Middle-aged Adults

Aniseh Hatami et al. (2026) · JBRA assisted reproduction

This randomized, double-blind, placebo-controlled trial with 60 women explored whether a standardized extract of Vitex agnus-castus (also called chasteberry or chaste tree) changes oxidative stress, blood fats, insulin resistance and visible symptoms in polycystic ovary syndrome (PCOS). PCOS is a common hormonal condition marked by irregular periods, excess androgens and often insulin resistance. Oxidative stress, an imbalance between damaging free radicals and the body's antioxidant defenses, is described by the authors as feeding a cycle with insulin resistance that worsens PCOS and raises long-term diabetes and heart risk. The women, aged 18 to 45 and treated at a hospital in Arak, Iran, were randomly assigned to 12 weeks of either Vitex tablets (5.8 mg of extract a day) or identical placebo tablets, 30 per group. All kept taking their usual metformin and birth-control pill. Blood tests measured antioxidant and oxidant markers, glucose, insulin, cholesterol and liver enzymes. Ultrasound measured ovary size, the Ferriman-Gallwey score rated excess hair growth, and menstrual frequency compared observed periods with expected ones. Compared with placebo, the Vitex group had higher total antioxidant capacity (0.60 to 1.10 mM versus no change, p < 0.001) and lower total oxidant status, a damage marker (MDA) and an oxidative stress index (all p < 0.001). Insulin resistance (HOMA-IR) fell from 6.40 to 0.98 versus 6.72 to 1.33 with placebo (p < 0.05), HDL cholesterol rose from 50 to 60 mg/dL (p < 0.001), LDL fell, and the hirsutism score dropped from 10.7 to 7.8 while rising on placebo (p < 0.001). Menstrual frequency rose to 0.955 of expected periods versus 0.844 (p = 0.046). Triglycerides, catalase and right ovary volume did not change significantly, weight and body mass index were unchanged, all 60 women completed the study, and no adverse events were reported. The authors view Vitex as a promising complement to standard care and note limits: 12 weeks, one center, convenience sampling, self-reported adherence and no hormone measurements such as LH, FSH or SHBG. Participants stayed on metformin and oral contraceptives, some table values are reported with unusually large effect sizes that look inconsistent with the text, and the authors call for longer, larger trials with several doses and mechanistic endpoints.

Dominic N Reeds et al. (2011) · Diabetes care

This randomized, double-blind, placebo-controlled pilot trial with 15 adults explored whether oral ginseng or a purified ginseng compound, ginsenoside Re, improves how the body handles blood sugar. Ginseng is a popular herbal product promoted for diabetes, and earlier work in cells and rodents, mostly using injected ginseng, suggested that ginsenoside Re raises insulin sensitivity, meaning how well tissues take up glucose in response to insulin. Participants were overweight or obese adults with impaired glucose tolerance or newly diagnosed type 2 diabetes, chosen because their metabolism was thought most likely to improve. The volunteers, 14 women and 1 man averaging 46 years old, took placebo capsules, Korean red ginseng extract (3 g a day for two weeks, then 8 g a day) or ginsenoside Re (250 mg a day, then 500 mg a day) for four weeks, with five people per group. Before and after, researchers used a frequent-sampling glucose tolerance test and the hyperinsulinemic-euglycemic clamp, a research method that holds blood sugar steady while insulin is infused, together with tracer sugars, to measure insulin sensitivity and beta-cell function (how well insulin-making cells respond). Nothing improved. The disposition index, a beta-cell function score, was unchanged in the placebo group (5.8 to 5.8 x 10^-3, P = 0.99), the ginseng group (7.7 to 6.0, P = 0.29) and the ginsenoside Re group (7.4 to 5.9, P = 0.50). Insulin sensitivity on the clamp also did not shift significantly: placebo 165% to 185% (P = 0.34), ginseng 171% to 137% (P = 0.88), ginsenoside Re 117% to 134% (P = 0.44). Body weight, fasting glucose, HbA1c and cholesterol stayed the same, and no adverse events were reported. Blood tests could not detect ginsenosides Re, Rb1 or Rb2 after dosing, so the compounds did not appear to reach the bloodstream in measurable amounts. Liver glucose output and fat breakdown, tracked with labeled glucose and glycerol, also responded the same way before and after treatment in every group. The authors interpret the results as evidence that these oral ginseng products do not improve glucose control, likely because absorption is poor, and they note that injected ginseng helped in animal studies. Limits include only 15 participants, a four-week duration, a single ginseng product, and the possibility that other ginseng components or other commercial products behave differently from those tested here.

