of work increases such that one burns less energy when walking than one normally would. This helps conserve energy and tends to cause the body to go back to the higher weight.
 

So, How Can One Change Metabolism?

Let’s say one did lose weight and wants to counteract this TEE loss and increased muscle efficiency at low levels of work.

To counteract this effect, one should increase muscle work beyond low level so that more energy is expended. Another way would be to increase muscle mass so that there is more muscle that can do work.

This is exactly how metabolism can be altered or increased. What can be changed most readily, and what we have the most power over in our bodies, is the NREE.

To do this, muscles need anabolic power — the power to heal and build muscle mass. Anabolic power comes from eating healthy protein sources such as lean chicken, fish, beef, and eggs as well as dry beans, tofu, and dairy products.. It seems that older adults (> 60 years) need more protein than younger adults to build muscle mass, due to the body’s natural aging process which leads to sarcopenia. How much more? Studies show between 1.2 and 1.5 g/kg of body weight per day, whereas younger persons need 0.80 g/kg.

Developing sarcopenia with age involves muscle losing the ability to use protein and amino acids to rebuild injured tissue.

Let’s put this in perspective for treating obesity.

Obesity is brought on by the body’s defense of a higher body weight by interaction with the environment of highly processed foods that work on the reward pathway, leading to weight gain and resistance to satiety. Weight loss via diet, exercise, and medications works, but this weight loss is also accompanied by a decrease in TEE.

Weight loss is primarily fat mass loss, but depending on the degree of protein intake and muscle resistance training, 20%-50% of the total weight loss is muscle mass loss. Therefore, higher-protein diets and resistance exercise can be useful in preserving muscle mass and counteracting the decrease in TEE, maintaining energy expenditure. In older patients, an additional factor is the muscle’s lack of ability to use protein as an anabolic agent to protect muscle mass and thus the need for higher protein loads to do this.

All in all, can doctors help patients boost their metabolism, especially as they lose weight and maintain that loss? Yes — through protein intake and resistance exercise training.

Here are some tips to help your patients get cardio and resistance exercise into their routine.

First find out whether your patient prefers a social exercise interaction or solo training. If social, then the gym or classes such as cycling or boot camps at those gyms may work for them, especially if they can go with a friend. If solo is better, than a gym in the home might work. Peloton bikes are expensive but the interaction is all on the website!

A personal trainer may help motivate the patient if they know someone is waiting for them.

Let’s hit the gym!

Another note: There are agents in the obesity treatment pipeline that purport to change body composition while helping patients lose weight. Some of these agents are myostatin antagonists and antibodies that inhibit the activity of myostatin to break down muscle. These agents have been found to build muscle mass, but whether the quality of the muscle mass leads to an increase in muscle strength or functionality remains controversial. The next frontier in obesity treatment will be about decreasing fat mass and increasing muscle mass while making sure that increased muscle mass leads to improved functionality.

In the meantime, aside from new agents on the horizon, the best and healthiest way to keep metabolism on the up and up is to eat healthy lean proteins and exercise. How much exercise? The recommendation is 30-60 minutes of moderate to vigorous physical activity at least 5 days per week; plus 20 minutes of resistance exercise training 2-3 days per week for upper- and lower-extremity and core strength.

Again, let’s hit the gym!
 

Dr. Apovian is in the department of medicine, and codirector, Center for Weight Management and Wellness, Section of Endocrinology, Diabetes, and Hypertension, at Brigham and Women’s Hospital, Harvard Medical School, Boston. She disclosed ties with Altimmune, Cowen and Company, Currax Pharmaceuticals, EPG Communication Holdings, Gelesis, Srl, L-Nutra, and NeuroBo Pharmaceuticals, and Novo Nordisk. She received research grant from the National Institutes of Health, Patient-Centered Outcomes Research Institute, and GI Dynamics.

A version of this article appeared on Medscape.com.

Many patients with obesity blame weight gain on their metabolism. The reality is that metabolism can be blamed for weight regain after people try to lose weight! As we age, our metabolism does slow down; sometimes we think it stops working.

Metabolism, or resting energy expenditure, is directly related to how much muscle mass we have. As we age, we lose muscle, which is called sarcopenia.

What happens to our metabolism when we try to lose weight? Let’s first discuss what metabolism is.
 

What Is Metabolism?

Metabolism refers to the chemical reactions in the body’s cells that convert food into energy for sustaining life, cellular processes, and as storage for a rainy day.

Total energy expenditure (TEE) is broken down into resting energy expenditure (REE), thermic effect of food (TEF), and nonresting expenditure (NREE) or physical activity, and is made up of: TEE = 60% REE + 10% TEF + 30% NREE.

An elegant study performed by Dr. Rudy Leibel explored the effects of weight loss or weight gain on metabolism in 23 lean and 18 patients with obesity who were placed in a metabolic chamber. Weight loss of 10% or 20% body weight led to a decrease in TEE roughly equal to about 300 kcal/d, and an increase in body weight of 10% caused an increase in TEE of about 500 kcal/d. These changes led to the patient reverting to the prior weight (before weight loss or gain). In other words, Dr. Leibel postulated a feedback mechanism for the effect of fat mass decrease or increase on energy metabolism. The feedback mechanism or signal from fat was subsequently found to be leptin.

In a later study, Dr. Leibel and colleagues investigated the effects of body fat mass change on TEE and found that a 10% reduction in weight caused a decrease of TEE by 21%, comprising a decrease in NREE of 37.5% and a decrease in REE of 11.6%.

Therefore, the biggest change in TEE comes from NREE or exercise energy expenditure. The 35% variance in NEE change was accounted for by a decrease in muscle work efficiency in generating 10 watts or low levels of work such as walking.

In other words, when persons with obesity or lean persons lose weight, the efficiency of muscle at low levels of work increases such that one burns less energy when walking than one normally would. This helps conserve energy and tends to cause the body to go back to the higher weight.
 

So, How Can One Change Metabolism?

Let’s say one did lose weight and wants to counteract this TEE loss and increased muscle efficiency at low levels of work.

To counteract this effect, one should increase muscle work beyond low level so that more energy is expended. Another way would be to increase muscle mass so that there is more muscle that can do work.

This is exactly how metabolism can be altered or increased. What can be changed most readily, and what we have the most power over in our bodies, is the NREE.

To do this, muscles need anabolic power — the power to heal and build muscle mass. Anabolic power comes from eating healthy protein sources such as lean chicken, fish, beef, and eggs as well as dry beans, tofu, and dairy products.. It seems that older adults (> 60 years) need more protein than younger adults to build muscle mass, due to the body’s natural aging process which leads to sarcopenia. How much more? Studies show between 1.2 and 1.5 g/kg of body weight per day, whereas younger persons need 0.80 g/kg.

Developing sarcopenia with age involves muscle losing the ability to use protein and amino acids to rebuild injured tissue.

Let’s put this in perspective for treating obesity.

Obesity is brought on by the body’s defense of a higher body weight by interaction with the environment of highly processed foods that work on the reward pathway, leading to weight gain and resistance to satiety. Weight loss via diet, exercise, and medications works, but this weight loss is also accompanied by a decrease in TEE.

Weight loss is primarily fat mass loss, but depending on the degree of protein intake and muscle resistance training, 20%-50% of the total weight loss is muscle mass loss. Therefore, higher-protein diets and resistance exercise can be useful in preserving muscle mass and counteracting the decrease in TEE, maintaining energy expenditure. In older patients, an additional factor is the muscle’s lack of ability to use protein as an anabolic agent to protect muscle mass and thus the need for higher protein loads to do this.

All in all, can doctors help patients boost their metabolism, especially as they lose weight and maintain that loss? Yes — through protein intake and resistance exercise training.

Here are some tips to help your patients get cardio and resistance exercise into their routine.

First find out whether your patient prefers a social exercise interaction or solo training. If social, then the gym or classes such as cycling or boot camps at those gyms may work for them, especially if they can go with a friend. If solo is better, than a gym in the home might work. Peloton bikes are expensive but the interaction is all on the website!

A personal trainer may help motivate the patient if they know someone is waiting for them.

Let’s hit the gym!

Another note: There are agents in the obesity treatment pipeline that purport to change body composition while helping patients lose weight. Some of these agents are myostatin antagonists and antibodies that inhibit the activity of myostatin to break down muscle. These agents have been found to build muscle mass, but whether the quality of the muscle mass leads to an increase in muscle strength or functionality remains controversial. The next frontier in obesity treatment will be about decreasing fat mass and increasing muscle mass while making sure that increased muscle mass leads to improved functionality.

In the meantime, aside from new agents on the horizon, the best and healthiest way to keep metabolism on the up and up is to eat healthy lean proteins and exercise. How much exercise? The recommendation is 30-60 minutes of moderate to vigorous physical activity at least 5 days per week; plus 20 minutes of resistance exercise training 2-3 days per week for upper- and lower-extremity and core strength.

Again, let’s hit the gym!
 

Dr. Apovian is in the department of medicine, and codirector, Center for Weight Management and Wellness, Section of Endocrinology, Diabetes, and Hypertension, at Brigham and Women’s Hospital, Harvard Medical School, Boston. She disclosed ties with Altimmune, Cowen and Company, Currax Pharmaceuticals, EPG Communication Holdings, Gelesis, Srl, L-Nutra, and NeuroBo Pharmaceuticals, and Novo Nordisk. She received research grant from the National Institutes of Health, Patient-Centered Outcomes Research Institute, and GI Dynamics.

A version of this article appeared on Medscape.com.

“She’s, like, 90 years old. I’m not going to ask her about sex!” says the cringing resident. “She’s older than my grandmother!”

Well, my young friend, our 80- and 90-year-old patients were in their 20s and 30s in the 1960s. You can bet some of them were pretty groovy! A Swedish study of septuagenarians revealed a shift in sexual attitudes: from 5% of 70-year-old women in the 1970s citing sex as a positive aspect of life, to 78% in 2000. Those of us in practice who came of age during the AIDS era and alongside the purity movement of the 1990s can be more sexually reserved than our grandparents. We might need to catch up. In fact, in another study, 82% of 97-year-old female participants felt that being asked about their sexuality in healthcare settings was positive.

While changes do occur in sexual physiology and behavior with age, satisfying sexual engagement may be an important factor in the general well-being and overall health of older women. Given the high prevalence of dementia among this population, it may be useful to know that positive sexual expression may delay cognitive decline. We also have evidence that sexual satisfaction is important for relational health, which in turn helps predict physical health.

