Ketosis vs ketoacidosis: What is the difference?

By Dr. Stephen Phinney and the Virta Team

Ketosis: Endogenous ketones are known to be safe at physiologic levels. It has long been known that ketones are an effective alternate metabolic fuel and recent studies have shown them to be potent epigenetic and hormonal signaling molecules as well (Newman, 2014; Rojas-Morales, 2016; Nagao, 2016). In nutritional ketosis, serum ketones range from 0.5 to 5 mM. This is the body’s normal state of lipolysis that occurs when carbohydrates are avoided (Manninen, 2004; Veech, 2004).

Ketoacidosis: In stark contrast to this normal physiology of ketosis, pathologic ketoacidosis manifests with serum levels ketone levels of 15-25 mM (i.e., three- to ten-fold higher than in nutritional ketosis). Lipolysis is exquisitely regulated, so it is exceedingly rare for a patient with normal pancreatic beta cell function to enter ketoacidosis.

Citations:

Manninen AH. Metabolic effects of the very-low-carbohydrate diets: misunderstood “villains” of human metabolism. J Int Soc Sports Nutr. 2004 Dec 31;1(2):7-11. doi: 10.1186/1550-2783-1-2-7. PubMed PMID: 18500949; PubMed Central PMCID: PMC2129159.

Nagao M, Toh R, Irino Y, Mori T, Nakajima H, Hara T, Honjo T, Satomi-Kobayashi S, Shinke T, Tanaka H, Ishida T, Hirata K. β-Hydroxybutyrate elevation as a compensatory response against oxidative stress in cardiomyocytes. Biochem Biophys Res Commun. 2016 Jul 8;475(4):322-8. doi: 10.1016/j.bbrc.2016.05.097. Epub 2016 May 20. PubMed PMID: 27216458.

Newman JC, Verdin E. Ketone bodies as signaling metabolites. Trends Endocrinol Metab. 2014 Jan;25(1):42-52. doi: 10.1016/j.tem.2013.09.002. Epub 2013 Oct 18. Review. PubMed PMID: 24140022; PubMed Central PMCID: PMC4176946.

Rojas-Morales P, Tapia E, Pedraza-Chaverri J. β-Hydroxybutyrate: A signaling metabolite in starvation response? Cell Signal. 2016 Aug;28(8):917-23. doi: 10.1016/j.cellsig.2016.04.005. Epub 2016 Apr 13. Review. PubMed PMID: 27083590.

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 Fatty Acids. 2004 Mar;70(3):309-19. Review. PubMed PMID: 14769489.

 

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