Modern Nutritional 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.

Maria Teresa Guagnano et al. (2021) · Nutrients

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

Ali Tabatabaeyan et al. (2025) · Scientific reports

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

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

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

Sandra Utz et al. (2025) · Biomedicines

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

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.

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.

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.

Nayon Hur et al. (2026) · Nutrients

This randomized, double-blind, placebo-controlled trial with 112 women explored whether an oral Centella asiatica extract, taken as a daily tablet, changes measurable signs of skin aging. Centella asiatica, also called gotu kola, is traditionally used in Asian and Ayurvedic medicine for wound healing and skin problems. Skin aging here means deeper wrinkles, lower hydration, a weaker skin barrier (measured as water loss through the skin, TEWL) and less elasticity. The authors note that evidence for taking Centella by mouth for skin was limited and often based on small or subjective studies. Women aged 30 to 60 with visible crow's feet and fairly dry cheek skin were randomly assigned in Seoul to take either 200 mg a day of a standardized leaf extract (InnerCica, with asiaticoside as the marker compound) or an identical placebo for 12 weeks. Neither participants nor assessors knew who received which. Wrinkle depth, volume and roughness were measured with 3D skin imaging, and hydration, TEWL, elasticity and skin color with non-invasive probes at baseline, 6 and 12 weeks. After 12 weeks, average wrinkle depth fell by 5.87 micrometres with the extract versus 1.96 with placebo (p = 0.018; an 11.1% drop from the extract group's baseline). The deepest wrinkle, wrinkle volume and roughness also improved more than with placebo. Cheek hydration rose and cheek water loss fell more with the extract (p < 0.001 and p = 0.005), but gains in elasticity and brightness were only about 0.7%, which the authors call modest. Three mild adverse events (one extract, two placebo) were judged unrelated, and blood tests stayed normal. The authors treat wrinkle depth as the confirmed result and everything else as supportive. They note the study included only women, tested one dose for 12 weeks, did not measure how the extract might work, and did not adjust for testing many outcomes, so long-term effects remain unknown. They call for longer, more diverse studies.

Béla E Tóth et al. (2025) · Nutrients

This prospective, double-blind, two-phase randomized controlled trial with 84 analyzed participants explored whether weekly high-dose vitamin D3 (a fat-soluble vitamin that also acts on hormone-producing tissue through its receptor, VDR) could improve ovarian function in polycystic ovary syndrome (PCOS), a common hormonal condition marked by irregular or absent ovulation (the release of an egg), elevated androgens ("male-pattern" hormones such as testosterone), and, frequently, vitamin D deficiency. Earlier studies had linked low vitamin D status to PCOS but disagreed on whether raising vitamin D levels actually changes ovulation, cycle length, or hormone levels. Conducted at eight Hungarian clinical sites between 2016 and 2020, the trial randomized women meeting Rotterdam PCOS criteria to one of two oral regimens: 30,000 IU of vitamin D3 weekly, plus calcium, either immediately for 24 continuous weeks or only after a 12-week placebo lead-in period. Ovarian morphology was tracked with transvaginal ultrasound, and ovulation was confirmed through luteal-phase progesterone testing (values above 10 ng/mL) rather than self-report alone, at baseline and after 12 and 24 weeks of treatment. After 12 weeks of vitamin D3, average menstrual cycle length dropped by 11.7 days (p = 0.032, meaning this reduction was unlikely to be due to chance), and confirmed ovulation rose from about 40% to 59-65% of participants (p = 0.044). Serum vitamin D rose to a mean of 45.1 ng/mL (p < 0.001), confirming adequate repletion. Testosterone fell significantly only in two specific subgroups: women with elevated androstenedione ("hyperandrogenic," p = 0.047) and those with a higher LH/FSH hormone ratio (p = 0.0082) — a pattern the authors connect to differing PCOS phenotypes rather than one uniform hormonal response. Ultrasound-confirmed normal ovarian appearance was reached in 20% of participants after 12 weeks (p < 0.05 versus placebo), improving further by 24 weeks, though that later difference was not statistically significant. No serious treatment-related side effects were reported, and vitamin D levels stayed within the study's predefined safety range throughout. The authors suggest vitamin D3 could serve as a standalone or add-on approach for PCOS, particularly for hyperandrogenic phenotypes and those with a higher LH/FSH ratio. They identify the trial's sample size (84 analyzed participants), the relatively short 12-plus-12-week duration, and luteal-phase-only hormone sampling as limitations restricting broader conclusions, and note that longer trials with serial ultrasound monitoring and larger, phenotype-defined groups are needed to confirm these phenotype-specific patterns and to establish how long the ovulatory and cycle-length benefits persist after treatment ends.