Shed the Dysfunction Mindset

Our medical bias has been that a fulfilling sexual life requires a hard penis and a lubricated vagina. This view of the range of healthy and satisfying sexual expression is lamentably limited. Older adults may have more problems with physiologic arousal in the form of more erectile dysfunction and decreased vaginal lubrication, but these issues may lead to partnerships in which there is less insertive/receiving sexual play and more oral sex, cuddling, kissing, and other forms of partnered sexual play. Older adults may focus less on performance and more on intimacy. In fact, as heterosexual couples encounter these physiologic changes, their sexual behavior may begin to focus more attention to female pleasure. Good news for older women!

As described by Dutch sexuality and aging expert Woet Gianotten, MD, older adults have a lot going for them in their sex lives. Many are retired with more time available, less work stress, greater comfort and familiarity with their partners, and less insecurity about their bodies.

Common Concerns

Many older adults are having satisfying sexual play and are less bothered by changes in their sexual physiology. Still, for those who aren’t happy with their sex lives, clinicians must be ready to address these concerns.

Nancy, an 87-year-old patient whose husband died 5 years ago after 59 years of marriage, has just met someone new. When they are intimate physically, she’s not feeling aroused in the way she recalls, and wonders, Where have my orgasms gone?

A host of physical changes among older women can affect the sexual experience, including the vulvovaginal changes of genitourinary syndrome of menopause (GSM), incontinence, uterine prolapse, diminished sensation, and reduced overall mobility. Although aging is responsible for some of these changes, chronic diseases and medical treatments can play an even larger role.

GSM is a major contributor to sexual pain, genital irritation, and reduced arousal and orgasm. It’s crazy that we don’t ask about and treat GSM. Beyond the sexual impact, the vaginal dryness of GSM can contribute to urinary tract infections, which can lead to sepsis and even death! Vaginal estrogens and other GSM treatments are safe and effective in the vast majority of women. Vaginal moisturizers, vaginal dilators, and increasing genital blood flow also help improve GSM.

Vaginal dilators are used in the management of vaginal stenosis, when the vaginal skin has contracted as a result of GSM or pelvic radiation to treat cancer. Dilators are also used to treat some forms of high-tone pelvic floor dysfunction. For expert guidance and coaching on the use of dilators, seek out sexual medicine specialists and pelvic floor physical therapists. Pelvic floor physical therapy is important in the management of a wide range of sexual concerns, from reduced arousal and orgasm to almost any kind of sexual pain.

For postmenopausal women who are distressed by hypoactive sexual desire disorder, transdermal low-dose testosterone may be considered when other causes of low libido have been ruled out.

Due to changes in nerve fiber sensitivity over time, older age is an ideal phase of life to incorporate higher-intensity vibration and other sexual devices into solo and partner sex. Mobility limitations and joint pain can be addressed with devices designed specifically for this purpose or with the use of pillows and other supports.

As Betty Dodson, a staunch advocate for women’s pleasure until her death in 2020 at 91, wisely said, “Masturbation will get you through childhood, puberty, romance, marriage, and divorce, and it will see you through old age.” We can encourage women to see sexual play and pleasure flexibly, as a lifelong process of self-knowledge and discovery.

Basic Tips for Patients

• More “fiction and friction,” as coined by sex therapist Barry McCarthy, is necessary. As bodies age, more stimulation, both mental and physical, is necessary and often requires more direct physical stimulation of genitals.
• More time: Everything seems to take more time as we age; sex is no different.
• Incontinence concerns can be addressed by open communication and collaboration with partners, and being prepared with waterproof pads for the bed and towels.
• Ask about medical intervention–related sexual side effects. A wide range of medications can decrease desire and arousal and delay orgasm. If a change in sexual function occurred with starting a medication, it may be worthwhile investigating alternatives or, if possible, discontinuing a medication. Surgical and procedural changes to the anatomy also can affect sexual function. While correction may be impossible once certain changes have occurred, clinicians can provide patients with both validation about the problem and hope that, for the most part, with creativity and flexibility, pleasurable sexual experience is possible in all bodies.

Pebble M. Kranz, MD, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

“She’s, like, 90 years old. I’m not going to ask her about sex!” says the cringing resident. “She’s older than my grandmother!”

Well, my young friend, our 80- and 90-year-old patients were in their 20s and 30s in the 1960s. You can bet some of them were pretty groovy! A Swedish study of septuagenarians revealed a shift in sexual attitudes: from 5% of 70-year-old women in the 1970s citing sex as a positive aspect of life, to 78% in 2000. Those of us in practice who came of age during the AIDS era and alongside the purity movement of the 1990s can be more sexually reserved than our grandparents. We might need to catch up. In fact, in another study, 82% of 97-year-old female participants felt that being asked about their sexuality in healthcare settings was positive.

While changes do occur in sexual physiology and behavior with age, satisfying sexual engagement may be an important factor in the general well-being and overall health of older women. Given the high prevalence of dementia among this population, it may be useful to know that positive sexual expression may delay cognitive decline. We also have evidence that sexual satisfaction is important for relational health, which in turn helps predict physical health.

Shed the Dysfunction Mindset

Our medical bias has been that a fulfilling sexual life requires a hard penis and a lubricated vagina. This view of the range of healthy and satisfying sexual expression is lamentably limited. Older adults may have more problems with physiologic arousal in the form of more erectile dysfunction and decreased vaginal lubrication, but these issues may lead to partnerships in which there is less insertive/receiving sexual play and more oral sex, cuddling, kissing, and other forms of partnered sexual play. Older adults may focus less on performance and more on intimacy. In fact, as heterosexual couples encounter these physiologic changes, their sexual behavior may begin to focus more attention to female pleasure. Good news for older women!

As described by Dutch sexuality and aging expert Woet Gianotten, MD, older adults have a lot going for them in their sex lives. Many are retired with more time available, less work stress, greater comfort and familiarity with their partners, and less insecurity about their bodies.

Common Concerns

Many older adults are having satisfying sexual play and are less bothered by changes in their sexual physiology. Still, for those who aren’t happy with their sex lives, clinicians must be ready to address these concerns.

Nancy, an 87-year-old patient whose husband died 5 years ago after 59 years of marriage, has just met someone new. When they are intimate physically, she’s not feeling aroused in the way she recalls, and wonders, Where have my orgasms gone?

A host of physical changes among older women can affect the sexual experience, including the vulvovaginal changes of genitourinary syndrome of menopause (GSM), incontinence, uterine prolapse, diminished sensation, and reduced overall mobility. Although aging is responsible for some of these changes, chronic diseases and medical treatments can play an even larger role.

GSM is a major contributor to sexual pain, genital irritation, and reduced arousal and orgasm. It’s crazy that we don’t ask about and treat GSM. Beyond the sexual impact, the vaginal dryness of GSM can contribute to urinary tract infections, which can lead to sepsis and even death! Vaginal estrogens and other GSM treatments are safe and effective in the vast majority of women. Vaginal moisturizers, vaginal dilators, and increasing genital blood flow also help improve GSM.

Vaginal dilators are used in the management of vaginal stenosis, when the vaginal skin has contracted as a result of GSM or pelvic radiation to treat cancer. Dilators are also used to treat some forms of high-tone pelvic floor dysfunction. For expert guidance and coaching on the use of dilators, seek out sexual medicine specialists and pelvic floor physical therapists. Pelvic floor physical therapy is important in the management of a wide range of sexual concerns, from reduced arousal and orgasm to almost any kind of sexual pain.

For postmenopausal women who are distressed by hypoactive sexual desire disorder, transdermal low-dose testosterone may be considered when other causes of low libido have been ruled out.

Due to changes in nerve fiber sensitivity over time, older age is an ideal phase of life to incorporate higher-intensity vibration and other sexual devices into solo and partner sex. Mobility limitations and joint pain can be addressed with devices designed specifically for this purpose or with the use of pillows and other supports.

As Betty Dodson, a staunch advocate for women’s pleasure until her death in 2020 at 91, wisely said, “Masturbation will get you through childhood, puberty, romance, marriage, and divorce, and it will see you through old age.” We can encourage women to see sexual play and pleasure flexibly, as a lifelong process of self-knowledge and discovery.

Basic Tips for Patients

• More “fiction and friction,” as coined by sex therapist Barry McCarthy, is necessary. As bodies age, more stimulation, both mental and physical, is necessary and often requires more direct physical stimulation of genitals.
• More time: Everything seems to take more time as we age; sex is no different.
• Incontinence concerns can be addressed by open communication and collaboration with partners, and being prepared with waterproof pads for the bed and towels.
• Ask about medical intervention–related sexual side effects. A wide range of medications can decrease desire and arousal and delay orgasm. If a change in sexual function occurred with starting a medication, it may be worthwhile investigating alternatives or, if possible, discontinuing a medication. Surgical and procedural changes to the anatomy also can affect sexual function. While correction may be impossible once certain changes have occurred, clinicians can provide patients with both validation about the problem and hope that, for the most part, with creativity and flexibility, pleasurable sexual experience is possible in all bodies.

Pebble M. Kranz, MD, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

“She’s, like, 90 years old. I’m not going to ask her about sex!” says the cringing resident. “She’s older than my grandmother!”

Well, my young friend, our 80- and 90-year-old patients were in their 20s and 30s in the 1960s. You can bet some of them were pretty groovy! A Swedish study of septuagenarians revealed a shift in sexual attitudes: from 5% of 70-year-old women in the 1970s citing sex as a positive aspect of life, to 78% in 2000. Those of us in practice who came of age during the AIDS era and alongside the purity movement of the 1990s can be more sexually reserved than our grandparents. We might need to catch up. In fact, in another study, 82% of 97-year-old female participants felt that being asked about their sexuality in healthcare settings was positive.

While changes do occur in sexual physiology and behavior with age, satisfying sexual engagement may be an important factor in the general well-being and overall health of older women. Given the high prevalence of dementia among this population, it may be useful to know that positive sexual expression may delay cognitive decline. We also have evidence that sexual satisfaction is important for relational health, which in turn helps predict physical health.

Shed the Dysfunction Mindset

Our medical bias has been that a fulfilling sexual life requires a hard penis and a lubricated vagina. This view of the range of healthy and satisfying sexual expression is lamentably limited. Older adults may have more problems with physiologic arousal in the form of more erectile dysfunction and decreased vaginal lubrication, but these issues may lead to partnerships in which there is less insertive/receiving sexual play and more oral sex, cuddling, kissing, and other forms of partnered sexual play. Older adults may focus less on performance and more on intimacy. In fact, as heterosexual couples encounter these physiologic changes, their sexual behavior may begin to focus more attention to female pleasure. Good news for older women!

