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Pathways To Growth

Pathways To Growth

Activating Nutritional Triggers of
Protein Synthesis For Maximum Mass Gain

Hard work is essential for success in modern sport. Nutritional status determines whether you thrive or break down from intense training. Heavy exercise without nutritional support shuts down protein synthesis in the muscle cells and makes it impossible to make optimal training gains.

Cells use amino acids to make new proteins, but amino acids do a lot more than build proteins. Amino acids activate signaling proteins in muscles that turn on protein synthesis and increase muscle fiber size. Muscle tension, blood levels of amino acids (particularly leucine), and insulin are key factors for triggering muscle growth. They activate signaling pathways inside the cells that promote protein synthesis in the muscles and modify muscle protein breakdown, remodeling, and repair. 

Chemicals called ribosomal protein S6 kinase (S6K1) and the target of rapamycin (mTOR) are important cell signaling molecules that are sensitive to small changes in amino acid status and are major forces in muscle protein synthesis and hypertrophy (see figure below). They work like biological computer programs to line up amino acids needed to produce new muscle tissue. After weight training, feeding essential amino acids activates protein-signaling molecules that promote protein synthesis and muscle growth. People who do resistive exercise might benefit from essential amino acids supplements before and after training to maximize protein synthesis.

Exercise and Hormones

Figure 1A basic rule of conditioning for sports is to train the body the way you want it to adapt. Bodybuilders and power athletes don’t run 80 miles per week because it causes undesirable adaptations that don’t match the requirements of the sports. The principle of specificity is nothing new to any knowledgeable athlete, but the underlying physiology has been a mystery. High intensity exercise, such as weight training, activates the mTOR- S6K1 pathway that promotes muscle hypertrophy, strength, and power. Conversely, endurance training activates the AMPK pathway, which increases muscle cell mitochondria and enhances the muscles’ energetic capacity.

Endurance and strength training in close proximity interferes with the adaptation to both types of exercise. High intensity muscle contractions, such as occurs during bodybuilding or weight lifting, promote muscle strength and growth, while low intensity, prolonged exercise, such as distance running or cycling, builds muscle cell mitochondria (cell energy centers) and promotes endurance. Endurance training activates the AMPK pathway linked to improved cell energetics and depresses the mTOR-S6K pathway linked to muscle growth. The reverse occurs following weight training.

Insulin-like growth factor (IGF-1), insulin, growth hormone, and testosterone activate protein synthesis. Muscle protein synthesis increases in people who take anabolic drugs. However, hormone regulation is extremely complex, so taking anabolic drugs is a short-term and shortsighted solution to increasing muscle size and strength. While the drugs obviously work in the short-term, they interfere with overall hormone regulation, which eventually has negative consequences.

Nutrition, exercise volume and intensity influence hormone regulation. Key amino acids, such as leucine, maximize blood levels of insulin, IGF-1, growth hormone, and testosterone. Low protein and amino acid intake reduces the activity of each of these anabolic hormones, which reduce the capacity to gain muscle mass and strength.

Training also plays a role in hormone regulation. Overtraining increases corticosteroid levels and decreases testosterone and growth hormone levels. While hard work is essential for success, excessive exercise can disturb the regulation of the hormones necessary for success. The best remedy is to train as hard as you can without breaking down and diminishing vital hormone regulators. The right blend of nutrients can help you push harder and make greater gains.

Nutrients and Muscle Cell Regulation

Muscle size is closely linked to nutrient availability. Muscles will not hypertrophy if the nutrient supply is inadequate. Amino acids, calories, and carbohydrates are central to this process. Amino acids serve as the building blocks of proteins. Key amino acids, such as leucine, also serve as regulating signals and fuel sensors to regulate protein synthesis, particularly after exercise.

AMPK (see figure above) is a critical fuel sensor. The cells suppress the mTOR system and protein synthesis when key amino acid levels (e.g., leucine) and caloric availability are low or when energy expenditure is high (i.e., endurance exercise). Nutrients determine the balance between AMPK and mTOR activity. They work by stimulating the mTOR pathway and by inhibiting the AMPK pathway.

