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Current Nutrition Reports
Published in: Current Nutrition Reports 4/2019

01-12-2019 | Obesity | Gastroenterology, Critical Care, and Lifestyle Medicine (SA McClave, Section Editor)

Ketogenic Diet: an Endocrinologist Perspective

Authors: Aravind Reddy Kuchkuntla, Meera Shah, Saketh Velapati, Victoria M. Gershuni, Tamim Rajjo, Sanjeev Nanda, Ryan T. Hurt, Manpreet S. Mundi

Published in: Current Nutrition Reports | Issue 4/2019

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Abstract

Purpose of Review

Obesity and its related comorbidities make up a large part of healthcare expenditures. Despite a wide array of options for treatment of obesity, rates of sustained weight loss continue to be low, leading patients to seek alternative treatment options. Although the first medically utilized ketogenic diet was described nearly 100 years ago, it has made a resurgence as a treatment option for obesity. Despite increased popularity in the lay public and increased use of ketogenic dietary strategies for metabolic therapy, we are still beginning to unravel the metabolic impact of long-term dietary ketosis.

Recent Findings

There are a number of recent trials that have highlighted the short- and long-term benefits of ketogenic diet on weight, glycemic control, and other endocrine functions including reproductive hormones.

Summary

This review is a summary of available data on the effectiveness and durability of the ketogenic diet when compared to conventional interventions. Ketogenic dietary strategies may play a role in short-term improvement of important metabolic parameters with potential for long-term benefit. However, response may vary due to inter-individual ability to maintain long-term carbohydrate restriction.
Literature
1.
Biener, A., J. Cawley, and C. Meyerhoefer, The high and rising costs of obesity to the US health care system. 2017, Springer.
2.
Ng M, et al. 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. Lancet. 2014;384(9945):766–81.PubMedPubMedCentral
3.
•• Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med. 2017;377(1):13–27 (A global study showing the impact of obesity in the last 2 decades, reported a two fold increase in obesity from the 1980s).
4.
Flegal KM, et al. Trends in Obesity Among Adults in the United States, 2005 to 2014. Jama. 2016;315(21):2284–91.PubMed
5.
Bray MS, et al. NIH working group report-using genomic information to guide weight management: from universal to precision treatment. Obesity (Silver Spring). 2016;24(1):14–22.
6.
van der Klaauw AA, Farooqi IS. The hunger genes: pathways to obesity. Cell. 2015;161(1):119–32.PubMed
7.
Church TS, et al. Trends over 5 decades in U.S. occupation-related physical activity and their associations with obesity. PLoS One. 2011;6(5):e19657.PubMedPubMedCentral
8.
McAllister EJ, et al. Ten putative contributors to the obesity epidemic. Crit Rev Food Sci Nutr. 2009;49(10):868–913.PubMedPubMedCentral
9.
Tchkonia T, et al. Mechanisms and metabolic implications of regional differences among fat depots. Cell Metab. 2013;17(5):644–56.PubMedPubMedCentral
10.
Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444(7121):860.PubMed
11.
Heymsfield SB, Wadden TA. Mechanisms, pathophysiology, and management of obesity. N Engl J Med. 2017;376(3):254–66.PubMed
12.
Ryan DH. Guidelines for obesity management. Endocrinol Metab Clin N Am. 2016;45(3):501–10.
13.
Velapati SR, et al. Weight regain after bariatric surgery: prevalence, etiology, and treatment. Curr Nutr Rep. 2018;7(4):329–34.PubMed
14.
Wheless JW. History of the ketogenic diet. Epilepsia. 2008;49(Suppl 8):3–5.PubMed
15.
Wilder RM, Winter MD. The threshold of ketogenesis. J Biol Chem. 1922;52(2):393–401.
16.
HELMHOLZ HF. The treatment of epilepsy in childhood: five years’ experience with the ketogenic diet. JAMA. 1927;88(26):2028–32.
17.
Peterman M. The ketogenic diet in epilepsy. J Am Med Assoc. 1925;84(26):1979–83.
18.
19.
Atkins RD. Dr. Government Institutes: Atkins’ new diet revolution; 2002.
20.
Feinman RD, et al. Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base. Nutrition. 2015;31(1):1–13.PubMed
21.
Kossoff EH, Dorward JL. The modified Atkins diet. Epilepsia. 2008;49(Suppl 8):37–41.PubMed
22.