As described by Dutch sexuality and aging expert Woet Gianotten, MD, older adults have a lot going for them in their sex lives. Many are retired with more time available, less work stress, greater comfort and familiarity with their partners, and less insecurity about their bodies.

Common Concerns

Many older adults are having satisfying sexual play and are less bothered by changes in their sexual physiology. Still, for those who aren’t happy with their sex lives, clinicians must be ready to address these concerns.

Nancy, an 87-year-old patient whose husband died 5 years ago after 59 years of marriage, has just met someone new. When they are intimate physically, she’s not feeling aroused in the way she recalls, and wonders, Where have my orgasms gone?

A host of physical changes among older women can affect the sexual experience, including the vulvovaginal changes of genitourinary syndrome of menopause (GSM), incontinence, uterine prolapse, diminished sensation, and reduced overall mobility. Although aging is responsible for some of these changes, chronic diseases and medical treatments can play an even larger role.

GSM is a major contributor to sexual pain, genital irritation, and reduced arousal and orgasm. It’s crazy that we don’t ask about and treat GSM. Beyond the sexual impact, the vaginal dryness of GSM can contribute to urinary tract infections, which can lead to sepsis and even death! Vaginal estrogens and other GSM treatments are safe and effective in the vast majority of women. Vaginal moisturizers, vaginal dilators, and increasing genital blood flow also help improve GSM.

Vaginal dilators are used in the management of vaginal stenosis, when the vaginal skin has contracted as a result of GSM or pelvic radiation to treat cancer. Dilators are also used to treat some forms of high-tone pelvic floor dysfunction. For expert guidance and coaching on the use of dilators, seek out sexual medicine specialists and pelvic floor physical therapists. Pelvic floor physical therapy is important in the management of a wide range of sexual concerns, from reduced arousal and orgasm to almost any kind of sexual pain.

For postmenopausal women who are distressed by hypoactive sexual desire disorder, transdermal low-dose testosterone may be considered when other causes of low libido have been ruled out.

Due to changes in nerve fiber sensitivity over time, older age is an ideal phase of life to incorporate higher-intensity vibration and other sexual devices into solo and partner sex. Mobility limitations and joint pain can be addressed with devices designed specifically for this purpose or with the use of pillows and other supports.

As Betty Dodson, a staunch advocate for women’s pleasure until her death in 2020 at 91, wisely said, “Masturbation will get you through childhood, puberty, romance, marriage, and divorce, and it will see you through old age.” We can encourage women to see sexual play and pleasure flexibly, as a lifelong process of self-knowledge and discovery.

Basic Tips for Patients

• More “fiction and friction,” as coined by sex therapist Barry McCarthy, is necessary. As bodies age, more stimulation, both mental and physical, is necessary and often requires more direct physical stimulation of genitals.
• More time: Everything seems to take more time as we age; sex is no different.
• Incontinence concerns can be addressed by open communication and collaboration with partners, and being prepared with waterproof pads for the bed and towels.
• Ask about medical intervention–related sexual side effects. A wide range of medications can decrease desire and arousal and delay orgasm. If a change in sexual function occurred with starting a medication, it may be worthwhile investigating alternatives or, if possible, discontinuing a medication. Surgical and procedural changes to the anatomy also can affect sexual function. While correction may be impossible once certain changes have occurred, clinicians can provide patients with both validation about the problem and hope that, for the most part, with creativity and flexibility, pleasurable sexual experience is possible in all bodies.

Pebble M. Kranz, MD, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Swiss scientists have identified immune system abnormalities in patients with long COVID that might open the door to new diagnostic tests and treatments.

The researchers found that a group of proteins in the blood that are part of the body’s immune response called the “complement system” are not working properly in patients with long COVID.

Blood samples turned up important differences between those who recovered from COVID and those who did not. These differences might be used as biomarkers to diagnose long COVID and might even point the way to new treatments for the condition, the researchers said.

By testing for 6500 blood proteins in about 300 patients, the Swiss researchers found that dysfunctional complement system proteins could possibly explain fatigue and “smoldering inflammation,” said Onur Boyman, MD, a professor of immunology from University Hospital Zurich in Zurich, Switzerland.

Long COVID has been linked to hundreds of symptoms including brain fog, chronic fatigue, pain, and digestive issues. Various factors drive the condition and likely work with one another other, said David Putrino, PhD, from the Icahn School of Medicine at Mount Sinai in New York City. The Swiss study is useful because “we’re trying to best understand how we can explain all of this far-reaching pathobiology,” he said.
 

Testing Across Continents

Dr. Boyman’s team collected blood samples from people with COVID in Europe and New York and tracked them. They compared those who developed long COVID with those who did not. One protein that was most unique to patients with long COVID is a blood complement that activates the immune system, Dr. Boyman said. But in people with long COVID, the immune response stays activated after the virus is gone. He described the response as “smoldering inflammation” in multiple organs, including the lungs and the gastrointestinal system.

The complement system also plays a role in clearing the body of dead cells. If the cells “lie around too much,” they can trigger an immune response, he said.

That may explain exercise intolerance in people with long COVID, Dr. Boyman said. Some people with long COVID have inflammation in the epithelium — the inner layer of their blood vessels. This would make it harder for the circulatory systems to recover from exercise, Dr. Boyman said.

“We think this regulated complement system is actually quite a central piece of the puzzle,” he said.
 

The Microclot Connection

The findings also support past research linking blood clots to long COVID. He suggested that clinicians and researchers consider testing drugs that regulate or inhibit the complementary system as a treatment of long COVID. Dr. Boyman said they are currently used for rare immune diseases.

Resia Pretorius, PhD, a professor of physiological sciences at Stellenbosch University in Stellenbosch, South Africa, said scientists studying the role of microclots in patients with long COVID often see complementary proteins inside the clots, so it has already been associated with long COVID. But she likened this clotting process to a garbage can that “just rolls along and collects everything that gets in its way. I think they are actively driving inflammation and disease.”

One factor complicating long COVID diagnosis and treatment is that it is a complex condition that involves multiple organ systems. That’s why the latest research suggests an underlying driver for the multiple symptoms of long COVID, Dr. Putrino said.

“Not every person has every symptom; not every person has every organ system affected,” Dr. Putrino said. “Whatever is happening is decided across the whole body.”
 

Research Offers New Direction

The Swiss paper contributes to the effort to identify systemic issues contributing to long COVID. It gives researchers one more thing to test for and link to specific, long COVID symptoms, opening the door to new treatments, Dr. Putrino said.

He doesn’t think the study supports treating the complement dysfunction if researchers don’t know what’s driving it. It may be complicated by the body’s failure to clear the virus completely, he said.

Dr. Pretorius recommended doctors test patients with long COVID for specific symptoms that may be treated using existing therapies. “If you think your patient had vascular pathology, you can test for it,” she said.

Some patients have found certain supplements and over-the-counter products helpful, she said. Among them: Coenzyme Q 10 and clot-busters such as streptokinase and Nattokinase (though she noted some doctors may not be comfortable with supplements).

“It’s the only thing we have until we’ve got trials,” she said.

Dr. Putrino said more research is needed to identify potential root causes and symptoms. A common refrain, but the only thing that will lead to specific treatments.

A version of this article appeared on Medscape.com.

Swiss scientists have identified immune system abnormalities in patients with long COVID that might open the door to new diagnostic tests and treatments.

The researchers found that a group of proteins in the blood that are part of the body’s immune response called the “complement system” are not working properly in patients with long COVID.

Blood samples turned up important differences between those who recovered from COVID and those who did not. These differences might be used as biomarkers to diagnose long COVID and might even point the way to new treatments for the condition, the researchers said.

By testing for 6500 blood proteins in about 300 patients, the Swiss researchers found that dysfunctional complement system proteins could possibly explain fatigue and “smoldering inflammation,” said Onur Boyman, MD, a professor of immunology from University Hospital Zurich in Zurich, Switzerland.

Long COVID has been linked to hundreds of symptoms including brain fog, chronic fatigue, pain, and digestive issues. Various factors drive the condition and likely work with one another other, said David Putrino, PhD, from the Icahn School of Medicine at Mount Sinai in New York City. The Swiss study is useful because “we’re trying to best understand how we can explain all of this far-reaching pathobiology,” he said.
 

Testing Across Continents

Dr. Boyman’s team collected blood samples from people with COVID in Europe and New York and tracked them. They compared those who developed long COVID with those who did not. One protein that was most unique to patients with long COVID is a blood complement that activates the immune system, Dr. Boyman said. But in people with long COVID, the immune response stays activated after the virus is gone. He described the response as “smoldering inflammation” in multiple organs, including the lungs and the gastrointestinal system.

The complement system also plays a role in clearing the body of dead cells. If the cells “lie around too much,” they can trigger an immune response, he said.

That may explain exercise intolerance in people with long COVID, Dr. Boyman said. Some people with long COVID have inflammation in the epithelium — the inner layer of their blood vessels. This would make it harder for the circulatory systems to recover from exercise, Dr. Boyman said.

“We think this regulated complement system is actually quite a central piece of the puzzle,” he said.
 

The Microclot Connection

The findings also support past research linking blood clots to long COVID. He suggested that clinicians and researchers consider testing drugs that regulate or inhibit the complementary system as a treatment of long COVID. Dr. Boyman said they are currently used for rare immune diseases.

Resia Pretorius, PhD, a professor of physiological sciences at Stellenbosch University in Stellenbosch, South Africa, said scientists studying the role of microclots in patients with long COVID often see complementary proteins inside the clots, so it has already been associated with long COVID. But she likened this clotting process to a garbage can that “just rolls along and collects everything that gets in its way. I think they are actively driving inflammation and disease.”

One factor complicating long COVID diagnosis and treatment is that it is a complex condition that involves multiple organ systems. That’s why the latest research suggests an underlying driver for the multiple symptoms of long COVID, Dr. Putrino said.

“Not every person has every symptom; not every person has every organ system affected,” Dr. Putrino said. “Whatever is happening is decided across the whole body.”
 

Research Offers New Direction

The Swiss paper contributes to the effort to identify systemic issues contributing to long COVID. It gives researchers one more thing to test for and link to specific, long COVID symptoms, opening the door to new treatments, Dr. Putrino said.

He doesn’t think the study supports treating the complement dysfunction if researchers don’t know what’s driving it. It may be complicated by the body’s failure to clear the virus completely, he said.

Dr. Pretorius recommended doctors test patients with long COVID for specific symptoms that may be treated using existing therapies. “If you think your patient had vascular pathology, you can test for it,” she said.

Some patients have found certain supplements and over-the-counter products helpful, she said. Among them: Coenzyme Q 10 and clot-busters such as streptokinase and Nattokinase (though she noted some doctors may not be comfortable with supplements).