Amino acid supplements and their metabolites (e.g., beta-hydroxy-beta-methylbutyrate, HMB) might work, in part, by suppressing the AMPK pathway. For example, HMB, a metabolite of the amino acid leucine, prevents muscle protein breakdown, stimulates muscle growth, and promotes fat breakdown. A sophisticated study from Charles University in Prague, Czech Republic using radioactive tracers found that HMB promoted muscle hypertrophy by preventing protein breakdown rather than stimulating protein synthesis. HMB also positively affected protein metabolism in the gut, which could have beneficial effects on whole body metabolism.

Resistance exercise and nutrition independently stimulate muscle growth. Consuming protein supplements high in key amino acids after exercise helps maximize training gains. Protein mixtures containing large amounts of leucine work best for boosting muscle hypertrophy. Weight trained athletes should train hard, eat plenty of calories, and consume well-formulated protein supplements after exercise. Consuming 25-30 grams of high quality protein stimulates muscle growth in both older and younger people. However, protein synthesis slows in aging muscle with inadequate protein intake (less than 20 grams per meal). Older adults should consume 25-30 grams of high quality protein that is high in leucine during each meal.

Consuming a combination of nutrients after exercise works best. Insulin is an important anabolic hormone that increases the movement of amino acids (the building blocks of protein) into muscle cells and turns on chemicals that stimulate protein synthesis.  As discussed, leucine is an important signaling chemical that promotes protein synthesis and slows protein breakdown. Leucine also stimulates insulin release. Consuming carbohydrates and leucine-rich protein increases insulin release and decreased blood sugar. Taking a hybrid supplement containing leucine and carbohydrates after exercise replenishes carbohydrate stores (i.e., glycogen), promotes muscle protein synthesis, and decreases protein breakdown.

Supplement Suggestion

[Editor’s Note: Any discussion of the perfect blend of a protein blend particularly rich in anabolism-triggering leucine and an advanced carb complex should begin and end with the legendary mass builder from BioQuest, MyoZene. The ultimate rapid-action post-workout formula has been designed to drive anabolism along each of the muscle-support pathways described here. Its patent-pending peptide carrier technology enables leucine to remain soluble and stable for enhanced utilization, resulting in a potent stream of highly bioavailable leucine content streaming directly to muscle tissue to super-efficiently trigger protein synthesis along the mTOR pathway. Ultra-pure and powerful whey hydrolysate and whey protein isolate serve to further augment recovery and increases in strength and muscle mass, while co-factors such as creatine monohydrate and N-acetyl-L-glutamine spur growth at the cellular level. At the same time, an advanced carbohydrate matrix plays a key role in potentiating insulin release, activating ribosomal activity and supporting growth initiation factors within skeletal muscle. MyoZene’s ingredient profile represents the summation of everything researchers currently know about muscle mass increase.]

Key amino acids (i.e., the branched chain amino acids (BCAAs: leucine, isoleucine, and valine) are used extensively during exercise. However, their beneficial effects occur after rather than during exercise. BCAAs promote recovery and adaptation and boost the immune system. BCAAs are also critical for manufacturing key cells and chemicals involved in the immune system. The capacity to train hard, recover, and train hard again is critical for successful athletes. Consuming key amino acids after exercise promote hard training and speed recovery.

[Editor’s Note: Keep in mind, too, that supplementing with ALL the BCAAs is clinically indicated, as they work in tandem to shut down post-workout catabolism and jumpstart recovery. A super-premium supplement like ProSource’s Mega BCAA is sourced with the absolute highest-quality ingredients available industry-wide, and is formulated in the preferred 2:1:1 leucine-to-isoleucine-to-valine ratio.]

You aren’t going to make gains if you don’t work hard. However, hard work without optimal nutrition leads to protein breakdown, injury, and fatigue. Taking the right nutrients could spell the difference between winning and losing and could determine if your hard work will pay off.

Read more about MyoZene here.

Read more about Mega BCAA here.

