Effects of Hypocaloric Low-Fat, Ketogenic, and Ketogenic and Ketone Supplement Diets on Aldosterone and Renin

Abstract Context Ketogenic diets (KDs) and low-fat diets (LFD) result in similar weight loss, but have differential cardiometabolic effects on lipids and insulin. Generally, weight loss decreases renin–angiotensin–aldosterone system (RAAS) activity. Objective Investigate the effects of KDs with varying sodium content vs LFD on RAAS in overweight and obese adults. Methods Twenty-eight participants were randomized 1:1 to a KD + ketone salt supplement (KD + KS) or a KD + placebo (KD + PL) arm with prepared hypocaloric meals. Twelve participants were enrolled in a post hoc LFD arm. Serum renin, aldosterone, and anthropometric and metabolic biomarkers were assessed at 0, 2, 4, and 6 weeks. Linear mixed models with random intercepts were used to compare between group differences controlling for sex and body mass index. Results Participants had a median age of 33 years, 51% female, weighed 91.3 kg, with body mass index 30.6 kg/m2. At 6 weeks, weight decreased by 6, 8, and 7 kg on average in the KD + KS, KD + PL, and LFD groups, respectively (P < .05). Aldosterone increased by 88% and 144% in the KD + PL and KD + KS groups, respectively, but did not change in the LFD after 6 weeks while renin decreased across groups. Systolic and diastolic blood pressure did not change in the KD + PL and KD + KS groups. Log ketones were positively associated with aldosterone (P < .001). Aldosterone was not associated with cardiovascular measures including blood pressure and ejection fraction (P > .05). Conclusion KD reduced weight and increased aldosterone without worsening cardiometabolic risk factors. Future KD studies are needed to elucidate mechanistic connections between ketones and aldosterone.