Julie Stewart

A noninvasive eye test could help people with Sjögren disease — a disorder that can go undiagnosed for years — get relief sooner, suggested a pilot study published in Therapeutic Advances in Musculoskeletal Disease.

Researchers led by Jing Wu, Department of Ophthalmology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, and colleagues used infrared imaging to detect atrophy of the oil-producing meibomian glands, which lubricate the eyelids and eyes, in 56 patients with suspected Sjögren disease. The test can be administered by an eye care practitioner using a Keratograph 5M machine. Patients also underwent salivary gland biopsies to detect Sjögren disease.

A total of 34 patients diagnosed with primary Sjögren disease had more significant atrophy and shortening of the meibomian glands in their upper eyelids than 22 patients with other types of dry eye who served as control patients. The accuracy of temporal and total meibomian gland dysfunction dropout rates in the upper eyelids to predict primary Sjögren disease classification was good, with an area under the curve of 0.94 and 0.91, respectively.

“Sjögren’s-related dry eye is definitely inflammatory,” said Esen Akpek, MD, director of the Ocular Surface Disease and Dry Eye Clinic at Johns Hopkins Medicine, Baltimore, who was not involved with the study. “It starts as inflammation, and then the inflammation spreads to the meibomian glands, to the conjunctiva, cornea, and there will be other findings, like corneal ulcers, corneal melts, cyclitis, retinitis, optic neuritis, uveitis, all these inflammatory diseases of the eye could happen with Sjögren’s.”

With other types of dry eye, such as blepharitis or even meibomian gland dysfunction without Sjögren disease, inflammation is usually confined to the ocular surface, Akpek said. As a result, symptoms tend to be less severe and progressive.

The results of this small study need validation in a larger cohort, said Steven Carsons, MD, chief of the Division of Rheumatology at NYU Langone Hospital–Long Island, who was not involved with the study. In general, however, noninvasive alternatives to today’s tests for Sjögren disease could be useful for patients and physicians.

“The definitive diagnosis is a minor salivary glandular biopsy, which is invasive and isn’t really appealing to a lot of patients,” Dr. Carsons said. This test can also be difficult to access if patients don’t live near a medical center that specializes in Sjögren disease, he said.

“I think it’s everybody’s goal to have a noninvasive test be able, at some point, to replace biopsy,” Dr. Carsons said.

Then there are blood tests. “The other more objective test, the SSA antibodies, are not very specific for Sjögren’s syndrome,” he said. “They’re fairly sensitive, but can also be seen in other autoimmune conditions, particularly lupus.”

With existing tools, however, optometrists and ophthalmologists can do more to diagnose Sjögren disease early, Dr. Akpek said.

“The issue with Sjögren’s is not that there are no earlier diagnostic aids or anything like that,” Dr. Akpek said.

Lissamine green, a dye that stains degraded cells on the eye’s surface, can reveal clues in young adult patients before other signs. “In my opinion, the earliest clinical finding that indicates presence of the disease is lissamine green staining of conjunctiva,” Akpek said.

Meibomian gland imaging would detect the disease at a later point. “By the time you get meibomian gland dysfunction, there has been longer-standing inflammation,” she said.

Two challenges hold back diagnoses, she said. One is that many practitioners mistakenly believe Sjögren disease is just a nuisance even though it can threaten vision through ocular complications and have more far-reaching effects, too.

“There are a lot of extraglandular systemic manifestations of Sjögren’s that cause morbidity in these patients,” Dr. Akpek said. For example, Sjögren disease is associated with lymphoma and other malignancies, interstitial nephritis, autoimmune hepatitis, and interstitial lung disease with fibrosis.

The second challenge, she said, is that many ophthalmologists and optometrists assume rheumatologists will make the Sjögren disease diagnosis first and then refer patients to them. But eye doctors are well positioned to spot the first signs — if they look for them.

“When you complain of dry eye, unless the doctor puts certain dyes and takes a look at the surface with the dye staining, they can’t see that you are dry,” Dr. Akpek said.

Unfortunately, these tests are underutilized. “I’m sorry to say, dry eye testing, like clinical testing, is not very commonly done,” she said. “Dry eye is managed according to patient symptoms. A lot of the time, Sjögren’s patients have such severe dry eye that they don’t complain of dryness anymore because their corneas become numb.”

Another way to prevent diagnostic delay is to collaborate, communicate, and carefully review patient records shared by other specialists.

“Particularly because of the wide involvement of different organ systems, such as the eyes, the mouth with dental problems, and then systemic features, including joints, it really does need the cooperation of ophthalmologists, dental specialists, and rheumatologists — immunologists sometimes — to come together and make this diagnosis,” Dr. Carsons said.

The study was supported by grants from the National Natural Science Foundation of China. The authors had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

A noninvasive eye test could help people with Sjögren disease — a disorder that can go undiagnosed for years — get relief sooner, suggested a pilot study published in Therapeutic Advances in Musculoskeletal Disease.

Researchers led by Jing Wu, Department of Ophthalmology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, and colleagues used infrared imaging to detect atrophy of the oil-producing meibomian glands, which lubricate the eyelids and eyes, in 56 patients with suspected Sjögren disease. The test can be administered by an eye care practitioner using a Keratograph 5M machine. Patients also underwent salivary gland biopsies to detect Sjögren disease.

A total of 34 patients diagnosed with primary Sjögren disease had more significant atrophy and shortening of the meibomian glands in their upper eyelids than 22 patients with other types of dry eye who served as control patients. The accuracy of temporal and total meibomian gland dysfunction dropout rates in the upper eyelids to predict primary Sjögren disease classification was good, with an area under the curve of 0.94 and 0.91, respectively.

“Sjögren’s-related dry eye is definitely inflammatory,” said Esen Akpek, MD, director of the Ocular Surface Disease and Dry Eye Clinic at Johns Hopkins Medicine, Baltimore, who was not involved with the study. “It starts as inflammation, and then the inflammation spreads to the meibomian glands, to the conjunctiva, cornea, and there will be other findings, like corneal ulcers, corneal melts, cyclitis, retinitis, optic neuritis, uveitis, all these inflammatory diseases of the eye could happen with Sjögren’s.”

With other types of dry eye, such as blepharitis or even meibomian gland dysfunction without Sjögren disease, inflammation is usually confined to the ocular surface, Akpek said. As a result, symptoms tend to be less severe and progressive.

The results of this small study need validation in a larger cohort, said Steven Carsons, MD, chief of the Division of Rheumatology at NYU Langone Hospital–Long Island, who was not involved with the study. In general, however, noninvasive alternatives to today’s tests for Sjögren disease could be useful for patients and physicians.

“The definitive diagnosis is a minor salivary glandular biopsy, which is invasive and isn’t really appealing to a lot of patients,” Dr. Carsons said. This test can also be difficult to access if patients don’t live near a medical center that specializes in Sjögren disease, he said.

“I think it’s everybody’s goal to have a noninvasive test be able, at some point, to replace biopsy,” Dr. Carsons said.

Then there are blood tests. “The other more objective test, the SSA antibodies, are not very specific for Sjögren’s syndrome,” he said. “They’re fairly sensitive, but can also be seen in other autoimmune conditions, particularly lupus.”

With existing tools, however, optometrists and ophthalmologists can do more to diagnose Sjögren disease early, Dr. Akpek said.

“The issue with Sjögren’s is not that there are no earlier diagnostic aids or anything like that,” Dr. Akpek said.

Lissamine green, a dye that stains degraded cells on the eye’s surface, can reveal clues in young adult patients before other signs. “In my opinion, the earliest clinical finding that indicates presence of the disease is lissamine green staining of conjunctiva,” Akpek said.

Meibomian gland imaging would detect the disease at a later point. “By the time you get meibomian gland dysfunction, there has been longer-standing inflammation,” she said.

Two challenges hold back diagnoses, she said. One is that many practitioners mistakenly believe Sjögren disease is just a nuisance even though it can threaten vision through ocular complications and have more far-reaching effects, too.

“There are a lot of extraglandular systemic manifestations of Sjögren’s that cause morbidity in these patients,” Dr. Akpek said. For example, Sjögren disease is associated with lymphoma and other malignancies, interstitial nephritis, autoimmune hepatitis, and interstitial lung disease with fibrosis.

The second challenge, she said, is that many ophthalmologists and optometrists assume rheumatologists will make the Sjögren disease diagnosis first and then refer patients to them. But eye doctors are well positioned to spot the first signs — if they look for them.

“When you complain of dry eye, unless the doctor puts certain dyes and takes a look at the surface with the dye staining, they can’t see that you are dry,” Dr. Akpek said.

Unfortunately, these tests are underutilized. “I’m sorry to say, dry eye testing, like clinical testing, is not very commonly done,” she said. “Dry eye is managed according to patient symptoms. A lot of the time, Sjögren’s patients have such severe dry eye that they don’t complain of dryness anymore because their corneas become numb.”

Another way to prevent diagnostic delay is to collaborate, communicate, and carefully review patient records shared by other specialists.

“Particularly because of the wide involvement of different organ systems, such as the eyes, the mouth with dental problems, and then systemic features, including joints, it really does need the cooperation of ophthalmologists, dental specialists, and rheumatologists — immunologists sometimes — to come together and make this diagnosis,” Dr. Carsons said.

The study was supported by grants from the National Natural Science Foundation of China. The authors had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

A noninvasive eye test could help people with Sjögren disease — a disorder that can go undiagnosed for years — get relief sooner, suggested a pilot study published in Therapeutic Advances in Musculoskeletal Disease.

Researchers led by Jing Wu, Department of Ophthalmology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, and colleagues used infrared imaging to detect atrophy of the oil-producing meibomian glands, which lubricate the eyelids and eyes, in 56 patients with suspected Sjögren disease. The test can be administered by an eye care practitioner using a Keratograph 5M machine. Patients also underwent salivary gland biopsies to detect Sjögren disease.

A total of 34 patients diagnosed with primary Sjögren disease had more significant atrophy and shortening of the meibomian glands in their upper eyelids than 22 patients with other types of dry eye who served as control patients. The accuracy of temporal and total meibomian gland dysfunction dropout rates in the upper eyelids to predict primary Sjögren disease classification was good, with an area under the curve of 0.94 and 0.91, respectively.

“Sjögren’s-related dry eye is definitely inflammatory,” said Esen Akpek, MD, director of the Ocular Surface Disease and Dry Eye Clinic at Johns Hopkins Medicine, Baltimore, who was not involved with the study. “It starts as inflammation, and then the inflammation spreads to the meibomian glands, to the conjunctiva, cornea, and there will be other findings, like corneal ulcers, corneal melts, cyclitis, retinitis, optic neuritis, uveitis, all these inflammatory diseases of the eye could happen with Sjögren’s.”

With other types of dry eye, such as blepharitis or even meibomian gland dysfunction without Sjögren disease, inflammation is usually confined to the ocular surface, Akpek said. As a result, symptoms tend to be less severe and progressive.

The results of this small study need validation in a larger cohort, said Steven Carsons, MD, chief of the Division of Rheumatology at NYU Langone Hospital–Long Island, who was not involved with the study. In general, however, noninvasive alternatives to today’s tests for Sjögren disease could be useful for patients and physicians.

“The definitive diagnosis is a minor salivary glandular biopsy, which is invasive and isn’t really appealing to a lot of patients,” Dr. Carsons said. This test can also be difficult to access if patients don’t live near a medical center that specializes in Sjögren disease, he said.

“I think it’s everybody’s goal to have a noninvasive test be able, at some point, to replace biopsy,” Dr. Carsons said.

Then there are blood tests. “The other more objective test, the SSA antibodies, are not very specific for Sjögren’s syndrome,” he said. “They’re fairly sensitive, but can also be seen in other autoimmune conditions, particularly lupus.”

With existing tools, however, optometrists and ophthalmologists can do more to diagnose Sjögren disease early, Dr. Akpek said.

“The issue with Sjögren’s is not that there are no earlier diagnostic aids or anything like that,” Dr. Akpek said.

Lissamine green, a dye that stains degraded cells on the eye’s surface, can reveal clues in young adult patients before other signs. “In my opinion, the earliest clinical finding that indicates presence of the disease is lissamine green staining of conjunctiva,” Akpek said.

Meibomian gland imaging would detect the disease at a later point. “By the time you get meibomian gland dysfunction, there has been longer-standing inflammation,” she said.

Two challenges hold back diagnoses, she said. One is that many practitioners mistakenly believe Sjögren disease is just a nuisance even though it can threaten vision through ocular complications and have more far-reaching effects, too.

“There are a lot of extraglandular systemic manifestations of Sjögren’s that cause morbidity in these patients,” Dr. Akpek said. For example, Sjögren disease is associated with lymphoma and other malignancies, interstitial nephritis, autoimmune hepatitis, and interstitial lung disease with fibrosis.

The second challenge, she said, is that many ophthalmologists and optometrists assume rheumatologists will make the Sjögren disease diagnosis first and then refer patients to them. But eye doctors are well positioned to spot the first signs — if they look for them.

“When you complain of dry eye, unless the doctor puts certain dyes and takes a look at the surface with the dye staining, they can’t see that you are dry,” Dr. Akpek said.

Unfortunately, these tests are underutilized. “I’m sorry to say, dry eye testing, like clinical testing, is not very commonly done,” she said. “Dry eye is managed according to patient symptoms. A lot of the time, Sjögren’s patients have such severe dry eye that they don’t complain of dryness anymore because their corneas become numb.”

Another way to prevent diagnostic delay is to collaborate, communicate, and carefully review patient records shared by other specialists.

“Particularly because of the wide involvement of different organ systems, such as the eyes, the mouth with dental problems, and then systemic features, including joints, it really does need the cooperation of ophthalmologists, dental specialists, and rheumatologists — immunologists sometimes — to come together and make this diagnosis,” Dr. Carsons said.

The study was supported by grants from the National Natural Science Foundation of China. The authors had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Meet your new patients.

You can’t see them, but trillions — maybe quadrillions — of them travel in and out of your practice every day. They’re hungry, mysterious, community-oriented, and small. Very, very small.

They’re the microbes occupying your current patients’ guts.

Someday soon, you’ll prescribe medicine not just for humans but also for these microbes.

“I am convinced in the future our medicine cabinets are going to have not just medications like a statin for treating us, but [also] pills that treat and inhibit an enzyme in our microbes and elicit a health benefit in some chronic disease,” said Stanley Hazen, MD, PhD, co-section head of Preventive Cardiology & Rehabilitation and director of the Center for Microbiome & Human Health at Cleveland Clinic, Cleveland, Ohio.

Evidence is mounting that the gut microbiome influences just about every major human disease. These trillions of microbes use our food to generate substances called metabolites that can protect or harm our health, with consequences reaching far beyond our gastrointestinal tracts.

Research has linked microbial metabolites to diabetes, cardiovascular disease, liver disease, obesity, high blood pressure, neurological disorders, depression, cancer, and more. Gastroenterologist Christopher Damman, MD, a clinical associate professor at the University of Washington Medical Center, Seattle, calls it a “growing theme” in microbiome science.

Now scientists are developing treatments targeting gut microbial pathways, designed to eliminate the bad metabolites and boost the good metabolites.

One close to human therapeutic intervention is an oral treatment from Dr. Hazen’s lab targeting the metabolite trimethylamine N-oxide (TMAO), a predictor of and contributor to both cardiovascular disease and chronic kidney disease. The drug, which blocks TMAO formation, is nearing clinical trials, Dr. Hazen said.

The advantage is safety. By targeting the microbe instead of, say, an enzyme, the host (your patient) must absorb little if any drug.

Implications for the future of medicine are huge. “Gut microbial pathways contribute to diabetes, obesity, virtually everything,” Dr. Hazen said. “Therapies that target gut microbiome processes will probably even be used for psychiatric disorders within, I’ll say, 10 or 20 years.”
 

The Science

About 100 trillion strains of bacteria live in our guts. As humans have evolved, so have they.

Between 70% and 90% come from the phyla Firmicutes and Bacteroidetes, with person-to-person variation shaped by genetics, environment, and lifestyle.

“Everyone’s microbiome is subtly different,” said Dr. Hazen. “So the combination of what they’re making is different. All these different biologically active compounds are influencing us in subtly different ways.”

How it works: When you eat, your microbes eat, breaking down food into metabolites that interact with the thin layer of epithelial cells lining your gut. Some can be absorbed through the lining and into your bloodstream, a phenomenon known as “leaky gut.” Once in your blood, they can trigger irritation and inflammation, potentially leading to a wide variety of health issues, from gas and bloating to autoimmune conditions and mood disorders.

“On the other side of the epithelial lining, you have some of the largest concentrations of immune cells,” said Narendra Kumar, PhD, associate professor of pharmaceutical sciences at Texas A&M University, College Station, Texas.

Metabolites can influence how these immune cells work, possibly explaining why each person’s immune system behaves distinctively.

Of the 1000-plus metabolites linked to the gut microbiome, scientists have identified several that matter.

Short-chain fatty acids. When we eat fiber, colon bacteria ferment it into the beneficial short-chain fatty acids acetate, propionate, and butyrate. These bind to receptors in muscle, liver, and fat tissue, affecting the secretion of gut hormones and peptides related to appetite, inflammation, energy expenditure, and fat oxidation.

Butyrate has been linked to health benefits. It supports the integrity of the gut’s lining, stifling pathogenic gut bacteria, fighting cancer-promoting inflammation, and protecting against obesity and diabetes. It can function as a prebiotic, helping beneficial bacteria thrive. And recent studies linked an abundance of butyrate-producing bacteria with reduced bone fracture risk and hospitalization for infectious disease.

TMAO and phenylacetylglutamine. When we eat foods rich in animal proteins — think eggs, milk, fish, and especially red meat — some gut bacteria convert nutrients like choline and L-carnitine into TMAO and phenylalanine into phenylacetylglutamine. Research conducted by Dr. Hazen’s lab and replicated by others has linked both metabolites to heart problems.

In a landmark study from Dr. Hazen’s group, healthy adults who went on to develop coronary artery disease had significantly higher plasma TMAO levels than those who did not wind up with the condition. The association remained strong, even after controlling for risk factors like age, sex, smoking, high blood pressure, and high cholesterol.

In preclinical studies, elevated TMAO enhanced cardiovascular disease. TMAO-producing microbes also accentuated cardiovascular disease phenotypes in mouse models, while blocking these pathways inhibited the phenotypes.

Research suggests TMAO may harm cardiomyocytes (cells that contract and relax the heart) in dozens of ways, such as activating the expression of proteins to promote hypertrophy and fibrosis, decreasing mitochondrial function, and disrupting calcium signaling.

Another study linked phenylacetylglutamine levels to cardiac event risk in patients with heart failure. Recent mechanistic investigations suggest the metabolite alters signaling in a beta-adrenergic receptor involved in our fight-or-flight response, said Hazen.

“It’s like a rheostat on the light switch, a dimmer switch, and it’s what’s called a negative allosteric modulator,” he said. “It’s the first time that this type of behavior has ever been shown to be present for a gut microbial metabolite and a host receptor.”

Tryptophan metabolites. Microbes in your colon can convert the amino acid tryptophan, also found in animal-based foods, into neurotransmitters like serotonin and melatonin.

“The enteric nervous system, the nervous system around the gut, is immense,” said James Versalovic, MD, PhD, professor of pathology and immunology at Baylor College of Medicine, Houston. “The gut-brain axis has become a very fertile area of research.”

Lesser-known tryptophan metabolites — like indole, tryptamine, and indoleethanol — have been linked to benefits like fortifying the gut barrier, promoting the release of glucagon-like peptide 1 to reduce appetite, and protecting the liver from hepatitis. However, indole can also spur the production of indoxyl sulfate, a toxin linked to chronic kidney disease. 

Bile acid byproducts. Your gut bugs also feast on (and transform) bile acids before they reabsorb and travel back to the liver.

Research is gaining traction on these secondary bile acids, which can affect inflammation and immune function in helpful and harmful ways.

One area of interest is how microbes break down hormones in bile. A recent study from Harvard showed that gut microbes convert corticoid hormones in bile into progestins, which could affect postpartum depression risk. And researchers are exploring the estrobolome — a gut microbial community dedicated to breaking down estrogen into its active form so it can be reabsorbed.

“Depending on the bacteria that you have, more or less can be recirculated back into your blood,” said Beatriz Peñalver Bernabé, PhD, an assistant professor of biomedical engineering and urology at the University of Illinois Chicago. “So you may be producing the same amount of estrogen, but depending on the bacteria you have, the real free estrogen that can bind to your cells may be very different.”

The gut microbiome can also regulate testosterone, with studies showing microbial differences in men with high testosterone vs those with less.
 

What Patients Can Do Now

Advances in the field of microbiome research — and the related “gut health” wellness craze — have spawned all kinds of new microbiome-based products: Like over-the-counter probiotic supplements and at-home test kits, which let you send a stool sample for analysis to reveal microbiome health and personalized diet recommendations.

But the science behind these tests is still evolving, said Dr. Damman. “The clinical inferences and applications are still pretty limited.”

For most people, the first step to fostering healthier microbial metabolites is much simpler: Diversify your diet.

“A lot of folks are missing that diversity,” Dr. Damman said.

“Eat foods and experiment with foods that you might not eat all the time,” especially fruits, vegetables, nuts, seeds, and beans.

Another strategy: Eat foods with probiotic bacteria. “I view it as an insurance policy,” said Dr. Versalovic, “fortifying my gut with probiotics, with daily yogurt, for example, at breakfast.”

Fermented foods like kimchi and kombucha can also increase microbial diversity and can even contain health-promoting postbiotics, research shows.

As for probiotic supplements, the jury’s still out.

Certain strains of probiotic bacteria may be beneficial for some patients, like those with diarrhea, Crohn’s disease, and irritable bowel syndrome, according to World Gastroenterology Organisation guidelines.

As with other interventions, individual responses can vary. A Stanford study showed that some people with metabolic syndrome improved when taking a probiotic, while others didn’t. Both groups had key differences in gut bacteria and dietary habits.

For best results, such microbiome-based interventions will need to be personalized, experts say. And the technology to do that is coming sooner than you might think.
 

Microbiome’s Medical Future: ‘We Are on the Cusp of a New Era’

In just a few years, artificial intelligence (AI) models could predict gut microbial composition based on data such as dietary habits and household characteristics, Dr. Kumar said.

Advancements in metabolomics and bioinformatics could soon help physicians and patients personalize their treatment approaches, said Dr. Damman.

One focus will be on fortifying the gut with whatever it lacks.

“In those individuals where certain microbes are missing, (a) how could we add them back potentially in a rational, science-driven way, and (b) maybe some of those factors that the microbes are producing out the other ends, you could give directly,” said Dr. Damman.

For example, multiple companies make butyrate as a dietary supplement, although the research is too early to support widespread use. Another option could be eating something that spurs butyrate production. One small study found that a fiber supplement formulated to increase butyrate levels in the colon reduced participants’ systolic blood pressure by an average of six points.

Another option could be synbiotics, products that combine bacteria and the food source they feed on. “If you just give a diet-based therapy, it is not going to work as much. Because what if that diet needs certain bacteria to have these beneficial metabolites?” said Ashutosh Mangalam, PhD, associate professor of pathology at the University of Iowa Carver College of Medicine, Iowa City.

Dr. Mangalam studies links between bacterial metabolism of phytoestrogens in soy foods and multiple sclerosis (MS) development. He is using AI to understand differences in metabolites in patients with MS vs healthy controls to determine how to target them.

Gut microbial metabolites could also affect disease screening and intervention. What if gut microbe sequencing could predict a pregnant person’s risk of developing depression, something now assessed through simple questionnaires?

“Imagine that your doctor says, ‘Okay, give me a poop sample,’ ” Dr. Bernabé said. “Then they phenotype it, and then they put it in your electronic medical record, and they say, ‘Well, you have high likelihood of having a mood disorder down the line in your pregnancy. Why don’t we directly refer you to a provider now so you can follow up?’ ”

Research is already underway to understand how metabolites might be linked to pregnancy outcomes, complex regional pain syndrome, and anxiety. Researchers are also investigating whether supplementing our diets with things like prebiotic fibers, apple polyphenols, or tomato paste might influence metabolites. And fecal transplants that shift the gut microbiome and metabolites could have potential in diseases like unexplained atherosclerosis, post-COVID syndrome, and hidradenitis suppurativa.

Dr. Hazen’s discovery linking TMAO with cardiovascular risk has already changed clinical practice. A blood TMAO test can help identify patients at risk who may not have traditional risk factors. “Millions have been done,” Dr. Hazen said.

