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  • Nutrition

    Nutrition
  • Ketogenic Diets Inhibit mTOR, Insulin, IGF-1 and Muscle Growth

    Nutrition is arguably the most important component of an athlete or bodybuilder's training regimen. A precise and effective nutritional diet plan produces a biochemical environment that promotes the most efficient muscular adaptations to resistance or endurance exercise. Throughout the years, bodybuilders and athletes have tried to improve their physiques by implementing the ketogenic diet that is high in fat and low in protein and carbohydrate. The fundamental idea behind the ketogenic diet, besides being hypocaloric, is to persuade the body to burn fats rather than carbohydrates 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 were suspected to possess appetite-suppressant properties— thus further facilitating caloric restriction and loss of body fat.

    KETOGENIC DIETS DRIVE AN EXTRAORDINARY LOSS OF MUSCLE MASS

    While ketogenic diets do tend to stimulate fast weight loss, one of the major drawbacks of the ketogenic diet is that a significant percentage of that bodyweight lost is muscle mass. This negative aspect of the ketogenic diet occurs despite the fact that the body typically prefers to burn either carbohydrates or fat for energy instead of muscle protein, even during times of reduced caloric consumption. For some reason, ketogenic diets generate a greater than normal preference for muscle protein as an energy source during hypocaloric consumption. This phenomenon appears to be partially due to the poor regulation of the all-important nutrient-sensing molecule mTOR from the low-carbohydrate ketogenic diet.

    During times of energy surplus, an activated mTOR turns on protein synthesis in muscle cells— leading to enhanced muscle growth and strength. During energy deficits, the inactivated mTOR leads to diminished muscle protein synthesis— leading to muscle atrophy.The consumption of the ketogenic diet has been shown by recent scientific investigation to negatively influence specific hormones and anabolic growth factors that are known to directly or indirectly activate mTOR.This negative influence on mTOR leads to the inhibition of muscle protein synthesis and contributes to the utilization of muscle protein as an energy source.This use of muscle protein as an energy source produces significant loss of muscle mass and strength.

    KETOGENIC DIETS INHIBIT INSULIN SIGNALING, PROTEIN SYNTHESIS AND MUSCULAR DEVELOPMENT

    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.1 Therefore, the low-carbohydrate feature of the ketogenic diet diminishes insulin signaling and may diminish mTOR signaling. In order to investigate this hypothesis, McDaniel et al.2 investigated the influence of ketogenic diets on insulin signaling. In this study, they showed that low-carbohydrate ketogenic diets significantly diminish insulin action— and this lack of insulin signaling weakens mTOR's ability to stimulate muscle protein synthesis.

    GROWTH HORMONE AND IGF-1 FUNCTION ARE DRASTICALLY REDUCED WHILE CONSUMING A KETOGENIC DIET

    Growth hormone also integrally participates in mTOR signaling. Since growth hormone is secreted after protein consumption3, the low-protein aspect of the ketogenic diet is further implicated as a potential cause for deficient muscle growth. Consequently, Bielohuby et a1.4 investigated the relationship between growth hormone and ketogenesis. In this study, they demonstrated that the low-carbohydrate aspect of ketogenic diets also leads to a decrease in growth hormone signaling by causing a decrease in the amount of growth hormone receptor levels in the liver. Growth hormone insensitivity in the liver leads to a lack of IGF-1 production, which in turn reduces IGF-1 activation of mTOR, leading to lower protein synthesis levels within muscle cells contributing to muscle atrophy.

    HIGH FAT CONSUMPTION FROM THE KETOGENIC DIET ACTIVATES AMPK AND DIMINISHES MUSCLE HYPERTROPHY

    Another deleterious consequence that may come from high fat consumption while on a ketogenic diet is the greater amount of fatty acid stored in adipose tissue. The increase in fat storage eventually leads to the release of hormone leptin from the fat cell5, which has been shown to activate the energy-sensing enzyme AMPK in muscle cells and elsewhere.6 AMPK is the cell's master metabolic energy regulator that is typically activated when cellular energy levels are low. However, when high-fat diets— like the ketogenic diet— are consumed, the abundance of fat stored in the fat cell overrides this regulatory principle of AMPK control and triggers AMPK activity, despite the energy status of the cell. AMPK then immediately stimulates fatty acid oxidation. Since AMPK plays such an important role regulating cellular energy, it's no great surprise that AMPK also interacts and regulates mTOR. Moreover, an activated AMPK has been shown to inhibit mTOR function, thus inhibiting muscle protein synthesis and muscle growth. In addition, this increase in adiposity would also lead to a desensitization of the insulin-signaling pathway, which again diminishes the activation of mTOR.

    IDEAL DIET CONTAINS A MORE EVEN BALANCE OF MACRONUTRIENTS THAN FOUND IN THE KETOGENIC DIET

    The ideal diet for building muscle and burning body fat apparently does not include extreme approaches such as the ketogenic diet, especially for the athlete and bodybuilder who wants to maximize muscle size and strength while losing body fat.The ketogenic diet's low-carbohydrate feature produces a cellular-energy deficit as the human body preferentially and optimally utilizes carbohydrates as an energy source. Carbohydrate depletion reduces the capacity to perform extremely intense resistance and endurance exercise protocols, which will also decrease the capacity to develop muscle mass and remove body fat. Also, the low-protein attribute of the ketogenic diet forces the utilization of muscle protein as an energy source by breaking down muscle protein into amino acids to burn for energy. This, of course, will drive muscle atrophy as well as deplete strength. Finally, the high fat consumption during the ketogenic diet behaves like a molecular monkey wrench within the muscle tissue— wreaking havoc on several biochemical signaling cascades that negatively influence the proper function of mTOR— depleting muscle mass.

    In conclusion, a well-balanced diet with plenty of lean protein to drive muscle protein synthesis with complex carbohydrates to supply plenty of energy during resistance training— along with an economic amount of essential fatty acids for long-term energy during endurance work— seems to be the most effective approach to your nutritional routine.

    By Michael J. Rudolph, Ph.D.


    References:
    1. Bolster DR, Jefferson LS, et al. Proc Nutr Soc 2004;63(2), 351-356.
    2. McDaniel SS, Reusing NR, et al. Epilepsia 2011;52(3), e7-11.
    3. van Vught AJ, Nieuwenhuizen AG, et al. Eur J Endocrinol 2008;159(1), 15-18.
    4. Bielohuby M, Sawitzky M, et al. Endocrinology 2011;152(5), 1948-1960.
    5. Jazet IM, Pijl H, et al. Neth J Med 2003;61(6), 194-212.
    6. MinokoshiY, KimYB, et al. Nature 2002; 415(6869), 339-343.






   
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