Maximal Protein Synthesis & Resistance Trained Athletes!
High protein diets are popular among resistance trained athletes due to the various beneficial effects such as increased lean muscle mass, decreased body fat, and improved exercise performance and recovery. The current RDA for protein intake in healthy adults is 0.8g/kg of body weight. Research has shown that heavy resistance training can increase those requirements as high as 1.7 g/kg of body weight.1
The purpose of this paper is to review current research to determine optimal protein intake at a single meal, optimal meal frequency to stimulate maximal protein synthesis, and total dietary intake based on optimal protein intake at a single meal and meal frequency.
Leucine & Protein Synthesis
During exercise muscle protein synthesis (MPS) decreases due to a net increase in protein degradation and stimulation of BCAA oxidation.
The decrease in MPS is due to inhibition of translation initiation factors which are controlled by intracellular insulin signaling and L-Leucine concentrations.
After exercise, dietary protein or BCAAs are required for the recovery of MPS by increasing L-Leucine concentrations. Increased L-Leucine concentrations post exercise releases the inhibition of the initiation factors through activation of the protein kinase mTOR.
Insulin and L-Leucine regulate MPS within skeletal muscle dependent upon physiological state and dietary intake. Studies have shown that Essential Amino Acid (EAA) mixtures infused with 26% (1.7 g) and 41% (2.79 g) L-Leucine stimulated muscle protein fractional synthetic rate (FSR).3
EAA & MPS
In a 2004 study, Paddon-Jones et al. looked at amino acid ingestion improvements on MPS in the young and elderly.4
The purpose of the study was to determine if a more practical mode of amino acid administration (15 g bolus oral ingestion) would produce a similar response in MPS stimulation in young and elderly individuals to a similar extent during a 3 hour amino acid infusion.
Subjects included 7 healthy elderly [3 male, 4 female, 67 ± 2 (SD) yr; 71 ± 5 kg; 169 ± 5 cm] and six healthy young [2 male, 4 female, 34 ± 4 (SD) yr; 63 ± 3 kg; 170 ± 3 cm] volunteers. All subjects were physically active and independent but were not athletically trained.
The study design involved a primed (2 µmol/kg) continuous (0.05 µmol·kg-1?min-1) infusion of L-[ring-2H5] phenylalanine which was initiated and maintained for 8 h. Catheters were inserted in the femoral artery and vein of one leg under local anesthesia.
Arterial and venous blood samples were obtained at 10- to 20-min intervals before and after EAA ingestion for determination of amino acid kinetics and plasma concentrations of glucose and insulin. Values for each collection period were averaged and used to represent blood flow during 1) the post absorptive period, 2) 0-120 min post-EAA drink, and 3) 120-210 min post-EAA drink.
Muscle biopsies (50 mg) were taken from the lateral portion of the vastus lateralis 10-15 cm above the knee. The final muscle biopsy was performed 3.5-4 h post-EAA ingestion.
Composition of the essential amino acid drink:
|Amino Acid||Grams||Total Percentage|
Essential amino acids were dissolved in 250 ml of a nonnutritive, noncaloric flavoring agent.
Blood measurements included femoral artery and vein samples, amino acids, phenylalanine enrichments and concentrations, and plasma insulin concentrations.
Muscle measurements included a biopsy sample of the vastus lateralis examining intracellular phenylalanine concentration and enrichment.
Mixed-Muscle FSR was measured via direct phenylalanine incorporation into muscle to examine amino acid kinetics in human skeletal muscle. Phenylalanine was selected to represent amino acid kinetics because it is neither produced nor metabolized in skeletal muscle.
Results determined Average arterial enrichments over the entire infusion period were 7.7 ± 0.4% (young) vs. 8.8 ± 0.4% (elderly; P = 0.049). Femoral venous enrichments were 6.9 ± 0.4% (young) vs. 7.9 ± 0.4% (elderly; P = 0.09).