Zahra Najdgholami et al. (2025) · Frontiers in endocrinology

This 12-week open-label randomized controlled trial with 70 women explored whether daily flaxseed intake could shift reproductive hormone patterns in polycystic ovary syndrome (PCOS), a common endocrine condition affecting 6 to 15 percent of women of reproductive age. PCOS involves hyperandrogenism (elevated androgen hormones) and disrupted ovulation, often accompanied by a low or borderline follicle-stimulating hormone (FSH) that limits egg follicles from fully maturing. Flaxseed is a plant-based food rich in phytoestrogenic lignans (plant compounds structurally similar to estrogen) and omega-3 fatty acids, both proposed to influence the hormone pathways governing follicle development and gonadotropin balance. Seventy women diagnosed with PCOS at a clinic in Ahvaz, Iran were randomly assigned to 12 weeks of either 30 grams of daily milled flaxseed added to salads, yogurt, or cold drinks, combined with standard diet and exercise guidance, or the same lifestyle guidance without flaxseed. Blood tests measuring FSH, luteinizing hormone (LH), anti-Mullerian hormone, estradiol, DHEAS, and androstenedione were drawn at baseline and after 12 weeks using enzyme immunoassays and chemiluminescent assays, timed to each participant's menstrual cycle phase where applicable. FSH rose significantly more in the flaxseed group than in controls (treatment effect 0.87, 95% CI 0.086-1.75, p=0.027), meaning flaxseed users saw a measurably larger increase in this follicle-stimulating hormone than those on lifestyle changes alone. The ratio of LH to FSH also dropped significantly with flaxseed (treatment effect -0.341, 95% CI -0.63 to -0.08, p=0.031), a lower ratio pointing toward more balanced gonadotropin secretion, since an elevated LH/FSH ratio is a hallmark of PCOS. No significant between-group changes appeared for AMH, LH alone, estradiol, DHEAS, or androstenedione, indicating flaxseed's measured effect was specific to FSH and its ratio to LH rather than the broader hormone panel. Weight, BMI, lipids, and blood sugar stayed similar between groups, and no adverse events were reported, suggesting the 30-gram daily dose was well tolerated over the 12 weeks. The authors propose that flaxseed's omega-3 fatty acids and lignans may support follicle-stimulating hormone receptor activity and gonadotropin regulation, though this mechanism was not directly tested in the trial. The open-label design, unavoidable for a dietary intervention, the single-center setting, and the absence of testosterone and insulin measurements limit how broadly the results extend. The authors identify larger, longer randomized trials incorporating androgen and insulin outcomes as the needed next step for confirming flaxseed's role in PCOS management.