“It’s the only thing we have until we’ve got trials,” she said.

Dr. Putrino said more research is needed to identify potential root causes and symptoms. A common refrain, but the only thing that will lead to specific treatments.

A version of this article appeared on Medscape.com.

Swiss scientists have identified immune system abnormalities in patients with long COVID that might open the door to new diagnostic tests and treatments.

The researchers found that a group of proteins in the blood that are part of the body’s immune response called the “complement system” are not working properly in patients with long COVID.

Blood samples turned up important differences between those who recovered from COVID and those who did not. These differences might be used as biomarkers to diagnose long COVID and might even point the way to new treatments for the condition, the researchers said.

By testing for 6500 blood proteins in about 300 patients, the Swiss researchers found that dysfunctional complement system proteins could possibly explain fatigue and “smoldering inflammation,” said Onur Boyman, MD, a professor of immunology from University Hospital Zurich in Zurich, Switzerland.

Long COVID has been linked to hundreds of symptoms including brain fog, chronic fatigue, pain, and digestive issues. Various factors drive the condition and likely work with one another other, said David Putrino, PhD, from the Icahn School of Medicine at Mount Sinai in New York City. The Swiss study is useful because “we’re trying to best understand how we can explain all of this far-reaching pathobiology,” he said.
 

Testing Across Continents

Dr. Boyman’s team collected blood samples from people with COVID in Europe and New York and tracked them. They compared those who developed long COVID with those who did not. One protein that was most unique to patients with long COVID is a blood complement that activates the immune system, Dr. Boyman said. But in people with long COVID, the immune response stays activated after the virus is gone. He described the response as “smoldering inflammation” in multiple organs, including the lungs and the gastrointestinal system.

The complement system also plays a role in clearing the body of dead cells. If the cells “lie around too much,” they can trigger an immune response, he said.

That may explain exercise intolerance in people with long COVID, Dr. Boyman said. Some people with long COVID have inflammation in the epithelium — the inner layer of their blood vessels. This would make it harder for the circulatory systems to recover from exercise, Dr. Boyman said.

“We think this regulated complement system is actually quite a central piece of the puzzle,” he said.
 

The Microclot Connection

The findings also support past research linking blood clots to long COVID. He suggested that clinicians and researchers consider testing drugs that regulate or inhibit the complementary system as a treatment of long COVID. Dr. Boyman said they are currently used for rare immune diseases.

Resia Pretorius, PhD, a professor of physiological sciences at Stellenbosch University in Stellenbosch, South Africa, said scientists studying the role of microclots in patients with long COVID often see complementary proteins inside the clots, so it has already been associated with long COVID. But she likened this clotting process to a garbage can that “just rolls along and collects everything that gets in its way. I think they are actively driving inflammation and disease.”

One factor complicating long COVID diagnosis and treatment is that it is a complex condition that involves multiple organ systems. That’s why the latest research suggests an underlying driver for the multiple symptoms of long COVID, Dr. Putrino said.

“Not every person has every symptom; not every person has every organ system affected,” Dr. Putrino said. “Whatever is happening is decided across the whole body.”
 

Research Offers New Direction

The Swiss paper contributes to the effort to identify systemic issues contributing to long COVID. It gives researchers one more thing to test for and link to specific, long COVID symptoms, opening the door to new treatments, Dr. Putrino said.

He doesn’t think the study supports treating the complement dysfunction if researchers don’t know what’s driving it. It may be complicated by the body’s failure to clear the virus completely, he said.

Dr. Pretorius recommended doctors test patients with long COVID for specific symptoms that may be treated using existing therapies. “If you think your patient had vascular pathology, you can test for it,” she said.

Some patients have found certain supplements and over-the-counter products helpful, she said. Among them: Coenzyme Q 10 and clot-busters such as streptokinase and Nattokinase (though she noted some doctors may not be comfortable with supplements).

“It’s the only thing we have until we’ve got trials,” she said.

Dr. Putrino said more research is needed to identify potential root causes and symptoms. A common refrain, but the only thing that will lead to specific treatments.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Rachel S. Rubin, MD: I’m Dr Rachel Rubin, urologist and sexual medicine specialist in the Washington, DC, area. This is Sex Matters, and I’m here today with my friend and colleague, Dr. Matt Ziegelmann, who is the sexual medicine expert at the Mayo Clinic and who does all things men’s health, including penile curvature, testosterone, and sexual function.

Let’s start with penile curvature. Many men come in very distressed. They felt a lump in their penis and go straight to their primary care physician. What do we do in that situation?

Matthew J. Ziegelmann, MD: Penile curvature (often due to Peyronie’s disease) is actually incredibly common; as many as 10% of men have this condition. We need to normalize it and let men know that this is something we see often, and we have treatments for it. One of the biggest concerns these men have is cancer, but I have yet to see this as an indicator of cancer.

Penile curvature has a significant impact on affected men — their relationships, psychological well-being, sexual functioning, and overall health. We can provide treatment if they are interested. A small subset of men are born with natural penile curvature, which is different from Peyronie’s disease. Natural curvature can still affect their mental health, and we have treatment options.

Rubin: What happens when a patient is referred to urology? We want to tell our patients what to expect. What’s in our toolbox to help patients with penile curvature?

Dr. Ziegelmann: Many patient resources are available. For example, the Sexual Medicine Society of North America (SMSNA) has a patient-facing website on sexual health with lots of information about Peyronie’s disease and other aspects of sexual health.

Patients who are bothered by their penile curvature can be referred to us to find out about treatment options, or even just to get reassurance. It might be as simple as a conversation and a physical exam — that’s all we need to make the diagnosis. We can provide reassurance and get an idea of how bothered they are by this condition without doing anything invasive.

If they are considering definitive treatment, we would need to do more invasive testing. Sometimes we have the patient bring in photos of their erection to help establish the change they see in the shape of their penis.

Dr. Rubin: What about the patient who asks, “Doc, did I do this to myself? Did I break my penis? What do I do?”

Dr. Ziegelmann: That’s a common question — “How the heck did this happen?” No, you didn’t do this to yourself. We still have much to understand about why this happens to some men. Our approach is to acknowledge what we do and don’t know, and partner with the patient to discuss treatment.

Dr. Rubin: It’s very important to support your patient’s mental health, because this can be really devastating. So, what are the treatment options from conservative to invasive? What do you recommend for patients?

Dr. Ziegelmann: It can be as simple as observation if the patient is just seeking reassurance that it’s not cancer. This is a benign condition, but for men who are more bothered by their curvature, we’ll talk about options. We have oral medications that help improved the rigidity of the penis. Many men are also suffering from inadequate functioning. We can use devices called traction or vacuum to stretch the area of the penis that’s curved. We can use injections of medications, including FDA-approved agents that are injected into the penis in the outpatient setting. For men who are either later in the treatment protocol or want to resolve the problem right away, we can offer surgical intervention. We have a host of options, and a very individualized approach and a shared decision-making model. It’s not a one-size-fits-all problem.

Dr. Rubin: The real takeaway is that there is a lot of hope for this condition. Many doctors care deeply about these issues and are ready to partner with specialists to figure out the right treatment strategy. The SMSNA is a great place to find a provider like Dr Ziegelmann or myself, or any of our incredible colleagues throughout North America and the world. Thank you for joining us today. 

Dr. Rubin is Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, DC; Private practice, North Bethesda, Maryland. She disclosed ties with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Rachel S. Rubin, MD: I’m Dr Rachel Rubin, urologist and sexual medicine specialist in the Washington, DC, area. This is Sex Matters, and I’m here today with my friend and colleague, Dr. Matt Ziegelmann, who is the sexual medicine expert at the Mayo Clinic and who does all things men’s health, including penile curvature, testosterone, and sexual function.

Let’s start with penile curvature. Many men come in very distressed. They felt a lump in their penis and go straight to their primary care physician. What do we do in that situation?

Matthew J. Ziegelmann, MD: Penile curvature (often due to Peyronie’s disease) is actually incredibly common; as many as 10% of men have this condition. We need to normalize it and let men know that this is something we see often, and we have treatments for it. One of the biggest concerns these men have is cancer, but I have yet to see this as an indicator of cancer.

Penile curvature has a significant impact on affected men — their relationships, psychological well-being, sexual functioning, and overall health. We can provide treatment if they are interested. A small subset of men are born with natural penile curvature, which is different from Peyronie’s disease. Natural curvature can still affect their mental health, and we have treatment options.

Rubin: What happens when a patient is referred to urology? We want to tell our patients what to expect. What’s in our toolbox to help patients with penile curvature?

Dr. Ziegelmann: Many patient resources are available. For example, the Sexual Medicine Society of North America (SMSNA) has a patient-facing website on sexual health with lots of information about Peyronie’s disease and other aspects of sexual health.

Patients who are bothered by their penile curvature can be referred to us to find out about treatment options, or even just to get reassurance. It might be as simple as a conversation and a physical exam — that’s all we need to make the diagnosis. We can provide reassurance and get an idea of how bothered they are by this condition without doing anything invasive.

If they are considering definitive treatment, we would need to do more invasive testing. Sometimes we have the patient bring in photos of their erection to help establish the change they see in the shape of their penis.

Dr. Rubin: What about the patient who asks, “Doc, did I do this to myself? Did I break my penis? What do I do?”

Dr. Ziegelmann: That’s a common question — “How the heck did this happen?” No, you didn’t do this to yourself. We still have much to understand about why this happens to some men. Our approach is to acknowledge what we do and don’t know, and partner with the patient to discuss treatment.

Dr. Rubin: It’s very important to support your patient’s mental health, because this can be really devastating. So, what are the treatment options from conservative to invasive? What do you recommend for patients?

Dr. Ziegelmann: It can be as simple as observation if the patient is just seeking reassurance that it’s not cancer. This is a benign condition, but for men who are more bothered by their curvature, we’ll talk about options. We have oral medications that help improved the rigidity of the penis. Many men are also suffering from inadequate functioning. We can use devices called traction or vacuum to stretch the area of the penis that’s curved. We can use injections of medications, including FDA-approved agents that are injected into the penis in the outpatient setting. For men who are either later in the treatment protocol or want to resolve the problem right away, we can offer surgical intervention. We have a host of options, and a very individualized approach and a shared decision-making model. It’s not a one-size-fits-all problem.

Dr. Rubin: The real takeaway is that there is a lot of hope for this condition. Many doctors care deeply about these issues and are ready to partner with specialists to figure out the right treatment strategy. The SMSNA is a great place to find a provider like Dr Ziegelmann or myself, or any of our incredible colleagues throughout North America and the world. Thank you for joining us today. 

