Adults with Chronic Conditions

Erik Hulander et al. (2022) · Nutrients

This randomised crossover trial with 42 adults who have rheumatoid arthritis (RA) explored whether a Mediterranean-style, anti-inflammatory diet changes body composition compared with a typical Western diet. RA is a chronic autoimmune condition that inflames the joints, and many patients lose muscle while keeping or gaining fat, a pattern called rheumatoid cachexia (defined here by fat-free mass and fat mass relative to Swiss reference values). Arthritis drugs do not reverse this, so the researchers asked whether food could. At Sahlgrenska University Hospital in Gothenburg, Sweden, outpatients with active RA ate each diet for 10 weeks, separated by a washout of about 4 months, in random order. Weekly food bags delivered to their homes provided 1,100 kcal a day on five days a week, roughly half their intake, and participants aimed to keep their weight steady. The Mediterranean-style diet included berries, walnuts, whole grains, fish three to four times a week, vegetarian meals and a probiotic fruit drink; the control diet had red meat and refined grains. Fat and lean mass were measured fasting by bioimpedance spectroscopy. Across all 42 participants the two diets did not differ in any body composition measure (all p > 0.20), and both periods saw lean mass rise and fat percentage fall. Employment status changed the picture: the 15 participants who were not working lost 1.77 kg of fat mass (p = 0.012) and 1.81 percentage points of body fat (p = 0.008) on the Mediterranean-style diet compared with the control diet, while those who worked showed no difference. Stomach discomfort was reported in 21% of diet periods, mostly during the Mediterranean-style diet. The authors suggest the diet may help address rheumatoid cachexia but note the employment finding may be chance, was not the trial's primary question, and was not powered for. Physical activity was not tracked during the trial, and measurements came from several operators using bioimpedance rather than DXA scanning. The authors call for studies on mechanisms and long-term effects.

Seyed Javad Kia et al. (2020) · BMC complementary medicine and therapies

This double-blinded randomised trial with 57 adults who have oral lichen planus (OLP) explored whether nano-curcumin, a highly absorbable form of the turmeric compound curcumin, could ease the condition as effectively as the steroid prednisolone. OLP is an autoimmune condition in which T cells attack the lining of the mouth, producing white streaks, erosions, burning and pain; steroids are the standard treatment but cause side effects when used long term. Curcumin has anti-inflammatory and antioxidant properties, but ordinary curcumin is poorly absorbed, so the researchers tested a nano-sized version taken by mouth. At an oral medicine department in Iran, 60 patients with erosive or atrophic OLP were randomly assigned to take either one 80 mg nano-curcumin capsule or one 10 mg prednisolone capsule each morning after breakfast for 4 weeks. An examiner who did not know the groups measured lesion size with calipers and a lesion-grading scale and asked patients to rate pain and burning from 0 to 10 at the start and at weeks 1, 2 and 4. Fifty-seven patients were analysed. Both treatments helped. Pain fell from 4.65 to 2.69 with nano-curcumin and from 4.89 to 2.33 with prednisolone (p < 0.001 over time), and lesions shrank from 3.83 to 2.34 versus 3.61 to 1.83 (p < 0.001 over time). The two groups did not differ significantly at any visit (pain p = 0.428, lesion size p = 0.568), although prednisolone was ahead on lesion size at week 4 by a margin that did not reach significance (p = 0.117). Curcumin's pain relief became significant from week 2, prednisolone's from week 1. The trial had no placebo arm, lasted only 4 weeks, and followed no one after treatment, so recurrence could not be measured. The authors suggest nano-curcumin may be an option for people who cannot take corticosteroids and that its dose may matter more than treatment length, and they call for longer studies.

Maria Teresa Guagnano et al. (2021) · Nutrients

This pilot randomised trial with 40 women who have long-standing rheumatoid arthritis (RA) explored whether cutting meat, gluten and lactose from the diet changes pain, quality of life and inflammation. RA is a chronic autoimmune condition in which the immune system attacks the joints, and diet is thought to influence it partly through gut bacteria. Meat, dairy and gluten have been suspected of worsening symptoms, so the researchers compared an exclusion diet, which they call a privative diet, with a balanced diet that kept those foods. At a rheumatology clinic in Chieti, Italy, women aged 31 to 72 on stable RA drugs, all overweight or obese, were randomly assigned to a meat-, gluten- and dairy-free diet with fish as the main animal protein, or to a balanced diet including poultry and dairy. Both diets provided about 1,500 kcal a day to lose weight. After 3 months, 28 completed the study. Pain was rated on a 100 mm visual scale, disease activity with the DAS 28, quality of life with the SF-36 and the Health Assessment Questionnaire, and blood tests tracked inflammation. On the exclusion diet, median pain dropped from 50 to 40 (p = 0.003) and the SF-36 health score rose from 42 to 59 (p < 0.001), whereas the balanced diet showed no significant change. Blood pressure fell (systolic p = 0.003, diastolic p = 0.025), and white cells, neutrophils and the inflammation marker hs-CRP decreased only on this diet. Both diets lowered weight, waist size, fat mass and leptin, but neither changed the DAS 28 joint-activity score or the cytokines measured. Nine people left because the diets were hard to keep and three because of bloating or nausea; none left because of a flare. The authors describe the study as a pilot and caution that the small sample, high dropout, all-female overweight group and lack of a mid-study check limit what can be concluded. They suggest the exclusion diet may carry benefits beyond weight loss alone, and call for larger studies.

