Modern Clinical Research

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.

Sara Izadi-Najafabadi et al. (2025) · Integrative cancer therapies

This retrospective study compared 67 people with grade IV glioblastoma (GBM), a fast-growing brain cancer, who received integrative naturopathic care at a Canadian clinic with 243 matched patients from the U.S. SEER cancer registry. The clinic's approach added modulated electro-hyperthermia (mEHT), a radiofrequency treatment that heats tumour tissue, plus high-dose intravenous vitamin C, supplements, acupuncture and diet counselling, on top of standard surgery, radiotherapy and temozolomide chemotherapy. Standard care for GBM extends median survival only to about 14.6 months, so the authors looked for any signal that the extra treatments might add survival time. Patients had at least six mEHT sessions between 2010 and 2024, with a median of 13 sessions of up to 60 minutes each at powers rising from 50 to 140 watts. Controls were matched on age, sex, diagnosis year and whether they had surgery, radiation and chemotherapy. To avoid giving the clinic group credit for the months before they arrived, survival was counted from the start of clinic treatment (or the matched patient's start date for controls) and compared with Kaplan-Meier curves and Cox regression. Median survival from that starting point was 15 months with integrative care versus 11 months in controls, and the hazard ratio of 0.72 (95% CI 0.53-1.00, p = 0.05) sat right at the edge of statistical significance (a 28% lower hazard of death). The difference was concentrated in people who started within 120 days of diagnosis (hazard ratio 0.52, p = 0.006, roughly half the hazard of death) and in those under 50 (0.51, p = 0.009); starting later or being 50 or older showed no difference (0.98 and 0.96). Treatment began a median of 124 days after diagnosis, so these patients had already survived that long. The authors saw no seizures or other side effects. Those subgroup analyses were exploratory, unadjusted for multiple testing, and the matched groups still differed in how many had chemotherapy and radiotherapy. Because treatment was not randomised and many factors that shape GBM survival, such as tumour genetics, extent of surgery and general fitness, were unavailable, the results cannot show that the integrative care caused the longer survival. Clinic patients also paid for their own care, which may favour those with more resources, and the dose and timing of mEHT varied between individuals. The authors describe the findings as hypothesis-generating, a signal rather than an effect estimate, and call for randomised trials.

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.

David Brulé et al. (2024) · Journal of integrative and complementary medicine

This randomized trial of 146 treated children and adolescents with attention-deficit/hyperactivity disorder (ADHD) explored whether homeopathy helps manage the condition, and which part of the treatment might be responsible. ADHD is a neurodevelopmental condition marked by inattention, hyperactivity and impulsivity, and roughly 30% of diagnosed children do not respond to standard medication or behavioral treatment. Homeopathy uses highly diluted natural substances prescribed one patient at a time, and in practice it combines a long consultation with a chosen remedy. Earlier open-label results could not tell those two components apart, so this study separated them. Children aged 6 to 16 in Toronto, Canada were randomly assigned to one of three groups. One group (47 children) received homeopathic consultations plus an individualized remedy, a second (48 children) received the same consultations plus a look-alike placebo granule, and a third (51 children) continued usual care only. Consultations lasted up to two hours at intake and recurred about monthly for 28 weeks. Parents rated symptoms with the Conners 3 Global Index-Parent T-score, where lower scores mean fewer symptoms. Symptom scores fell by about 6.2 points in the remedy group and 6.4 points in the placebo group, compared with 2.2 points in usual care (complete-case analysis, 126 children). After adjustment, the remedy-plus-consultation group differed from usual care (p=0.037), while the placebo-plus-consultation group fell just short of the corrected significance threshold (p=0.026 against a cutoff of 0.025). The two consultation groups did not differ from each other (p=0.93). A clinically meaningful improvement (a drop of at least 7.36 Conners T-score points) occurred in 35.9%, 44.2% and 13.6% of the three groups respectively (p=0.006). Parents in both consultation groups also reported better coping (p=0.012 and p=0.003). Side effects were all mild (Grade 1), mainly increased hyperactivity, emotional outbursts and tics, and did not differ between groups. Because the remedy and placebo groups improved similarly, the authors attribute the benefit to the consultation rather than the remedy itself. Participants knew whether they were receiving consultations, parents scored the main outcome, and recruitment fell short of the planned 177 because the COVID-19 pandemic halted trials, so expectation effects and limited statistical power remain possible. The authors recommend further research into the mechanism and into whether other forms of consultation or psychological support produce comparable results.

