Insulin Resistance

Valentin Borzan et al. (2023) · BMC endocrine disorders

This phase IV, double-blind randomized controlled trial with 180 participants (ProPCO-RCT) explored whether a multi-strain probiotic supplement can improve hormone and metabolic markers in women with Polycystic Ovary Syndrome (PCOS), a condition affecting up to one in five women that combines irregular periods, excess androgen (male hormone) activity, and polycystic ovaries. The trial's premise builds on prior findings that women with PCOS have a less diverse gut microbiome, which past research has linked to higher testosterone and greater insulin resistance. The study also examines equol, a compound gut bacteria make from soy isoflavones that has anti-androgenic properties, framing the gut microbiome as a possible lever on PCOS hormone levels. Participants (ages 18-45, meeting standard Rotterdam PCOS diagnostic criteria) were split into three groups of 60: a seven-strain probiotic sachet, a matching placebo, or open-label metformin (a standard PCOS drug), each taken daily for six months. The probiotic-versus-placebo comparison was blinded and allocation-concealed; the metformin group was not blinded. Measurements included blood hormone panels, an oral glucose tolerance test, a hirsutism (excess hair growth) score, body measurements, gut permeability and stool-microbiome testing (via genetic sequencing), and symptom and mood questionnaires, taken at the start and repeated at six months. As a protocol paper, this publication describes the trial's design rather than its findings — the primary comparison (change in free testosterone, probiotic versus placebo) had not yet been unblinded or analyzed at the time of publication. The one concrete number reported comes from the research group's earlier, smaller pilot study: 10 women taking the same probiotic for three months saw their free testosterone drop by a median of 0.3 pg/ml (range 1.7 down to 2.5 up), a result the team used to calculate that 60 participants per group would give the trial 80% power to detect a larger, expected 0.6 pg/ml reduction. The full trial adds metformin as a benchmark and follows participants for twice as long as most prior probiotic-PCOS studies the authors cite, several of which reported androgen and metabolic improvements with about 60 participants total. Because the results are not yet in, the paper's value lies in its design: registered with clinical trial authorities (ClinicalTrials.gov NCT04593459), ethics-approved, and built to isolate a probiotic's effect from both an inert placebo and an established drug. The authors describe it as the first trial to test a probiotic against both comparators in PCOS. The protocol also flags a limitation the authors state plainly: recruitment began before the COVID-19 pandemic, and the trial's long six-month intervention window may make some participants unable to fully follow the schedule, which is why the statistical plan pre-specifies analyzing everyone as originally assigned. Readers looking for evidence of probiotic effectiveness in PCOS will need the trial's later results publication, not this one.

Hadis Hooshmandi et al. (2024) · Journal of ovarian research

This 8-week randomized, double-blind, placebo-controlled trial with 66 women explored whether licorice (Glycyrrhiza glabra) root extract could ease some of the metabolic burden of polycystic ovary syndrome (PCOS), a hormonal condition marked by irregular ovulation, elevated androgen levels, and polycystic ovaries on ultrasound. PCOS frequently occurs alongside obesity and insulin resistance, the body's reduced response to insulin, which raises blood sugar and makes weight loss harder to achieve. The trial paired licorice extract with a calorie-restricted diet to test whether the herb added benefit beyond diet alone. Seventy-two overweight or obese women with PCOS, ages 18 to 45, at a clinic in Yazd, Iran, were randomly assigned to 1,500 mg of standardized licorice extract daily, taken as three capsules before meals, or a matching placebo, both alongside the same reduced-calorie diet, for 8 weeks. Sixty-six women completed the study. Body composition was measured with a bioelectrical impedance analyzer, and blood tests tracked fasting glucose, insulin, and cholesterol levels before and after treatment. Women taking licorice lost more weight than those on diet alone (82.60 kg versus 86.09 kg, a statistically significant difference at p<0.001) and showed larger drops in body mass index and body fat percentage. Their fasting blood sugar (74.0 versus 94.0 mg/dl), insulin (6.68 versus 11.06 µIU/ml), and an insulin-resistance score called HOMA-IR (1.23 versus 2.55) all improved significantly more than in the placebo group (p<0.001), as did triglycerides and total and LDL cholesterol (all lower with licorice) and HDL cholesterol (higher, the more favorable direction) (p between <0.001 and 0.01). A separate measure of insulin-producing capacity, HOMA-B, improved within the licorice group and looked better than placebo before statistical adjustment, but that edge disappeared once the analysis accounted for baseline differences and other factors, a reminder that not every raw difference holds up under closer scrutiny. Diet and activity levels were identical between the two groups throughout the study, and the low-calorie diet alone produced no measurable change in any of these markers over the 8 weeks. The authors propose that licorice's compounds act on fat metabolism, insulin signaling, and cholesterol handling through several biological pathways, though those pathways were not directly measured in this trial. The study ran for only 8 weeks, did not test licorice without the accompanying diet, and relied on 24-hour dietary recall, a self-reported method that can be imprecise. Longer trials isolating licorice's own effect and testing its proposed mechanisms, in more diverse populations than this single-center Iranian cohort, are needed to confirm these results.

Yan-Kun Chen et al. (2023) · Frontiers in endocrinology

This literature review asks two connected questions: what actually drives obesity and type 2 diabetes at a biological level, and whether Traditional Chinese Medicine has anything to offer in managing them. The two conditions are closely linked — the review notes that type 2 diabetes accounts for roughly 90% of all diabetes cases and is strongly tied to excess weight. There is a practical bind behind the question, too: several standard diabetes drugs, including insulin and sulfonylureas, make weight loss harder rather than easier. The authors searched PubMed, Scopus and Web of Science for work published between 2019 and 2023, covering molecular, cellular and clinical studies of how obesity, diabetes and TCM interact. It is important to be clear about what kind of review this is: a narrative overview rather than a systematic one. There is no count of included trials, no pooled statistics and no formal assessment of study quality, so it maps a field rather than measuring an effect. On mechanism, the review draws a useful distinction between visceral fat — stored around the liver, pancreas and kidneys, hormonally active, and the type that drives insulin resistance — and subcutaneous fat sitting under the skin. This is why apple-shaped fat distribution carries more metabolic risk than pear-shaped. The scale of the problem is stark: the World Health Organization counted 1.9 billion overweight adults in 2016, 650 million of them with obesity, and 38.2 million children under five overweight or obese in 2019. The TCM proposal is that acupuncture, herbal remedies and dietary therapy act on inflammation, oxidative stress, insulin resistance and the balance of gut bacteria. What this review does not provide is evidence of how well any of that works. No effect sizes, no confidence intervals, no trial results for any specific TCM intervention appear. The authors themselves conclude only that TCM may be promising and that well-designed studies are still needed to confirm both efficacy and safety. Read it as a map of plausible mechanisms and an argument for research, not as grounds for choosing a treatment.