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

Madison L Kackley, Christopher D Crabtree, Jeff S Volek, Paul Belany, Songzhu Zhao, Bjorn Kluwe, Alex Buga, Divya Nedungadi, David Kline, Guy Brock, Orlando P Simonetti, Joshua J Joseph

Journal: The Journal of clinical endocrinology and metabolism 2023;108(7):1727-1739

PMID: 36629058

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Plain Language Summary

Aldosterone and renin are two hormones that regulate blood pressure. High levels of aldosterone have been linked to high blood pressure, heart disease, obesity and blood sugar imbalance.The ketogenic diet (KD) has been shown to improve risk factors for heart disease, such as obesity and type 2 diabetes, however there is limited knowledge on the effect of the KD on aldosterone and renin. The aim of this study was to determine the effects of a KD alone and a KD plus the addition of extra ketones in individuals who are overweight or have obesity. The results showed that both diets resulted in weight loss but had differing effects on aldosterone and renin. Aldosterone increased and renin decreased to a greater extent in the KD with added ketones compared to the KD alone. However, this had no effect on systolic or diastolic blood pressure, which did not change with either diet. It was concluded that KD reduced weight and increased aldosterone without worsening factors associated with heart disease. This study could be used by healthcare professionals to understand that dietary composition and not just calorie restriction can influence hormonal pathways related to blood pressure and heart disease.

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.

Address: Division of Endocrinology, Diabetes and Metabolism, The Ohio State University College of Medicine, Columbus, OH 43210, USA.; Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA.; Department of Biomedical Informatics and Center for Biostatistics, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.; Department of Radiology, Davis Heart & Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.; Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA.; Department of Radiology, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA.

DOI: 10.1210/clinem/dgad009