H J Hamre et al. (2023) · Systematic reviews

This systematic review examined six earlier meta-analyses (statistical pooling studies) of placebo-controlled randomized trials of homeopathy for any health condition in humans, asking whether homeopathy shows an effect beyond placebo. Homeopathy is built on drug provings (recording symptoms in healthy people), the principle that a substance causing a symptom pattern is used to treat a similar one, and potentization, which means serial dilution with vigorous shaking. Because the six meta-analyses, published between 1997 and 2017, used different methods and reached different conclusions, the authors reviewed them together under a published protocol and judged their risk of bias and the certainty of the overall evidence. The authors searched eight databases plus a private collection and contacted experts, identifying 16 reports covering six meta-analyses, with searches running to December 2020 and an update to April 2023. Two reviewers screened and extracted data independently. The meta-analyses together covered 310 trials or trial comparisons (182 distinct trials published between 1943 and 2014), most often on respiratory conditions such as allergic rhinitis and influenza. Each meta-analysis was rated for risk of bias with ROBIS, and the combined evidence was graded with a GRADE-based approach. All five meta-analyses with reported pooled estimates found a significant effect favouring homeopathy across all trials, for example an odds ratio of 2.45 (95% CI 2.05-2.93) across 89 trials in the 1997 analysis and a standardized mean difference of 0.33 (0.21-0.44) across 54 non-individualised trials in 2017. When only high-quality trials were kept, three of four analyses stayed significant, but the 2017 analysis did not (SMD 0.18, -0.09 to 0.46, 3 trials). Only 6-29% of trials met each analysis's high-quality criteria. Three analyses showed significant heterogeneity and funnel plot asymmetry, a pattern that can signal publication or small-study bias; individualised homeopathy showed neither. Two analyses that combined quality and trial-size restrictions found no significant difference from placebo. Three meta-analyses were rated low and three high risk of bias. The authors rated evidence certainty as high for individualised homeopathy and moderate for the other categories. The authors conclude that the data do not support the hypothesis of no difference from placebo and that placebo-controlled evidence gives no justification for regulatory action against homeopathy. The review only covers trials already in six meta-analyses, so trials after 2011 (individualised) and 2014 (non-individualised) are missing. It also reports no indication-specific results, and its use of GRADE tested whether any effect exists rather than how large it is. The authors recommend updating the individualised homeopathy analysis and studying specific non-individualised treatments for specific conditions.

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.

Joyce Cristina Freitas et al. (2026) · Lasers in medical science

This randomized, sham-controlled trial with 48 physically active young men (45 analyzed for performance, aged 18 to 35) at a Brazilian university explored whether photobiomodulation (PBM) and osteopathic manipulation (OM) change recovery after exercise-induced muscle damage (EIMD). PBM applies red light from light-emitting diodes to the skin, a process the authors link to mitochondrial energy production in muscle fibers. OM is a manual therapy; here it meant high-velocity low-amplitude thrusts, quick, small-range joint manipulations. EIMD is the inflammation, strength loss and raised creatine kinase (CK, an enzyme leaking from damaged muscle fibers) that follow unaccustomed jumping or lowering exercise, usually peaking 24 to 72 hours later. Participants were randomized to placebo, PBM, OM, or PBM plus OM, 12 per group. PBM meant a 650 nm red light device pressed against 16 points on the right thigh and calf (144 joules in total, about 8 minutes). OM meant a lumbar roll and a pelvic manipulation by an osteopath. Both were given once before 100 drop jumps from a 50 cm platform, with sham versions for blinding. CK, quadriceps strength, knee flexibility and horizontal jump distance were measured before, right after, and at 24, 48 and 72 hours. The groups did not differ statistically on any outcome (CK group effect p = 0.950; strength p = 0.283; jump p = 0.199, meaning no measurable difference between the four arms). Within groups, CK rose immediately after exercise in placebo (p = 0.01) and OM (p = 0.02), but only at 24 hours in PBM and PBM plus OM, and the combined group showed a significant fall by 72 hours (p = 0.001, suggesting faster clearance of the damage marker). Strength dropped 6.3% to 12.4% after exercise; in exploratory tests the combined group regained significant strength by 48 hours (p = 0.036) and sat 1.4% from baseline. Jump distance rose 8.5 to 11.9 cm in all groups. CK did not track functional recovery. No adverse events were reported. The authors describe a possible modest, complementary benefit of combining the two approaches, while labeling the strength trend exploratory and non-significant. Limitations include 12 participants per group, a single session, only young men, red light that penetrates tissue less deeply than near-infrared light, and no formal check of blinding. Findings apply to physically active young men under acute jumping stress. The authors propose testing other light wavelengths and doses, repeated sessions, and a broader osteopathic approach in future trials.

