The Effect of Integrative Naturopathic Oncology Including Modulated Electrohyperthermia on Survival Outcome among Glioblastoma Multiforme Patients: A Retrospective Study.
Sara Izadi-Najafabadi et al. (2025) · Integrative cancer therapies
This retrospective study compared 67 people with grade IV glioblastoma (GBM), a fast-growing brain cancer, who received integrative naturopathic care at a Canadian clinic with 243 matched patients from the U.S. SEER cancer registry. The clinic's approach added modulated electro-hyperthermia (mEHT), a radiofrequency treatment that heats tumour tissue, plus high-dose intravenous vitamin C, supplements, acupuncture and diet counselling, on top of standard surgery, radiotherapy and temozolomide chemotherapy. Standard care for GBM extends median survival only to about 14.6 months, so the authors looked for any signal that the extra treatments might add survival time.
Patients had at least six mEHT sessions between 2010 and 2024, with a median of 13 sessions of up to 60 minutes each at powers rising from 50 to 140 watts. Controls were matched on age, sex, diagnosis year and whether they had surgery, radiation and chemotherapy. To avoid giving the clinic group credit for the months before they arrived, survival was counted from the start of clinic treatment (or the matched patient's start date for controls) and compared with Kaplan-Meier curves and Cox regression.
Median survival from that starting point was 15 months with integrative care versus 11 months in controls, and the hazard ratio of 0.72 (95% CI 0.53-1.00, p = 0.05) sat right at the edge of statistical significance (a 28% lower hazard of death). The difference was concentrated in people who started within 120 days of diagnosis (hazard ratio 0.52, p = 0.006, roughly half the hazard of death) and in those under 50 (0.51, p = 0.009); starting later or being 50 or older showed no difference (0.98 and 0.96). Treatment began a median of 124 days after diagnosis, so these patients had already survived that long. The authors saw no seizures or other side effects. Those subgroup analyses were exploratory, unadjusted for multiple testing, and the matched groups still differed in how many had chemotherapy and radiotherapy.
Because treatment was not randomised and many factors that shape GBM survival, such as tumour genetics, extent of surgery and general fitness, were unavailable, the results cannot show that the integrative care caused the longer survival. Clinic patients also paid for their own care, which may favour those with more resources, and the dose and timing of mEHT varied between individuals. The authors describe the findings as hypothesis-generating, a signal rather than an effect estimate, and call for randomised trials.
A Prospective Observational Study of a 2-Week Integrative Inpatient Therapy on Patients with Fibromyalgia Syndrome.
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.
Efficacy of antioxidant supplementation in alleviating endometriosis-related pain: insights from a systematic review and meta-analysis of RCTs.
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.
Effect of Fish-Derived Lipids on Inflammation Status and Health-Related Quality of Life in Women with Endometriosis.
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.
The Use of Herbal Remedies among Mothers of Young Children Living in the Central Appalachian Region.
Monira Alwhaibi et al. (2017) · Evidence-based complementary and alternative medicine : eCAM
This cross-sectional survey of 178 mothers of young children in the Central Appalachian Region of the United States explored how many use herbal remedies and which factors are linked to that use. Herbal remedies are plant-based products taken for health purposes, and they are the most common form of complementary and alternative medicine (CAM, health approaches used alongside or instead of conventional care) among American adults. The authors framed the work with the Comprehensive Model of Information Seeking, which holds that a person's background, past experiences, mood and beliefs shape where information is sought and, in turn, whether action follows, here the use of herbal remedies.
The participants were women aged 18 or older with at least one child under three years of age, living in Central Appalachia and mostly in West Virginia, with a mean age of 31.3 years. They were recruited through social media groups, listserv emails, daycares and physician's offices, and completed an online survey. One item asked whether any herbal remedy had been used in the past six months, with follow-ups on which remedy and which condition. Two new five-point scales captured how often six information sources were used and how strongly herbal remedies were believed to be safe and effective.
