By Daniel Gwartney, M.D.
For the bodybuilder or image-conscious person, the purpose of dieting is to improve one’s appearance by reducing body fat to reveal a healthy and impressive physique. Few people diet with the intention of losing muscle; certainly not bodybuilders and athletes. Unfortunately, most dieters suffer a balanced loss of both lean and fat mass due to extreme caloric restriction, excessive cardio, or unwise use of stimulant-based weight loss products and thyroid hormones.1 The physical and emotional stress can also disrupt sleep, which promotes fat gain and interferes with optimal hormonal balance.
The preservation of muscle mass during hypocaloric dieting, especially in a setting of physical exercise or labor, is challenging. Not only must sufficient calories be consumed, but also amino acids to avoid limiting any anabolic processes. Dieters also need to manage their macro- and micro-nutrients necessary to support lean mass function, repair, and growth.
The basis for all successful diets is caloric restriction and long-term compliance, coupled with appropriate lifestyle interventions (e.g., exercise, sleep, alcohol intake). However, calories are not calories, as many advocates of the Atkins Diet and similar programs have learned. Though initially challenged by many in the health care professions, largely due to increased consumption of saturated fat during the induction phase, the Atkins Diet has been shown to be as effective in regard to weight loss, quicker, and surprisingly has heart-healthy effects.2
The Atkins diet is not a true ketogenic diet in that it gradually re-introduces carbohydrates to the diet after an induction phase of variable length. However, the dramatic changes that occur during the ketogenic phase have caused that component to be the lightning rod of media attention. A parade of ketogenic-based diets followed. However, with time, it became evident that many individuals are unable to comply with the severe carbohydrate restrictions.
Ketogenesis refers to the creation of small molecules called ketone bodies, primarily by the liver, when the body is desperate for energy, during periods of low sugar availability for calorie burning.3 Type 1 or insulin-dependent diabetics can experience a severe, life-threatening form of ketosis due to their inability to drive sugar into the active tissue that needs sugar-based calories, even though the bloodstream is practically syrup. Instead, stored fat is released in greater quantities, as well as protein from skeletal muscle to provide fuel for energy production. It is the metabolic equivalent to burning the furniture and hardwood floors to heat the home during a life-threatening freeze.
The body has a complex interplay of sensing mechanisms and communication channels to detect what is happening in the environment and respond appropriately. At the cellular level, most of these detection and response pathways serve more than one purpose. One such pathway that is particularly relevant to bodybuilders and athletes is called mTOR. mTOR is a powerful signaling pathway that is present in most cells. It is a common pathway to energy, nutrient, and growth factor fluxes, regulating a broad spectrum of cellular functions.4
Nutrients and growth factors activate mTOR; energy deprivation inhibits it.5 In other words, when the body is well-fed and growing, mTOR is “turned on;” conversely, when energy (most strongly affected by glucose availability to the cell) is low, mTOR is “turned off.” Bodybuilders are most interested in activating mTOR in muscle, as well as turning it off in fat tissue. Unfortunately, the natural signals are generally not tissue-specific, meaning that what increases muscle-building also tends to promote fat gain; the opposite is also true, to increase fat loss, one risks increasing muscle loss. This may account for some degree of the association of muscle loss during dieting. There is some research into pharmaceutical compounds that would be tissue-specific in activating or inhibiting mTOR.
One of the most potent activators of mTOR is insulin, the hormone released when blood sugar goes up during a meal.6 Insulin rapidly stops the protein breakdown that can occur during strenuous exercise, especially when glycogen (stored sugar) levels are low in the muscle and liver, as well as increasing anabolic processes and glucose uptake. Insulin also promotes fat storage in fat tissue, so the challenge for bodybuilders is balancing and timing insulin surges to promote muscle gains as they maintain a low basal insulin presence. Bodybuilders may be familiar with the many high-carbohydrate creatine products, using as much as 75 grams of dextrose (sugar) to induce a high-amplitude insulin surge.
Ketogenic diets purposefully restrict carbohydrates to very low amounts, perhaps 10 to 20 grams daily. At this level, insulin is greatly reduced, stimulated only by protein content of food, which is a weaker signal than sugar. Neurologists noted that children with epilepsy (a seizure disorder) experienced significantly fewer and less severe seizures when placed on a ketogenic diet.4 For these patients, it is critical that they remain in a relatively ketogenic state. The success of this dietary manipulation appears to be due in part, or in whole, upon the effect of the ketogenic diet on the mTOR pathway in the affected region of the brain. To determine this, a group of researchers studied a group of normal rats, then those who were treated with a drug that induces a form of epilepsy.4
In the relevant area of the brain and the liver, normal mice experienced a decrease in a factor that stimulates mTOR (Akt), as well as a factor that carries out the mTOR signal in promoting protein synthesis and cell growth (S6) while on the ketogenic diet. Also, a factor that inhibits mTOR (AMPK) was increased considerably. These effects were also seen in the mice subjected to the “epilepsy drug,” with reduced seizures in the ketogenic diet rats, suggesting that suppressing the mTOR pathway may be the way the diet helps epileptic children. Interestingly, the suppressive power of the ketogenic diet was greater than the stimulating effect of the “epilepsy drug” kainic acid, a mTOR hyperactivator.
