Barbell Medicine - From Bench to Bedside

The word protein is derived from the Greek proteios meaning “primary” or “taking first place.” This is appropriate, as proteins are found everywhere in the body, from skeletal muscle to visceral organs as well as the skin and blood. Wu 2016 

What is Protein?

Structurally, proteins are made up of individual amino acids linked by peptide bonds. A peptide bond is formed when one carboxy group (-COOH) reacts with an amino group (-NH2). Compared to the other dietary macronutrients, e.g. carbohydrates, fats, and alcohol, proteins are unique in that they contain nitrogen (N)- about 160 mg of nitrogen per gram of protein. We can therefore assess whether someone is in a negative or positive “nitrogen balance” by comparing how much nitrogen they’re consuming (protein intake) to how much nitrogen they’re losing in the urine, feces, and skin. If someone is in a positive nitrogen balance, they are said to be retaining dietary protein in one of the various tissue compartments, e.g. muscle, organs, blood, or skin. Conversely, if someone is in a negative nitrogen balance, they are thought to be losing protein from one of those same tissue compartments. In general, muscle mass accounts for about 25-35% of all protein turnover in the body and is likely the main site for nitrogen retention or losses due to its mass. Gropper 2012

Key Points:

  1. The current Recommended Daily Allowance (RDA) for dietary protein intake in adults is 0.8-1.0 grams per kilogram bodyweight per day. This is insufficient for maximizing strength, hypertrophy, endurance performance, or reducing body fat. We recommend a protein intake of 1.6-3.1 grams per kilogram bodyweight per day.
  2. The essential amino acid (EAA) and leucine content of a meal are the primary drivers of muscle protein synthesis. Both animal and plant protein sources contain EAAs and leucine to varying degrees.
  3. Protein source, whether plant or animal-based, does not appear to influence strength, hypertrophy, or other training outcomes provided the correct amount of protein is being consumed.

Proteins are essential in human nutrition, as the body cannot make a number of amino acids under any circumstance.Gropper 2012 These are termed essential amino acids (EAA’s) and include the Branched Chain Amino Acids (BCAAs), which are listed in Table 1. A food that contains all of the EAAs is termed a “complete” protein, e.g. milk, yogurt, cheese, eggs, meat, fish, soy, etc. A food missing one or more EAAs is termed an incomplete protein, e.g. legumes, vegetables, cereals, and grain products. 

Figure 1- Essential Amino Acids (EAA). *Branched Chain Amino Acids (BCAA)

Protein Digestion and Absorption

Dietary protein digestion begins in the stomach via the action of hydrochloric acid (HCl), which typically has a pH of 1-2 (very acidic!) and is secreted by the parietal cells of the stomach in response to protein being ingested. The main function of HCl is not to break apart the proteins per se’, but rather to uncoil them in the stomach. Additionally, HCl activates another enzyme in the stomach, pepsinogen, which gets activated into pepsin. Pepsin is an enzyme that breaks down large proteins into smaller proteins (e.g. peptides) and free amino acids. At this point, the smaller peptides and free amino acids are emptied into the small intestine where both pancreatic and small intestine-produced enzymes further break down the protein into free amino acids and short peptides comprised of two or three amino acids. These amino acids and short peptides are absorbed through the cells of the small intestine and into the bloodstream, principally the portal vein, which heads straight to the liver. Gropper 2012

Muscle Protein Synthesis

While a complete review of amino acid metabolism is beyond the scope of this review, one important pathway to discuss is how dietary protein drives muscle protein synthesis. Based on present evidence, it appears that protein synthesis in a particular muscle is dependent on the post-prandial (after a meal) availability of EAAs (and leucine in particular) in the blood that supplies the muscle. Gorrisen 2018 

In other words, anything that impairs dietary protein digestion, absorption, or blood supply to the skeletal muscle may compromise muscle protein synthesis. Groen 2015 All amino acids are required for protein synthesis, and missing one or more amino acids may compromise the muscle protein synthetic response. For example, consuming individual BCAAs alone cannot enhance muscle protein synthesis when the availability of other EAAs are limited. Leenders 2011 Overall, any protein-containing meal that results in a substantial increase in EAAs (including leucine) in the bloodstream is likely to produce a muscle protein synthesis response.