Dr. Rubin is Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, DC; Private practice, North Bethesda, Maryland. She disclosed ties with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Rachel S. Rubin, MD: I’m Dr Rachel Rubin, urologist and sexual medicine specialist in the Washington, DC, area. This is Sex Matters, and I’m here today with my friend and colleague, Dr. Matt Ziegelmann, who is the sexual medicine expert at the Mayo Clinic and who does all things men’s health, including penile curvature, testosterone, and sexual function.

Let’s start with penile curvature. Many men come in very distressed. They felt a lump in their penis and go straight to their primary care physician. What do we do in that situation?

Matthew J. Ziegelmann, MD: Penile curvature (often due to Peyronie’s disease) is actually incredibly common; as many as 10% of men have this condition. We need to normalize it and let men know that this is something we see often, and we have treatments for it. One of the biggest concerns these men have is cancer, but I have yet to see this as an indicator of cancer.

Penile curvature has a significant impact on affected men — their relationships, psychological well-being, sexual functioning, and overall health. We can provide treatment if they are interested. A small subset of men are born with natural penile curvature, which is different from Peyronie’s disease. Natural curvature can still affect their mental health, and we have treatment options.

Rubin: What happens when a patient is referred to urology? We want to tell our patients what to expect. What’s in our toolbox to help patients with penile curvature?

Dr. Ziegelmann: Many patient resources are available. For example, the Sexual Medicine Society of North America (SMSNA) has a patient-facing website on sexual health with lots of information about Peyronie’s disease and other aspects of sexual health.

Patients who are bothered by their penile curvature can be referred to us to find out about treatment options, or even just to get reassurance. It might be as simple as a conversation and a physical exam — that’s all we need to make the diagnosis. We can provide reassurance and get an idea of how bothered they are by this condition without doing anything invasive.

If they are considering definitive treatment, we would need to do more invasive testing. Sometimes we have the patient bring in photos of their erection to help establish the change they see in the shape of their penis.

Dr. Rubin: What about the patient who asks, “Doc, did I do this to myself? Did I break my penis? What do I do?”

Dr. Ziegelmann: That’s a common question — “How the heck did this happen?” No, you didn’t do this to yourself. We still have much to understand about why this happens to some men. Our approach is to acknowledge what we do and don’t know, and partner with the patient to discuss treatment.

Dr. Rubin: It’s very important to support your patient’s mental health, because this can be really devastating. So, what are the treatment options from conservative to invasive? What do you recommend for patients?

Dr. Ziegelmann: It can be as simple as observation if the patient is just seeking reassurance that it’s not cancer. This is a benign condition, but for men who are more bothered by their curvature, we’ll talk about options. We have oral medications that help improved the rigidity of the penis. Many men are also suffering from inadequate functioning. We can use devices called traction or vacuum to stretch the area of the penis that’s curved. We can use injections of medications, including FDA-approved agents that are injected into the penis in the outpatient setting. For men who are either later in the treatment protocol or want to resolve the problem right away, we can offer surgical intervention. We have a host of options, and a very individualized approach and a shared decision-making model. It’s not a one-size-fits-all problem.

Dr. Rubin: The real takeaway is that there is a lot of hope for this condition. Many doctors care deeply about these issues and are ready to partner with specialists to figure out the right treatment strategy. The SMSNA is a great place to find a provider like Dr Ziegelmann or myself, or any of our incredible colleagues throughout North America and the world. Thank you for joining us today. 

Dr. Rubin is Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, DC; Private practice, North Bethesda, Maryland. She disclosed ties with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.

A version of this article appeared on Medscape.com.

Among patients with psoriasis, the risk of mortality was strongly associated with hepatic injury, cardiovascular disease, and psychiatric affective disorders, but was reduced among those who received systemic therapy with biologics, researchers from Canada report.

Those are key findings from a large retrospective registry study of patients with psoriasis, published in The Journal of the American Academy of Dermatology.

“Psoriasis, a chronic inflammatory condition affecting approximately 3% of the western populations, bears a higher risk of mortality compared to healthy individuals, possibly by inducing systemic inflammation associated with numerous comorbidities, especially cardiovascular diseases, metabolic syndrome, and others,” wrote corresponding author Robert Gniadecki, MD, PhD, of the division of dermatology at the University of Alberta, Canada, and colleagues. “It has been argued that the use of systemic immunomodulatory agents quenches systemic inflammation and potentially improves patient survival. However, the evidence to support this hypothesis is limited.”

To investigate the impact of comorbidities and systemic therapies on all-cause mortality in psoriasis, the researchers used the Alberta Health Services Data Repository of Reporting database from January 1, 2012, to June 1, 2019, which represents a population base of 4.47 million individuals. They extracted data on 18,618 psoriasis cases and 55,854 controls, stratified cases according to the Charlson Comorbidity Index (CCI), a surrogate measure for comorbidity burden, and by the type of therapy received, and conducted statistical analyses including Cox proportional hazards regression to determine absolute hazard ratios representing relative effects of specific demographic and comorbidity factors on mortality within groups.

The median age in both cohorts was 48 years, and 51% were male. The researchers observed that mortality in the psoriasis cohort was significantly higher than in the controls (5.7% vs. 3.8%, respectively; P < .05), with a median age at the time of death of 72 vs. 74.4 years.

The CCI and comorbidities strongly predicted mortality, especially drug-induced liver injury (hazard ratio [HR], 1.78), bipolar disorder and suicidal ideation (HR, 1.24-1.58), and major cardiovascular diseases, which included myocardial infarction (MI), congestive heart failure (CHF), and cerebrovascular disease (CVA) (HR, 1.2-1.4).

Among patients in the psoriasis cohort, survival of those treated with biologic agents was higher than in controls, even after matching for CCI (3.2% vs. 4.4%, respectively, P < .05). “These patients also exhibit reduced overall mortality compared to those treated with methotrexate or topical agents,” Dr. Gniadecki and colleagues wrote. “There was no difference in mortality between methotrexate patients and the topical therapy patients, but any of those treatment groups had superior survival compared to the no-treatment cohort.”

They added that despite better survival among patients treated with biologic agents, no significant improvements were detected in their comorbidity profiles. “Notably, the frequency of major cardiovascular disease (MI, CHF, CVA) was the same as in the controls, and overall, the frequency of diseases coded as cardiovascular was slightly increased,” they wrote.

The fact that some factors could not be measured, including the type and severity of psoriasis, response to treatment, smoking history, and alcohol intake, was a study limitation, they noted.

Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center at the University of Pennsylvania, Philadelphia, who was asked to comment on the analysis, said the study confirms prior work indicating that having psoriasis is a predictor of mortality. In addition, “there is a strong healthy user affect among patients who take and stay on biologics for psoriasis,” he told this news organization.

Courtesy Dr. Gelfand

Among patients with psoriasis, the risk of mortality was strongly associated with hepatic injury, cardiovascular disease, and psychiatric affective disorders, but was reduced among those who received systemic therapy with biologics, researchers from Canada report.

Those are key findings from a large retrospective registry study of patients with psoriasis, published in The Journal of the American Academy of Dermatology.

“Psoriasis, a chronic inflammatory condition affecting approximately 3% of the western populations, bears a higher risk of mortality compared to healthy individuals, possibly by inducing systemic inflammation associated with numerous comorbidities, especially cardiovascular diseases, metabolic syndrome, and others,” wrote corresponding author Robert Gniadecki, MD, PhD, of the division of dermatology at the University of Alberta, Canada, and colleagues. “It has been argued that the use of systemic immunomodulatory agents quenches systemic inflammation and potentially improves patient survival. However, the evidence to support this hypothesis is limited.”

To investigate the impact of comorbidities and systemic therapies on all-cause mortality in psoriasis, the researchers used the Alberta Health Services Data Repository of Reporting database from January 1, 2012, to June 1, 2019, which represents a population base of 4.47 million individuals. They extracted data on 18,618 psoriasis cases and 55,854 controls, stratified cases according to the Charlson Comorbidity Index (CCI), a surrogate measure for comorbidity burden, and by the type of therapy received, and conducted statistical analyses including Cox proportional hazards regression to determine absolute hazard ratios representing relative effects of specific demographic and comorbidity factors on mortality within groups.

The median age in both cohorts was 48 years, and 51% were male. The researchers observed that mortality in the psoriasis cohort was significantly higher than in the controls (5.7% vs. 3.8%, respectively; P < .05), with a median age at the time of death of 72 vs. 74.4 years.

The CCI and comorbidities strongly predicted mortality, especially drug-induced liver injury (hazard ratio [HR], 1.78), bipolar disorder and suicidal ideation (HR, 1.24-1.58), and major cardiovascular diseases, which included myocardial infarction (MI), congestive heart failure (CHF), and cerebrovascular disease (CVA) (HR, 1.2-1.4).

Among patients in the psoriasis cohort, survival of those treated with biologic agents was higher than in controls, even after matching for CCI (3.2% vs. 4.4%, respectively, P < .05). “These patients also exhibit reduced overall mortality compared to those treated with methotrexate or topical agents,” Dr. Gniadecki and colleagues wrote. “There was no difference in mortality between methotrexate patients and the topical therapy patients, but any of those treatment groups had superior survival compared to the no-treatment cohort.”

They added that despite better survival among patients treated with biologic agents, no significant improvements were detected in their comorbidity profiles. “Notably, the frequency of major cardiovascular disease (MI, CHF, CVA) was the same as in the controls, and overall, the frequency of diseases coded as cardiovascular was slightly increased,” they wrote.

The fact that some factors could not be measured, including the type and severity of psoriasis, response to treatment, smoking history, and alcohol intake, was a study limitation, they noted.

Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center at the University of Pennsylvania, Philadelphia, who was asked to comment on the analysis, said the study confirms prior work indicating that having psoriasis is a predictor of mortality. In addition, “there is a strong healthy user affect among patients who take and stay on biologics for psoriasis,” he told this news organization.

Courtesy Dr. Gelfand

Among patients with psoriasis, the risk of mortality was strongly associated with hepatic injury, cardiovascular disease, and psychiatric affective disorders, but was reduced among those who received systemic therapy with biologics, researchers from Canada report.

Those are key findings from a large retrospective registry study of patients with psoriasis, published in The Journal of the American Academy of Dermatology.

“Psoriasis, a chronic inflammatory condition affecting approximately 3% of the western populations, bears a higher risk of mortality compared to healthy individuals, possibly by inducing systemic inflammation associated with numerous comorbidities, especially cardiovascular diseases, metabolic syndrome, and others,” wrote corresponding author Robert Gniadecki, MD, PhD, of the division of dermatology at the University of Alberta, Canada, and colleagues. “It has been argued that the use of systemic immunomodulatory agents quenches systemic inflammation and potentially improves patient survival. However, the evidence to support this hypothesis is limited.”