Meanwhile, his drug targeting the TMAO pathway inches closer to clinical trials.

“In an animal model, we elicit improvement in heart failure, renal disease, atherosclerosis, thrombosis, aortic aneurysm, and obesity,” Dr. Hazen said. The first clinical trials will focus on renal disease.

As with any drug, the road to approval takes time. And success is not guaranteed.

But Dr. Hazen for one is optimistic.

“We are on the cusp of a new era,” Dr. Hazen said. “Like when humans first discovered insulin and glucagon were hormones that impact sugar metabolism. We now recognize myriad new ‘hormones’ in the form of gut microbiome metabolites that impact our physiology and susceptibility to diseases.”
 

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

Meet your new patients.

You can’t see them, but trillions — maybe quadrillions — of them travel in and out of your practice every day. They’re hungry, mysterious, community-oriented, and small. Very, very small.

They’re the microbes occupying your current patients’ guts.

Someday soon, you’ll prescribe medicine not just for humans but also for these microbes.

“I am convinced in the future our medicine cabinets are going to have not just medications like a statin for treating us, but [also] pills that treat and inhibit an enzyme in our microbes and elicit a health benefit in some chronic disease,” said Stanley Hazen, MD, PhD, co-section head of Preventive Cardiology & Rehabilitation and director of the Center for Microbiome & Human Health at Cleveland Clinic, Cleveland, Ohio.

Evidence is mounting that the gut microbiome influences just about every major human disease. These trillions of microbes use our food to generate substances called metabolites that can protect or harm our health, with consequences reaching far beyond our gastrointestinal tracts.

Research has linked microbial metabolites to diabetes, cardiovascular disease, liver disease, obesity, high blood pressure, neurological disorders, depression, cancer, and more. Gastroenterologist Christopher Damman, MD, a clinical associate professor at the University of Washington Medical Center, Seattle, calls it a “growing theme” in microbiome science.

Now scientists are developing treatments targeting gut microbial pathways, designed to eliminate the bad metabolites and boost the good metabolites.

One close to human therapeutic intervention is an oral treatment from Dr. Hazen’s lab targeting the metabolite trimethylamine N-oxide (TMAO), a predictor of and contributor to both cardiovascular disease and chronic kidney disease. The drug, which blocks TMAO formation, is nearing clinical trials, Dr. Hazen said.

The advantage is safety. By targeting the microbe instead of, say, an enzyme, the host (your patient) must absorb little if any drug.

Implications for the future of medicine are huge. “Gut microbial pathways contribute to diabetes, obesity, virtually everything,” Dr. Hazen said. “Therapies that target gut microbiome processes will probably even be used for psychiatric disorders within, I’ll say, 10 or 20 years.”
 

The Science

About 100 trillion strains of bacteria live in our guts. As humans have evolved, so have they.

Between 70% and 90% come from the phyla Firmicutes and Bacteroidetes, with person-to-person variation shaped by genetics, environment, and lifestyle.

“Everyone’s microbiome is subtly different,” said Dr. Hazen. “So the combination of what they’re making is different. All these different biologically active compounds are influencing us in subtly different ways.”

How it works: When you eat, your microbes eat, breaking down food into metabolites that interact with the thin layer of epithelial cells lining your gut. Some can be absorbed through the lining and into your bloodstream, a phenomenon known as “leaky gut.” Once in your blood, they can trigger irritation and inflammation, potentially leading to a wide variety of health issues, from gas and bloating to autoimmune conditions and mood disorders.

“On the other side of the epithelial lining, you have some of the largest concentrations of immune cells,” said Narendra Kumar, PhD, associate professor of pharmaceutical sciences at Texas A&M University, College Station, Texas.

Metabolites can influence how these immune cells work, possibly explaining why each person’s immune system behaves distinctively.

Of the 1000-plus metabolites linked to the gut microbiome, scientists have identified several that matter.

Short-chain fatty acids. When we eat fiber, colon bacteria ferment it into the beneficial short-chain fatty acids acetate, propionate, and butyrate. These bind to receptors in muscle, liver, and fat tissue, affecting the secretion of gut hormones and peptides related to appetite, inflammation, energy expenditure, and fat oxidation.

Butyrate has been linked to health benefits. It supports the integrity of the gut’s lining, stifling pathogenic gut bacteria, fighting cancer-promoting inflammation, and protecting against obesity and diabetes. It can function as a prebiotic, helping beneficial bacteria thrive. And recent studies linked an abundance of butyrate-producing bacteria with reduced bone fracture risk and hospitalization for infectious disease.

TMAO and phenylacetylglutamine. When we eat foods rich in animal proteins — think eggs, milk, fish, and especially red meat — some gut bacteria convert nutrients like choline and L-carnitine into TMAO and phenylalanine into phenylacetylglutamine. Research conducted by Dr. Hazen’s lab and replicated by others has linked both metabolites to heart problems.

In a landmark study from Dr. Hazen’s group, healthy adults who went on to develop coronary artery disease had significantly higher plasma TMAO levels than those who did not wind up with the condition. The association remained strong, even after controlling for risk factors like age, sex, smoking, high blood pressure, and high cholesterol.

In preclinical studies, elevated TMAO enhanced cardiovascular disease. TMAO-producing microbes also accentuated cardiovascular disease phenotypes in mouse models, while blocking these pathways inhibited the phenotypes.

Research suggests TMAO may harm cardiomyocytes (cells that contract and relax the heart) in dozens of ways, such as activating the expression of proteins to promote hypertrophy and fibrosis, decreasing mitochondrial function, and disrupting calcium signaling.

Another study linked phenylacetylglutamine levels to cardiac event risk in patients with heart failure. Recent mechanistic investigations suggest the metabolite alters signaling in a beta-adrenergic receptor involved in our fight-or-flight response, said Hazen.

“It’s like a rheostat on the light switch, a dimmer switch, and it’s what’s called a negative allosteric modulator,” he said. “It’s the first time that this type of behavior has ever been shown to be present for a gut microbial metabolite and a host receptor.”

Tryptophan metabolites. Microbes in your colon can convert the amino acid tryptophan, also found in animal-based foods, into neurotransmitters like serotonin and melatonin.

“The enteric nervous system, the nervous system around the gut, is immense,” said James Versalovic, MD, PhD, professor of pathology and immunology at Baylor College of Medicine, Houston. “The gut-brain axis has become a very fertile area of research.”

Lesser-known tryptophan metabolites — like indole, tryptamine, and indoleethanol — have been linked to benefits like fortifying the gut barrier, promoting the release of glucagon-like peptide 1 to reduce appetite, and protecting the liver from hepatitis. However, indole can also spur the production of indoxyl sulfate, a toxin linked to chronic kidney disease. 

Bile acid byproducts. Your gut bugs also feast on (and transform) bile acids before they reabsorb and travel back to the liver.

Research is gaining traction on these secondary bile acids, which can affect inflammation and immune function in helpful and harmful ways.

One area of interest is how microbes break down hormones in bile. A recent study from Harvard showed that gut microbes convert corticoid hormones in bile into progestins, which could affect postpartum depression risk. And researchers are exploring the estrobolome — a gut microbial community dedicated to breaking down estrogen into its active form so it can be reabsorbed.

“Depending on the bacteria that you have, more or less can be recirculated back into your blood,” said Beatriz Peñalver Bernabé, PhD, an assistant professor of biomedical engineering and urology at the University of Illinois Chicago. “So you may be producing the same amount of estrogen, but depending on the bacteria you have, the real free estrogen that can bind to your cells may be very different.”

The gut microbiome can also regulate testosterone, with studies showing microbial differences in men with high testosterone vs those with less.
 

What Patients Can Do Now

Advances in the field of microbiome research — and the related “gut health” wellness craze — have spawned all kinds of new microbiome-based products: Like over-the-counter probiotic supplements and at-home test kits, which let you send a stool sample for analysis to reveal microbiome health and personalized diet recommendations.

But the science behind these tests is still evolving, said Dr. Damman. “The clinical inferences and applications are still pretty limited.”

For most people, the first step to fostering healthier microbial metabolites is much simpler: Diversify your diet.

“A lot of folks are missing that diversity,” Dr. Damman said.

“Eat foods and experiment with foods that you might not eat all the time,” especially fruits, vegetables, nuts, seeds, and beans.

Another strategy: Eat foods with probiotic bacteria. “I view it as an insurance policy,” said Dr. Versalovic, “fortifying my gut with probiotics, with daily yogurt, for example, at breakfast.”

Fermented foods like kimchi and kombucha can also increase microbial diversity and can even contain health-promoting postbiotics, research shows.

As for probiotic supplements, the jury’s still out.

Certain strains of probiotic bacteria may be beneficial for some patients, like those with diarrhea, Crohn’s disease, and irritable bowel syndrome, according to World Gastroenterology Organisation guidelines.

As with other interventions, individual responses can vary. A Stanford study showed that some people with metabolic syndrome improved when taking a probiotic, while others didn’t. Both groups had key differences in gut bacteria and dietary habits.

For best results, such microbiome-based interventions will need to be personalized, experts say. And the technology to do that is coming sooner than you might think.
 

Microbiome’s Medical Future: ‘We Are on the Cusp of a New Era’

In just a few years, artificial intelligence (AI) models could predict gut microbial composition based on data such as dietary habits and household characteristics, Dr. Kumar said.

Advancements in metabolomics and bioinformatics could soon help physicians and patients personalize their treatment approaches, said Dr. Damman.

One focus will be on fortifying the gut with whatever it lacks.

“In those individuals where certain microbes are missing, (a) how could we add them back potentially in a rational, science-driven way, and (b) maybe some of those factors that the microbes are producing out the other ends, you could give directly,” said Dr. Damman.

For example, multiple companies make butyrate as a dietary supplement, although the research is too early to support widespread use. Another option could be eating something that spurs butyrate production. One small study found that a fiber supplement formulated to increase butyrate levels in the colon reduced participants’ systolic blood pressure by an average of six points.

Another option could be synbiotics, products that combine bacteria and the food source they feed on. “If you just give a diet-based therapy, it is not going to work as much. Because what if that diet needs certain bacteria to have these beneficial metabolites?” said Ashutosh Mangalam, PhD, associate professor of pathology at the University of Iowa Carver College of Medicine, Iowa City.

Dr. Mangalam studies links between bacterial metabolism of phytoestrogens in soy foods and multiple sclerosis (MS) development. He is using AI to understand differences in metabolites in patients with MS vs healthy controls to determine how to target them.

Gut microbial metabolites could also affect disease screening and intervention. What if gut microbe sequencing could predict a pregnant person’s risk of developing depression, something now assessed through simple questionnaires?

“Imagine that your doctor says, ‘Okay, give me a poop sample,’ ” Dr. Bernabé said. “Then they phenotype it, and then they put it in your electronic medical record, and they say, ‘Well, you have high likelihood of having a mood disorder down the line in your pregnancy. Why don’t we directly refer you to a provider now so you can follow up?’ ”

Research is already underway to understand how metabolites might be linked to pregnancy outcomes, complex regional pain syndrome, and anxiety. Researchers are also investigating whether supplementing our diets with things like prebiotic fibers, apple polyphenols, or tomato paste might influence metabolites. And fecal transplants that shift the gut microbiome and metabolites could have potential in diseases like unexplained atherosclerosis, post-COVID syndrome, and hidradenitis suppurativa.

Dr. Hazen’s discovery linking TMAO with cardiovascular risk has already changed clinical practice. A blood TMAO test can help identify patients at risk who may not have traditional risk factors. “Millions have been done,” Dr. Hazen said.

Meanwhile, his drug targeting the TMAO pathway inches closer to clinical trials.

“In an animal model, we elicit improvement in heart failure, renal disease, atherosclerosis, thrombosis, aortic aneurysm, and obesity,” Dr. Hazen said. The first clinical trials will focus on renal disease.

As with any drug, the road to approval takes time. And success is not guaranteed.

But Dr. Hazen for one is optimistic.

“We are on the cusp of a new era,” Dr. Hazen said. “Like when humans first discovered insulin and glucagon were hormones that impact sugar metabolism. We now recognize myriad new ‘hormones’ in the form of gut microbiome metabolites that impact our physiology and susceptibility to diseases.”
 

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

Meet your new patients.

You can’t see them, but trillions — maybe quadrillions — of them travel in and out of your practice every day. They’re hungry, mysterious, community-oriented, and small. Very, very small.

They’re the microbes occupying your current patients’ guts.

Someday soon, you’ll prescribe medicine not just for humans but also for these microbes.

“I am convinced in the future our medicine cabinets are going to have not just medications like a statin for treating us, but [also] pills that treat and inhibit an enzyme in our microbes and elicit a health benefit in some chronic disease,” said Stanley Hazen, MD, PhD, co-section head of Preventive Cardiology & Rehabilitation and director of the Center for Microbiome & Human Health at Cleveland Clinic, Cleveland, Ohio.

Evidence is mounting that the gut microbiome influences just about every major human disease. These trillions of microbes use our food to generate substances called metabolites that can protect or harm our health, with consequences reaching far beyond our gastrointestinal tracts.

Research has linked microbial metabolites to diabetes, cardiovascular disease, liver disease, obesity, high blood pressure, neurological disorders, depression, cancer, and more. Gastroenterologist Christopher Damman, MD, a clinical associate professor at the University of Washington Medical Center, Seattle, calls it a “growing theme” in microbiome science.

Now scientists are developing treatments targeting gut microbial pathways, designed to eliminate the bad metabolites and boost the good metabolites.

One close to human therapeutic intervention is an oral treatment from Dr. Hazen’s lab targeting the metabolite trimethylamine N-oxide (TMAO), a predictor of and contributor to both cardiovascular disease and chronic kidney disease. The drug, which blocks TMAO formation, is nearing clinical trials, Dr. Hazen said.

The advantage is safety. By targeting the microbe instead of, say, an enzyme, the host (your patient) must absorb little if any drug.

Implications for the future of medicine are huge. “Gut microbial pathways contribute to diabetes, obesity, virtually everything,” Dr. Hazen said. “Therapies that target gut microbiome processes will probably even be used for psychiatric disorders within, I’ll say, 10 or 20 years.”
 

The Science

About 100 trillion strains of bacteria live in our guts. As humans have evolved, so have they.

Between 70% and 90% come from the phyla Firmicutes and Bacteroidetes, with person-to-person variation shaped by genetics, environment, and lifestyle.

“Everyone’s microbiome is subtly different,” said Dr. Hazen. “So the combination of what they’re making is different. All these different biologically active compounds are influencing us in subtly different ways.”

How it works: When you eat, your microbes eat, breaking down food into metabolites that interact with the thin layer of epithelial cells lining your gut. Some can be absorbed through the lining and into your bloodstream, a phenomenon known as “leaky gut.” Once in your blood, they can trigger irritation and inflammation, potentially leading to a wide variety of health issues, from gas and bloating to autoimmune conditions and mood disorders.

“On the other side of the epithelial lining, you have some of the largest concentrations of immune cells,” said Narendra Kumar, PhD, associate professor of pharmaceutical sciences at Texas A&M University, College Station, Texas.

Metabolites can influence how these immune cells work, possibly explaining why each person’s immune system behaves distinctively.

Of the 1000-plus metabolites linked to the gut microbiome, scientists have identified several that matter.

Short-chain fatty acids. When we eat fiber, colon bacteria ferment it into the beneficial short-chain fatty acids acetate, propionate, and butyrate. These bind to receptors in muscle, liver, and fat tissue, affecting the secretion of gut hormones and peptides related to appetite, inflammation, energy expenditure, and fat oxidation.

Butyrate has been linked to health benefits. It supports the integrity of the gut’s lining, stifling pathogenic gut bacteria, fighting cancer-promoting inflammation, and protecting against obesity and diabetes. It can function as a prebiotic, helping beneficial bacteria thrive. And recent studies linked an abundance of butyrate-producing bacteria with reduced bone fracture risk and hospitalization for infectious disease.

TMAO and phenylacetylglutamine. When we eat foods rich in animal proteins — think eggs, milk, fish, and especially red meat — some gut bacteria convert nutrients like choline and L-carnitine into TMAO and phenylalanine into phenylacetylglutamine. Research conducted by Dr. Hazen’s lab and replicated by others has linked both metabolites to heart problems.

In a landmark study from Dr. Hazen’s group, healthy adults who went on to develop coronary artery disease had significantly higher plasma TMAO levels than those who did not wind up with the condition. The association remained strong, even after controlling for risk factors like age, sex, smoking, high blood pressure, and high cholesterol.

In preclinical studies, elevated TMAO enhanced cardiovascular disease. TMAO-producing microbes also accentuated cardiovascular disease phenotypes in mouse models, while blocking these pathways inhibited the phenotypes.

Research suggests TMAO may harm cardiomyocytes (cells that contract and relax the heart) in dozens of ways, such as activating the expression of proteins to promote hypertrophy and fibrosis, decreasing mitochondrial function, and disrupting calcium signaling.

Another study linked phenylacetylglutamine levels to cardiac event risk in patients with heart failure. Recent mechanistic investigations suggest the metabolite alters signaling in a beta-adrenergic receptor involved in our fight-or-flight response, said Hazen.

“It’s like a rheostat on the light switch, a dimmer switch, and it’s what’s called a negative allosteric modulator,” he said. “It’s the first time that this type of behavior has ever been shown to be present for a gut microbial metabolite and a host receptor.”

Tryptophan metabolites. Microbes in your colon can convert the amino acid tryptophan, also found in animal-based foods, into neurotransmitters like serotonin and melatonin.

“The enteric nervous system, the nervous system around the gut, is immense,” said James Versalovic, MD, PhD, professor of pathology and immunology at Baylor College of Medicine, Houston. “The gut-brain axis has become a very fertile area of research.”

Lesser-known tryptophan metabolites — like indole, tryptamine, and indoleethanol — have been linked to benefits like fortifying the gut barrier, promoting the release of glucagon-like peptide 1 to reduce appetite, and protecting the liver from hepatitis. However, indole can also spur the production of indoxyl sulfate, a toxin linked to chronic kidney disease. 

Bile acid byproducts. Your gut bugs also feast on (and transform) bile acids before they reabsorb and travel back to the liver.

Research is gaining traction on these secondary bile acids, which can affect inflammation and immune function in helpful and harmful ways.

One area of interest is how microbes break down hormones in bile. A recent study from Harvard showed that gut microbes convert corticoid hormones in bile into progestins, which could affect postpartum depression risk. And researchers are exploring the estrobolome — a gut microbial community dedicated to breaking down estrogen into its active form so it can be reabsorbed.

“Depending on the bacteria that you have, more or less can be recirculated back into your blood,” said Beatriz Peñalver Bernabé, PhD, an assistant professor of biomedical engineering and urology at the University of Illinois Chicago. “So you may be producing the same amount of estrogen, but depending on the bacteria you have, the real free estrogen that can bind to your cells may be very different.”

The gut microbiome can also regulate testosterone, with studies showing microbial differences in men with high testosterone vs those with less.
 

What Patients Can Do Now

Advances in the field of microbiome research — and the related “gut health” wellness craze — have spawned all kinds of new microbiome-based products: Like over-the-counter probiotic supplements and at-home test kits, which let you send a stool sample for analysis to reveal microbiome health and personalized diet recommendations.

But the science behind these tests is still evolving, said Dr. Damman. “The clinical inferences and applications are still pretty limited.”

For most people, the first step to fostering healthier microbial metabolites is much simpler: Diversify your diet.

“A lot of folks are missing that diversity,” Dr. Damman said.

“Eat foods and experiment with foods that you might not eat all the time,” especially fruits, vegetables, nuts, seeds, and beans.

Another strategy: Eat foods with probiotic bacteria. “I view it as an insurance policy,” said Dr. Versalovic, “fortifying my gut with probiotics, with daily yogurt, for example, at breakfast.”

Fermented foods like kimchi and kombucha can also increase microbial diversity and can even contain health-promoting postbiotics, research shows.

As for probiotic supplements, the jury’s still out.

Certain strains of probiotic bacteria may be beneficial for some patients, like those with diarrhea, Crohn’s disease, and irritable bowel syndrome, according to World Gastroenterology Organisation guidelines.

As with other interventions, individual responses can vary. A Stanford study showed that some people with metabolic syndrome improved when taking a probiotic, while others didn’t. Both groups had key differences in gut bacteria and dietary habits.

For best results, such microbiome-based interventions will need to be personalized, experts say. And the technology to do that is coming sooner than you might think.
 

Microbiome’s Medical Future: ‘We Are on the Cusp of a New Era’

In just a few years, artificial intelligence (AI) models could predict gut microbial composition based on data such as dietary habits and household characteristics, Dr. Kumar said.

Advancements in metabolomics and bioinformatics could soon help physicians and patients personalize their treatment approaches, said Dr. Damman.

One focus will be on fortifying the gut with whatever it lacks.

“In those individuals where certain microbes are missing, (a) how could we add them back potentially in a rational, science-driven way, and (b) maybe some of those factors that the microbes are producing out the other ends, you could give directly,” said Dr. Damman.

For example, multiple companies make butyrate as a dietary supplement, although the research is too early to support widespread use. Another option could be eating something that spurs butyrate production. One small study found that a fiber supplement formulated to increase butyrate levels in the colon reduced participants’ systolic blood pressure by an average of six points.

Another option could be synbiotics, products that combine bacteria and the food source they feed on. “If you just give a diet-based therapy, it is not going to work as much. Because what if that diet needs certain bacteria to have these beneficial metabolites?” said Ashutosh Mangalam, PhD, associate professor of pathology at the University of Iowa Carver College of Medicine, Iowa City.

Dr. Mangalam studies links between bacterial metabolism of phytoestrogens in soy foods and multiple sclerosis (MS) development. He is using AI to understand differences in metabolites in patients with MS vs healthy controls to determine how to target them.

Gut microbial metabolites could also affect disease screening and intervention. What if gut microbe sequencing could predict a pregnant person’s risk of developing depression, something now assessed through simple questionnaires?

“Imagine that your doctor says, ‘Okay, give me a poop sample,’ ” Dr. Bernabé said. “Then they phenotype it, and then they put it in your electronic medical record, and they say, ‘Well, you have high likelihood of having a mood disorder down the line in your pregnancy. Why don’t we directly refer you to a provider now so you can follow up?’ ”

Research is already underway to understand how metabolites might be linked to pregnancy outcomes, complex regional pain syndrome, and anxiety. Researchers are also investigating whether supplementing our diets with things like prebiotic fibers, apple polyphenols, or tomato paste might influence metabolites. And fecal transplants that shift the gut microbiome and metabolites could have potential in diseases like unexplained atherosclerosis, post-COVID syndrome, and hidradenitis suppurativa.

Dr. Hazen’s discovery linking TMAO with cardiovascular risk has already changed clinical practice. A blood TMAO test can help identify patients at risk who may not have traditional risk factors. “Millions have been done,” Dr. Hazen said.

Meanwhile, his drug targeting the TMAO pathway inches closer to clinical trials.

“In an animal model, we elicit improvement in heart failure, renal disease, atherosclerosis, thrombosis, aortic aneurysm, and obesity,” Dr. Hazen said. The first clinical trials will focus on renal disease.

As with any drug, the road to approval takes time. And success is not guaranteed.

But Dr. Hazen for one is optimistic.

“We are on the cusp of a new era,” Dr. Hazen said. “Like when humans first discovered insulin and glucagon were hormones that impact sugar metabolism. We now recognize myriad new ‘hormones’ in the form of gut microbiome metabolites that impact our physiology and susceptibility to diseases.”
 

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

Not a morning person? For patients with fibromyalgia, the answer to that question could be a clue about their treatment response with a serotonin and norepinephrine reuptake inhibitor (SNRI), suggested a new cross-sectional study published in Rheumatology International.

Compared with patients who had 30% or more pain relief after 8 or more weeks on an SNRI (duloxetine, venlafaxine, or milnacipran), those with less pain relief reported rougher mornings and worse sleep overall. Morningness, morning affect, diurnal dysrhythmia, anytime wakeability, overall sleep quality, subjective sleep quality and disturbances, sleep medication use, and daytime dysfunction were all predictors of nonresponse to SNRI treatment.

“The observed chronobiological characteristics of patients resistant to SNRI treatment are important because they can be targeted with adjunctive circadian interventions, ie, morning light therapy, in order to normalize circadian rhythms and improve sleep, and in effect, overcome the resistance to treatment and alleviate [the] patient’s pain,” said study author Anna Julia Krupa, MD, a psychiatrist and research assistant in the Department of Affective Disorders at Jagiellonian University Medical College, Kraków, Poland.