In relation to post absorptive values, this post-EAA expansion of the muscle intracellular phenylalanine pool was significantly greater in elderly subjects, with increases of 86.2 ± 15.4 (elderly) vs. 44.8 ± 7.1 (young) nmol/ml (P = 0.025). Post absorptive FSR values were similar in each age group, with values of 0.064 ± 0.007%/h (young) and 0.056 ± 0.004%/h (elderly; P = 0.36).
After EAA ingestion, FSR values increased significantly in both age groups, with values of 0.103 ± 0.011%/h (young) and 0.088 ± 0.011%/h (elderly). This increase was similar in both age groups (P = 0.35).
Although the influence of insulin and the time course of muscle protein anabolism after the bolus ingestion of EAA differ in young and elderly, EAA ingestion is nonetheless effective at acutely stimulating muscle protein synthesis in both age groups.
Optimal Protein Intake At A Single Meal
Paddon-Jones demonstrated that an EAA mixture containing 2.8 g of L-Leucine increased MPS by ~60% (4). Tipton demonstrated that an MAA (Mixed amino acid) and EAA mixture containing 4.4 g and 8.3 g L-Leucine increased MPS by ~70% and ~50%, respectively.5
Based upon the findings of the above studies, a recommended intake of ~3 to 4 g of L-Leucine per meal would elicit an increase in MPS. Common sources of protein for resistance trained athletes include whey protein, eggs, chicken, and beef.
Protein intake (total grams of protein) required to reach ~3 to 4 g of L-Leucine: 26 to 33 grams from whey protein isolate, 36 to 47 grams from eggs, 41 to 54 grams from chicken, and 38 to 51 grams from beef.
In a 2001 study, Bohe et al. looked at the latency and duration of stimulation of human muscle protein synthesis during continuous infusion of amino acids.6
The purpose of the study was to describe the time course of the response of human muscle protein synthesis (MPS) to a square wave increase in availability of amino acids (AAs) in plasma.
Subjects included 6 normal, healthy volunteers (5 men, 1 woman, 33 ± 1 years, 80 ± 5 kg) Subjects were admitted to the Clinical Research Centre of the University of Texas Medical Branch the evening before the study and ate nothing between 24.00 h and coming to the laboratory early in the morning of the study.
The study investigated the responses of quadriceps MPS to a ≈1.7-fold increase in plasma AA concentrations using an intravenous infusion of 162 mg (kg body weight) -1 h-1 of mixed AAs. MPS was estimated from D3-leucine labeling in protein after a primed, constant intravenous infusion of D3-ketoisocaproate, increased appropriately during AA infusion.
Blood samples were taken before the tracer infusion and at 30-60 min for up to 9 hr. Biopsies of the vastus lateralis muscle were taken from both legs under local anesthetic at 30 and 180 min of the basal period (before amino acid infusion) and then at 30-240 min intervals during 6 h of the amino acid infusion.
Muscle was separated into myofibrillar, sarcoplasmic and mitochondrial fractions. MPS, both of mixed muscle and of fractions, was estimated during a basal period (2.5 h) and at 0.5-4 h intervals for 6 h of AA infusion.
Results determined there was no detectable change within the first 30 min of amino acid infusion but thereafter the rate of incorporation rose rapidly and significantly: P < 0.05 (to 0.21 ± 0.07 between 30 and 60 min and 0.24 ± 0.04 % h-1 between 60 and 120 min of amino acid infusion).
Between 120 and 360 min of amino acid infusion the rate of mixed muscle synthesis fell markedly from the peak value, becoming not significantly different from the basal value. The responses in the myofibrillar, sarcoplasmic and mitochondrial fractions were very similar in pattern and relative extent to that observed in the mixed muscle protein.
