MDedge Internal Medicine

BOSTON — Social adversity is associated with worse survival among patients with pulmonary hypertension (PH), according to a new retrospective study of a New York City population. Among HIV+ patients with heart failure, PH was associated with about a threefold increase in all-cause mortality, but that risk increased to about sevenfold when social adversity, identified by a licensed social worker, was also present.

A sub-analysis of both HIV+ and HIV– patients showed worse mortality outcomes with social adversity in both groups.

“Almost the majority of patients that we treat have either some social adversity or no insurance or are undocumented, so as a group of residents, we decided to study the impact of these factors on their health and the care that can be provided. We started using the two cohorts and now we keep it going with every new resident,” said Luca Biavati, MD, who presented the study at the CHEST Annual Meeting.

“The presence of any form of socioeconomic disadvantage is negatively impacting care and for a large part of the population, there are some factors that could probably be addressed by either an institutional or hospital policy,” said Dr. Biavati, who is an internal medicine resident at Jacobi Medical Center, New York.

Other factors are more difficult to address, such as lack of education. “[Some patients] don’t understand the gravity of their issue and medical condition until it’s too late, and then they’re not fit enough for the treatment, or just because of the social situation, they cannot qualify for advanced therapies,” said Dr. Biavati.

The researchers established two cohorts: One consisting of patients with HIV and heart failure who may or may not have had PH and one comprising patients with PH with or without HIV and heart failure. In the HIV/heart failure group, PH without social adversity was associated with a nearly threefold increase in all-cause mortality (hazard ratio [HR], 2.83; P = .004), whereas PH with social adversity was linked to a more than sevenfold increase in all-cause mortality (HR, 7.14; P < .001). Social adversity without PA was associated with a more than fourfold increase (HR, 4.47; P < .001).

Within the PH cohort, social adversity was associated with lower survival (P < .001). When the researchers broke down the results by types of social adversity, they found statistically significant relationships between greater mortality risk and economic instability within the HIV+ population (HR, 2.59; P = .040), transportation issues within the HIV– population (HR, 12.8; P < .001), and lack of social or family support within both the HIV– (HR, 5.49; P < .001) and the HIV+ population (HR, 2.03; P = .028). 

The research has prompted interventions, which are now being studied at the institution, according to Dr. Biavati. “We have a policy of giving medications in bags when we discharge a patient with a social adversity. We literally go to the pharmacy, bring up the bag of medication, and we [put it] in their hands before they leave the hospital. They get a 1- or 3-month supply, depending on the medication, and then we usually discharge them with a clinical appointment already scheduled with either a pulmonary or primary care provider, and we usually call them before every appointment to confirm that they’re coming. That increases the chances of some success, but there’s still a very long way to go,” said Dr. Biavati.

Dr. Biavati was blinded to the results of the intervention, so he could not report on whether it was working. “But I can tell you that I’ve had busier clinics, so hopefully that means that they’re showing up more,” he said.

The problem is complex, according to Sandeep Jain, MD, who moderated the session. “Social adversity means lack of education. Lack of education means lack of compliance. Lack of compliance means what can you do if people are not taking medications? So it’s all matched together. It’s all lack of education and lack of money, lack of family support. And these drugs they have to take every single day. It’s not that easy. It’s very easy for us to say I had antiretroviral treatment for 6 months. It is almost impossible to continue regular treatment for that long [for a patient with social adversity]. You can’t blame them if they aren’t taking treatments. It’s very difficult for them,” said Dr. Jain.

That underscores the need for interventions that can address the needs of patients with social adversity. “We have to [practice] medicine considering the social situation of the patient and not just the medicine that we study in books. That’s kind of what we are faced with every day. We have therapies, and then life happens. It’s much harder to care for those patients,” said Dr. Biavati.

Dr. Biavati and Dr. Jain reported no relevant financial relationships.
 

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

BOSTON — Social adversity is associated with worse survival among patients with pulmonary hypertension (PH), according to a new retrospective study of a New York City population. Among HIV+ patients with heart failure, PH was associated with about a threefold increase in all-cause mortality, but that risk increased to about sevenfold when social adversity, identified by a licensed social worker, was also present.

A sub-analysis of both HIV+ and HIV– patients showed worse mortality outcomes with social adversity in both groups.

“Almost the majority of patients that we treat have either some social adversity or no insurance or are undocumented, so as a group of residents, we decided to study the impact of these factors on their health and the care that can be provided. We started using the two cohorts and now we keep it going with every new resident,” said Luca Biavati, MD, who presented the study at the CHEST Annual Meeting.

“The presence of any form of socioeconomic disadvantage is negatively impacting care and for a large part of the population, there are some factors that could probably be addressed by either an institutional or hospital policy,” said Dr. Biavati, who is an internal medicine resident at Jacobi Medical Center, New York.

Other factors are more difficult to address, such as lack of education. “[Some patients] don’t understand the gravity of their issue and medical condition until it’s too late, and then they’re not fit enough for the treatment, or just because of the social situation, they cannot qualify for advanced therapies,” said Dr. Biavati.

The researchers established two cohorts: One consisting of patients with HIV and heart failure who may or may not have had PH and one comprising patients with PH with or without HIV and heart failure. In the HIV/heart failure group, PH without social adversity was associated with a nearly threefold increase in all-cause mortality (hazard ratio [HR], 2.83; P = .004), whereas PH with social adversity was linked to a more than sevenfold increase in all-cause mortality (HR, 7.14; P < .001). Social adversity without PA was associated with a more than fourfold increase (HR, 4.47; P < .001).

Within the PH cohort, social adversity was associated with lower survival (P < .001). When the researchers broke down the results by types of social adversity, they found statistically significant relationships between greater mortality risk and economic instability within the HIV+ population (HR, 2.59; P = .040), transportation issues within the HIV– population (HR, 12.8; P < .001), and lack of social or family support within both the HIV– (HR, 5.49; P < .001) and the HIV+ population (HR, 2.03; P = .028). 

The research has prompted interventions, which are now being studied at the institution, according to Dr. Biavati. “We have a policy of giving medications in bags when we discharge a patient with a social adversity. We literally go to the pharmacy, bring up the bag of medication, and we [put it] in their hands before they leave the hospital. They get a 1- or 3-month supply, depending on the medication, and then we usually discharge them with a clinical appointment already scheduled with either a pulmonary or primary care provider, and we usually call them before every appointment to confirm that they’re coming. That increases the chances of some success, but there’s still a very long way to go,” said Dr. Biavati.

Dr. Biavati was blinded to the results of the intervention, so he could not report on whether it was working. “But I can tell you that I’ve had busier clinics, so hopefully that means that they’re showing up more,” he said.

The problem is complex, according to Sandeep Jain, MD, who moderated the session. “Social adversity means lack of education. Lack of education means lack of compliance. Lack of compliance means what can you do if people are not taking medications? So it’s all matched together. It’s all lack of education and lack of money, lack of family support. And these drugs they have to take every single day. It’s not that easy. It’s very easy for us to say I had antiretroviral treatment for 6 months. It is almost impossible to continue regular treatment for that long [for a patient with social adversity]. You can’t blame them if they aren’t taking treatments. It’s very difficult for them,” said Dr. Jain.

That underscores the need for interventions that can address the needs of patients with social adversity. “We have to [practice] medicine considering the social situation of the patient and not just the medicine that we study in books. That’s kind of what we are faced with every day. We have therapies, and then life happens. It’s much harder to care for those patients,” said Dr. Biavati.

Dr. Biavati and Dr. Jain reported no relevant financial relationships.
 

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

BOSTON — Social adversity is associated with worse survival among patients with pulmonary hypertension (PH), according to a new retrospective study of a New York City population. Among HIV+ patients with heart failure, PH was associated with about a threefold increase in all-cause mortality, but that risk increased to about sevenfold when social adversity, identified by a licensed social worker, was also present.

A sub-analysis of both HIV+ and HIV– patients showed worse mortality outcomes with social adversity in both groups.

“Almost the majority of patients that we treat have either some social adversity or no insurance or are undocumented, so as a group of residents, we decided to study the impact of these factors on their health and the care that can be provided. We started using the two cohorts and now we keep it going with every new resident,” said Luca Biavati, MD, who presented the study at the CHEST Annual Meeting.

“The presence of any form of socioeconomic disadvantage is negatively impacting care and for a large part of the population, there are some factors that could probably be addressed by either an institutional or hospital policy,” said Dr. Biavati, who is an internal medicine resident at Jacobi Medical Center, New York.

Other factors are more difficult to address, such as lack of education. “[Some patients] don’t understand the gravity of their issue and medical condition until it’s too late, and then they’re not fit enough for the treatment, or just because of the social situation, they cannot qualify for advanced therapies,” said Dr. Biavati.

The researchers established two cohorts: One consisting of patients with HIV and heart failure who may or may not have had PH and one comprising patients with PH with or without HIV and heart failure. In the HIV/heart failure group, PH without social adversity was associated with a nearly threefold increase in all-cause mortality (hazard ratio [HR], 2.83; P = .004), whereas PH with social adversity was linked to a more than sevenfold increase in all-cause mortality (HR, 7.14; P < .001). Social adversity without PA was associated with a more than fourfold increase (HR, 4.47; P < .001).

Within the PH cohort, social adversity was associated with lower survival (P < .001). When the researchers broke down the results by types of social adversity, they found statistically significant relationships between greater mortality risk and economic instability within the HIV+ population (HR, 2.59; P = .040), transportation issues within the HIV– population (HR, 12.8; P < .001), and lack of social or family support within both the HIV– (HR, 5.49; P < .001) and the HIV+ population (HR, 2.03; P = .028). 

The research has prompted interventions, which are now being studied at the institution, according to Dr. Biavati. “We have a policy of giving medications in bags when we discharge a patient with a social adversity. We literally go to the pharmacy, bring up the bag of medication, and we [put it] in their hands before they leave the hospital. They get a 1- or 3-month supply, depending on the medication, and then we usually discharge them with a clinical appointment already scheduled with either a pulmonary or primary care provider, and we usually call them before every appointment to confirm that they’re coming. That increases the chances of some success, but there’s still a very long way to go,” said Dr. Biavati.

Dr. Biavati was blinded to the results of the intervention, so he could not report on whether it was working. “But I can tell you that I’ve had busier clinics, so hopefully that means that they’re showing up more,” he said.

