BCAAs for Bodybuilders: Just the Science (Part 3)

Firstly, I’d like to apologise for my lack of activity on my blog. I have been extremely busy over the past few weeks and was lucky enough to have Matt Jones of Nutrition Condition to fill my shoes and post a couple of guest articles. As his content has been well received, you can expect to see future posts from him here.

Today, I aim to tie up the article series looking at BCAA supplementation and its effects on body composition. Before moving onto part 3, I first want to quote the summary from part 2, as it will set the stage for this post:

  • The amount of muscle mass a person has depends on the long-term relationship between muscle protein breakdown and synthesis.

  • A threshold amount of leucine of 2-3 g (~ roughly 0.05g/kg body weight) is thought to exist, with no apparent further stimulation of MPS with higher intakes.

  • This would translate to 25-37.5 g of leucine-rich protein sources.

  • Yes, you can absorb more than 30g of protein in one sitting!

  • Due to the apparent refractory nature of MPS, it would seem that eating meals spaced every 3/4-6 hours apart would optimise MPS within a 24-hour period.

  • However, it appears that there is more to muscle gain than frequently stimulating MPS; the reasons being as follows:

  1. A recommendation for higher daily amounts of protein than is likely to ‘max’ out MPS.
  2. Concept of the anabolic drive and hidden signaling pathways involved in protein turnover and AA oxidation.
  3. Real-world observations of excellent improvements in muscle mass despite theoretically ‘too high/too low’ meal frequencies.
  1. Apparent lack of effects on LBM whilst dieting with reduced meal frequencies (i.e. 1-2 meals per day).
  • It therefore seems that total protein intake is the most important variable, and how this intake is distributed, impacts body composition to a lesser degree.
  • For this reason, I don’t see any reason for meal frequency to be higher than the typical 3-4 meals per day for most people seeking optimal rates of muscle gain.
  • Though it is unknown whether moving to the ‘optimal frequency’ would be of benefit, it seems unlikely in the real world; and if so, it may only benefit the elite physique athlete looking for that 1-2% over their competition. Likewise, eating less than twice per day may compromise rates of muscle gain, however, no solid data exist to be make definitive conclusions.

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Whole proteins vs. free form amino acids: between-meal dosing

Having mentioned the practise of consuming free-form amino acids such as leucine and BCAAs on top of an existing sufficiency of protein in part 1, it is now time to get to the main point of this article and discuss the more theoretical uses of BCAAs. Having nicely set the stage by taking a look at the topic of meal frequency, the information that follows will hopefully make a bit more sense.

It was Dr. Layne Norton who originally popularised the notion of consuming free-form amino acids (e.g. BCAA) between meals. In recent years, several others have latched on to this concept and recommended their own protocols, such as dosing leucine between meals, on top of meals, between exercise sets etc.; I’m still waiting for someone to recommend snorting pure leucine!

If you remember from part 2, I talked about the refractory phenomenon associated with MPS, which has been explained by the ‘protein stat hypothesis’. It is argued that because free-form BCAAs aren't protein-bound within the matrix of the food, they are more quickly absorbed than intact proteins such as whey. It is further argued that because of this protein stat hypothesis - which indicates that an extracellular membrane-bound sensor is influenced by relative changes in amino acid concentrations as opposed to absolute concentrations - whole proteins don’t elicit a rapid rise and subsequent fall in amino acid levels, unlike their free-form counterparts. As such, Norton has advised that a BCAA mix containing 2-3g leucine (with our without additional carbohydrates – as the time course of MPS somewhat reflects plasma insulin levels) should be consumed between meals spaced 4-6 hours apart, with the aim of circumventing this refractory phenomenon associated with protein synthesis in response to the first meal. Theoretically, blunting the decrease in MPS (with a BCAA/BCAA-CHO mixture), which may occur a couple hours following the first meal, would lead to increased muscle hypertrophy over time.

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Is there any data to support this theory?