Ali Tabatabaeyan et al. (2025) · Scientific reports

This triple-blind randomised trial with 59 adults who have rheumatoid arthritis (RA) explored whether inulin, a fermentable plant fibre found in foods such as chicory, garlic and onions, can calm the inflammation and joint symptoms of the disease. RA is an autoimmune condition in which the immune system attacks the joints, and the researchers noted that long-term steroids and anti-inflammatory drugs carry real side effects. Because gut bacteria are altered in people with RA, they asked whether a prebiotic that feeds beneficial bacteria could help as an add-on. Researchers in Isfahan, Iran, enrolled 60 patients with active RA (59 were analysed). For 8 weeks, one group took a 10 g sachet of inulin with a main meal each day, and the other took identical-looking maltodextrin sachets, all alongside their usual medicines. Staff measured blood inflammation markers (CRP and ESR), counted tender and swollen joints out of 28, rated pain and morning stiffness on 0 to 100 scales, tested grip strength, and scored disease activity (DAS-28) and everyday function with the Health Assessment Questionnaire. Inflammation fell more with inulin: CRP dropped by 11.72 mg/L while it rose slightly with placebo (p = 0.02). Tender joints fell by 8.1 versus 2.9 (p = 0.002), swollen joints by 3.5 versus 1.8 (p = 0.04), and disease activity by 1.57 points versus 0.67 (p = 0.02). Daily function and morning stiffness improved (both p = 0.02) and grip strength rose by about 27 units versus 4 (p = 0.02). ESR improved within the inulin group, but the difference from placebo was not significant after adjustment (p = 0.13), and pain scores fell in both groups without a significant gap (p = 0.11). No side effects were reported. The authors treat the findings as promising but note they did not measure gut bacteria or gut-lining permeability, so the mechanism remains unconfirmed. The trial lasted only 8 weeks, tested one inulin dose, and did not assess how much inulin participants already ate. The authors call for larger studies with different doses and with cytokine, microbiome and permeability measures.

Fatemeh Bourbour et al. (2026) · Endocrinology, diabetes & metabolism

This double-blind randomised trial with 57 adults who have Hashimoto's thyroiditis explored whether curcumin, the yellow polyphenol in turmeric (Curcuma longa), adds benefit to an anti-inflammatory diet. Hashimoto's thyroiditis is an autoimmune condition in which the immune system attacks the thyroid gland, shown in blood tests by anti-thyroid peroxidase antibodies (anti-TPO) and treated in many patients with lifelong levothyroxine. Because many people with the condition carry extra weight and chronic inflammation, the researchers asked whether an anti-inflammatory eating pattern plus curcumin could shift thyroid markers, body measurements and cholesterol. Researchers in Tehran, Iran, enrolled adults aged 20 to 70 with a confirmed diagnosis. Every participant ate the same structured anti-inflammatory diet of whole grains, olive oil, berries, nuts, legumes, vegetables and fatty fish. For 12 weeks, half also took 1,320 mg of curcumin daily as three capsules with meals, and half took look-alike rice-flour placebo capsules. Blood tests measured anti-TPO, thyroid-stimulating hormone (TSH), T3, T4 and lipids, and tape measures tracked waist and hips. Anti-TPO antibodies fell significantly more with curcumin than with placebo (p = 0.006), where antibodies rose numerically (within-group change not significant), which points to a possible effect on thyroid autoimmunity. Within the curcumin group waist circumference dropped 4.2 cm (p = 0.042) and TSH dropped 2.38 mIU/L (p = 0.014), but neither difference was significant against placebo after adjustment, so these changes may come partly from the diet. T3 fell in both groups, which supports that interpretation. Cholesterol, triglycerides and T4 did not differ between groups, and HDL-C moved only toward significance (p = 0.053). The curcumin group's gains held when men were excluded (anti-TPO p = 0.010). The authors call the results preliminary and note the small sample, the short 12-week window, and reliance on self-reported food recalls. Because both groups changed their diets, the trial cannot fully separate curcumin from the diet itself. Lower antibody levels may also fluctuate over time and do not prove long-term disease change. Larger, longer studies with designs that separate diet from supplement are needed before any treatment role for curcumin in Hashimoto's thyroiditis can be judged.

Sandra Utz et al. (2025) · Biomedicines

This prospective observational study followed 101 adults with long-standing fibromyalgia syndrome (FMS) through a two-week integrative inpatient stay in Bamberg, Germany, with no control group. FMS is a chronic condition marked by widespread pain, fatigue, sleep problems, anxiety and depression, and the authors describe it as the third most common rheumatic disease. The program was built on classical European naturopathy: water-based therapies and heat, exercise, plant-based nutrition or medical fasting, herbal remedies and mind-body practices such as relaxation. The question was whether such a combined approach would ease symptoms at discharge and six months later. Of 134 patients who joined (127 women, ages 22 to 80), 101 returned questionnaires on admission, at discharge and after six months. During the stay they took part in meditative movement, physical therapy, hydrotherapy, lectures and cooking classes, and some had whole-body heat sessions or a 5-day fast on under 300 kcal a day. Pain, fatigue, anxiety, depression, stress and quality of life were measured with standard questionnaires (such as the HADS for anxiety and depression and the MFI-20 for fatigue) and compared over time with repeated-measures statistics. Overall pain intensity dropped from 71.5 to 63.0 on a 0-100 scale at discharge (a moderate effect, dz = 0.62) and was still lower at six months (64.4). Current pain fell sharply during the stay (6.56 to 4.37 out of 10) but crept back to 5.96 at six months. Fatigue improved from 71.1 to 63.3 and then partly returned (68.0). Anxiety and depression scores each fell by roughly 2.5 points at discharge and were still lower than baseline at six months. Stress and feelings of helplessness improved mainly after discharge, and mental quality of life rose between discharge and follow-up. Patients who fasted kept their pain gains at six months (p = 0.006), whereas non-fasters did not (p = 0.062), although this difference was borderline (interaction p = 0.050) and not randomised. The results come from an uncontrolled, single-centre sample in which a quarter of the participants did not complete the six-month questionnaire, so the changes cannot be attributed to the program alone. More than half the patients reported obstacles to continuing the methods at home, such as lack of time and exhaustion. The authors call for randomised trials with long-term follow-up and propose a follow-up day-clinic programme to help consolidate the learned self-management skills and everyday routines.

