Supplementation With Ketones?

Ketosis is a term that gets thrown around a lot by dieting bodybuilders and their prep coaches. Unfortunately, due to a proliferation of “bro science” by so-called self-learned nutrition gurus and synthol-touting ‘roid chemists, most bodybuilders and physique athletes believe that a low-carbohydrate diet equates to a ketosis-producing diet. This just simply isn’t the case, as you will learn here.

It is true that a “ketogenic diet” can be very effective at burning fat, dropping weight and even improving blood lipids in obese test subjects, but is it really useful for bodybuilding? Furthermore, would it be prudent to supplement your diet with liquid ketones or ketogenic, medium-chain triglycerides? To answer this, we will have to go into more detailed physiology.

A Critical Process for Human Survival

In order to understand ketosis or the ketogenic diet, one must understand what ketones are and how our body handles them. Metabolic adaptation to starvation is a critical process for human survival that involves a series of profound physiological, hormonal, behavioral and biochemical events designed to maintain energy homeostasis. This occurs through suppression of energy-consuming processes, such as growth and reproduction, while preserving basal metabolic functions like brain, heart and kidney function.

The first event that occurs in starvation is that the liver must mobilize remaining glucose stored as glycogen, and produce more glucose via a process called gluconeogenesis. The brain prefers glucose metabolism and the liver’s job is to maintain blood glucose for brain function. However, as low blood glucose availability persists (starvation or lack of carbohydrate), the liver starts to generate “ketone bodies” for fuel of non-hepatic tissues like the brain, heart and muscles. During lack of glucose availability, the brain can utilize ketones for over 60 percent of its function.

Ketone bodies are small molecules, particularly beta-hydroxybutyrate (BHB) and acetoacetate (AcAc), which have vital roles in energy homeostasis in almost all living organisms. Ketones are created from the oxidation of fats into acetyl-coenzyme A (Acetyl-CoA), which also feeds energy production in the Krebs cycle, sending energy intermediates into the election transport chain to eventually create downstream ATP (adenosine triphosphate; the fuel for metabolism and motion). Ketones are water-soluble, and they can travel easily through the bloodstream, cross the blood-brain barrier and be converted back into Acetyl-CoA to fuel ATP production in the brain. Since we have humongous fat stores compared to stores of glucose as glycogen, fat oxidation is critical to survival when food is sparse.

Ketones are produced in everyday physiology, not just during starvation. After an evening of fasting, ketone levels are slightly elevated when you wake, to a level of 0.1-0.3 mM. With lower blood glucose and glycogen depletion in a very low-carbohydrate diet of <50 grams per day, there is a tendency to produce more ketones, especially after exhaustive exercise (1.0 to 3.0 mM). Combining the overnight fast with morning fasted cardio, this physiology is thought to improve the mobilization of fat as fuel for that cardio, thus efficiently burning fat.

Naturally, the formation of ketones suggests that we are breaking down more fat. Thus, a ketogenic or ketone-forming diet is thought to be a great way to enhance the burning of fat. Certainly, very low-carbohydrate, ketogenic diets have been shown to be effective at weight loss in obese patients. But the protocols for weight loss and ketosis may not be ideal for bodybuilding.

Ketogenic Diets and Bodybuilders

One of the most important aspects of human physiology in a low-carb state— the production of glucose from proteins (gluconeogenesis)— is often forgotten by those who recommend “ketogenic” diets to bodybuilders. The problem is that most bodybuilders consume much more protein than would typically be seen on a ketogenic diet. The ACSM and ISSN agree that consuming nearly one gram of protein per pound of bodyweight is beneficial to the muscle-building strength athlete. Unfortunately, this level of protein intake (anything above 0.5 grams per pound) will likely take the bodybuilder out of ketosis due to gluconeogenesis producing more glucose and other mechanisms of ketogenic suppression (such as activation of mTOR; to follow).

Ketogenic diets are very high in fat, low in carbohydrate and much more moderate in protein than the typical bodybuilder would consume. In fact, to optimize leucine consumption for the activation of muscle protein synthesis, higher amounts of protein are needed when lower quality proteins are consumed to meet those needs. For instance, 50 grams of protein from tilapia may be needed when 40 grams from a lean filet will meet your leucine needs.  This added 10 grams of protein will certainly contribute to leaving ketosis behind.

Interestingly, just like how we have learned that the amino acid leucine has signaling properties to turn on muscle protein synthesis, so do other nutrient molecules like ketones and short-chain fatty acids. BHB and AcAc are not only simple energy intermediates, they also function as a signaling molecules in different physiological contexts.1 BHB can bind to cell receptors and turn on anti-inflammatory processes. The anti-inflammatory actions of BHB and its clean burning in low oxygen make it an excellent fuel source in the low-oxygen states of heart attack and brain injury (i.e., stroke).

Ketone Supplements and ‘Nutritional Ketosis’

Researchers have supplemented humans and animals with ketone supplements to induce a “nutritional ketosis” to treat heart and brain conditions.2 Ingesting medium-chain triglycerides can slightly elevate ketone levels, but supplementing with ketones themselves as ketone esters can achieve higher blood levels on the magnitude similar to starvation or exhaustive, carb-depleted exercise. The thought is that perhaps, supplying BHB will give cells an energy source to spare glycolysis, which produces lactic acid or consumes more oxygen.

