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Volume 9, Issue 6, November 2020, Page: 154-162
The Effects of Exogenous Beta-Hydroxybutyrate Supplementation on Metrics of Safety and Health
Matthew Stefan, Research Department, The Applied Science and Performance Institute, Tampa, Florida, USA
Matthew Sharp, Research Department, The Applied Science and Performance Institute, Tampa, Florida, USA
Raad Gheith, Research Department, The Applied Science and Performance Institute, Tampa, Florida, USA
Ryan Lowery, Research Department, The Applied Science and Performance Institute, Tampa, Florida, USA
Jacob Wilson, Research Department, The Applied Science and Performance Institute, Tampa, Florida, USA
Received: Nov. 9, 2020;       Accepted: Nov. 24, 2020;       Published: Dec. 8, 2020
DOI: 10.11648/j.ijnfs.20200906.13      View  86      Downloads  273
The ketogenic diet is a high-fat, very low-carbohydrate, moderate-protein diet that will induce a state of ketosis. Ketosis is a metabolic state characterized by elevated ketone body production in response to the absence of carbohydrates. Some drawbacks of the ketogenic diet are that it can be difficult to adhere to due to its restrictive nature, and it can also cause some undesirable side effects like gastrointestinal distress and increases in apoB-lipoproteins. In order to maximize the benefit of ketosis and to minimize side effects, supplementing with exogenous beta-hydroxybutyrate may induce a state of temporary ketosis without undesirable side effects. In the present study, 22 healthy male and female adults consumed 12.75 grams of beta-hydroxybutyrate salts or maltodextrin placebo twice daily for 90 days. Comprehensive blood safety analysis, body composition, bone densitometry, psychological and immune surveys, and blood pressure were administered at baseline, 30, 60, and 90 days. There were no significant differences in any measures collected, indicating that exogenous beta-hydroxybutyrate had no detrimental impact on fasting blood values such as electrolyte levels, glucose, hemoglobin A1c, complete blood count, body composition, bone density, psychological well-being, immune status, or blood pressure. We conclude that supplementing with exogenous beta-hydroxybutyrate is safe and well-tolerated by healthy adults.
Beta-Hydroxybutyrate, Ketosis, Safety, Exogenous Ketones
To cite this article
Matthew Stefan, Matthew Sharp, Raad Gheith, Ryan Lowery, Jacob Wilson, The Effects of Exogenous Beta-Hydroxybutyrate Supplementation on Metrics of Safety and Health, International Journal of Nutrition and Food Sciences. Vol. 9, No. 6, 2020, pp. 154-162. doi: 10.11648/j.ijnfs.20200906.13
Copyright © 2020 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Paoli A, Rubini A, Volek JS, et al. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr 2013; 67: 789–796.
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, Leukotrienes, and Essential Fatty Acids 2004; 70: 309–319.
Ballard KD, Quann EE, Kupchak BR, et al. Dietary carbohydrate restriction improves insulin sensitivity, blood pressure, microvascular function, and cellular adhesion markers in individuals taking statins. Nutr Res 2013; 33: 905–912.
Hyatt HW, Kephart WC, Holland AM, et al. A Ketogenic Diet in Rodents Elicits Improved Mitochondrial Adaptations in Response to Resistance Exercise Training Compared to an Isocaloric Western Diet. Front Physiol 2016; 7 Im Internet:
Petersen KF, Dufour S, Befroy D, et al. Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. The New England Journal of Medicine 2004; 350: 664–671.
Young CM, Scanlan SS, Im HS, et al. Effect on body composition and other parameters in obese young men of carbohydrate level of reduction diet. Am J Clin Nutr 1971; 24: 290–296.
Sumithran P, Prendergast LA, Delbridge E, et al. Ketosis and appetite-mediating nutrients and hormones after weight loss. European Journal of Clinical Nutrition 2013; 67: 759–764.
Rosen JC, Gross J, Loew D, et al. Mood and appetite during minimal-carbohydrate and carbohydrate-supplemented hypocaloric diets. The American Journal of Clinical Nutrition 1985; 42: 371–379.
Poff, A., Koutnik, A., Deblasi, J., Rogers, C., Kesl, S., Ward, N. and D'Agostino, D. (2018), Characterizing the physiologic effects of exogenous ketone supplements – an alternative or adjuvant to the ketogenic diet. The FASEB Journal, 32: 812.38-812.38.
Krotkiewski M. Value of VLCD supplementation with medium chain triglycerides. International Journal of Obesity and Related Metabolic Disorders: Journal of the International Association for the Study of Obesity 2001; 25: 1393–1400.
Neal EG, Chaffe H, Schwartz RH, et al. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. The Lancet Neurology 2008; 7: 500–506.
Vanitallie TB, Nonas C, Di Rocco A, et al. Treatment of Parkinson disease with diet-induced hyperketonemia: a feasibility study. Neurology 2005; 64: 728–730.