The problem is complex, according to Sandeep Jain, MD, who moderated the session. “Social adversity means lack of education. Lack of education means lack of compliance. Lack of compliance means what can you do if people are not taking medications? So it’s all matched together. It’s all lack of education and lack of money, lack of family support. And these drugs they have to take every single day. It’s not that easy. It’s very easy for us to say I had antiretroviral treatment for 6 months. It is almost impossible to continue regular treatment for that long [for a patient with social adversity]. You can’t blame them if they aren’t taking treatments. It’s very difficult for them,” said Dr. Jain.

That underscores the need for interventions that can address the needs of patients with social adversity. “We have to [practice] medicine considering the social situation of the patient and not just the medicine that we study in books. That’s kind of what we are faced with every day. We have therapies, and then life happens. It’s much harder to care for those patients,” said Dr. Biavati.

Dr. Biavati and Dr. Jain reported no relevant financial relationships.
 

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

TOPLINE: 

Virtual yoga classes significantly reduced chronic low back pain intensity and improved back-related function in health system employees. Improvements were sustained at 24 weeks, with reduced pain medication use and better sleep quality.

METHODOLOGY:

• A single-blinded, 24-week, 2-arm, randomized clinical trial was conducted from May 3, 2022, through May 23, 2023, comparing live-streamed yoga classes with a wait-list control among adults with chronic low back pain.
• A total of 140 participants aged 18-64 years with chronic low back pain were recruited from the Cleveland Clinic Employee Health Plan.
• Inclusion criteria included a mean low back pain intensity score of at least 4 on an 11-point numerical rating scale and daily back pain interference about half or more of the days.
• The intervention consisted of 12 consecutive weekly, 60-minute, virtual, live-streamed hatha yoga group classes.

Coprimary outcomes were mean pain intensity in the previous week on the 11-point numerical rating scale and back-related function as assessed using the 23-point modified Roland Morris Disability Questionnaire at 12 weeks.

TAKEAWAY:

• Participants in the virtual yoga group showed greater reductions in mean pain intensity at 12 weeks (mean change, –1.5 points; P < .001) and 24 weeks (mean change, –2.3 points; P < .001) compared to the wait-list control group.
• Back-related function improved significantly in the virtual yoga group at 12 weeks (mean change, –2.8 points; P < .001) and 24 weeks (mean change, –4.6 points; P < .001), compared with the control group.
• Virtual yoga participants reported 21.2 percentage points less use of any analgesic medication during the past week at 24 weeks, compared with the control group.
• Sleep quality improved more in the virtual yoga group at 12 weeks (mean change, 0.4 points; P = .008) and 24 weeks (mean change, 0.4 points; P = .005), compared with the control group.

IN PRACTICE:

“Given the demonstrated noninferiority of yoga to physical therapy, structured virtual yoga programs and physical therapy are reasonable choices for patients with [chronic low back pain] depending on accessibility, cost, and patient preference. These findings support the call by the National Academy of Medicine for increased evidenced-based pain treatments that can be disseminated via technology-based platforms,” wrote the authors of the study.

SOURCE:

The study was led by Hallie Tankha, PhD, Cleveland Clinic in Ohio. It was published online on November 1, 2024, in JAMA Network Open.

LIMITATIONS: 

The study had a low adherence rate, with only 36.6% of participants attending at least 50% of the yoga classes. There was also a higher rate of missing data in the yoga group compared to the control group. The study did not include a longer-term follow-up assessment beyond 24 weeks.

DISCLOSURES:

This study was supported by grants from Cleveland Clinic Healthcare Delivery and Implementation Science Center. One coauthor disclosed receiving personal fees from the Blue Cross Blue Shield Association. Eric Roseen, DC, PhD, reported receiving grants from the National Institutes of Health National Center for Complementary and Integrative Health. One coauthor disclosed receiving personal fees from UpToDate and grants from NCCIH related to yoga and tai chi for treatment of pain. Additional disclosures are noted in the original article.

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

TOPLINE: 

Virtual yoga classes significantly reduced chronic low back pain intensity and improved back-related function in health system employees. Improvements were sustained at 24 weeks, with reduced pain medication use and better sleep quality.

METHODOLOGY:

• A single-blinded, 24-week, 2-arm, randomized clinical trial was conducted from May 3, 2022, through May 23, 2023, comparing live-streamed yoga classes with a wait-list control among adults with chronic low back pain.
• A total of 140 participants aged 18-64 years with chronic low back pain were recruited from the Cleveland Clinic Employee Health Plan.
• Inclusion criteria included a mean low back pain intensity score of at least 4 on an 11-point numerical rating scale and daily back pain interference about half or more of the days.
• The intervention consisted of 12 consecutive weekly, 60-minute, virtual, live-streamed hatha yoga group classes.

Coprimary outcomes were mean pain intensity in the previous week on the 11-point numerical rating scale and back-related function as assessed using the 23-point modified Roland Morris Disability Questionnaire at 12 weeks.

TAKEAWAY:

• Participants in the virtual yoga group showed greater reductions in mean pain intensity at 12 weeks (mean change, –1.5 points; P < .001) and 24 weeks (mean change, –2.3 points; P < .001) compared to the wait-list control group.
• Back-related function improved significantly in the virtual yoga group at 12 weeks (mean change, –2.8 points; P < .001) and 24 weeks (mean change, –4.6 points; P < .001), compared with the control group.
• Virtual yoga participants reported 21.2 percentage points less use of any analgesic medication during the past week at 24 weeks, compared with the control group.
• Sleep quality improved more in the virtual yoga group at 12 weeks (mean change, 0.4 points; P = .008) and 24 weeks (mean change, 0.4 points; P = .005), compared with the control group.

IN PRACTICE:

“Given the demonstrated noninferiority of yoga to physical therapy, structured virtual yoga programs and physical therapy are reasonable choices for patients with [chronic low back pain] depending on accessibility, cost, and patient preference. These findings support the call by the National Academy of Medicine for increased evidenced-based pain treatments that can be disseminated via technology-based platforms,” wrote the authors of the study.

SOURCE:

The study was led by Hallie Tankha, PhD, Cleveland Clinic in Ohio. It was published online on November 1, 2024, in JAMA Network Open.

LIMITATIONS: 

The study had a low adherence rate, with only 36.6% of participants attending at least 50% of the yoga classes. There was also a higher rate of missing data in the yoga group compared to the control group. The study did not include a longer-term follow-up assessment beyond 24 weeks.

DISCLOSURES:

This study was supported by grants from Cleveland Clinic Healthcare Delivery and Implementation Science Center. One coauthor disclosed receiving personal fees from the Blue Cross Blue Shield Association. Eric Roseen, DC, PhD, reported receiving grants from the National Institutes of Health National Center for Complementary and Integrative Health. One coauthor disclosed receiving personal fees from UpToDate and grants from NCCIH related to yoga and tai chi for treatment of pain. Additional disclosures are noted in the original article.

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

TOPLINE: 

Virtual yoga classes significantly reduced chronic low back pain intensity and improved back-related function in health system employees. Improvements were sustained at 24 weeks, with reduced pain medication use and better sleep quality.

METHODOLOGY:

• A single-blinded, 24-week, 2-arm, randomized clinical trial was conducted from May 3, 2022, through May 23, 2023, comparing live-streamed yoga classes with a wait-list control among adults with chronic low back pain.
• A total of 140 participants aged 18-64 years with chronic low back pain were recruited from the Cleveland Clinic Employee Health Plan.
• Inclusion criteria included a mean low back pain intensity score of at least 4 on an 11-point numerical rating scale and daily back pain interference about half or more of the days.
• The intervention consisted of 12 consecutive weekly, 60-minute, virtual, live-streamed hatha yoga group classes.

Coprimary outcomes were mean pain intensity in the previous week on the 11-point numerical rating scale and back-related function as assessed using the 23-point modified Roland Morris Disability Questionnaire at 12 weeks.

TAKEAWAY:

• Participants in the virtual yoga group showed greater reductions in mean pain intensity at 12 weeks (mean change, –1.5 points; P < .001) and 24 weeks (mean change, –2.3 points; P < .001) compared to the wait-list control group.
• Back-related function improved significantly in the virtual yoga group at 12 weeks (mean change, –2.8 points; P < .001) and 24 weeks (mean change, –4.6 points; P < .001), compared with the control group.
• Virtual yoga participants reported 21.2 percentage points less use of any analgesic medication during the past week at 24 weeks, compared with the control group.
• Sleep quality improved more in the virtual yoga group at 12 weeks (mean change, 0.4 points; P = .008) and 24 weeks (mean change, 0.4 points; P = .005), compared with the control group.

IN PRACTICE:

“Given the demonstrated noninferiority of yoga to physical therapy, structured virtual yoga programs and physical therapy are reasonable choices for patients with [chronic low back pain] depending on accessibility, cost, and patient preference. These findings support the call by the National Academy of Medicine for increased evidenced-based pain treatments that can be disseminated via technology-based platforms,” wrote the authors of the study.

SOURCE:

The study was led by Hallie Tankha, PhD, Cleveland Clinic in Ohio. It was published online on November 1, 2024, in JAMA Network Open.

LIMITATIONS: 

The study had a low adherence rate, with only 36.6% of participants attending at least 50% of the yoga classes. There was also a higher rate of missing data in the yoga group compared to the control group. The study did not include a longer-term follow-up assessment beyond 24 weeks.

DISCLOSURES:

This study was supported by grants from Cleveland Clinic Healthcare Delivery and Implementation Science Center. One coauthor disclosed receiving personal fees from the Blue Cross Blue Shield Association. Eric Roseen, DC, PhD, reported receiving grants from the National Institutes of Health National Center for Complementary and Integrative Health. One coauthor disclosed receiving personal fees from UpToDate and grants from NCCIH related to yoga and tai chi for treatment of pain. Additional disclosures are noted in the original article.

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

Many people with rheumatologic diseases try supplements for symptom relief. Here’s what you need to know about some common picks.

Dietary supplements were a $159 billion business in the United States in 2023, and many people with rheumatologic diseases are buying in. Research suggests more than 6 in 10 people with fibromyalgia, nearly 8 in 10 people with Sjögren’s disease, and more than 8 in 10 people with rheumatoid arthritis (RA) take dietary supplements.

Whatever the symptom — pain, swelling, or fatigue — you can probably find a supplement purporting to relieve it. But do these supplements work, and are they safe? A study review in RMD Open comprising 24 systematic reviews and 150 original articles suggests more high-quality research is needed on the effects of dietary supplements on rheumatologic diseases. Most studies have focused on RA or osteoarthritis (OA), where the evidence level is moderate at best.