Zhiyong Long et al. (2023) · Frontiers in immunology

Whether the plant compounds often discussed for rheumatoid arthritis — turmeric, green tea, pomegranate, garlic — actually do anything is the question this meta-analysis set out to answer. This review gathered every randomized trial it could find on the question: 47 trials, nearly 3,900 people, fifteen different plant polyphenols, from Iran, China, Korea, Egypt, Japan, Brazil, India and the United States. The clearest picture came from two of them. The first is total glucosides of paeony, an extract of Chinese peony root that is a licensed prescription medicine in China. Twenty-three trials tested it — always added to standard RA drugs like methotrexate, never instead of them. Disease activity scores came down, and so did CRP, ESR and rheumatoid factor, the blood markers doctors track. The most interesting result: people taking it reported *fewer* side effects than people on the standard drugs alone. That fits how it is used clinically — it appears to soften the toll the conventional drugs take on the liver and stomach. The second is curcumin, the yellow compound in turmeric. Five trials, and the same direction: lower disease activity, lower inflammatory markers, no extra side effects. Green tea polyphenols looked promising across two trials. Saffron did not show a clear effect. Everything else — pomegranate, garlic, resveratrol, sesame, cinnamon, ginger, kudzu, cranberry, olive oil, quercetin — rests on one or two small trials apiece, which is encouraging but not yet evidence that bears weight. The honest caveat, which the authors state plainly themselves: the trials disagreed with each other a great deal, most were small, and when the researchers sliced the data by dose and duration some of the headline benefits faded. Nearly all of these were add-on studies. Nobody tested a polyphenol against methotrexate, so the evidence says nothing about replacing a prescribed medication. What it does support is turmeric and peony extract as the best-evidenced candidates, studied as additions to existing treatment rather than replacements for it.

Metha Yaikwawong et al. (2024) · Nutrition journal

This 12-month randomized, double-blind, placebo-controlled trial with 272 adults with type 2 diabetes (T2DM) and obesity explored whether curcumin, the active compound in turmeric (Curcuma longa), could protect the pancreatic beta cells that produce insulin. In T2DM, obesity drives insulin resistance (cells responding poorly to insulin), which forces beta cells to work harder until their function starts to decline. Researchers tracked beta-cell function using HOMA-beta, an index calculated from fasting insulin and glucose, alongside HOMA-IR (a related index for insulin resistance) and two hormones made by fat tissue: adiponectin, which improves insulin sensitivity, and leptin, which signals fullness but runs high with excess body fat. Participants, all 35 or older and already taking metformin, were randomly assigned to six capsules a day (1,500 mg total) of standardized curcumin extract or an identical-looking placebo for 12 months, with 115 people in the placebo group and 114 in the curcumin group at randomization. Neither participants nor staff knew who received which capsule. Blood was drawn at baseline and every three months to measure fasting glucose, HbA1c (average blood sugar over about three months), body weight, BMI, insulin, HOMA-beta, HOMA-IR, adiponectin, and leptin. By 12 months, curcumin-treated participants had notably better beta-cell function than the placebo group (HOMA-beta 136.2 vs. 105.2; P<0.01, meaning their beta cells were working more efficiently), a difference that only became significant at 9 and 12 months, suggesting the benefit builds gradually rather than appearing right away. Insulin resistance dropped further with curcumin (HOMA-IR 4.86 vs. 6.04; P<0.001, lower is better), and blood sugar control improved (fasting glucose 115 vs. 131 mg/dL, P<0.05; HbA1c 6.12% vs. 6.47%, P<0.05). The curcumin group also lost more weight (66.1 vs. 69.3 kg, P<0.001) and lowered BMI (25.98 vs. 27.34, P<0.001), while adiponectin rose (14.5 vs. 10.4 ug/mL, P<0.001, more of the "good" fat hormone) and leptin fell (9.4 vs. 20.7 ug/mL, P<0.001, less of the fullness hormone that runs high in obesity). The authors connect these changes to curcumin's anti-inflammatory activity, since inflammation is a known driver of beta-cell decline. Mild side effects, abdominal pain, diarrhea, and headache, occurred in both groups with no one dropping out because of them, and liver and kidney markers stayed normal, suggesting curcumin extract is reasonably safe as a year-long add-on for people already managing T2DM with metformin. Because the trial tested only one dose at a single Thai hospital, it cannot show whether a different dose would work better or whether these results generalize elsewhere. Larger, multi-center trials testing a range of doses would help confirm curcumin's place alongside standard diabetes care.

