Leucine Versus Whey Protein: Which is More Anabolic?

Everyone these days is talking about leucine! Taking leucine during, after, and between meals seems to be the rage for bodybuilders looking to increase or maintain muscle while dieting. However, compared to whey protein, which one of the two is more cost-effective and also more anabolic?

 A Brief Bio on Leucine!

Leucine has both anabolic effects in skeletal muscle, reflecting both stimulated protein synthesis and inhibited protein breakdown. Studies suggest that some of the anabolic effects of leucine are regulated by mechanisms similar to those regulating the effects of insulin.^{1, 2} Leucine is now known to interact with the insulin-signaling pathway with apparent control of protein synthesis, resulting in maintenance of muscle protein during periods of restricted energy intake.    Leucine appears to also stimulate protein synthesis independent of insulin.³ For example, a dosage of leucine resulted in a stimulation of protein synthesis that was independent of changes of plasma insulin concentrations, whereas a dosage containing carbohydrates (glucose plus sucrose) that raised insulin concentrations over 2.5 times the fasting glucose concentration did not affect protein synthesis.³ Overall, the results demonstrate that leucine can cause increases in protein synthesis rates that are independent of insulin.

 Anti-Catabolic Actions of Leucine

Oral intake of leucine stimulates muscle protein synthesis after exercise or an overnight fast.^5,6 These studies support the role of leucine as a key amino acid for reversing catabolic conditions. In previous studies, there is evidence that in catabolic conditions, muscle tissue becomes resistant to some of the anabolic effects of leucine,⁷ and it is possible that this ‘anabolic resistance’ reflects why cortisol breaks down muscle tissue. More recent studies from laboratories provided direct evidence for a role of cortisol in ‘anabolic resistance’ in skeletal muscle.

For example, Shah, et al.⁸ reported that cortisol opposes the control of protein synthesis by leucine in skeletal muscle. Additionally, Rieu et al.⁹ examined the effects of cortisol in young (4-5 weeks), adult (10-11 months), and old (21-22 months) rats and made the interesting observation that cortisol induced leucine resistance in adult and old rats, but not in young rats.⁴ Considering those findings, the authors speculated that muscle loss during aging may reflect cortisol- induced ‘leucine resistance.’ This may be the reason why you do just about anything in the gym and still grow; however, with aging the gains are not as apparent. Fasting and calorie restriction also results in an increase in leucine appearance rate in the blood, an index of whole-body protein breakdown.

The increase in leucine appearance is consistent with a decline in insulin, because insulin normally suppresses protein breakdown. Additionally, fasting increases the hormone glucagon which has a catabolic effect on leucine.¹⁰ In skeletal muscle, exposure to cortisol is characterized by a reduction in protein synthetic rate coincident with hampered protein synthesis rates; however, oral administration of leucine reversed the catabolic effects within one hour of administration.¹¹ It seems that intense training and calorie restriction both increase cortisol; however, leucine seems to counteract the negative effects of cortisol. 

 Hold on a Second!!

Before you go out and buy a 10-pound box of leucine powder, an interesting study was released this month, written by Dr. Robert R. Wolfe, one of the leading experts in protein synthesis, and published in Applied Physiology, Nutrition, and Metabolism. The study questions the use of leucine supplementation. They investigated the response of net muscle protein balance to ingestion of additional leucine with whey protein in association with resistance exercise in healthy young men. Two groups performed an intense bout of leg resistance exercise, following ingestion of one of two drinks: flavored water; or 16.6 grams of whey protein + 3.4 grams of leucine.

The combination of whey protein and added leucine increased protein synthesis, but the results indicate that the whey protein plus leucine in healthy young volunteers results in an anabolic response in muscle that is not greater than the previously-reported response to whey protein alone.

I had an interesting conversation with Dr. Wolfe and he commented on several points:

1. Leucine supplementation seems to be beneficial for older adults, but leucine supplementation does not seem to have added benefit to younger adults.

2. Leucine taken alone will deplete other branched-chain amino (i.e. isoleucine and valine) acids when taken in high dosages.

3. Younger athletes get more of an anabolic effect by taking either branched-chain amino acids or a larger dose of whey protein.

Leucine is an an essential amino acid, but based on Dr. Wolfe’s new research, taking BCAA or whey protein seems to have more of an anabolic effect than taking leucine alone.

 References:

1. Paddon-Jones D, Sheffield-Moore M, Creson DL, Sanford AP, Wolf SE, Wolfe RR, Ferrando AA. Hypercortisolemia alters muscle protein anabolism following ingestion of essential amino acids. Am J Physiol Endocrinol Metab, 2003 May;284(5):E946-53. Epub 2003 Feb 4.

2. Paddon-Jones D, Wolfe RR, Ferrando AA. Amino acid supplementation for reversing bed rest and steroid myopathies. J Nutr, 2005 Jul;135(7):1809S-1812S.

3. Anthony JC, Lang CH, Crozier SJ, Anthony TG, MacLean DA, Kimball SR, Jefferson LS. Contribution of insulin to the translational control of protein synthesis in skeletal muscle by leucine. Am J Physiol Endocrinol Metab, 2002 May;282(5):E1092-101.

4. Anthony JC, Anthony TG, Kimball SR, et al: Orally administered leucine stimulates protein synthesis in skeletal muscle of postabsorptive rats in association with increased eIF4F formation. J Nutr, 2000; 130:139-145.

5. Biolo G, Tipton KD, Klein S, Wolfe RR. An abundant supply of amino acids enhances the metabolic effect of exercise on muscle protein. Am J Physiol, 1997 Jul;273(1 Pt 1):E122-9.

6. Volpi E, Kobayashi H, Sheffield-Moore M, Mittendorfer B, Wolfe RR. Essential amino acids are primarily responsible for the amino acid stimulation of muscle protein anabolism in healthy elderly adults. Am J Clin Nutr, 2003;78:250-8.

7. Paddon-Jones D, Wolfe RR, Ferrando AA. Amino acid supplementation for reversing bed rest and steroid myopathies. J Nutr, 2005 Jul;135(7):1809S-1812S.

8. Shah OJ, Anthony JC, Kimball SR, et al: Glucocorticoids oppose translational control by leucine in skeletal muscle. Am J Physiol, 2000; 279:E1185-E1190.

9. Rieu I, Sornet C, Grizard J, et al: Glucocorticoid excess induces a prolonged leucine resistance on muscle protein synthesis in old rats. Exp Gerontol, 2004; 39:1315-1321.

10. Charlton MR, Adey DB, Nair KS. Evidence for a catabolic role of glucagon during an amino acid load. J Clin Invest, 1996 Jul 1;98(1):90-9.

11. Shah OJ, Anthony JC, Kimball SR, Jefferson LS. Glucocorticoids oppose translational control by leucine in skeletal muscle. Am J Physiol Endocrinol Metab, 2000 Nov;279(5):E1185-90.