Dr. Janet Funk

“The studies in this space are usually not very high quality because there’s no money to support them, among other things, plus the products are disparate,” said Janet Funk, MD, MS, professor in the School of Nutritional Sciences and Wellness at the University of Arizona, Tucson. She recommended brushing up on supplements and finding out what patients are taking so you can offer advice and watch for drug-supplement interactions.

When asked for a medication list, many patients forget to report supplements, Funk said. “You have to prompt them specifically. I think some physicians have very negative views about supplements because so little data is known, and patients might pick up on that and decide not to report their use.” She recommended saying something like: “To give you the best possible care, I want to know everything you’re taking, including supplements. The things I’m prescribing could maybe interact with the things you’re taking, so I want to make sure I know about all of it so that together we can figure out if the combination of things is safe.”

The quality of dietary supplements varies, and they aren’t regulated like drugs by the Food and Drug Administration. Funk recommended selecting products verified by NSF or ConsumerLab. They test supplements to ensure the label reflects what’s inside.

This news organization scoured the literature and asked experts to weigh in on the evidence behind popular supplements in rheumatology today.
 

The Essential Nutrients

Vitamin supplements are a staple in many homes — but are they helpful? “Individual vitamin supplements will not provide any benefit unless the person is deficient in a specific vitamin or mineral,” according to Elena Philippou, PhD, RD, associate professor of nutrition-dietetics at the University of Nicosia in Cyprus, and Elena Nikiphorou, MBBS, a rheumatologist at King’s College London in England. For some patients, deficiency is a reality. A retrospective cohort study in The Journal of Clinical Medicine found that people with RA were 17% more likely than age-matched control individuals to have nutrient deficiencies, perhaps because symptoms like fatigue, pain, and nausea affect their eating habits. Here’s what the science says about common vitamin supplements.

Dr. Elena Philippou

Vitamin D. This hormone-like vitamin, which attaches to receptors on immune cells to tamp down inflammation, was the most popular dietary supplement among rheumatology patients in a recent study from the United Kingdom. Vitamin D deficiency is common in people with RA, lupus, Sjögren’s disease, ankylosing spondylitis, systemic sclerosis, and fibromyalgia. In some cases, vitamin D levels track with disease activity, research suggests. Corticosteroids can also make vitamin D deficiency more likely. Can supplements help?

In RA, evidence points to small improvements. A systematic review of 11 studies including 3049 patients published in Nutrition Reviews showed that vitamin D supplements significantly reduced patients’ pain and Disease Activity Score in 28 joints (DAS28) using both C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).

The research is mixed on the benefits of vitamin D supplementation for fibromyalgia symptoms, according to a study review in SN Comprehensive Clinical Medicine that included two studies and 80 patients on supplementation. However, researchers said it’s still worth discussing the potential benefits of taking vitamin D.

“Vitamin D supplementation is important in the context of various rheumatic diseases to prevent or treat bone disease,” said Philippou and Nikiphorou. “People with rheumatic disease should speak to their healthcare provider and ask to check their blood vitamin D concentration.” The results can help you recommend a dose.

Folate. Patients on methotrexate should take folic acid supplements under the guidance of a healthcare provider, said Philippou and Nikiphorou. The reason: Methotrexate can deplete folic acid levels, increasing the risk for side effects. An analysis of adverse event reports published showed that methotrexate users who took folic acid (or tumor necrosis factor–alpha inhibitors) had a reduced risk for hepatotoxicity or myelosuppression. A commonly recommended dose is 1 mg/d.

Vitamin B12. In a 2024 perspective paper in Rheumatology International, researchers said physicians should assess vitamin B12 levels early in the diagnostic process of rheumatologic diseases. One reason: Many symptoms of pernicious anemia, like fatigue, mimic symptoms of rheumatologic diseases. The gastrointestinal (GI) effects of systemic sclerosis could bring on vitamin B12 deficiency. In a small study in The Journal of Clinical Rheumatology, 44 of 62 patients with systemic sclerosis had low vitamin B12 levels.

Vitamin E. Vitamin E deficiency is rare in healthy adults. However, some medical conditions, like inflammatory bowel disease and malabsorption disorders, can make vitamin E deficiency more likely. In RA, a vitamin E supplement could help reduce joint swelling and sensitivity, according to a systematic review of nine studies including 39,845 patients in The European Journal of Clinical Nutrition. Researchers credit the nutrient’s role in aiding intestinal repair. Use with caution, as this supplement can increase bleeding risk in doses over 1000 mg/d.

Vitamin A. Like vitamin E, vitamin A deficiency is rare in the United States. The risk of oversupplementing is higher than undersupplementing. However, vitamin A deficiency can happen in people with chronic pancreatic, liver, or GI problems. In people with deficiency, a vitamin A supplement can help relieve dry eye symptoms common in Sjögren’s disease, suggests a narrative review published in Nutrients. Vitamin A might help reduce ocular surface changes by supporting the production of proteins that protect the outermost surfaces of the eyes. The recommended daily allowance for vitamin A is 900 μg. High-dose supplements can cause toxicity, resulting in GI symptoms and problems like lethargy, drowsiness, increased intracranial pressure, and skin changes.
 

The Replacements

These substances are similar to naturally occurring compounds in our bodies. The question is whether ingesting them yields benefits.

Glucosamine and chondroitin. Glucosamine and chondroitin occur naturally in our bodies and help us form and protect connective tissues. In pill form, this combo is the most popular dietary supplement for OA, according to research in the journal Maturitas. But studies of its effectiveness yield mixed results. A systematic review of 25 studies published in Inflammopharmacology showed that, in patients with knee OA, supplementation with about 1500 mg of glucosamine per day reduced tibiofemoral joint space narrowing, while supplementation with about 800 mg/d of chondroitin reduced pain intensity and improved physical function, compared with placebo. The duo of glucosamine and chondroitin did not bring significant benefits, perhaps because more studies are needed. Most side effects were mild, but some literature points to the potential for glucosamine to increase warfarin’s blood-thinning effects.

Omega-3 fatty acids. Fish oil is a top-selling supplement, and it might be helpful in inflammatory rheumatologic diseases. A systematic review of 30 studies including 710 patients published in Arthritis Research & Therapy showed that omega-3 fatty acid supplements can improve pain, swollen and tender joint count, DAS28 scores, and Health Assessment Questionnaire scores in patients with RA, psoriatic arthritis, or ankylosing spondylitis. In patients with lupus, a study review that included five studies and 284 patients in The International Journal of Environmental Research and Public Health suggested omega-3 fatty acid supplements could improve ESR, CRP, disease activity, inflammatory markers, oxidative stress, lipid levels, and endothelial function.

Omega-3 fatty acids have anti-inflammatory effects that might explain their benefits. In patients with RA, for example, fish oil supplementation was associated with elevated blood levels of resolvins and protectins, which help quell inflammation, according to a study in Prostaglandins, Leukotrienes and Essential Fatty Acids.

Philippou and Nikiphorou recommended combining food and supplements: Eat oily fish at least twice a week, regularly consume plant-based sources of omega-3s — like chia seeds, flaxseeds, or walnuts — and consider a daily supplement that contains 2 g of omega-3s from docosahexaenoic acid and eicosapentaenoic acid. Most fish oil side effects are mild, like heartburn and bad breath. Fish oil can have blood-thinning effects at high doses, so special attention is needed for patients on anticoagulants.

Probiotics. Building up the good bacteria in your gut might help you fight the effects of rheumatologic diseases. A systematic review of 80 randomized controlled trials in BMC Medicine suggested that therapies targeting the gut microbiota might improve the symptoms or inflammatory factors in celiac disease, lupus, juvenile idiopathic arthritis, psoriasis, Sjögren’s disease, multiple sclerosis, systemic sclerosis, Crohn’s disease, and ulcerative colitis. Probiotics were also shown to relieve pain in fibromyalgia, but they didn’t affect scores on the Fibromyalgia Impact Questionnaire. Probiotics were not helpful in spondyloarthritis or RA. There were no adverse events. By improving the balance of bacteria in the gut, probiotics might inhibit pro-inflammatory factors and signaling pathways and regulate CD4+ T-cell differentiation, the researchers wrote.

Not all probiotic supplements are created equal. Effects can vary by microorganism and dose. Until more high-quality studies are published, Philippou and Nikiphorou recommend daily consumption of probiotic food sources such as yogurt, kefir, sauerkraut, kimchi, tempeh, miso, and kombucha, along with prebiotic food sources such as bananas, onion, artichokes, asparagus, oats, leeks, and garlic.

Collagen. An increasingly popular supplement for hair, skin, and nails, some collagen peptide or hydrolyzed collagen supplements come with claims about joint health, too. Inside our bodies, collagen helps build joints. As a supplement, the jury is still out. A systematic review of 19 studies in The International Journal of Rheumatic Diseases suggested more research is needed to determine whether collagen supplements are harmful or helpful in OA or RA. Studies haven’t shown adverse events, and doses typically range from 2.5 to 15 g/d.

Coenzyme Q10 (CoQ10). This antioxidant occurs naturally in our cells and is produced through microbial fermentation for use in dietary supplements. A study review of 20 articles including 483 patients in Clinical Nutrition ESPEN concluded that CoQ10 supplementation up to 300 mg/d was beneficial in RA, fibromyalgia, or antiphospholipid syndrome (APS).

In RA, CoQ10 supplementation improved disease activity index, ESR, and cytokine levels and decreased malondialdehyde. CoQ10 might protect against the overproduction of reactive oxygen species that can promote inflammation and joint damage, the researchers said. In fibromyalgia, CoQ10 was linked with improvements in pain, fatigue, sleep, tender points count, mood disorders, and scores on the Fibromyalgia Impact Questionnaire in most of the included studies. CoQ10 might help in fibromyalgia by improving mitochondrial dysfunction. In APS, CoQ10 improved endothelial function and decreased prothrombotic and pro-inflammatory mediators. CoQ10 might change the expression of genes that promote atherosclerosis. A few patients had GI side effects like nausea and diarrhea, but the supplements were generally well tolerated.

Melatonin. Commonly touted as a sleep aid, this hormone has immune and anti-inflammatory activities that could benefit people with rheumatologic diseases. A study review of 13 articles including 533 patients in Clinical Nutrition ESPEN concluded that melatonin can help improve sleep, pain, and mood in fibromyalgia, OA, and osteoporosis but not in RA. Side effects were minimal, but a few people experienced nausea, drowsiness, nightmares, or headaches. Doses of 5-6 mg/d are likely safe for most adults.
 

