When to use a ketogenic diet

Normally what you need before you can start up aerobic respiration in the mitochondria is a multienzyme complex known as pyruvate dehydrogenase complex—of which the main enzyme is pyruvate decarboxylase. The complex acts on pyruvate, produced from glycolysis, in an oxidative decarboxylation reaction to produce acetyl-coA, which then enters the citric acid cycle (1).

What happens when pyruvate dehydrogenase is deficient? An actual genetic deficiency is rare, but it is the most common mitochondria-associated neurodegenerative disorder (2). When it does occur it significantly effects energy metabolism, poor use of glucose and build-up of lactic acid (2). Along with probable neurological impairments, too much glucose can exacerbate the problem leading to hyperglycemia and diabetes (2).

Diabetics , in essence, can also be described as a condition where pyruvate dehydrogenase complex activity is reduced(3-5). The lack of insulin to bring glucose into cells may be a factor, leading to little activity, or a nutritional deficiency of a vitamin such as thiamine (vitamin B-1) due to poor diet or starvation may lead to decreased production of the complex (3-5). In these cases, just as genetic deficiency, inefficient use of glucose results in hyperglycemia.

A ketogenic diet is used to manage the disease of pyruvate dehydrogenase deficiency (2). And it’s important to understand why this higher-fat, adequate protein, low-carb diet works for possible use with diabetes. It is because production of acetyl-coA can come from lipid metabolism via beta-oxidation as well as from amino acids isoleucine, lysine, phenylalanine, tyrosine and leucine (other amino acids are formed into pyruvate) (1p252).

There is plenty of research available showing that a ketogenic diet can help to control blood sugar (6-10). As a short-term therapy, the diet has had success even with children with Type II diabetes (11). But what of the side effects? As we know from critiques of the Atkin’s diet, a ketogenic diet produces fast weight loss through polyuria, but comes back with water retention from refeeding of carbohydrates (12) . The diet increases plasma cholesterol, uric acid, and may even cause hypokalemia (12). Further, you suffer nausea, fatigue, and hypotension (12). One must weigh the goods and bads of a ketogenic diet and make modifications as necessary.

Reference List

1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.

2. Henwood MJ, Thornton PS, Preis CM, Chee C, Grimberg A. Reconciling diabetes management and the ketogenic diet in a child with pyruvate dehydrogenase deficiency. J Child Neurol 2006;21:436-9.

3. Koivisto VA, Yki-Jarvinen H. Changes in muscle glucose metabolism in type 1 diabetes. Ann Med 1990;22:201-5.

4. Beltramo E, Berrone E, Tarallo S, Porta M. Effects of thiamine and benfotiamine on intracellular glucose metabolism and relevance in the prevention of diabetic complications. Acta Diabetol 2008;45:131-41.

5. Hutson NJ, Kerbey AL, Randle PJ, Sugden PH. Regulation of pyruvate dehydrogenase by insulin action. Prog Clin Biol Res 1979;31:707-19.

6. Westman EC, Yancy WS, Jr., Mavropoulos JC, Marquart M, McDuffie JR. The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus. Nutr Metab (Lond) 2008;5:36.

7. Feinman RD, Makowske M. Metabolic syndrome and low-carbohydrate ketogenic diets in the medical school biochemistry curriculum. Metab Syndr Relat Disord 2003;1:189-97.

8. Nuttall FQ, Schweim K, Hoover H, Gannon MC. Effect of the LoBAG30 diet on blood glucose control in people with type 2 diabetes. Br J Nutr 2008;99:511-9.

9. Dashti HM, Mathew TC, Khadada M et al. Beneficial effects of ketogenic diet in obese diabetic subjects. Mol Cell Biochem 2007;302:249-56.

10. Henwood MJ, Thornton PS, Preis CM, Chee C, Grimberg A. Reconciling diabetes management and the ketogenic diet in a child with pyruvate dehydrogenase deficiency. J Child Neurol 2006;21:436-9.

11. Willi SM, Martin K, Datko FM, Brant BP. Treatment of type 2 diabetes in childhood using a very-low-calorie diet. Diabetes Care 2004;27:348-53.

12. Hirschel B. [Dr. Atkins’ dietetic revolution: a critique]. Schweiz Med Wochenschr 1977;107:1017-25.

Published by David Despain, MS, CFS

David is a science and health writer living on Long Island, New York. He's written for a variety of publications including Scientific American, Outside Online, the American Society for Nutrition's (ASN) Nutrition Notes Daily, and Institute of Food Technologists' (IFT) Food Technology magazine and Live! blog. He's also covered new findings reported at scientific meetings including Experimental Biology, AAAS, AOCS, CASW, Sigma Xi, IFT, and others on his personal blog "Evolving Health." David is also an active member of organizations including the National Association of Science Writers (NASW), the American Association for the Advancement of Science (AAAS), the American Society for Nutrition, the Institute of Food Technologists, and the National Audubon Society. David has a master's degree in human nutrition from the University of Bridgeport, and a bachelor's degree in English from University of Illinois at Springfield. He also earned his Certified Food Scientist credential from the Institute of Food Technologists.

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