Suhas Balakrishna et al. (2026) · Journal of lifestyle medicine

This systematic review and meta-analysis pooled 33 controlled studies with 2,651 adults to ask whether pelotherapy, the application of mineral-rich mud, peat or clay as packs, wraps or full baths, eases musculoskeletal disorders. These include osteoarthritis (joint cartilage wear), rheumatoid arthritis (an autoimmune joint disease), fibromyalgia (widespread pain) and chronic low back pain. Pelotherapy is a traditional naturopathic practice used in spas, balneological centres and clinics in at least 40 countries, and the authors set out to test it against modern standards: pre-registration, risk-of-bias rating and GRADE certainty scoring. The team searched eight databases and trial registers up to April 2026. Included trials enrolled adults with a confirmed musculoskeletal diagnosis, applied mud as the main treatment for 10 to 21 sessions over two to three weeks, and compared it with sham treatment, usual care, waiting lists or nothing. Pain was mostly rated on a 0-100 mm visual analogue scale or a 0-10 numeric scale, and function on questionnaires such as the WOMAC. Two reviewers worked independently and combined results with random-effects statistics. Pain dropped clearly after mud treatment (standardised mean difference -0.74, a moderate-to-large effect, roughly 18.5 mm on the 100 mm scale and above the 15 mm threshold for a meaningful change). The effect was still present at 3 months (-0.61) and at 6 months (-0.49, low certainty). Physical function (-0.69) and quality of life (+0.58 on SF-36) improved as well, with osteoarthritis trials using the WOMAC at -0.82 and rheumatoid arthritis trials using the HAQ at -0.58. Morning stiffness (-0.52) and C-reactive protein, a blood marker of inflammation (-0.44), fell modestly, while the erythrocyte sedimentation rate did not change significantly. Knee osteoarthritis showed the biggest benefit (-0.86), and Dead Sea mud the strongest peloid effect (-0.84). Serious adverse events were no more common than in controls (relative risk 0.98); about 6.5% of mud recipients had mild, short-lived skin redness, largely from heat. The authors note several limits: participants cannot be blinded to mud, peloid type, temperature and protocol varied widely, results differed between trials (I2 = 62% for pain), a correction for possible publication bias lowered the pain estimate to -0.66, most trials came from European spa settings, and safety beyond 12 months is unknown. They call for larger blinded trials with standardised peloids and longer follow-up, and frame pelotherapy as an adjunct to, not a replacement for, drug and physiotherapy care.

María Magdalena Vaccarezza et al. (2026) · PloS one

This systematic review with meta-analysis pooled 17 randomized controlled trials of ketogenic diet therapies (KDTs) for drug-resistant epilepsy, meaning epilepsy that keeps causing seizures after two or three appropriately chosen antiseizure medications have failed. About 30% of people with epilepsy fall into this group. KDTs are high-fat, low-carbohydrate, adequate-protein diets that shift the body toward burning fat and producing ketone bodies, which are fat-derived fuel molecules that may calm brain activity and support neuron energy metabolism. Several forms exist: the classical ketogenic diet, the medium-chain triglyceride (MCT) diet, the modified Atkins diet with unrestricted protein, and the low glycemic index treatment. A 2020 Cochrane review left the evidence uncertain, and this update added newer trials. Eleven trials enrolled children and six enrolled adolescents and adults, with follow-up of up to 24 months. In nearly all trials, a ketogenic diet was compared with usual care, most often an added medication. The authors searched four databases in February 2024 and again in June 2025, screened 1,193 unique records in duplicate, and pooled results as relative risks (RR) using random-effects models. Study bias was rated with the Cochrane RoB 2 tool, and confidence in each result was graded from high to very low using GRADE. In children, a 50% or greater drop in seizures was far more likely with KDT (RR 4.06, meaning roughly four times the likelihood; 49.7% versus 12.2%, or 37 more children per 100). A 90% or greater drop was borderline (RR 1.74, 95% CI 1.00 to 3.03). Adverse events were similar to usual care (RR 1.03), and dropout was not significantly different (RR 1.64, 95% CI 0.88 to 3.07). In adolescents and adults, 50% or greater seizure reduction was also more likely (RR 7.73, which translates to 16 more per 100), with moderate certainty. Near-complete seizure control (RR 13.00, with a very wide interval of 0.74 to 226.98), side effects and dropout could not be judged because of very low certainty. Reported side effects were mainly gastrointestinal and resolved when the diet stopped. Quality of life findings were mixed: one infant trial found small differences favoring medication in temperament and peer relationships, while parents in another trial reported improved alertness and sleep. The authors interpret the findings as a clinically meaningful benefit for moderate seizure reduction, strongest in children. Certainty was limited by the impossibility of blinding a diet, small event counts and high heterogeneity for some outcomes. Most trials came from high-income countries, which may limit generalizability, and publication bias could not be excluded. No trial reported hospitalizations, status epilepticus or survival. The authors call for better evidence on safety, adherence, cognition and quality of life.

