A comprehensive meta-analysis suggests ketogenic diets can deliver short-term metabolic and hormonal improvements in women with PCOS, but high study heterogeneity and limited long-term data call for cautious interpretation and better trials.
Study: The effects of ketogenic diet on polycystic ovary syndrome: a systematic review and meta-analysis. Image Credit: New Africa / Shutterstock
In a recent study published in the journal Clinical Nutrition, researchers investigated the effects of a ketogenic diet (KD) on endocrinological, metabolic, and anthropometric outcomes in females with PCOS.
PCOS is the most common endocrinopathy in females of reproductive age. It is associated with multiple features, including anovulation, hyperandrogenism, infertility, insulin resistance, obesity, and hyperinsulinism, and increases the risk of cardiovascular disease, cancer, and T2D. Lifestyle changes, along with weight loss in overweight patients, are crucial components of PCOS treatment.
A KD is characterized by high fat intake, moderate protein consumption, and low carbohydrate intake. Evidence suggests that KD adherence leads to nutritional ketosis and ketogenesis, improving insulin sensitivity and enhancing fat mass and weight loss. Consequently, postprandial insulin secretion is decreased. Given the benefits of KD in T2D, it may be a therapeutic intervention for PCOS, as both conditions feature insulin resistance. However, the relative contribution of carbohydrate restriction versus weight loss per se remains uncertain and may vary across individuals and study designs.
Systematic Review and Meta-Analysis Design
In the present study, researchers evaluated the effects of KD on anthropometric, endocrinological, and metabolic outcomes in females with PCOS. The team searched several electronic databases, including the Web of Science, PubMed, Scopus, Cochrane Central, and ClinicalTrials.gov, for relevant publications. Studies reporting on these outcomes in PCOS patients following a KD were included in the systematic review. The meta-analysis included studies that reported results from a comparator group.
Reviews, dissertations, and studies reporting in vitro fertilization (IVF) outcomes were excluded from quantitative synthesis, although IVF-related findings were discussed narratively where relevant. Case series and case reports were included in the review but not in the quantitative analysis. Risk of bias was assessed using the MINORS, the RoB-2 tool for randomized controlled trials, and the JBI checklists for case reports and case series. The GRADE approach was used to evaluate the overall quality of evidence.
Outcomes included body mass index (BMI), waist circumference, body weight, lipid parameters, menstrual cycle duration, reproductive hormones, and insulin resistance markers such as HOMA-IR and insulin. Effect sizes were pooled using random-effects models, with heterogeneity assessed using the I-squared statistic. Primary analyses compared baseline and post-KD values, while secondary analyses compared KD with other dietary interventions. Subgroup analyses explored sources of heterogeneity by age, diet duration, study design, intervention definition, and risk of bias.
Study Characteristics and Risk of Bias
Database searches identified 485 publications, of which 15 studies were included in the systematic review, comprising eight cohort studies, five randomized controlled trials, one case series, and one case report conducted across Europe, Asia, and the Americas. The meta-analysis included 10 studies. Across all studies, the average BMI exceeded 25 kg/m².
Risk of bias varied substantially. Among RCTs, two had a low risk of bias, while three showed high risk or some concerns. Most cohort studies had a low risk of bias, whereas case series and case reports were judged to have a high risk. Common limitations included small sample sizes, lack of blinding, and short follow-up durations.
Effects of Ketogenic Diet on PCOS Outcomes
The primary analysis demonstrated significant improvements in multiple anthropometric outcomes following KD. BMI, body weight, and waist circumference decreased substantially compared to baseline, although heterogeneity was high and confidence intervals were wide for several outcomes.
Metabolic outcomes also improved, with significant reductions in total cholesterol, LDL cholesterol, and triglycerides. HDL cholesterol increased following KD, but this change was not statistically significant. Endocrinological outcomes showed reductions in luteinizing hormone (LH) and testosterone levels, while follicle-stimulating hormone (FSH) levels remained largely unchanged. Measures of insulin resistance, including HOMA-IR and insulin levels, decreased significantly, though effect sizes varied widely and appeared influenced by baseline metabolic status and degree of weight loss.
In secondary analyses comparing KD with other dietary interventions, KD was associated with greater reductions in BMI, waist circumference, and body weight. Triglyceride and total cholesterol levels were also lower in the KD group, while HDL and LDL levels were similar between diets. Among hormonal outcomes, LH levels decreased, and FSH levels slightly increased in the KD group, whereas testosterone levels did not differ between groups. HOMA-IR was significantly reduced with KD, although pooled insulin levels did not differ and showed substantial heterogeneity.
Subgroup analyses produced broadly consistent results but did not fully explain heterogeneity or address concerns related to selection bias and dietary adherence.
Clinical Implications and Evidence Limitations
Overall, the findings indicate that a ketogenic diet can improve anthropometric, metabolic, and selected endocrinological outcomes in females with PCOS, particularly among those with overweight or obesity. Many of these benefits are likely mediated by weight loss and improved insulin sensitivity, rather than by ketosis alone, and may not directly translate into long-term reproductive or fertility outcomes.
Despite showing greater benefits than other diets in several domains, the evidence base is limited by substantial heterogeneity, short intervention durations, and generally low to very low certainty of evidence. Adverse events were inconsistently reported, and long-term safety, adherence, and sustainability data are lacking.
Taken together, the results suggest that KD may be a promising dietary option for selected PCOS patients, but cautious interpretation is warranted. Large, well-designed, long-term randomized controlled trials are needed to clarify the safety, durability, and clinical relevance of KD in the management of PCOS.
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