There are two main pieces of data used to support this hypothesis. The first is the already cited amino acid infusion data by Bohe et al. (2001). Secondly, Norton uses the study by Paddon-Jones et al. (2005) to justify his between-meal dosing strategy. In this trial, the authors compared the effects of supplement containing 30g of carbohydrate and 15g of essential amino acids (EAA) ingested between meals (consisting of 23.4g PRO, 126.6g CHO, 4g FAT) spaced five hours apart, with ingesting nothing between meals. The authors found that the supplement group experienced a greater overall anabolic response (nitrogen balance and fractional muscle protein synthesis) compared with the control group. This is all well and good but the problem with these findings are that the supplement group consumed 45g extra EAA (equivalent to 90g of whey or roughly 20g BCAA) and 90g extra carbohydrate than the control group. Furthermore, since total protein intake in the experimental group was 109g compared to 64 in the control group, what we’re actually comparing is an adequate intake (1.25g/kg) with an intake below the RDA of 0.8g/kg (0.74g/kg). As such, it is extremely unsurprising that a sufficient protein intake plus extra carbs is potentially more anabolic than an insufficient protein intake.

Ultimately, the practise of ingesting BCAAs between meals is largely based on amino acid infusion data - that doesn’t accurately represent oral protein ingestion – and a heavily flawed piece of research by Paddon-Jones et al. (2005). As such, between-meal dosing is an extremely optimistic strategy, based on questionable theoretical evidence. For such a strategy to prove its worth, I’d like to see a between-meal dosing strategy set up around a sufficient protein intake, in trained individuals undergoing a structured resistance programme with body composition endpoints. Will we ever see this data? I doubt it, but I can always dream! But unless it happens, I wouldn’t recommend it to my clients.

Moreover, as discussed in my last article, given the apparent lack of difference in body composition with a decent protein intake spread over 3-4 meals compared with six meals, it is highly unlikely that a slight extension of MPS with a given meal will make any meaningful differences in terms of muscle mass accrual; it almost certainly wouldn’t make a difference in terms of maintenance of muscle mass.

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BCAAs and fat loss?

As you recall from part 2, reducing meal frequency doesn’t seem to affect muscle mass retention as long as sufficient protein is being consumed. This is why intermittent fasting (LeanGains style) works very well for those looking to lose fat and retain muscle. In fact, an interesting review by Varaday (2011) concluded that intermittent calorie restriction (ICR) is just as effective as daily calorie restriction (DCR) at promoting fat and weight loss, though ICR may be more effective for retaining lean mass. However, before the intermittent fasting crowd gets too excited, it is worth remembering that the majority of the ICR studies used bioelectrical impedance (BIA) as a measure of body composition. Anyone familiar with BIA knows that it’s inaccurate at the best of times.

Therefore, it appears that an optimal meal frequency whilst dieting is the one you can best stick to. Because of this, attempting to increase the number of stimulations in MPS, or extend this process, during dieting seems a futile one.

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What about their caloric efficiency?

Given that BCAAs are the only amino acids that stimulate protein synthesis, another rationale for the use of BCAAs whilst dieting is due to their greater caloric economy in comparison to whole protein sources. In other words, if your aim were to get 3g of leucine in a given meal, ingesting whole protein food such as whey would require about 25g (100kcal), whereas 6g (24kcal) of BCAAs would provide the same amount of leucine.

By the same logic, if things were only as simple as getting enough leucine to max out MPS at each meal (~4-6g of most brands of BCAAs), we would theoretically only need 24-36g of BCAAs per day to cover protein requirements. However, it’s no use having leucine to initiate protein synthesis if there is no protein (i.e. other amino acids) to actually carry on this process. What will basically happen is that things will short circuit, meaning that MPS may begin but then stop soon after. A quote from a review by Balage & Dardevet (2010) on the topic sums this up nicely:

“There is some evidence that long-term leucine availability is sufficient to improve muscle mass or performance during exercise training. However, it needs to be associated with other amino acids to be efficient (for example, through leucine-rich proteins).”

This wouldn’t seem to be a problem for the between-meal dosing of BCAAs since there are already other amino acids in circulation. The aim of this strategy isn't to stimulate MPS using BCAAs by themselves; rather, it is to extend MPS.

