In an evolving health landscape, emerging research continues to highlight concerns that could impact everyday wellbeing. Here’s the key update you should know about:
A new synthesis of randomized trials reveals that a carefully supervised very low-carbohydrate ketogenic diet can improve weight, insulin control, and androgen levels in women with PCOS, offering short-term clinical gains while underscoring the need for longer-term safety data.
Study: Effects of the very low-carbohydrate ketogenic diet in women with Polycystic Ovary Syndrome: a systematic review with meta-analysis of clinical trials. Image Credit: mady70 / Shutterstock
In a recent study published in the British Journal of Nutrition, a group of researchers synthesized randomized clinical trials (RCTs) on the effects of the very low-carbohydrate ketogenic diet (VLCKD) in women with Polycystic Ovary Syndrome (PCOS), covering anthropometric, hormonal, and metabolic outcomes.
PCOS Symptoms, Insulin Resistance, and Diet Challenges
One in ten women of reproductive age lives with PCOS, a condition tightly linked to insulin resistance (IR), weight gain, and low-grade inflammation, which are factors that ripple into everyday life through irregular cycles, fertility worries, and cardiometabolic risk. Small, strategic weight loss can normalize periods and improve chances of conception, yet many diets feel impractical for busy households. VLCKD induces nutritional ketosis and may lower insulin levels, reduce visceral fat, and rebalance androgen levels, offering a potentially practical, food-based approach. However, because VLCKD trials are short, highly variable, and often restrictive, long-term safety, adherence, and comparative effectiveness versus other eating patterns remain uncertain, and hence further research is needed.
Search Strategy and PCOS Trial Eligibility Criteria
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance and a protocol registered in the International Prospective Register of Systematic Reviews (PROSPERO), investigators searched Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Medical Literature Analysis and Retrieval System Online (MEDLINE) via PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and Web of Science for RCTs through July 2025. Eligible participants were adult women with PCOS assigned to a VLCKD.
Anthropometric, Hormonal, and Metabolic Endpoints Assessed
Outcomes included anthropometric measures such as weight, body mass index (BMI), waist circumference (WC), fat body mass (FBM), and waist-to-hip ratio (WHR); hormonal markers such as sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), free and total testosterone, and the LH/FSH ratio; and metabolic endpoints such as fasting glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglycerides, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and total cholesterol.
Meta-Analysis Methods and Evidence Grading
Data were extracted in duplicate with disagreements resolved by a reviewer. Meta-analyses used weighted mean differences (WMDs) with 95 percent confidence intervals (CIs). Random-effects models, Hartung-Knapp adjustments, Cochran’s Q, and I² quantified uncertainty and heterogeneity, and funnel plots screened publication bias. Certainty of evidence was graded using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE).
Scope of VLCKD Trials Across Countries and Protocols
Across the evidence base, 12 trials were included qualitatively and 11 in meta-analyses, enrolling more than 800 women with PCOS from Italy, China, Pakistan, and the United States, and using parallel and crossover designs over approximately 4 to 24 weeks. Diet protocols ranged from VLCKD (~750–800 kcal/day) to energy-restricted VLCKD (~1300–1500 kcal/day), consistently restricting carbohydrates sufficiently to induce ketosis while providing adequate protein. Several outcomes exhibited very high statistical heterogeneity, reflecting differences in caloric levels, carbohydrate thresholds, lipid composition, adherence monitoring, and concurrent treatments.
Anthropometric Changes Supporting Weight and Fat Loss
Anthropometry showed clinically meaningful improvements that map to real-life wins, such as looser waistbands, better sleep, and easier movement. Body weight fell substantially (WMD −9.57 kg), alongside reductions in WC (WMD −7.75 cm) and FBM (WMD −7.44 kg). BMI decreased (WMD −3.45 kg/m²), and WHR modestly improved (WMD −0.02). Sensitivity analyses supported the direction of these effects, despite I² values often exceeding 90%, and there was no consistent sign of publication bias in the funnel plots.
Hormonal Shifts Indicating Reduced Hyperandrogenism
Hormonal profiles moved in a direction consistent with reduced hyperandrogenism and improved ovulatory potential, outcomes that matter to women tracking cycles at home or planning pregnancy. Free testosterone decreased (WMD −0.31 ng/dL) and total testosterone decreased (WMD −7.21 ng/dL), while SHBG increased (WMD +15.22 nmol/L). LH fell (WMD −3.97 U/L), the LH/FSH ratio declined (WMD −1.04), and FSH showed no significant change, an overall pattern compatible with easing androgen excess and better follicular dynamics.
Glucose and Insulin Improvements Reflect Better Metabolic Control
Glucose-insulin outcomes echoed the anthropometric and hormonal shifts. Fasting glucose dropped (WMD −9.65 mg/dL), fasting insulin declined (WMD −2.41), and HOMA-IR improved (WMD −2.46). These shifts translate to fewer “sugar crashes,” steadier energy, and potentially lower long-term risk for type 2 diabetes mellitus (T2DM). In lipid outcomes, triglycerides were reduced (WMD −29.95 mg/dL), whereas total cholesterol, LDL-c, and HDL-c showed no significant pooled changes during the short-to-intermediate follow-up.
Bias, Heterogeneity, and Reporting Limitations
Risk-of-bias assessments rated most domains low or with some concerns, but three trials were explicitly judged to have high risk of bias due to non-true randomization or missing outcome data. Importantly, the certainty of evidence by GRADE was generally moderate across key outcomes, reflecting both consistent directionality and substantial heterogeneity, variability in dietary protocols, and limitations in adherence reporting. While adverse effects were not the primary focus of the pooled analyses, reported issues in the broader ketogenic literature, such as transient gastrointestinal discomfort, nutrient gaps without supplementation, and lipid shifts, underscore the need for clinical supervision, a staged reintroduction of carbohydrates, and attention to overall dietary quality. Additionally, none of the included trials stratified results by PCOS phenotype, which may limit interpretability because phenotypes differ markedly in hyperandrogenism, metabolic risk, and potential dietary responsiveness.
Evidence Summary on VLCKD Benefits for PCOS Symptoms
Across RCTs, the VLCKD meaningfully improves weight, WC, FBM, BMI, and selected reproductive hormones in women with PCOS, while enhancing glucose-insulin control and lowering triglycerides. These changes support practical, near-term benefits such as more regular cycles, greater comfort, and potentially improved fertility when VLCKD is professionally supervised. However, most trials are short, heterogeneous, and not designed to test long-term safety, lipid trajectories, phenotype-specific responses, or real-world adherence.
Future Research Needs for Diet Comparisons and Long-Term Safety
Future work should compare VLCKD with other evidence-based patterns over longer periods, track phenotypes, and integrate behavioral support to sustain gains. More consistent protocol standardization and improved adverse-event reporting would further strengthen the evidence base.