Sedighe Esmaeilzadeh et al. (2025) · Reproductive biology and endocrinology : RB&E

This systematic review and meta-analysis combined 17 randomized controlled trials (15 pooled, 996 women) to ask whether antioxidant supplements ease the pain of endometriosis, a chronic inflammatory condition in which tissue like the uterine lining grows outside the uterus. Oxidative stress (damage from unstable oxygen molecules called free radicals) is thought to feed the inflammation and pain, so antioxidants such as melatonin, vitamins C, D, and E, curcumin (from turmeric), garlic, silymarin (from milk thistle), and resveratrol have been tested. Results across individual trials have been inconsistent, and earlier reviews were narrower, so this one searched seven sources through January 2025 and graded the certainty of the evidence. Included trials enrolled women aged 18 to 49 with confirmed endometriosis, mostly in Iran, plus Egypt, Brazil, the United States, China, and Sweden. Women took an oral antioxidant or a comparator (placebo, standard care, or nothing) for 8 to 24 weeks. The review pooled three pain outcomes using standardized mean differences (a way to combine different pain scales into one measure): painful periods (dysmenorrhea), painful intercourse (dyspareunia), and chronic pelvic pain. Study quality was graded with Cochrane RoB 2, and evidence certainty with GRADE. For painful periods, 12 trials (706 women) showed lower pain with antioxidants (SMD -1.26; 95% CI -2.19 to -0.32, equal to about 3 points on a 0 to 10 scale), but results varied enormously between trials (I² = 90.1%), so the evidence was rated low certainty. Melatonin stood out (SMD -1.89; 95% CI -2.48 to -1.31), while vitamin D, vitamins C plus E, omega-3, resveratrol, and curcumin did not reach significance. Painful intercourse showed no significant effect (SMD -1.01; 95% CI -2.27 to 0.24). Chronic pelvic pain fell in the pooled analysis (SMD -1.07; 95% CI -1.71 to -0.42), but the evidence was very low certainty and the effect vanished when trials with conflicts of interest were removed. Single trials of garlic powder and silymarin reported lower pain, whereas curcumin did not. Only 7 of 17 trials had low risk of bias. The authors say the findings do not support routine antioxidant use for endometriosis pain, and describe melatonin as the most promising candidate for painful periods, pending confirmation. Limitations include very high heterogeneity, small trials, different antioxidants and doses, bigger effects in weaker studies, and little control of baseline vitamin levels or diet. The paper did not report adverse events. The garlic and silymarin findings come from single trials, and publication-bias testing found no small-study effects for chronic pelvic pain. The authors call for larger, standardized trials.

Sophia Tsokkou et al. (2026) · International journal of molecular sciences

This systematic review pulled together seven randomized controlled trials to ask whether vitamin D, vitamin C, and vitamin E supplements affect endometriosis, a long-term inflammatory condition in which tissue like the uterine lining grows outside the uterus and affects roughly 1 in 10 women of reproductive age. Common symptoms include painful periods (dysmenorrhea), chronic pelvic pain, pain during intercourse (dyspareunia), and difficulty conceiving. The vitamins were chosen because vitamin D helps regulate immune signaling, while vitamins C and E act as antioxidants that neutralize reactive oxygen species (unstable molecules that damage cells and add to inflammation). Both processes are central to how endometriosis develops and causes pain. The authors registered their protocol in PROSPERO and searched PubMed, Scopus, and ScienceDirect, screening 5,639 records down to seven eligible trials. Two reviewers screened independently, and trial quality was graded with the Jadad scale and the Cochrane RoB 2 tool. The trials varied widely: vitamin D doses ranged from 2000 IU daily to 50,000 IU weekly, vitamin C and E doses from 343 mg and 84 mg to 1000 mg and 800 IU daily, and treatment lasted from about 8 weeks to 6 months. Because of this variation, results were described narratively rather than pooled. High-dose vitamin D (50,000 IU every two weeks) cut pelvic pain scores by 1.12 points (95% CI -2.1 to -0.09; p = 0.03) and lowered hs-CRP, an inflammation marker, by 0.64 mg/L. A weekly 50,000 IU regimen lowered active β-catenin (a signaling protein linked to lesion invasion) in endometrial tissue. Lower daily doses did not clearly beat placebo, since both groups improved by similar amounts. Vitamin C plus E for eight weeks reduced oxidative stress markers, and one trial reported pain drops of 43% for daily pelvic pain, 37% for painful periods, and 24% for painful intercourse. Pregnancy rates did not rise in the trial that measured them. Side effects were generally minor, mostly occasional digestive upset. Three trials were rated low risk of bias and four had some concerns. The authors describe vitamins as a possible well-tolerated adjunct for pain and oxidative stress, though not for fertility. The evidence base is small, with only seven trials, English-language inclusion only, very different dosing across studies, and no trial using a publicly available preregistered protocol. Few trials checked participants' baseline vitamin levels, so it remains unclear whether any benefit depends on deficiency. The authors call for larger multicenter trials with standardized doses, longer follow-up, and fertility and lesion outcomes.