However, like a complete protein, it also appears that an EAA mixture may optimise MPS. As such, consuming sufficient whole protein the majority of the time and then replacing around-workout whey protein with BCAAs may also have the intended benefit (i.e. optimal MPS stimulation) but with greater caloric efficiency. For example, whey contains roughly 25% BCAA, so assuming someone consumes 30g of whey protein pre and post training, this would amount to 60g of whey (240kcal), whereas isolated BCAAs will account for 15g total (60 kcal), a saving of 180kcal per workout day. If this person trained four times per week, this would be a saving of 720kcal per week, just over 100 kcal per day.

However, I honestly can’t see why someone would want to save calories by reducing protein intake in the first place, never mind go to all that effort just to save themselves 100kcal per day. The same reduction could be achieved by sticking with whey and reducing fat by 11g or carbohydrate by 25g per day, or a combination of the two. Not only will this save you money, you’ll get as much BCAA as well as all the other essential and non-essential amino acids (which may impart added benefit). You’ll also get the

I don't know about you but I'd prefer more to a meal than this whilst dieting.

potentially therapeutic compounds contained in whey such as immunoglobins and lactoferrin, as well potentially anabolic properties of whey independent of its constituent amino acids. Finally, you’ll likely experience greater satiety with whey compared to isolated BCAAs (something that would benefit dieters). In clinical research, BCAAs have been used to stimulate appetite in populations at risk for muscle wasting. The mechanism to explain why this is the case involves BCAAs competing with tryptophan for entry into the brain, thereby reducing the production of a satiating neurotransmitter, serotonin.  As such, it is ironic that the same supplement many take for dieting purposes may actually make dieting a more difficult experience than it needs to be. Conversely, the satiating effects of whey protein are well documented.

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Conclusions & Practical Recommendations

In summary, form part 1 of this article series, I discussed BCAA supplementation on top of a pre-existing sufficiency of protein and came to the conclusion that BCAAs would seem to make little, if any, difference in terms of muscle gain. In part 2, the stage was set for the current article in where I discussed the issue of meal frequency, the conclusion of which is outlined at the beginning of this article.

In this final instalment, we dug deeper into the more theoretical arguments for BCCA supplementation. Specifically,  the claims behind the between-meal dosing of BCAAs and how this might positively impact on muscle hypertrophy were examined, as well as their potential benefits whilst dieting.

The protocol advised by Layne Norton involves using doses of BCAAs likely to maximally stimulate MPS (~4-6g) in between meals spaced 4-6 hours apart. However, this strategy is largely based on amino acid infusion data and a deeply flawed study with highly predictable findings. Therefore, the practise of between-meal BCAA doing is essentially a hypothesis (that extending MPS slightly will lead to greater gains in strength/hypertrophy over time) based on a hypothesis (that such dosing protocols will actually extend MPS  under more realistic dietary conditions) based on a hypothesis (that the protein stat hypothesis holds true), thus extremely optimistic.

In terms of muscle retention whilst dieting, the frequency of protein ingestion doesn’t seem to make a difference as long as sufficient total protein is being consumed, meaning that between-meal dosing is irrelevant under dieting scenarios, at least in terms of optimising MPS on a meal-per-meal basis. As such, the caloric economy of BCAAs is their main attraction for dieters. However, at best, this tactic will save you a few calories, possibly at the expense of hunger, other beneficial properties associated with complete protein sources and money. It is much less hassle, cheaper, and potentially more beneficial to cut calories from either fat or carbohydrate.

Layne Norton may indeed be ahead of the game when it comes to his suggested BCAA protocol taken between meals separated by 4-6 hours. However, when compared to a sufficient protein intake (2.5-3g/kg) spread over the typical 3-4 meals (as suggested in part 2), I can’t see how this tactic could be much more beneficial, if at all. To quote Alan Aragon speaking about Layne Norton about the very topic:

“it’s crucial to realize that [Layne’s BCAA protocol] might be miniscule and not worth the effort or expense for non-competitive populations. In repeated personal communication, he has admitted to me that this tactic is done in attempt to clinch a very small edge to win. As a top-level, drug-free competitor, it’s justifiable to exploit all hypothetical nutritional means within reason in order to conjure the last bit of potential.”

