Review
Ketogenic diets for weight loss: A review of their principles, safety and efficacy

https://doi.org/10.1016/j.orcp.2007.11.003Get rights and content

Summary

Low-carbohydrate “ketogenic” diets have increased in popularity over recent years as a means of weight loss. Published studies of these diets have been highly heterogeneous, and it remains unclear to what degree dietary carbohydrate intake must be restricted in order to induce ketosis. Despite concern that they are often relatively high in fat, ketogenic low-carbohydrate diets have been generally shown to compare favourably with low-fat diets in terms of weight loss and improvements in triglyceride and high-density lipoprotein levels. This review includes a brief overview of ketone body metabolism, and summarises the literature regarding the safety and efficacy of ketogenic diets for weight loss.

Introduction

The increasing prevalence of overweight and obesity has been widely reported. In recent years, low-carbohydrate “ketogenic” diets have received much attention as a means of rapid weight loss. However, there is no clear consensus in the literature as to what carbohydrate intake constitutes a low-carbohydrate diet, or to what degree carbohydrates must be restricted in order to cause ketosis. Furthermore, since ketogenic low-carbohydrate diets are often high in fat, there have been concerns about their potential adverse effects on cardiovascular risk.

The use of ketogenic diets in refractory paediatric epilepsy has been extensively reviewed elsewhere [1]. These diets have a different composition and aim to generate higher ketone levels than the ketogenic diets used for weight loss. This article will briefly overview ketone body metabolism and review the available evidence relating to the efficacy and safety of ketogenic low-carbohydrate diets for weight loss.

Section snippets

Ketone body metabolism

The term “ketone bodies” refers to three compounds: acetoacetate (AcAc), 3-β-hydroxybutyrate (3HB—not strictly a ketone but rather a hydroxy fatty acid) and acetone (Fig. 1). The circulating levels of ketone bodies are dependent both on their rate of production (ketogenesis) and their rate of utilisation (ketolysis). AcAc and 3HB are the two main ketone bodies generated and used for fuel under low-carbohydrate conditions. Acetone is formed by spontaneous decarboxylation of AcAc [2] and gives a

Measurement of ketone bodies

Standard tests for blood and urinary ketones are semi-quantitative, and reflect the presence of AcAc or acetone via a reaction with nitroprusside, which produces a complex detectable on a test strip. Ketone tests based on the nitroprusside reaction can give false positive results in the presence of drugs containing sulfhydryl groups (including captopril, N-acetylcysteine and penicillamine) [13], [14]. False negative results may occur if test strips have been exposed to air for an extended

How low in carbohydrates?

The English-language literature has no clear consensus about the definition of a “low-carbohydrate diet”. A 2003 systematic review of the efficacy and safety of low-carbohydrate diets for weight loss included diets with carbohydrate contents ranging from 0 to 263 g/day [17]. Commonly, low-carbohydrate diets are considered to contain <100 g/day or <30% of energy from carbohydrates [18], [19], [20]. Since a diet restricted in carbohydrates usually contains a relatively increased proportion of the

Conclusions

Ketogenic low-carbohydrate diets have increased in popularity over recent years, but the degree of carbohydrate restriction required to achieve ketosis remains unclear. In general, studies have shown greater weight loss at 3–6 months with KLC diets compared with LF diets, however this difference is no longer apparent at 12 months. The majority of studies have found that KLC diets are associated with favourable changes in triglyceride and HDL levels, but higher LDL levels than LF diets. The

Conflicts of interest

None.

Acknowledgements

She is supported by an Endocrine Society of Australia scholarship and a Royal Australasian College of Physicians Shields Research Entry scholarship.

References (100)

  • M.J. Sharman et al.

    Very low-carbohydrate and low-fat diets affect fasting lipids and postprandial lipemia differently in overweight men

    J Nutr

    (2004)
  • S.B. Sondike et al.

    Effects of a low-carbohydrate diet on weight loss and cardiovascular risk factor in overweight adolescents

    J Pediatr

    (2003)
  • J.S. Volek et al.

    Body composition and hormonal responses to a carbohydrate-restricted diet

    Metabolism

    (2002)
  • M.A. Denke

    Metabolic effects of high-protein, low-carbohydrate diets

    Am J Cardiol

    (2001)
  • A. Astrup et al.

    Atkins and other low-carbohydrate diets: hoax or an effective tool for weight loss?

    Lancet

    (2004)
  • S.M. Nickols-Richardson et al.

    Perceived hunger is lower and weight loss is greater in overweight premenopausal women consuming a low-carbohydrate/high-protein vs high-carbohydrate/low-fat diet

    J Am Diet Assoc

    (2005)
  • J.T. Silverstone et al.

    Hunger during total starvation

    Lancet

    (1966)
  • J.C. Rosen et al.

    Mood and appetite during minimal-carbohydrate and carbohydrate-supplemented hypocaloric diets

    Am J Clin Nutr

    (1985)
  • B. Gumbiner et al.

    Effects of diet composition and ketosis on glycemia during very-low-energy-diet therapy in obese patients with non-insulin-dependent diabetes mellitus

    Am J Clin Nutr

    (1996)
  • R.L. Veech

    The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism

    Prostag Leukot Essent Fatty Acids

    (2004)
  • E.C. Westman et al.

    Low-carbohydrate nutrition and metabolism

    Am J Clin Nutr

    (2007)
  • G.J. Buse et al.

    Patient with gemfibrozil-controlled hypertriglyceridemia that developed acute pancreatitis after starting ketogenic diet

    Curr Surg

    (2004)
  • T.-Y. Chen et al.

    A life-threatening complication of Atkins diet

    Lancet

    (2006)
  • M.J. Sharman et al.

    A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men

    J Nutr

    (2002)
  • E.C. Westman et al.

