Protein and muscle gain: Are we closer to an optimal dosing strategy? – REVIEW

Daytime pattern of post-exercise protein intake affects whole-body protein turnover in resistance-trained males.

Moore DR, Areta J, Coffey VG, Stellingwerf T, Phillips SM, Burke LM, Cleroux M, Godin JP, Hawley JA.

Nutrition & Metabolism 2012, 16;9(1):91 [Epub ahead of print]



The pattern of protein intake following exercise may impact whole-body protein turnover and net protein retention. We determined the effects of protein feeding strategies on protein metabolism in resistance-trained young men.


Participants were randomly assigned to ingest either 80g of whey protein as 8x10g every 1.5h (PULSE; n=8), 4x20g every 3h (intermediate, INT; n=7), or 2x40g every 6hr (BOLUS; n=8) after an acute bout of bilateral knee extension exercise (4×10 repetitions at 80% maximal strength). Whole-body protein turnover (Q), synthesis (S), breakdown (B), and net balance (NB) were measured throughout 12h of recovery by a bolus ingestion of [15N]glycine with urinary [15N]ammonia enrichment as the collected end-product.


PULSE Q rates were greater than BOLUS (~19%, P<0.05) with a trend towards being greater than INT (~9%, P=0.08). Rates of S were 32% and 19% greater and rates of B were 51% and 57% greater for PULSE as compared to INT and BOLUS, respectively (P<0.05), with no difference between INT and BOLUS. There were no statistical differences in NB between groups (P=0.23); however, magnitude-based inferential statistics revealed likely small (mean effect +/-90%CI; 0.59+/-0.87) and moderate (0.80+/-0.91) increases in NB for PULSE and INT compared to BOLUS and possible small increase (0.42+/-1.00) for INT vs. PULSE.


We conclude that the pattern of ingested protein, and not only the total daily amount, can impact whole-body protein metabolism. Individuals aiming for maximize NB would likely benefit from repeated ingestion of moderate amounts of protein (~20g) at regular intervals (~3h) throughout the day.

Opening Comments

Today’s topic is likely going to gin up strong sentiment from both sides of the meal-frequency aisle when it comes to eating protein and gaining muscle. Indeed, the article above fires a clear shot across the bow at those consuming meals in the lower-frequency-range and thus fewer protein feedings (i.e. potential anabolic muscle-building events) throughout the day. It the literature it has been proposed that multiple (~3-4) protein feedings throughout the day are required in order to optimally gain muscle [1]. For most, this is not an issue given that multiple protein-rich meals are consumed in order to hit daily caloric needs anyway. However, in the past 5-10 years, a new take on dieting has emerged that – at the very least – makes us reconsider how lean mass is gained/preserved. I am of course referring to Intermittent Fasting (IF), a dieting protocol wherein participants fast for a majority of the day (~16-20hrs), complete their workout, and then consume anywhere from 1-3 meals within a short window of time (~4-8hrs on average).

Fewer protein feedings for attenuating muscle loss

Despite its recent surge in popularity, the scientific data behind IF is preliminary at best and includes data that closely characterizes people eating in the lower range of meal frequency (2 meals spread throughout the day) for weight loss as opposed to actual IF protocols (eating within a designated window post-workout). Nevertheless, the data does support at least equal benefits in terms of muscle retention during weight loss/maintenance when consuming fewer, and thus larger protein meals compared to smaller, more frequent ones [2-6]. Moreover, there may even be a slight advantage to doing so under maintenance conditions [4], although any advantages seen in body composition were verified using BIA rather than more accurate measures such as DEXA or MRI. I should also note that most studies were conducted in the absence of a structured training program. All areas for future study!

Optimal protein dosing strategy for muscle gain

On the other side of the coin, research looking at lower meal frequencies (read: fewer protein feedings) compared to higher meal frequencies and subsequent muscle gain have never really been conducted. To my knowledge, the study above is the first one of its kind to look at varying isonitrogenous diets in terms of dosing strategy and whole-body protein balance while not under hypocaloric conditions. Indeed, last month, a 6-week trial did look at varying isonitrogenous diets in terms of dosing strategy on body composition (and therefore muscle mass retention), but did so under hypocaloric conditions and noticed that both groups lost an equal amount of muscle tissue and body fat as measured by DEXA [6]. Unfortunately this does not get us closer to an ‘optimal dosing strategy’ for protein and muscle gain.

So, coming back to today’s study, there are some hefty limitations that do warrant a healthy dose of skepticism and criticism before we go jumping to conclusions about protein dosing and muscle gain. So without further ado, let’s dive right in!

