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

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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.

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Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013.

Marie Ng, Tom Fleming, Margaret W. Robinson … (2015)

In 2010, overweight and obesity were estimated to cause 3·4 million deaths, 3·9% of years of life lost, and 3·8% of disability-adjusted life-years (DALYs) worldwide. The rise in obesity has led to widespread calls for regular monitoring of changes in overweight and obesity prevalence in all populations. Comparable, up-to-date information about levels and trends is essential to quantify population health effects and to prompt decision makers to prioritise action. We estimate the global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013. We systematically identified surveys, reports, and published studies (n=1769) that included data for height and weight, both through physical measurements and self-reports. We used mixed effects linear regression to correct for bias in self-reports. We obtained data for prevalence of obesity and overweight by age, sex, country, and year (n=19,244) with a spatiotemporal Gaussian process regression model to estimate prevalence with 95% uncertainty intervals (UIs). Worldwide, the proportion of adults with a body-mass index (BMI) of 25 kg/m(2) or greater increased between 1980 and 2013 from 28·8% (95% UI 28·4-29·3) to 36·9% (36·3-37·4) in men, and from 29·8% (29·3-30·2) to 38·0% (37·5-38·5) in women. Prevalence has increased substantially in children and adolescents in developed countries; 23·8% (22·9-24·7) of boys and 22·6% (21·7-23·6) of girls were overweight or obese in 2013. The prevalence of overweight and obesity has also increased in children and adolescents in developing countries, from 8·1% (7·7-8·6) to 12·9% (12·3-13·5) in 2013 for boys and from 8·4% (8·1-8·8) to 13·4% (13·0-13·9) in girls. In adults, estimated prevalence of obesity exceeded 50% in men in Tonga and in women in Kuwait, Kiribati, Federated States of Micronesia, Libya, Qatar, Tonga, and Samoa. Since 2006, the increase in adult obesity in developed countries has slowed down. Because of the established health risks and substantial increases in prevalence, obesity has become a major global health challenge. Not only is obesity increasing, but no national success stories have been reported in the past 33 years. Urgent global action and leadership is needed to help countries to more effectively intervene. Bill & Melinda Gates Foundation. Copyright © 2014 Elsevier Ltd. All rights reserved.

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Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants

Emily Sonestedt, Kim Overvad (2016)

Summary Background Underweight and severe and morbid obesity are associated with highly elevated risks of adverse health outcomes. We estimated trends in mean body-mass index (BMI), which characterises its population distribution, and in the prevalences of a complete set of BMI categories for adults in all countries. Methods We analysed, with use of a consistent protocol, population-based studies that had measured height and weight in adults aged 18 years and older. We applied a Bayesian hierarchical model to these data to estimate trends from 1975 to 2014 in mean BMI and in the prevalences of BMI categories (<18·5 kg/m2 [underweight], 18·5 kg/m2 to <20 kg/m2, 20 kg/m2 to <25 kg/m2, 25 kg/m2 to <30 kg/m2, 30 kg/m2 to <35 kg/m2, 35 kg/m2 to <40 kg/m2, ≥40 kg/m2 [morbid obesity]), by sex in 200 countries and territories, organised in 21 regions. We calculated the posterior probability of meeting the target of halting by 2025 the rise in obesity at its 2010 levels, if post-2000 trends continue. Findings We used 1698 population-based data sources, with more than 19·2 million adult participants (9·9 million men and 9·3 million women) in 186 of 200 countries for which estimates were made. Global age-standardised mean BMI increased from 21·7 kg/m2 (95% credible interval 21·3–22·1) in 1975 to 24·2 kg/m2 (24·0–24·4) in 2014 in men, and from 22·1 kg/m2 (21·7–22·5) in 1975 to 24·4 kg/m2 (24·2–24·6) in 2014 in women. Regional mean BMIs in 2014 for men ranged from 21·4 kg/m2 in central Africa and south Asia to 29·2 kg/m2 (28·6–29·8) in Polynesia and Micronesia; for women the range was from 21·8 kg/m2 (21·4–22·3) in south Asia to 32·2 kg/m2 (31·5–32·8) in Polynesia and Micronesia. Over these four decades, age-standardised global prevalence of underweight decreased from 13·8% (10·5–17·4) to 8·8% (7·4–10·3) in men and from 14·6% (11·6–17·9) to 9·7% (8·3–11·1) in women. South Asia had the highest prevalence of underweight in 2014, 23·4% (17·8–29·2) in men and 24·0% (18·9–29·3) in women. Age-standardised prevalence of obesity increased from 3·2% (2·4–4·1) in 1975 to 10·8% (9·7–12·0) in 2014 in men, and from 6·4% (5·1–7·8) to 14·9% (13·6–16·1) in women. 2·3% (2·0–2·7) of the world’s men and 5·0% (4·4–5·6) of women were severely obese (ie, have BMI ≥35 kg/m2). Globally, prevalence of morbid obesity was 0·64% (0·46–0·86) in men and 1·6% (1·3–1·9) in women. Interpretation If post-2000 trends continue, the probability of meeting the global obesity target is virtually zero. Rather, if these trends continue, by 2025, global obesity prevalence will reach 18% in men and surpass 21% in women; severe obesity will surpass 6% in men and 9% in women. Nonetheless, underweight remains prevalent in the world’s poorest regions, especially in south Asia. Funding Wellcome Trust, Grand Challenges Canada.