Westman EC, et al. Low-carbohydrate nutrition and metabolism. Am J Clin Nutr. 2007;86(2):276–84.PubMed
23.
Veech RL. The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism. Prostaglandins Leukot Essent Fat Acids. 2004;70(3):309–19.
24.
Thomsen HH, et al. Effects of 3-hydroxybutyrate and free fatty acids on muscle protein kinetics and signaling during LPS-induced inflammation in humans: anticatabolic impact of ketone bodies. Am J Clin Nutr. 2018;108(4):857–67.PubMed
25.
Koppel SJ, Swerdlow RH. Neuroketotherapeutics: a modern review of a century-old therapy. Neurochem Int. 2018;117:114–25.PubMed
26.
Crawford P. Multi-dimensional roles of ketone bodies in fuel metabolism, signaling, and therapeutics. Biophys J. 2019;116(3, Supplement 1):2a.
27.
Ma D, et al. Ketogenic diet enhances neurovascular function with altered gut microbiome in young healthy mice. Sci Rep. 2018;8(1):6670.PubMedPubMedCentral
28.
Kuchkuntla AR, et al. Fad diets: hype or hope? Curr Nutr Rep. 2018;7(4):310–23.PubMed
29.
Newsholme EA, Dimitriadis G. Integration of biochemical and physiologic effects of insulin on glucose metabolism. Exp Clin Endocrinol Diabetes. 2001;109(Suppl 2):S122–34.PubMed
30.
Plum L, Belgardt BF, Brüning JC. Central insulin action in energy and glucose homeostasis. J Clin Invest. 2006;116(7):1761–6.PubMedPubMedCentral
31.
Taborsky GJ Jr. The physiology of glucagon. SAGE Publications. 2010;4(6):1338–44.
32.
33.
Rui L. Energy metabolism in the liver. Compr Physiol. 2011;4(1):177–97.
34.
35.
VanItallie TB, Nufert TH. Ketones: metabolism’s ugly duckling. Nutr Rev. 2003;61(10):327–41.PubMed
36.
37.
Laffel L. Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes. Diabetes Metab Res Rev. 1999;15(6):412–26.PubMed
38.
39.
Owen OE, et al. Comparative measurements of glucose, beta-hydroxybutyrate, acetoacetate, and insulin in blood and cerebrospinal fluid during starvation. Metabolism. 1974;23(1):7–14.PubMed
40.
Atkins RC, D.A.D. Revolution. The high calorie way to stay thin forever. New York: McKay Co.; 1972.
41.
Atkins, R.C., Dr. Atkins’ diet revolution. 1981: Bantam Books New York.
42.
Heinbecker P. Studies on the metabolism. J Biol Chem. 1928;80:461–75.
43.
Jungas RL, Halperin ML, Brosnan JT. Quantitative analysis of amino acid oxidation and related gluconeogenesis in humans. Physiol Rev. 1992;72(2):419–48.PubMed
44.
Volek JS, et al. Body composition and hormonal responses to a carbohydrate-restricted diet. Metab-Clin Exp. 2002;51(7):864–70.PubMed
45.
Ludwig DS, Friedman MI. Increasing adiposity: consequence or cause of overeating? Jama. 2014;311(21):2167–8.PubMed
46.
Kabir M, et al. A high glycemic index starch diet affects lipid storage–related enzymes in normal and to a lesser extent in diabetic rats. J Nutr. 1998;128(11):1878–83.PubMed
47.
Hall KD. A review of the carbohydrate-insulin model of obesity. Eur J Clin Nutr. 2017;71(3):323–6.PubMed
48.
Howell S, Kones R. “Calories in, calories out” and macronutrient intake: the hope, hype, and science of calories. Am J Physiol Endocrinol Metab. 2017;313(5):E608–e612.PubMed
49.
Klein S, Wolfe RR. Carbohydrate restriction regulates the adaptive response to fasting. Am J Phys. 1992;262(5 Pt 1):E631–6.
50.
Cox PJ, et al. Nutritional ketosis alters fuel preference and thereby endurance performance in athletes. Cell Metab. 2016;24(2):256–68.PubMed
51.
Goedecke JH, et al. Metabolic adaptations to a high-fat diet in endurance cyclists. Metabolism. 1999;48(12):1509–17.PubMed
52.
Westman EC, et al. A review of low-carbohydrate ketogenic diets. Curr Atheroscler Rep. 2003;5(6):476–83.PubMed
53.
Kuchkuntla AR, et al. Fad diets: hype or hope? Current nutrition reports. 2018;7(4):310–23.PubMed
54.
Ebbeling CB, et al. Effects of dietary composition on energy expenditure during weight-loss maintenance. Jama. 2012;307(24):2627–34.PubMedPubMedCentral
55.
Hall KD, et al. Energy expenditure and body composition changes after an isocaloric ketogenic diet in overweight and obese men, 2. Am J Clin Nutr. 2016;104(2):324–33.PubMedPubMedCentral
56.
•• Ebbeling CB, et al. Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial. BMJ. 2018;363:k4583 (An important study evaluating the physiological changes with weight loss on Ketogenic diet focussing on energy expenditure). PubMedPubMedCentral