Fibromyalgia symptoms like sleep disturbance, low mood, fatigue, stiffness, cognitive impairment, and anxiety are often interlinked in positive feedback loops, meaning that the presence of one symptom (ie, sleep problems or depression) exacerbates the other (ie, pain or anxiety), Dr. Krupa said. While SNRIs can reduce pain, anxiety, and depression, they don’t directly improve sleep. Sometimes, pain relief smooths out minor sleep problems, but not always.

“Therefore, if circadian rhythm disruptions and sleep problems are significant, they may constitute a factor which limits SNRI effects on pain in people with fibromyalgia,” Dr. Krupa said.

With 60 patients with fibromyalgia (30 responsive to treatment and 30 nonresponsive to treatment) and 30 healthy controls, this was a small study, noted Daniel G. Arkfeld, MD, DDS, a rheumatologist and associate professor of clinical medicine at Keck School of Medicine, University of Southern California, Los Angeles. However, “sleep is probably one of the most difficult things in fibromyalgia, and it definitely needs to be targeted.”

Decades of research suggest that important neurochemicals, like growth hormone, are released in deep sleep. “We know that sleep disturbances and time frame and release of neurochemicals [are] all super important in fibromyalgia,” he said.

Side effects of medication could be another factor at play here. As with any drug, the side effects of SNRIs vary widely from person to person, but palpitations, tremulousness, and insomnia are common, said Daniel J. Clauw, MD, professor of anesthesiology, internal medicine/rheumatology, and psychiatry and director of the Chronic Pain & Fatigue Research Center at the University of Michigan, Ann Arbor.

“SNRIs are often ‘activating’ because of the increase in norepinephrine,” Dr. Clauw said. “This is often helpful for symptoms such as fatigue and memory problems — but could worsen sleep.”

That’s why he always recommends that patients take an SNRI in the morning, not at night. Try that and the following tips to help patients with fibromyalgia sleep better and feel better, too.

Start with the basics. It’s worth reminding patients about the tried-and-true tips like going to bed and waking up at the same time every day and keeping your bedroom quiet and dark. “Patients should first try ‘sleep hygiene’ strategies,” said Dr. Clauw. “If that doesn’t help then cognitive-behavioral therapy (CBT) for insomnia can be very helpful.”

A systematic review and meta-analysis showed that CBT for insomnia helped patients with fibromyalgia improve sleep quality, pain, anxiety, and depression compared with nonpharmacologic treatments. And if that doesn’t help? “If need be, they can try nonbenzodiazepine hypnotic drugs, eg, tricyclics or gabapentinoids taken at bedtime,” said Dr. Clauw.

Help them fall in love with exercise. A personalized approach to exercise can help patients with fibromyalgia feel better, suggested a study review in Clinical and Experimental Rheumatology. Exercise can also help reset the circadian clock. Morning activity helps night owls get on an earlier schedule, suggested a study review published in Physical Activity and Nutrition. 

Consider yoga, tai chi, or qigong. A study review published in Seminars in Arthritis and Rheumatism suggested mind-body and combined exercises help improve sleep for people with fibromyalgia, while aerobic or strength training alone does not. One explanation is that mind-body exercises might do more than other types to tamp down sympathetic-excitatory overactivation in fibromyalgia, the researchers said. Use this handy guide from the European Pain Federation to help you start the exercise conversation.

Talk about sleep alongside other aspects of fibromyalgia. Psychoeducation for fibromyalgia often includes information about the distinction between acute and chronic pain, the nature of fibromyalgia syndrome, disease-contributing factors, safe and effective treatments, symptoms and characteristics, and coping strategies, according to a study review in the journal Behavioral Sciences. “As a psychiatrist and someone who often consults patients with fibromyalgia, I would also add the information about links between pain and mood, anxiety as well as sleep,” said Dr. Krupa.

Try morning light. Use light to shift circadian rhythms, suggested Dr. Krupa. People who struggle in the morning might benefit from 30-60 minutes of morning light therapy immediately after waking using a 10,000-lux light box or light glasses, as suggested by a study review from the University of Michigan.

Help them get off the night shift. “Fibromyalgia patients probably shouldn’t work the night shift and throw their circadian rhythm off,” said Dr. Arkfeld. Depending on a patient’s work and financial circumstances, a job change might not be possible, but consider writing a note to the patient’s employer asking them to switch the patient to the day shift. Dr. Arkfeld said this approach has worked for some of his patients.

Refer them for a sleep study. Many patients with fibromyalgia have obstructive sleep apnea or other sleep disorders that require additional intervention. “Sleep studies are important to kind of define the actual sleep problem that’s occurring as well, whether it’s the stage for interruption of sleep or sleep apnea or wakefulness,” said Dr. Arkfeld.

The study was funded by Jagiellonian University Medical College. The authors had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Not a morning person? For patients with fibromyalgia, the answer to that question could be a clue about their treatment response with a serotonin and norepinephrine reuptake inhibitor (SNRI), suggested a new cross-sectional study published in Rheumatology International.

Compared with patients who had 30% or more pain relief after 8 or more weeks on an SNRI (duloxetine, venlafaxine, or milnacipran), those with less pain relief reported rougher mornings and worse sleep overall. Morningness, morning affect, diurnal dysrhythmia, anytime wakeability, overall sleep quality, subjective sleep quality and disturbances, sleep medication use, and daytime dysfunction were all predictors of nonresponse to SNRI treatment.

“The observed chronobiological characteristics of patients resistant to SNRI treatment are important because they can be targeted with adjunctive circadian interventions, ie, morning light therapy, in order to normalize circadian rhythms and improve sleep, and in effect, overcome the resistance to treatment and alleviate [the] patient’s pain,” said study author Anna Julia Krupa, MD, a psychiatrist and research assistant in the Department of Affective Disorders at Jagiellonian University Medical College, Kraków, Poland.

Fibromyalgia symptoms like sleep disturbance, low mood, fatigue, stiffness, cognitive impairment, and anxiety are often interlinked in positive feedback loops, meaning that the presence of one symptom (ie, sleep problems or depression) exacerbates the other (ie, pain or anxiety), Dr. Krupa said. While SNRIs can reduce pain, anxiety, and depression, they don’t directly improve sleep. Sometimes, pain relief smooths out minor sleep problems, but not always.

“Therefore, if circadian rhythm disruptions and sleep problems are significant, they may constitute a factor which limits SNRI effects on pain in people with fibromyalgia,” Dr. Krupa said.

With 60 patients with fibromyalgia (30 responsive to treatment and 30 nonresponsive to treatment) and 30 healthy controls, this was a small study, noted Daniel G. Arkfeld, MD, DDS, a rheumatologist and associate professor of clinical medicine at Keck School of Medicine, University of Southern California, Los Angeles. However, “sleep is probably one of the most difficult things in fibromyalgia, and it definitely needs to be targeted.”

Decades of research suggest that important neurochemicals, like growth hormone, are released in deep sleep. “We know that sleep disturbances and time frame and release of neurochemicals [are] all super important in fibromyalgia,” he said.

Side effects of medication could be another factor at play here. As with any drug, the side effects of SNRIs vary widely from person to person, but palpitations, tremulousness, and insomnia are common, said Daniel J. Clauw, MD, professor of anesthesiology, internal medicine/rheumatology, and psychiatry and director of the Chronic Pain & Fatigue Research Center at the University of Michigan, Ann Arbor.

“SNRIs are often ‘activating’ because of the increase in norepinephrine,” Dr. Clauw said. “This is often helpful for symptoms such as fatigue and memory problems — but could worsen sleep.”

That’s why he always recommends that patients take an SNRI in the morning, not at night. Try that and the following tips to help patients with fibromyalgia sleep better and feel better, too.

Start with the basics. It’s worth reminding patients about the tried-and-true tips like going to bed and waking up at the same time every day and keeping your bedroom quiet and dark. “Patients should first try ‘sleep hygiene’ strategies,” said Dr. Clauw. “If that doesn’t help then cognitive-behavioral therapy (CBT) for insomnia can be very helpful.”

A systematic review and meta-analysis showed that CBT for insomnia helped patients with fibromyalgia improve sleep quality, pain, anxiety, and depression compared with nonpharmacologic treatments. And if that doesn’t help? “If need be, they can try nonbenzodiazepine hypnotic drugs, eg, tricyclics or gabapentinoids taken at bedtime,” said Dr. Clauw.

Help them fall in love with exercise. A personalized approach to exercise can help patients with fibromyalgia feel better, suggested a study review in Clinical and Experimental Rheumatology. Exercise can also help reset the circadian clock. Morning activity helps night owls get on an earlier schedule, suggested a study review published in Physical Activity and Nutrition. 

Consider yoga, tai chi, or qigong. A study review published in Seminars in Arthritis and Rheumatism suggested mind-body and combined exercises help improve sleep for people with fibromyalgia, while aerobic or strength training alone does not. One explanation is that mind-body exercises might do more than other types to tamp down sympathetic-excitatory overactivation in fibromyalgia, the researchers said. Use this handy guide from the European Pain Federation to help you start the exercise conversation.

Talk about sleep alongside other aspects of fibromyalgia. Psychoeducation for fibromyalgia often includes information about the distinction between acute and chronic pain, the nature of fibromyalgia syndrome, disease-contributing factors, safe and effective treatments, symptoms and characteristics, and coping strategies, according to a study review in the journal Behavioral Sciences. “As a psychiatrist and someone who often consults patients with fibromyalgia, I would also add the information about links between pain and mood, anxiety as well as sleep,” said Dr. Krupa.

Try morning light. Use light to shift circadian rhythms, suggested Dr. Krupa. People who struggle in the morning might benefit from 30-60 minutes of morning light therapy immediately after waking using a 10,000-lux light box or light glasses, as suggested by a study review from the University of Michigan.

Help them get off the night shift. “Fibromyalgia patients probably shouldn’t work the night shift and throw their circadian rhythm off,” said Dr. Arkfeld. Depending on a patient’s work and financial circumstances, a job change might not be possible, but consider writing a note to the patient’s employer asking them to switch the patient to the day shift. Dr. Arkfeld said this approach has worked for some of his patients.

Refer them for a sleep study. Many patients with fibromyalgia have obstructive sleep apnea or other sleep disorders that require additional intervention. “Sleep studies are important to kind of define the actual sleep problem that’s occurring as well, whether it’s the stage for interruption of sleep or sleep apnea or wakefulness,” said Dr. Arkfeld.

The study was funded by Jagiellonian University Medical College. The authors had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Not a morning person? For patients with fibromyalgia, the answer to that question could be a clue about their treatment response with a serotonin and norepinephrine reuptake inhibitor (SNRI), suggested a new cross-sectional study published in Rheumatology International.

Compared with patients who had 30% or more pain relief after 8 or more weeks on an SNRI (duloxetine, venlafaxine, or milnacipran), those with less pain relief reported rougher mornings and worse sleep overall. Morningness, morning affect, diurnal dysrhythmia, anytime wakeability, overall sleep quality, subjective sleep quality and disturbances, sleep medication use, and daytime dysfunction were all predictors of nonresponse to SNRI treatment.

“The observed chronobiological characteristics of patients resistant to SNRI treatment are important because they can be targeted with adjunctive circadian interventions, ie, morning light therapy, in order to normalize circadian rhythms and improve sleep, and in effect, overcome the resistance to treatment and alleviate [the] patient’s pain,” said study author Anna Julia Krupa, MD, a psychiatrist and research assistant in the Department of Affective Disorders at Jagiellonian University Medical College, Kraków, Poland.

Fibromyalgia symptoms like sleep disturbance, low mood, fatigue, stiffness, cognitive impairment, and anxiety are often interlinked in positive feedback loops, meaning that the presence of one symptom (ie, sleep problems or depression) exacerbates the other (ie, pain or anxiety), Dr. Krupa said. While SNRIs can reduce pain, anxiety, and depression, they don’t directly improve sleep. Sometimes, pain relief smooths out minor sleep problems, but not always.

“Therefore, if circadian rhythm disruptions and sleep problems are significant, they may constitute a factor which limits SNRI effects on pain in people with fibromyalgia,” Dr. Krupa said.

With 60 patients with fibromyalgia (30 responsive to treatment and 30 nonresponsive to treatment) and 30 healthy controls, this was a small study, noted Daniel G. Arkfeld, MD, DDS, a rheumatologist and associate professor of clinical medicine at Keck School of Medicine, University of Southern California, Los Angeles. However, “sleep is probably one of the most difficult things in fibromyalgia, and it definitely needs to be targeted.”

Decades of research suggest that important neurochemicals, like growth hormone, are released in deep sleep. “We know that sleep disturbances and time frame and release of neurochemicals [are] all super important in fibromyalgia,” he said.

Side effects of medication could be another factor at play here. As with any drug, the side effects of SNRIs vary widely from person to person, but palpitations, tremulousness, and insomnia are common, said Daniel J. Clauw, MD, professor of anesthesiology, internal medicine/rheumatology, and psychiatry and director of the Chronic Pain & Fatigue Research Center at the University of Michigan, Ann Arbor.

“SNRIs are often ‘activating’ because of the increase in norepinephrine,” Dr. Clauw said. “This is often helpful for symptoms such as fatigue and memory problems — but could worsen sleep.”

That’s why he always recommends that patients take an SNRI in the morning, not at night. Try that and the following tips to help patients with fibromyalgia sleep better and feel better, too.

Start with the basics. It’s worth reminding patients about the tried-and-true tips like going to bed and waking up at the same time every day and keeping your bedroom quiet and dark. “Patients should first try ‘sleep hygiene’ strategies,” said Dr. Clauw. “If that doesn’t help then cognitive-behavioral therapy (CBT) for insomnia can be very helpful.”

A systematic review and meta-analysis showed that CBT for insomnia helped patients with fibromyalgia improve sleep quality, pain, anxiety, and depression compared with nonpharmacologic treatments. And if that doesn’t help? “If need be, they can try nonbenzodiazepine hypnotic drugs, eg, tricyclics or gabapentinoids taken at bedtime,” said Dr. Clauw.

Help them fall in love with exercise. A personalized approach to exercise can help patients with fibromyalgia feel better, suggested a study review in Clinical and Experimental Rheumatology. Exercise can also help reset the circadian clock. Morning activity helps night owls get on an earlier schedule, suggested a study review published in Physical Activity and Nutrition. 

Consider yoga, tai chi, or qigong. A study review published in Seminars in Arthritis and Rheumatism suggested mind-body and combined exercises help improve sleep for people with fibromyalgia, while aerobic or strength training alone does not. One explanation is that mind-body exercises might do more than other types to tamp down sympathetic-excitatory overactivation in fibromyalgia, the researchers said. Use this handy guide from the European Pain Federation to help you start the exercise conversation.

Talk about sleep alongside other aspects of fibromyalgia. Psychoeducation for fibromyalgia often includes information about the distinction between acute and chronic pain, the nature of fibromyalgia syndrome, disease-contributing factors, safe and effective treatments, symptoms and characteristics, and coping strategies, according to a study review in the journal Behavioral Sciences. “As a psychiatrist and someone who often consults patients with fibromyalgia, I would also add the information about links between pain and mood, anxiety as well as sleep,” said Dr. Krupa.

Try morning light. Use light to shift circadian rhythms, suggested Dr. Krupa. People who struggle in the morning might benefit from 30-60 minutes of morning light therapy immediately after waking using a 10,000-lux light box or light glasses, as suggested by a study review from the University of Michigan.

Help them get off the night shift. “Fibromyalgia patients probably shouldn’t work the night shift and throw their circadian rhythm off,” said Dr. Arkfeld. Depending on a patient’s work and financial circumstances, a job change might not be possible, but consider writing a note to the patient’s employer asking them to switch the patient to the day shift. Dr. Arkfeld said this approach has worked for some of his patients.

Refer them for a sleep study. Many patients with fibromyalgia have obstructive sleep apnea or other sleep disorders that require additional intervention. “Sleep studies are important to kind of define the actual sleep problem that’s occurring as well, whether it’s the stage for interruption of sleep or sleep apnea or wakefulness,” said Dr. Arkfeld.

The study was funded by Jagiellonian University Medical College. The authors had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Is going sugar free really good advice for patients with cardiometabolic risk factors? 

That’s the question raised by new Cleveland Clinic research, which suggests that consuming erythritol, a sweetener widely found in sugar-free and keto food products, could spur a prothrombotic response. 

In the study, published in Arteriosclerosis, Thrombosis, and Vascular Biology, 10 healthy participants ate 30 grams of erythritol. Thirty minutes later, their blood showed enhanced platelet aggregation and increased markers of platelet responsiveness and activation. 

Specifically, the researchers saw enhanced stimulus-dependent release of serotonin (a marker of platelet dense granules) and CXCL4 (a platelet alpha-granule marker). 

“ With every single person, you see a prothrombotic effect with every single test that we did,” said study author Stanley Hazen, MD, PhD, chair of the Department of Cardiovascular & Metabolic Sciences at Cleveland Clinic in Ohio. By contrast, participants who ate 30 grams of glucose saw no such effect. 

The erythritol itself does not activate the platelets, Dr. Hazen said, rather it lowers the threshold for triggering a response. This could make someone more prone to clotting, raising heart attack and stroke risk over time.

Though the mechanism is unknown, Dr. Hazen has an idea. 

“There appears to be a receptor on platelets that is recognizing and sensing these sugar alcohols,” Dr. Hazen said, “much in the same way your taste bud for sweet is a receptor for recognizing a glucose or sugar molecule.” 

“We’re very interested in trying to figure out what the receptor is,” Dr. Hazen said, “because I think that then becomes a very interesting potential target for further investigation and study into how this is linked to causing heart disease.”
 

The Past and Future of Erythritol Research

In 2001, the Food and Drug Administration classified erythritol as a “generally recognized as safe” food additive. A sugar alcohol that occurs naturally in foods like melon and grapes, erythritol is also manufactured by fermenting sugars. It’s about 70% as sweet as table sugar. Humans also produce small amounts of erythritol naturally: Our blood cells make it from glucose via the pentose phosphate pathway. 

Previous research from Dr. Hazen’s group linked erythritol to a risk for major adverse cardiovascular events and clotting. 

“Based on their previous study, I think this was a really important study to do in healthy individuals,” said Martha Field, PhD, assistant professor in the Division of Nutritional Sciences at Cornell University, Ithaca, New York, who was not involved in the study.

The earlier paper analyzed blood samples from participants with unknown erythritol intake, including some taken before the sweetener, and it was as widespread as it is today. That made disentangling the effects of eating erythritol vs naturally producing it more difficult. 

By showing that eating erythritol raises markers associated with thrombosis, the new paper reinforces the importance of thinking about and developing a deeper understanding of what we put into our bodies. 

“This paper was conducted in healthy individuals — might this be particularly dangerous for individuals who are at increased risk of clotting?” asked Dr. Field. “There are lots of genetic polymorphisms that increase your risk for clotting disorders or your propensity to form thrombosis.” 

Field would like to see similar analyses of xylitol and sorbitol, other sugar alcohols found in sugar-free foods. And she called for more studies on erythritol that look at lower erythritol consumption over longer time periods. 

Registered dietitian nutritionist Valisa E. Hedrick, PhD, agreed: Much more work is needed in this area, particularly in higher-risk groups, such as those with prediabetes and diabetes, said Dr. Hedrick, an associate professor in the Department of Human Nutrition, Foods, and Exercise at Virginia Tech, Blacksburg, who was not involved in the study. 

“Because this study was conducted in healthy individuals, the impact of a small dose of glucose was negligible, as their body can effectively regulate blood glucose levels,” she said. “Because high blood glucose concentrations have also been shown to increase platelet reactivity, and consequently increase thrombosis potential, individuals who are not able to regulate their blood glucose levels, such as those with prediabetes and diabetes, could potentially see a similar effect on the body as erythritol when consuming large amounts of sugar.” 

At the same time, “individuals with diabetes or prediabetes may be more inclined to consume erythritol as an alternative to sugar,” Dr. Hedrick added. “It will be important to design studies that include these individuals to determine if erythritol has an additive adverse effect on cardiac event risk.”
 

Criticism and Impact 

Critics have suggested the 30-gram dose of erythritol ingested by study participants is unrealistic. Dr. Hazen said that it’s not. 

Erythritol is often recommended as a one-to-one sugar replacement. And you could top 30 grams with a few servings of erythritol-sweetened ice cream or soda, Dr. Hazen said. 

“The dose that we used, it’s on the high end, but it’s well within a physiologically relevant level,” he said. 

Still others say the results are only relevant for people with preexisting heart trouble. But Dr. Hazen said they matter for the masses. 

“I think there’s a significant health concern at a population level that this work is underscoring,” he said. 

After all, heart disease risk factors like obesity, hypertension, diabetes, and smoking are common and quickly add up. 

“If you look at middle-aged America, most people who experience a heart attack or stroke do not know that they have coronary artery disease, and the first recognition of it is that event,” Dr. Hazen said. 

For now, Dr. Hazen recommends eating real sugar in moderation. He hopes future research will reveal a nonnutritive sweetener that doesn’t activate platelets. 
 

The Bigger Picture

The new research adds yet another piece to the puzzle of whether nonnutritive sweeteners are better than sugar. 

“I think these results are concerning,” said JoAnn E. Manson, MD, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts. They “ may help explain the surprising results in some observational studies that artificial sweeteners are linked to an increased risk of cardiovascular disease.”

Dr. Manson, who was not involved in the new study, has conducted other research linking artificial sweetener use with stroke risk.

In an upcoming randomized clinical study, her team is comparing head-to-head sugar-sweetened beverages, drinks sweetened with calorie-free substitutes, and water to determine which is best for a range of cardiometabolic outcomes. 

“We need more research on this question,” she said, “because these artificial sweeteners are commonly used, and many people are assuming that their health outcomes will be better with the artificial sweeteners than with sugar-sweetened products.”

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

Is going sugar free really good advice for patients with cardiometabolic risk factors? 

That’s the question raised by new Cleveland Clinic research, which suggests that consuming erythritol, a sweetener widely found in sugar-free and keto food products, could spur a prothrombotic response. 

In the study, published in Arteriosclerosis, Thrombosis, and Vascular Biology, 10 healthy participants ate 30 grams of erythritol. Thirty minutes later, their blood showed enhanced platelet aggregation and increased markers of platelet responsiveness and activation. 

Specifically, the researchers saw enhanced stimulus-dependent release of serotonin (a marker of platelet dense granules) and CXCL4 (a platelet alpha-granule marker). 

“ With every single person, you see a prothrombotic effect with every single test that we did,” said study author Stanley Hazen, MD, PhD, chair of the Department of Cardiovascular & Metabolic Sciences at Cleveland Clinic in Ohio. By contrast, participants who ate 30 grams of glucose saw no such effect. 

The erythritol itself does not activate the platelets, Dr. Hazen said, rather it lowers the threshold for triggering a response. This could make someone more prone to clotting, raising heart attack and stroke risk over time.

Though the mechanism is unknown, Dr. Hazen has an idea. 

“There appears to be a receptor on platelets that is recognizing and sensing these sugar alcohols,” Dr. Hazen said, “much in the same way your taste bud for sweet is a receptor for recognizing a glucose or sugar molecule.” 

“We’re very interested in trying to figure out what the receptor is,” Dr. Hazen said, “because I think that then becomes a very interesting potential target for further investigation and study into how this is linked to causing heart disease.”
 

The Past and Future of Erythritol Research

In 2001, the Food and Drug Administration classified erythritol as a “generally recognized as safe” food additive. A sugar alcohol that occurs naturally in foods like melon and grapes, erythritol is also manufactured by fermenting sugars. It’s about 70% as sweet as table sugar. Humans also produce small amounts of erythritol naturally: Our blood cells make it from glucose via the pentose phosphate pathway. 

Previous research from Dr. Hazen’s group linked erythritol to a risk for major adverse cardiovascular events and clotting. 

“Based on their previous study, I think this was a really important study to do in healthy individuals,” said Martha Field, PhD, assistant professor in the Division of Nutritional Sciences at Cornell University, Ithaca, New York, who was not involved in the study.

The earlier paper analyzed blood samples from participants with unknown erythritol intake, including some taken before the sweetener, and it was as widespread as it is today. That made disentangling the effects of eating erythritol vs naturally producing it more difficult. 

By showing that eating erythritol raises markers associated with thrombosis, the new paper reinforces the importance of thinking about and developing a deeper understanding of what we put into our bodies. 

“This paper was conducted in healthy individuals — might this be particularly dangerous for individuals who are at increased risk of clotting?” asked Dr. Field. “There are lots of genetic polymorphisms that increase your risk for clotting disorders or your propensity to form thrombosis.” 