Leucine And Protein Synthesis Duration
After oral administration of Leucine, both serum and muscle concentrations of the amino acid were elevated within 15 min, reached maximum values between 30 and 45 min, and remained greater than control for at least 120 min.7
MPS Following A Complete Meal
Rats were provided 3 meals containing 20% protein, 50% carbohydrate, and 30% lipids. Plasma Leucine increased at 45 minutes and remained elevated through 180 minutes. MPS peaked at 45 to 90 minutes and returned to baseline by 180 minutes. Plasma Leucine remained elevated although MPS decreased to baseline by 180 minutes.8
Amino Acid Supplementation And Meal Anabolic Response Interference
Ingestion of a 15 g CHO + 15 g EAA produced a greater anabolic effect compared to a nutritionally mixed meal despite a similar EAA content. The CAA supplement did not affect the normal anabolic response to ingestion of a nutritionally mixed meal.9
Optimal Meal Frequency To Stimulate MPS
Bohe and Anthony demonstrated that an EAA infusion or Oral Leucine enhanced rates of protein synthesis between 30 and 60 minutes and returned to baseline by 120 minutes after infusion or administration in rats and humans.6,7 Frequency would be suggested to consume a high amount of Leucine (~3 to 4 g) every 2 hours but, Bohe also demonstrated that amino acid pool levels stayed elevated 4 hours into the EAA infusion.6
Based upon Bohe, Paddon-Jones, Norton, and Anthony's studies, one might suggest consuming a meal containing a sufficient protein source providing ~3 to 4 grams of Leucine every 4 hours and supplementing with a free form Leucine supplement every 2 hours.
Total Dietary Protein Intake Based On Optimal Protein Intake At A Single Meal
General recommendations can be made to consume a meal consisting of a protein source sufficient enough to provide ~3 to 4 grams of Leucine every 4 hours and consume a supplement containing ~3 to 4 grams of Free Form Leucine every 2 hours between meals.
Based upon my findings, more research needs to be performed on resistance trained athletes in order to determine an optimal dietary protein intake per kg of body weight and an optimal amount of Leucine per kg of body weight.
- Lemon, P.W.R. Effects of exercise on dietary protein requirements. Int J Sport Nutr., 8:426-447. December 1998.
- Norton, L.E. & Layman, D.K. Leucine Regulates Translation Initiation of Protein Synthesis in Skeletal Muscle after Exercise. J. Nutr., 136:533S-537S, February 2006.
- Katsanos, C.S., Kobayashi, H., Sheffield-Moore, M., Aarsland, A. & Wolfe, R.R. A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly. Am J Physiol Endocrinol Metab., 291: E381-E387, February 2006.
- Paddon-Jones, D., Sheffield-Moore, M., Zhang, X.J., Volpi, E., Wolf, S.E., Aarsland, A., Ferrando, A.A. & Wolfe, R.R. Amino acid ingestion improves muscle protein synthesis in the young and elderly. Am J Physiol Endocrinol Metab., 286: E321-E328, March 2004.
- Tipton, K.D., Ferrando, A.A., Phillips, S.M., Doyle Jr., D. & Wolfe, R.R. Postexercise net protein synthesis in human muscle from orally administered amino acids. Am J Physiol Endocrinol Metab., 276: E628-E634, April 1999.
- Bohe, J., Low, J.F.A., Wolfe, R.R. & Rennie, M.J. Latency and duration of stimulation of human muscle protein synthesis during continuous infusion of amino acids. J Physiol., 532(Pt 2): 575-579. April 2001.
- Anthony, J.C., Lang, C.H., Crozier, S.J., Anthony, T.G., MacLean, D.A., Kimball, S.R. & Jefferson, L.S. Contribution of insulin to the translational control of protein synthesis in skeletal muscle by leucine. Am J Physiol Endocrinol Metab., 282: E1092-E1101, May 2002.
- Norton L.E., Layman D.K., Bunpo P., Anthony T.G., Brana D.V. & Garlick P.J. The Leucine Content of a Complete Meal Directs Peak Activation but Not Duration of Skeletal Muscle Protein Synthesis and Mammalian Target of Rapamycin Signaling in Rats. J. Nutr., [Epub ahead of print] April 2009.
- Paddon-Jones D., Sheffield-Moore M., Aarsland A., Wolfe R.R. & Ferrando A.A. Exogenous amino acids stimulate human muscle anabolism without interfering with the response to mixed meal ingestion. Am J Physiol Endocrinol Metab., 288: E761-E767, April 2005.