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.

Yang Zhu et al. (2026) · PeerJ

This systematic review and meta-analysis pooled 22 randomized controlled trials with 375 mostly male participants to ask when, if at all, a single cold-water immersion (CWI) after exercise helps muscles recover. CWI means immersing the body, from navel depth up to the neck, in water of roughly 5 to 20 degrees C for about 6 to 20 minutes. Exercise-induced muscle damage (EIMD) is the loss of force, soreness and raised creatine kinase (CK, a blood marker leaking from stressed muscle cells) that follows hard or unaccustomed exercise, often with delayed onset muscle soreness (DOMS). Earlier reviews mixed time points, so this one separated results at 0, 24, 48 and 72 hours. The included trials enrolled healthy non-athletes and athletes aged about 16 to 49, who exercised with intervals, simulated matches, distance running or heavy eccentric lifting. After exercise, one group sat in cold water and the comparison group rested seated for a similar time. Researchers measured maximal voluntary isometric contraction (MVIC, the hardest possible static muscle squeeze), countermovement jump (CMJ, jump height as a gauge of explosive power), CK, and soreness on a visual analog scale (VAS, a line marked from no pain to worst pain). Maximal strength was unchanged by CWI (g = 0.08, 95% CI -0.11 to 0.26, p = 0.42; a negligible effect) at every time point. Jump performance was worse immediately afterward (g = -0.68, p = 0.01; a medium-sized drop) and showed no difference by 24 to 48 hours (g = 0.38 at 24 h, p = 0.06; g = 0.06 at 48 h, p = 0.68). CK looked lower after CWI (g = -0.43, p < 0.001; a small effect), but the result shrank to non-significance after correcting for likely missing small studies (g = -0.16, 95% CI -0.44 to 0.12; the original benefit was probably overestimated). Soreness was lower (g = -0.58, p = 0.006; a medium effect), though the trials disagreed widely (I² = 87%) and the certainty of evidence was rated very low. The evidence has clear limits: 362 of 375 participants were male, participants could not be blinded to cold water, several trials were tiny, and only one immersion with follow-up of 72 hours or less was studied. The authors suggest the soreness effect is the most plausible benefit and the temporary jump decrement is the main drawback. Repeated use during training and its effect on muscle adaptation were not examined, and they call for larger trials that include women and standardize temperature and duration.

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.