Angelika Bogusz et al. (2026) · Nutrients

This randomized controlled trial of 46 women with endometriosis explored whether a fish-derived lipid supplement (a mixture of marine omega-3 fats such as EPA and DHA, plus compounds called squalene and alkylglycerols) adds anything to a Healthy Eating Plate diet. Endometriosis is a long-term, estrogen-dependent condition in which tissue similar to the uterine lining grows outside the uterus. Researchers increasingly describe it as an inflammatory condition, in which signaling proteins called cytokines (messengers that coordinate immune cells) help drive pelvic pain. Omega-3 fats are known to influence these immune pathways, but evidence in endometriosis has been limited, so the team treated the work as exploratory. Women aged 22 to 48 with confirmed endometriosis were randomly assigned to one of two groups for 12 weeks. Both groups followed an individualized Healthy Eating Plate diet with meal plans from a dietitian. One group also took the fish-derived lipid product, dosed by body weight (0.5 mL per kilogram daily). Blood and stool samples were collected before and after to measure five cytokines and fecal calprotectin (a marker of gut inflammation). Pain was rated on a 0 to 10 visual analog scale, and quality of life was scored with the 30-item Endometriosis Health Profile. The clearest signal was in IL-10, a cytokine that restrains immune activation: levels rose in the supplement group and the adjusted difference between groups was significant (about 5-fold higher; 95% CI 1.32 to 19.48; p = 0.019). Other cytokines gave mixed results, with IL-1β, TNF-α, and IL-6 landing right at the edge of significance (p = 0.050 to 0.057) and fecal calprotectin unchanged. Average pain scores dropped within the supplement group (5.0 to 4.3; p = 0.011), yet the difference between groups was not significant. A pain drop of at least 1 point was more common with the supplement (73.9% versus 34.8%; adjusted risk ratio 2.11, meaning roughly twice the likelihood). Quality-of-life scores did not differ between groups, and the paper did not report safety outcomes. The authors describe the pain and IL-10 findings as hints worth testing rather than proof of benefit, since most outcomes showed no consistent advantage over diet alone. The study was small, lasted only 12 weeks, had no placebo, relied on self-reported food records, and ran many secondary analyses without statistical correction. The supplement was also a complex mixture, so the effects cannot be pinned on omega-3 fats alone. The authors call for larger, longer trials that measure fatty acid levels in blood and examine immune cells directly.

Philipp Klemm et al. (2026) · European journal of physical and rehabilitation medicine

This randomized, double-blind, sham-controlled trial of 38 analyzed adults in Bad Nauheim, Germany, explored whether mineral water baths for the hands ease pain from hand osteoarthritis (HOA). HOA is wear-and-tear damage in the finger and thumb joints that causes pain, stiffness and reduced grip. Balneotherapy, the treatment of conditions with natural mineral waters, is well known for knee osteoarthritis, but evidence for hand osteoarthritis was thin. The tested water was natural thermal brine, a salty spring water (sodium chloride and hydrogen carbonate, rich in carbon dioxide), used at its natural 25 degrees C. Participants averaged 72 years, 86% were women, and all had painful, X-ray-confirmed HOA. One group soaked both hands in thermal brine and the other in ordinary tap water at the same temperature, in identical covered bowls so neither participants nor staff knew which was which. Each bath lasted 15 minutes, with six baths over three weeks. Pain was rated on a 100 mm visual analog scale (VAS, 0 meaning no pain), alongside hand function questionnaires, grip strength, skin blood flow and a blood marker (VEGF). After six baths, pain averaged 7 mm with thermal brine versus 33 mm with tap water, a 26.4 mm gap (P < 0.0001) larger than the 20 mm threshold for a clinically meaningful change. The gap was already present after the first bath (5.3 mm, P = 0.0017) and was still about 26 to 27 mm at 4 and 12 weeks. Pain on the hand index (AUSCAN pain subscore) was also lower (5.86 points, P < 0.0001), though that difference was gone at follow-up. Stiffness, function, grip strength, skin blood flow and VEGF did not differ between groups. Satisfaction favored thermal brine: 72% (13 of 18) rated pain relief good or very good versus 32% (6 of 19) with tap water. No adverse events occurred. The trial was small, ran at one center during the COVID-19 pandemic, and lost 12 of 50 participants, so only 38 were analyzed. Tap water may also have effects of its own. Because blood flow and VEGF showed no change, how the baths relieve pain remains unexplained; the authors note that 25 degrees C is below the 32 to 35 degrees C range where carbon dioxide baths are expected to widen blood vessels. They propose thermal brine baths as a non-pharmacological adjunct and call for larger multicenter trials with longer treatment and optimized temperatures.

Tatiana Leite Müller et al. (2026) · International journal of biometeorology

This systematic review of nine studies with 465 adults looked at climatotherapy, the therapeutic use of climate and natural settings, for musculoskeletal and rheumatologic disorders such as osteoarthritis, rheumatoid arthritis, fibromyalgia and ankylosing spondylitis. The settings were the Dead Sea (very salty water, low humidity, distinctive solar radiation and air pressure about 5% above sea level) and coastal sites using thalassotherapy, which means bathing and exercising in seawater, sometimes with marine mud, sun exposure and sea air. Because these programs vary widely, the authors wanted to gather what trials say about pain, physical function, quality of life and safety. The reviewers searched three databases through September 2025 and included eight randomized trials and one non-randomized study from 1995 to 2011, mostly in Israel. Participants were aged 18 to 65 and stayed at a spa or coast for 10 days up to 12 weeks. Comparison groups used freshwater pools, usual care, pool exercise or the same program in Norway. Pain was usually rated on a 0 to 100 visual analog scale, and quality of life was measured with questionnaires such as the SF-36. Most studies reported short-term improvements in pain, stiffness, function and quality of life, mainly within groups. Only two studies could be pooled for pain, giving an inconclusive overall result (SMD -0.47, 95% CI -5.47 to 4.53; an interval too wide to show benefit or no benefit). Split by condition, osteoarthritis showed a large effect (SMD -1.01, meaning pain fell by roughly one standard deviation more than with comparison) while fibromyalgia showed a small non-significant one (SMD -0.18, p = 0.158). In fibromyalgia, single-study estimates showed fewer tender points (SMD -0.50, p = 0.0047) and better physical quality of life (SF-36 physical score 0.36, p = 0.0391), but mood scores (p = 0.5968) and overall fibromyalgia impact (p = 0.0612) did not change significantly. No serious adverse events were reported, though only one study recorded adverse events explicitly. The evidence has important limits: trials were small and published between 1995 and 2011, participants and therapists could not be blinded, safety was inconsistently recorded, and several programs combined many components, so the effect of the climate itself is hard to separate. Only one trial analyzed all participants as randomized, and the pooled estimate rests on two studies. Certainty was judged low. The authors suggest climatotherapy may be a complementary option, particularly for osteoarthritis, and call for multicenter randomized trials with standard outcome sets and systematic safety reporting.