The Plant-Derived Antioxidants

Many supplements used in rheumatology are antioxidants derived from herbs, spices, or other plants. When plants encounter stressors, like temperature changes or hungry insects, their secondary metabolism revs up and creates compounds with biological properties. Some of these substances influence inflammatory pathways in the human body, said Luís Silva, PhD, a medicinal chemistry researcher at the Polytechnic Institute of Guarda in Portugal. “If it is possible to reduce these kinds of anti-inflammatory processes, it is also possible that we could help people with inflammatory diseases to a good life, or a better life.”

Dr. Luís Silva

Turmeric and curcumin. You might see this supplement labeled as turmeric, a golden spice in curry powder, or curcumin, an antioxidant compound known as a curcuminoid in turmeric. Curcuminoids might reduce inflammation by scavenging free radicals and inhibiting enzymes that make prostaglandins, Silva said.

Turmeric is the most popular herbal supplement for people with RA, according to Funk’s research. A study review of six publications including 539 patients in Frontiers in Immunology showed that curcumin supplements improved RA patients’ ESR, DAS, swollen joint count, and tender joint count. Turmeric could help patients with OA, too. Patients with OA who took 1000 mg/d of curcumin improved their pain and function, according to a systematic review including 12 studies and 1438 participants in the journal Nutrients. In lupus, small studies are promising but inconclusive, suggested a study review in Frontiers in Immunology.

Watch patients taking turmeric and methotrexate closely, Funk said. Both have been associated with liver problems. Some users also experience GI symptoms like diarrhea because turmeric doesn’t absorb well in the GI tract.

Milk thistle (silymarin). This flowering plant is often marketed as a liver-supporting supplement, but research also suggests promise in RA and OA. A systematic review of 12 studies in Current Rheumatology Reviews suggested that silymarin supplements might help relieve pain, reduce inflammation, and protect the cartilage matrix, synovial membrane, and cartilage cells in joints. This supplement might help via immunomodulatory, anti-inflammatory, antioxidant, and anti-apoptotic properties, the researchers said. Doses of 250-750 mg appear to be safe. Side effects such as gastroenteritis, diarrhea, bloating, and headache can occur.

Boswellia serrata. Sourced from the resin of a tree that grows in dry, mountainous regions of Asia and Africa, Boswellia serrata can help relieve joint pain and stiffness and improve joint function in OA, suggested a systematic review of seven trials involving 545 patients in BMC Complementary Medicine and Therapies. Users saw benefits when taking 100-250 mg/d for 4 weeks or more. Compounds in Boswellia serrata may inhibit 5-lipoxygenase, an enzyme involved in producing inflammatory leukotrienes. No adverse events were reported. In some studies, users have reported GI side effects.

Ginger. Ginger is a popular herbal supplement among people with RA, Funk’s research suggested. One small clinical trial involving 70 patients with RA in the journal Gene showed that taking 1500 mg/d of ginger for 12 weeks improved their DAS and boosted their expression of FoxP3 genes, which are linked with the function of regulatory T cells. A meta-analysis including three studies with 330 patients taking ginger published in the journal Nutrients suggested ginger can reduce pain and systemic inflammation in people with OA. Preclinical studies suggested phenolic compounds in this spicy root, such as gingerols, reduce inflammation through multiple mechanisms.

Funk’s research revealed wide variation in the quality of ginger supplements, reinforcing the importance of selecting an independently verified product. Research suggested a safe dose is up to 2-2.5 g/kg body weight.

Resveratrol. Found in red grapes and red wine, this compound is particularly good at blocking COX-2 enzymes, an important step in the inflammatory cascade, Silva said. “Because of their chemical structure, they have great affinity to these enzymes to lead to their inhibition,” he said. A study review of five articles including 481 patients in The European Journal of Rheumatology showed that people with OA, RA, or Takayasu arteritis who took 250-1000 mg/d of resveratrol saw improvements in pain, function, disease activity, joint swelling, and inflammation, with no side effects.

Cinnamon. This warming spice is gaining popularity as a supplement, reported the American Botanical Council. Cinnamon is often marketed as lowering blood sugar and supporting bone health. In a small study of 36 women with RA published in The Journal of the American College of Nutrition, participants who consumed 2 g/d of cinnamon powder had reduced DASs along with reduced pain and tender and swollen joint counts. Cinnamon may reduce pain by inhibiting prostaglandin and blunt inflammation by reducing the release of arachidonic acid from cell membranes, according to a study review in Frontiers in Pharmacology. GI problems and allergic reactions are among the most common side effects.

Funk, Nikiphorou, Philippou, and Silva all had no relevant disclosures.

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

Many people with rheumatologic diseases try supplements for symptom relief. Here’s what you need to know about some common picks.

Dietary supplements were a $159 billion business in the United States in 2023, and many people with rheumatologic diseases are buying in. Research suggests more than 6 in 10 people with fibromyalgia, nearly 8 in 10 people with Sjögren’s disease, and more than 8 in 10 people with rheumatoid arthritis (RA) take dietary supplements.

Whatever the symptom — pain, swelling, or fatigue — you can probably find a supplement purporting to relieve it. But do these supplements work, and are they safe? A study review in RMD Open comprising 24 systematic reviews and 150 original articles suggests more high-quality research is needed on the effects of dietary supplements on rheumatologic diseases. Most studies have focused on RA or osteoarthritis (OA), where the evidence level is moderate at best.

Dr. Janet Funk

“The studies in this space are usually not very high quality because there’s no money to support them, among other things, plus the products are disparate,” said Janet Funk, MD, MS, professor in the School of Nutritional Sciences and Wellness at the University of Arizona, Tucson. She recommended brushing up on supplements and finding out what patients are taking so you can offer advice and watch for drug-supplement interactions.

When asked for a medication list, many patients forget to report supplements, Funk said. “You have to prompt them specifically. I think some physicians have very negative views about supplements because so little data is known, and patients might pick up on that and decide not to report their use.” She recommended saying something like: “To give you the best possible care, I want to know everything you’re taking, including supplements. The things I’m prescribing could maybe interact with the things you’re taking, so I want to make sure I know about all of it so that together we can figure out if the combination of things is safe.”

The quality of dietary supplements varies, and they aren’t regulated like drugs by the Food and Drug Administration. Funk recommended selecting products verified by NSF or ConsumerLab. They test supplements to ensure the label reflects what’s inside.

This news organization scoured the literature and asked experts to weigh in on the evidence behind popular supplements in rheumatology today.
 

The Essential Nutrients

Vitamin supplements are a staple in many homes — but are they helpful? “Individual vitamin supplements will not provide any benefit unless the person is deficient in a specific vitamin or mineral,” according to Elena Philippou, PhD, RD, associate professor of nutrition-dietetics at the University of Nicosia in Cyprus, and Elena Nikiphorou, MBBS, a rheumatologist at King’s College London in England. For some patients, deficiency is a reality. A retrospective cohort study in The Journal of Clinical Medicine found that people with RA were 17% more likely than age-matched control individuals to have nutrient deficiencies, perhaps because symptoms like fatigue, pain, and nausea affect their eating habits. Here’s what the science says about common vitamin supplements.

Dr. Elena Philippou

Vitamin D. This hormone-like vitamin, which attaches to receptors on immune cells to tamp down inflammation, was the most popular dietary supplement among rheumatology patients in a recent study from the United Kingdom. Vitamin D deficiency is common in people with RA, lupus, Sjögren’s disease, ankylosing spondylitis, systemic sclerosis, and fibromyalgia. In some cases, vitamin D levels track with disease activity, research suggests. Corticosteroids can also make vitamin D deficiency more likely. Can supplements help?

In RA, evidence points to small improvements. A systematic review of 11 studies including 3049 patients published in Nutrition Reviews showed that vitamin D supplements significantly reduced patients’ pain and Disease Activity Score in 28 joints (DAS28) using both C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).

The research is mixed on the benefits of vitamin D supplementation for fibromyalgia symptoms, according to a study review in SN Comprehensive Clinical Medicine that included two studies and 80 patients on supplementation. However, researchers said it’s still worth discussing the potential benefits of taking vitamin D.

“Vitamin D supplementation is important in the context of various rheumatic diseases to prevent or treat bone disease,” said Philippou and Nikiphorou. “People with rheumatic disease should speak to their healthcare provider and ask to check their blood vitamin D concentration.” The results can help you recommend a dose.

Folate. Patients on methotrexate should take folic acid supplements under the guidance of a healthcare provider, said Philippou and Nikiphorou. The reason: Methotrexate can deplete folic acid levels, increasing the risk for side effects. An analysis of adverse event reports published showed that methotrexate users who took folic acid (or tumor necrosis factor–alpha inhibitors) had a reduced risk for hepatotoxicity or myelosuppression. A commonly recommended dose is 1 mg/d.

Vitamin B12. In a 2024 perspective paper in Rheumatology International, researchers said physicians should assess vitamin B12 levels early in the diagnostic process of rheumatologic diseases. One reason: Many symptoms of pernicious anemia, like fatigue, mimic symptoms of rheumatologic diseases. The gastrointestinal (GI) effects of systemic sclerosis could bring on vitamin B12 deficiency. In a small study in The Journal of Clinical Rheumatology, 44 of 62 patients with systemic sclerosis had low vitamin B12 levels.

Vitamin E. Vitamin E deficiency is rare in healthy adults. However, some medical conditions, like inflammatory bowel disease and malabsorption disorders, can make vitamin E deficiency more likely. In RA, a vitamin E supplement could help reduce joint swelling and sensitivity, according to a systematic review of nine studies including 39,845 patients in The European Journal of Clinical Nutrition. Researchers credit the nutrient’s role in aiding intestinal repair. Use with caution, as this supplement can increase bleeding risk in doses over 1000 mg/d.

Vitamin A. Like vitamin E, vitamin A deficiency is rare in the United States. The risk of oversupplementing is higher than undersupplementing. However, vitamin A deficiency can happen in people with chronic pancreatic, liver, or GI problems. In people with deficiency, a vitamin A supplement can help relieve dry eye symptoms common in Sjögren’s disease, suggests a narrative review published in Nutrients. Vitamin A might help reduce ocular surface changes by supporting the production of proteins that protect the outermost surfaces of the eyes. The recommended daily allowance for vitamin A is 900 μg. High-dose supplements can cause toxicity, resulting in GI symptoms and problems like lethargy, drowsiness, increased intracranial pressure, and skin changes.
 

The Replacements

These substances are similar to naturally occurring compounds in our bodies. The question is whether ingesting them yields benefits.