To investigate the impact of comorbidities and systemic therapies on all-cause mortality in psoriasis, the researchers used the Alberta Health Services Data Repository of Reporting database from January 1, 2012, to June 1, 2019, which represents a population base of 4.47 million individuals. They extracted data on 18,618 psoriasis cases and 55,854 controls, stratified cases according to the Charlson Comorbidity Index (CCI), a surrogate measure for comorbidity burden, and by the type of therapy received, and conducted statistical analyses including Cox proportional hazards regression to determine absolute hazard ratios representing relative effects of specific demographic and comorbidity factors on mortality within groups.

The median age in both cohorts was 48 years, and 51% were male. The researchers observed that mortality in the psoriasis cohort was significantly higher than in the controls (5.7% vs. 3.8%, respectively; P < .05), with a median age at the time of death of 72 vs. 74.4 years.

The CCI and comorbidities strongly predicted mortality, especially drug-induced liver injury (hazard ratio [HR], 1.78), bipolar disorder and suicidal ideation (HR, 1.24-1.58), and major cardiovascular diseases, which included myocardial infarction (MI), congestive heart failure (CHF), and cerebrovascular disease (CVA) (HR, 1.2-1.4).

Among patients in the psoriasis cohort, survival of those treated with biologic agents was higher than in controls, even after matching for CCI (3.2% vs. 4.4%, respectively, P < .05). “These patients also exhibit reduced overall mortality compared to those treated with methotrexate or topical agents,” Dr. Gniadecki and colleagues wrote. “There was no difference in mortality between methotrexate patients and the topical therapy patients, but any of those treatment groups had superior survival compared to the no-treatment cohort.”

They added that despite better survival among patients treated with biologic agents, no significant improvements were detected in their comorbidity profiles. “Notably, the frequency of major cardiovascular disease (MI, CHF, CVA) was the same as in the controls, and overall, the frequency of diseases coded as cardiovascular was slightly increased,” they wrote.

The fact that some factors could not be measured, including the type and severity of psoriasis, response to treatment, smoking history, and alcohol intake, was a study limitation, they noted.

Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center at the University of Pennsylvania, Philadelphia, who was asked to comment on the analysis, said the study confirms prior work indicating that having psoriasis is a predictor of mortality. In addition, “there is a strong healthy user affect among patients who take and stay on biologics for psoriasis,” he told this news organization.

Courtesy Dr. Gelfand

The US Food and Drug Administration (FDA) is warning against the use of smartwatches and rings that are claimed to measure a person’s glucose levels without piercing the skin.

The warning doesn’t apply to authorized smartwatch applications that display glucose values from an FDA-approved continuous glucose monitor with a sensor implanted under the skin.

Rather, the warning pertains to watches or rings sold through online marketplaces or directly from sellers who claim that the devices measure blood sugar noninvasively without requiring the wearer to prick their finger or pierce their skin. These products are manufactured by dozens of companies and sold under many different brand names. The FDA’s warning applies to all of them.

These devices have not been evaluated by the FDA for safety and effectiveness, and their use by people with diabetes could result in inaccurate blood glucose measurements, with potentially serious consequences if relied upon for medication dosing.

“The FDA has not authorized, cleared, or approved any smartwatch or smart ring that is intended to measure or estimate blood glucose values on its own,” the agency said in a statement issued on February 21, 2024.

They added, “The agency is working to ensure that manufacturers, distributors, and sellers do not illegally market unauthorized smartwatches or smart rings that claim to measure blood glucose levels.”

People who experience any problems with inaccurate blood glucose measurement or experience any adverse events from using an unauthorized smartwatch or smart ring are urged to report it to the FDA through its MedWatch program.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) is warning against the use of smartwatches and rings that are claimed to measure a person’s glucose levels without piercing the skin.

The warning doesn’t apply to authorized smartwatch applications that display glucose values from an FDA-approved continuous glucose monitor with a sensor implanted under the skin.

Rather, the warning pertains to watches or rings sold through online marketplaces or directly from sellers who claim that the devices measure blood sugar noninvasively without requiring the wearer to prick their finger or pierce their skin. These products are manufactured by dozens of companies and sold under many different brand names. The FDA’s warning applies to all of them.

These devices have not been evaluated by the FDA for safety and effectiveness, and their use by people with diabetes could result in inaccurate blood glucose measurements, with potentially serious consequences if relied upon for medication dosing.

“The FDA has not authorized, cleared, or approved any smartwatch or smart ring that is intended to measure or estimate blood glucose values on its own,” the agency said in a statement issued on February 21, 2024.

They added, “The agency is working to ensure that manufacturers, distributors, and sellers do not illegally market unauthorized smartwatches or smart rings that claim to measure blood glucose levels.”

People who experience any problems with inaccurate blood glucose measurement or experience any adverse events from using an unauthorized smartwatch or smart ring are urged to report it to the FDA through its MedWatch program.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) is warning against the use of smartwatches and rings that are claimed to measure a person’s glucose levels without piercing the skin.

The warning doesn’t apply to authorized smartwatch applications that display glucose values from an FDA-approved continuous glucose monitor with a sensor implanted under the skin.

Rather, the warning pertains to watches or rings sold through online marketplaces or directly from sellers who claim that the devices measure blood sugar noninvasively without requiring the wearer to prick their finger or pierce their skin. These products are manufactured by dozens of companies and sold under many different brand names. The FDA’s warning applies to all of them.

These devices have not been evaluated by the FDA for safety and effectiveness, and their use by people with diabetes could result in inaccurate blood glucose measurements, with potentially serious consequences if relied upon for medication dosing.

“The FDA has not authorized, cleared, or approved any smartwatch or smart ring that is intended to measure or estimate blood glucose values on its own,” the agency said in a statement issued on February 21, 2024.

They added, “The agency is working to ensure that manufacturers, distributors, and sellers do not illegally market unauthorized smartwatches or smart rings that claim to measure blood glucose levels.”

People who experience any problems with inaccurate blood glucose measurement or experience any adverse events from using an unauthorized smartwatch or smart ring are urged to report it to the FDA through its MedWatch program.

A version of this article appeared on Medscape.com.

Postinfectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a distinct, centrally mediated condition, with evidence of autonomic, immune, and metabolic dysfunction, new "deep phenotyping" data suggested.

The study was initiated in 2016 at the US National Institutes of Health. Its aim was to better elucidate the underlying pathophysiology of ME/CFS, a multisystem disorder characterized by persistent and disabling fatigue, post-exertional malaise, cognitive complaints, and other physical symptoms. A total of 17 carefully selected individuals with PI-ME/CFS onset within the prior 5 years were compared with 21 healthy volunteers on a more extensive set of biologic measurements than has been examined in any prior study of the condition.

Overall, the findings suggested that ME/CFS is “a distinct entity characterized by somatic and cognitive complaints that are centrally mediated,” with fatigue that is “defined by effort preferences and central autonomic dysfunction,” Brian T. Walitt, MD, of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Maryland, and colleagues wrote in the paper, published on February 21 in Nature Communications.

In addition, “there are distinct sex signatures of immune and metabolic dysregulation which suggest persistent antigenic stimulation.” Physical deconditioning over time, while not the source of the condition, “is an important consequence,” the authors added.

Asked to comment, Hector Bonilla, MD, director of the ME/CFS Clinic and codirector of the Stanford Post-Acute COVID-19 Syndrome Clinic, Atherton, California, pointed out that the sample was small and the study was cross-sectional and therefore likely missed dynamic changes in the patients.

Nonetheless, Dr. Bonilla told this news organization, “they have shown clear objective changes in patients with ME/CFS not seen in the controls. These are present in the microbiome, in the immune system, and in metabolites, especially in spinal fluid, that lead to a neuroinflammatory condition. And these are linked with autonomic dysfunction that can explain many of the symptoms that patients experience ... The symptoms are not manufactured by them.”

Thus far, the only treatments for ME/CFS are symptomatic. Understanding the pathophysiology is essential to identifying disease-modifying therapy, study lead author Avindra Nath, MD, Senior Investigator and Clinical Director of Intramural Research at NINDS, told this news organization.

“The disease is real. But our medical profession is limited in what they can do to diagnose or impact them ... The first thing we need to do is try to understand the pathophysiology. So that’s why the study was put together,” Dr. Nath said.

Postinfectious syndromes including ME/CFS have been given many names, including post-Lyme disease, Gulf War illness, and more recently, long COVID. With ME/CFS, the Epstein-Barr virus has historically been one of the most commonly associated triggers, although several other viral, bacterial, and environmental toxins have been implicated.

“There are a whole host of these things that have very similar symptoms or overlapping symptoms ... It’s quite possible that the underlying pathophysiology overlaps between all these syndromes,” Dr. Nath noted.

Another ME/CFS expert not involved in the study, researcher Michael VanElzakker, PhD, of the Neurotherapeutics Division at Harvard Medical School and Massachusetts General Hospital, Boston, said that the possibility of antigen persistence of the infectious pathogen arising from the immune system profiling conducted in the study is noteworthy and merits further study.

“To me, the obvious next step would be techniques like tissue-based assays and T-cell sequencing to try and understand what exactly those antigens are and what their source might be. Importantly, it is probably not the same antigen or pathogen source in all patients, but that’s a question that needs an answer,” Dr. VanElzakker said.

Of note, the 17 study participants had been adjudicated by an expert panel from an initial 484 inquiries and 217 who underwent detailed case reviews. They had to meet at least one of three published ME/CFS criteria and to have moderate to severe clinical symptom severity as determined by several fatigue scores. None met the criteria for psychiatric diagnoses.

Yet, even in the cases that met study criteria, underlying causes emerged in 20% of the participants over time, suggesting diagnostic misattribution. “This misclassification bias has important ramifications on the interpretation of the existing ME/CFS research literature,” the authors wrote.

Dr. VanElzakker noted, “The fact that this research study was probably the most detailed workup many of these patients had ever gotten is a serious indictment of our current profit-based healthcare system’s prioritization of 15-minute doctor’s appointments. It is almost certain that other patients would also benefit from an intensive detailed workup.”
 

Multiple Abnormalities Identified

There were no differences between the PI-ME/CFS and control groups in ventilatory function, muscle oxygenation, mechanical efficiency, resting energy expenditure, basal mitochondrial function of immune cells, muscle fiber composition, or body composition, suggesting the absence of a resting low-energy state, the authors said.