57.
Cheatham B, Kahn CR. Insulin action and the insulin signaling network*. Endocr Rev. 1995;16(2):117–42.PubMed
58.
Smith U, et al. Insulin signaling and action in fat cells: associations with insulin resistance and type 2 diabetes. Ann N Y Acad Sci. 1999;892(1):119–26.PubMed
59.
Kelley DE, et al. The effect of non-insulin-dependent diabetes mellitus and obesity on glucose transport and phosphorylation in skeletal muscle. J Clin Invest. 1996;97(12):2705–13.PubMedPubMedCentral
60.
Rothman DL, et al. Decreased muscle glucose transport/phosphorylation is an early defect in the pathogenesis of non-insulin-dependent diabetes mellitus. Proc Natl Acad Sci. 1995;92(4):983–7.PubMed
61.
Shulman GI, et al. Quantitation of muscle glycogen synthesis in normal subjects and subjects with non-insulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopy. N Engl J Med. 1990;322(4):223–8.PubMed
62.
Yang Q, et al. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature. 2005;436(7049):356.PubMed
63.
Perseghin G, et al. Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H-13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents. Diabetes. 1999;48(8):1600–6.PubMed
64.
Roden M, et al. Mechanism of free fatty acid-induced insulin resistance in humans. J Clin Invest. 1996;97(12):2859–65.PubMedPubMedCentral
65.
Carey DG, et al. Abdominal fat and insulin resistance in normal and overweight women: direct measurements reveal a strong relationship in subjects at both low and high risk of NIDDM. Diabetes. 1996;45(5):633–8.PubMed
66.
Jung U, Choi M-S. Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci. 2014;15(4):6184–223.PubMedPubMedCentral
67.
•• Volek JS, et al. Body composition and hormonal responses to a carbohydrate-restricted diet. Metabolism. 2002;51(7):864–70 (A key study that evaluated the effects of KD on endocrine changes).PubMed
68.
Krauss RM, et al. Separate effects of reduced carbohydrate intake and weight loss on atherogenic dyslipidemia. Am J Clin Nutr. 2006;83(5):1025–31 quiz 1205.PubMed
69.
Hu T, et al. Effects of low-carbohydrate diets versus low-fat diets on metabolic risk factors: a meta-analysis of randomized controlled clinical trials. Am J Epidemiol. 2012;176(Suppl 7):S44–54.PubMedPubMedCentral
70.
•• Samaha FF, et al. A low-carbohydrate as compared with a low-fat diet in severe obesity. N Engl J Med. 2003;348(21):2074–81 (One of the earliest RCTs comparing the KD vs Low fat diet, showing the weight loss potential of KD). PubMed
71.
•• Dansinger ML, et al. Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial. JAMA. 2005;293(1):43–53 (A key landmark study comparing the metabolic effects and weight loss potentials of different diets). PubMed
72.
•• Shai I, et al. Weight loss with a low-carbohydrate, mediterranean, or low-fat diet. N Engl J Med. 2008;359(3):229–41 (One of the long term RCTs comparing the effectiveness of different diets and their implications into clinical practice). PubMed
73.
Abbasi J. Interest in the ketogenic diet grows for weight loss and type 2 diabetes. Jama. 2018;319(3):215–7.PubMed
74.
Westman EC, et al. The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus. Nutr Metab. 2008;5(1):36.
75.
Hussain TA, et al. Effect of low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes. Nutrition. 2012;28(10):1016–21.PubMed
76.
Yancy WS, et al. A low-carbohydrate, ketogenic diet to treat type 2 diabetes. Nutr Metab. 2005;2(1):34.
77.
•• Meng Y, et al. Efficacy of low carbohydrate diet for type 2 diabetes mellitus management: a systematic review and meta-analysis of randomized controlled trials. Diabetes Res Clin Pract. 2017;131:124–31 (Systematic review of 7 RCTs evaluating the effectiveness of KD in T2DM). PubMed
78.
Huntriss R, Campbell M, Bedwell C. The interpretation and effect of a low-carbohydrate diet in the management of type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials. Eur J Clin Nutr. 2018;72(3):311–25.PubMed
79.
•• Davis NJ, et al. Comparative study of the effects of a 1-year dietary intervention of a low-carbohydrate diet versus a low-fat diet on weight and glycemic control in type 2 diabetes. Diabetes Care. 2009;32(7):1147–52 (An important RCT showing the short-term benefits of KD in glycemic control). PubMedPubMedCentral
