Background: Very low-calorie ketogenic diet (VLCKD) was shown to be effective in reducing weight and insulin resistance (IR) in obese patients. Considering that IR is very common in women with polycystic ovary syndrome (PCOS), and that IR worsens hyperandrogenism, ovulatory disfunction, and body fat accumulation, conceivably VLCKD could alleviate PCOS manifestations in the obese phenotype.
Objective: This study compared the effects of a commercial VLCKD (“PnK® method”) and the control low calorie standard diet (LCD) on body weight and composition, insulin resistance, ovulation and hyperandrogenism in a population of obese PCOS.
Methods: This is an open-label, monocentric, randomized controlled trial (NCT04801173), supported by Pronokal Health group S.L. Women aged 18-45 years with PCOS diagnosed using the NIH criteria were randomized into the VLCKD or LCD group (15 vs 15). VLCKD group followed the VLCKD for 8 weeks, switching to the LCD for 8 weeks more, while the LCD group followed the LCD for 16 weeks. Ovulation monitoring by progesterone measurement and pelvic ultrasound was done at baseline and at the end of the study (week 16), while a clinical exam, bioelectrical impedance analysis (BIA) anthropometry, and biochemical analyses were performed at baseline, at week 8, and at week 16 of the study. Androgens were measured by tandem liquid chromatography-mass spectrometry. Free testosterone (freeT) was calculated using the Vermeulen formula. Repeated measures general linear model was used to evaluate within- and between-group differences for continuous variables.
Results: 2 dropouts occurred in the VLCKD group, 1 in the LCD group. Body weight decreased significantly in both groups, but more so in the VLCKD group − average difference 12.4 kg (-13.6%) vs 4.7 kg (-5.3%) (P<0.001). Significant differences between the VLCKD and LCD groups were also seen in waist circumference (-8.1% vs -2.2%), BIA-measured body fat (-15.1% vs -8.5%), and freeT (-30.3% vs +10.6%), over the course of the study (P=0.004, P=0.02, andP=0.002, respectively). HOMA-IR index also decreased more in the VLCKD group during the first 8 weeks (-36.1% vs -26.1%, P=0.02). At baseline, 5/13 (38.5%) participants in the VLCKD group and 2/14 (14.3%) participants in the LCD group had ovulatory cycles, which differentially increased to 11/13 (84.6%) and 5/14 (35.7%) at post-intervention monitoring, respectively (McNemar, P=0.031).
Conclusion: This data shows that VLCKD is a valid method for reducing body fat and rapidly ameliorating hyperandrogenism and ovulatory dysfunction in obese PCOS women.