Glucosamine and chondroitin. Glucosamine and chondroitin occur naturally in our bodies and help us form and protect connective tissues. In pill form, this combo is the most popular dietary supplement for OA, according to research in the journal Maturitas. But studies of its effectiveness yield mixed results. A systematic review of 25 studies published in Inflammopharmacology showed that, in patients with knee OA, supplementation with about 1500 mg of glucosamine per day reduced tibiofemoral joint space narrowing, while supplementation with about 800 mg/d of chondroitin reduced pain intensity and improved physical function, compared with placebo. The duo of glucosamine and chondroitin did not bring significant benefits, perhaps because more studies are needed. Most side effects were mild, but some literature points to the potential for glucosamine to increase warfarin’s blood-thinning effects.

Omega-3 fatty acids. Fish oil is a top-selling supplement, and it might be helpful in inflammatory rheumatologic diseases. A systematic review of 30 studies including 710 patients published in Arthritis Research & Therapy showed that omega-3 fatty acid supplements can improve pain, swollen and tender joint count, DAS28 scores, and Health Assessment Questionnaire scores in patients with RA, psoriatic arthritis, or ankylosing spondylitis. In patients with lupus, a study review that included five studies and 284 patients in The International Journal of Environmental Research and Public Health suggested omega-3 fatty acid supplements could improve ESR, CRP, disease activity, inflammatory markers, oxidative stress, lipid levels, and endothelial function.

Omega-3 fatty acids have anti-inflammatory effects that might explain their benefits. In patients with RA, for example, fish oil supplementation was associated with elevated blood levels of resolvins and protectins, which help quell inflammation, according to a study in Prostaglandins, Leukotrienes and Essential Fatty Acids.

Philippou and Nikiphorou recommended combining food and supplements: Eat oily fish at least twice a week, regularly consume plant-based sources of omega-3s — like chia seeds, flaxseeds, or walnuts — and consider a daily supplement that contains 2 g of omega-3s from docosahexaenoic acid and eicosapentaenoic acid. Most fish oil side effects are mild, like heartburn and bad breath. Fish oil can have blood-thinning effects at high doses, so special attention is needed for patients on anticoagulants.

Probiotics. Building up the good bacteria in your gut might help you fight the effects of rheumatologic diseases. A systematic review of 80 randomized controlled trials in BMC Medicine suggested that therapies targeting the gut microbiota might improve the symptoms or inflammatory factors in celiac disease, lupus, juvenile idiopathic arthritis, psoriasis, Sjögren’s disease, multiple sclerosis, systemic sclerosis, Crohn’s disease, and ulcerative colitis. Probiotics were also shown to relieve pain in fibromyalgia, but they didn’t affect scores on the Fibromyalgia Impact Questionnaire. Probiotics were not helpful in spondyloarthritis or RA. There were no adverse events. By improving the balance of bacteria in the gut, probiotics might inhibit pro-inflammatory factors and signaling pathways and regulate CD4+ T-cell differentiation, the researchers wrote.

Not all probiotic supplements are created equal. Effects can vary by microorganism and dose. Until more high-quality studies are published, Philippou and Nikiphorou recommend daily consumption of probiotic food sources such as yogurt, kefir, sauerkraut, kimchi, tempeh, miso, and kombucha, along with prebiotic food sources such as bananas, onion, artichokes, asparagus, oats, leeks, and garlic.

Collagen. An increasingly popular supplement for hair, skin, and nails, some collagen peptide or hydrolyzed collagen supplements come with claims about joint health, too. Inside our bodies, collagen helps build joints. As a supplement, the jury is still out. A systematic review of 19 studies in The International Journal of Rheumatic Diseases suggested more research is needed to determine whether collagen supplements are harmful or helpful in OA or RA. Studies haven’t shown adverse events, and doses typically range from 2.5 to 15 g/d.

Coenzyme Q10 (CoQ10). This antioxidant occurs naturally in our cells and is produced through microbial fermentation for use in dietary supplements. A study review of 20 articles including 483 patients in Clinical Nutrition ESPEN concluded that CoQ10 supplementation up to 300 mg/d was beneficial in RA, fibromyalgia, or antiphospholipid syndrome (APS).

In RA, CoQ10 supplementation improved disease activity index, ESR, and cytokine levels and decreased malondialdehyde. CoQ10 might protect against the overproduction of reactive oxygen species that can promote inflammation and joint damage, the researchers said. In fibromyalgia, CoQ10 was linked with improvements in pain, fatigue, sleep, tender points count, mood disorders, and scores on the Fibromyalgia Impact Questionnaire in most of the included studies. CoQ10 might help in fibromyalgia by improving mitochondrial dysfunction. In APS, CoQ10 improved endothelial function and decreased prothrombotic and pro-inflammatory mediators. CoQ10 might change the expression of genes that promote atherosclerosis. A few patients had GI side effects like nausea and diarrhea, but the supplements were generally well tolerated.

Melatonin. Commonly touted as a sleep aid, this hormone has immune and anti-inflammatory activities that could benefit people with rheumatologic diseases. A study review of 13 articles including 533 patients in Clinical Nutrition ESPEN concluded that melatonin can help improve sleep, pain, and mood in fibromyalgia, OA, and osteoporosis but not in RA. Side effects were minimal, but a few people experienced nausea, drowsiness, nightmares, or headaches. Doses of 5-6 mg/d are likely safe for most adults.
 

The Plant-Derived Antioxidants

Many supplements used in rheumatology are antioxidants derived from herbs, spices, or other plants. When plants encounter stressors, like temperature changes or hungry insects, their secondary metabolism revs up and creates compounds with biological properties. Some of these substances influence inflammatory pathways in the human body, said Luís Silva, PhD, a medicinal chemistry researcher at the Polytechnic Institute of Guarda in Portugal. “If it is possible to reduce these kinds of anti-inflammatory processes, it is also possible that we could help people with inflammatory diseases to a good life, or a better life.”

Dr. Luís Silva

Turmeric and curcumin. You might see this supplement labeled as turmeric, a golden spice in curry powder, or curcumin, an antioxidant compound known as a curcuminoid in turmeric. Curcuminoids might reduce inflammation by scavenging free radicals and inhibiting enzymes that make prostaglandins, Silva said.

Turmeric is the most popular herbal supplement for people with RA, according to Funk’s research. A study review of six publications including 539 patients in Frontiers in Immunology showed that curcumin supplements improved RA patients’ ESR, DAS, swollen joint count, and tender joint count. Turmeric could help patients with OA, too. Patients with OA who took 1000 mg/d of curcumin improved their pain and function, according to a systematic review including 12 studies and 1438 participants in the journal Nutrients. In lupus, small studies are promising but inconclusive, suggested a study review in Frontiers in Immunology.

Watch patients taking turmeric and methotrexate closely, Funk said. Both have been associated with liver problems. Some users also experience GI symptoms like diarrhea because turmeric doesn’t absorb well in the GI tract.

Milk thistle (silymarin). This flowering plant is often marketed as a liver-supporting supplement, but research also suggests promise in RA and OA. A systematic review of 12 studies in Current Rheumatology Reviews suggested that silymarin supplements might help relieve pain, reduce inflammation, and protect the cartilage matrix, synovial membrane, and cartilage cells in joints. This supplement might help via immunomodulatory, anti-inflammatory, antioxidant, and anti-apoptotic properties, the researchers said. Doses of 250-750 mg appear to be safe. Side effects such as gastroenteritis, diarrhea, bloating, and headache can occur.

Boswellia serrata. Sourced from the resin of a tree that grows in dry, mountainous regions of Asia and Africa, Boswellia serrata can help relieve joint pain and stiffness and improve joint function in OA, suggested a systematic review of seven trials involving 545 patients in BMC Complementary Medicine and Therapies. Users saw benefits when taking 100-250 mg/d for 4 weeks or more. Compounds in Boswellia serrata may inhibit 5-lipoxygenase, an enzyme involved in producing inflammatory leukotrienes. No adverse events were reported. In some studies, users have reported GI side effects.

Ginger. Ginger is a popular herbal supplement among people with RA, Funk’s research suggested. One small clinical trial involving 70 patients with RA in the journal Gene showed that taking 1500 mg/d of ginger for 12 weeks improved their DAS and boosted their expression of FoxP3 genes, which are linked with the function of regulatory T cells. A meta-analysis including three studies with 330 patients taking ginger published in the journal Nutrients suggested ginger can reduce pain and systemic inflammation in people with OA. Preclinical studies suggested phenolic compounds in this spicy root, such as gingerols, reduce inflammation through multiple mechanisms.

Funk’s research revealed wide variation in the quality of ginger supplements, reinforcing the importance of selecting an independently verified product. Research suggested a safe dose is up to 2-2.5 g/kg body weight.

Resveratrol. Found in red grapes and red wine, this compound is particularly good at blocking COX-2 enzymes, an important step in the inflammatory cascade, Silva said. “Because of their chemical structure, they have great affinity to these enzymes to lead to their inhibition,” he said. A study review of five articles including 481 patients in The European Journal of Rheumatology showed that people with OA, RA, or Takayasu arteritis who took 250-1000 mg/d of resveratrol saw improvements in pain, function, disease activity, joint swelling, and inflammation, with no side effects.

Cinnamon. This warming spice is gaining popularity as a supplement, reported the American Botanical Council. Cinnamon is often marketed as lowering blood sugar and supporting bone health. In a small study of 36 women with RA published in The Journal of the American College of Nutrition, participants who consumed 2 g/d of cinnamon powder had reduced DASs along with reduced pain and tender and swollen joint counts. Cinnamon may reduce pain by inhibiting prostaglandin and blunt inflammation by reducing the release of arachidonic acid from cell membranes, according to a study review in Frontiers in Pharmacology. GI problems and allergic reactions are among the most common side effects.

Funk, Nikiphorou, Philippou, and Silva all had no relevant disclosures.

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

Many people with rheumatologic diseases try supplements for symptom relief. Here’s what you need to know about some common picks.

Dietary supplements were a $159 billion business in the United States in 2023, and many people with rheumatologic diseases are buying in. Research suggests more than 6 in 10 people with fibromyalgia, nearly 8 in 10 people with Sjögren’s disease, and more than 8 in 10 people with rheumatoid arthritis (RA) take dietary supplements.

Whatever the symptom — pain, swelling, or fatigue — you can probably find a supplement purporting to relieve it. But do these supplements work, and are they safe? A study review in RMD Open comprising 24 systematic reviews and 150 original articles suggests more high-quality research is needed on the effects of dietary supplements on rheumatologic diseases. Most studies have focused on RA or osteoarthritis (OA), where the evidence level is moderate at best.