Lolita Rapolienė et al. (2026) · BMC complementary medicine and therapies

This multicenter randomized controlled trial of 243 analyzed adults in Lithuania explored whether a short course of balneotherapy, a spa-based therapy using mineral water, therapeutic mud and salt, eases stress, anxiety and depression. Balneotherapy has a long tradition in European spa towns and is increasingly discussed as a complementary approach to stress-related mental health problems. The researchers wanted to know whether an 11-day standardized program works, whether adding a nature walk or an inpatient stay changes the results, and whether benefits last six months. Adults aged 18 to 65 who rated their stress as moderate to high were assigned to one of four groups: outpatient balneotherapy (64 people), outpatient balneotherapy plus nature therapy (63), an inpatient balneotherapy stay (64), or a no-treatment control group (52). The daily program combined a pool session with light exercise, a warm mineral water bath, a 20-minute sapropel mud wrap and 25 minutes of salt therapy. Questionnaires measured stress, depression, anxiety, fatigue, sleep and daily functioning, and saliva samples tracked the stress hormone cortisol, at baseline, right after treatment, and after 3 and 6 months. Right after treatment, people in all three spa groups reported clear improvements. Stress intensity dropped by about 2.6 points on a 10-point scale (p < 0.001), and depression scores fell by 10.7 to 12.5 points on an 80-point scale (p < 0.001), compared with a 1.3-point change in the control group (p = 0.253, no real change). Anxiety, fatigue and sleep problems improved too: fatigue fell by 4.1 to 5.1 points on the 10-50 Fatigue Assessment Scale (p < 0.001) while the control group did not change (p = 0.775), sleep quality rose by about 2 points on a 10-point scale (p < 0.001), and cortisol fell significantly in two of the three groups. Many gains were still present at six months, strongest after the inpatient stay. About 15% of participants had mild skin reactions to the mineral water, and no serious adverse events occurred. The authors suggest balneotherapy could be a safe complementary option for stress. Important limits apply: the paper reports mainly within-group changes rather than direct group comparisons, controls received no treatment, participants knew what they were getting, many people dropped out by six months, spa resources differed by center, and some questionnaires were not formally validated in Lithuanian. The control group also reported lower stress intensity (-1.18 points, p < 0.001), which shows that part of the improvement occurred without treatment. Larger, longer trials are recommended.

Vahid Reisi-Vanani et al. (2025) · The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale

This double-blind, randomized trial of 66 hospitalized COVID-19 pneumonia patients in Shahrekord, Iran, tested whether pomegranate tea added to standard hospital care improves recovery. Pomegranate (Punica granatum) is rich in plant polyphenols such as punicalagin and anthocyanins, compounds that antioxidant and antiviral lab studies suggest could dampen inflammation and block the virus's spike protein from binding to its human receptor, ACE2. Lab results do not always carry over to patients, so the researchers tested the idea in a placebo-controlled clinical trial. Patients aged 18 or older with a positive SARS-CoV-2 test, low blood oxygen (SpO2 of 93% or less) and pneumonia on imaging were randomly assigned, balanced by how much oxygen support they needed. Half received a freeze-dried pomegranate fruit extract syrup (110 mg per 10 cc), dissolved in warm water as a tea, four times a day; the rest received a matching coloured placebo syrup. Treatment continued through the hospital stay and after discharge until symptoms eased. The team tracked recovery, hospital days, deterioration, death, symptom severity on a four-point scale, blood tests and side effects. The results were flat. By day 14, 84.8% of the tea group and 83.3% of the placebo group had improved (p = 1.0, meaning no difference). Median time to improvement was 6 versus 5 days (p = 0.83), and hospital stay 6 versus 5 days (p = 0.87). Deterioration occurred in 18.2% versus 20.0% (p = 1.0). Death at 28 days was 18.2% versus 6.7%, a gap that was not statistically significant (p = 0.26) in groups this small. Cough, fever, fatigue, breathlessness and other symptom scores did not differ, and day-14 blood markers such as CRP, ferritin and ESR were similar between groups. Some serious events such as ARDS (15.2% versus 3.3%) and liver dysfunction (15.2% versus 6.7%) were numerically more common with pomegranate but not significantly different, and no allergic reactions were reported. The authors conclude that pomegranate tea did not help in COVID-19. The small trial had unevenly matched groups at baseline, including time since symptom onset, and used an extract that was not chemically standardized. They recommend standardized extracts and adaptive trial designs, noting that laboratory activity does not guarantee clinical benefit. Nearly all patients in both groups also received antivirals (93.9% and 93.3%), and only 63 completed follow-up, so larger trials would be needed to detect modest effects or rare harms.