Randomized Controlled Trial

Erik Hulander et al. (2022) · Nutrients

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

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

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

Maria Teresa Guagnano et al. (2021) · Nutrients

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

Ali Tabatabaeyan et al. (2025) · Scientific reports

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

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

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

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

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

Angelika Bogusz et al. (2026) · Nutrients

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

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

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

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

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

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.

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

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

Ying Cao et al. (2025) · QJM : monthly journal of the Association of Physicians

This randomized trial with 84 emergency department patients explored whether acupuncture started right away, before a diagnosis is confirmed, eases the pain of suspected renal colic, the sudden, severe cramping pain in the back or abdomen that usually comes from a kidney or urinary stone. Imaging to confirm a stone takes time while patients are in extreme pain, and the authors note that the usual painkillers have drawbacks: anti-inflammatory drugs can raise heart risk with higher doses and longer use, and opioids cause side effects including nausea, drowsiness and dependence concerns. Acupuncture, a traditional Chinese medicine technique that places thin needles at specific body points, had already been reported by this group to reduce pain in confirmed cases. Adults aged 18 to 80 with one-sided colicky pain and tenderness over the kidney area, and pain of at least 4 on a 0 to 10 scale, were treated at a Beijing hospital emergency department. Half received needles in the back of both hands at Yaotongdian, a point the authors use for lumbar pain, with the needles lifted and rotated until a soreness or heaviness sensation appeared and then left in for 30 minutes. The other half had very shallow needling with tiny short needles at spots that are not acupuncture points, with no manipulation. Ten minutes after needling, 64.3% of the acupuncture group (27 of 42) had at least halved their pain, versus 16.7% of the sham group (7 of 42), a 47.6 percentage point gap (P < 0.01, so chance is very unlikely to explain it). By 30 minutes the figures were 85.7% versus 31.0%. Average pain scores at 10 minutes were 3.38 versus 6.00. Fewer acupuncture patients needed an analgesic injection by 30 minutes (33.3% vs 59.5%; P = 0.03) and satisfaction scores were higher (4.69 vs 3.69). Patients, outcome assessors and statisticians did not know the group, and patients guessed their group at similar rates, so the blinding held. Surgery and return visits did not differ between groups, and each group had one adverse event (bleeding with acupuncture; nausea and vomiting with sham). The authors suggest that early acupuncture is a safe option for pain relief while a diagnosis is awaited and that it did not appear to interfere with later care. The authors also note that a single acupuncture point may give limited improvement in critically ill patients. They state plainly that the study was done at one center with experienced acupuncturists, included only 3 acupuncture-group patients who turned out not to have a urinary stone, and did not analyze results by stone size. They call for multicenter confirmation.

Jian-Feng Tu et al. (2022) · JAMA network open

This randomized trial with 80 emergency department patients explored whether adding acupuncture to a standard painkiller injection brings faster relief from renal colic, the severe cramping flank pain that occurs when a kidney stone blocks or moves through the urinary tract. Renal colic is described by the authors as one of the worst types of pain, and the guideline first-choice drugs, nonsteroidal anti-inflammatory medicines such as diclofenac, take time to work: in an earlier study, 37.5% of patients still had moderate or severe pain 15 minutes after an injection. Acupuncture, a traditional Chinese medicine technique that inserts thin needles at specific body points, had shown quick pain reduction in other settings. Adults aged 18 to 75 with stone-related renal colic and pain of at least 4 out of 10 on a visual analog scale (a line on which patients mark their pain) were treated at a Beijing hospital emergency department in 2020. Everyone received a 50 mg diclofenac injection into the muscle. Half then had 30 minutes of needling at Yaotongdian, a point on the back of each hand, with the needles twisted and lifted until a soreness or heaviness sensation (called De qi) appeared. The other half had shallow needle pricks at forearm spots that are not acupuncture points. Ten minutes after needling, 77.5% of the acupuncture group (31 of 40) had at least halved their pain score, compared with 10.0% of the sham group (4 of 40), a gap of 67.5 percentage points (P < .001, so chance is very unlikely to explain it). Average pain fell to 3.0 versus 5.9 out of 10. Acupuncture also led at 0, 5, 15, 20 and 30 minutes (97.5% vs 80.0% at 30 minutes; P = .03). Patients, assessors and the statistician did not know the group, and patients guessed their group about equally often in both arms (P = .48). The advantage faded as the injection took effect: by 45 and 60 minutes both groups had about 92% to 98% responding (P = .62), and only 1 patient needed stronger rescue medication. No adverse events were recorded. The authors suggest acupuncture may serve as an optional add-on for faster relief, since it uses a single point and needs no individual diagnosis. They attribute the absence of a rescue-medication difference to a possible ceiling effect from the diclofenac. They note limitations plainly: one hospital, treatment given after diagnostic imaging, experienced acupuncturists who could not be blinded, and no follow-up of pain beyond 60 minutes or analysis by stone size. They plan to study acupuncture before imaging.

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

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