Dr. Janet Funk

“The studies in this space are usually not very high quality because there’s no money to support them, among other things, plus the products are disparate,” said Janet Funk, MD, MS, professor in the School of Nutritional Sciences and Wellness at the University of Arizona, Tucson. She recommended brushing up on supplements and finding out what patients are taking so you can offer advice and watch for drug-supplement interactions.

When asked for a medication list, many patients forget to report supplements, Funk said. “You have to prompt them specifically. I think some physicians have very negative views about supplements because so little data is known, and patients might pick up on that and decide not to report their use.” She recommended saying something like: “To give you the best possible care, I want to know everything you’re taking, including supplements. The things I’m prescribing could maybe interact with the things you’re taking, so I want to make sure I know about all of it so that together we can figure out if the combination of things is safe.”

The quality of dietary supplements varies, and they aren’t regulated like drugs by the Food and Drug Administration. Funk recommended selecting products verified by NSF or ConsumerLab. They test supplements to ensure the label reflects what’s inside.

This news organization scoured the literature and asked experts to weigh in on the evidence behind popular supplements in rheumatology today.
 

The Essential Nutrients

Vitamin supplements are a staple in many homes — but are they helpful? “Individual vitamin supplements will not provide any benefit unless the person is deficient in a specific vitamin or mineral,” according to Elena Philippou, PhD, RD, associate professor of nutrition-dietetics at the University of Nicosia in Cyprus, and Elena Nikiphorou, MBBS, a rheumatologist at King’s College London in England. For some patients, deficiency is a reality. A retrospective cohort study in The Journal of Clinical Medicine found that people with RA were 17% more likely than age-matched control individuals to have nutrient deficiencies, perhaps because symptoms like fatigue, pain, and nausea affect their eating habits. Here’s what the science says about common vitamin supplements.

Dr. Elena Philippou

Vitamin D. This hormone-like vitamin, which attaches to receptors on immune cells to tamp down inflammation, was the most popular dietary supplement among rheumatology patients in a recent study from the United Kingdom. Vitamin D deficiency is common in people with RA, lupus, Sjögren’s disease, ankylosing spondylitis, systemic sclerosis, and fibromyalgia. In some cases, vitamin D levels track with disease activity, research suggests. Corticosteroids can also make vitamin D deficiency more likely. Can supplements help?

In RA, evidence points to small improvements. A systematic review of 11 studies including 3049 patients published in Nutrition Reviews showed that vitamin D supplements significantly reduced patients’ pain and Disease Activity Score in 28 joints (DAS28) using both C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).

The research is mixed on the benefits of vitamin D supplementation for fibromyalgia symptoms, according to a study review in SN Comprehensive Clinical Medicine that included two studies and 80 patients on supplementation. However, researchers said it’s still worth discussing the potential benefits of taking vitamin D.

“Vitamin D supplementation is important in the context of various rheumatic diseases to prevent or treat bone disease,” said Philippou and Nikiphorou. “People with rheumatic disease should speak to their healthcare provider and ask to check their blood vitamin D concentration.” The results can help you recommend a dose.

Folate. Patients on methotrexate should take folic acid supplements under the guidance of a healthcare provider, said Philippou and Nikiphorou. The reason: Methotrexate can deplete folic acid levels, increasing the risk for side effects. An analysis of adverse event reports published showed that methotrexate users who took folic acid (or tumor necrosis factor–alpha inhibitors) had a reduced risk for hepatotoxicity or myelosuppression. A commonly recommended dose is 1 mg/d.

Vitamin B12. In a 2024 perspective paper in Rheumatology International, researchers said physicians should assess vitamin B12 levels early in the diagnostic process of rheumatologic diseases. One reason: Many symptoms of pernicious anemia, like fatigue, mimic symptoms of rheumatologic diseases. The gastrointestinal (GI) effects of systemic sclerosis could bring on vitamin B12 deficiency. In a small study in The Journal of Clinical Rheumatology, 44 of 62 patients with systemic sclerosis had low vitamin B12 levels.

Vitamin E. Vitamin E deficiency is rare in healthy adults. However, some medical conditions, like inflammatory bowel disease and malabsorption disorders, can make vitamin E deficiency more likely. In RA, a vitamin E supplement could help reduce joint swelling and sensitivity, according to a systematic review of nine studies including 39,845 patients in The European Journal of Clinical Nutrition. Researchers credit the nutrient’s role in aiding intestinal repair. Use with caution, as this supplement can increase bleeding risk in doses over 1000 mg/d.

Vitamin A. Like vitamin E, vitamin A deficiency is rare in the United States. The risk of oversupplementing is higher than undersupplementing. However, vitamin A deficiency can happen in people with chronic pancreatic, liver, or GI problems. In people with deficiency, a vitamin A supplement can help relieve dry eye symptoms common in Sjögren’s disease, suggests a narrative review published in Nutrients. Vitamin A might help reduce ocular surface changes by supporting the production of proteins that protect the outermost surfaces of the eyes. The recommended daily allowance for vitamin A is 900 μg. High-dose supplements can cause toxicity, resulting in GI symptoms and problems like lethargy, drowsiness, increased intracranial pressure, and skin changes.
 

The Replacements

These substances are similar to naturally occurring compounds in our bodies. The question is whether ingesting them yields benefits.

Glucosamine and chondroitin. Glucosamine and chondroitin occur naturally in our bodies and help us form and protect connective tissues. In pill form, this combo is the most popular dietary supplement for OA, according to research in the journal Maturitas. But studies of its effectiveness yield mixed results. A systematic review of 25 studies published in Inflammopharmacology showed that, in patients with knee OA, supplementation with about 1500 mg of glucosamine per day reduced tibiofemoral joint space narrowing, while supplementation with about 800 mg/d of chondroitin reduced pain intensity and improved physical function, compared with placebo. The duo of glucosamine and chondroitin did not bring significant benefits, perhaps because more studies are needed. Most side effects were mild, but some literature points to the potential for glucosamine to increase warfarin’s blood-thinning effects.

Omega-3 fatty acids. Fish oil is a top-selling supplement, and it might be helpful in inflammatory rheumatologic diseases. A systematic review of 30 studies including 710 patients published in Arthritis Research & Therapy showed that omega-3 fatty acid supplements can improve pain, swollen and tender joint count, DAS28 scores, and Health Assessment Questionnaire scores in patients with RA, psoriatic arthritis, or ankylosing spondylitis. In patients with lupus, a study review that included five studies and 284 patients in The International Journal of Environmental Research and Public Health suggested omega-3 fatty acid supplements could improve ESR, CRP, disease activity, inflammatory markers, oxidative stress, lipid levels, and endothelial function.

Omega-3 fatty acids have anti-inflammatory effects that might explain their benefits. In patients with RA, for example, fish oil supplementation was associated with elevated blood levels of resolvins and protectins, which help quell inflammation, according to a study in Prostaglandins, Leukotrienes and Essential Fatty Acids.

Philippou and Nikiphorou recommended combining food and supplements: Eat oily fish at least twice a week, regularly consume plant-based sources of omega-3s — like chia seeds, flaxseeds, or walnuts — and consider a daily supplement that contains 2 g of omega-3s from docosahexaenoic acid and eicosapentaenoic acid. Most fish oil side effects are mild, like heartburn and bad breath. Fish oil can have blood-thinning effects at high doses, so special attention is needed for patients on anticoagulants.

Probiotics. Building up the good bacteria in your gut might help you fight the effects of rheumatologic diseases. A systematic review of 80 randomized controlled trials in BMC Medicine suggested that therapies targeting the gut microbiota might improve the symptoms or inflammatory factors in celiac disease, lupus, juvenile idiopathic arthritis, psoriasis, Sjögren’s disease, multiple sclerosis, systemic sclerosis, Crohn’s disease, and ulcerative colitis. Probiotics were also shown to relieve pain in fibromyalgia, but they didn’t affect scores on the Fibromyalgia Impact Questionnaire. Probiotics were not helpful in spondyloarthritis or RA. There were no adverse events. By improving the balance of bacteria in the gut, probiotics might inhibit pro-inflammatory factors and signaling pathways and regulate CD4+ T-cell differentiation, the researchers wrote.

Not all probiotic supplements are created equal. Effects can vary by microorganism and dose. Until more high-quality studies are published, Philippou and Nikiphorou recommend daily consumption of probiotic food sources such as yogurt, kefir, sauerkraut, kimchi, tempeh, miso, and kombucha, along with prebiotic food sources such as bananas, onion, artichokes, asparagus, oats, leeks, and garlic.

Collagen. An increasingly popular supplement for hair, skin, and nails, some collagen peptide or hydrolyzed collagen supplements come with claims about joint health, too. Inside our bodies, collagen helps build joints. As a supplement, the jury is still out. A systematic review of 19 studies in The International Journal of Rheumatic Diseases suggested more research is needed to determine whether collagen supplements are harmful or helpful in OA or RA. Studies haven’t shown adverse events, and doses typically range from 2.5 to 15 g/d.

Coenzyme Q10 (CoQ10). This antioxidant occurs naturally in our cells and is produced through microbial fermentation for use in dietary supplements. A study review of 20 articles including 483 patients in Clinical Nutrition ESPEN concluded that CoQ10 supplementation up to 300 mg/d was beneficial in RA, fibromyalgia, or antiphospholipid syndrome (APS).

In RA, CoQ10 supplementation improved disease activity index, ESR, and cytokine levels and decreased malondialdehyde. CoQ10 might protect against the overproduction of reactive oxygen species that can promote inflammation and joint damage, the researchers said. In fibromyalgia, CoQ10 was linked with improvements in pain, fatigue, sleep, tender points count, mood disorders, and scores on the Fibromyalgia Impact Questionnaire in most of the included studies. CoQ10 might help in fibromyalgia by improving mitochondrial dysfunction. In APS, CoQ10 improved endothelial function and decreased prothrombotic and pro-inflammatory mediators. CoQ10 might change the expression of genes that promote atherosclerosis. A few patients had GI side effects like nausea and diarrhea, but the supplements were generally well tolerated.

Melatonin. Commonly touted as a sleep aid, this hormone has immune and anti-inflammatory activities that could benefit people with rheumatologic diseases. A study review of 13 articles including 533 patients in Clinical Nutrition ESPEN concluded that melatonin can help improve sleep, pain, and mood in fibromyalgia, OA, and osteoporosis but not in RA. Side effects were minimal, but a few people experienced nausea, drowsiness, nightmares, or headaches. Doses of 5-6 mg/d are likely safe for most adults.
 