Field would like to see similar analyses of xylitol and sorbitol, other sugar alcohols found in sugar-free foods. And she called for more studies on erythritol that look at lower erythritol consumption over longer time periods. 

Registered dietitian nutritionist Valisa E. Hedrick, PhD, agreed: Much more work is needed in this area, particularly in higher-risk groups, such as those with prediabetes and diabetes, said Dr. Hedrick, an associate professor in the Department of Human Nutrition, Foods, and Exercise at Virginia Tech, Blacksburg, who was not involved in the study. 

“Because this study was conducted in healthy individuals, the impact of a small dose of glucose was negligible, as their body can effectively regulate blood glucose levels,” she said. “Because high blood glucose concentrations have also been shown to increase platelet reactivity, and consequently increase thrombosis potential, individuals who are not able to regulate their blood glucose levels, such as those with prediabetes and diabetes, could potentially see a similar effect on the body as erythritol when consuming large amounts of sugar.” 

At the same time, “individuals with diabetes or prediabetes may be more inclined to consume erythritol as an alternative to sugar,” Dr. Hedrick added. “It will be important to design studies that include these individuals to determine if erythritol has an additive adverse effect on cardiac event risk.”
 

Criticism and Impact 

Critics have suggested the 30-gram dose of erythritol ingested by study participants is unrealistic. Dr. Hazen said that it’s not. 

Erythritol is often recommended as a one-to-one sugar replacement. And you could top 30 grams with a few servings of erythritol-sweetened ice cream or soda, Dr. Hazen said. 

“The dose that we used, it’s on the high end, but it’s well within a physiologically relevant level,” he said. 

Still others say the results are only relevant for people with preexisting heart trouble. But Dr. Hazen said they matter for the masses. 

“I think there’s a significant health concern at a population level that this work is underscoring,” he said. 

After all, heart disease risk factors like obesity, hypertension, diabetes, and smoking are common and quickly add up. 

“If you look at middle-aged America, most people who experience a heart attack or stroke do not know that they have coronary artery disease, and the first recognition of it is that event,” Dr. Hazen said. 

For now, Dr. Hazen recommends eating real sugar in moderation. He hopes future research will reveal a nonnutritive sweetener that doesn’t activate platelets. 
 

The Bigger Picture

The new research adds yet another piece to the puzzle of whether nonnutritive sweeteners are better than sugar. 

“I think these results are concerning,” said JoAnn E. Manson, MD, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts. They “ may help explain the surprising results in some observational studies that artificial sweeteners are linked to an increased risk of cardiovascular disease.”

Dr. Manson, who was not involved in the new study, has conducted other research linking artificial sweetener use with stroke risk.

In an upcoming randomized clinical study, her team is comparing head-to-head sugar-sweetened beverages, drinks sweetened with calorie-free substitutes, and water to determine which is best for a range of cardiometabolic outcomes. 

“We need more research on this question,” she said, “because these artificial sweeteners are commonly used, and many people are assuming that their health outcomes will be better with the artificial sweeteners than with sugar-sweetened products.”

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

Is going sugar free really good advice for patients with cardiometabolic risk factors? 

That’s the question raised by new Cleveland Clinic research, which suggests that consuming erythritol, a sweetener widely found in sugar-free and keto food products, could spur a prothrombotic response. 

In the study, published in Arteriosclerosis, Thrombosis, and Vascular Biology, 10 healthy participants ate 30 grams of erythritol. Thirty minutes later, their blood showed enhanced platelet aggregation and increased markers of platelet responsiveness and activation. 

Specifically, the researchers saw enhanced stimulus-dependent release of serotonin (a marker of platelet dense granules) and CXCL4 (a platelet alpha-granule marker). 

“ With every single person, you see a prothrombotic effect with every single test that we did,” said study author Stanley Hazen, MD, PhD, chair of the Department of Cardiovascular & Metabolic Sciences at Cleveland Clinic in Ohio. By contrast, participants who ate 30 grams of glucose saw no such effect. 

The erythritol itself does not activate the platelets, Dr. Hazen said, rather it lowers the threshold for triggering a response. This could make someone more prone to clotting, raising heart attack and stroke risk over time.

Though the mechanism is unknown, Dr. Hazen has an idea. 

“There appears to be a receptor on platelets that is recognizing and sensing these sugar alcohols,” Dr. Hazen said, “much in the same way your taste bud for sweet is a receptor for recognizing a glucose or sugar molecule.” 

“We’re very interested in trying to figure out what the receptor is,” Dr. Hazen said, “because I think that then becomes a very interesting potential target for further investigation and study into how this is linked to causing heart disease.”
 

The Past and Future of Erythritol Research

In 2001, the Food and Drug Administration classified erythritol as a “generally recognized as safe” food additive. A sugar alcohol that occurs naturally in foods like melon and grapes, erythritol is also manufactured by fermenting sugars. It’s about 70% as sweet as table sugar. Humans also produce small amounts of erythritol naturally: Our blood cells make it from glucose via the pentose phosphate pathway. 

Previous research from Dr. Hazen’s group linked erythritol to a risk for major adverse cardiovascular events and clotting. 

“Based on their previous study, I think this was a really important study to do in healthy individuals,” said Martha Field, PhD, assistant professor in the Division of Nutritional Sciences at Cornell University, Ithaca, New York, who was not involved in the study.

The earlier paper analyzed blood samples from participants with unknown erythritol intake, including some taken before the sweetener, and it was as widespread as it is today. That made disentangling the effects of eating erythritol vs naturally producing it more difficult. 

By showing that eating erythritol raises markers associated with thrombosis, the new paper reinforces the importance of thinking about and developing a deeper understanding of what we put into our bodies. 

“This paper was conducted in healthy individuals — might this be particularly dangerous for individuals who are at increased risk of clotting?” asked Dr. Field. “There are lots of genetic polymorphisms that increase your risk for clotting disorders or your propensity to form thrombosis.” 

Field would like to see similar analyses of xylitol and sorbitol, other sugar alcohols found in sugar-free foods. And she called for more studies on erythritol that look at lower erythritol consumption over longer time periods. 

Registered dietitian nutritionist Valisa E. Hedrick, PhD, agreed: Much more work is needed in this area, particularly in higher-risk groups, such as those with prediabetes and diabetes, said Dr. Hedrick, an associate professor in the Department of Human Nutrition, Foods, and Exercise at Virginia Tech, Blacksburg, who was not involved in the study. 

“Because this study was conducted in healthy individuals, the impact of a small dose of glucose was negligible, as their body can effectively regulate blood glucose levels,” she said. “Because high blood glucose concentrations have also been shown to increase platelet reactivity, and consequently increase thrombosis potential, individuals who are not able to regulate their blood glucose levels, such as those with prediabetes and diabetes, could potentially see a similar effect on the body as erythritol when consuming large amounts of sugar.” 

At the same time, “individuals with diabetes or prediabetes may be more inclined to consume erythritol as an alternative to sugar,” Dr. Hedrick added. “It will be important to design studies that include these individuals to determine if erythritol has an additive adverse effect on cardiac event risk.”
 

Criticism and Impact 

Critics have suggested the 30-gram dose of erythritol ingested by study participants is unrealistic. Dr. Hazen said that it’s not. 

Erythritol is often recommended as a one-to-one sugar replacement. And you could top 30 grams with a few servings of erythritol-sweetened ice cream or soda, Dr. Hazen said. 

“The dose that we used, it’s on the high end, but it’s well within a physiologically relevant level,” he said. 

Still others say the results are only relevant for people with preexisting heart trouble. But Dr. Hazen said they matter for the masses. 

“I think there’s a significant health concern at a population level that this work is underscoring,” he said. 

After all, heart disease risk factors like obesity, hypertension, diabetes, and smoking are common and quickly add up. 

“If you look at middle-aged America, most people who experience a heart attack or stroke do not know that they have coronary artery disease, and the first recognition of it is that event,” Dr. Hazen said. 

For now, Dr. Hazen recommends eating real sugar in moderation. He hopes future research will reveal a nonnutritive sweetener that doesn’t activate platelets. 
 

The Bigger Picture

The new research adds yet another piece to the puzzle of whether nonnutritive sweeteners are better than sugar. 

“I think these results are concerning,” said JoAnn E. Manson, MD, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts. They “ may help explain the surprising results in some observational studies that artificial sweeteners are linked to an increased risk of cardiovascular disease.”

Dr. Manson, who was not involved in the new study, has conducted other research linking artificial sweetener use with stroke risk.

In an upcoming randomized clinical study, her team is comparing head-to-head sugar-sweetened beverages, drinks sweetened with calorie-free substitutes, and water to determine which is best for a range of cardiometabolic outcomes. 

“We need more research on this question,” she said, “because these artificial sweeteners are commonly used, and many people are assuming that their health outcomes will be better with the artificial sweeteners than with sugar-sweetened products.”

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

Many patients struggle with healthcare costs and basic expenses, according to new research.

People with rheumatologic diseases often experience a hidden symptom: financial toxicity or significant economic strain from out-of-pocket costs. A new study of 41,502 patients published in JCR: Journal of Clinical Rheumatology showed that 20% of those with rheumatologic diseases faced financial hardship from medical expenses, with 55% of those unable to pay their bills. 

Compared with patients who do not have rheumatologic diseases, and after clinical and sociodemographic factors were controlled for, patients with rheumatologic diseases were:

• 29% more likely to have high levels of financial hardship — difficulty paying; needing to pay over time; or inability to pay bills for doctors, dentists, hospitals, therapists, medication, equipment, nursing homes, or home care.
• 53% more likely to have high levels of financial distress — significant worry about having enough money for retirement, paying medical costs in the event of a serious illness or accident, maintaining their standard of living, paying their usual healthcare costs, and affording their normal monthly bills and housing costs.
• 29% more likely to experience food insecurity, defined as limited or uncertain access to adequate food.
• 58% more likely to report cost-related medication nonadherence — skipping doses, taking less medication, or delaying filling a prescription to save money.

People who were younger than 64 years, male, Black, or uninsured had higher odds of experiencing financial hardship, financial distress, food insecurity, and cost-related medication nonadherence. 

This study highlights “just how costly everyday rheumatologic conditions can be for your average American,” said lead study author Troy Amen, MD, MBA, an orthopedic surgery resident at the Hospital for Special Surgery in New York City. These diseases can be disabling, limiting a patient’s ability to work at the very time when expensive medications are needed. 

“It’s critical for clinicians to recognize how common the financial burden from healthcare costs can be, and only then can they take steps to better support patients,” said G. Caleb Alexander, MD, MS, professor of epidemiology at Johns Hopkins University in Baltimore, who was not involved in the study. 

Here’s how healthcare providers can help. 

Consider skipped medication a red flag. It’s often the first sign of a financial concern. “Sometimes with these problems, it looks like simple medication noncompliance, but it’s really a more complex form of nonadherence,” said Susan M. Goodman, MD, professor of clinical medicine at Weill Cornell Medicine in New York City and a coauthor of the study. “And I think if someone’s not taking the medication that had been very helpful, it does behoove the physician to try and figure out why that is.”

Normalize the issue to help patients open up. “I will often say, ‘You know, many, many patients don’t take their medicines exactly as prescribed. About how many days a week do you take this medicine?’” said Dr. Alexander. “If you ask in a nonconfrontational, supportive manner, I’ve found that patients are quite candid.” 

Don’t assume insurance has it covered. If patients are uninsured, help them enroll in (or renew) insurance coverage. But don’t assume insurance will solve the whole problem. “There are many people who, although they do have coverage, still can’t afford their medications,” said Dr. Goodman.

For products on high formulary tiers, the patient’s monthly cost can be hundreds to thousands of dollars. “Over the past 10-20 years, we’ve seen remarkable technological innovation in the types of medicines being brought to market, and here, I’m referring primarily to biologics and medicines made from living cells,” said Dr. Alexander, “but many of these have a price tag that is simply astronomical, and insurers aren’t going to bear the brunt of these costs alone.” 

Biosimilars can be a bit more affordable, but “the dirty little secret of biosimilars is that they’re not really very much less expensive,” said Dr. Goodman. “If your patient is doing well on a drug that gets dropped from their insurance plan’s formulary, or if they switch to a plan that doesn’t cover it, try calling and advocating for an exception. It’s an uphill battle, but it sometimes works,” she said.

If not? Help your patients apply for a patient assistance program. Many drug manufacturers offer copay assistance through their websites, and nonprofit patient assistance organizations such as the PAN Foundation, the Patient Advocate Foundation’s Co-Pay Relief Program, or The Assistance Fund can also help fill the gaps. One study published in the Journal of Managed Care and Specialty Pharmacy showed that in patients with rheumatoid arthritis, copay assistance was associated with 79% lower odds of prescription abandonment (failure to fill within 30 days of health plan approval).

Beware of “shiny penny syndrome.” It’s easy to get excited about new, innovative medications, especially when sales reps provide plenty of free samples. “There is a tendency to treat every new medicine as if it’s a bright shiny object in the streambed, and you know that’s not always the case,” said Dr. Alexander. “So, I think we have to be careful, especially in settings when we’re talking about ultra–high-cost medicines, that we’re aware of the burden these medicines may place on patients and that we’re navigating that with patients together, and not simply leaving that as a conversation that never happens in the exam room.”

Maybe there’s an older, time-tested drug that works just as well as the newer, more expensive one. Perhaps there is a slightly less effective medicine that costs a lot less. “These are cost–quality trade-offs that clinicians and patients should be navigating together,” said Dr. Alexander. For example, in a patient with rheumatoid arthritis, a tumor necrosis factor alpha inhibitor might work similarly to or almost as well as an interleukin inhibitor, the newer and typically more expensive choice. 

“Some clinicians may find it quite unpalatable to be potentially compromising on safety or efficacy in the interest of reducing the cost of therapies, but as former Surgeon General C. Everett Koop said, ‘Drugs don’t work in patients who don’t take them,’ ” said Dr. Alexander. “So, if the choice is for someone not to be taking a treatment, or to be taking one that may be a little bit less good, I’ll take the latter.”

Consider the patient’s broader care team. Encourage patients to discuss costs with their other healthcare providers. For patients taking multiple medications, a few adjustments could make a big impact on their wallets. Primary care providers or other specialists might recommend some older and less expensive, but still effective, drugs, such as thiazides for hypertension or metformin for type 2 diabetes. Another option might be to simplify the patient’s regimen or include some fixed-dose combination pills in place of two others.

And if no one has referred the patient to a medical social worker, make the connection. A social worker can put patients in touch with local agencies that can help them with food, housing, and other nonmedical costs. 

Talk about this problem with anyone who will listen. One of the best ways to help patients with rheumatologic diseases is to ensure that decision-makers don’t overlook them. Professional societies such as the American College of Rheumatology can be great resources for advocacy in Washington, DC. Political movements can make drugs more affordable — for example, insulin prices have dropped in recent years because of political pressure, said Dr. Goodman.

“A lot of our national policy now focuses on aiding patients with single high-cost events, but we hope studies like these can really get policymakers to think through how to better support patients with chronic conditions that may have been historically ignored, such as patients with rheumatologic disease,” said Dr. Amen. 

The first step is raising awareness and telling your story. “As providers, we are often [at the] forefront in witnessing how chronic conditions and their associated costs can negatively affect patients’ lives and even alter clinical outcomes,” Dr. Amen added. “By publishing data and sharing meaningful patient stories and clinical vignettes, we can begin to advocate and humanize these patients to policymakers.” 

Information on study funding was not available. All authors reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Many patients struggle with healthcare costs and basic expenses, according to new research.

People with rheumatologic diseases often experience a hidden symptom: financial toxicity or significant economic strain from out-of-pocket costs. A new study of 41,502 patients published in JCR: Journal of Clinical Rheumatology showed that 20% of those with rheumatologic diseases faced financial hardship from medical expenses, with 55% of those unable to pay their bills. 

Compared with patients who do not have rheumatologic diseases, and after clinical and sociodemographic factors were controlled for, patients with rheumatologic diseases were:

• 29% more likely to have high levels of financial hardship — difficulty paying; needing to pay over time; or inability to pay bills for doctors, dentists, hospitals, therapists, medication, equipment, nursing homes, or home care.
• 53% more likely to have high levels of financial distress — significant worry about having enough money for retirement, paying medical costs in the event of a serious illness or accident, maintaining their standard of living, paying their usual healthcare costs, and affording their normal monthly bills and housing costs.
• 29% more likely to experience food insecurity, defined as limited or uncertain access to adequate food.
• 58% more likely to report cost-related medication nonadherence — skipping doses, taking less medication, or delaying filling a prescription to save money.

People who were younger than 64 years, male, Black, or uninsured had higher odds of experiencing financial hardship, financial distress, food insecurity, and cost-related medication nonadherence. 

This study highlights “just how costly everyday rheumatologic conditions can be for your average American,” said lead study author Troy Amen, MD, MBA, an orthopedic surgery resident at the Hospital for Special Surgery in New York City. These diseases can be disabling, limiting a patient’s ability to work at the very time when expensive medications are needed. 

“It’s critical for clinicians to recognize how common the financial burden from healthcare costs can be, and only then can they take steps to better support patients,” said G. Caleb Alexander, MD, MS, professor of epidemiology at Johns Hopkins University in Baltimore, who was not involved in the study. 

Here’s how healthcare providers can help. 

Consider skipped medication a red flag. It’s often the first sign of a financial concern. “Sometimes with these problems, it looks like simple medication noncompliance, but it’s really a more complex form of nonadherence,” said Susan M. Goodman, MD, professor of clinical medicine at Weill Cornell Medicine in New York City and a coauthor of the study. “And I think if someone’s not taking the medication that had been very helpful, it does behoove the physician to try and figure out why that is.”

Normalize the issue to help patients open up. “I will often say, ‘You know, many, many patients don’t take their medicines exactly as prescribed. About how many days a week do you take this medicine?’” said Dr. Alexander. “If you ask in a nonconfrontational, supportive manner, I’ve found that patients are quite candid.” 

Don’t assume insurance has it covered. If patients are uninsured, help them enroll in (or renew) insurance coverage. But don’t assume insurance will solve the whole problem. “There are many people who, although they do have coverage, still can’t afford their medications,” said Dr. Goodman.

For products on high formulary tiers, the patient’s monthly cost can be hundreds to thousands of dollars. “Over the past 10-20 years, we’ve seen remarkable technological innovation in the types of medicines being brought to market, and here, I’m referring primarily to biologics and medicines made from living cells,” said Dr. Alexander, “but many of these have a price tag that is simply astronomical, and insurers aren’t going to bear the brunt of these costs alone.” 

Biosimilars can be a bit more affordable, but “the dirty little secret of biosimilars is that they’re not really very much less expensive,” said Dr. Goodman. “If your patient is doing well on a drug that gets dropped from their insurance plan’s formulary, or if they switch to a plan that doesn’t cover it, try calling and advocating for an exception. It’s an uphill battle, but it sometimes works,” she said.

If not? Help your patients apply for a patient assistance program. Many drug manufacturers offer copay assistance through their websites, and nonprofit patient assistance organizations such as the PAN Foundation, the Patient Advocate Foundation’s Co-Pay Relief Program, or The Assistance Fund can also help fill the gaps. One study published in the Journal of Managed Care and Specialty Pharmacy showed that in patients with rheumatoid arthritis, copay assistance was associated with 79% lower odds of prescription abandonment (failure to fill within 30 days of health plan approval).

Beware of “shiny penny syndrome.” It’s easy to get excited about new, innovative medications, especially when sales reps provide plenty of free samples. “There is a tendency to treat every new medicine as if it’s a bright shiny object in the streambed, and you know that’s not always the case,” said Dr. Alexander. “So, I think we have to be careful, especially in settings when we’re talking about ultra–high-cost medicines, that we’re aware of the burden these medicines may place on patients and that we’re navigating that with patients together, and not simply leaving that as a conversation that never happens in the exam room.”

Maybe there’s an older, time-tested drug that works just as well as the newer, more expensive one. Perhaps there is a slightly less effective medicine that costs a lot less. “These are cost–quality trade-offs that clinicians and patients should be navigating together,” said Dr. Alexander. For example, in a patient with rheumatoid arthritis, a tumor necrosis factor alpha inhibitor might work similarly to or almost as well as an interleukin inhibitor, the newer and typically more expensive choice. 

“Some clinicians may find it quite unpalatable to be potentially compromising on safety or efficacy in the interest of reducing the cost of therapies, but as former Surgeon General C. Everett Koop said, ‘Drugs don’t work in patients who don’t take them,’ ” said Dr. Alexander. “So, if the choice is for someone not to be taking a treatment, or to be taking one that may be a little bit less good, I’ll take the latter.”

Consider the patient’s broader care team. Encourage patients to discuss costs with their other healthcare providers. For patients taking multiple medications, a few adjustments could make a big impact on their wallets. Primary care providers or other specialists might recommend some older and less expensive, but still effective, drugs, such as thiazides for hypertension or metformin for type 2 diabetes. Another option might be to simplify the patient’s regimen or include some fixed-dose combination pills in place of two others.

And if no one has referred the patient to a medical social worker, make the connection. A social worker can put patients in touch with local agencies that can help them with food, housing, and other nonmedical costs. 

Talk about this problem with anyone who will listen. One of the best ways to help patients with rheumatologic diseases is to ensure that decision-makers don’t overlook them. Professional societies such as the American College of Rheumatology can be great resources for advocacy in Washington, DC. Political movements can make drugs more affordable — for example, insulin prices have dropped in recent years because of political pressure, said Dr. Goodman.

“A lot of our national policy now focuses on aiding patients with single high-cost events, but we hope studies like these can really get policymakers to think through how to better support patients with chronic conditions that may have been historically ignored, such as patients with rheumatologic disease,” said Dr. Amen. 

The first step is raising awareness and telling your story. “As providers, we are often [at the] forefront in witnessing how chronic conditions and their associated costs can negatively affect patients’ lives and even alter clinical outcomes,” Dr. Amen added. “By publishing data and sharing meaningful patient stories and clinical vignettes, we can begin to advocate and humanize these patients to policymakers.” 

Information on study funding was not available. All authors reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Many patients struggle with healthcare costs and basic expenses, according to new research.

People with rheumatologic diseases often experience a hidden symptom: financial toxicity or significant economic strain from out-of-pocket costs. A new study of 41,502 patients published in JCR: Journal of Clinical Rheumatology showed that 20% of those with rheumatologic diseases faced financial hardship from medical expenses, with 55% of those unable to pay their bills. 

Compared with patients who do not have rheumatologic diseases, and after clinical and sociodemographic factors were controlled for, patients with rheumatologic diseases were:

• 29% more likely to have high levels of financial hardship — difficulty paying; needing to pay over time; or inability to pay bills for doctors, dentists, hospitals, therapists, medication, equipment, nursing homes, or home care.
• 53% more likely to have high levels of financial distress — significant worry about having enough money for retirement, paying medical costs in the event of a serious illness or accident, maintaining their standard of living, paying their usual healthcare costs, and affording their normal monthly bills and housing costs.
• 29% more likely to experience food insecurity, defined as limited or uncertain access to adequate food.
• 58% more likely to report cost-related medication nonadherence — skipping doses, taking less medication, or delaying filling a prescription to save money.

People who were younger than 64 years, male, Black, or uninsured had higher odds of experiencing financial hardship, financial distress, food insecurity, and cost-related medication nonadherence. 

This study highlights “just how costly everyday rheumatologic conditions can be for your average American,” said lead study author Troy Amen, MD, MBA, an orthopedic surgery resident at the Hospital for Special Surgery in New York City. These diseases can be disabling, limiting a patient’s ability to work at the very time when expensive medications are needed. 

“It’s critical for clinicians to recognize how common the financial burden from healthcare costs can be, and only then can they take steps to better support patients,” said G. Caleb Alexander, MD, MS, professor of epidemiology at Johns Hopkins University in Baltimore, who was not involved in the study. 

Here’s how healthcare providers can help. 

Consider skipped medication a red flag. It’s often the first sign of a financial concern. “Sometimes with these problems, it looks like simple medication noncompliance, but it’s really a more complex form of nonadherence,” said Susan M. Goodman, MD, professor of clinical medicine at Weill Cornell Medicine in New York City and a coauthor of the study. “And I think if someone’s not taking the medication that had been very helpful, it does behoove the physician to try and figure out why that is.”

Normalize the issue to help patients open up. “I will often say, ‘You know, many, many patients don’t take their medicines exactly as prescribed. About how many days a week do you take this medicine?’” said Dr. Alexander. “If you ask in a nonconfrontational, supportive manner, I’ve found that patients are quite candid.” 