80.
Guldbrand H, et al. In type 2 diabetes, randomisation to advice to follow a low-carbohydrate diet transiently improves glycaemic control compared with advice to follow a low-fat diet producing a similar weight loss. Diabetologia. 2012;55(8):2118–27.PubMedPubMedCentral
81.
Oyabu C, et al. Impact of low-carbohydrate diet on renal function: a meta-analysis of over 1000 individuals from nine randomised controlled trials. Br J Nutr. 2016;116(4):632–8.PubMed
82.
Bonikowska K, Magnusson P, Sjoholm A. Life-threatening ketoacidosis in patients with type 2 diabetes on LCHF diet. Lakartidningen. 2018;115:E4AD.PubMed
83.
Clifton PM, Condo D, Keogh JB. Long term weight maintenance after advice to consume low carbohydrate, higher protein diets--a systematic review and meta analysis. Nutr Metab Cardiovasc Dis. 2014;24(3):224–35.PubMed
84.
Sim KA, et al. Weight loss improves reproductive outcomes in obese women undergoing fertility treatment: a randomized controlled trial. Clin Obes. 2014;4(2):61–8.PubMed
85.
Sim KA, Partridge SR, Sainsbury A. Does weight loss in overweight or obese women improve fertility treatment outcomes? A systematic review. Obes Rev. 2014;15(10):839–50.PubMed
86.
McGrice M, Porter J. The effect of low carbohydrate diets on fertility hormones and outcomes in overweight and obese women: a systematic review. Nutrients. 2017;9(3):204.PubMedCentral
87.
Ehrmann DA. Polycystic ovary syndrome. N Engl J Med. 2005;352(12):1223–36.PubMed
88.
Moran LJ, et al. Dietary composition in the treatment of polycystic ovary syndrome: a systematic review to inform evidence-based guidelines. J Acad Nutr Diet. 2013;113(4):520–45.PubMed
89.
Mavropoulos JC, et al. The effects of a low-carbohydrate, ketogenic diet on the polycystic ovary syndrome: a pilot study. Nutr Metab. 2005;2(1):35.
90.
Volek JS, et al. Metabolic characteristics of keto-adapted ultra-endurance runners. Metabolism. 2016;65(3):100–10.PubMed
91.
Urbain P, et al. Impact of a 6-week non-energy-restricted ketogenic diet on physical fitness, body composition and biochemical parameters in healthy adults. Nutr Metab. 2017;14(1):17.
92.
Paoli A, et al. Ketogenic diet does not affect strength performance in elite artistic gymnasts. J Int Soc Sports Nutr. 2012;9(1):34.PubMedPubMedCentral
93.
Wilson JM, et al., The effects of ketogenic dieting on body composition, strength, power, and hormonal profiles in resistance training males. J Strength Cond Res, 2017.
94.
Santos HO. Ketogenic diet and testosterone increase: is the increased cholesterol intake responsible? To what extent and under what circumstances can there be benefits? Hormones (Athens). 2017;16(3):266–70.
95.
Kopp W. Nutrition, evolution and thyroid hormone levels - a link to iodine deficiency disorders? Med Hypotheses. 2004;62(6):871–5.PubMed
96.
Pasquali R, et al. Relationships between iodothyronine peripheral metabolism and ketone bodies during hypocaloric dietary manipulations. J Endocrinol Investig. 1983;6(2):81–9.
97.
Reinhardt W, et al. Effect of small doses of iodine on thyroid function during caloric restriction in normal subjects. Horm Res. 1993;39(3-4):132–7.PubMed
98.
Serog P, et al. Effects of slimming and composition of diets on VO2 and thyroid hormones in healthy subjects. Am J Clin Nutr. 1982;35(1):24–35.PubMed
99.
•• Kose E, et al. Changes of thyroid hormonal status in patients receiving ketogenic diet due to intractable epilepsy. J Pediatr Endocrinol Metab. 2017;30(4):411–6 (Pediatric study that has reported a risk of hypothyroidism with long-term use of KD).
100.
Iacovides S, Meiring RM. The effect of a ketogenic diet versus a high-carbohydrate, low-fat diet on sleep, cognition, thyroid function, and cardiovascular health independent of weight loss: study protocol for a randomized controlled trial. Trials. 2018;19(1):62.PubMedPubMedCentral
Metadata
Title
Ketogenic Diet: an Endocrinologist Perspective
Authors
Aravind Reddy Kuchkuntla
Meera Shah
Saketh Velapati
Victoria M. Gershuni
Tamim Rajjo
Sanjeev Nanda
Ryan T. Hurt
Manpreet S. Mundi
Publication date
01-12-2019
Publisher
Springer US
Published in
Current Nutrition Reports / Issue 4/2019
Electronic ISSN: 2161-3311
DOI
https://doi.org/10.1007/s13668-019-00297-x

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