Protein Quality

Animal-based proteins have been shown to produce a rapid rise in postprandial blood EAA levels, which subsequently produces a large increase in muscle protein synthesis rates. Conversely, the muscle protein synthesis responses to the ingestion of plant-based proteins, e.g. soy and wheat, have been shown to be smaller by comparison which is attributed to decreased EAA and leucine content. Gorrisen 2018 This brings up the importance of protein quality, which we can measure using the Protein Digestibility-Corrected Amino Acid Score (PDCAAS). 

The PDCAAS is plotted from 0.0 (worst) to 1.0 (best) and is calculated based on the ratio of the first EAA to become “limiting” in a test protein compared to the same amino acid in the reference protein, which is usually egg or milk in most tests.FAO/WHO 1991 For example, tryptophan and methionine are the EAA that is present in the lowest quantities in pea protein (100 g of pea protein has about 1 g of each).

As we might expect, these two EAAs are completely metabolized prior to the other EAAs contained in pea protein. Thus, tryptophan and methionine are  the “limiting” amino acids for pea protein. To get the PDCAAS for pea protein, we compare the amount of tryptophan (or methionine) in 1 g of pea protein to the amount present in 1 g of the reference protein (egg or milk). Then we multiply the ratio by the true digestibility of the protein, which is a measure of how well the protein is absorbed and is determined experimentally. The PDCAAS of whey, soy, pea, and wheat gluten protein are 1.0, 0.99, 0.893, and 0.25, respectively. Rutherfurd 2015 In general, animal proteins have been found to be 90-99% digestible, whereas plant proteins are 70-90% digestible. Gropper 2012

With that being said, the total protein, EAA, and leucine content can vary significantly amongst different protein sources. For example, then protein content in whey, pea, and soy protein supplements can vary from 72-84%, 77-81% protein, and 61-91%, respectively. Gorrisen 2018  (Of note, WheyRx is ~90% by weight. 

Additionally, EAA and leucine content also vary markedly between different protein sources. It has been demonstrated that the EAA and leucine content in 25 grams of whey protein can near-maximally stimulate muscle protein synthesis in humans. Gorrisen 2018  While 25 grams of whey contains about  2.7 g of leucine and 10.9 g total of EAAs one would need to consume 31 g corn protein powder or 105 g hemp protein powder to get the same leucine and EAA doses. Gorrisen 2018

Different protein sources can also result in different speeds of postprandial EAA increases in the blood. Boirie et al showed that consumption of whey protein induced a more rapid rise in EAA with a greater total amplitude than casein protein. Boirie 1997 Taken together, these data show that different protein sources have different concentrations of EAAs, digestibility, and absorption characteristics that can influence muscle protein synthesis responses in the acutely, but this may not matter long-term.

For example, a recent study looking at the effects of either whey or pea protein supplementation found no difference between groups in strength, power, CrossFit performance, lean body mass, and body composition after 8-weeks of training. Banaszek 2019 Of note, the average protein consumption was approximately the same at 1.8 and 1.7 grams of protein per kilogram bodyweight for the whey and pea protein groups, respectively. In other words, the protein dose was pretty high and overcame any apparent differences in EAA content or bioavailability. 

In another study, Joy et al. took 24 college-aged males and trained them 3x/wk for 8 weeks while providing them with 48 grams of protein from whey or rice. The authors hypothesized that at this level of protein intake, muscle protein synthesis would be maximized from either protein supplement. Similar to the Banaszek study, both groups saw similar increases in 1RM bench press and leg press, and increases in peak power in a Wingate test. The authors also noted that there were, “No detectable differences were present in psychometric scores of perceived recovery, soreness, or readiness to train.”Joy 2013.

Hartman et al. measured the strength and muscle gain of 56 young men after 12 weeks of training 5 days per week. The men were randomized into one of three groups that consumed milk, soy, or sugar after each training session. There were significant increases in strength for all groups, but no differences between the soy or milk protein groups following 12-weeks of resistance training. With respect to hypertrophy, it did appear that there was a slight advantage in those who consumed milk compared to the soy group, however this finding was barely statistically significant.  Additionally, the soy group was consuming 1.2 g/kg/day of protein compared to the milk group consuming 1.4 g/kg/day, which may have influenced this small finding.Hartman 2007 

Babault et al. took 161 bros and separated them into three groups: placebo, whey, or pea protein. Each group was instructed to take 25 g of protein (or placebo) twice per day in addition to training 3x/week for 12 weeks. Both protein supplementation groups outperformed the placebo group for strength and hypertrophy, however there were no significant differences between pea and whey protein supplements. Babault 2015 

“In addition to an appropriate training, the supplementation with pea protein promoted a greater increase of muscle thickness as compared to Placebo and especially for people starting or returning to a muscular strengthening. Since no difference was obtained between the two protein groups, vegetable pea proteins could be used as an alternative to Whey-based dietary products.” -Babault et al.