Don’t assume insurance has it covered. If patients are uninsured, help them enroll in (or renew) insurance coverage. But don’t assume insurance will solve the whole problem. “There are many people who, although they do have coverage, still can’t afford their medications,” said Dr. Goodman.

For products on high formulary tiers, the patient’s monthly cost can be hundreds to thousands of dollars. “Over the past 10-20 years, we’ve seen remarkable technological innovation in the types of medicines being brought to market, and here, I’m referring primarily to biologics and medicines made from living cells,” said Dr. Alexander, “but many of these have a price tag that is simply astronomical, and insurers aren’t going to bear the brunt of these costs alone.” 

Biosimilars can be a bit more affordable, but “the dirty little secret of biosimilars is that they’re not really very much less expensive,” said Dr. Goodman. “If your patient is doing well on a drug that gets dropped from their insurance plan’s formulary, or if they switch to a plan that doesn’t cover it, try calling and advocating for an exception. It’s an uphill battle, but it sometimes works,” she said.

If not? Help your patients apply for a patient assistance program. Many drug manufacturers offer copay assistance through their websites, and nonprofit patient assistance organizations such as the PAN Foundation, the Patient Advocate Foundation’s Co-Pay Relief Program, or The Assistance Fund can also help fill the gaps. One study published in the Journal of Managed Care and Specialty Pharmacy showed that in patients with rheumatoid arthritis, copay assistance was associated with 79% lower odds of prescription abandonment (failure to fill within 30 days of health plan approval).

Beware of “shiny penny syndrome.” It’s easy to get excited about new, innovative medications, especially when sales reps provide plenty of free samples. “There is a tendency to treat every new medicine as if it’s a bright shiny object in the streambed, and you know that’s not always the case,” said Dr. Alexander. “So, I think we have to be careful, especially in settings when we’re talking about ultra–high-cost medicines, that we’re aware of the burden these medicines may place on patients and that we’re navigating that with patients together, and not simply leaving that as a conversation that never happens in the exam room.”

Maybe there’s an older, time-tested drug that works just as well as the newer, more expensive one. Perhaps there is a slightly less effective medicine that costs a lot less. “These are cost–quality trade-offs that clinicians and patients should be navigating together,” said Dr. Alexander. For example, in a patient with rheumatoid arthritis, a tumor necrosis factor alpha inhibitor might work similarly to or almost as well as an interleukin inhibitor, the newer and typically more expensive choice. 

“Some clinicians may find it quite unpalatable to be potentially compromising on safety or efficacy in the interest of reducing the cost of therapies, but as former Surgeon General C. Everett Koop said, ‘Drugs don’t work in patients who don’t take them,’ ” said Dr. Alexander. “So, if the choice is for someone not to be taking a treatment, or to be taking one that may be a little bit less good, I’ll take the latter.”

Consider the patient’s broader care team. Encourage patients to discuss costs with their other healthcare providers. For patients taking multiple medications, a few adjustments could make a big impact on their wallets. Primary care providers or other specialists might recommend some older and less expensive, but still effective, drugs, such as thiazides for hypertension or metformin for type 2 diabetes. Another option might be to simplify the patient’s regimen or include some fixed-dose combination pills in place of two others.

And if no one has referred the patient to a medical social worker, make the connection. A social worker can put patients in touch with local agencies that can help them with food, housing, and other nonmedical costs. 

Talk about this problem with anyone who will listen. One of the best ways to help patients with rheumatologic diseases is to ensure that decision-makers don’t overlook them. Professional societies such as the American College of Rheumatology can be great resources for advocacy in Washington, DC. Political movements can make drugs more affordable — for example, insulin prices have dropped in recent years because of political pressure, said Dr. Goodman.

“A lot of our national policy now focuses on aiding patients with single high-cost events, but we hope studies like these can really get policymakers to think through how to better support patients with chronic conditions that may have been historically ignored, such as patients with rheumatologic disease,” said Dr. Amen. 

The first step is raising awareness and telling your story. “As providers, we are often [at the] forefront in witnessing how chronic conditions and their associated costs can negatively affect patients’ lives and even alter clinical outcomes,” Dr. Amen added. “By publishing data and sharing meaningful patient stories and clinical vignettes, we can begin to advocate and humanize these patients to policymakers.” 

Information on study funding was not available. All authors reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

The next frontier in cancer detection could be the humble urine test.

Emerging science suggests that the body’s “liquid gold” could be particularly useful for liquid biopsies, offering a convenient, pain-free, and cost-effective way to spot otherwise hard-to-detect cancers.

“The search for cancer biomarkers that can be detected in urine could provide an enormous step forward to decrease cancer patient mortality,” said Kenneth R. Shroyer, MD, PhD, a pathologist at Stony Brook University, Stony Brook, New York, who studies cancer biomarkers.

Physicians have long known that urine can reveal a lot about our health — that’s why urinalysis has been part of medicine for 6000 years. Urine tests can detect diabetes, pregnancy, drug use, and urinary or kidney conditions.

But other conditions leave clues in urine, too, and cancer may be one of the most promising. “Urine testing could detect biomarkers of early-stage cancers, not only from local but also distant sites,” Dr. Shroyer said. It could also help flag recurrence in cancer survivors who have undergone treatment.

Granted, cancer biomarkers in urine are not nearly as widely studied as those in the blood, Dr. Shroyer noted. But a new wave of urine tests suggests research is gaining pace.

“The recent availability of high-throughput screening technologies has enabled researchers to investigate cancer from a top-down, comprehensive approach,” said Pak Kin Wong, PhD, professor of mechanical engineering, biomedical engineering, and surgery at The Pennsylvania State University. “We are starting to understand the rich information that can be obtained from urine.”

Urine is mostly water (about 95%) and urea, a metabolic byproduct that imparts that signature yellow color (about 2%). The other 3% is a mix of waste products, minerals, and other compounds the kidneys removed from the blood. Even in trace amounts, these substances say a lot.

Among them are “exfoliated cancer cells, cell-free DNA, hormones, and the urine microbiota — the collection of microbes in our urinary tract system,” Dr. Wong said.

“It is highly promising to be one of the major biological fluids used for screening, diagnosis, prognosis, and monitoring treatment efficiency in the era of precision medicine,” Dr. Wong said.

How Urine Testing Could Reveal Cancer

Still, as exciting as the prospect is, there’s a lot to consider in the hunt for cancer biomarkers in urine. These biomarkers must be able to pass through the renal nephrons (filtering units), remain stable in urine, and have high-level sensitivity, Dr. Shroyer said. They should also have high specificity for cancer vs benign conditions and be expressed at early stages, before the primary tumor has spread.

“At this stage, few circulating biomarkers have been found that are both sensitive and specific for early-stage disease,” said Dr. Shroyer.

But there are a few promising examples under investigation in humans:

Prostate cancer. Researchers at the University of Michigan have developed a urine test that detects high-grade prostate cancer more accurately than existing tests, including PHI, SelectMDx, 4Kscore, EPI, MPS, and IsoPSA.

The MyProstateScore 2.0 (MPS2) test, which looks for 18 genes associated with high-grade tumors, could reduce unnecessary biopsies in men with elevated prostate-specific antigen levels, according to a paper published in JAMA Oncology.

It makes sense. The prostate gland secretes fluid that becomes part of the semen, traces of which enter urine. After a digital rectal exam, even more prostate fluid enters the urine. If a patient has prostate cancer, genetic material from the cancer cells will infiltrate the urine.

In the MPS2 test, researchers used polymerase chain reaction (PCR) testing in urine. “The technology used for COVID PCR is essentially the same as the PCR used to detect transcripts associated with high-grade prostate cancer in urine,” said study author Arul Chinnaiyan, MD, PhD, director of the Michigan Center for Translational Pathology at the University of Michigan, Ann Arbor. “In the case of the MPS2 test, we are doing PCR on 18 genes simultaneously on urine samples.”

A statistical model uses levels of that genetic material to predict the risk for high-grade disease, helping doctors decide what to do next. At 95% sensitivity, the MPS2 model could eliminate 35%-45% of unnecessary biopsies, compared with 15%-30% for the other tests, and reduce repeat biopsies by 46%-51%, compared with 9%-21% for the other tests.

Head and neck cancer. In a paper published in JCI Insight, researchers described a test that finds ultra-short fragments of DNA in urine to enable early detection of head and neck cancers caused by human papillomavirus.

“Our data show that a relatively small volume of urine (30-60 mL) gives overall detection results comparable to a tube of blood,” said study author Muneesh Tewari, MD, PhD, professor of hematology and oncology at the University of Michigan .

A larger volume of urine could potentially “make cancer detection even more sensitive than blood,” Dr. Tewari said, “allowing cancers to be detected at the earliest stages when they are more curable.”

The team used a technique called droplet digital PCR to detect DNA fragments that are “ultra-short” (less than 50 base pairs long) and usually missed by conventional PCR testing. This transrenal cell-free tumor DNA, which travels from the tumor into the bloodstream, is broken down small enough to pass through the kidneys and into the urine. But the fragments are still long enough to carry information about the tumor’s genetic signature.

This test could spot cancer before a tumor grows big enough — about a centimeter wide and carrying a billion cells — to spot on a CT scan or other imaging test. “When we are instead detecting fragments of DNA released from a tumor,” said Dr. Tewari, “our testing methods are very sensitive and can detect DNA in urine that came from just 5-10 cells in a tumor that died and released their DNA into the blood, which then made its way into the urine.”

Pancreatic cancer. Pancreatic ductal adenocarcinoma is one of the deadliest cancers, largely because it is diagnosed so late. A urine panel now in clinical trials could help doctors diagnose the cancer before it has spread so more people can have the tumor surgically removed, improving prognosis.

Using enzyme-linked immunosorbent assay test, a common lab method that detects antibodies and other proteins, the team measured expression levels for three genes (LYVE1, REG1B, and TFF1) in urine samples collected from people up to 5 years before they were diagnosed with pancreatic cancer. The researchers combined this result with patients’ urinary creatinine levels, a common component of existing urinalysis, and their age to develop a risk score.

This score performed similarly to an existing blood test, CA19-9, in predicting patients’ risk for pancreatic cancer up to 1 year before diagnosis. When combined with CA19-9, the urinary panel helped spot cancer up to 2 years before diagnosis.

According to a paper in the International Journal of Cancer, “the urine panel and affiliated PancRISK are currently being validated in a prospective clinical study (UroPanc).” If all goes well, they could be implemented in clinical practice in a few years as a “noninvasive stratification tool” to identify patients for further testing, speeding up diagnosis, and saving lives.

Limitations and Promises

Each cancer type is different, and more research is needed to map out which substances in urine predict which cancers and to develop tests for mass adoption. “There are medical and technological hurdles to the large-scale implementation of urine analysis for complex diseases such as cancer,” said Dr. Wong.

One possibility: Scientists and clinicians could collaborate and use artificial intelligence techniques to combine urine test results with other data.

“It is likely that future diagnostics may combine urine with other biological samples such as feces and saliva, among others,” said Dr. Wong. “This is especially true when novel data science and machine learning techniques can integrate comprehensive data from patients that span genetic, proteomic, metabolic, microbiomic, and even behavioral data to evaluate a patient’s condition.”

One thing that excites Dr. Tewari about urine-based cancer testing: “We think it could be especially impactful for patients living in rural areas or other areas with less access to healthcare services,” he said.
 

A version of this article appeared on Medscape.com.

The next frontier in cancer detection could be the humble urine test.

Emerging science suggests that the body’s “liquid gold” could be particularly useful for liquid biopsies, offering a convenient, pain-free, and cost-effective way to spot otherwise hard-to-detect cancers.

“The search for cancer biomarkers that can be detected in urine could provide an enormous step forward to decrease cancer patient mortality,” said Kenneth R. Shroyer, MD, PhD, a pathologist at Stony Brook University, Stony Brook, New York, who studies cancer biomarkers.

Physicians have long known that urine can reveal a lot about our health — that’s why urinalysis has been part of medicine for 6000 years. Urine tests can detect diabetes, pregnancy, drug use, and urinary or kidney conditions.

But other conditions leave clues in urine, too, and cancer may be one of the most promising. “Urine testing could detect biomarkers of early-stage cancers, not only from local but also distant sites,” Dr. Shroyer said. It could also help flag recurrence in cancer survivors who have undergone treatment.

Granted, cancer biomarkers in urine are not nearly as widely studied as those in the blood, Dr. Shroyer noted. But a new wave of urine tests suggests research is gaining pace.

“The recent availability of high-throughput screening technologies has enabled researchers to investigate cancer from a top-down, comprehensive approach,” said Pak Kin Wong, PhD, professor of mechanical engineering, biomedical engineering, and surgery at The Pennsylvania State University. “We are starting to understand the rich information that can be obtained from urine.”

Urine is mostly water (about 95%) and urea, a metabolic byproduct that imparts that signature yellow color (about 2%). The other 3% is a mix of waste products, minerals, and other compounds the kidneys removed from the blood. Even in trace amounts, these substances say a lot.

Among them are “exfoliated cancer cells, cell-free DNA, hormones, and the urine microbiota — the collection of microbes in our urinary tract system,” Dr. Wong said.

“It is highly promising to be one of the major biological fluids used for screening, diagnosis, prognosis, and monitoring treatment efficiency in the era of precision medicine,” Dr. Wong said.

How Urine Testing Could Reveal Cancer

Still, as exciting as the prospect is, there’s a lot to consider in the hunt for cancer biomarkers in urine. These biomarkers must be able to pass through the renal nephrons (filtering units), remain stable in urine, and have high-level sensitivity, Dr. Shroyer said. They should also have high specificity for cancer vs benign conditions and be expressed at early stages, before the primary tumor has spread.

“At this stage, few circulating biomarkers have been found that are both sensitive and specific for early-stage disease,” said Dr. Shroyer.

But there are a few promising examples under investigation in humans:

Prostate cancer. Researchers at the University of Michigan have developed a urine test that detects high-grade prostate cancer more accurately than existing tests, including PHI, SelectMDx, 4Kscore, EPI, MPS, and IsoPSA.

The MyProstateScore 2.0 (MPS2) test, which looks for 18 genes associated with high-grade tumors, could reduce unnecessary biopsies in men with elevated prostate-specific antigen levels, according to a paper published in JAMA Oncology.

It makes sense. The prostate gland secretes fluid that becomes part of the semen, traces of which enter urine. After a digital rectal exam, even more prostate fluid enters the urine. If a patient has prostate cancer, genetic material from the cancer cells will infiltrate the urine.

In the MPS2 test, researchers used polymerase chain reaction (PCR) testing in urine. “The technology used for COVID PCR is essentially the same as the PCR used to detect transcripts associated with high-grade prostate cancer in urine,” said study author Arul Chinnaiyan, MD, PhD, director of the Michigan Center for Translational Pathology at the University of Michigan, Ann Arbor. “In the case of the MPS2 test, we are doing PCR on 18 genes simultaneously on urine samples.”

A statistical model uses levels of that genetic material to predict the risk for high-grade disease, helping doctors decide what to do next. At 95% sensitivity, the MPS2 model could eliminate 35%-45% of unnecessary biopsies, compared with 15%-30% for the other tests, and reduce repeat biopsies by 46%-51%, compared with 9%-21% for the other tests.

Head and neck cancer. In a paper published in JCI Insight, researchers described a test that finds ultra-short fragments of DNA in urine to enable early detection of head and neck cancers caused by human papillomavirus.

“Our data show that a relatively small volume of urine (30-60 mL) gives overall detection results comparable to a tube of blood,” said study author Muneesh Tewari, MD, PhD, professor of hematology and oncology at the University of Michigan .

A larger volume of urine could potentially “make cancer detection even more sensitive than blood,” Dr. Tewari said, “allowing cancers to be detected at the earliest stages when they are more curable.”

The team used a technique called droplet digital PCR to detect DNA fragments that are “ultra-short” (less than 50 base pairs long) and usually missed by conventional PCR testing. This transrenal cell-free tumor DNA, which travels from the tumor into the bloodstream, is broken down small enough to pass through the kidneys and into the urine. But the fragments are still long enough to carry information about the tumor’s genetic signature.

This test could spot cancer before a tumor grows big enough — about a centimeter wide and carrying a billion cells — to spot on a CT scan or other imaging test. “When we are instead detecting fragments of DNA released from a tumor,” said Dr. Tewari, “our testing methods are very sensitive and can detect DNA in urine that came from just 5-10 cells in a tumor that died and released their DNA into the blood, which then made its way into the urine.”

Pancreatic cancer. Pancreatic ductal adenocarcinoma is one of the deadliest cancers, largely because it is diagnosed so late. A urine panel now in clinical trials could help doctors diagnose the cancer before it has spread so more people can have the tumor surgically removed, improving prognosis.

Using enzyme-linked immunosorbent assay test, a common lab method that detects antibodies and other proteins, the team measured expression levels for three genes (LYVE1, REG1B, and TFF1) in urine samples collected from people up to 5 years before they were diagnosed with pancreatic cancer. The researchers combined this result with patients’ urinary creatinine levels, a common component of existing urinalysis, and their age to develop a risk score.

This score performed similarly to an existing blood test, CA19-9, in predicting patients’ risk for pancreatic cancer up to 1 year before diagnosis. When combined with CA19-9, the urinary panel helped spot cancer up to 2 years before diagnosis.

According to a paper in the International Journal of Cancer, “the urine panel and affiliated PancRISK are currently being validated in a prospective clinical study (UroPanc).” If all goes well, they could be implemented in clinical practice in a few years as a “noninvasive stratification tool” to identify patients for further testing, speeding up diagnosis, and saving lives.

Limitations and Promises

Each cancer type is different, and more research is needed to map out which substances in urine predict which cancers and to develop tests for mass adoption. “There are medical and technological hurdles to the large-scale implementation of urine analysis for complex diseases such as cancer,” said Dr. Wong.

One possibility: Scientists and clinicians could collaborate and use artificial intelligence techniques to combine urine test results with other data.

“It is likely that future diagnostics may combine urine with other biological samples such as feces and saliva, among others,” said Dr. Wong. “This is especially true when novel data science and machine learning techniques can integrate comprehensive data from patients that span genetic, proteomic, metabolic, microbiomic, and even behavioral data to evaluate a patient’s condition.”

One thing that excites Dr. Tewari about urine-based cancer testing: “We think it could be especially impactful for patients living in rural areas or other areas with less access to healthcare services,” he said.
 

A version of this article appeared on Medscape.com.

The next frontier in cancer detection could be the humble urine test.

Emerging science suggests that the body’s “liquid gold” could be particularly useful for liquid biopsies, offering a convenient, pain-free, and cost-effective way to spot otherwise hard-to-detect cancers.

“The search for cancer biomarkers that can be detected in urine could provide an enormous step forward to decrease cancer patient mortality,” said Kenneth R. Shroyer, MD, PhD, a pathologist at Stony Brook University, Stony Brook, New York, who studies cancer biomarkers.

Physicians have long known that urine can reveal a lot about our health — that’s why urinalysis has been part of medicine for 6000 years. Urine tests can detect diabetes, pregnancy, drug use, and urinary or kidney conditions.

But other conditions leave clues in urine, too, and cancer may be one of the most promising. “Urine testing could detect biomarkers of early-stage cancers, not only from local but also distant sites,” Dr. Shroyer said. It could also help flag recurrence in cancer survivors who have undergone treatment.

Granted, cancer biomarkers in urine are not nearly as widely studied as those in the blood, Dr. Shroyer noted. But a new wave of urine tests suggests research is gaining pace.

“The recent availability of high-throughput screening technologies has enabled researchers to investigate cancer from a top-down, comprehensive approach,” said Pak Kin Wong, PhD, professor of mechanical engineering, biomedical engineering, and surgery at The Pennsylvania State University. “We are starting to understand the rich information that can be obtained from urine.”

Urine is mostly water (about 95%) and urea, a metabolic byproduct that imparts that signature yellow color (about 2%). The other 3% is a mix of waste products, minerals, and other compounds the kidneys removed from the blood. Even in trace amounts, these substances say a lot.

Among them are “exfoliated cancer cells, cell-free DNA, hormones, and the urine microbiota — the collection of microbes in our urinary tract system,” Dr. Wong said.

“It is highly promising to be one of the major biological fluids used for screening, diagnosis, prognosis, and monitoring treatment efficiency in the era of precision medicine,” Dr. Wong said.

How Urine Testing Could Reveal Cancer

Still, as exciting as the prospect is, there’s a lot to consider in the hunt for cancer biomarkers in urine. These biomarkers must be able to pass through the renal nephrons (filtering units), remain stable in urine, and have high-level sensitivity, Dr. Shroyer said. They should also have high specificity for cancer vs benign conditions and be expressed at early stages, before the primary tumor has spread.

“At this stage, few circulating biomarkers have been found that are both sensitive and specific for early-stage disease,” said Dr. Shroyer.

But there are a few promising examples under investigation in humans:

Prostate cancer. Researchers at the University of Michigan have developed a urine test that detects high-grade prostate cancer more accurately than existing tests, including PHI, SelectMDx, 4Kscore, EPI, MPS, and IsoPSA.

The MyProstateScore 2.0 (MPS2) test, which looks for 18 genes associated with high-grade tumors, could reduce unnecessary biopsies in men with elevated prostate-specific antigen levels, according to a paper published in JAMA Oncology.

It makes sense. The prostate gland secretes fluid that becomes part of the semen, traces of which enter urine. After a digital rectal exam, even more prostate fluid enters the urine. If a patient has prostate cancer, genetic material from the cancer cells will infiltrate the urine.

In the MPS2 test, researchers used polymerase chain reaction (PCR) testing in urine. “The technology used for COVID PCR is essentially the same as the PCR used to detect transcripts associated with high-grade prostate cancer in urine,” said study author Arul Chinnaiyan, MD, PhD, director of the Michigan Center for Translational Pathology at the University of Michigan, Ann Arbor. “In the case of the MPS2 test, we are doing PCR on 18 genes simultaneously on urine samples.”

A statistical model uses levels of that genetic material to predict the risk for high-grade disease, helping doctors decide what to do next. At 95% sensitivity, the MPS2 model could eliminate 35%-45% of unnecessary biopsies, compared with 15%-30% for the other tests, and reduce repeat biopsies by 46%-51%, compared with 9%-21% for the other tests.

Head and neck cancer. In a paper published in JCI Insight, researchers described a test that finds ultra-short fragments of DNA in urine to enable early detection of head and neck cancers caused by human papillomavirus.

“Our data show that a relatively small volume of urine (30-60 mL) gives overall detection results comparable to a tube of blood,” said study author Muneesh Tewari, MD, PhD, professor of hematology and oncology at the University of Michigan .

A larger volume of urine could potentially “make cancer detection even more sensitive than blood,” Dr. Tewari said, “allowing cancers to be detected at the earliest stages when they are more curable.”

The team used a technique called droplet digital PCR to detect DNA fragments that are “ultra-short” (less than 50 base pairs long) and usually missed by conventional PCR testing. This transrenal cell-free tumor DNA, which travels from the tumor into the bloodstream, is broken down small enough to pass through the kidneys and into the urine. But the fragments are still long enough to carry information about the tumor’s genetic signature.

This test could spot cancer before a tumor grows big enough — about a centimeter wide and carrying a billion cells — to spot on a CT scan or other imaging test. “When we are instead detecting fragments of DNA released from a tumor,” said Dr. Tewari, “our testing methods are very sensitive and can detect DNA in urine that came from just 5-10 cells in a tumor that died and released their DNA into the blood, which then made its way into the urine.”

Pancreatic cancer. Pancreatic ductal adenocarcinoma is one of the deadliest cancers, largely because it is diagnosed so late. A urine panel now in clinical trials could help doctors diagnose the cancer before it has spread so more people can have the tumor surgically removed, improving prognosis.

Using enzyme-linked immunosorbent assay test, a common lab method that detects antibodies and other proteins, the team measured expression levels for three genes (LYVE1, REG1B, and TFF1) in urine samples collected from people up to 5 years before they were diagnosed with pancreatic cancer. The researchers combined this result with patients’ urinary creatinine levels, a common component of existing urinalysis, and their age to develop a risk score.

This score performed similarly to an existing blood test, CA19-9, in predicting patients’ risk for pancreatic cancer up to 1 year before diagnosis. When combined with CA19-9, the urinary panel helped spot cancer up to 2 years before diagnosis.

