All Ages

H J Hamre et al. (2023) · Systematic reviews

This systematic review examined six earlier meta-analyses (statistical pooling studies) of placebo-controlled randomized trials of homeopathy for any health condition in humans, asking whether homeopathy shows an effect beyond placebo. Homeopathy is built on drug provings (recording symptoms in healthy people), the principle that a substance causing a symptom pattern is used to treat a similar one, and potentization, which means serial dilution with vigorous shaking. Because the six meta-analyses, published between 1997 and 2017, used different methods and reached different conclusions, the authors reviewed them together under a published protocol and judged their risk of bias and the certainty of the overall evidence. The authors searched eight databases plus a private collection and contacted experts, identifying 16 reports covering six meta-analyses, with searches running to December 2020 and an update to April 2023. Two reviewers screened and extracted data independently. The meta-analyses together covered 310 trials or trial comparisons (182 distinct trials published between 1943 and 2014), most often on respiratory conditions such as allergic rhinitis and influenza. Each meta-analysis was rated for risk of bias with ROBIS, and the combined evidence was graded with a GRADE-based approach. All five meta-analyses with reported pooled estimates found a significant effect favouring homeopathy across all trials, for example an odds ratio of 2.45 (95% CI 2.05-2.93) across 89 trials in the 1997 analysis and a standardized mean difference of 0.33 (0.21-0.44) across 54 non-individualised trials in 2017. When only high-quality trials were kept, three of four analyses stayed significant, but the 2017 analysis did not (SMD 0.18, -0.09 to 0.46, 3 trials). Only 6-29% of trials met each analysis's high-quality criteria. Three analyses showed significant heterogeneity and funnel plot asymmetry, a pattern that can signal publication or small-study bias; individualised homeopathy showed neither. Two analyses that combined quality and trial-size restrictions found no significant difference from placebo. Three meta-analyses were rated low and three high risk of bias. The authors rated evidence certainty as high for individualised homeopathy and moderate for the other categories. The authors conclude that the data do not support the hypothesis of no difference from placebo and that placebo-controlled evidence gives no justification for regulatory action against homeopathy. The review only covers trials already in six meta-analyses, so trials after 2011 (individualised) and 2014 (non-individualised) are missing. It also reports no indication-specific results, and its use of GRADE tested whether any effect exists rather than how large it is. The authors recommend updating the individualised homeopathy analysis and studying specific non-individualised treatments for specific conditions.

María Magdalena Vaccarezza et al. (2026) · PloS one

This systematic review with meta-analysis pooled 17 randomized controlled trials of ketogenic diet therapies (KDTs) for drug-resistant epilepsy, meaning epilepsy that keeps causing seizures after two or three appropriately chosen antiseizure medications have failed. About 30% of people with epilepsy fall into this group. KDTs are high-fat, low-carbohydrate, adequate-protein diets that shift the body toward burning fat and producing ketone bodies, which are fat-derived fuel molecules that may calm brain activity and support neuron energy metabolism. Several forms exist: the classical ketogenic diet, the medium-chain triglyceride (MCT) diet, the modified Atkins diet with unrestricted protein, and the low glycemic index treatment. A 2020 Cochrane review left the evidence uncertain, and this update added newer trials. Eleven trials enrolled children and six enrolled adolescents and adults, with follow-up of up to 24 months. In nearly all trials, a ketogenic diet was compared with usual care, most often an added medication. The authors searched four databases in February 2024 and again in June 2025, screened 1,193 unique records in duplicate, and pooled results as relative risks (RR) using random-effects models. Study bias was rated with the Cochrane RoB 2 tool, and confidence in each result was graded from high to very low using GRADE. In children, a 50% or greater drop in seizures was far more likely with KDT (RR 4.06, meaning roughly four times the likelihood; 49.7% versus 12.2%, or 37 more children per 100). A 90% or greater drop was borderline (RR 1.74, 95% CI 1.00 to 3.03). Adverse events were similar to usual care (RR 1.03), and dropout was not significantly different (RR 1.64, 95% CI 0.88 to 3.07). In adolescents and adults, 50% or greater seizure reduction was also more likely (RR 7.73, which translates to 16 more per 100), with moderate certainty. Near-complete seizure control (RR 13.00, with a very wide interval of 0.74 to 226.98), side effects and dropout could not be judged because of very low certainty. Reported side effects were mainly gastrointestinal and resolved when the diet stopped. Quality of life findings were mixed: one infant trial found small differences favoring medication in temperament and peer relationships, while parents in another trial reported improved alertness and sleep. The authors interpret the findings as a clinically meaningful benefit for moderate seizure reduction, strongest in children. Certainty was limited by the impossibility of blinding a diet, small event counts and high heterogeneity for some outcomes. Most trials came from high-income countries, which may limit generalizability, and publication bias could not be excluded. No trial reported hospitalizations, status epilepticus or survival. The authors call for better evidence on safety, adherence, cognition and quality of life.

Sophia Tsokkou et al. (2026) · International journal of molecular sciences

This systematic review pulled together seven randomized controlled trials to ask whether vitamin D, vitamin C, and vitamin E supplements affect endometriosis, a long-term inflammatory condition in which tissue like the uterine lining grows outside the uterus and affects roughly 1 in 10 women of reproductive age. Common symptoms include painful periods (dysmenorrhea), chronic pelvic pain, pain during intercourse (dyspareunia), and difficulty conceiving. The vitamins were chosen because vitamin D helps regulate immune signaling, while vitamins C and E act as antioxidants that neutralize reactive oxygen species (unstable molecules that damage cells and add to inflammation). Both processes are central to how endometriosis develops and causes pain. The authors registered their protocol in PROSPERO and searched PubMed, Scopus, and ScienceDirect, screening 5,639 records down to seven eligible trials. Two reviewers screened independently, and trial quality was graded with the Jadad scale and the Cochrane RoB 2 tool. The trials varied widely: vitamin D doses ranged from 2000 IU daily to 50,000 IU weekly, vitamin C and E doses from 343 mg and 84 mg to 1000 mg and 800 IU daily, and treatment lasted from about 8 weeks to 6 months. Because of this variation, results were described narratively rather than pooled. High-dose vitamin D (50,000 IU every two weeks) cut pelvic pain scores by 1.12 points (95% CI -2.1 to -0.09; p = 0.03) and lowered hs-CRP, an inflammation marker, by 0.64 mg/L. A weekly 50,000 IU regimen lowered active β-catenin (a signaling protein linked to lesion invasion) in endometrial tissue. Lower daily doses did not clearly beat placebo, since both groups improved by similar amounts. Vitamin C plus E for eight weeks reduced oxidative stress markers, and one trial reported pain drops of 43% for daily pelvic pain, 37% for painful periods, and 24% for painful intercourse. Pregnancy rates did not rise in the trial that measured them. Side effects were generally minor, mostly occasional digestive upset. Three trials were rated low risk of bias and four had some concerns. The authors describe vitamins as a possible well-tolerated adjunct for pain and oxidative stress, though not for fertility. The evidence base is small, with only seven trials, English-language inclusion only, very different dosing across studies, and no trial using a publicly available preregistered protocol. Few trials checked participants' baseline vitamin levels, so it remains unclear whether any benefit depends on deficiency. The authors call for larger multicenter trials with standardized doses, longer follow-up, and fertility and lesion outcomes.