If only the contestants in the show “The Biggest Loser” had this information before they destroyed their health with gruesome regimens of fasting, low-carb diets and exhaustive exercise. As it stands, those poor souls ended up not only regaining all of the weight they lost, even on reduced calorie diets after the show ended, but lost a major part of their muscle mass during the contest, and then regained most of that weight back in the form of fat. Truly a tragedy. As has become common for mainstream medicine, the official claims that “one has to burn fat in order lose fat” have very little evidence behind them. Often, the truth is 180 degrees away from what is officially pushed as “healthy”. In this specific case, the study found that administering the drug dichloroacetate (DCA), restored activity of the enzyme pyruvate dehydrogenase (PDH) and led losing a good portion of fat in the already obese subjects. As my readers know, PDH is the rate-limiting step for glucose oxidation and is known to be down regulated not only in obesity, but also diabetes, heart disease, and especially cancer. Speaking of cancer, the drug DCA is mostly known from its highly “controversial” (read: inconvenient) results in limited human cancer trials about a decade ago. In those trials it was found to induce complete regression in the tumors of some people with very advanced (even terminal) disease. Of course, those promising results went nowhere, as they directly challenged the dogma that cancer is a mutation-driven, instead of metabolic, disease. The fact that DCA is toxic when used in high-doses also served as good deterrent for the general public to try it for their chronic conditions. However, one does not need to gamble with DCA in order to get the same effects. The main co-factors for PDH are vitamin B1 and magnesium. In addition, PDH activity is also modulated by the mitochondrial NAD+/NADH ratio, with higher ratio leading to higher PDH activity. Thus a combination of B1, niacinamide (NAD+ precursor) and magnesium would probably have achieved the same effects as DCA in the current study, with few known risks even at very high doses. Since the NAD+/NADH ratio is also known to be modulated by the Randle Cycle, restricting dietary fat (which lower NAD+/NADH ratio) and increasing carb intake would also likely have a positive effect, and it would be synergistic with the supplementation mentioned above.
https://www.jpost.com/health-and-wellness/article-874860
“…The research, Targeting Metabolic Dysregulation in Obesity: The Interplay Between Pyruvate Dehydrogenase and Weight Loss, part of a master’s thesis by Indiresh A. Mangra-Bala, focused on a small molecule called dichloroacetate, or DCA. For decades, scientists have known that DCA can push cells to burn sugar more completely in their “power stations,” the mitochondria. In this study, the question was simple but ambitious: if you force the body to use sugar differently after obesity has already developed, can you actually reduce fat and improve health? At the heart of the work is an enzyme system called the pyruvate dehydrogenase complex, or PDH. In simple terms, PDH is like a gate that decides what happens to sugar once it enters the cell. When the gate is open, sugar is sent into the mitochondria and burned for energy. When the gate is closed, much of that sugar is diverted into other pathways that can end up as fat or as lactate in the blood. In obesity and diabetes, that metabolic gate tends to be “closed” more often than it should be, because a family of enzymes called pyruvate dehydrogenase kinases, or PDHKs, act like brakes on PDH.”
“…DCA works by blocking PDHKs, which in theory removes some of those brakes and keeps the PDH gate more open. The new study investigated the effects of applying this concept to obese animals. Researchers first fed male and female mice a high-fat diet for ten weeks until they became obese. Only then did they begin treating the animals with DCA to mimic a real-world situation in which patients are already overweight before a drug is started.