Poff A, Koutnik AP, Egan KM, et al. Targeting the Warburg effect for cancer treatment: Ketogenic diets for management of glioma. Seminars in Cancer Biology 2019; 56: 135–148.
Feinman RD, Pogozelski WK, Astrup A, et al. Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base. Nutrition (Burbank, Los Angeles County, Calif) 2015; 31: 1–13.
Yancy WS, Vernon MC, Westman EC. A pilot trial of a low-carbohydrate, ketogenic diet in patients with type 2 diabetes. Metabolic Syndrome and Related Disorders 2003; 1: 239–243.
Cox PJ, Kirk T, Ashmore T, et al. Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes. Cell Metabolism 2016; 24: 256–268.
Cox PJ, Clarke K. Acute nutritional ketosis: implications for exercise performance and metabolism. Extrem Physiol Med 2014; 3: 17.
Safety and tolerability of the ketogenic diet used for the treatment of refractory childhood epilepsy: a systematic review of published prospective studies - PubMed. Im Internet:
Kwiterovich PO, Vining EPG, Pyzik P, et al. Effect of a high-fat ketogenic diet on plasma levels of lipids, lipoproteins, and apolipoproteins in children. JAMA 2003; 290: 912–920.
Poff A, Koutnik A, Egan B. Nutritional Ketosis with Ketogenic Diets or Exogenous Ketones: Features, Convergence, and Divergence. Current Sports Medicine Reports 2020; 19; 7: 251-259.
Veech RL. Ketone ester effects on metabolism and transcription. Journal of Lipid Research 2014; 55: 2004–2006.
Harvey CJ d C, Schofield GM, Williden M. The use of nutritional supplements to induce ketosis and reduce symptoms associated with keto-induction: a narrative review. PeerJ 2018; 6 Im Internet:
Soto-Mota A, Vansant H, Evans R, Clarke K. Safety and tolerability of sustained exogenous ketosis using ketone monoester drinks for 28 days in healthy adults. Regulatory Toxicology and Pharmacology 2019; 109: 104506.
Blood and cardiovascular health parameters after supplementing with ketone salts for six weeks | Holland | Journal of Insulin Resistance. Im Internet:
Wilod Versprille LJF, van de Loo AJAE, Mackus M, et al. Development and Validation of the Immune Status Questionnaire (ISQ). Int J Environ Res Public Health 2019; 16 Im Internet:
Grove R, Prapavessis H. Abbreviated POMS Questionnaire (40 items). 2013.
McGettigan B, McMahan R, Orlicky D, et al. Dietary Lipids Differentially Shape Nonalcoholic Steatohepatitis Progression and the Transcriptome of Kupffer Cells and Infiltrating Macrophages. Hepatology 2019; 70: 67–83.
Reddy ST, Wang C-Y, Sakhaee K, et al. Effect of low-carbohydrate high-protein diets on acid-base balance, stone-forming propensity, and calcium metabolism. American Journal of Kidney Diseases 2002; 40: 265–274.
Luukkonen PK, Dufour S, Lyu K, et al. Effect of a ketogenic diet on hepatic steatosis and hepatic mitochondrial metabolism in nonalcoholic fatty liver disease. Proc Natl Acad Sci U S A 2020; 117: 7347–7354.
Franco Cavaleri, Emran Bashar, "Potential Synergies of β-Hydroxybutyrate and Butyrate on the Modulation of Metabolism, Inflammation, Cognition, and General Health", Journal of Nutrition and Metabolism, vol. 2018, Article ID 7195760, 13 pages, 2018.
Tendler D, Lin S, Yancy WS, et al. The Effect of a Low-Carbohydrate, Ketogenic Diet on Nonalcoholic Fatty Liver Disease: A Pilot Study. Dig Dis Sci 2007; 52: 589–593.
Kossoff EH, Pyzik PL, Furth SL, et al. Kidney Stones, Carbonic Anhydrase Inhibitors, and the Ketogenic Diet. Epilepsia 2002; 43: 1168–1171.
Hahn TJ, Halstead LR, DeVivo DC. Disordered mineral metabolism produced by ketogenic diet therapy. Calcif Tissue Int 1979; 28: 17–22.
Progressive bone mineral content loss in children with intractable epilepsy treated with the ketogenic diet | The American Journal of Clinical Nutrition | Oxford Academic. Im Internet:
Willi SM, Oexmann MJ, Wright NM, et al. The Effects of a High-protein, Low-fat, Ketogenic Diet on Adolescents With Morbid Obesity: Body Composition, Blood Chemistries, and Sleep Abnormalities. Pediatrics 1998; 101: 61–67.
Iqbal S, Klammer N, Ekmekcioglu C. The Effect of Electrolytes on Blood Pressure: A Brief Summary of Meta-Analyses. Nutrients 2019; 11 Im Internet:
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