One-third of the women (33.5%) reported using herbal remedies in the past six months. Fenugreek was the most widely used remedy (35.1%), followed by honey (8.8%), chamomile (5.3%) and ginger (5.3%). The main reasons were stimulating or increasing breast milk production (38.6%) and treating cold or flu symptoms (26.3%). Women with the highest information seeking scores had 3.61 times the odds of using herbal remedies compared with those with the lowest (95% CI 1.433-9.77), meaning that more active information seeking went with more use. Women with the highest belief in herbal safety and efficacy had 4.02 times the odds (95% CI 1.468-9.57). Part-time or unemployed women had 2.98 times the odds of full-time employed women (95% CI 1.05-8.47), while education, income and Appalachian identity showed no association. The internet was the most frequently used information source (mean 3.2 out of 5).
The authors conclude that herbal remedy use is common in this region and propose that public health efforts and communication from health care providers could raise awareness of the safety and efficacy of herbal remedies. The survey recorded use and beliefs only; it did not test whether any remedy worked, and safety was not assessed. Limitations include a sample drawn mostly from West Virginia, self-selection in an internet-based survey, self-reported answers open to recall bias, and no data on whether use was regular or occasional. The authors call for further research, including qualitative work, on what health information women seek.
Combined effects of photobiomodulation and osteopathic manipulation on the physical performance of young adults subjected to exercise-induced muscle damage: a randomized placebo-controlled trial.
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.
Temporal dynamics of muscle strength recovery following acute cold-water immersion: a systematic review and meta-analysis.
Yang Zhu et al. (2026) · PeerJ
This systematic review and meta-analysis pooled 22 randomized controlled trials with 375 mostly male participants to ask when, if at all, a single cold-water immersion (CWI) after exercise helps muscles recover. CWI means immersing the body, from navel depth up to the neck, in water of roughly 5 to 20 degrees C for about 6 to 20 minutes. Exercise-induced muscle damage (EIMD) is the loss of force, soreness and raised creatine kinase (CK, a blood marker leaking from stressed muscle cells) that follows hard or unaccustomed exercise, often with delayed onset muscle soreness (DOMS). Earlier reviews mixed time points, so this one separated results at 0, 24, 48 and 72 hours.
The included trials enrolled healthy non-athletes and athletes aged about 16 to 49, who exercised with intervals, simulated matches, distance running or heavy eccentric lifting. After exercise, one group sat in cold water and the comparison group rested seated for a similar time. Researchers measured maximal voluntary isometric contraction (MVIC, the hardest possible static muscle squeeze), countermovement jump (CMJ, jump height as a gauge of explosive power), CK, and soreness on a visual analog scale (VAS, a line marked from no pain to worst pain).
Maximal strength was unchanged by CWI (g = 0.08, 95% CI -0.11 to 0.26, p = 0.42; a negligible effect) at every time point. Jump performance was worse immediately afterward (g = -0.68, p = 0.01; a medium-sized drop) and showed no difference by 24 to 48 hours (g = 0.38 at 24 h, p = 0.06; g = 0.06 at 48 h, p = 0.68). CK looked lower after CWI (g = -0.43, p < 0.001; a small effect), but the result shrank to non-significance after correcting for likely missing small studies (g = -0.16, 95% CI -0.44 to 0.12; the original benefit was probably overestimated). Soreness was lower (g = -0.58, p = 0.006; a medium effect), though the trials disagreed widely (I² = 87%) and the certainty of evidence was rated very low.
The evidence has clear limits: 362 of 375 participants were male, participants could not be blinded to cold water, several trials were tiny, and only one immersion with follow-up of 72 hours or less was studied. The authors suggest the soreness effect is the most plausible benefit and the temporary jump decrement is the main drawback. Repeated use during training and its effect on muscle adaptation were not examined, and they call for larger trials that include women and standardize temperature and duration.
Climatotherapy in marine and dead sea environments for musculoskeletal and rheumatologic conditions: a systematic review of effectiveness and safety.