For those fortunate enough to be healthy, the question then arises: will following a ketogenic diet reduce muscle gains, or enhance muscle loss? Sadly, it appears this may be the case, particularly for drug-free bodybuilders. The authors noted that ketogenic diets resulted in much lower insulin concentrations in prior animal studies (an effect also seen in humans).7 Insulin is one of the more potent driving forces in activating mTOR (via PI3K and Akt).
What about other growth factors, such as IGF-1? Like insulin, IGF-1 has a potent effect on mTOR activation. Studies in children on ketogenic diets have shown that they experience growth impairments both in height and mass.7,8 Analyzing the hormone profile shows this is closely-related to a significant decrease in free and total IGF-1. Blunting both insulin and IGF-1 removes two of the most potent activators of mTOR.
One question that might be raised is why IGF-1 is low, when ketogenic diets often low blood sugar should cause a rise in the counter-regulatory hormones (cortisol, growth hormone, glucagon, and epinephrine). Most of these are catabolic hormones, which may account to a degree for the rise in AMPK noted in the rat study. However, an elevated growth hormone should result in an increase in IGF-1. Remember that IGF-1 is produced primarily in the liver, though skeletal muscle is another source. Yet, findings from another rat study (it is hard to find humans who will volunteer to have their livers and brains biopsied) show that a low-carbohydrate diet creates growth hormone resistance in the liver.9 Growth hormone’s anabolic effects also utilize mTOR, so any state that impair mTOR activation would be deleterious to muscle growth.10 This was demonstrated in a 2009 study published in the Journal of Physiology, in which people who were experimentally treated with rapamycin failed to respond to muscle contractions (exercise) by increasing protein synthesis (muscle-building).11 Also, high-fat diets (such as the ketogenic diet) and increases in fat stored within muscle cells also induce insulin resistance in that tissue, possibly impairing IGF-1 production there, similar to the liver.12
One last major pathway leading to muscle loss, or at least reduced muscle growth, is myostatin. This hormone actually is a negative regulator of muscle mass; it promotes atrophy or muscle loss. Myostatin acts a preserver of (reduced) muscle function, reducing the amount of muscle and attempting to draw in more sugar through specific receptor-transporters (GLUT1, GLUT4, etc).13 This results in greater insulin sensitivity in the muscle, but seemingly fails to keep pace with the increase in insulin resistance caused by increases in stored fat and fatty acids inside the muscle cell.
Myostatin production is increased in a setting of energy-perceived energy deficiency. In type 1 diabetics, the obese, and other conditions associated with insulin resistance, this may be due to poor sugar uptake by the muscle. During ketogenic dieting, there is little sugar to take in, regardless of how insulin-sensitive the body may be. Also, the low insulin and IGF-1 signaling makes the muscle cell more sensitive to the “wasting” effect of myostatin.14
Myostatin activates the mTOR inhibiting pathway (AMPK), and reduces the mTOR activating response to insulin/IGF-1 (Akt).14,15 It is a vicious cycle, designed to allow the body to survive periods of famine. Very few cavemen were engaged in the sport of bodybuilding during the Paleolithic era; the genes in modern man are designed to store energy, not waste it.
It should be noted that the insulin resistance that occurs during low-carbohydrate dieting is beneficial in that it reduces the competition for sugar for the brain. When the liver, muscle and other tissues are responding to insulin, they preferentially absorb sugar. Brain tissue is not insulin-sensitive, so it suffers temporarily when an insulin surge occurs. This is the sugar crash that causes suburban kids to go into a three-hour coma on Halloween, after gorging on fun-sized Snickers and Twizzlers.
It should also be noted that muscle growth is a balance between anabolic and catabolic pathways. Briefly, it is likely that the catabolic pathways that result in “FOXO” activation are either activated or Akt suppression is increased during ketogenic dieting.16,17
Most bodybuilders who follow low-carbohydrate plans do not follow true ketogenic diets. For epileptic children, the ketogenic diet is 70 percent fat (by calories).4 Bodybuilders consume great quantities of protein, and while some amino acids are ketogenic, others are gluconeogenic, which means they can be converted into glucose (sugar) in the liver if needed. Also, calories are rarely restricted to extreme deficits; there is reliance upon exercise to burn calories, rather than just depending upon calorie restriction. Exercise reverses some of the effects of ketogenic diets, by activating PI3K directly by contractile-dependent means.18,19
Nonetheless, for the drug-free bodybuilder, very low-carbohydrate diets can enhance muscle loss. The loss of anabolic/anti-catabolic signaling from reduced insulin concentrations, along with increased thyroid hormone activity (a catabolic hormone, though permissive for some anabolic actions), and reduced basal (resting) testosterone concentration, combine to promote muscle loss and inhibit muscle gains.20
Even for a drug-enhanced bodybuilder, especially at the pro level where a small difference can be the difference between being “in the money” or standing back during the pose down, a ketogenic diet may be the minor but significant deficit. Some may increase the use of growth factors in an attempt to promote muscle growth or maintenance during this period (assuming their “guru” is aware of mTOR effects). However, as noted earlier— insulin use impairs fat loss; the liver is much less responsive to growth hormone, producing less IGF-1; and myostatin reduces the muscle cell’s sensitivity to mTOR activation and makes it more susceptible to mTOR inhibition.
When dieting, people seek the fastest and most potent pathway to fat loss. However, for the athlete and bodybuilder, ketogenic dieting does not appear to be the optimal plan. Muscle loss is too high a price to pay and in the high stakes game of professional bodybuilding, the small difference may be all the difference.
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