Ketogenic diets: from cancer to mitochondrial diseases and beyond

Abstract

Background The employment of dietary strategies such as ketogenic diets, which force cells to alter their energy source, has shown efficacy in the treatment of several diseases. Ketogenic diets are composed of high fat, moderate protein and low carbohydrates, which favour mitochondrial respiration rather than glycolysis for energy metabolism.

Mitochondrial fusion, fission, and mitochondrial toxicity

“…It will also be important to put toxicants’ effects on mitochondrial dynamics in the context of other environmental variables that affect mitochondria, such as diet (Branco et al 2016; Hepple 2009) and exercise (Bo et al 2010); as described above, these are currently among the better-described environmental regulators of mitochondrial fusion and fission. Indeed, dietary and exercise variables have been reported to cause “mitohormesis” (Held and Houtkooper 2015; Merry and Ristow 2016), suggesting a possible protective effect.…”

A 1-week extension of a ketogenic diet provides a further decrease in myocardial 18F-FDG uptake and a high detectability of myocarditis with FDG-PET

“…Such protocols have previously been shown to be well tolerated, even when prolonged several weeks or months in various diseases, including with an established efficacy in pediatric pharmaco-resistant epilepsy. [13][14][15] Ketogenic diet may also be prescribed in diabetic patients without significant risk and at the condition of adapting the antidiabetic treatment to the improvement in blood glucose levels and to the reduction of the need for insulin, which are currently induced by such diets. 30 In addition, low-carbohydrate diets have shown a significant albeit variable effectiveness for decreasing myocardial 18 F-FDG uptake in a number of 18 F-FDG-PET studies conducted in humans 4,[8][9][10] or animals.…”

“…This study was aimed at determining whether a drastic ketogenic diet provides a further decrease in physiological myocardial 18 F-FDG uptake and a high detectability of myocarditis by 18 F-FDG-PET in rats, when this diet is prolonged up to 1 week, as compared with a standard 18-hour fasting conditioning. Such diet can be prescribed at a much longer term than fasting, [13][14][15] leading to metabolic changes that are known to progressively suppress the metabolic use of glucose, even in the brain, within at least a 3-to 5-day period. [15][16][17][18] …”

The Expanding Role of Ketogenic Diets in Adult Neurological Disorders

“…Emerging research efforts over the past two decades seek to exploit a known cancer hallmark of abnormal energy metabolism in tumor cells named the “Warburg effect” following the discovery of physician, biochemist and Nobel laureate Otto Warburg that tumors exhibit high rates of aerobic glycolysis followed by predominant fermentation of pyruvate to lactate despite sufficient oxygen availability [71,72]. This metabolic phenotype confers several potential advantages to the cancer cell that include (1) more efficient generation of carbon equivalents for macromolecular synthesis; (2) bypassed mitochondrial oxidative metabolism and its concurrent production of reactive oxygen species and (3) acidification of the tumor site to facilitate invasion and progression [73]. As a result of this metabolic alteration, malignant glioma cells critically depend on glucose as the main energy source to survive and sustain their aggressive proliferative properties [74].…”