Scientific References

1. Baar, K., G. Nader, and S. Bodine. Resistance exercise, muscle loading/unloading and the control of muscle mass. Essays Biochem. 42:61-74, 2006.

2.    Balasubramanian, S., R. K. Johnston, P. C. Moschella, S. K. Mani, W. J. Tuxworth, Jr., and D. Kuppuswamy. mTOR in growth and protection of hypertrophying myocardium. Cardiovasc Hematol Agents Med Chem. 7:52-63, 2009.

3.    Coffey, V.G. et al. Consecutive bouts of diverse contractile activity alter acute responses in human skeletal muscle. J Appl Physiol. 106: 1187-1197, 2009.

4.    Csibi, A., L. A. Tintignac, M. P. Leibovitch, and S. A. Leibovitch. Eif3-f function in skeletal muscles: To stand at the crossroads of atrophy and hypertrophy. Cell Cycle. 7:1698-1701, 2008.

5.    Dreyer, H. C., M. J. Drummond, E. L. Glynn, S. Fujita, D. L. Chinkes, E. Volpi, and B. B. Rasmussen. Resistance exercise increases human skeletal muscle as160/tbc1d4 phosphorylation in association with enhanced leg glucose uptake during postexercise recovery. J Appl Physiol. 105:1967-1974, 2008.

6.    Drummond, H. A., S. C. Grifoni, and N. L. Jernigan. A new trick for an old dogma: Enac proteins as mechanotransducers in vascular smooth muscle. Physiology (Bethesda). 23:23-31, 2008.

7.    Drummond, M. J., J. A. Bell, S. Fujita, H. C. Dreyer, E. L. Glynn, E. Volpi, and B. B. Rasmussen. Amino acids are necessary for the insulin-induced activation of mtor/s6k1 signaling and protein synthesis in healthy and insulin resistant human skeletal muscle. Clin Nutr. 27:447-456, 2008.

8.    Drummond, M. J., H. C. Dreyer, C. S. Fry, E. L. Glynn, and B. B. Rasmussen. Nutritional and contractile regulation of human skeletal muscle protein synthesis and mtorc1 signaling. J Appl Physiol, 2009.

9.    Drummond, M. J., H. C. Dreyer, B. Pennings, C. S. Fry, S. Dhanani, E. L. Dillon, M. Sheffield-Moore, E. Volpi, and B. B. Rasmussen. Skeletal muscle protein anabolic response to resistance exercise and essential amino acids is delayed with aging. J Appl Physiol. 104:1452-1461, 2008.

10.    Drummond, M. J., C. S. Fry, E. L. Glynn, H. C. Dreyer, S. Dhanani, K. L. Timmerman, E. Volpi, and B. B. Rasmussen. Rapamycin administration in humans blocks the contraction-induced increase in skeletal muscle protein synthesis. J Physiol, 2009.

11.    Drummond, M. J., E. L. Glynn, H. L. Lujan, S. E. Dicarlo, and B. B. Rasmussen. Gene and protein expression associated with protein synthesis and breakdown in paraplegic skeletal muscle. Muscle Nerve. 37:505-513, 2008.

12.    Drummond, M. J., J. J. McCarthy, C. S. Fry, K. A. Esser, and B. B. Rasmussen. Aging differentially affects human skeletal muscle microrna expression at rest and after an anabolic stimulus of resistance exercise and essential amino acids. Am J Physiol Endocrinol Metab. 295:E1333-1340, 2008.

13.    Drummond, M. J. and B. B. Rasmussen. Leucine-enriched nutrients and the regulation of mammalian target of rapamycin signaling and human skeletal muscle protein synthesis. Curr Opin Clin Nutr Metab Care. 11:222-226, 2008.

14.    Esser, K. Regulation of mTOR signaling in skeletal muscle hypertrophy. J Musculoskelet Neuronal Interact. 8:338-339, 2008.

15.    Fujita, S., H. C. Dreyer, M. J. Drummond, E. L. Glynn, J. G. Cadenas, F. Yoshizawa, E. Volpi, and B. B. Rasmussen. Nutrient signalling in the regulation of human muscle protein synthesis. J Physiol. 582:813-823, 2007.