Shujie Wang et al. (2022) · Gut microbes

This randomized trial with 365 adults who had newly diagnosed type 2 diabetes explored whether combining berberine, a plant compound extracted from the Chinese herb Coptis chinensis (Huanglian), with a probiotic mix lowers postprandial lipidemia, the rise in blood fats and cholesterol after a meal. The authors note that cholesterol measured after eating is also an important heart-disease risk marker, that after-meal blood fats are common in diabetes, and that very few treatments target them. Berberine was already known to lower fasting cholesterol, but whether it helps after meals was unknown. Probiotics are live bacteria, and the nine-strain mix here included Bifidobacterium breve. This analysis came from a 12-week, double-blind, placebo-controlled trial at 20 centers in China, with 365 participants split into four groups: placebo (91), probiotics alone (92), berberine alone (84), and both (98). Participants were drug-naive adults aged 20 to 70, averaging about 52. They took berberine pills twice daily before meals, and probiotic powder once daily at bedtime. After a standard 100 g carbohydrate meal, blood drawn 120 minutes later measured cholesterol and triglycerides, and stool samples tracked gut bacteria. Only the combination significantly cut after-meal total cholesterol (24.29 mg/dL drop versus 8.66 with placebo, adjusted P = .001, a gap that chance is very unlikely to explain) and after-meal LDL cholesterol (16.54 versus 7.35 mg/dL, P = .043). Berberine alone and probiotics alone did not differ significantly from placebo for these two measures. After-meal triglycerides fell with berberine alone (P = .037) and the combination (P = .035) equally, so probiotics added nothing there, and HDL (good) cholesterol did not differ between groups. Thirty-one blood lipid molecules changed only with the combination, versus eight with berberine and two with probiotics. In stool, B. breve rose with the combination, and higher levels went with lower after-meal cholesterol. In lab dishes, berberine slowed B. breve growth but switched on its fatty-acid-uptake genes (called fadD). Adverse events were not reported in this paper. The authors conclude that berberine plus probiotics acts synergistically on after-meal blood fats, with the probiotic replacing Bifidobacteria that berberine suppresses and berberine activating the bacteria's fat-handling genes. They state the limits plainly: only 13 weeks and no heart-attack or stroke outcomes, testing only after a carbohydrate meal, and unknown applicability to people already on statins. The authors propose that probiotics containing Bifidobacterium may be needed when berberine is used as a lipid-lowering agent. They suggest studying fatty meals and other gut-related pathways in future work.

S B Erickson et al. (2011) · Phytomedicine : international journal of phytotherapy and phytopharmacology

This small randomized trial with 10 people explored whether Cystone, an Ayurvedic herbal tablet sold for kidney stones, changes the urine chemistry that drives stone formation or reduces the amount of stone in the kidneys. Kidney stones are painful and often recur, and the available prevention options (diet changes and medicines such as thiazides, potassium citrate and allopurinol) have drawbacks. Cystone is a blend of seven plants plus purified Shilajeet and a mineral preparation (bhasma), traditionally used for urinary problems, but the authors say earlier studies of it were small and poorly controlled. Ten adults from the Mayo Stone Clinic who repeatedly formed calcium oxalate stones took two Cystone tablets twice a day, or matching placebo, for six weeks each in a crossover design, switching after a one-week break. All then took Cystone openly for another 48 weeks. Urine collected over 24 hours measured how saturated it was with stone-forming minerals. CT scans at the start and after a year, scored with the same method used for heart-artery calcium, measured stone volume, and a radiologist reviewed them without knowing the timing. Cystone did not change urinary measurements in the short term (6 weeks) or the long term (52 weeks). Average stone burden per kidney actually rose from 93 to 114 cubic millimetres (P = 0.07) and from 108 to 136 on the Agatston scale (P = 0.10), neither statistically significant. The radiologist counted 8 kidneys with more stone, 8 unchanged and 2 with less, and four kidneys passed stones spontaneously. No participant described side effects they attributed to Cystone. The authors conclude the trial does not support Cystone for preventing calcium oxalate stones, while noting the sample was tiny, participants had stones that standard treatment had not controlled, and some factors that inhibit stone formation were not measured. They say a longer study with more patients would be needed to look at stone passage or other stone types.