According to a paper in the International Journal of Cancer, “the urine panel and affiliated PancRISK are currently being validated in a prospective clinical study (UroPanc).” If all goes well, they could be implemented in clinical practice in a few years as a “noninvasive stratification tool” to identify patients for further testing, speeding up diagnosis, and saving lives.

Limitations and Promises

Each cancer type is different, and more research is needed to map out which substances in urine predict which cancers and to develop tests for mass adoption. “There are medical and technological hurdles to the large-scale implementation of urine analysis for complex diseases such as cancer,” said Dr. Wong.

One possibility: Scientists and clinicians could collaborate and use artificial intelligence techniques to combine urine test results with other data.

“It is likely that future diagnostics may combine urine with other biological samples such as feces and saliva, among others,” said Dr. Wong. “This is especially true when novel data science and machine learning techniques can integrate comprehensive data from patients that span genetic, proteomic, metabolic, microbiomic, and even behavioral data to evaluate a patient’s condition.”

One thing that excites Dr. Tewari about urine-based cancer testing: “We think it could be especially impactful for patients living in rural areas or other areas with less access to healthcare services,” he said.
 

A version of this article appeared on Medscape.com.

Like it or not, artificial intelligence (AI) is coming to medicine. For many physicians — maybe you — it’s already here.

More than a third of physicians use AI in their practice. And the vast majority of healthcare companies — 94%, according to Morgan Stanley — use some kind of AI machine learning.

“It’s incumbent on physicians, as well as physicians in training, to become familiar with at least the basics [of AI],” said internist Matthew DeCamp, MD, PhD, an associate professor in the Center for Bioethics and Humanities at the University of Colorado Anschutz Medical Campus, Aurora, Colorado.

Understanding AI can help you leverage it safely and effectively — plus “make better-informed decisions about whether or not to use it in [your] practice,” Dr. DeCamp said.

“Frankly, the people who are deciding whether to implement algorithms in our day-to-day lives are oftentimes not physicians,” noted Ravi B. Parikh, MD, an assistant professor at the University of Pennsylvania and director of augmented and artificial intelligence at the Penn Center for Cancer Care Innovation, Philadelphia. Yet, physicians are most qualified to assess an AI tool’s usefulness in clinical practice.

That brings us to the best starting place for your AI education: Your own institution. Find out what AI tools your organization is implementing — and how you can influence them.

“Getting involved with our hospital data governance is the best way not only to learn practically what these AI tools do but also to influence the development process in positive ways,” Dr. Parikh said.

From there, consider the following resources to enhance your AI knowledge.
 

Get a Lay of the Land: Free Primers

Many clinical societies and interest groups have put out AI primers, an easy way to get a broad overview of the technology. The following were recommended or developed by the experts we spoke to, and all are free:

• The American Medical Association’s (AMA’s) framework for advancing healthcare AI lays out actionable guidance. Ask three key questions, the AMA recommends: Does it work? Does it work for my patients? Does it improve health outcomes?
• The Coalition for Health AI’s Blueprint for Trustworthy AI Implementation Guidance and Assurance for Healthcare provides a high-level summary of how to evaluate AI in healthcare, plus steps for implementing it. AI systems should be useful, safe, accountable, explainable, fair, and secure, the report asserted.
• The National Academy of Medicine’s draft code of conduct for AI in healthcare proposes core principles and commitments. These “reflect simple guideposts to guide and gauge behavior in a complex system and provide a starting point for real-time decision-making,” the report said.
• Health AI Partnership — a collaboration of Duke Health and Microsoft — outlines eight key decision points to consider at any stage of AI implementation, whether you’re still planning how to use it or you’ve started but want to improve it. The site also provides a breakdown of standards by regulatory agencies, organizations, and oversight bodies — so you can make sure your practices align with their guidance.

Make the Most of Conferences

Next time you’re at a conference, check the agenda for sessions on AI. “For someone who’s interested in this, I would be looking for content in my next national meeting because, undoubtedly, it’s going to be there,” said Dr. DeCamp. In a fast-moving field like AI, it’s a great way to get fresh, up-to-the-moment insights.

Listen to This Podcast

The New England Journal of Medicine’s free monthly podcast AI Grand Rounds is made for researchers and clinicians. Available on Apple, Spotify, and YouTube, the pod is good for “someone who’s looking to see both where the field is going [and to hear] a retrospective on big-name papers,” said Dr. Parikh . Episodes run for about an hour.

To learn about the challenges of applying AI to biology: Listen to Daphne Koller, PhD, founder of AI-driven drug discovery and development company insitro. For insights on the potential of AI in medicine, tune into the one with Eric Horvitz, MD, PhD, Microsoft’s chief scientific officer.
 

Consider a Class

Look for courses that focus on AI applications in clinical practice rather than a deep dive into theory. (You need to understand how these tools will influence your work, not the intricacies of large language model development.) Be wary of corporate-funded training that centers on one product , which could present conflicts of interest, said Dr. DeCamp. See the chart for courses that meet these criteria.

A version of this article appeared on Medscape.com.

Like it or not, artificial intelligence (AI) is coming to medicine. For many physicians — maybe you — it’s already here.

More than a third of physicians use AI in their practice. And the vast majority of healthcare companies — 94%, according to Morgan Stanley — use some kind of AI machine learning.

“It’s incumbent on physicians, as well as physicians in training, to become familiar with at least the basics [of AI],” said internist Matthew DeCamp, MD, PhD, an associate professor in the Center for Bioethics and Humanities at the University of Colorado Anschutz Medical Campus, Aurora, Colorado.

Understanding AI can help you leverage it safely and effectively — plus “make better-informed decisions about whether or not to use it in [your] practice,” Dr. DeCamp said.

“Frankly, the people who are deciding whether to implement algorithms in our day-to-day lives are oftentimes not physicians,” noted Ravi B. Parikh, MD, an assistant professor at the University of Pennsylvania and director of augmented and artificial intelligence at the Penn Center for Cancer Care Innovation, Philadelphia. Yet, physicians are most qualified to assess an AI tool’s usefulness in clinical practice.

That brings us to the best starting place for your AI education: Your own institution. Find out what AI tools your organization is implementing — and how you can influence them.

“Getting involved with our hospital data governance is the best way not only to learn practically what these AI tools do but also to influence the development process in positive ways,” Dr. Parikh said.

From there, consider the following resources to enhance your AI knowledge.
 

Get a Lay of the Land: Free Primers

Many clinical societies and interest groups have put out AI primers, an easy way to get a broad overview of the technology. The following were recommended or developed by the experts we spoke to, and all are free:

• The American Medical Association’s (AMA’s) framework for advancing healthcare AI lays out actionable guidance. Ask three key questions, the AMA recommends: Does it work? Does it work for my patients? Does it improve health outcomes?
• The Coalition for Health AI’s Blueprint for Trustworthy AI Implementation Guidance and Assurance for Healthcare provides a high-level summary of how to evaluate AI in healthcare, plus steps for implementing it. AI systems should be useful, safe, accountable, explainable, fair, and secure, the report asserted.
• The National Academy of Medicine’s draft code of conduct for AI in healthcare proposes core principles and commitments. These “reflect simple guideposts to guide and gauge behavior in a complex system and provide a starting point for real-time decision-making,” the report said.
• Health AI Partnership — a collaboration of Duke Health and Microsoft — outlines eight key decision points to consider at any stage of AI implementation, whether you’re still planning how to use it or you’ve started but want to improve it. The site also provides a breakdown of standards by regulatory agencies, organizations, and oversight bodies — so you can make sure your practices align with their guidance.

Make the Most of Conferences

Next time you’re at a conference, check the agenda for sessions on AI. “For someone who’s interested in this, I would be looking for content in my next national meeting because, undoubtedly, it’s going to be there,” said Dr. DeCamp. In a fast-moving field like AI, it’s a great way to get fresh, up-to-the-moment insights.

Listen to This Podcast

The New England Journal of Medicine’s free monthly podcast AI Grand Rounds is made for researchers and clinicians. Available on Apple, Spotify, and YouTube, the pod is good for “someone who’s looking to see both where the field is going [and to hear] a retrospective on big-name papers,” said Dr. Parikh . Episodes run for about an hour.

To learn about the challenges of applying AI to biology: Listen to Daphne Koller, PhD, founder of AI-driven drug discovery and development company insitro. For insights on the potential of AI in medicine, tune into the one with Eric Horvitz, MD, PhD, Microsoft’s chief scientific officer.
 

Consider a Class

Look for courses that focus on AI applications in clinical practice rather than a deep dive into theory. (You need to understand how these tools will influence your work, not the intricacies of large language model development.) Be wary of corporate-funded training that centers on one product , which could present conflicts of interest, said Dr. DeCamp. See the chart for courses that meet these criteria.

A version of this article appeared on Medscape.com.

Like it or not, artificial intelligence (AI) is coming to medicine. For many physicians — maybe you — it’s already here.

More than a third of physicians use AI in their practice. And the vast majority of healthcare companies — 94%, according to Morgan Stanley — use some kind of AI machine learning.

“It’s incumbent on physicians, as well as physicians in training, to become familiar with at least the basics [of AI],” said internist Matthew DeCamp, MD, PhD, an associate professor in the Center for Bioethics and Humanities at the University of Colorado Anschutz Medical Campus, Aurora, Colorado.

Understanding AI can help you leverage it safely and effectively — plus “make better-informed decisions about whether or not to use it in [your] practice,” Dr. DeCamp said.

“Frankly, the people who are deciding whether to implement algorithms in our day-to-day lives are oftentimes not physicians,” noted Ravi B. Parikh, MD, an assistant professor at the University of Pennsylvania and director of augmented and artificial intelligence at the Penn Center for Cancer Care Innovation, Philadelphia. Yet, physicians are most qualified to assess an AI tool’s usefulness in clinical practice.

That brings us to the best starting place for your AI education: Your own institution. Find out what AI tools your organization is implementing — and how you can influence them.

“Getting involved with our hospital data governance is the best way not only to learn practically what these AI tools do but also to influence the development process in positive ways,” Dr. Parikh said.

From there, consider the following resources to enhance your AI knowledge.
 

Get a Lay of the Land: Free Primers

Many clinical societies and interest groups have put out AI primers, an easy way to get a broad overview of the technology. The following were recommended or developed by the experts we spoke to, and all are free:

• The American Medical Association’s (AMA’s) framework for advancing healthcare AI lays out actionable guidance. Ask three key questions, the AMA recommends: Does it work? Does it work for my patients? Does it improve health outcomes?
• The Coalition for Health AI’s Blueprint for Trustworthy AI Implementation Guidance and Assurance for Healthcare provides a high-level summary of how to evaluate AI in healthcare, plus steps for implementing it. AI systems should be useful, safe, accountable, explainable, fair, and secure, the report asserted.
• The National Academy of Medicine’s draft code of conduct for AI in healthcare proposes core principles and commitments. These “reflect simple guideposts to guide and gauge behavior in a complex system and provide a starting point for real-time decision-making,” the report said.
• Health AI Partnership — a collaboration of Duke Health and Microsoft — outlines eight key decision points to consider at any stage of AI implementation, whether you’re still planning how to use it or you’ve started but want to improve it. The site also provides a breakdown of standards by regulatory agencies, organizations, and oversight bodies — so you can make sure your practices align with their guidance.

Make the Most of Conferences

Next time you’re at a conference, check the agenda for sessions on AI. “For someone who’s interested in this, I would be looking for content in my next national meeting because, undoubtedly, it’s going to be there,” said Dr. DeCamp. In a fast-moving field like AI, it’s a great way to get fresh, up-to-the-moment insights.

Listen to This Podcast

The New England Journal of Medicine’s free monthly podcast AI Grand Rounds is made for researchers and clinicians. Available on Apple, Spotify, and YouTube, the pod is good for “someone who’s looking to see both where the field is going [and to hear] a retrospective on big-name papers,” said Dr. Parikh . Episodes run for about an hour.

To learn about the challenges of applying AI to biology: Listen to Daphne Koller, PhD, founder of AI-driven drug discovery and development company insitro. For insights on the potential of AI in medicine, tune into the one with Eric Horvitz, MD, PhD, Microsoft’s chief scientific officer.
 

Consider a Class

Look for courses that focus on AI applications in clinical practice rather than a deep dive into theory. (You need to understand how these tools will influence your work, not the intricacies of large language model development.) Be wary of corporate-funded training that centers on one product , which could present conflicts of interest, said Dr. DeCamp. See the chart for courses that meet these criteria.

A version of this article appeared on Medscape.com.

Weight loss drugs have surged in popularity — in part because they work. Patients on glucagon-like peptide 1 (GLP-1) agonists like liraglutide, semaglutide, and tirzepatide (which is technically also a glucose-dependent insulinotropic polypeptide agonist) can lose 10%, 20%, or even 25% of their body weight.

But if those patients stop taking GLP-1s, they tend to regain most of that weight within a year, studies showed.

“These drugs work inside the person from a biologic point of view to alter appetite,” said Robert Kushner, MD, an endocrinologist and professor at Northwestern University Feinberg School of Medicine, Chicago, Illinois, who specializes in obesity medicine. “And when the drug is gone, that disease comes back.” 

Ongoing treatment may seem like the obvious solution, but reality can complicate that. High costs, supply shortages, and faltering insurance coverage can render the drugs inaccessible.

Often, “patients are told by their insurers that they are no longer going to cover a GLP-1 for obesity,” said Carolyn Bramante, MD, MPH, an assistant professor at the University of Minnesota Medical School, Minneapolis, Minnesota, who sees patients at the M Health Fairview weight management clinic.

Other barriers include side effects like nausea, diarrhea, stomach pain, and vomiting. Some patients simply don’t want to take a medication forever, instead choosing to take their chances keeping the weight off sans drug.

If your patient must stop GLP-1s, or really wants to, here’s how to help.

Find out why the patient wants to go off the GLP-1. Ask them to help you understand, suggested Jaime Almandoz, MD, associate professor of internal medicine and medical director of the University of Texas Southwestern Medical Center’s Weight Wellness Program. Sometimes, the patient or family members worry about safety, Dr. Almandoz said. “They may be concerned about the risks and may not have had an opportunity to ask questions.” Dr. Almandoz reviews the drug safety data and tells patients that studies show, on average, people gain back two-thirds of the weight they’ve lost within a year. You’re not trying to persuade them, only to equip them to make a well-informed choice.

Don’t let bias affect treatment decisions. Patients on GLP-1s often ask: How long will I have to take this? The reason: “We’re biased to believe that this is not a disease state, that this is a character flaw,” said Sean Wharton, MD, PharmD, medical director of the Wharton Medical Clinic for weight management in Burlington, Ontario, Canada. Remind your patient that obesity is not a personal failure but rather a complex mix of genetic and biological factors.

Give patients a primer on the biology of obesity. Science shows that when we lose weight, our bodies fight back, trying to return to our highest-ever fat mass. Changes in neurohormones, gut hormones, satiety mechanisms, metabolism, and muscle function all converge to promote weight recurrence, Dr. Almandoz said. To explain this to patients, Dr. Almandoz compares gaining fat to depositing money in a savings account. “When we try to lose weight, it isn’t as simple as withdrawing this money,” he’ll tell them. “It is almost like the money that we put into the savings account is now tied up in investments that we can’t liquidate easily.”

Prepare patients for an uptick in appetite. When patients stop GLP-1s, their hunger and food cravings tend to increase. “I explain that GLP-1 medications mimic a hormone that is released from our intestines when they sense we have eaten,” said Dr. Almandoz. This signals the brain and body that food is on board, decreasing appetite and cravings. Ask patients what hungry and full feel like on the medication, Dr. Almandoz suggested. “Many will report that their hunger and cravings are low, that they now have an indifference to foods,” said Dr. Almandoz. Such probing questions can help patients be more aware of the medication’s effects. “This positions a more informed conversation if medications are to be discontinued,” Dr. Almandoz said.

Help their body adjust. “Slowly wean down on the dose, if possible, to avoid a big rebound in hunger,” said Dr. Bramante. If your patient has the time — say, they received a letter from their insurance that coverage will end in 3 months — use it to taper the dose as low as possible before stopping. The slower and more gradual, the better. Dr. Almandoz checks in with patients every 4-8 weeks. If they›re maintaining weight well, he considers decreasing the dose again and repeating with follow-up visits.

Substitute one intervention for another. In general, maintaining weight loss requires some intervention, Dr. Wharton said. “But that intervention does not need to be the same as the intervention that got the weight down.” If the patient can›t continue a GLP-1, consider an alternate medication, cognitive behavioral therapy, or a combination of the two. When patients lose coverage for GLP-1s, Dr. Bramante sometimes prescribes an older, less-expensive weight loss drug, such as phentermine, topiramate, or metformin. And sometimes, insurers that don’t cover GLP-1s (like Medicare), do cover bariatric surgery, a potential option depending on the patient›s body mass index, overall health, and comorbidities, said Dr. Almandoz.

Create a habit template. Dr. Kushner asks patients who have successfully lost weight to take an inventory of everything they’re doing to support their efforts. He’ll have them describe how they plan their diet, what types of food they’re eating, how much they eat, and when they eat it. He’ll also ask about physical activity, exercise patterns, and sleep. He logs all the habits into a bulleted list in the patient’s after-visit summary and hands them a printout before they leave. “That’s your template,” he’ll tell them. “That’s what you’re going to try to maintain to the best of your ability because it’s working for you.”

Prescribe exercise. “Increasing exercise is not usually effective for initial weight loss, but it is important for maintaining weight loss,” said Dr. Bramante. Tell patients to start right away, ideally while they’re still on the drug. In a study published last month, patients on liraglutide (Saxenda) who exercised 4 days a week were much more likely to keep weight off after stopping the drug than those who didn’t work out. (The study was partially funded by Novo Nordisk Foundation, the charitable arm of Saxenda’s maker, also the maker of semaglutide meds Ozempic and Wegovy.) By establishing strong exercise habits while on the medication, they were able to sustain higher physical activity levels after they stopped. Ask your patient to identify someone or something to help them stick to their plan, “whether it’s seeing a personal trainer or being accountable to a friend or family member or to themselves through record keeping,” said Dr. Kushner. Learn more about how to prescribe exercise to patients here.

Help them create a “microenvironment” for success. Dr. Kushner asks patients which of the recommended dietary habits for weight loss are hardest to follow: Eating more plant-based foods? Cutting back on ultra-processed foods, fatty foods, fast foods, and/or sugary beverages? Depending on the patient’s answers, he tries to recommend strategies — maybe going meatless a few days a week or keeping tempting foods out of the house. “If you go off medication, food may become more enticing, and you may not feel as content eating less,” Dr. Kushner said. “Make sure your own what we call microenvironment, your home environment, is filled with healthy foods.”

Rely on multidisciplinary expertise. Obesity is a complex, multifactorial disease, so call in reinforcements. “When I see someone, I’m always evaluating what other team members they would benefit from,” said Dr. Kushner. If the patient lacks nutrition knowledge, he refers them to a registered dietitian. If they struggle with self-blame, low self-esteem, and emotional eating, he’ll refer them to a psychologist. It can make a difference: A 2023 study showed that people who lost weight and received support from professionals like trainers, dietitians, and mental health therapists regained less weight over 2 years than those who did not receive the same help.

Reassure patients you will help them no matter what. Ask patients to follow-up within the first month of quitting medication or to call back sooner if they gain 5 pounds. People who stop taking GLP-1s often report less satisfaction with eating, or that they think about food more. That’s when Dr. Kushner asks whether they want to go back on the medication or focus on other strategies. Sometimes, patients who gain weight feel embarrassed and delay their follow-up visits. If that happens, welcome them back and let them know that all chronic conditions ebb and flow. “I constantly remind them that I am here to help you, and there are many tools or resources that will help you,” Dr. Kushner said. “And dispel the notion that it’s somehow your fault.”

Dr. Kushner reported participation on the medical advisory board or consultancy with Novo Nordisk, WeightWatchers, Eli Lilly and Company, Boehringer Ingelheim, Structure Therapeutics, and Altimmune. He added he does not own stock or participate in any speaker’s bureau. Dr. Almandoz reported participation on advisory boards with Novo Nordisk, Boehringer Ingelheim, and Eli Lilly and Company. Dr. Wharton reported participation on advisory boards and honoraria for academic talks and clinical research with Novo Nordisk, Eli Lilly and Company, Boehringer Ingelheim, Amgen, Regeneron, and BioHaven.

A version of this article appeared on Medscape.com.

Weight loss drugs have surged in popularity — in part because they work. Patients on glucagon-like peptide 1 (GLP-1) agonists like liraglutide, semaglutide, and tirzepatide (which is technically also a glucose-dependent insulinotropic polypeptide agonist) can lose 10%, 20%, or even 25% of their body weight.

But if those patients stop taking GLP-1s, they tend to regain most of that weight within a year, studies showed.

“These drugs work inside the person from a biologic point of view to alter appetite,” said Robert Kushner, MD, an endocrinologist and professor at Northwestern University Feinberg School of Medicine, Chicago, Illinois, who specializes in obesity medicine. “And when the drug is gone, that disease comes back.” 

Ongoing treatment may seem like the obvious solution, but reality can complicate that. High costs, supply shortages, and faltering insurance coverage can render the drugs inaccessible.

Often, “patients are told by their insurers that they are no longer going to cover a GLP-1 for obesity,” said Carolyn Bramante, MD, MPH, an assistant professor at the University of Minnesota Medical School, Minneapolis, Minnesota, who sees patients at the M Health Fairview weight management clinic.

Other barriers include side effects like nausea, diarrhea, stomach pain, and vomiting. Some patients simply don’t want to take a medication forever, instead choosing to take their chances keeping the weight off sans drug.

If your patient must stop GLP-1s, or really wants to, here’s how to help.

Find out why the patient wants to go off the GLP-1. Ask them to help you understand, suggested Jaime Almandoz, MD, associate professor of internal medicine and medical director of the University of Texas Southwestern Medical Center’s Weight Wellness Program. Sometimes, the patient or family members worry about safety, Dr. Almandoz said. “They may be concerned about the risks and may not have had an opportunity to ask questions.” Dr. Almandoz reviews the drug safety data and tells patients that studies show, on average, people gain back two-thirds of the weight they’ve lost within a year. You’re not trying to persuade them, only to equip them to make a well-informed choice.

Don’t let bias affect treatment decisions. Patients on GLP-1s often ask: How long will I have to take this? The reason: “We’re biased to believe that this is not a disease state, that this is a character flaw,” said Sean Wharton, MD, PharmD, medical director of the Wharton Medical Clinic for weight management in Burlington, Ontario, Canada. Remind your patient that obesity is not a personal failure but rather a complex mix of genetic and biological factors.

Give patients a primer on the biology of obesity. Science shows that when we lose weight, our bodies fight back, trying to return to our highest-ever fat mass. Changes in neurohormones, gut hormones, satiety mechanisms, metabolism, and muscle function all converge to promote weight recurrence, Dr. Almandoz said. To explain this to patients, Dr. Almandoz compares gaining fat to depositing money in a savings account. “When we try to lose weight, it isn’t as simple as withdrawing this money,” he’ll tell them. “It is almost like the money that we put into the savings account is now tied up in investments that we can’t liquidate easily.”

Prepare patients for an uptick in appetite. When patients stop GLP-1s, their hunger and food cravings tend to increase. “I explain that GLP-1 medications mimic a hormone that is released from our intestines when they sense we have eaten,” said Dr. Almandoz. This signals the brain and body that food is on board, decreasing appetite and cravings. Ask patients what hungry and full feel like on the medication, Dr. Almandoz suggested. “Many will report that their hunger and cravings are low, that they now have an indifference to foods,” said Dr. Almandoz. Such probing questions can help patients be more aware of the medication’s effects. “This positions a more informed conversation if medications are to be discontinued,” Dr. Almandoz said.

Help their body adjust. “Slowly wean down on the dose, if possible, to avoid a big rebound in hunger,” said Dr. Bramante. If your patient has the time — say, they received a letter from their insurance that coverage will end in 3 months — use it to taper the dose as low as possible before stopping. The slower and more gradual, the better. Dr. Almandoz checks in with patients every 4-8 weeks. If they›re maintaining weight well, he considers decreasing the dose again and repeating with follow-up visits.

Substitute one intervention for another. In general, maintaining weight loss requires some intervention, Dr. Wharton said. “But that intervention does not need to be the same as the intervention that got the weight down.” If the patient can›t continue a GLP-1, consider an alternate medication, cognitive behavioral therapy, or a combination of the two. When patients lose coverage for GLP-1s, Dr. Bramante sometimes prescribes an older, less-expensive weight loss drug, such as phentermine, topiramate, or metformin. And sometimes, insurers that don’t cover GLP-1s (like Medicare), do cover bariatric surgery, a potential option depending on the patient›s body mass index, overall health, and comorbidities, said Dr. Almandoz.