Tae-Ha Chung et al. (2021) · Nutrients

This randomized, double-blind, placebo-controlled trial with 63 postmenopausal women in Seoul, Korea, explored whether Korean red ginseng changes markers of biological aging, antioxidant capacity and fatigue. Korean red ginseng (KRG) is Panax ginseng root that is steamed and dried with its skin on. After menopause, falling estrogen is linked to more oxidative stress (damage from unstable molecules called free radicals) and to a drop in mitochondrial DNA copy number, a count of the DNA copies inside the cell's energy-producing structures that is used as an indicator of biological aging. Total antioxidant status (TAS) measures how well the blood neutralizes free radicals. The women were aged 46 to 69. Over 8 weeks, 33 completers took 2 g of KRG daily as four 500 mg tablets and 30 completers took matching placebo tablets of cornstarch and cellulose. Blood tests at the start and end measured TAS with an automated assay and mitochondrial DNA copy number with real-time PCR, while the 9-item Fatigue Severity Scale (FSS, scored 7 to 63, higher meaning worse fatigue) tracked tiredness. TAS rose by 0.11 mmol/L with KRG and fell by 0.04 with placebo (p = 0.011, meaning a gap this large is unlikely to be chance). Mitochondrial DNA copy number rose by 1.58 with KRG versus 0.28 with placebo (p = 0.023), a 1.44-fold increase versus 1.15-fold. Fatigue scores dropped 7 points with KRG versus 1 point with placebo (p = 0.033). LDL cholesterol tended to decline from 136 to 127 mg/dL on KRG, but the difference from placebo was not significant (p = 0.064). Body mass index, blood pressure and blood counts did not change. The groups also differed at baseline in white blood cell count and total cholesterol, and ten of the 73 enrolled women left the analysis, including two placebo participants who took other red ginseng products. The authors view the results as supporting KRG's antioxidant and anti-fatigue effects, drawing on animal and cell research for mechanisms such as the PGC-1alpha pathway that builds mitochondria. Limitations include one dose, an 8-week period, uncontrolled lifestyle, a modest sample and participants who were all Korean postmenopausal women, so findings may not transfer to other groups. Dose, duration and effects on cholesterol need larger, longer studies, and safety was not formally reported.

Valérie Dormal et al. (2025) · Nutrients

This randomized, double-blind, placebo-controlled trial with 149 adults explored whether a specially grown red Panax ginseng root powder changes perceived stress, mood and thinking speed. Perceived stress is a person's own sense that demands outweigh their ability to cope, and it is tied to anxiety, depression, heart disease and weaker cognition. Panax ginseng, also called Asian or Korean ginseng, is a root used as an adaptogen, meaning a substance proposed to help the body handle stress. Steaming the root turns its common ginsenosides (the main active compounds) into rare ginsenosides, which the authors describe as absorbed better and more pharmacologically active. The volunteers were adults aged 18 to 60 in Belgium with moderate stress scores on the Perceived Stress Scale. For 21 days, 72 took a daily 200 mg capsule of the ginseng powder, which supplied 22.4 mg of ginsenosides, and 77 took a look-alike placebo made of rice flour and brown sugar. Before and after, everyone completed stress, depression and mood questionnaires and two computer-based Cambridge Neuropsychological Test Automated Battery (CANTAB) tasks of visual memory and spatial planning. Stress scores dropped in both groups, but the drop was larger with ginseng (4.3 points versus 2.7 points on the scale; p = 0.040, meaning the gap is unlikely to be chance). Negative mood fell only in the ginseng group (2.6 points; difference between groups p = 0.032). Depression scores improved in both groups, and the extra improvement with ginseng did not reach significance (p = 0.073). On the planning task, ginseng users took about 1.6 seconds less to make a first choice (p = 0.002 within the group; p = 0.036 against placebo). Memory-task errors fell only in the ginseng group, yet the groups did not differ significantly, and the number of planning problems solved correctly on the first try was similar in both. No serious adverse events occurred, mild and moderate events were not significantly different between groups, and compliance was above 97% in both groups. Seven volunteers dropped out, five of them from the placebo group. The authors describe the benefits as moderate and view ginseng as a complement to broader treatment rather than a stand-alone approach. Limits include the short three-week period, volunteers who were stressed but not clinically unwell, sizable improvement in the placebo group, and many outcomes tested without a described correction. Long-term safety and effects in people with higher stress, anxiety or depression remain unstudied, and the results apply to this one proprietary preparation tested in a single trial.