Dan Wang et al. (2026) · JAMA network open

This phase 3 randomized trial of 606 adults in China explored whether Guang Jing, a capsule made from the total flavonoids (plant pigment compounds with antioxidant activity) of the traditional Chinese herb Desmodium styracifolium, helps ureteral stones pass out of the body. A ureteral stone is a mineral deposit lodged in the tube that carries urine from the kidney to the bladder. Treatment that encourages passage is called medical expulsive therapy, and the authors note that alpha-blocker drugs, the guideline option, have shown mixed results in large trials. No oral medicine is currently approved for urolithiasis, and Guang Jing is already approved in China for ureteral stones. Participants were adults aged 18 to 70 with a newly diagnosed ureteral stone of 5 to 10 mm and a traditional Chinese medicine pattern called damp-heat accumulation (urethral burning, lower back pain or blood in the urine). At 34 hospitals, three of every four received 3 capsules (0.6 g) of Guang Jing three times daily for 28 days, and the rest received identical placebo capsules. Neither participants nor investigators knew who received which. Passage was confirmed by CT scan on day 28, read by blinded investigators. By day 28, 44.6% of the Guang Jing group (204 of 457) had passed their stone versus 33.8% of the placebo group (50 of 148). That is a 10.9 percentage point difference (relative risk 1.32, so passage was about one-third more likely; P = .03). At day 14 the groups did not differ significantly (29.1% vs 22.3%; P = .14), and stone movement distance was almost identical (29.5 vs 29.7 mm). Among those with 0.6 to 1.0 cm stones, passage was 37.2% vs 24.4% (a larger gap in the bigger stones), and 66.2% of Guang Jing participants with distal stones, the lower part of the ureter near the bladder, passed them. Adverse events were similar (19.3% vs 18.2%, meaning side effects were about as common with the capsule as with placebo), with no medication-related serious events. The authors describe the absolute benefit as modest, since 55.4% of the Guang Jing group did not pass a stone by day 28. The trial enrolled a fairly uniform group, mostly from southern China, and the subgroup results were exploratory. The authors state that this homogeneous population limits how far the findings generalize, and that CT slice thickness may have missed small differences in stone movement. They plan further trials in Europe and North America and call for studies to identify who benefits most and to establish how the extract works in humans.

Manobala V R et al. (2026) · Bioinformation

This single-arm pilot trial with 30 participants explored whether a 90-day Siddhar yogam programme could reduce the symptom burden of varicose veins, which are dilated, twisted veins of 3 mm or more in the legs. Siddhar yogam belongs to the Siddha system of medicine, a South Indian tradition that explains illness through three humors, Vatham (air), Pitham (fire) and Kabham (water), and counts Siddhar yogam among its Kayakarpam (rejuvenation science) methods. The practice combines yoga postures, controlled breathing and meditation. The authors note that no standardized, non-invasive therapy exists for varicose veins, a condition they say affects about 5% of people in India. The 30 patients (10 men and 20 women, aged 30 to 55) were recruited at the National Institute of Siddha's Ayothidoss Pandithar Hospital. All practised the same 35-minute routine for 90 days: a few minutes of relaxation, 21 minutes of postures such as raised-leg pose, half plough, inverted pose and cycling pose, and 5 minutes of Thirumoolar breathing practice. Symptoms and quality of life were scored with the Aberdeen Varicose Vein Questionnaire (AVVQ), where a lower score means less impact, before and after the programme. There was no comparison group. Average AVVQ scores dropped from 16.2 to 12.0 (a fall of 4.2 points; reported as significant at p < 0.05 by Wilcoxon signed rank test). Most participants (over 85%) reported long periods of standing, and the Siddha assessments, which grade humors, body constituents and an eight-fold examination, showed derangement mainly in Vatham and Pitham before treatment and a reduction in these findings afterwards, though the paper gives no figures for that change. The authors suggest the postures lower pressure in the leg veins and help blood return to the heart by working the calf muscles, but they did not measure this. Because the trial had one arm, no follow-up and only one outcome measure, and excluded severe cases, the authors say the efficacy of the regimen cannot be established. They recommend larger randomized trials.

Zheping Quan et al. (2026) · Frontiers in immunology

This systematic review and network meta-analysis of 16 randomized controlled trials (943 participants) explored which forms of exercise are linked to better outcomes in irritable bowel syndrome (IBS). IBS is a functional gut disorder, meaning the bowel looks normal on testing but causes recurring abdominal pain and altered bowel habits, and it often occurs alongside anxiety and depression. The authors framed the gut and brain as communicating through the brain-gut axis, with the immune system, intestinal barrier and gut microbiota also involved. A network meta-analysis is a statistical method that compares several treatments at once, even when some were never tested head to head, and ranks them using SUCRA, a percentage score where higher values mean a greater chance of being best. The included trials, published between 2004 and 2025, tested yoga, Pilates, Baduanjin (a traditional Chinese gentle movement routine), running and moderate-intensity aerobic exercise for 4 to 24 weeks. Participants were adults with constipation-predominant, diarrhea-predominant or mixed IBS, mostly in Asia, Europe and North America. Comparison groups received conventional treatment, dietary advice, probiotics or education. Researchers measured symptom severity with the IBS Symptom Severity Scale, quality of life with the IBS Quality of Life scale, and mood with anxiety and depression scores. Exercise improved several outcomes. Depression scores fell overall (SMD -0.56, a moderate-sized benefit), though heterogeneity was very high (I2 = 95%, meaning results varied widely between trials), and yoga alone was not significant. Anxiety dropped with yoga (SMD -1.82), Pilates (SMD -3.84) and aerobic exercise (SMD -6.31). Symptom severity improved with running (MD -72.68 points), Pilates (-71.32), aerobic exercise (-46.50) and Baduanjin (-16.94), with running ranked first (SUCRA 90.3%). Quality of life ranked Baduanjin first (99.9%) and yoga second (80.1%), while aerobic exercise showed no significant difference from conventional treatment. In subscale analyses, Pilates cut pain severity (MD -17.90) and aerobic exercise improved dysphoria, activity interference, body image, health worries and relationships, while yoga helped only bowel satisfaction and interference with life. Rankings differed by outcome, which the authors describe as functional specificity. The authors describe exercise as a safe, low-cost non-pharmacological option that may hold value in comprehensive IBS management, but the evidence carries clear limits. Heterogeneity was high, many trials did not clearly blind participants or assessors, and some effect sizes were unusually large, which the authors attribute to small samples. Study counts were reported inconsistently across sections, and safety was not analysed. Too few trials came from outside East Asia to judge differences across ethnic groups. The immune mechanisms remain unproven, and the authors call for trials that add immune markers, biomarkers and gut microbiome measures.

