Effects of serial thermal brine hand baths on hand osteoarthritis: a randomized, double-blind, sham-controlled trial.
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.
Effects of balneotherapy on stress, anxiety, and depression: results of a multicenter randomized controlled trial with six-month follow-up.
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.
An examination into the mental and physical effects of a saffron extract (affron®) in recreationally-active adults: A randomized, double-blind, placebo-controlled study.
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.
LDL-Cholesterol-Lowering Effects of a Dietary Supplement Containing Onion and Garlic Extract Used in Healthy Volunteers.
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.
Flaxseed intervention and reproductive endocrine profiles in patients with polycystic ovary syndrome: an open-labeled randomized controlled clinical trial.
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.
The effects of 12 weeks of chiropractic spinal adjustments on physiological biomarkers in adults: A pragmatic randomized controlled trial.
Imran Amjad et al. (2025) · PloS one
This pragmatic randomized controlled trial with 106 adults explored whether chiropractic spinal adjustments change measurable biological markers, not just how patients feel. Researchers tracked three systems: neuroplasticity (the nervous system's capacity to adapt, measured via brain-derived neurotrophic factor or BDNF — a protein that supports brain and nerve health), stress response (measured through cortisol, the body's primary stress hormone, sampled from blood, saliva, and hair), and inflammation (tracked via cytokines like IL-6 and TNF-α, signaling proteins immune cells use to coordinate the body's inflammatory response). The goal was to see whether chiropractic care's known benefits for pain and function might trace back to changes at this biological level.
Pain-free adults aged 20-60 with a history of recurrent (subclinical) spinal discomfort were randomly assigned to 12 weeks of chiropractic spinal manipulation — delivered about three times weekly by a registered chiropractor — or a closely matched sham procedure with no actual spinal thrust. Eighty-eight of the 106 enrolled completed the 12-week assessment. Blood, saliva, and hair samples were analyzed via laboratory immunoassay at baseline, 12 weeks, and a 16-week follow-up. Blinding worked well: 94% of participants in both groups believed they had received real chiropractic care.
After 12 weeks, the chiropractic group showed meaningfully higher blood BDNF (up 150 units, p=0.009 — a strong statistical signal this wasn't due to chance) and higher IL-6 (p<0.001) than the sham group, alongside lower TNF-α at both 12 and 16 weeks (p=0.023 and p=0.028). The researchers interpret the IL-6 rise not as harmful inflammation but as a "myokine" effect — the same kind of signal muscles release after exercise — since it appeared alongside lower TNF-α and IFN-γ, the markers more classically tied to harmful inflammation. By 16 weeks, blood cortisol and IFN-γ were lower in the chiropractic group than sham, though this reflected the sham group's levels rising over that period more than a further chiropractic effect. Markers like CRP and several immune cell counts (CD4, CD8, CD56) showed no clear group differences. Only five participants reported mild, short-lived muscle soreness; no other adverse events occurred.
This is among the first studies to track chiropractic's biological effects over months rather than single sessions, offering a possible mechanism — neuroplasticity, stress-hormone, and inflammation changes — behind chiropractic's reported clinical benefits. But the effects were modest, confidence intervals were wide, and the single-site Pakistani sample of 88 completers, with over 30% dropout by 16 weeks, limits how far these findings generalize. Larger trials that connect these biomarker shifts to actual pain relief and function are the next step.