Overall, the evidence suggests that the source of protein, e.g. animal or plant, does not effect training outcomes when dosed appropriately. While the EAA and leucine content are thought to be principally responsible for driving the muscle protein synthesis response to a meal, there are a substantial amount contained in both animal and plant-derived proteins. Finally, appropriate resistance training programming is probably the most important variable in determining training outcomes in this context. Morton 2018

Practical Protein Recommendations

The current Recommended Dietary Allowance (RDA) for protein is 0.8-1.0 grams of protein per kilogram bodyweight per day in order to meet the nutrient requirements for healthy adults. IOM 2005  Recently, it has been suggested that the RDA-recommended protein intake may be inadequate for individuals who regularly exercise,  are losing weight, and for aging individuals (more on this here, here, here, and here). Deer 2016 Phillips 2016 Wolfe 2008 Lonnie 2018

With respect to resistance training, a 2018 meta-analysis reviewed 49 studies that included 1,863 subjects to determine what level of protein intake was associated with the greatest strength and muscle mass improvements. In that study, it was found that intakes of 1.6 grams of protein per kilogram bodyweight per day optimized resistance training outcomes, e.g. muscle hypertrophy and 1RM improvements.Morton 2018 A recent review recommends a similar protein intake, e.g. 1.4 g/kg/day, for endurance athletes. Vitale 2019 The 2019 International Association of Athletics Federations Consensus Statement supports these findings and recommends that athletes who are maintaining or gaining weight ingest 1.3 to 1.7 grams of protein per kilogram bodyweight per day.Burke 2019

However, it has been shown that very lean, hard-training individuals may require up to 2.3-3.1 grams of protein per kilogram per day in order to minimize lean body mass losses, e.g. a negative nitrogen balance.Helms 2014  This later finding is corroborated by the The International Society of Sports Nutrition (ISSN) in their 2018 sports nutrition review where they suggest that individuals who are losing weight may benefit from this higher level of protein intake. Kersick 2018

Finally, protein intakes higher than the RDA appear to safe and well-tolerated in individuals without apparent kidney disease.  Antonio 2014  Wu 2016 Poortmans 2000 Brandle 1996  It is less clear that reducing dietary protein intake (~0.6g/kg/day) in those with kidney disease preserves kidney function, reduces the risk of premature death, or improves quality of life compared to higher protein intakes. Hahn 2020 Lee 2019  We’ll tease out the nuances of safety in a future article, but for now, multiple converging lines of data suggest that high dietary protein intakes can be a part of a health-promoting dietary pattern.

The following represents our current recommendations on protein intake for adults. As always, these are subject to change based on future evidence.

  1. For building and maintaining muscle mass, a total daily protein intake of 1.3–3.1 grams of protein per kilogram bodyweight per day is recommended.
  2. Protein intakes  of 1.3-2.2 g/kg/day are likely more than adequate for most individuals, especially among those who are gaining or maintaining weight. 
  3. Higher protein intakes  of 2.3–3.1 g/kg/day may be beneficial for those who are lean and actively losing weight, and/or who are training vigorously 5 times or more per week, and/or who have conditions that produce marked anabolic resistance.
  4. Protein intakes up to 4.4 g/kg/day have been shown to be safe and well-tolerated in humans. However, this level of protein intake has not shown to improve strength, hypertrophy, body composition, or performance outcomes.
  5. Each meal should contain ~0.25–0.6 grams of protein per kilogram bodyweight, or an absolute dose of ~20–45 grams of protein.
  6. Protein-containing meal doses should ideally be evenly distributed every 3–5 hours across the day, although this is less important than the total daily intake.
  7. If these recommendations for total daily intake are being met, the source of protein should be based on the individual’s preferences, e.g. both animal and plant proteins have high levels of EAAs and BCAAs at this level of protein intake. We do not feel strongly about recommending whole food over protein supplements or vice versa, as the overall dietary pattern is most important here, e.g. total energy intake, dietary fiber, fruit and vegetable intake, etc. 
  8. Protein supplements should adhere to FDA regulations for Current Good Manufacturing Processes (CGMP) and be third-party tested by NSF, Informed Consent, USP, or similar. These should be prominent on the label,
  9. Weight-based calculations for protein intake should use total body weight, as most data on protein intake use this approach.