Study strengths

The biggest strength of this study is its innovativeness, as it is – to my knowledge – the first study to look at varying isonitrogenous diets in terms of dosing strategy on whole-body protein retention in humans devoid of a caloric deficit. Other strengths include using resistance-trained males (eliminates “newbie” bias), controlling dietary intake 72h prior to testing (effectively standardizing all the participants), and instructing participants not to engage in any physical activity 72h before testing. I should note that the use of a DEXA to assess body composition was made. However, given the brevity of the study (12h), and no follow-up body composition measures, I see this as neither a strength nor a weakness.

Study limitations

The most glaringly obvious weakness is the acute nature of the study (12h in duration). Any relevant/practical conclusions about smaller, more frequent protein feedings as being optimal for muscle gain are completely speculative and will need longer-term trials in order to verify. Secondly, total protein intakes were 80g over the course of the study period (~0.9g/kg); an intake significantly less than what most trainees consume on a daily basis, and an intake that can be argued to be insufficient for optimal muscle gain [1].

Lastly, the researcher’s use of ammonia end-product to assess whole-body protein balance does not directly measure muscle protein synthesis (MPS); the one factor most people are concerned about when talking about protein ingestion following resistance training. To this end, the authors do cite the limitations of using whole-body tracer methodologies. To quote them;

A limitation of [this methodology] is the inability to delineate tissue-specific changes in protein metabolism.”

Indeed, a much better methodology would have been stable isotope infusion in conjunction with muscle biopsy so that actual MPS could be quantified and analyzed; not just net whole-body retention. Therefore, because they did not use stable isotope infusion, nor did they follow up with biopsy or subsequent body comp measures such as DEXA or MRI, we are left to speculate the true effects of protein dosing strategy on MPS and body composition. Truthfully, all we are left with is data using a poor surrogate for tissue specific muscle gain under insufficient dietary protein intakes.


Given the multitude of limitations contained within the study above, we just can’t say for sure that smaller, more frequent protein feedings are optimal for muscle protein accretion. To be blunt, it wasn’t truly looked at! In reality, all we know is that there was no significant difference between each protocol on whole-body protein balance over a 12h period (although a slight edge was seen in the 20gx4 group). Nevertheless, the overall effect speaks more to the importance of hitting total daily protein intake rather than focusing on dosing strategy when it comes to achieving an anabolic state. Moreover, had optimal protein intakes been achieved (i.e. >0.9g/kg and more in the range of 1.2-1.7g/kg), I believe that any differences – as slight as they were above – would effectively be negated.

So, where does this leave us? What is the take-home message? In a recent article by Alan Aragon on the lower threshold of meal frequency for optimizing muscle gain [7], Alan makes some practical recommendations (that I happen to agree with), based on the evidence to-date. To quote, Alan;

I would error on the safe side and go with three protein-rich meals as an ‘optimal minimum frequency’ for anabolism. It strikes a compromise between conservative practicality [and] exploiting the hypotheticals.”

For now we know that reducing meal frequency, and thus protein feedings, is more than effective when it comes to attenuating muscle loss during weight loss, as long as dietary protein is sufficient. However, we are still in the dark when it comes to optimal meal frequency, and thus protein feedings, when it comes to increasing muscle mass. The study above by no means opens the door to revealing this answer but rather puts it fingers on the handle so that we may start to investigate further. In the end, as long as you are hitting your daily goal of protein intake, I see no need to fret over dosing strategy. On the whole, most people who care about increasing muscle mass are already eating multiple protein-rich meals per day. If this sounds like you, then you are already ahead of the game.


1. Phillips SM, van Loon LJ. Dietary protein for athletes: from requirements to optimum adaptation. J Sports Sci. 2011;29(Suppl 1):S29-38.

2. Arnal MA, Masoni L, Boirie Y, et al. Protein pulse feeding improves protein retention in elderly women. Am J Clin Nutr. 1999;69(6):1202-8.

3. Arnal MA, Masoni L, Boirie Y, et al. Protein feeding pattern does not affect protein retention in young women. J Nutr. 2000;130(7):1700-4.

4. Stote KS, et al. A controlled trial of reduced meal frequency without caloric restriction in healthy, normal-weight, middle-aged adults. Am J Clin Nutr. 2007;85(4):981-8.

5. Soeters MR, et al. Intermittent fasting does not affect whole-body glucose, lipid, or protein metabolism. Am J Clin Nutr. 2009;90(5):1244-51.

6. Adechian S, Balage S, Remond D, et al. Protein feeding patter, casein feeding, or milk-soluble protein feeding did not change the evolution of body composition during a short-term weight loss program. Am J Physiol Endocrinol Metab. 2012;303(8):E973-82.

7. Aragon A. What’s the lower threshold of meal frequency for optimizing muscle gain? AARR 2012 May;2-5.

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1 Response to Protein and muscle gain: Are we closer to an optimal dosing strategy? – REVIEW

  1. S.P. says:

    Fantastic analysis as always, great read.

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