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The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis.

G P Chrousos, P Gold (1992)

This article defines stress and related concepts and reviews their historical development. The notion of a stress system as the effector of the stress syndrome is suggested, and its physiologic and pathophysiologic manifestations are described. A new perspective on human disease states associated with dysregulation of the stress system is provided. Published original articles from human and animal studies and selected reviews. Literature was surveyed utilizing MEDLINE and the Index Medicus. Original articles from the basic science and human literature consisted entirely of controlled studies based on verified methodologies and, with the exception of the most recent studies, replicated by more than one laboratory. Many of the basic science and clinical studies had been conducted in our own laboratories and clinical research units. Reviews cited were written by acknowledged leaders in the fields of neurobiology, endocrinology, and behavior. Independent extraction and cross-referencing by the authors. Stress and related concepts can be traced as far back as written science and medicine. The stress system coordinates the generalized stress response, which takes place when a stressor of any kind exceeds a threshold. The main components of the stress system are the corticotropin-releasing hormone and locus ceruleus-norepinephrine/autonomic systems and their peripheral effectors, the pituitary-adrenal axis, and the limbs of the autonomic system. Activation of the stress system leads to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chances for survival. There has been an exponential increase in knowledge regarding the interactions among the components of the stress system and between the stress system and other brain elements involved in the regulation of emotion, cognitive function, and behavior, as well as with the axes responsible for reproduction, growth, and immunity. This new knowledge has allowed association of stress system dysfunction, characterized by sustained hyperactivity and/or hypoactivity, to various pathophysiologic states that cut across the traditional boundaries of medical disciplines. These include a range of psychiatric, endocrine, and inflammatory disorders and/or susceptibility to such disorders. We hope that knowledge from apparently disparate fields of science and medicine integrated into a working theoretical framework will allow generation and testing of new hypotheses on the pathophysiology and diagnosis of, and therapy for, a variety of human illnesses reflecting systematic alterations in the principal effectors of the generalized stress response. We predict that pharmacologic agents capable of altering the central apparatus that governs the stress response will be useful in the treatment of many of these illnesses.

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Author and article information

Contributors

G. Muscogiuri:

ORCID: http://orcid.org/0000-0002-8809-4931

giovanna.muscogiuri@unina.com

Journal

Journal ID (nlm-ta): J Endocrinol Invest

Journal ID (iso-abbrev): J Endocrinol Invest

Title: Journal of Endocrinological Investigation

Publisher: Springer International Publishing (Cham )

ISSN (Print): 0391-4097

ISSN (Electronic): 1720-8386

Publication date (Electronic): 5 April 2023

Publication date PMC-release: 5 April 2023

Publication date (Print): 2023

Volume: 46

Issue: 8

Pages: 1509-1520

Affiliations

[1 ]Dipartimento di Scienze Umanistiche, Università Telematica Pegaso, Via Porzio, Centro Direzionale, Isola F2, 80143 Naples, Italy

[2 ]Department of Clinical Medicine and Surgery, Endocrinology Unit, Centro Italiano per la cura e il Benessere del Paziente con Obesità (C.I.B.O), University Medical School of Naples, Via Sergio Pansini 5, 80131 Naples, Italy

[3 ]GRID grid.4691.a, ISNI 0000 0001 0790 385X, Department of Public Health, , Federico II University, ; Naples, Italy

[4 ]GRID grid.466134.2, ISNI 0000 0004 4912 5648, Department of Human Sciences and Promotion of the Quality of Life, , San Raffaele Roma Open University, ; 00166 Rome, Italy

[5 ]GRID grid.418577.8, ISNI 0000 0000 8743 1110, Department for Obesity, Metabolic and Reproductive Disorders, Clinic for Endocrinology, Diabetes and Metabolic Diseases, , University Clinical Centre of Serbia, ; Belgrade, Serbia

[6 ]GRID grid.4691.a, ISNI 0000 0001 0790 385X, Dipartimento di Medicina Clinica e Chirurgia, Diabetologia ed Andrologia, , Unità di Endocrinologia, Università Federico II, ; Via Sergio Pansini 5, 80131 Naples, Italy

[7 ]GRID grid.4691.a, ISNI 0000 0001 0790 385X, Cattedra Unesco “Educazione Alla Salute E Allo Sviluppo Sostenibile”, University Federico II, ; Naples, Italy

[8 ]GRID grid.18887.3e, ISNI 0000000417581884, Laboratory of Cardiovascular Endocrinology, , IRCCS San Raffaele Roma, ; 00166 Rome, Italy

Author information

G. Muscogiuri http://orcid.org/0000-0002-8809-4931

Article

Publisher ID: 2068

DOI: 10.1007/s40618-023-02068-6

PMC ID: 10349006

PubMed ID: 37017918

SO-VID: dbd9dd03-a055-444d-bb3a-e02eea4285a5

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 15 January 2023

Date accepted : 10 March 2023

Funding

Funded by: Università degli Studi di Napoli Federico II

Open Access :

Open access funding provided by Università degli Studi di Napoli Federico II within the CRUI-CARE Agreement.

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Keywords: cortisol,hpa axis,stress,obesity,diet,very low-calorie ketogenic diet

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Keywords: cortisol, hpa axis, stress, obesity, diet, very low-calorie ketogenic diet

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

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Most cited references 106

Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013.

Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants

The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis.

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Cited by 9

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