References:

  1. Burke, L. M., Castell, L. M., Casa, D. J., Close, G. L., Costa, R. J. S., Desbrow, B.,..Stellingwerff, T. (2019). International Association of Athletics Federations Consensus Statement 2019: Nutrition for Athletics. International Journal of Sport Nutrition and Exercise Metabolism, 1–12. March, 2019.
  2. Morton RW, Murphy KT, McKellar SR, et al. A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults. Br J Sports Med. 2018;52(6):376–384. doi:10.1136/bjsports-2017-097608
  3. Helms, E. R., Zinn, C., Rowlands, D. S., & Brown, S. R. A Systematic Review of Dietary Protein during Caloric Restriction in Resistance Trained Lean Athletes: A Case for Higher Intakes. International Journal of Sport Nutrition and Exercise Metabolism, 24(2), 127–138. April, 2014.
  4. Gorissen SHM, Crombag JJR, Senden JMG, et al. Protein content and amino acid composition of commercially available plant-based protein isolates. Amino Acids. 2018;50(12):1685–1695. doi:10.1007/s00726-018-2640-5
  5. Rutherfurd, S. M., Fanning, A. C., Miller, B. J., & Moughan, P. J. Protein Digestibility-Corrected Amino Acid Scores and Digestible Indispensable Amino Acid Scores Differentially Describe Protein Quality in Growing Male Rats. The Journal of Nutrition, 145(2), 372–379.Feb, 2015. 
  6. Hartman J.W., Tang J.E., Wilkinson S.B., Tarnopolsky M.A., Lawrence R.L., Fullerton A.V., Phillips S.M. Consumption of fat-free fluid milk after resistance exercise promotes greater lean mass accretion than does consumption of soy or carbohydrate in young, novice, male weightlifters. Am. J. Clin.Nutr. 2007;86:373–381
  7. Babault N., Païzis C., Deley G., Guérin-Deremaux L., Saniez M.-H., Lefranc-Millot C., Allaert F.A. Pea proteins oral supplementation promotes muscle thickness gains during resistance training: A double-blind, randomized, placebo-controlled clinical trial vs. Whey protein. J. Int. Soc. Sports Nutr. 2015;12:3. 
  8. Joy J.M., Lowery R.P., Wilson J.M., Purpura M., De Souza E.O., Wilson S.M., Kalman D.S., Dudeck J.E., Jäger R. The effects of 8 weeks of whey or rice protein supplementation on body composition and exercise performance. Nutr. J. 2013;12:86. 
  9. FAO/WHO. Protein quality evaluation: Report of the Joint FAO/WHO Expert Consultation, FAO food and nutrition paper no. 51. Rome (Italy): FAO; 1991.
  10. Wu, G. (2016). Dietary protein intake and human health. Food & Function, 7(3), 1251–1265.doi:10.1039/c5fo01530h 
  11. Leenders, M., Verdijk, L. B., van der Hoeven, L., van Kranenburg, J., Hartgens, F., Wodzig, W. K. W. H., … van Loon, L. J. C. (2011). Prolonged Leucine Supplementation Does Not Augment Muscle Mass or Affect Glycemic Control in Elderly Type 2 Diabetic Men. The Journal of Nutrition, 141(6), 1070–1076.doi:10.3945/jn.111.138495 
  12. Negro M, Segreto V, Barbero M, et al. Essential Amino Acids (EAA) Mixture Supplementation: Effects of an Acute Administration Protocol on Myoelectric Manifestations of Fatigue in the Biceps Brachii After Resistance Exercise. Front Physiol. 2018;9:1140. Published 2018 Aug 17. doi:10.3389/fphys.2018.01140
  13. Kerksick, C. M., Wilborn, C. D., Roberts, M. D., Smith-Ryan, A., Kleiner, S. M., Jäger, R., … Kreider, R. B. (2018). ISSN exercise & sports nutrition review update: research & recommendations. Journal of the International Society of Sports Nutrition, 15(1). 
  14. Achamrah N, Colange G, Delay J, et al. Comparison of body composition assessment by DXA and BIA according to the body mass index: A retrospective study on 3655 measures. PLoS One. 2018;13(7):e0200465. Published 2018 Jul 12. doi:10.1371/journal.pone.0200465