In 40-minute head-up tilt-table testing, there were no differences between the ME/CFS and control groups in frequency or orthostatic hypotension or extensive orthostatic tachycardia. However, a 24-hour ambulatory electrocardiogram showed that the patients with PI-ME/CFS had diminished heart rate variability. They also showed increased heart rate throughout the day, suggesting increased sympathetic activity, and a diminished drop in nighttime heart rate, suggesting decreased parasympathetic activity.

“Considered together, these data suggest that there is an alteration in autonomic tone, implying central nervous system regulatory change,” Dr. Walitt and colleagues wrote.

On the “Effort-Expenditure for Rewards Task,” the participants with PI-ME/CFS showed significant differences in “effort preference,” or a tendency to avoid the harder tasks, as well as a slowing of button-pushing over time, compared with the controls, even with easier tasks. This pattern suggests that those with PI-ME/CFS were “pacing to limit exertion and associated feelings of discomfort,” the authors wrote.

Dr. Nath describes this behavior as akin to “if you develop a flu, you feel that you just want to lay down in bed and not hurt yourself. It’s not that you’re not capable of doing [the task], but your body tells you don’t do it. Your body just wants to fight the infection ... these people just never bounce back.”

Compared with the controls, the participants with PI-ME/CFS failed to maintain a moderate grip force even though there was no difference in maximum grip strength or arm muscle mass. This performance difference correlated with decreased activity of the right temporal-parietal junction, a novel observation suggesting that the fatigue in the PI-ME/CFS group “is due to dysfunction of integrative brain regions that drive the motor cortex, the cause of which needs to be further explored,” Dr. Walitt and colleagues wrote.

On cardiopulmonary testing, peak power, peak respiratory rate, peak heart rate, and peak VO₂ were all lower in the PI-ME/CFS group, correlating to a difference of approximately 3.3 metabolic equivalent of task units. The differential cardiorespiratory performance relates to “autonomic function, hypothalamic-pituitary-adrenal axis hyporesponsiveness, and muscular deconditioning from disuse that clinically impacts activities of daily life,” they said.

In the participants with PI-ME/CFS, catechol levels in cerebrospinal fluid correlated with grip strength and effort preference, and several metabolites of the dopamine pathway correlated with several cognitive symptoms.

“This suggests that central nervous system catechol pathways are dysregulated in PI-ME/CFS and may play a role in effort preference and cognitive complaints,” as well as decreased central catecholamine biosynthesis. Similar findings have been seen in patients with long COVID, the authors noted.

There were increased naive B cells and decreased switched memory B cells in blood of participants with PI-ME/CFS. Contrary to prior studies, there was no consistent pattern of autoimmunity across all participants with PI-ME/CFS, and no previously undescribed antibodies were identified.

However, programmed cell death protein 1, a marker of T-cell exhaustion and activation, was elevated in the cerebrospinal fluid of the patients with PI-ME/CFS.

Several sex-based differences were noted, including in immune cell expression in cerebrospinal fluid, peripheral blood mononuclear cell gene expression, and muscle gene expression. Males and females also differed in the cerebrospinal metabolomics that distinguished the participants with PI-ME/CFS from controls.
 

What Do These Findings Suggest About Treatment?

The data point to several treatment implications. For one, the finding of possible immune exhaustion suggests that immune checkpoint inhibitors may be therapeutic by promoting clearance of foreign antigens. Immune dysfunction leads to neurochemical alterations that affect neuronal circuits, which may be another point of intervention, the authors suggested.

On the other hand, “attempting to target downstream mechanisms with exercise, cognitive behavioral therapy, or autonomic directed therapies may have limited impact on symptom burden, as it would not address the root cause of PI-ME/CFS,” they noted.

Combination therapy targeting multiple pathways along with a personalized medicine approach should be considered, they said.

“I think the most important thing is not to discount these patients,” Dr. Nath told this news organization. “They have a real disease, and we need to be empathetic towards them. We also need to make sure that they don’t have something underlying that is treatable, and then treat them symptomatically the best that you can. If not, then refer them to ME/CFS studies or clinics where people specialize in these conditions and work with them.”

The study authors and Dr. VanElzakker reported no relevant financial relationships. Dr. Bonilla consults for United Health and Resverlogix.
 

A version of this article appeared on Medscape.com.

Postinfectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a distinct, centrally mediated condition, with evidence of autonomic, immune, and metabolic dysfunction, new "deep phenotyping" data suggested.

The study was initiated in 2016 at the US National Institutes of Health. Its aim was to better elucidate the underlying pathophysiology of ME/CFS, a multisystem disorder characterized by persistent and disabling fatigue, post-exertional malaise, cognitive complaints, and other physical symptoms. A total of 17 carefully selected individuals with PI-ME/CFS onset within the prior 5 years were compared with 21 healthy volunteers on a more extensive set of biologic measurements than has been examined in any prior study of the condition.

Overall, the findings suggested that ME/CFS is “a distinct entity characterized by somatic and cognitive complaints that are centrally mediated,” with fatigue that is “defined by effort preferences and central autonomic dysfunction,” Brian T. Walitt, MD, of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Maryland, and colleagues wrote in the paper, published on February 21 in Nature Communications.

In addition, “there are distinct sex signatures of immune and metabolic dysregulation which suggest persistent antigenic stimulation.” Physical deconditioning over time, while not the source of the condition, “is an important consequence,” the authors added.

Asked to comment, Hector Bonilla, MD, director of the ME/CFS Clinic and codirector of the Stanford Post-Acute COVID-19 Syndrome Clinic, Atherton, California, pointed out that the sample was small and the study was cross-sectional and therefore likely missed dynamic changes in the patients.

Nonetheless, Dr. Bonilla told this news organization, “they have shown clear objective changes in patients with ME/CFS not seen in the controls. These are present in the microbiome, in the immune system, and in metabolites, especially in spinal fluid, that lead to a neuroinflammatory condition. And these are linked with autonomic dysfunction that can explain many of the symptoms that patients experience ... The symptoms are not manufactured by them.”

Thus far, the only treatments for ME/CFS are symptomatic. Understanding the pathophysiology is essential to identifying disease-modifying therapy, study lead author Avindra Nath, MD, Senior Investigator and Clinical Director of Intramural Research at NINDS, told this news organization.

“The disease is real. But our medical profession is limited in what they can do to diagnose or impact them ... The first thing we need to do is try to understand the pathophysiology. So that’s why the study was put together,” Dr. Nath said.

Postinfectious syndromes including ME/CFS have been given many names, including post-Lyme disease, Gulf War illness, and more recently, long COVID. With ME/CFS, the Epstein-Barr virus has historically been one of the most commonly associated triggers, although several other viral, bacterial, and environmental toxins have been implicated.

“There are a whole host of these things that have very similar symptoms or overlapping symptoms ... It’s quite possible that the underlying pathophysiology overlaps between all these syndromes,” Dr. Nath noted.

Another ME/CFS expert not involved in the study, researcher Michael VanElzakker, PhD, of the Neurotherapeutics Division at Harvard Medical School and Massachusetts General Hospital, Boston, said that the possibility of antigen persistence of the infectious pathogen arising from the immune system profiling conducted in the study is noteworthy and merits further study.

“To me, the obvious next step would be techniques like tissue-based assays and T-cell sequencing to try and understand what exactly those antigens are and what their source might be. Importantly, it is probably not the same antigen or pathogen source in all patients, but that’s a question that needs an answer,” Dr. VanElzakker said.

Of note, the 17 study participants had been adjudicated by an expert panel from an initial 484 inquiries and 217 who underwent detailed case reviews. They had to meet at least one of three published ME/CFS criteria and to have moderate to severe clinical symptom severity as determined by several fatigue scores. None met the criteria for psychiatric diagnoses.

Yet, even in the cases that met study criteria, underlying causes emerged in 20% of the participants over time, suggesting diagnostic misattribution. “This misclassification bias has important ramifications on the interpretation of the existing ME/CFS research literature,” the authors wrote.

Dr. VanElzakker noted, “The fact that this research study was probably the most detailed workup many of these patients had ever gotten is a serious indictment of our current profit-based healthcare system’s prioritization of 15-minute doctor’s appointments. It is almost certain that other patients would also benefit from an intensive detailed workup.”
 

Multiple Abnormalities Identified

There were no differences between the PI-ME/CFS and control groups in ventilatory function, muscle oxygenation, mechanical efficiency, resting energy expenditure, basal mitochondrial function of immune cells, muscle fiber composition, or body composition, suggesting the absence of a resting low-energy state, the authors said.

In 40-minute head-up tilt-table testing, there were no differences between the ME/CFS and control groups in frequency or orthostatic hypotension or extensive orthostatic tachycardia. However, a 24-hour ambulatory electrocardiogram showed that the patients with PI-ME/CFS had diminished heart rate variability. They also showed increased heart rate throughout the day, suggesting increased sympathetic activity, and a diminished drop in nighttime heart rate, suggesting decreased parasympathetic activity.

“Considered together, these data suggest that there is an alteration in autonomic tone, implying central nervous system regulatory change,” Dr. Walitt and colleagues wrote.

On the “Effort-Expenditure for Rewards Task,” the participants with PI-ME/CFS showed significant differences in “effort preference,” or a tendency to avoid the harder tasks, as well as a slowing of button-pushing over time, compared with the controls, even with easier tasks. This pattern suggests that those with PI-ME/CFS were “pacing to limit exertion and associated feelings of discomfort,” the authors wrote.

Dr. Nath describes this behavior as akin to “if you develop a flu, you feel that you just want to lay down in bed and not hurt yourself. It’s not that you’re not capable of doing [the task], but your body tells you don’t do it. Your body just wants to fight the infection ... these people just never bounce back.”

Compared with the controls, the participants with PI-ME/CFS failed to maintain a moderate grip force even though there was no difference in maximum grip strength or arm muscle mass. This performance difference correlated with decreased activity of the right temporal-parietal junction, a novel observation suggesting that the fatigue in the PI-ME/CFS group “is due to dysfunction of integrative brain regions that drive the motor cortex, the cause of which needs to be further explored,” Dr. Walitt and colleagues wrote.

On cardiopulmonary testing, peak power, peak respiratory rate, peak heart rate, and peak VO₂ were all lower in the PI-ME/CFS group, correlating to a difference of approximately 3.3 metabolic equivalent of task units. The differential cardiorespiratory performance relates to “autonomic function, hypothalamic-pituitary-adrenal axis hyporesponsiveness, and muscular deconditioning from disuse that clinically impacts activities of daily life,” they said.