Create a habit template. Dr. Kushner asks patients who have successfully lost weight to take an inventory of everything they’re doing to support their efforts. He’ll have them describe how they plan their diet, what types of food they’re eating, how much they eat, and when they eat it. He’ll also ask about physical activity, exercise patterns, and sleep. He logs all the habits into a bulleted list in the patient’s after-visit summary and hands them a printout before they leave. “That’s your template,” he’ll tell them. “That’s what you’re going to try to maintain to the best of your ability because it’s working for you.”

Prescribe exercise. “Increasing exercise is not usually effective for initial weight loss, but it is important for maintaining weight loss,” said Dr. Bramante. Tell patients to start right away, ideally while they’re still on the drug. In a study published last month, patients on liraglutide (Saxenda) who exercised 4 days a week were much more likely to keep weight off after stopping the drug than those who didn’t work out. (The study was partially funded by Novo Nordisk Foundation, the charitable arm of Saxenda’s maker, also the maker of semaglutide meds Ozempic and Wegovy.) By establishing strong exercise habits while on the medication, they were able to sustain higher physical activity levels after they stopped. Ask your patient to identify someone or something to help them stick to their plan, “whether it’s seeing a personal trainer or being accountable to a friend or family member or to themselves through record keeping,” said Dr. Kushner. Learn more about how to prescribe exercise to patients here.

Help them create a “microenvironment” for success. Dr. Kushner asks patients which of the recommended dietary habits for weight loss are hardest to follow: Eating more plant-based foods? Cutting back on ultra-processed foods, fatty foods, fast foods, and/or sugary beverages? Depending on the patient’s answers, he tries to recommend strategies — maybe going meatless a few days a week or keeping tempting foods out of the house. “If you go off medication, food may become more enticing, and you may not feel as content eating less,” Dr. Kushner said. “Make sure your own what we call microenvironment, your home environment, is filled with healthy foods.”

Rely on multidisciplinary expertise. Obesity is a complex, multifactorial disease, so call in reinforcements. “When I see someone, I’m always evaluating what other team members they would benefit from,” said Dr. Kushner. If the patient lacks nutrition knowledge, he refers them to a registered dietitian. If they struggle with self-blame, low self-esteem, and emotional eating, he’ll refer them to a psychologist. It can make a difference: A 2023 study showed that people who lost weight and received support from professionals like trainers, dietitians, and mental health therapists regained less weight over 2 years than those who did not receive the same help.

Reassure patients you will help them no matter what. Ask patients to follow-up within the first month of quitting medication or to call back sooner if they gain 5 pounds. People who stop taking GLP-1s often report less satisfaction with eating, or that they think about food more. That’s when Dr. Kushner asks whether they want to go back on the medication or focus on other strategies. Sometimes, patients who gain weight feel embarrassed and delay their follow-up visits. If that happens, welcome them back and let them know that all chronic conditions ebb and flow. “I constantly remind them that I am here to help you, and there are many tools or resources that will help you,” Dr. Kushner said. “And dispel the notion that it’s somehow your fault.”

Dr. Kushner reported participation on the medical advisory board or consultancy with Novo Nordisk, WeightWatchers, Eli Lilly and Company, Boehringer Ingelheim, Structure Therapeutics, and Altimmune. He added he does not own stock or participate in any speaker’s bureau. Dr. Almandoz reported participation on advisory boards with Novo Nordisk, Boehringer Ingelheim, and Eli Lilly and Company. Dr. Wharton reported participation on advisory boards and honoraria for academic talks and clinical research with Novo Nordisk, Eli Lilly and Company, Boehringer Ingelheim, Amgen, Regeneron, and BioHaven.

A version of this article appeared on Medscape.com.

Weight loss drugs have surged in popularity — in part because they work. Patients on glucagon-like peptide 1 (GLP-1) agonists like liraglutide, semaglutide, and tirzepatide (which is technically also a glucose-dependent insulinotropic polypeptide agonist) can lose 10%, 20%, or even 25% of their body weight.

But if those patients stop taking GLP-1s, they tend to regain most of that weight within a year, studies showed.

“These drugs work inside the person from a biologic point of view to alter appetite,” said Robert Kushner, MD, an endocrinologist and professor at Northwestern University Feinberg School of Medicine, Chicago, Illinois, who specializes in obesity medicine. “And when the drug is gone, that disease comes back.” 

Ongoing treatment may seem like the obvious solution, but reality can complicate that. High costs, supply shortages, and faltering insurance coverage can render the drugs inaccessible.

Often, “patients are told by their insurers that they are no longer going to cover a GLP-1 for obesity,” said Carolyn Bramante, MD, MPH, an assistant professor at the University of Minnesota Medical School, Minneapolis, Minnesota, who sees patients at the M Health Fairview weight management clinic.

Other barriers include side effects like nausea, diarrhea, stomach pain, and vomiting. Some patients simply don’t want to take a medication forever, instead choosing to take their chances keeping the weight off sans drug.

If your patient must stop GLP-1s, or really wants to, here’s how to help.

Find out why the patient wants to go off the GLP-1. Ask them to help you understand, suggested Jaime Almandoz, MD, associate professor of internal medicine and medical director of the University of Texas Southwestern Medical Center’s Weight Wellness Program. Sometimes, the patient or family members worry about safety, Dr. Almandoz said. “They may be concerned about the risks and may not have had an opportunity to ask questions.” Dr. Almandoz reviews the drug safety data and tells patients that studies show, on average, people gain back two-thirds of the weight they’ve lost within a year. You’re not trying to persuade them, only to equip them to make a well-informed choice.

Don’t let bias affect treatment decisions. Patients on GLP-1s often ask: How long will I have to take this? The reason: “We’re biased to believe that this is not a disease state, that this is a character flaw,” said Sean Wharton, MD, PharmD, medical director of the Wharton Medical Clinic for weight management in Burlington, Ontario, Canada. Remind your patient that obesity is not a personal failure but rather a complex mix of genetic and biological factors.

Give patients a primer on the biology of obesity. Science shows that when we lose weight, our bodies fight back, trying to return to our highest-ever fat mass. Changes in neurohormones, gut hormones, satiety mechanisms, metabolism, and muscle function all converge to promote weight recurrence, Dr. Almandoz said. To explain this to patients, Dr. Almandoz compares gaining fat to depositing money in a savings account. “When we try to lose weight, it isn’t as simple as withdrawing this money,” he’ll tell them. “It is almost like the money that we put into the savings account is now tied up in investments that we can’t liquidate easily.”

Prepare patients for an uptick in appetite. When patients stop GLP-1s, their hunger and food cravings tend to increase. “I explain that GLP-1 medications mimic a hormone that is released from our intestines when they sense we have eaten,” said Dr. Almandoz. This signals the brain and body that food is on board, decreasing appetite and cravings. Ask patients what hungry and full feel like on the medication, Dr. Almandoz suggested. “Many will report that their hunger and cravings are low, that they now have an indifference to foods,” said Dr. Almandoz. Such probing questions can help patients be more aware of the medication’s effects. “This positions a more informed conversation if medications are to be discontinued,” Dr. Almandoz said.

Help their body adjust. “Slowly wean down on the dose, if possible, to avoid a big rebound in hunger,” said Dr. Bramante. If your patient has the time — say, they received a letter from their insurance that coverage will end in 3 months — use it to taper the dose as low as possible before stopping. The slower and more gradual, the better. Dr. Almandoz checks in with patients every 4-8 weeks. If they›re maintaining weight well, he considers decreasing the dose again and repeating with follow-up visits.

Substitute one intervention for another. In general, maintaining weight loss requires some intervention, Dr. Wharton said. “But that intervention does not need to be the same as the intervention that got the weight down.” If the patient can›t continue a GLP-1, consider an alternate medication, cognitive behavioral therapy, or a combination of the two. When patients lose coverage for GLP-1s, Dr. Bramante sometimes prescribes an older, less-expensive weight loss drug, such as phentermine, topiramate, or metformin. And sometimes, insurers that don’t cover GLP-1s (like Medicare), do cover bariatric surgery, a potential option depending on the patient›s body mass index, overall health, and comorbidities, said Dr. Almandoz.

Create a habit template. Dr. Kushner asks patients who have successfully lost weight to take an inventory of everything they’re doing to support their efforts. He’ll have them describe how they plan their diet, what types of food they’re eating, how much they eat, and when they eat it. He’ll also ask about physical activity, exercise patterns, and sleep. He logs all the habits into a bulleted list in the patient’s after-visit summary and hands them a printout before they leave. “That’s your template,” he’ll tell them. “That’s what you’re going to try to maintain to the best of your ability because it’s working for you.”

Prescribe exercise. “Increasing exercise is not usually effective for initial weight loss, but it is important for maintaining weight loss,” said Dr. Bramante. Tell patients to start right away, ideally while they’re still on the drug. In a study published last month, patients on liraglutide (Saxenda) who exercised 4 days a week were much more likely to keep weight off after stopping the drug than those who didn’t work out. (The study was partially funded by Novo Nordisk Foundation, the charitable arm of Saxenda’s maker, also the maker of semaglutide meds Ozempic and Wegovy.) By establishing strong exercise habits while on the medication, they were able to sustain higher physical activity levels after they stopped. Ask your patient to identify someone or something to help them stick to their plan, “whether it’s seeing a personal trainer or being accountable to a friend or family member or to themselves through record keeping,” said Dr. Kushner. Learn more about how to prescribe exercise to patients here.

Help them create a “microenvironment” for success. Dr. Kushner asks patients which of the recommended dietary habits for weight loss are hardest to follow: Eating more plant-based foods? Cutting back on ultra-processed foods, fatty foods, fast foods, and/or sugary beverages? Depending on the patient’s answers, he tries to recommend strategies — maybe going meatless a few days a week or keeping tempting foods out of the house. “If you go off medication, food may become more enticing, and you may not feel as content eating less,” Dr. Kushner said. “Make sure your own what we call microenvironment, your home environment, is filled with healthy foods.”

Rely on multidisciplinary expertise. Obesity is a complex, multifactorial disease, so call in reinforcements. “When I see someone, I’m always evaluating what other team members they would benefit from,” said Dr. Kushner. If the patient lacks nutrition knowledge, he refers them to a registered dietitian. If they struggle with self-blame, low self-esteem, and emotional eating, he’ll refer them to a psychologist. It can make a difference: A 2023 study showed that people who lost weight and received support from professionals like trainers, dietitians, and mental health therapists regained less weight over 2 years than those who did not receive the same help.

Reassure patients you will help them no matter what. Ask patients to follow-up within the first month of quitting medication or to call back sooner if they gain 5 pounds. People who stop taking GLP-1s often report less satisfaction with eating, or that they think about food more. That’s when Dr. Kushner asks whether they want to go back on the medication or focus on other strategies. Sometimes, patients who gain weight feel embarrassed and delay their follow-up visits. If that happens, welcome them back and let them know that all chronic conditions ebb and flow. “I constantly remind them that I am here to help you, and there are many tools or resources that will help you,” Dr. Kushner said. “And dispel the notion that it’s somehow your fault.”

Dr. Kushner reported participation on the medical advisory board or consultancy with Novo Nordisk, WeightWatchers, Eli Lilly and Company, Boehringer Ingelheim, Structure Therapeutics, and Altimmune. He added he does not own stock or participate in any speaker’s bureau. Dr. Almandoz reported participation on advisory boards with Novo Nordisk, Boehringer Ingelheim, and Eli Lilly and Company. Dr. Wharton reported participation on advisory boards and honoraria for academic talks and clinical research with Novo Nordisk, Eli Lilly and Company, Boehringer Ingelheim, Amgen, Regeneron, and BioHaven.

A version of this article appeared on Medscape.com.

Have patients who want to lose weight? Tell them to put on their dancing shoes. 

Dancing can be an effective fat-loss tool for people who are overweight or have obesity, according to a recent meta-analysis in PLOS One. People who danced regularly lost about four more pounds — including three and a half pounds of fat — than those who didn’t dance. They also shaved an extra inch off their waists. 

Participants who danced three times a week for at least 3 months reaped maximum benefits. And the more they let loose, the better — more creative dance forms led to more pronounced improvements in body composition. 

The study builds on previous research that suggests dance can be beneficial for weight loss and overall health. A 2017 meta-analysis found that dance significantly improved body composition, blood biomarkers, and musculoskeletal function. Other research has linked dance with improvements in cognitive function, mental health, and quality of life.  

What makes dance special? It’s a full-body workout that might be easier to stick with than other exercises. “Enjoyment” is key for sustainability, the researchers wrote: “As a form of physical activity that integrates exercise, entertainment, and sociality, dance possesses innate advantages in fostering motivation for exercise.”

“The best exercise is the one you’ll do every day, and something that you like to do,” said Nicholas Pennings, DO, chair and associate professor of family medicine at Campbell University, Buies Creek, NC. (Dr. Pennings was not involved in the study.) For patients who enjoy dancing, dance could be that thing — or at least one workout to add to the mix. 

Help your patients get started with these tips. 

Frame it as a hobby, not exercise. Ask what hobbies they used to enjoy in high school, suggests Deirdre Mattina, MD, a cardiologist at the Cleveland Clinic and a former professional dancer. “ This can sometimes evoke happy memories of younger years and perhaps hobbies that they’d given up because they thought they were too old,” she said. If they used to play sports or dance, that’s your in. “I usually talk about hot yoga as a transition to get back their flexibility and then something like a dance aerobics or Zumba class to start.”

Recommend a group class. “Any intervention promoting social relationships is expected to increase adherence,” said Giulio Marchesini Reggiani, MD, a recently retired professor of internal medicine and dietetics at the University of Bologna in Italy. “You are motivated by the group, and you create a relationship among participants, and this means that you are no longer alone.” Try local gyms, health clubs, or even dance studios (yes, where kids go — they offer adult classes, too).

Help patients find their unique groove. Dr. Mattina has some patients who take cardio dance classes, some who line dance, and others who pole dance or heels dance. “Those are the things that keep it fun,” she said. “It doesn’t seem like exercise. It seems more like going out and hanging out.” 

Encourage those who “don’t know how to dance.” You don’t need fancy choreography or the grace of a prima ballerina.”Simply move aided by the music,” said Dr. Reggiani. “As long as you start engaging in physical activity, you improve your health, and you improve your movement.” Suggest patients start with beginner Zumba or a step class to get the hang of moving to a beat. Or try a home dance video, like Barre Blend by BODi (which offers a 14-day free trial). “You can try taking a couple classes in the privacy of your own home first, so you feel comfortable getting out there and doing it with a group,” said Dr. Mattina.

Modify as needed. If a patient has mobility limitations or lower-body pain, they can still dance — just do the upper-body portion of the moves. “Dance involves both upper and lower body movement, and so many dance activities could easily be performed in a chair,” said Dr. Pennings. A good joint-friendly option: Some health clubs offer dance classes that take place in a swimming pool.

Involve the whole family. Support from a partner can help patients stick with exercise, said Dr. Reggiani, and dance can also help a couple strengthen their bond. Invite kids and grandparents to join, too. “Dancing is something that can be done at any age,” said Dr. Reggiani. “For kids, it is important to make it fun,” said Dr. Pennings. “Start when they are young with music they are familiar with and enjoy.” For skeptical partners? “Keep it simple and nonjudgmental,” he said.

Remind patients to warm up. We lose flexibility with age, so ease into it, said Dr. Mattina. Many classes include warmups, but if you’re at home, do a few minutes of light, low-impact cardio — jumping jacks, mountain climbers, jogging, or brisk walking — before stretching. Or just put on a slow song and start lightly bouncing to the beat or stepping your feet to one side, together, then to the other side and together.

Tell them to take dance breaks. No time to join a class? Break up the workday with a few 10-minute dance parties. (That’s about three songs.) “Short bursts of exercise throughout the day, like if you do 10 minutes of exercise six times a day, actually has a greater health benefit than doing 60 minutes of continuous exercise,” said Dr. Pennings. It helps counter the negative effects of prolonged sitting “by increasing blood flow and increasing utilization of your muscles.”

Manage expectations about weight loss. Patients often have outsized expectations about how much weight they’ll lose when starting a new exercise regimen, Dr. Pennings said. Dancing burns about 300 calories per hour, so it takes roughly 12 hours to lose one pound. Consistency over time is the key. “My goal is to both emphasize the health benefits of exercise while maintaining realistic expectations about weight loss,” said Dr. Pennings. Focus less on the weight part and highlight other benefits: Dancing builds strength, balance, and coordination, said Dr. Pennings. It can help improve blood pressure and other heart health markers and boost cognition in older adults. And it’s fun.  
 

A version of this article appeared on Medscape.com.

Have patients who want to lose weight? Tell them to put on their dancing shoes. 

Dancing can be an effective fat-loss tool for people who are overweight or have obesity, according to a recent meta-analysis in PLOS One. People who danced regularly lost about four more pounds — including three and a half pounds of fat — than those who didn’t dance. They also shaved an extra inch off their waists. 

Participants who danced three times a week for at least 3 months reaped maximum benefits. And the more they let loose, the better — more creative dance forms led to more pronounced improvements in body composition. 

The study builds on previous research that suggests dance can be beneficial for weight loss and overall health. A 2017 meta-analysis found that dance significantly improved body composition, blood biomarkers, and musculoskeletal function. Other research has linked dance with improvements in cognitive function, mental health, and quality of life.  

What makes dance special? It’s a full-body workout that might be easier to stick with than other exercises. “Enjoyment” is key for sustainability, the researchers wrote: “As a form of physical activity that integrates exercise, entertainment, and sociality, dance possesses innate advantages in fostering motivation for exercise.”

“The best exercise is the one you’ll do every day, and something that you like to do,” said Nicholas Pennings, DO, chair and associate professor of family medicine at Campbell University, Buies Creek, NC. (Dr. Pennings was not involved in the study.) For patients who enjoy dancing, dance could be that thing — or at least one workout to add to the mix. 

Help your patients get started with these tips. 

Frame it as a hobby, not exercise. Ask what hobbies they used to enjoy in high school, suggests Deirdre Mattina, MD, a cardiologist at the Cleveland Clinic and a former professional dancer. “ This can sometimes evoke happy memories of younger years and perhaps hobbies that they’d given up because they thought they were too old,” she said. If they used to play sports or dance, that’s your in. “I usually talk about hot yoga as a transition to get back their flexibility and then something like a dance aerobics or Zumba class to start.”

Recommend a group class. “Any intervention promoting social relationships is expected to increase adherence,” said Giulio Marchesini Reggiani, MD, a recently retired professor of internal medicine and dietetics at the University of Bologna in Italy. “You are motivated by the group, and you create a relationship among participants, and this means that you are no longer alone.” Try local gyms, health clubs, or even dance studios (yes, where kids go — they offer adult classes, too).

Help patients find their unique groove. Dr. Mattina has some patients who take cardio dance classes, some who line dance, and others who pole dance or heels dance. “Those are the things that keep it fun,” she said. “It doesn’t seem like exercise. It seems more like going out and hanging out.” 

Encourage those who “don’t know how to dance.” You don’t need fancy choreography or the grace of a prima ballerina.”Simply move aided by the music,” said Dr. Reggiani. “As long as you start engaging in physical activity, you improve your health, and you improve your movement.” Suggest patients start with beginner Zumba or a step class to get the hang of moving to a beat. Or try a home dance video, like Barre Blend by BODi (which offers a 14-day free trial). “You can try taking a couple classes in the privacy of your own home first, so you feel comfortable getting out there and doing it with a group,” said Dr. Mattina.

Modify as needed. If a patient has mobility limitations or lower-body pain, they can still dance — just do the upper-body portion of the moves. “Dance involves both upper and lower body movement, and so many dance activities could easily be performed in a chair,” said Dr. Pennings. A good joint-friendly option: Some health clubs offer dance classes that take place in a swimming pool.

Involve the whole family. Support from a partner can help patients stick with exercise, said Dr. Reggiani, and dance can also help a couple strengthen their bond. Invite kids and grandparents to join, too. “Dancing is something that can be done at any age,” said Dr. Reggiani. “For kids, it is important to make it fun,” said Dr. Pennings. “Start when they are young with music they are familiar with and enjoy.” For skeptical partners? “Keep it simple and nonjudgmental,” he said.

Remind patients to warm up. We lose flexibility with age, so ease into it, said Dr. Mattina. Many classes include warmups, but if you’re at home, do a few minutes of light, low-impact cardio — jumping jacks, mountain climbers, jogging, or brisk walking — before stretching. Or just put on a slow song and start lightly bouncing to the beat or stepping your feet to one side, together, then to the other side and together.

Tell them to take dance breaks. No time to join a class? Break up the workday with a few 10-minute dance parties. (That’s about three songs.) “Short bursts of exercise throughout the day, like if you do 10 minutes of exercise six times a day, actually has a greater health benefit than doing 60 minutes of continuous exercise,” said Dr. Pennings. It helps counter the negative effects of prolonged sitting “by increasing blood flow and increasing utilization of your muscles.”

Manage expectations about weight loss. Patients often have outsized expectations about how much weight they’ll lose when starting a new exercise regimen, Dr. Pennings said. Dancing burns about 300 calories per hour, so it takes roughly 12 hours to lose one pound. Consistency over time is the key. “My goal is to both emphasize the health benefits of exercise while maintaining realistic expectations about weight loss,” said Dr. Pennings. Focus less on the weight part and highlight other benefits: Dancing builds strength, balance, and coordination, said Dr. Pennings. It can help improve blood pressure and other heart health markers and boost cognition in older adults. And it’s fun.  
 

A version of this article appeared on Medscape.com.

Have patients who want to lose weight? Tell them to put on their dancing shoes. 

Dancing can be an effective fat-loss tool for people who are overweight or have obesity, according to a recent meta-analysis in PLOS One. People who danced regularly lost about four more pounds — including three and a half pounds of fat — than those who didn’t dance. They also shaved an extra inch off their waists. 

Participants who danced three times a week for at least 3 months reaped maximum benefits. And the more they let loose, the better — more creative dance forms led to more pronounced improvements in body composition. 

The study builds on previous research that suggests dance can be beneficial for weight loss and overall health. A 2017 meta-analysis found that dance significantly improved body composition, blood biomarkers, and musculoskeletal function. Other research has linked dance with improvements in cognitive function, mental health, and quality of life.  

What makes dance special? It’s a full-body workout that might be easier to stick with than other exercises. “Enjoyment” is key for sustainability, the researchers wrote: “As a form of physical activity that integrates exercise, entertainment, and sociality, dance possesses innate advantages in fostering motivation for exercise.”

“The best exercise is the one you’ll do every day, and something that you like to do,” said Nicholas Pennings, DO, chair and associate professor of family medicine at Campbell University, Buies Creek, NC. (Dr. Pennings was not involved in the study.) For patients who enjoy dancing, dance could be that thing — or at least one workout to add to the mix. 

Help your patients get started with these tips. 

Frame it as a hobby, not exercise. Ask what hobbies they used to enjoy in high school, suggests Deirdre Mattina, MD, a cardiologist at the Cleveland Clinic and a former professional dancer. “ This can sometimes evoke happy memories of younger years and perhaps hobbies that they’d given up because they thought they were too old,” she said. If they used to play sports or dance, that’s your in. “I usually talk about hot yoga as a transition to get back their flexibility and then something like a dance aerobics or Zumba class to start.”

Recommend a group class. “Any intervention promoting social relationships is expected to increase adherence,” said Giulio Marchesini Reggiani, MD, a recently retired professor of internal medicine and dietetics at the University of Bologna in Italy. “You are motivated by the group, and you create a relationship among participants, and this means that you are no longer alone.” Try local gyms, health clubs, or even dance studios (yes, where kids go — they offer adult classes, too).

Help patients find their unique groove. Dr. Mattina has some patients who take cardio dance classes, some who line dance, and others who pole dance or heels dance. “Those are the things that keep it fun,” she said. “It doesn’t seem like exercise. It seems more like going out and hanging out.” 

Encourage those who “don’t know how to dance.” You don’t need fancy choreography or the grace of a prima ballerina.”Simply move aided by the music,” said Dr. Reggiani. “As long as you start engaging in physical activity, you improve your health, and you improve your movement.” Suggest patients start with beginner Zumba or a step class to get the hang of moving to a beat. Or try a home dance video, like Barre Blend by BODi (which offers a 14-day free trial). “You can try taking a couple classes in the privacy of your own home first, so you feel comfortable getting out there and doing it with a group,” said Dr. Mattina.