  15. Boirie Y, Dangin M, Gachon P, Vasson MP, Maubois JL, Beaufrere B. Slow and fast dietary proteins differently modulate postprandial protein accretion. Proc Natl Acad SciUSA 1997;94:14930 –5.
  16. Gropper, Sareen S.; Smith, Jack L.. Advanced Nutrition and Human Metabolism. 2012. Pages 183-238. Cengage Textbook. Kindle Edition.
  17. Groen BB, Horstman AM, Hamer HM, de Haan M, van Kranenburg J, Bierau J, Poeze M, Wodzig WK, Rasmussen BB, van Loon LJ. Post-prandial protein handling: you are what you just ate. PLoS One. 2015;10(11):e0141582. doi: 10.1371/journal.pone.0141582.
  18. Institute of Medicine. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. 2005
  19. Antonio, Jose & Peacock, Corey & Ellerbroek, Anya & Fromhoff, Brandon & Silver, Tobin. (2014). The effects of consuming a high protein diet (4.4 g/kg/d) on body composition in resistance-trained individuals. Journal of the International Society of Sports Nutrition. 11. 19. 10.1186/1550-2783-11-19.
  20. Deer RR, Volpi E. Protein intake and muscle function in older adults. Curr Opin Clin Nutr Metab Care. 2015;18(3):248-253. doi:10.1097/MCO.0000000000000162
  21. Phillips SM, Chevalier S, Leidy HJ. Protein “requirements” beyond the RDA: implications for optimizing health. Appl Physiol Nutr Metab. 2016 May;41(5):565-72. doi: 10.1139/apnm-2015-0550. Epub 2016 Feb 9. PMID: 26960445.
  22. Wolfe RR, Miller SL, Miller KB. Optimal protein intake in the elderly. Clin Nutr. 2008 Oct;27(5):675-84. doi: 10.1016/j.clnu.2008.06.008. Epub 2008 Sep 25. PMID: 18819733.
  23. Lonnie M, Hooker E, Brunstrom JM, et al. Protein for Life: Review of Optimal Protein Intake, Sustainable Dietary Sources and the Effect on Appetite in Ageing Adults. Nutrients. 2018;10(3):360. Published 2018 Mar 16. doi:10.3390/nu10030360
  24. Vitale K, Getzin A. Nutrition and Supplement Update for the Endurance Athlete: Review and Recommendations. Nutrients. 2019;11(6):1289. Published 2019 Jun 7. doi:10.3390/nu11061289
  25. Brändle E, Sieberth HG, Hautmann RE. Effect of chronic dietary protein intake on the renal function in healthy subjects. Eur J Clin Nutr. 1996 Nov;50(11):734-40. PMID: 8933120.
  26. Poortmans JR, Dellalieux O. Do regular high protein diets have potential health risks on kidney function in athletes? Int J Sport Nutr Exerc Metab. 2000 Mar;10(1):28-38. doi: 10.1123/ijsnem.10.1.28. PMID: 10722779.
  27. Hahn D, Hodson EM, Fouque D. Low protein diets for non-diabetic adults with chronic kidney disease. Cochrane Database Syst Rev. 2020 Oct 29;10(10):CD001892. doi: 10.1002/14651858.CD001892.pub5. PMID: 33118160; PMCID: PMC8095031.
  28. Lee SW, Kim YS, Kim YH, et al. Dietary Protein Intake, Protein Energy Wasting, and the Progression of Chronic Kidney Disease: Analysis from the KNOW-CKD Study. Nutrients. 2019;11(1):121. Published 2019 Jan 8. doi:10.3390/nu11010121

About Jordan Feigenbaum

Jordan Feigenbaum, owner of Barbell Medicine, has an academic background including a Bachelor of Science in Biology, Master of Science in Anatomy and Physiology, and Doctor of Medicine. Jordan also holds accreditations from many professional training organizations including the American College of Sports Medicine, National Strength and Conditioning Association, USA Weightlifting, CrossFit, and is a former Starting Strength coach and staff member. He’s been coaching folks from all over the world  for over a decade through Barbell Medicine. As a competitive powerlifter, Jordan has competition best lifts of a 640lb squat, 430lb bench press, 275lb overhead press, and 725lb deadlift as a 198lb raw lifter.

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