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.

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.

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.

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.

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.

Valérie Dormal et al. (2025) · Nutrients

This randomized, double-blind, placebo-controlled trial with 180 adults in Belgium asked whether two plant extracts, saffron and Chinese skullcap (Scutellaria baicalensis), help people with mild-to-moderate depressive symptoms, alone or together. Saffron's compounds crocin and safranal are thought to keep the brain chemicals norepinephrine, dopamine and serotonin active for longer, a mechanism similar to common antidepressants. Skullcap's flavonoids, mainly baicalin, had shown calming and mood-lifting effects in animal studies, but had never been tested for mood in people. The researchers also wanted to see whether combining the two gave extra benefit. Participants aged 18 to 75, all with a recent depressive episode and Beck Depression Inventory (BDI) scores of 14 to 28, were split into four groups of 42 to 48. For six weeks each person took one capsule every morning: 30 mg saffron extract, 20 mg skullcap extract, both together, or a placebo of 450 mg maltodextrin. Depression was scored with the BDI and the clinician-rated Hamilton scale, anxiety with the STAI-S, and mood and well-being with PANAS, WHO-5 and other short questionnaires at weeks 0, 3, 6 and 8. Everyone improved, including the placebo group: BDI fell significantly in all four groups (p < 0.001), with no difference between them. Differences appeared only in the second half of treatment. Between week 3 and week 6, depression scores kept dropping in the saffron group (-2.4 points, p = 0.036) and combination group (-3.5 points, p = 0.004) but not placebo, and the Hamilton score fell more with saffron than placebo (p = 0.024). Anxiety fell in all three active groups, and well-being (WHO-5) rose more with skullcap and the combination than placebo. Compliance was about 99% in every group, and two weeks after stopping, scores had mostly held steady. The authors attribute the large placebo gains partly to participants being engaged in a study that encouraged them to talk about their problems and act to improve their well-being. Side effects were mostly minor, such as headaches and gastrointestinal complaints. The authors suggest saffron, skullcap and their combination may help mood, and propose a synergistic effect. The strong placebo response, scarce between-group differences, six-week duration, self-report measures and exclusion of severe depression limit how far the results reach. An author works for an ingredient supplier, and whether the findings extend beyond French-speaking adults at one Belgian center is not established. Longer trials, higher doses, severe depression and objective biomarkers such as stress hormones or neurotransmitter levels are recommended for future work, since long-term safety remains unestablished.

Adrian L Lopresti et al. (2022) · Journal of the International Society of Sports Nutrition

This randomized, double-blind, placebo-controlled trial with 62 recreationally active adults tested whether a standardized saffron extract changes how much people enjoy exercise, how they feel, how they sleep and how their heart rate varies. Saffron comes from the dried stigmas of the Crocus sativus flower, and its extract affron® is standardized to contain safranal and crocin, compounds studied for mood-enhancing effects at about 28-30 mg a day in adults with low mood or anxiety. Heart rate variability (HRV), the beat-to-beat variation in heart rate, serves as a marker of the body's calming parasympathetic activity. Adults aged 18 to 65 who exercised more than three times a week were randomly assigned for six weeks to take either 14 mg of saffron extract or a matching placebo tablet twice daily (28 mg of saffron a day). They kept exercising as usual. The main measure was the Physical Activity Enjoyment Scale, an 18-item questionnaire. The team also tracked mood with a 40-item survey, sleep and HRV with a WHOOP wrist strap, and blood levels of three brain-related chemicals at the start and end. Across everyone, saffron did not beat placebo on any measure (exercise enjoyment p = 0.276, mood p = 0.787, HRV p = 0.502, sleep time p = 0.598, meaning no real difference between groups). Enjoyment did climb within the saffron group, from 107.99 to 114.44 points (p = 0.001), but placebo also drifted upward. In an exploratory split by sex, the 22 men on saffron gained more enjoyment than the 15 men on placebo (113.81 versus 106.20 points, p = 0.009), and their HRV rose about 9% while placebo men's fell 5.7% (p = 0.001). No such differences appeared in the 9 women on saffron or the 16 on placebo. Side effects were mild and uncommon. The authors describe the male-only findings as preliminary, since the groups were small and uneven by sex, and the headline result was null. Healthy, already-active volunteers may leave little room for improvement, women's hormonal cycle phase was not controlled, and the wrist-worn tracker is less precise than laboratory sleep and heart measures. They recommend larger trials with varied doses and durations.