The Plant-Derived Antioxidants

Many supplements used in rheumatology are antioxidants derived from herbs, spices, or other plants. When plants encounter stressors, like temperature changes or hungry insects, their secondary metabolism revs up and creates compounds with biological properties. Some of these substances influence inflammatory pathways in the human body, said Luís Silva, PhD, a medicinal chemistry researcher at the Polytechnic Institute of Guarda in Portugal. “If it is possible to reduce these kinds of anti-inflammatory processes, it is also possible that we could help people with inflammatory diseases to a good life, or a better life.”

Dr. Luís Silva

Turmeric and curcumin. You might see this supplement labeled as turmeric, a golden spice in curry powder, or curcumin, an antioxidant compound known as a curcuminoid in turmeric. Curcuminoids might reduce inflammation by scavenging free radicals and inhibiting enzymes that make prostaglandins, Silva said.

Turmeric is the most popular herbal supplement for people with RA, according to Funk’s research. A study review of six publications including 539 patients in Frontiers in Immunology showed that curcumin supplements improved RA patients’ ESR, DAS, swollen joint count, and tender joint count. Turmeric could help patients with OA, too. Patients with OA who took 1000 mg/d of curcumin improved their pain and function, according to a systematic review including 12 studies and 1438 participants in the journal Nutrients. In lupus, small studies are promising but inconclusive, suggested a study review in Frontiers in Immunology.

Watch patients taking turmeric and methotrexate closely, Funk said. Both have been associated with liver problems. Some users also experience GI symptoms like diarrhea because turmeric doesn’t absorb well in the GI tract.

Milk thistle (silymarin). This flowering plant is often marketed as a liver-supporting supplement, but research also suggests promise in RA and OA. A systematic review of 12 studies in Current Rheumatology Reviews suggested that silymarin supplements might help relieve pain, reduce inflammation, and protect the cartilage matrix, synovial membrane, and cartilage cells in joints. This supplement might help via immunomodulatory, anti-inflammatory, antioxidant, and anti-apoptotic properties, the researchers said. Doses of 250-750 mg appear to be safe. Side effects such as gastroenteritis, diarrhea, bloating, and headache can occur.

Boswellia serrata. Sourced from the resin of a tree that grows in dry, mountainous regions of Asia and Africa, Boswellia serrata can help relieve joint pain and stiffness and improve joint function in OA, suggested a systematic review of seven trials involving 545 patients in BMC Complementary Medicine and Therapies. Users saw benefits when taking 100-250 mg/d for 4 weeks or more. Compounds in Boswellia serrata may inhibit 5-lipoxygenase, an enzyme involved in producing inflammatory leukotrienes. No adverse events were reported. In some studies, users have reported GI side effects.

Ginger. Ginger is a popular herbal supplement among people with RA, Funk’s research suggested. One small clinical trial involving 70 patients with RA in the journal Gene showed that taking 1500 mg/d of ginger for 12 weeks improved their DAS and boosted their expression of FoxP3 genes, which are linked with the function of regulatory T cells. A meta-analysis including three studies with 330 patients taking ginger published in the journal Nutrients suggested ginger can reduce pain and systemic inflammation in people with OA. Preclinical studies suggested phenolic compounds in this spicy root, such as gingerols, reduce inflammation through multiple mechanisms.

Funk’s research revealed wide variation in the quality of ginger supplements, reinforcing the importance of selecting an independently verified product. Research suggested a safe dose is up to 2-2.5 g/kg body weight.

Resveratrol. Found in red grapes and red wine, this compound is particularly good at blocking COX-2 enzymes, an important step in the inflammatory cascade, Silva said. “Because of their chemical structure, they have great affinity to these enzymes to lead to their inhibition,” he said. A study review of five articles including 481 patients in The European Journal of Rheumatology showed that people with OA, RA, or Takayasu arteritis who took 250-1000 mg/d of resveratrol saw improvements in pain, function, disease activity, joint swelling, and inflammation, with no side effects.

Cinnamon. This warming spice is gaining popularity as a supplement, reported the American Botanical Council. Cinnamon is often marketed as lowering blood sugar and supporting bone health. In a small study of 36 women with RA published in The Journal of the American College of Nutrition, participants who consumed 2 g/d of cinnamon powder had reduced DASs along with reduced pain and tender and swollen joint counts. Cinnamon may reduce pain by inhibiting prostaglandin and blunt inflammation by reducing the release of arachidonic acid from cell membranes, according to a study review in Frontiers in Pharmacology. GI problems and allergic reactions are among the most common side effects.

Funk, Nikiphorou, Philippou, and Silva all had no relevant disclosures.

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

LOS ANGELES — Metformin prescribed within a week of SARS-CoV-2 infection was associated with a 53% reduction in long COVID or death over 6 months in people without diabetes or prediabetes, according to data presented at the Infectious Disease Week (IDWeek) 2024 Annual Meeting.

Long COVID was determined by using the diagnostic code U09.9 or a computable phenotype based on symptoms and conditions. Most participants in this study were infected with the Omicron variant.

Researchers, led by Carolyn Bramante, MD, MPH, an internist, pediatrician, and obesity medicine specialist at the University of Minnesota Medical School in Minneapolis, simulated a randomized controlled trial of metformin vs control using the National COVID Cohort Collaborative (N3C) Electronic Health Record Database.

The intervention was a prescription for metformin within 6 days of SARS-CoV-2 infection. Those in the control group, which was designed to mimic placebo, had a prescription for fluvoxamine, fluticasone, ivermectin, or montelukast (all drugs that have been used off-label for COVID but have shown no effect on acute COVID outcomes in clinical trials). Exclusions included anyone with a previous metformin prescription or a comparator prescription; any indication for chronic metformin use; or a contraindication for metformin.
 

Why Study Metformin for Long COVID?

Dr. Bramante led a previous randomized controlled trial, COVID-OUT, with 1323 people that indicated metformin showed possible benefit for preventing the more severe components of COVID-19. She also led a 2020 review, in which she examined electronic health records from adults with type 2 diabetes or obesity. The researchers found that women taking metformin before they developed COVID-19 were significantly less likely to die after being hospitalized — although men didn’t see the same protective effect. Another randomized trial of 20 people found that 60% of those taking metformin vs 100% of those given a placebo had detectable SARS-CoV-2 viral load by day 4.

Other trials have highlighted the anti-inflammatory and antiviral properties of metformin. The existing evidence coupled with metformin’s well-established safety profile, led Dr. Bramante’s team to conduct the current simulated trial in people without diabetes or prediabetes. Dr. Bramante noted that metformin’s only US Food and Drug Administration–approved indication is for diabetes.

The current study featured a similar racial/ethnic makeup in the metformin and control groups: 16% and 17% were Black and 16% and 13% were Hispanic, respectively. Within 6 months, 4.0% in the metformin group developed long COVID or died compared with 8.5% in the control group (Relative Risk [RR], 0.47; 95% CI, 0.25-0.89). For prescriptions made on days 0-1 relative to infection, the RR was 0.39 (95% CI, 0.12-1.24). When metformin was prescribed on days 0-14, the RR was 0.75 (95% CI, 0.52-1.08).

The reason it’s important to have an active comparator is to control for things that can’t be measured, such as engagement in healthcare and the placebo effect, Dr. Bramante said.

Emily Erbelding, MD, MPH, director of the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, who was not part of the study, noted the potential implications of the findings.
 

Proven Safety and Low Cost of Metformin 

“We don’t have therapies for long COVID, and we don’t know how to prevent it in people who have SARS-CoV-2 infections,” Dr. Erbelding noted. “This analysis points to metformin, a drug that millions of people have taken safely for their diabetes or their borderline diabetes. It’s licensed, it’s out there, and it’s inexpensive. The fact that we have data that point to this potentially being a therapy is important. I think that’s the power of this.”

Dr. Erbelding said a strength of the study is the size of the N3C Electronic Health Record Database (with data on nearly 9 million COVID cases) the researchers used to simulate the randomized controlled trial.

“(These results) gives us a reason to think about doing a large randomized controlled study with metformin,” she said. However, there are some limitations, she noted.

“The definition of long COVID may not have been applied exactly the same way across all the patients and you don’t know what led the prescribers to prescribe metformin. There might have been confounders that couldn’t be controlled for or weren’t evident in the way they approached the data.”

This study has “relatively rigorous methodology for an observational study,” Dr. Erbelding said. “It’s novel to try to simulate a randomized controlled trial through a large, observational, electronic record–based cohort. Maybe we should be doing more of this because these bioinformatic systems exist now. And we need to get all the public health use out of them that we can.” 

“The fact that they may be unlocking something new here that needs follow-up in a truly randomized controlled trial is important as well because there are a lot of people out there suffering from long COVID.”

Bramante and Erbelding disclosed no relevant financial relationships. This research was supported in part by the intramural/extramural research program of the National Center for Advancing Translational Science, National Institutes of Health.
 

A version of this article appeared on Medscape.com.

LOS ANGELES — Metformin prescribed within a week of SARS-CoV-2 infection was associated with a 53% reduction in long COVID or death over 6 months in people without diabetes or prediabetes, according to data presented at the Infectious Disease Week (IDWeek) 2024 Annual Meeting.

Long COVID was determined by using the diagnostic code U09.9 or a computable phenotype based on symptoms and conditions. Most participants in this study were infected with the Omicron variant.

Researchers, led by Carolyn Bramante, MD, MPH, an internist, pediatrician, and obesity medicine specialist at the University of Minnesota Medical School in Minneapolis, simulated a randomized controlled trial of metformin vs control using the National COVID Cohort Collaborative (N3C) Electronic Health Record Database.

The intervention was a prescription for metformin within 6 days of SARS-CoV-2 infection. Those in the control group, which was designed to mimic placebo, had a prescription for fluvoxamine, fluticasone, ivermectin, or montelukast (all drugs that have been used off-label for COVID but have shown no effect on acute COVID outcomes in clinical trials). Exclusions included anyone with a previous metformin prescription or a comparator prescription; any indication for chronic metformin use; or a contraindication for metformin.
 

Why Study Metformin for Long COVID?

Dr. Bramante led a previous randomized controlled trial, COVID-OUT, with 1323 people that indicated metformin showed possible benefit for preventing the more severe components of COVID-19. She also led a 2020 review, in which she examined electronic health records from adults with type 2 diabetes or obesity. The researchers found that women taking metformin before they developed COVID-19 were significantly less likely to die after being hospitalized — although men didn’t see the same protective effect. Another randomized trial of 20 people found that 60% of those taking metformin vs 100% of those given a placebo had detectable SARS-CoV-2 viral load by day 4.