Tatiana Leite Müller et al. (2026) · International journal of biometeorology
This systematic review of nine studies with 465 adults looked at climatotherapy, the therapeutic use of climate and natural settings, for musculoskeletal and rheumatologic disorders such as osteoarthritis, rheumatoid arthritis, fibromyalgia and ankylosing spondylitis. The settings were the Dead Sea (very salty water, low humidity, distinctive solar radiation and air pressure about 5% above sea level) and coastal sites using thalassotherapy, which means bathing and exercising in seawater, sometimes with marine mud, sun exposure and sea air. Because these programs vary widely, the authors wanted to gather what trials say about pain, physical function, quality of life and safety.
The reviewers searched three databases through September 2025 and included eight randomized trials and one non-randomized study from 1995 to 2011, mostly in Israel. Participants were aged 18 to 65 and stayed at a spa or coast for 10 days up to 12 weeks. Comparison groups used freshwater pools, usual care, pool exercise or the same program in Norway. Pain was usually rated on a 0 to 100 visual analog scale, and quality of life was measured with questionnaires such as the SF-36.
Most studies reported short-term improvements in pain, stiffness, function and quality of life, mainly within groups. Only two studies could be pooled for pain, giving an inconclusive overall result (SMD -0.47, 95% CI -5.47 to 4.53; an interval too wide to show benefit or no benefit). Split by condition, osteoarthritis showed a large effect (SMD -1.01, meaning pain fell by roughly one standard deviation more than with comparison) while fibromyalgia showed a small non-significant one (SMD -0.18, p = 0.158). In fibromyalgia, single-study estimates showed fewer tender points (SMD -0.50, p = 0.0047) and better physical quality of life (SF-36 physical score 0.36, p = 0.0391), but mood scores (p = 0.5968) and overall fibromyalgia impact (p = 0.0612) did not change significantly. No serious adverse events were reported, though only one study recorded adverse events explicitly.
The evidence has important limits: trials were small and published between 1995 and 2011, participants and therapists could not be blinded, safety was inconsistently recorded, and several programs combined many components, so the effect of the climate itself is hard to separate. Only one trial analyzed all participants as randomized, and the pooled estimate rests on two studies. Certainty was judged low. The authors suggest climatotherapy may be a complementary option, particularly for osteoarthritis, and call for multicenter randomized trials with standard outcome sets and systematic safety reporting.
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.
The Effects of Combined Scutellaria and Saffron Supplementation on Mood Regulation in Participants with Mild-to-Moderate Depressive Symptoms: A Randomized, Double-Blind, Placebo-Controlled Study.
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.
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.
Combined berberine and probiotic treatment as an effective regimen for improving postprandial hyperlipidemia in type 2 diabetes patients: a double blinded placebo controlled randomized study.
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.
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.
Early acupuncture intervention for pain relief in emergency department patients with suspected acute renal colic caused by urinary calculi: a randomized clinical trial.
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.
Effect of Adjunctive Acupuncture on Pain Relief Among Emergency Department Patients With Acute Renal Colic Due to Urolithiasis: A Randomized Clinical Trial.
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.
Desmodium styracifolium Total Flavone Capsules for Urolithiasis: A Phase 3 Randomized Clinical Trial.
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.
Therapeutic effect of Siddhar yogam on varicose veins - A pilot clinical trial.
Manobala V R et al. (2026) · Bioinformation
This single-arm pilot trial with 30 participants explored whether a 90-day Siddhar yogam programme could reduce the symptom burden of varicose veins, which are dilated, twisted veins of 3 mm or more in the legs. Siddhar yogam belongs to the Siddha system of medicine, a South Indian tradition that explains illness through three humors, Vatham (air), Pitham (fire) and Kabham (water), and counts Siddhar yogam among its Kayakarpam (rejuvenation science) methods. The practice combines yoga postures, controlled breathing and meditation. The authors note that no standardized, non-invasive therapy exists for varicose veins, a condition they say affects about 5% of people in India.
