Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Aug;46(8):1509-1520.
doi: 10.1007/s40618-023-02068-6. Epub 2023 Apr 5.

Effects of very low-calorie ketogenic diet on hypothalamic-pituitary-adrenal axis and renin-angiotensin-aldosterone system

L Barrea #  1   2 , L Verde #  2   3 , E Camajani  4 , A S Šojat  5 , L Marina  5 , S Savastano  2   6 , A Colao  2   6   7 , M Caprio #  4   8 , G Muscogiuri #  9   10   11
Affiliations
Review

Effects of very low-calorie ketogenic diet on hypothalamic-pituitary-adrenal axis and renin-angiotensin-aldosterone system

L Barrea et al. J Endocrinol Invest. 2023 Aug.

Abstract

Background: The hypothalamic-pituitary-adrenal (HPA) axis is a neuroendocrine system involved in controlling stress responses in humans under physiological and pathological conditions; cortisol is the main hormone produced by the HPA axis. It is known that calorie restriction acts as a stressor and can lead to an increase in cortisol production. Renin-angiotensin-aldosterone system (RAAS) is a complex endocrine network regulating blood pressure and hydrosaline metabolism, whose final hormonal effector is aldosterone. RAAS activation is linked to cardiometabolic diseases, such as heart failure and obesity. Obesity has become a leading worldwide pandemic, associated with serious health outcomes. Calorie restriction represents a pivotal strategy to tackle obesity. On the other hand, it is well known that an increased activity of the HPA may favour visceral adipose tissue expansion, which may jeopardize a successful diet-induced weight loss. Very low-calorie ketogenic diet (VLCKD) is a normoprotein diet with a drastic reduction of the carbohydrate content and total calorie intake. Thanks to its sustained protein content, VLCKD is extremely effective to reduce adipose tissue while preserving lean body mass and resting metabolic rate.

Purpose: The purpose of this narrative review is to gain more insights on the effects of VLCKD on the HPA axis and RAAS, in different phases of weight loss and in different clinical settings.

Keywords: Cortisol; Diet; HPA axis; Obesity; Stress; Very low-calorie ketogenic diet.

PubMed Disclaimer

Conflict of interest statement

Ljiljana Marina and Massimiliano Caprio are members of the editorial board of the Journal of Endocrinological Investigation.

Figures

Fig. 1
Fig. 1
Adrenal gland and the division of the two distinct anatomical areas, with their hormone production
Fig. 2
Fig. 2
Short-term positive mechanisms of action of the ketogenic diet on energy metabolism and muscle mass
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Guthrie HD, Barber JA, Leighton JK, Hammond JM. Steroidogenic cytochrome P450 enzyme messenger ribonucleic acids and follicular fluid steroids in individual follicles during preovulatory maturation in the pig. Biol Reprod. 1994;51(3):465–471. doi: 10.1095/biolreprod51.3.465. - DOI - PubMed
    1. Kim JH, Choi MH. Embryonic development and adult regeneration of the adrenal gland. Endocrinol Metab (Seoul) 2020;35(4):765–773. doi: 10.3803/EnM.2020.403. - DOI - PMC - PubMed
    1. Niemeyer CS, Mescher T, Griggs R, Orlicky DJ, Wilkerson GK, Bubak AN, et al. Histopathological analysis of adrenal glands after simian varicella virus infection. Viruses. 2021;13(7):1245. doi: 10.3390/v13071245. - DOI - PMC - PubMed
    1. Wolfraim LA, Langis R, Tyson H, Dhindsa RS. cDNA sequence, expression, and transcript stability of a cold acclimation-specific gene, cas18, of alfalfa (Medicago falcata) cells. Plant Physiol. 1993;101(4):1275–1282. doi: 10.1104/pp.101.4.1275. - DOI - PMC - PubMed
    1. Lightman SL, Birnie MT, Conway-Campbell BL. Dynamics of ACTH and cortisol secretion and implications for disease. Endocr Rev. 2020 doi: 10.1210/endrev/bnaa002. - DOI - PMC - PubMed

LinkOut - more resources