Other trials have highlighted the anti-inflammatory and antiviral properties of metformin. The existing evidence coupled with metformin’s well-established safety profile, led Dr. Bramante’s team to conduct the current simulated trial in people without diabetes or prediabetes. Dr. Bramante noted that metformin’s only US Food and Drug Administration–approved indication is for diabetes.

The current study featured a similar racial/ethnic makeup in the metformin and control groups: 16% and 17% were Black and 16% and 13% were Hispanic, respectively. Within 6 months, 4.0% in the metformin group developed long COVID or died compared with 8.5% in the control group (Relative Risk [RR], 0.47; 95% CI, 0.25-0.89). For prescriptions made on days 0-1 relative to infection, the RR was 0.39 (95% CI, 0.12-1.24). When metformin was prescribed on days 0-14, the RR was 0.75 (95% CI, 0.52-1.08).

The reason it’s important to have an active comparator is to control for things that can’t be measured, such as engagement in healthcare and the placebo effect, Dr. Bramante said.

Emily Erbelding, MD, MPH, director of the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, who was not part of the study, noted the potential implications of the findings.
 

Proven Safety and Low Cost of Metformin 

“We don’t have therapies for long COVID, and we don’t know how to prevent it in people who have SARS-CoV-2 infections,” Dr. Erbelding noted. “This analysis points to metformin, a drug that millions of people have taken safely for their diabetes or their borderline diabetes. It’s licensed, it’s out there, and it’s inexpensive. The fact that we have data that point to this potentially being a therapy is important. I think that’s the power of this.”

Dr. Erbelding said a strength of the study is the size of the N3C Electronic Health Record Database (with data on nearly 9 million COVID cases) the researchers used to simulate the randomized controlled trial.

“(These results) gives us a reason to think about doing a large randomized controlled study with metformin,” she said. However, there are some limitations, she noted.

“The definition of long COVID may not have been applied exactly the same way across all the patients and you don’t know what led the prescribers to prescribe metformin. There might have been confounders that couldn’t be controlled for or weren’t evident in the way they approached the data.”

This study has “relatively rigorous methodology for an observational study,” Dr. Erbelding said. “It’s novel to try to simulate a randomized controlled trial through a large, observational, electronic record–based cohort. Maybe we should be doing more of this because these bioinformatic systems exist now. And we need to get all the public health use out of them that we can.” 

“The fact that they may be unlocking something new here that needs follow-up in a truly randomized controlled trial is important as well because there are a lot of people out there suffering from long COVID.”

Bramante and Erbelding disclosed no relevant financial relationships. This research was supported in part by the intramural/extramural research program of the National Center for Advancing Translational Science, National Institutes of Health.
 

A version of this article appeared on Medscape.com.

LOS ANGELES — Metformin prescribed within a week of SARS-CoV-2 infection was associated with a 53% reduction in long COVID or death over 6 months in people without diabetes or prediabetes, according to data presented at the Infectious Disease Week (IDWeek) 2024 Annual Meeting.

Long COVID was determined by using the diagnostic code U09.9 or a computable phenotype based on symptoms and conditions. Most participants in this study were infected with the Omicron variant.

Researchers, led by Carolyn Bramante, MD, MPH, an internist, pediatrician, and obesity medicine specialist at the University of Minnesota Medical School in Minneapolis, simulated a randomized controlled trial of metformin vs control using the National COVID Cohort Collaborative (N3C) Electronic Health Record Database.

The intervention was a prescription for metformin within 6 days of SARS-CoV-2 infection. Those in the control group, which was designed to mimic placebo, had a prescription for fluvoxamine, fluticasone, ivermectin, or montelukast (all drugs that have been used off-label for COVID but have shown no effect on acute COVID outcomes in clinical trials). Exclusions included anyone with a previous metformin prescription or a comparator prescription; any indication for chronic metformin use; or a contraindication for metformin.
 

Why Study Metformin for Long COVID?

Dr. Bramante led a previous randomized controlled trial, COVID-OUT, with 1323 people that indicated metformin showed possible benefit for preventing the more severe components of COVID-19. She also led a 2020 review, in which she examined electronic health records from adults with type 2 diabetes or obesity. The researchers found that women taking metformin before they developed COVID-19 were significantly less likely to die after being hospitalized — although men didn’t see the same protective effect. Another randomized trial of 20 people found that 60% of those taking metformin vs 100% of those given a placebo had detectable SARS-CoV-2 viral load by day 4.

Other trials have highlighted the anti-inflammatory and antiviral properties of metformin. The existing evidence coupled with metformin’s well-established safety profile, led Dr. Bramante’s team to conduct the current simulated trial in people without diabetes or prediabetes. Dr. Bramante noted that metformin’s only US Food and Drug Administration–approved indication is for diabetes.

The current study featured a similar racial/ethnic makeup in the metformin and control groups: 16% and 17% were Black and 16% and 13% were Hispanic, respectively. Within 6 months, 4.0% in the metformin group developed long COVID or died compared with 8.5% in the control group (Relative Risk [RR], 0.47; 95% CI, 0.25-0.89). For prescriptions made on days 0-1 relative to infection, the RR was 0.39 (95% CI, 0.12-1.24). When metformin was prescribed on days 0-14, the RR was 0.75 (95% CI, 0.52-1.08).

The reason it’s important to have an active comparator is to control for things that can’t be measured, such as engagement in healthcare and the placebo effect, Dr. Bramante said.

Emily Erbelding, MD, MPH, director of the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, who was not part of the study, noted the potential implications of the findings.
 

Proven Safety and Low Cost of Metformin 

“We don’t have therapies for long COVID, and we don’t know how to prevent it in people who have SARS-CoV-2 infections,” Dr. Erbelding noted. “This analysis points to metformin, a drug that millions of people have taken safely for their diabetes or their borderline diabetes. It’s licensed, it’s out there, and it’s inexpensive. The fact that we have data that point to this potentially being a therapy is important. I think that’s the power of this.”

Dr. Erbelding said a strength of the study is the size of the N3C Electronic Health Record Database (with data on nearly 9 million COVID cases) the researchers used to simulate the randomized controlled trial.

“(These results) gives us a reason to think about doing a large randomized controlled study with metformin,” she said. However, there are some limitations, she noted.

“The definition of long COVID may not have been applied exactly the same way across all the patients and you don’t know what led the prescribers to prescribe metformin. There might have been confounders that couldn’t be controlled for or weren’t evident in the way they approached the data.”

This study has “relatively rigorous methodology for an observational study,” Dr. Erbelding said. “It’s novel to try to simulate a randomized controlled trial through a large, observational, electronic record–based cohort. Maybe we should be doing more of this because these bioinformatic systems exist now. And we need to get all the public health use out of them that we can.” 

“The fact that they may be unlocking something new here that needs follow-up in a truly randomized controlled trial is important as well because there are a lot of people out there suffering from long COVID.”

Bramante and Erbelding disclosed no relevant financial relationships. This research was supported in part by the intramural/extramural research program of the National Center for Advancing Translational Science, National Institutes of Health.
 

A version of this article appeared on Medscape.com.

A “digital twin” model successfully predicted adverse outcomes in intensive care unit (ICU) patients treated for sepsis. The research used an adaptive approach, updating time-sensitive values such as blood pressure and vitals every 15 minutes. The approach also took into account treatment decisions and has potential as a decision-making and educational tool.

The digital twin could reduce the risk for some interventions, according to Amos Lal, MD, who presented the study at the CHEST Annual Meeting. That’s because the model can predict the outcome. “You don’t actually have to make an intervention to the patient, which might be risky. By doing that, you can actually prevent a lot of harm,” said Dr. Lal, assistant professor of medicine at Mayo Clinic in Rochester, Minnesota.

The researchers used a one-dimensional convolutional neural network (CNN), similar to two-dimensional CNNs that are used to classify images, substituting the color channels used in imaging with 38 time-dependent variables. They applied it to predicting outcomes in the ICU, focusing on data generated within the first 24 hours of admission. The team made the model dynamic by adding time-sensitive data like vitals, laboratory values, and interventions every 15 minutes. That contrasts with existing models that are usually static, relying on values at admission or at 24 hours, for example. It also takes into account time-insensitive data like age, gender, and comorbidities. “Combining these two and coming up with the prediction model in real time can give you a more informed decision about how these patients are going to perform over a period of 2 weeks or 4 weeks of their stay within the ICU. And of course, as we get more and more data within the first 24 hours, the performance of the model improves as well,” said Dr. Lal.

The researchers tested the model by creating a virtual model of the patient and then performing an intervention on the patient and a simulated intervention on the virtual patient. “Then we advance the clock and the patient either improved or deteriorated, and we compared how the digital twin performed, whether the changes were concordant or discordant [between the virtual and real-world patients],” said Dr. Lal.

The model was designed to predict which patients with sepsis would be at greater risk for death or ICU stays longer than 14 days. It was created using data from 28,617 patients with critical care sepsis at a single hospital who were treated between 2011 and 2018, with 70% used as a training set, 20% as a test set, and 10% as a validation set. The researchers conducted an external validation using MIMIC-IV data on 30,903 patients from the Beth Israel Deaconess Medical Center in Boston. The model included 31 time-independent variables and 38 time-dependent variables that were collected every 15 minutes at the Mayo Clinic and every 60 minutes at Beth Israel Deaconess. Surgical patients represented 24% of the Mayo dataset and 58% of the MIMIC-IV dataset, but otherwise the two groups were demographically similar.

At 24 hours, the area under the receiver operating characteristic curve for predicting 14-day mortality was −0.82 in the Mayo validation cohort and −0.78 in the MIMIC validation cohort. The model improved in accuracy over time as more data were accumulated.

The session’s co-moderators, Sandeep Jain, MD, and Casey Cable, MD, praised the work. Dr. Cable, associate professor of pulmonary care medicine at VCU Health, Richmond, Virginia, noted that the model used both surgical patients and medical patients with sepsis, and the two groups can present quite differently. Another variable was the COVID pandemic, where some patients presented at the hospital when they were quite sick. “I’m curious how different starting points would play into it,” she said.

She called for institutions to develop such models on their own rather than relying on companies that might develop software solutions. “I think that this needs to be clinician-led, from the ground up,” said Dr. Cable.

Dr. Jain, an associate professor of pulmonary care medicine at Broward Health, suggested that such models might need to be individualized for each institution, but “my fear is it could become too expensive, so I think a group like CHEST could come together and [create] an open source system to have their researchers jumpstart the research on this,” he said.

Dr. Lal, Dr. Jain, and Dr. Cable reported no relevant financial relationships.

A version of this article appeared on Medscape.com.