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.
