Written by Michael J. Rudolph, Ph.D.
02 January 2019


The Ketogenic Diet - The Good, Bad & Ugly



The best nutritional approach for greater muscularity involves the stimulation of the all-important energy-sensing molecule mTOR, which directly increases muscle protein synthesis while reducing muscle protein breakdown, ultimately leading to enhanced muscle mass. Despite the well-known influence that mTOR function has on muscle growth, many have tried to improve their physiques by implementing a ketogenic diet that is high in fat, low in protein and even lower in carbohydrate intake. The fundamental idea behind the ketogenic diet is to force the body to burn fat rather than carbohydrate or protein, due to the lack of carbohydrate and protein in the diet. The excessive fatty acid oxidation in the liver leads to the inevitable conversion of accumulated fatty acid oxidation intermediates into ketone bodies, which are believed to possess appetite-suppressant properties, thus facilitating weight loss. Unfortunately, while ketogenic diets do stimulate weight loss, a significant percentage of that bodyweight lost is muscle mass. This is because ketogenic diets inhibit the muscle-sparing activity of mTOR, causing an increased use of muscle protein for energy— resulting in a loss of muscle.


The Good: Ketogenic Diets Appear to Impede Cancer

So, you might be wondering— if ketogenic diets reduce muscle growth, then what could possibly be “good” about ketogenic diets? Well, astonishingly, it looks like ketogenic diets may actually mitigate certain cancers to a large degree, by inhibiting mTOR.1 This is because mTOR influences certain cellular processes that can promote uncontrolled growth of cancer cells. For instance, the ability of mTOR to control the cell’s protein synthesis machinery gives it the ability to trigger the production of certain proteins required for cell division2,3, which could result in unwanted cell division, supporting the progression of cancer.

Cancer cells rely heavily on glucose for energy, and mTOR inhibition by ketogenic diets reduces the production of several enzymes involved in the conversion of glucose into energy— decreasing the energy supply and thus, the viability of the cancer cell.4 In addition to inhibiting mTOR, the lack of carbohydrate consumed during the ketogenic diet should also impede cancer by further removing the cancer cells’ access to glucose-derived energy, and starving the cancer cell to death.1,5

Altogether, the ability of the ketogenic diet to reduce mTOR function and glucose availability to the cancer cell highlights its potential to combat cancer. In fact, several studies have shown that ketogenic diets do lessen the negative impact of cancer. One study6 that looked at several cancer patients consuming a ketogenic diet for a month showed that patients with the highest ketone levels, indicating a more robust response to the diet, saw the most improvement— with several patients having no tumor growth, while others actually saw their tumors shrink. In a second report of two young women with brain cancer7, one week of ketogenic dieting reduced glucose levels within their tumors by 22 percent, leading to a tremendous improvement in one of the patients where the disease did not progress for an entire year.


The Bad: Anabolic Hormone Activity Is Inhibited— and So Is Muscle Growth

As impressive as ketogenic diets appear to be in the battle against cancer, the diets are equally unimpressive if one is trying to pack on muscle mass. This is largely caused by the negative impact that ketogenic diets have on the activity of anabolic hormones such as insulin and growth hormone.

Insulin is the primary hormone that responds to increases in blood sugar, causing sugar to be shuttled into the cell for energy consumption or storage. Insulin has also been shown to be one of the most potent activators of mTOR.8 Therefore, the low-carbohydrate feature of the ketogenic diet diminishes insulin signaling— and likely diminishes mTOR function. Demonstrating this fact, a study by McDaniel et al.1 investigated the influence of ketogenic diets on insulin signaling. In this study, they showed that low-carbohydrate ketogenic diets significantly diminished insulin action, and this lack of insulin signaling weakens mTOR’s ability to stimulate muscle protein synthesis.

Growth hormone also plays an essential role in mTOR signaling. A ketogenic diet could conceivably reduce growth hormone levels, representing another reason for deficient muscle when using the ketogenic diet.9 What's more, Bielohuby et al.10 also looked at the relationship between growth hormone secretion and the low carbohydrate intake during ketogenic diets, to see if this aspect of the ketogenic diet also decreased growth hormone signaling. In fact, it not only decreased growth hormone signaling, but it also decreased the amount of growth hormone receptor levels in the liver, effectively desensitizing the liver toward growth hormone. The insensitivity of the liver to growth hormone caused a lack of IGF-1 production, which in turn reduced IGF-1 activation of mTOR— leading to lower protein production within muscle cells, eventually contributing to muscle atrophy.


The Ugly: High Fat Consumption Plausibly Triggers Muscle Loss

Another deleterious effect on muscle growth that may come from high fat consumption while on a ketogenic diet is the greater amount of fat stored in adipose tissue. The increase in fat storage eventually leads to the release of the hormone leptin from the fat cell11, which has been shown to activate the energy-sensing enzyme AMPK in muscle cells and elsewhere.12 AMPK is the cell’s master metabolic energy regulator that is typically activated when cellular energy levels are low, and inactivated when cellular energy is high. However, high-fat diets, like the ketogenic diet, override the normal regulatory control of AMPK— triggering its activity, despite the obvious high-energy status associated with elevated fat storage. The activation of AMPK is an attempt by the body to lessen the level of stored fat, as AMPK triggers fatty acid oxidation. While increased fatty acid oxidation is most likely not a problem, it is AMPK’s negative influence on mTOR activity that is an issue, as this will reduce muscle protein synthesis and therefore muscle growth. In addition, the increase in adiposity from ketogenic diets may also lead to a desensitization of the insulin-signaling pathway, which further diminishes mTOR function and muscle growth.


For most of Michael Rudolph’s career he has been engrossed in the exercise world as either an athlete (he played college football at Hofstra University), personal trainer or as a research scientist (he earned a B.Sc. in Exercise Science at Hofstra University and a Ph.D. in Biochemistry and Molecular Biology from Stony Brook University). After earning his Ph.D., Michael investigated the molecular biology of exercise as a fellow at Harvard Medical School and Columbia University for over eight years. That research contributed seminally to understanding the function of the incredibly important cellular energy sensor AMPK— leading to numerous publications in peer-reviewed journals including the journal Nature. Michael is currently a scientist working at the New York Structural Biology Center doing contract work for the Department of Defense on a project involving national security.






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