The 30 patients (10 men and 20 women, aged 30 to 55) were recruited at the National Institute of Siddha's Ayothidoss Pandithar Hospital. All practised the same 35-minute routine for 90 days: a few minutes of relaxation, 21 minutes of postures such as raised-leg pose, half plough, inverted pose and cycling pose, and 5 minutes of Thirumoolar breathing practice. Symptoms and quality of life were scored with the Aberdeen Varicose Vein Questionnaire (AVVQ), where a lower score means less impact, before and after the programme. There was no comparison group.
Average AVVQ scores dropped from 16.2 to 12.0 (a fall of 4.2 points; reported as significant at p < 0.05 by Wilcoxon signed rank test). Most participants (over 85%) reported long periods of standing, and the Siddha assessments, which grade humors, body constituents and an eight-fold examination, showed derangement mainly in Vatham and Pitham before treatment and a reduction in these findings afterwards, though the paper gives no figures for that change.
The authors suggest the postures lower pressure in the leg veins and help blood return to the heart by working the calf muscles, but they did not measure this. Because the trial had one arm, no follow-up and only one outcome measure, and excluded severe cases, the authors say the efficacy of the regimen cannot be established. They recommend larger randomized trials.
Does radiographic imaging for spinal pain in patients receiving chiropractic care change patient outcomes? A pilot randomised controlled trial.
Hazel J Jenkins et al. (2026) · Chiropractic & manual therapies
This pilot randomised trial with 20 patients and 11 chiropractors explored whether it is practical to run a large study asking a simple question: does taking spinal x-rays change outcomes for people receiving chiropractic care for back or neck pain? In medical settings, trials have found routine imaging does not improve non-specific low back pain, yet chiropractors use x-rays at widely varying rates (8% to 84%), partly to screen for reasons spinal manipulation might be unsuitable. No randomised trial had tested imaging where manipulation is also part of care, so the authors first tested whether such a trial could work.
Chiropractors in Sydney, Australia, invited adults with a new episode of spinal pain, where the chiropractor was unsure whether an x-ray was needed. A computer randomly assigned each consenting patient to get spinal radiographs or not, and everything else, including manipulation, was decided between chiropractor and patient. Pain, disability (Roland Morris Disability Questionnaire for the back, Neck Disability Index), satisfaction and side effects were collected at 2, 6 and 12 weeks, and chiropractors were interviewed about the experience.
Recruitment was the main difficulty: 135 patients were screened, 33 (24%) were eligible and 20 took part, short of the 50 planned. Three of 10 patients assigned to imaging did not get it, and 2 of 10 assigned to no imaging did, always after a clinical change. Follow-up fell from 90% of patients at 2 weeks to 75% at 12 weeks. Pain and disability fell in both groups, but differences between groups were small and the trial was too small to compare them. Mild, short-lived side effects such as muscle soreness affected 4 of 20 participants (1 imaging, 3 no imaging).
The authors judged that most criteria for a larger trial were met but recruitment and cross-over would need strategies, since COVID-19, time pressure and discomfort explaining diagnostic uncertainty to patients limited enrolment. Limitations include a self-selected group of chiropractors, probably non-consecutive recruitment and mostly young, low-disability participants.
Efficacy of manual therapy by different healthcare professionals on pain and function in temporomandibular disorders: a systematic review of randomized controlled trials.
Rita Chiaramonte et al. (2026) · The Journal of manual & manipulative therapy
This systematic review of 18 randomized controlled trials explored whether hands-on treatment eases pain and improves jaw movement in adults with temporomandibular disorders (TMD). TMD is a group of conditions affecting the jaw joint, the chewing muscles and nearby tissues, and it is estimated to affect about 31% of adults. Its subtypes include muscle pain (myalgia), disc displacement (the cushioning disc slips out of position, sometimes locking the jaw) and joint pain. Manual therapy covers thrust manipulation, soft-tissue release, massage and intra-oral techniques, delivered by physiotherapists, chiropractors, osteopaths, dentists and physicians. The review asked which techniques help most and whether results differ by profession.