16.    Glass, D. J. Skeletal muscle hypertrophy and atrophy signaling pathways. Int J Biochem Cell Biol. 37:1974-1984, 2005.

17.    Gurpur, P. B., J. Liu, D. J. Burkin, and S. J. Kaufman. Valproic acid activates the pi3k/akt/mtor pathway in muscle and ameliorates pathology in a mouse model of Duchenne muscular dystrophy. Am J Pathol. 174:999-1008, 2009.

18.    Holecek, M., T. Muthny, M. Kovarik, and L. Sispera. Effect of beta-hydroxy-beta-methylbutyrate (HMB) on protein metabolism in whole body and in selected tissues. Food Chem Toxicol. 47:255-259, 2009.

19.    Hourde, C., C. Jagerschmidt, P. Clement-Lacroix, A. Vignaud, P. Ammann, G. S. Butler-Browne, and A. Ferry. Androgen replacement therapy improves function in male rat muscles independently of hypertrophy and activation of the Akt/mTOR pathway. Acta Physiol (Oxf), 2008.

20.    Lee, C. H., K. Inoki, and K. L. Guan. Mtor pathway as a target in tissue hypertrophy. Annu Rev Pharmacol Toxicol. 47:443-467, 2007.

21.    Miyazaki, M. and K. A. Esser. Cellular mechanisms regulating protein synthesis and skeletal muscle hypertrophy in animals. J Appl Physiol, 2008.

22.    Mounier, R., L. Lantier, J. Leclerc, A. Sotiropoulos, M. Pende, D. Daegelen, K. Sakamoto, M. Foretz, and B. Viollet. Important role for AMPK{alpha}1 in limiting skeletal muscle cell hypertrophy. FASEB J, 2009.

23.    Nader, G. A. Muscle growth learns new tricks from an old dog. Nat Med. 13:1016-1018, 2007.

24.    Nader, G. A., T. J. McLoughlin, and K. A. Esser. Mtor function in skeletal muscle hypertrophy: Increased ribosomal RNA via cell cycle regulators. Am J Physiol Cell Physiol. 289:C1457-1465, 2005.

25.    Novak, M. L., W. Billich, S. M. Smith, K. B. Sukhija, T. J. McLoughlin, T. A. Hornberger, and T. J. Koh. Cox-2 inhibitor reduces skeletal muscle hypertrophy in mice. Am J Physiol Regul Integr Comp Physiol, 2009.

26.    Proud, C. G. Signalling to translation: How signal transduction pathways control the protein synthetic machinery. Biochem J. 403:217-234, 2007.

27.    Rosner, M., M. Hanneder, N. Siegel, A. Valli, C. Fuchs, and M. Hengstschlager. The mTOR pathway and its role in human genetic diseases. Mutat Res. 659:284-292, 2008.

28.    Stuck, B. J., M. Lenski, M. Bohm, and U. Laufs. Metabolic switch and hypertrophy of cardiomyocytes following treatment with angiotensin ii are prevented by amp-activated protein kinase. J Biol Chem. 283:32562-32569, 2008.

29.    Tee, A. R. and J. Blenis. mTOR, translational control and human disease. Semin Cell Dev Biol. 16:29-37, 2005.

30.    Wilson, G. J., J. M. Wilson, and A. H. Manninen. Effects of beta-hydroxy-beta-methylbutyrate (HMB) on exercise performance and body composition across varying levels of age, sex, and training experience: A review. Nutr Metab (Lond). 5:1, 2008.

31.    Xu, X., X. Hu, Z. Lu, P. Zhang, L. Zhao, J. L. Wessale, R. J. Bache, and Y. Chen. Xanthine oxidase inhibition with febuxostat attenuates systolic overload-induced left ventricular hypertrophy and dysfunction in mice. J Card Fail. 14:746-753, 2008.

32. Zanchi, N. E. and A. H. Lancha, Jr. Mechanical stimuli of skeletal muscle: Implications on mTOR/p70s6k and protein synthesis. Eur J Appl Physiol. 102:253-263, 2008.

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