In the participants with PI-ME/CFS, catechol levels in cerebrospinal fluid correlated with grip strength and effort preference, and several metabolites of the dopamine pathway correlated with several cognitive symptoms.

“This suggests that central nervous system catechol pathways are dysregulated in PI-ME/CFS and may play a role in effort preference and cognitive complaints,” as well as decreased central catecholamine biosynthesis. Similar findings have been seen in patients with long COVID, the authors noted.

There were increased naive B cells and decreased switched memory B cells in blood of participants with PI-ME/CFS. Contrary to prior studies, there was no consistent pattern of autoimmunity across all participants with PI-ME/CFS, and no previously undescribed antibodies were identified.

However, programmed cell death protein 1, a marker of T-cell exhaustion and activation, was elevated in the cerebrospinal fluid of the patients with PI-ME/CFS.

Several sex-based differences were noted, including in immune cell expression in cerebrospinal fluid, peripheral blood mononuclear cell gene expression, and muscle gene expression. Males and females also differed in the cerebrospinal metabolomics that distinguished the participants with PI-ME/CFS from controls.
 

What Do These Findings Suggest About Treatment?

The data point to several treatment implications. For one, the finding of possible immune exhaustion suggests that immune checkpoint inhibitors may be therapeutic by promoting clearance of foreign antigens. Immune dysfunction leads to neurochemical alterations that affect neuronal circuits, which may be another point of intervention, the authors suggested.

On the other hand, “attempting to target downstream mechanisms with exercise, cognitive behavioral therapy, or autonomic directed therapies may have limited impact on symptom burden, as it would not address the root cause of PI-ME/CFS,” they noted.

Combination therapy targeting multiple pathways along with a personalized medicine approach should be considered, they said.

“I think the most important thing is not to discount these patients,” Dr. Nath told this news organization. “They have a real disease, and we need to be empathetic towards them. We also need to make sure that they don’t have something underlying that is treatable, and then treat them symptomatically the best that you can. If not, then refer them to ME/CFS studies or clinics where people specialize in these conditions and work with them.”

The study authors and Dr. VanElzakker reported no relevant financial relationships. Dr. Bonilla consults for United Health and Resverlogix.
 

A version of this article appeared on Medscape.com.

Postinfectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a distinct, centrally mediated condition, with evidence of autonomic, immune, and metabolic dysfunction, new "deep phenotyping" data suggested.

The study was initiated in 2016 at the US National Institutes of Health. Its aim was to better elucidate the underlying pathophysiology of ME/CFS, a multisystem disorder characterized by persistent and disabling fatigue, post-exertional malaise, cognitive complaints, and other physical symptoms. A total of 17 carefully selected individuals with PI-ME/CFS onset within the prior 5 years were compared with 21 healthy volunteers on a more extensive set of biologic measurements than has been examined in any prior study of the condition.

Overall, the findings suggested that ME/CFS is “a distinct entity characterized by somatic and cognitive complaints that are centrally mediated,” with fatigue that is “defined by effort preferences and central autonomic dysfunction,” Brian T. Walitt, MD, of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Maryland, and colleagues wrote in the paper, published on February 21 in Nature Communications.

In addition, “there are distinct sex signatures of immune and metabolic dysregulation which suggest persistent antigenic stimulation.” Physical deconditioning over time, while not the source of the condition, “is an important consequence,” the authors added.

Asked to comment, Hector Bonilla, MD, director of the ME/CFS Clinic and codirector of the Stanford Post-Acute COVID-19 Syndrome Clinic, Atherton, California, pointed out that the sample was small and the study was cross-sectional and therefore likely missed dynamic changes in the patients.

Nonetheless, Dr. Bonilla told this news organization, “they have shown clear objective changes in patients with ME/CFS not seen in the controls. These are present in the microbiome, in the immune system, and in metabolites, especially in spinal fluid, that lead to a neuroinflammatory condition. And these are linked with autonomic dysfunction that can explain many of the symptoms that patients experience ... The symptoms are not manufactured by them.”

Thus far, the only treatments for ME/CFS are symptomatic. Understanding the pathophysiology is essential to identifying disease-modifying therapy, study lead author Avindra Nath, MD, Senior Investigator and Clinical Director of Intramural Research at NINDS, told this news organization.

“The disease is real. But our medical profession is limited in what they can do to diagnose or impact them ... The first thing we need to do is try to understand the pathophysiology. So that’s why the study was put together,” Dr. Nath said.

Postinfectious syndromes including ME/CFS have been given many names, including post-Lyme disease, Gulf War illness, and more recently, long COVID. With ME/CFS, the Epstein-Barr virus has historically been one of the most commonly associated triggers, although several other viral, bacterial, and environmental toxins have been implicated.

“There are a whole host of these things that have very similar symptoms or overlapping symptoms ... It’s quite possible that the underlying pathophysiology overlaps between all these syndromes,” Dr. Nath noted.

Another ME/CFS expert not involved in the study, researcher Michael VanElzakker, PhD, of the Neurotherapeutics Division at Harvard Medical School and Massachusetts General Hospital, Boston, said that the possibility of antigen persistence of the infectious pathogen arising from the immune system profiling conducted in the study is noteworthy and merits further study.

“To me, the obvious next step would be techniques like tissue-based assays and T-cell sequencing to try and understand what exactly those antigens are and what their source might be. Importantly, it is probably not the same antigen or pathogen source in all patients, but that’s a question that needs an answer,” Dr. VanElzakker said.

Of note, the 17 study participants had been adjudicated by an expert panel from an initial 484 inquiries and 217 who underwent detailed case reviews. They had to meet at least one of three published ME/CFS criteria and to have moderate to severe clinical symptom severity as determined by several fatigue scores. None met the criteria for psychiatric diagnoses.

Yet, even in the cases that met study criteria, underlying causes emerged in 20% of the participants over time, suggesting diagnostic misattribution. “This misclassification bias has important ramifications on the interpretation of the existing ME/CFS research literature,” the authors wrote.

Dr. VanElzakker noted, “The fact that this research study was probably the most detailed workup many of these patients had ever gotten is a serious indictment of our current profit-based healthcare system’s prioritization of 15-minute doctor’s appointments. It is almost certain that other patients would also benefit from an intensive detailed workup.”
 

Multiple Abnormalities Identified

There were no differences between the PI-ME/CFS and control groups in ventilatory function, muscle oxygenation, mechanical efficiency, resting energy expenditure, basal mitochondrial function of immune cells, muscle fiber composition, or body composition, suggesting the absence of a resting low-energy state, the authors said.

In 40-minute head-up tilt-table testing, there were no differences between the ME/CFS and control groups in frequency or orthostatic hypotension or extensive orthostatic tachycardia. However, a 24-hour ambulatory electrocardiogram showed that the patients with PI-ME/CFS had diminished heart rate variability. They also showed increased heart rate throughout the day, suggesting increased sympathetic activity, and a diminished drop in nighttime heart rate, suggesting decreased parasympathetic activity.

“Considered together, these data suggest that there is an alteration in autonomic tone, implying central nervous system regulatory change,” Dr. Walitt and colleagues wrote.

On the “Effort-Expenditure for Rewards Task,” the participants with PI-ME/CFS showed significant differences in “effort preference,” or a tendency to avoid the harder tasks, as well as a slowing of button-pushing over time, compared with the controls, even with easier tasks. This pattern suggests that those with PI-ME/CFS were “pacing to limit exertion and associated feelings of discomfort,” the authors wrote.

Dr. Nath describes this behavior as akin to “if you develop a flu, you feel that you just want to lay down in bed and not hurt yourself. It’s not that you’re not capable of doing [the task], but your body tells you don’t do it. Your body just wants to fight the infection ... these people just never bounce back.”

Compared with the controls, the participants with PI-ME/CFS failed to maintain a moderate grip force even though there was no difference in maximum grip strength or arm muscle mass. This performance difference correlated with decreased activity of the right temporal-parietal junction, a novel observation suggesting that the fatigue in the PI-ME/CFS group “is due to dysfunction of integrative brain regions that drive the motor cortex, the cause of which needs to be further explored,” Dr. Walitt and colleagues wrote.

On cardiopulmonary testing, peak power, peak respiratory rate, peak heart rate, and peak VO₂ were all lower in the PI-ME/CFS group, correlating to a difference of approximately 3.3 metabolic equivalent of task units. The differential cardiorespiratory performance relates to “autonomic function, hypothalamic-pituitary-adrenal axis hyporesponsiveness, and muscular deconditioning from disuse that clinically impacts activities of daily life,” they said.

In the participants with PI-ME/CFS, catechol levels in cerebrospinal fluid correlated with grip strength and effort preference, and several metabolites of the dopamine pathway correlated with several cognitive symptoms.

“This suggests that central nervous system catechol pathways are dysregulated in PI-ME/CFS and may play a role in effort preference and cognitive complaints,” as well as decreased central catecholamine biosynthesis. Similar findings have been seen in patients with long COVID, the authors noted.

There were increased naive B cells and decreased switched memory B cells in blood of participants with PI-ME/CFS. Contrary to prior studies, there was no consistent pattern of autoimmunity across all participants with PI-ME/CFS, and no previously undescribed antibodies were identified.

However, programmed cell death protein 1, a marker of T-cell exhaustion and activation, was elevated in the cerebrospinal fluid of the patients with PI-ME/CFS.

Several sex-based differences were noted, including in immune cell expression in cerebrospinal fluid, peripheral blood mononuclear cell gene expression, and muscle gene expression. Males and females also differed in the cerebrospinal metabolomics that distinguished the participants with PI-ME/CFS from controls.
 

What Do These Findings Suggest About Treatment?

The data point to several treatment implications. For one, the finding of possible immune exhaustion suggests that immune checkpoint inhibitors may be therapeutic by promoting clearance of foreign antigens. Immune dysfunction leads to neurochemical alterations that affect neuronal circuits, which may be another point of intervention, the authors suggested.

On the other hand, “attempting to target downstream mechanisms with exercise, cognitive behavioral therapy, or autonomic directed therapies may have limited impact on symptom burden, as it would not address the root cause of PI-ME/CFS,” they noted.

Combination therapy targeting multiple pathways along with a personalized medicine approach should be considered, they said.

“I think the most important thing is not to discount these patients,” Dr. Nath told this news organization. “They have a real disease, and we need to be empathetic towards them. We also need to make sure that they don’t have something underlying that is treatable, and then treat them symptomatically the best that you can. If not, then refer them to ME/CFS studies or clinics where people specialize in these conditions and work with them.”

The study authors and Dr. VanElzakker reported no relevant financial relationships. Dr. Bonilla consults for United Health and Resverlogix.
 

A version of this article appeared on Medscape.com.