Ziqing Soh et al. (2025) · Journal of food and drug analysis

This double-blind, randomized, placebo-controlled trial with 30 young Malaysian women explored whether a beverage combining chamomile and l-theanine could ease primary dysmenorrhea - menstrual cramping that occurs without any underlying pelvic disease. Chamomile (Matricaria recutita) is a flowering herb long used as a calming remedy; the study intervention used a standardized flower extract of it. L-theanine is a non-protein amino acid concentrated in tea leaves (Camellia sinensis), used in supplements to support relaxation. The trial paired both in a functional beverage (CTT) and tested it against a chamomile-flavored placebo (non-CTT) to see whether the combination eased pain, mood, and sleep during menstruation. Thirty women aged 18-30 with primary dysmenorrhea (pain rated at least 4 of 10 on a visual scale across three cycles) were randomly split into a CTT group (480 mg chamomile extract plus 200 mg l-theanine daily) or a non-CTT control group, drinking two 240 mL packs daily - one on waking, one before bed - for five days spanning two days before their period through its third day. Pain was tracked with two 0-10 scales, symptoms with the 18-item Cox Menstrual Symptom Scale, sleep with the Pittsburgh Sleep Quality Index, and mood with the Profile of Mood States. Compared to their own baseline, women drinking CTT saw pain scores drop by roughly 57% on both pain scales (p<0.001), a large reduction over five days. Eight menstrual symptoms also eased significantly, including lower abdominal pain (down 53%), back pain (down 56%), and irritability (down 45%, all p<0.05). Mood shifted too: depression scores fell 12% and vigor (energy and alertness) rose 62% (p<0.05). On sleep, only "daytime dysfunction" - grogginess, poor concentration, and low energy during the day - improved (down 32%, p<0.05); overall sleep quality, how long it took to fall asleep, and total sleep time did not change significantly. Hemoglobin levels, checked with a finger-prick test, were unaffected in either group, likely because red blood cells take weeks to months to regenerate, too slow to show up in five days. Interestingly, the placebo group also felt calmer on a few measures, which the researchers link to the shared chamomile scent and flavor rather than to any active ingredient. For young women managing primary dysmenorrhea without relying on NSAIDs, a short course of this chamomile-l-theanine beverage appears to meaningfully ease pain and several physical and emotional symptoms, with no reported side effects. Because chamomile and l-theanine were only tested together, it is not yet clear how much each contributes individually, and the tiny sample (15 per group) and single five-day cycle mean the results are preliminary. Longer trials spanning multiple cycles, larger and more diverse groups, and a scent-neutral placebo are needed before firmer conclusions can be drawn.

Ping-Tao Tseng et al. (2023) · Advances in nutrition (Bethesda, Md.)

This network meta-analysis pooled 40 randomized controlled trials with 6,616 migraine sufferers to answer a question few doctors are asked but many patients wonder: can fish-oil omega-3s genuinely compete with prescription drugs for preventing migraines? Migraine affects roughly one in ten people worldwide, and standard preventive medications work for only 40–50% of those who try them, often with side effects that drive people to quit. Network meta-analysis is a technique that connects every studied treatment through shared comparison arms — here, 40 trials from the United States, Iran, Brazil, France, Norway and beyond, covering omega-3 supplements (EPA and DHA, the two main long-chain omega-3 fatty acids) alongside FDA-approved preventives like topiramate, valproate, amitriptyline, and propranolol. Participants averaged 35 years old and 79% were women, matching migraine's real-world demographics. Treatments ran 8 to 16 weeks, with migraine frequency and dropout rates as the primary measuring sticks. High-dose EPA/DHA ranked first in the entire network on every efficacy measure. It cut migraine frequency more than any drug (standardized mean difference −1.36 versus placebo, 95% CI −2.32 to −0.39 — a large effect) and reduced attack severity even more decisively (SMD −2.23, 95% CI −3.17 to −1.30). Just as important, people stuck with it: dropout was identical to placebo (odds ratio 1.00), while every prescription preventive in the network lost more patients along the way. The trade-off for honesty: the omega-3 trials were smaller than the drug trials, and the confidence intervals around these estimates are wide. This analysis moves high-dose omega-3 supplementation from "can't hurt" folk advice to a first-line candidate with top-of-network evidence, most relevant where preventive-drug side effects have been limiting. The benefit tracked the high-dose regimens, not the small amounts found in a typical daily fish-oil capsule.