    Effect of a low-carbohydrate, ketogenic diet program compared to a low-fat diet on fasting lipoprotein subclasses

    Int J Cardiol

    (2006)
  • B.A. Griffin et al.

    Role of plasma triglyceride in the regulation of plasma low density lipoprotein (LDL) subfractions: relative contribution of small, dense LDL to coronary heart disease risk

    Atherosclerosis

    (1994)
  • P. Seshadri et al.

    A randomized study comparing the effects of a low-carbohydrate diet and a conventional diet on lipoprotein subfractions and C-reactive protein levels in patients with severe obesity

    Am J Med

    (2004)
  • R.M. Krauss et al.

    Separate effects of reduced carbohydrate intake and weight loss on atherogenic dyslipidemia

    Am J Clin Nutr

    (2006)
  • S.T. Reddy et al.

    Effect of low-carbohydrate high-protein diets on acid-base balance, stone-forming propensity, and calcium metabolism

    Am J Kidney Dis

    (2002)
  • J. Freeman et al.

    The ketogenic diet: from molecular mechanisms to clinical effects

    Epilepsy Res

    (2006)
  • G.A. Mitchell et al.

    Medical aspects of ketone body metabolism

    Clin Invest Med

    (1995)
  • A.J. Garber et al.

    Hepatic ketogenesis and gluconeogenesis in humans

    J Clin Invest

    (1974)
  • L. Laffel

    Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes

    Diabetes Metab Res Rev

    (1999)
  • B.J. Brehm et al.

    The role of energy expenditure in the differential weight loss in obese women on low-fat and low-carbohydrate diets

    J Clin Endocrinol Metab

    (2005)
  • T.B. Van Itallie et al.

    Ketones: metabolism's ugly duckling

    Nutr Rev

    (2003)
  • D. Foster

    Diabetes mellitus

  • A.M. Robinson et al.

    Physiological roles of ketone bodies as substrates and signals in mammalian tissues

    Physiol Rev

    (1980)
  • O.E. Owen et al.

    Human forearm metabolism during progressive starvation

    J Clin Invest

    (1971)
  • G. Csako et al.

    Spurious ketonuria due to captopril and other free sulfhydryl drugs

    Diabetes Care

    (1996)
  • J. Williamson et al.

    Contamination of a specimen with N-acetyl cysteine infusion: a cause of spurious ketonaemia and hyperglycaemia

    Ann Clin Biochem

    (1989)
  • D.M. Bravata et al.

    Efficacy and safety of low-carbohydrate diets: a systematic review

    JAMA

    (2003)
  • I. Abete et al.

    Different dietary strategies for weight loss in obesity: role of energy and macronutrient content

    Nutr Res Rev

    (2006)
  • A. Adam-Perrot et al.

    Low-carbohydrate diets: nutritional and physiological aspects

    Obes Rev

    (2006)
  • S.A. Bilsborough et al.

    Low-carbohydrate diets: what are the potential short- and long-term health implications?

    Asia Pac J Clin Nutr

    (2003)
  • G.A. Bray

    Low-carbohydrate diets and realities of weight loss

    JAMA

    (2003)
  • J.S. Volek et al.

    Very-low-carbohydrate weight-loss diets revisited

    Cleve Clin J Med

    (2002)
  • K.A. Meckling et al.

    Effects of a hypocaloric, low-carbohydrate diet on weight loss, blood lipids, blood pressure, glucose tolerance, and body composition in free-living overweight women

    Can J Physiol Pharmacol

    (2002)
  • W.S. Yancy et al.

    A low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia: a randomized, controlled trial

    Ann Intern Med

    (2004)
  • R.L. Jungas et al.

    Quantitative analysis of amino acid oxidation and related gluconeogenesis in humans

    Physiol Rev

    (1992)
  • A.L. Hartman et al.

    Clinical aspects of the ketogenic diet

    Epilepsia

    (2007)
  • Cited by (55)

    • Knowledge and perception of the ketogenic diet followers among Arab adults in seventeen countries

      2021, Obesity Medicine
      Citation Excerpt :

      The majority of participants agreed that the ketogenic diet is a common weight-loss method, with more than half of them confirming that purpose. According to the literature review to support this perception, weight loss and different positive health outcomes can be resulted from using a ketogenic diet (Gomez-Arbelaez et al., 2017; Sumithran and Proietto, 2008). These benefits outcomes the risks as believed by more than half of the participants.

    • Effects of calorie restricted low carbohydrate high fat ketogenic vs. non-ketogenic diet on strength, body-composition, hormonal and lipid profile in trained middle-aged men

      2021, Clinical Nutrition
      Citation Excerpt :

      It indicates that the body has the potential to compensate lack of CHO intake required for intense muscle hypertrophy strength workout. This overall effect could be a combination of direct using of ketones during intense muscle contraction and glucose sparing through the greater brain and other body tissues utilization [3]. For complete understanding and explaining this problem of low carb diet combined with hypertrophy strength training, it is necessary to have in mind the ability of the body to convert a certain amount of protein and fat into glucose, in the total absence of dietary carbohydrates [2].

    • Effect of short-term ketogenic diet on end-tidal carbon dioxide

      2021, Clinical Nutrition ESPEN
      Citation Excerpt :

      The main product of KD is the presence of ketone bodies namely the beta-hydroxybutyrate (β-OHB), acetoacetate (AcAc) and acetone [16–19]. Ketosis is defined upon presence of at least 0.5 mmol/L of ketones in the blood and is the state when the body utilizes the supraphysiologic concentration of ketones from the oxidation of fats as the main source of energy [16,20–24]. Ketosis could be achieved via fasting, starvation and consumption of exogenous ketones [21,25,26].

    View all citing articles on Scopus
    View full text