Qiaoyun Liu et al. (2026) · Frontiers in endocrinology

This systematic review and meta-analysis of 56 randomized controlled trials (4,605 participants) examined whether herbal formulae containing Smilax glabra, known in Chinese as Tufuling, help people with acute gout. Gout is a painful inflammatory arthritis caused by uric acid crystals depositing in joints. In traditional Chinese medicine, many acute flares are classed as dampness-heat accumulation, a pattern defined by red, swollen, hot, painful joints and dark urine, and treated by clearing heat and resolving dampness. The authors also used computer-based network pharmacology to predict which plant compounds and proteins might explain the effects. All 56 trials took place in China and enrolled adults, with ages ranging from 18 to 80 years, diagnosed with gout and the dampness-heat pattern. Participants received a Tufuling-containing herbal formula, sometimes with external applications or acupuncture, either alone or added to standard drugs such as NSAIDs, colchicine, allopurinol or benzbromarone, for 14 days or less. Comparison groups received the standard drugs alone. Pain was measured on a 10-point visual analog scale, and blood uric acid, C-reactive protein and erythrocyte sedimentation rate (inflammation markers) were also tracked. Herbal formulae added to standard drugs reduced pain by 0.94 points on the 10-point scale (a modest but statistically significant gain across 17 trials), raised the chance of a treatment response by 15% (risk ratio 1.15), and lowered blood uric acid by 57 micromoles per litre. Herbal formulae alone did not beat standard drugs for pain (a 0.33-point difference, not significant) but did lower uric acid. Adverse events, mostly stomach and intestinal complaints, totalled 73 in herbal groups versus 161 in comparison groups, all mild to moderate. Certainty of evidence was rated low to moderate, and heterogeneity was very high for pain (I² = 93.2%). Network analysis predicted 49 gout-related protein targets for Tufuling, centred on PTGS2, IL1B, PPARG and TP53 (proteins governing inflammation and metabolism), and docking suggested diosgenin binds PTGS2 strongly (-11.6 kcal/mol). The authors suggest Tufuling-based formulae may be a useful adjunct in acute gout, but the evidence carries clear limits. Most trials lacked blinding and trial registration, all came from China, treatment lasted at most 14 days, a quarter of trials did not report adverse events, and only four reported follow-up. The findings do not extend to chronic gout or other traditional patterns, and the network predictions are untested hypotheses. The authors call for larger, rigorous trials with longer follow-up and laboratory validation of the predicted targets.

Massimo Chiaretti et al. (2020) · Scientific reports

This randomized clinical trial with 199 adults at an Italian university proctology clinic compared two plant-based venotonic products, called phlebotonics, with routine care for hemorrhoidal disease (swollen anal cushions that cause bleeding, itching or irritation, and pain) and for recovery after hemorrhoid surgery. One product was a flavonoid preparation containing rutin, borage, horse chestnut and witch hazel. The other was a Centella asiatica (gotu kola) preparation containing triterpenic acids, asiaticoside, arnica and aloe. Flavonoids are plant antioxidants reported to improve venous tone and reduce inflammation, while Centella is reported to stimulate collagen and repair connective tissue. Participants aged 18 to 85 were randomized to three groups. Group A (73 people) took 300 mg flavonoid tablets twice daily for 15 days and applied a 3 g ointment inside the anus once daily. Group B (66 people) took 60 mg Centella tablets twice daily for 15 days and used a 3 g Centella-based ointment. Group C (60 people) received routine care only. Everyone followed a water- and vegetable-rich diet and used a medicated soap for 42 days. Time until bleeding stopped was tracked, and irritation or pain was rated on a visual analogue scale. Among 130 people with hemorrhoidal disease, bleeding stopped after a median of 2 weeks with flavonoids and 3 weeks with Centella or routine care (flavonoids versus routine care p < 0.001, meaning a clear difference; Centella versus routine care p = 0.152, meaning no significant difference). Irritation scores were lower than routine care for both products (flavonoids p = 0.007; Centella p = 0.041), and the two products did not differ (p = 0.782). After hemorrhoidectomy (31 people), bleeding time did not differ significantly between groups, and pain differed only for flavonoids versus routine care (p = 0.045). In 34 people with thrombosed hemorrhoids, pain fell faster with either product (all p < 0.001). Tissue examination linked flavonoids to fibrosis, a fibrous tissue change in the excised piles (p = 0.008). No adverse reactions were reported except burning from the Centella ointment in one person, which led to suspension of that ointment. The authors interpret the results as favouring flavonoids for bleeding and irritation, with Centella comparable on irritation. Limitations are stated plainly: a single centre, only 42 days of follow-up, small surgical and thrombosis subgroups added after the original protocol, no described blinding of participants, and multi-ingredient products that prevent attributing effects to individual plants. A medicated soap containing Centella was also given to every group. The authors suggest longer trials to test whether the benefits last.