Modify as needed. If a patient has mobility limitations or lower-body pain, they can still dance — just do the upper-body portion of the moves. “Dance involves both upper and lower body movement, and so many dance activities could easily be performed in a chair,” said Dr. Pennings. A good joint-friendly option: Some health clubs offer dance classes that take place in a swimming pool.

Involve the whole family. Support from a partner can help patients stick with exercise, said Dr. Reggiani, and dance can also help a couple strengthen their bond. Invite kids and grandparents to join, too. “Dancing is something that can be done at any age,” said Dr. Reggiani. “For kids, it is important to make it fun,” said Dr. Pennings. “Start when they are young with music they are familiar with and enjoy.” For skeptical partners? “Keep it simple and nonjudgmental,” he said.

Remind patients to warm up. We lose flexibility with age, so ease into it, said Dr. Mattina. Many classes include warmups, but if you’re at home, do a few minutes of light, low-impact cardio — jumping jacks, mountain climbers, jogging, or brisk walking — before stretching. Or just put on a slow song and start lightly bouncing to the beat or stepping your feet to one side, together, then to the other side and together.

Tell them to take dance breaks. No time to join a class? Break up the workday with a few 10-minute dance parties. (That’s about three songs.) “Short bursts of exercise throughout the day, like if you do 10 minutes of exercise six times a day, actually has a greater health benefit than doing 60 minutes of continuous exercise,” said Dr. Pennings. It helps counter the negative effects of prolonged sitting “by increasing blood flow and increasing utilization of your muscles.”

Manage expectations about weight loss. Patients often have outsized expectations about how much weight they’ll lose when starting a new exercise regimen, Dr. Pennings said. Dancing burns about 300 calories per hour, so it takes roughly 12 hours to lose one pound. Consistency over time is the key. “My goal is to both emphasize the health benefits of exercise while maintaining realistic expectations about weight loss,” said Dr. Pennings. Focus less on the weight part and highlight other benefits: Dancing builds strength, balance, and coordination, said Dr. Pennings. It can help improve blood pressure and other heart health markers and boost cognition in older adults. And it’s fun.  
 

A version of this article appeared on Medscape.com.

It’s an appealing concept: Stop addictive behaviors for a while — think social media, video games, gambling, porn, junk food, drugs, alcohol (dry January, anyone?) — to reset your brain’s reward circuitry, so you can feel great minus the bad habits.

People call it dopamine fasting, abstinence sampling, or dopamine detox. But is shutting off the rush of that feel-good neurotransmitter really the key to kicking addictions?

TikTok influencers and Silicon Valley execs seem to think so. But so do some physicians.

Prominent among the proponents is Anna Lembke, MD, professor of psychiatry at Stanford University School of Medicine and chief of the Stanford Addiction Medicine Dual Diagnosis Clinic. There, the dopamine fast is an early intervention framework for many of her patients.

“What we have seen in those patients is that not only does craving begin to subside in about 4 weeks, but that mood and anxiety and sleep and all these other parameters and markers of good mental health also improve,” Dr. Lembke said.

Any clinician, regardless of background, can adopt this framework, the Dopamine Nation author said during her talk at the American College of Lifestyle Medicine (ACLM) conference last fall. “There is this idea in medicine that we have to leave addiction to the Betty Ford Clinic or to an addiction psychiatrist,” she told the gathering. “But there’s so much that we can do, no matter what our training and no matter our treatment setting.”  

But is dopamine fasting right for your patients? Some experts said it’s an oversimplified or even dangerous approach. Here’s what to know.

Dopamine and the Brain

From the prefrontal cortex — your brain’s control center — to the nucleus accumbens and ventral tegmental area located deep in your limbic system, dopamine bridges gaps between neurons to deliver critical messages about pleasure, reward, and motivation. 

We all have a baseline level of dopamine. Substances and behaviors we like — everything from chocolate and sex to cocaine and amphetamines — increase dopamine firing. 

“When we seek healthy rewards, like a good meal out in a restaurant or having a nice chat with friends, dopaminergic neurons fire, and dopamine is released,” said Birgitta Dresp, PhD, a cognitive psychologist and research director with the Centre National de la Recherche Scientifique in Paris. “That gives us a good feeling.”

But over time, with chronic exposure to hyperpleasurable stimuli, your brain adapts. Dopamine receptors downregulate and shrink, and your “hedonic setpoint,” or baseline happiness level, drops. You now need more of your favorite stimuli to feel as good as you did before.

This primitive brain wiring served evolutionary purposes, helping our ancestors relentlessly pursue scarce resources like food. But in our modern world full of easily accessible, novel, potent, and stimulating activities, our brains are constantly trying to compensate. Paradoxically, this constant “self-titillation” may be contributing to our national and global mental health crisis, Dr. Lembke suggested.

“Human activity has changed the world we live in,” said Dr. Lembke, “and now this ancient mechanistic structure has become a liability of sorts.”

The Dopamine Fast in Action

To reset this wiring, Dr. Lembke recommended a 4-week fast from a person’s “drug of choice.” But this isn’t the trendy tech-bro quick cure-all where you abstain from everything that brings you joy. It’s a targeted intervention usually aimed at one behavior or substance at a time. The fast allows a person to understand “the nature of the hijacked brain,” and breaking free motivates them to change habits long term, said Dr. Lembke.

Although the first 2 weeks are difficult, she found that many patients feel better and more motivated after 4 weeks.

How do you identify patients who might benefit from a dopamine fast? Start with “how much” and proceed to “why.” Instead of asking how much of a substance or behavior they indulge in per week, which can be inaccurate, Dr. Lembke uses a “timeline follow-back” technique — how much yesterday, the day before that, and so on. This can lead to an “aha” moment when they see the week’s true total, she told the ACLM conference.  

She also explored why they do it. Often patients say they are self-medicating or that the substance helps with their anxiety or depression. When people are compulsively continuing to use despite negative consequences, she might recommend a 4-week reset.

Important exceptions: Dr. Lembke did not recommend dopamine fasting to anyone who has repeatedly and unsuccessfully tried to quit a drug on their own nor anyone for whom withdrawal is life-threatening.

For people who can safely try the dopamine fast, she recommended “self-binding” strategies to help them stay the course. Consider the people, places, and things that encourage you to use, and try to avoid them. For example, delete your social media apps if you’re trying to detox from social media. Put physical distance between you and your phone. For foods and substances, keep them out of the house. 

Dr. Lembke also recommended “hormesis,” painful but productive activities like exercise. Your brain’s system for pleasure and pain are closely related, so these activities affect reward circuitry.

“You’re intentionally doing things that are hard, which doesn’t initially release dopamine, in contrast to intoxicants, but you get a gradual increase that remains elevated even after that activity is stopped, which is a nice way to get dopamine indirectly,” she said.

If patients plan to resume their “drug of choice” after the dopamine fast, Dr. Lembke helps them plan how much they will consume and when. For some, this works. Others, unfortunately, go back to using as much or more than they did before. But in many cases, she said, patients feel better and find that their “drug of choice” wasn’t serving them as well as they thought. 

Critiques of Dopamine Fasting

Dopamine fasting isn’t for everyone, and experts debate its safety and effectiveness. Here are some common concerns: 

It’s too simplistic. Peter Grinspoon, MD, a primary care physician at Massachusetts General Hospital and instructor at Harvard Medical School, said dopamine fasting isn’t really fasting — you don’t have a finite store of dopamine to conserve or deplete in a fixed amount of time. Even if you abstain from certain pleasures, your brain will still produce some dopamine.

What makes more sense, he said, is gradual “dopamine retargeting,” seeking rewards from healthy pleasurable activities.

“Addiction is a disease of isolation, and learning to take pleasure in the healthy things in life, like a nice home-cooked meal or a walk in the woods or a hug or a swim in the ocean, is exactly what addiction recovery is about,” he said. “Because once you learn to do that and to be happy, there’s no longer any room for the drug and you’re not nearly as susceptible to relapse.”

A related concern is that the dopamine system isn’t the only part of your brain that matters in addiction. “There are other bits of the brain which are much more important for controlling temptation,” said Trevor W. Robbins, PhD, professor of cognitive neuroscience and director of research at the Behavioural and Clinical Neuroscience Institute at the University of Cambridge. Dopamine plays an important role in addiction and recovery, “but to call this a dopamine fast, it’s just a trendy saying to make it sound exciting,” he said.

Empirical evidence is lacking. Without clinical trials to back it up, dopamine fasting lacks evidence on safety and effectiveness, said David Tzall, PsyD, a psychologist practicing in Brooklyn. “It sounds kind of fun, right? To think like, oh, I’ll just stop doing this for a while, and my body will correct itself,” said Dr. Tzall. “I think that’s a very dangerous thing because we don’t have enough evidence on it to think of how it can be effective or how it can be dangerous.”

Dr. Lembke “would like to see more evidence, too,” beyond clinical observation and expert consensus. Future research could also reveal who is most likely to benefit and how long the fast should last for maximum benefit.

It’s too much a one-size-fits-all approach. “Stopping a drug of choice is going to look different for a lot of people,” said Dr. Tzall. Some people can quit smoking cold turkey; others need to phase it out. Some need nicotine patches; some don’t. Some can do it alone; others need help. 

The individual’s why behind addiction is also crucial. Without their drug or habit, can they “cope with the stressors of life?” Dr. Tzall asked. They may need new strategies. And if they quit before they are ready and fail, they could end up feeling even worse than they did before.

Experts do agree on one thing: We can do more to help people who are struggling. “It’s very good that people are having discussions around tempering consumption because we clearly have a serious drug and alcohol addiction, obesity, and digital media problem,” said Dr. Lembke.

A version of this article appeared on Medscape.com.

It’s an appealing concept: Stop addictive behaviors for a while — think social media, video games, gambling, porn, junk food, drugs, alcohol (dry January, anyone?) — to reset your brain’s reward circuitry, so you can feel great minus the bad habits.

People call it dopamine fasting, abstinence sampling, or dopamine detox. But is shutting off the rush of that feel-good neurotransmitter really the key to kicking addictions?

TikTok influencers and Silicon Valley execs seem to think so. But so do some physicians.

Prominent among the proponents is Anna Lembke, MD, professor of psychiatry at Stanford University School of Medicine and chief of the Stanford Addiction Medicine Dual Diagnosis Clinic. There, the dopamine fast is an early intervention framework for many of her patients.

“What we have seen in those patients is that not only does craving begin to subside in about 4 weeks, but that mood and anxiety and sleep and all these other parameters and markers of good mental health also improve,” Dr. Lembke said.

Any clinician, regardless of background, can adopt this framework, the Dopamine Nation author said during her talk at the American College of Lifestyle Medicine (ACLM) conference last fall. “There is this idea in medicine that we have to leave addiction to the Betty Ford Clinic or to an addiction psychiatrist,” she told the gathering. “But there’s so much that we can do, no matter what our training and no matter our treatment setting.”  

But is dopamine fasting right for your patients? Some experts said it’s an oversimplified or even dangerous approach. Here’s what to know.

Dopamine and the Brain

From the prefrontal cortex — your brain’s control center — to the nucleus accumbens and ventral tegmental area located deep in your limbic system, dopamine bridges gaps between neurons to deliver critical messages about pleasure, reward, and motivation. 

We all have a baseline level of dopamine. Substances and behaviors we like — everything from chocolate and sex to cocaine and amphetamines — increase dopamine firing. 

“When we seek healthy rewards, like a good meal out in a restaurant or having a nice chat with friends, dopaminergic neurons fire, and dopamine is released,” said Birgitta Dresp, PhD, a cognitive psychologist and research director with the Centre National de la Recherche Scientifique in Paris. “That gives us a good feeling.”

But over time, with chronic exposure to hyperpleasurable stimuli, your brain adapts. Dopamine receptors downregulate and shrink, and your “hedonic setpoint,” or baseline happiness level, drops. You now need more of your favorite stimuli to feel as good as you did before.

This primitive brain wiring served evolutionary purposes, helping our ancestors relentlessly pursue scarce resources like food. But in our modern world full of easily accessible, novel, potent, and stimulating activities, our brains are constantly trying to compensate. Paradoxically, this constant “self-titillation” may be contributing to our national and global mental health crisis, Dr. Lembke suggested.

“Human activity has changed the world we live in,” said Dr. Lembke, “and now this ancient mechanistic structure has become a liability of sorts.”

The Dopamine Fast in Action

To reset this wiring, Dr. Lembke recommended a 4-week fast from a person’s “drug of choice.” But this isn’t the trendy tech-bro quick cure-all where you abstain from everything that brings you joy. It’s a targeted intervention usually aimed at one behavior or substance at a time. The fast allows a person to understand “the nature of the hijacked brain,” and breaking free motivates them to change habits long term, said Dr. Lembke.

Although the first 2 weeks are difficult, she found that many patients feel better and more motivated after 4 weeks.

How do you identify patients who might benefit from a dopamine fast? Start with “how much” and proceed to “why.” Instead of asking how much of a substance or behavior they indulge in per week, which can be inaccurate, Dr. Lembke uses a “timeline follow-back” technique — how much yesterday, the day before that, and so on. This can lead to an “aha” moment when they see the week’s true total, she told the ACLM conference.  

She also explored why they do it. Often patients say they are self-medicating or that the substance helps with their anxiety or depression. When people are compulsively continuing to use despite negative consequences, she might recommend a 4-week reset.

Important exceptions: Dr. Lembke did not recommend dopamine fasting to anyone who has repeatedly and unsuccessfully tried to quit a drug on their own nor anyone for whom withdrawal is life-threatening.

For people who can safely try the dopamine fast, she recommended “self-binding” strategies to help them stay the course. Consider the people, places, and things that encourage you to use, and try to avoid them. For example, delete your social media apps if you’re trying to detox from social media. Put physical distance between you and your phone. For foods and substances, keep them out of the house. 

Dr. Lembke also recommended “hormesis,” painful but productive activities like exercise. Your brain’s system for pleasure and pain are closely related, so these activities affect reward circuitry.

“You’re intentionally doing things that are hard, which doesn’t initially release dopamine, in contrast to intoxicants, but you get a gradual increase that remains elevated even after that activity is stopped, which is a nice way to get dopamine indirectly,” she said.

If patients plan to resume their “drug of choice” after the dopamine fast, Dr. Lembke helps them plan how much they will consume and when. For some, this works. Others, unfortunately, go back to using as much or more than they did before. But in many cases, she said, patients feel better and find that their “drug of choice” wasn’t serving them as well as they thought. 

Critiques of Dopamine Fasting

Dopamine fasting isn’t for everyone, and experts debate its safety and effectiveness. Here are some common concerns: 

It’s too simplistic. Peter Grinspoon, MD, a primary care physician at Massachusetts General Hospital and instructor at Harvard Medical School, said dopamine fasting isn’t really fasting — you don’t have a finite store of dopamine to conserve or deplete in a fixed amount of time. Even if you abstain from certain pleasures, your brain will still produce some dopamine.

What makes more sense, he said, is gradual “dopamine retargeting,” seeking rewards from healthy pleasurable activities.

“Addiction is a disease of isolation, and learning to take pleasure in the healthy things in life, like a nice home-cooked meal or a walk in the woods or a hug or a swim in the ocean, is exactly what addiction recovery is about,” he said. “Because once you learn to do that and to be happy, there’s no longer any room for the drug and you’re not nearly as susceptible to relapse.”

A related concern is that the dopamine system isn’t the only part of your brain that matters in addiction. “There are other bits of the brain which are much more important for controlling temptation,” said Trevor W. Robbins, PhD, professor of cognitive neuroscience and director of research at the Behavioural and Clinical Neuroscience Institute at the University of Cambridge. Dopamine plays an important role in addiction and recovery, “but to call this a dopamine fast, it’s just a trendy saying to make it sound exciting,” he said.

Empirical evidence is lacking. Without clinical trials to back it up, dopamine fasting lacks evidence on safety and effectiveness, said David Tzall, PsyD, a psychologist practicing in Brooklyn. “It sounds kind of fun, right? To think like, oh, I’ll just stop doing this for a while, and my body will correct itself,” said Dr. Tzall. “I think that’s a very dangerous thing because we don’t have enough evidence on it to think of how it can be effective or how it can be dangerous.”

Dr. Lembke “would like to see more evidence, too,” beyond clinical observation and expert consensus. Future research could also reveal who is most likely to benefit and how long the fast should last for maximum benefit.

It’s too much a one-size-fits-all approach. “Stopping a drug of choice is going to look different for a lot of people,” said Dr. Tzall. Some people can quit smoking cold turkey; others need to phase it out. Some need nicotine patches; some don’t. Some can do it alone; others need help. 

The individual’s why behind addiction is also crucial. Without their drug or habit, can they “cope with the stressors of life?” Dr. Tzall asked. They may need new strategies. And if they quit before they are ready and fail, they could end up feeling even worse than they did before.

Experts do agree on one thing: We can do more to help people who are struggling. “It’s very good that people are having discussions around tempering consumption because we clearly have a serious drug and alcohol addiction, obesity, and digital media problem,” said Dr. Lembke.

A version of this article appeared on Medscape.com.

It’s an appealing concept: Stop addictive behaviors for a while — think social media, video games, gambling, porn, junk food, drugs, alcohol (dry January, anyone?) — to reset your brain’s reward circuitry, so you can feel great minus the bad habits.

People call it dopamine fasting, abstinence sampling, or dopamine detox. But is shutting off the rush of that feel-good neurotransmitter really the key to kicking addictions?

TikTok influencers and Silicon Valley execs seem to think so. But so do some physicians.

Prominent among the proponents is Anna Lembke, MD, professor of psychiatry at Stanford University School of Medicine and chief of the Stanford Addiction Medicine Dual Diagnosis Clinic. There, the dopamine fast is an early intervention framework for many of her patients.

“What we have seen in those patients is that not only does craving begin to subside in about 4 weeks, but that mood and anxiety and sleep and all these other parameters and markers of good mental health also improve,” Dr. Lembke said.

Any clinician, regardless of background, can adopt this framework, the Dopamine Nation author said during her talk at the American College of Lifestyle Medicine (ACLM) conference last fall. “There is this idea in medicine that we have to leave addiction to the Betty Ford Clinic or to an addiction psychiatrist,” she told the gathering. “But there’s so much that we can do, no matter what our training and no matter our treatment setting.”  

But is dopamine fasting right for your patients? Some experts said it’s an oversimplified or even dangerous approach. Here’s what to know.

Dopamine and the Brain

From the prefrontal cortex — your brain’s control center — to the nucleus accumbens and ventral tegmental area located deep in your limbic system, dopamine bridges gaps between neurons to deliver critical messages about pleasure, reward, and motivation. 

We all have a baseline level of dopamine. Substances and behaviors we like — everything from chocolate and sex to cocaine and amphetamines — increase dopamine firing. 

“When we seek healthy rewards, like a good meal out in a restaurant or having a nice chat with friends, dopaminergic neurons fire, and dopamine is released,” said Birgitta Dresp, PhD, a cognitive psychologist and research director with the Centre National de la Recherche Scientifique in Paris. “That gives us a good feeling.”

But over time, with chronic exposure to hyperpleasurable stimuli, your brain adapts. Dopamine receptors downregulate and shrink, and your “hedonic setpoint,” or baseline happiness level, drops. You now need more of your favorite stimuli to feel as good as you did before.

This primitive brain wiring served evolutionary purposes, helping our ancestors relentlessly pursue scarce resources like food. But in our modern world full of easily accessible, novel, potent, and stimulating activities, our brains are constantly trying to compensate. Paradoxically, this constant “self-titillation” may be contributing to our national and global mental health crisis, Dr. Lembke suggested.

“Human activity has changed the world we live in,” said Dr. Lembke, “and now this ancient mechanistic structure has become a liability of sorts.”

The Dopamine Fast in Action

To reset this wiring, Dr. Lembke recommended a 4-week fast from a person’s “drug of choice.” But this isn’t the trendy tech-bro quick cure-all where you abstain from everything that brings you joy. It’s a targeted intervention usually aimed at one behavior or substance at a time. The fast allows a person to understand “the nature of the hijacked brain,” and breaking free motivates them to change habits long term, said Dr. Lembke.

Although the first 2 weeks are difficult, she found that many patients feel better and more motivated after 4 weeks.

How do you identify patients who might benefit from a dopamine fast? Start with “how much” and proceed to “why.” Instead of asking how much of a substance or behavior they indulge in per week, which can be inaccurate, Dr. Lembke uses a “timeline follow-back” technique — how much yesterday, the day before that, and so on. This can lead to an “aha” moment when they see the week’s true total, she told the ACLM conference.  

She also explored why they do it. Often patients say they are self-medicating or that the substance helps with their anxiety or depression. When people are compulsively continuing to use despite negative consequences, she might recommend a 4-week reset.

Important exceptions: Dr. Lembke did not recommend dopamine fasting to anyone who has repeatedly and unsuccessfully tried to quit a drug on their own nor anyone for whom withdrawal is life-threatening.

For people who can safely try the dopamine fast, she recommended “self-binding” strategies to help them stay the course. Consider the people, places, and things that encourage you to use, and try to avoid them. For example, delete your social media apps if you’re trying to detox from social media. Put physical distance between you and your phone. For foods and substances, keep them out of the house. 

Dr. Lembke also recommended “hormesis,” painful but productive activities like exercise. Your brain’s system for pleasure and pain are closely related, so these activities affect reward circuitry.

“You’re intentionally doing things that are hard, which doesn’t initially release dopamine, in contrast to intoxicants, but you get a gradual increase that remains elevated even after that activity is stopped, which is a nice way to get dopamine indirectly,” she said.

If patients plan to resume their “drug of choice” after the dopamine fast, Dr. Lembke helps them plan how much they will consume and when. For some, this works. Others, unfortunately, go back to using as much or more than they did before. But in many cases, she said, patients feel better and find that their “drug of choice” wasn’t serving them as well as they thought. 

Critiques of Dopamine Fasting

Dopamine fasting isn’t for everyone, and experts debate its safety and effectiveness. Here are some common concerns: 

It’s too simplistic. Peter Grinspoon, MD, a primary care physician at Massachusetts General Hospital and instructor at Harvard Medical School, said dopamine fasting isn’t really fasting — you don’t have a finite store of dopamine to conserve or deplete in a fixed amount of time. Even if you abstain from certain pleasures, your brain will still produce some dopamine.

What makes more sense, he said, is gradual “dopamine retargeting,” seeking rewards from healthy pleasurable activities.

“Addiction is a disease of isolation, and learning to take pleasure in the healthy things in life, like a nice home-cooked meal or a walk in the woods or a hug or a swim in the ocean, is exactly what addiction recovery is about,” he said. “Because once you learn to do that and to be happy, there’s no longer any room for the drug and you’re not nearly as susceptible to relapse.”

A related concern is that the dopamine system isn’t the only part of your brain that matters in addiction. “There are other bits of the brain which are much more important for controlling temptation,” said Trevor W. Robbins, PhD, professor of cognitive neuroscience and director of research at the Behavioural and Clinical Neuroscience Institute at the University of Cambridge. Dopamine plays an important role in addiction and recovery, “but to call this a dopamine fast, it’s just a trendy saying to make it sound exciting,” he said.

Empirical evidence is lacking. Without clinical trials to back it up, dopamine fasting lacks evidence on safety and effectiveness, said David Tzall, PsyD, a psychologist practicing in Brooklyn. “It sounds kind of fun, right? To think like, oh, I’ll just stop doing this for a while, and my body will correct itself,” said Dr. Tzall. “I think that’s a very dangerous thing because we don’t have enough evidence on it to think of how it can be effective or how it can be dangerous.”

Dr. Lembke “would like to see more evidence, too,” beyond clinical observation and expert consensus. Future research could also reveal who is most likely to benefit and how long the fast should last for maximum benefit.

It’s too much a one-size-fits-all approach. “Stopping a drug of choice is going to look different for a lot of people,” said Dr. Tzall. Some people can quit smoking cold turkey; others need to phase it out. Some need nicotine patches; some don’t. Some can do it alone; others need help. 

The individual’s why behind addiction is also crucial. Without their drug or habit, can they “cope with the stressors of life?” Dr. Tzall asked. They may need new strategies. And if they quit before they are ready and fail, they could end up feeling even worse than they did before.

Experts do agree on one thing: We can do more to help people who are struggling. “It’s very good that people are having discussions around tempering consumption because we clearly have a serious drug and alcohol addiction, obesity, and digital media problem,” said Dr. Lembke.

A version of this article appeared on Medscape.com.