Hamed Delam et al. (2023) · BMC complementary medicine and therapies

This randomized controlled trial of 72 postmenopausal women in Iran asked a simple question: does drinking saffron tea every day make women feel happier? Menopause marks the end of menstruation and fertility, and falling estrogen levels combined with changes in family roles and aging are linked in the paper to low mood, anxiety and depression. Saffron (Crocus sativus L.), a spice from the dried stigmas of a purple crocus flower, contains crocin and safranal, compounds that laboratory work suggests affect the brain chemicals dopamine, norepinephrine and serotonin, which govern mood and motivation. The 72 women, averaging about 54 years old, were recruited through community health centers in Larestan, Iran, in 2021 and randomly placed into two groups of 36. One group drank a cup of saffron tea each morning for six weeks, made by steeping 30 mg of dried stigmas in 300 ml of hot water and served with white rock candy. The comparison group drank lukewarm water with rock candy. Happiness was measured with the Oxford Happiness Questionnaire, a 29-item survey scored from 29 to 116, at the start and after two, four and six weeks. Both groups began at almost the same level (about 43 points). The saffron group climbed steadily to 51.4 after two weeks, 55.5 after four weeks and 61.6 after six weeks (a rise of roughly 19 points, p < 0.001, meaning the change is very unlikely to be chance). The water group did not move, ending at 42.8 (p = 0.861, no real change). The gap between groups at week six was statistically significant (p < 0.001), and it held after the researchers adjusted for demographic variables. The paper does not report any side effects data, only that the dose was small. The authors suggest saffron tea may be useful as a complementary approach alongside conventional care. The study has clear limits: participants knew which drink they received, happiness was self-reported, only 72 women from one region took part, the trial lasted six weeks, and it overlapped with a COVID-19 wave in Iran. Depression was not measured directly, and how saffron might produce the effect was not tested. The authors recommend larger trials in other populations and research into the mechanism.

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.

Teresa Vezza et al. (2024) · Nutrients

This randomized trial with 66 healthy volunteers explored whether a daily capsule combining garlic powder and a concentrated onion extract lowers LDL cholesterol, the "bad" cholesterol that builds up in artery walls and drives heart and blood vessel disease. Medicines such as statins are usually kept for people with clearly raised LDL cholesterol or several risk factors, so people with slight elevations are generally pointed toward diet and lifestyle changes. Garlic and onion contain organosulfur compounds (sulfur-rich plant chemicals), which the authors say are linked to cholesterol-lowering, antioxidant and anti-inflammatory effects. To the authors' knowledge, human research had mostly looked at garlic alone, and none had combined the two plants in one capsule. Volunteers living in Granada, Spain, with LDL cholesterol between 100 and 190 mg/dL were split at random into two groups of 33. One group took a capsule called Aliocare daily with lunch, holding 86 mg of onion extract and 14 mg of garlic powder, and the other took an identical-looking placebo of plain cellulose. Neither participants nor researchers knew who received which. Blood samples and blood pressure were checked at the start and after 2, 4 and 8 weeks, including markers of oxidation and inflammation, liver and kidney function. After 8 weeks, LDL cholesterol was 6% lower in the capsule group (4% lower at 4 weeks), and total cholesterol about 6% lower. Among those starting above 110 mg/dL, LDL cholesterol dropped 12% by week 8. Triglycerides (blood fats) also fell, while good HDL cholesterol stayed unchanged and glucose did not differ. Oxidized LDL, a form of LDL damaged by oxidation and linked to artery disease, fell about 32% by week 8. Blood pressure was about 5% lower, and no adverse events were reported, with liver and kidney tests staying in the normal range. Compliance exceeded 95%, and participants did not guess their group assignment. Interleukin-6, an inflammation marker, tended to fall with the capsule without reaching significance, and malondialdehyde, another oxidation marker, did not differ. The authors conclude the capsule was safe and improved several heart-related measures, and they suggest garlic and onion may act together, though the study did not test each plant separately. They state plainly that the volunteers were mostly young with LDL cholesterol at the low end of the range, the pandemic limited recruitment, the sample was small and the 8-week duration short. The authors add that recruiting under different conditions would likely have produced higher baseline values and more robust results. They plan larger, longer studies in people with higher LDL cholesterol.