However, the signaling effects of BHB may be counterproductive on a number of levels. Keep in mind that ketones are meant to be elevated and exist during a state of fasting or starvation. Thus, if they are to have any signaling roles in the body (beyond their role as energy-producing metabolites), they will likely aid in energy and vital tissue conservation as well.

The first signaling action of ketones is a feedback loop to prevent excessive ketone formation as might be seen in uncontrolled diabetic ketoacidosis. Ketogenic diets don’t lead to ketoacidosis because elevated levels of ketones turn off the burning of any more fat than is needed. Studies show that ketones like BHB turn off stored fat breakdown (lipolysis), reduce metabolic rate via decreased adrenalin release and reductions of thermogenesis, and promote insulin resistance to prevent muscle from taking in any glucose that should be available for the brain.1

Another ketone-induced signaling problem relates to the leucine-sensitive regulator of muscle protein synthesis called mTOR. As you may recall from previous MD articles, the activation of mTOR from leucine turns on muscle protein synthesis in our muscle. Supplying adequate amounts of leucine with each meal from high-quality proteins or supplements like whey will activate mTOR and muscle protein synthesis. Since ketones are elevated in starvation, they have evolved with the function of limiting processes that try to use energy to build tissues like energy-expensive muscle. Studies suggest that along with creating insulin resistance, ketones also inhibit mTOR activation.1,3

Furthermore, mTOR activation by adequate quantities of leucine tell the body that food is available and the production of ketones is no longer necessary. As we already mentioned, bodybuilders need to consume adequate amounts of leucine to build muscle that is primed by intense exercise. Supplementing added ketones on top of that may theoretically limit mTOR activation and thus muscle growth, just as occurs in starvation.4

Negative Effects on Fat Burning or Muscle Growth?

The concept of supplementing very bitter, unpalatable ketones for the enhancement of performance is an interesting one. Dr. Jeff Volek has long been a proponent of very low-carbohydrate ketogenic dieting to improve the fat-burning efficiency of endurance-trained athletes. After months on a truly ketogenic diet, mitochondrial biogenesis and metabolic adaptations occur— allowing these athletes to better use fat for energy, which makes them “bonk proof” in that they don’t crash when glycogen is no longer available. These athletes can burn more fat per minute than was ever thought possible— and despite low-carb diets, they had the same glycogen stores as those on a traditional high-carbohydrate diet before and after three hours of running.5

Unfortunately, long-term ketogenic dieting is not useful for bodybuilding for reasons mentioned above. However, supplementing ketones when a diet contains adequate protein or carbohydrate is unlikely to result in metabolic adaptation to ketones, per Dr. Volek’s research, as these nutrients would just be competing with each other. In fact, if you are using ketones to supply energy in these athletes, you may induce negative effects on further fat burning or muscle growth. Much more research needs to be performed to understand the risks and benefits.

As an example of the potential risks, the effect of ketones and ketogenic dieting has been extensively explored in the treatment of cancers. Some scientists suggest that the elevation of blood ketones in insulin-dependent diabetics may partly explain why they have a higher incidence of cancer.6 Researchers have suggested that some types of cancer may be able to use ketones as fuel for growth and metastasis when they are growing rapidly and out of proportion to their blood supply, as ketones use less oxygen to burn. Others say that cancer cells often lack the ability to burn ketones for fuel, and that ketogenic diets reduce the glucose and insulin promotion of tumor growth. Much research needs to be done.

One thing is for sure— despite the fact that MCT oils and ketones are burned and transported in the body in different ways than your typical fats, they are still calories. If you are dieting for a show, replace calories rather than adding them as if they have no consequence. Sure, if you are shooting for some energy that is burned more readily and efficiently, with the lower likelihood of storage in a low-carb state, MCT oil can replace that oil and vinegar on your salad— without a significant amount of “nutritional ketosis” disrupting your muscle-building and fat-burning capacity.

1. Rojas-Morales P, et al. Beta-Hydroxybutyrate: A signaling metabolite in starvation response? Cell Signal 2016;Apr 13;28(8):917-923.
2. Cox PJ and Clarke K. Acute nutritional ketosis: implications for exercise performance and metabolism. Extrem Physiol Med 2014;Oct 29;3:17.
3. McDaniel SS, et al. The ketogenic diet inhibits the mammalian target of rapamycin (mTOR) pathway. Epilepsia 2011;Mar;52(3):e7-11.
4. Wijngaarden MA, et al. Regulation of skeletal muscle energy/nutrient-sensing pathways during metabolic adaptation to fasting in healthy humans. Am J Physiol Endocrinol Metab 2014;Nov 15;307(10):E885-95.
5. Volek JS, et al. Metabolic characteristics of keto-adapted ultra-endurance runners. Metabolism 2016;Mar;65(3):100-10.
6. Bonuccelli G, et al. Ketones and lactate “fuel” tumor growth and metastasis: Evidence that epithelial cancer cells use oxidative mitochondrial metabolism. Cell Cycle 2010;Sep 1; 9(17): 3506-3514.

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