Researchers searched four databases through March 2025 and screened 561 records, keeping 18 trials of adults with a clinical TMD diagnosis. Trials compared manual therapy with sham treatment, no treatment, splints, medication, exercise or education. Pain was rated on the visual analogue or numeric rating scale (0 to 10), and maximum mouth opening was measured in millimetres. Risk of bias was checked with the Cochrane tool and certainty with GRADE. Because the trials differed so widely in technique, dose, comparator and follow-up, results were summarized in words rather than pooled statistically.
Most trials reported short-term pain reduction and wider mouth opening, but certainty was low to moderate for pain and low for mouth opening. High-velocity low-amplitude (HVLA) thrusts made up 56% of interventions and fascial manipulation with myofascial release made up 37.5%. Dry needling plus upper neck HVLA beat splint therapy, diclofenac and joint mobilization at three months (p < 0.001), and intra-oral therapy kept benefits for one year in chronic jaw-muscle pain. Upper thoracic HVLA showed no significant effect (p > 0.05), and jog manipulation gained only 6.86 mm of mouth opening at first visit with no later group difference. Massage and fascial manipulation by physiotherapists were linked to relief of jaw-muscle symptoms, while chiropractic, osteopathic and dental trials also reported gains. Physiotherapy trials were the most numerous, which the authors attribute to publication volume rather than superior effectiveness.
The authors describe manual therapy as associated with short-term benefit and treat professional comparisons as descriptive, since profession was tangled with setting, technique and country. Limitations include small samples, short follow-up, mixed diagnoses, English-only searching and no meta-analysis. Safety findings were not reported in pooled form, and the evidence mostly covers weeks to months rather than years. The authors call for larger trials with longer follow-up and standardized protocols, and they state that manual therapy is best delivered by trained, licensed professionals.
Immediate clinical and neuromechanical effects of cervical spine manipulation compared to cervical spine mobilization among individuals with chronic neck pain: a randomized mechanistic cross-over trial.
Salma Bouqartacha et al. (2026) · Chiropractic & manual therapies
This randomized mechanistic cross-over trial with 89 adults explored how two hands-on neck treatments differ right after they are delivered. Chronic neck pain, defined here as pain lasting at least 12 weeks, is one of the leading causes of disability worldwide. Spinal manipulation (SM) is a single quick, shallow thrust applied to a joint, and spinal mobilization (Smob) is a slower, repeated rocking pressure on the same area. Both are recommended in clinical guidelines, but they are often lumped together, so little was known about how their effects on pain, movement and muscle activity compare.
Participants were aged 18 to 65, with an average of 35 years, and 65% were women. They were recruited in Zurich, Switzerland, and Trois-Rivieres, Canada. Each person attended two sessions three days apart, receiving SM in one and Smob in the other in random order. SM was one thrust to the most painful neck joint while lying face up, and Smob was 30 seconds of repeated pressure on the same level while lying face down. Pain was rated from 0 to 10, and neck movement, tenderness to pressure, grip strength and muscle electrical activity were measured before and after.
Pain dropped by 0.79 points after SM and 0.37 points after Smob, a gap of 0.41 points (p = 0.002), which stayed below the 1.3 points considered clinically meaningful. Neck movement improved after both treatments, by about 4.6 degrees after SM and 3.7 degrees after Smob in bending forward and back, with no difference between them. Neck muscles responded more strongly during SM, with activity in the sternocleidomastoid about six times higher (0.144 versus 0.023). Tenderness and grip strength changed inconsistently, and the grip decrease of 1.13 kg was far under the 6 kg detectable change. Participants' own global impression of change favored SM (p < 0.001) but also stayed below the clinical threshold. Upper trapezius activity was likewise higher during SM (0.083 versus 0.024). No serious adverse events were reported.
The authors state that statistically significant differences did not reach clinical significance, so the trial cannot support conclusions about which treatment works better in practice. Only immediate effects after one session were measured, many outcomes were tested, participants could tell the treatments apart, and baseline disability was mostly mild to moderate. Clinician training also differed between sites. The authors propose that future trials examine several sessions of each treatment, since a multi-session or combined approach may reach clinical relevance.