As such, unless you are a physique competitor in search of that extra 1-2% (if it exists), it may be feasible to experiment with such tactics in the effort to gain an advantage. For the rest of us (>99.99 of people) looking to get in better shape, I see little point in supplementing with BCAAs. Instead, I’d urge you to save your money and invest in what delivers. That is, consume a sufficient amount (2.5-3g/kg) of high quality protein that will put you in good stead for making solid gains in the gym, whilst constantly hitting other macronutrient targets across a range of minimally processed foods. From there spread this intake evenly over the typical 3-4 meals, with two of these protein-containing meals placed within windows 90-120 minutes prior to and after weight training. If you have difficulty in reaching such intakes with solid proteins, opt for a decent whey protein concentrate or isolate in order to make up the difference. Speaking of weight training, focus on adding manageable weight in the main compound movements. Not only will this save you money, you will surpass the vast majority of people who use isolated BCAA supplements.

Guest Post: The effect of omega-3 fatty acids on muscle and body composition (by Matt Jones)

Omega 3Whole-body protein turnover is the continuous process within the human body by which protein is created (anabolism) and broken down (catabolism), it is believed to occur at a rate of 300 g/day in an average 70 kg man. Whole-body protein turnover is largely regulated by feeding, a number of specific nutritional factors, along with fasting, hormonal factors and certain disease states. Gains in skeletal muscle occur following prolonged periods of net protein deposition; where muscle protein synthesis exceeds net muscle protein breakdown, thus resulting in a net gain in muscle protein (Wagenmakers, 1999).

Humans, especially athletes often seek net gains in muscle protein; such gains enable increased muscle mass and enhance muscle recovery. As mentioned, a number of nutritional and hormonal factors regulate protein synthesis and thus have a significant impact on body composition; the way you look.

Protein intake is known to have a significant effect on whole-body protein turnover, but what effect does fish oil have, if any?

Recent studies have suggested long-chain omega-3 fatty acids enhance the efficiency and effectiveness of insulin pathway signalling, therefore generating mTOR activity. The mammalian target of rapamycin (mTOR) regulates a number of physiological components, including; interestingly protein synthesis. Signalling through the mTOR is activated by amino acids, insulin, and growth factors, but impaired by nutrient or overall energy deficiency.

So mTOR regulates muscle protein synthesis; and mTOR signalling is activated by insulin, the efficiency of which is enhanced by omega-3 fatty acids.

In a study of fish oil supplementation (4 g/day) providing 1.86 and 1.50 g/day EPA and DHA for 8-weeks in nine healthy middle aged subjects, Smith et al (2011a) revealed the anabolic response to insulin and amino acid infusion was greater in those subjects supplemented fish oils. In addition, muscle protein concentration and muscle cell size were both greater after fish oil supplementation; clearly demonstrating fish oil aids the activation of mTOR. This has previously been demonstrated in older adults (Smith et al. 2011b), and Gingras et al (2007) also demonstrated a positive effect of fish oil supplementation on mTOR activation and subsequent muscle protein synthesis through enhanced insulin signalling.

This apparent activation of the insulin signalling pathway is thought to derive from the anti-inflammatory effects of long-chain omega-3 fatty acids. Insulin resistance is associated with chronic inflammation; both EPA and DHA exert significant anti-inflammatory effects, and actively reduce inflammatory signalling molecule production. In an intricate study on mice, Young Oh et al. (2010) reported omega-3 fatty acid supplementation inhibited inflammation and enhanced insulin sensitivity. A similar mechanism has also been demonstrated in humans, Tsitouras et al. (2008) revealed adults fed a high omega-3 fatty acid diet for 8-weeks increased insulin sensitivity through improved inflammatory status.

So how is that of benefit?

Well supplementation of omega-3 fatty acids increase insulin sensitivity which allows for more effective activation of the insulin signalling pathway ultimately leading to mTOR stimulation and muscle protein synthesis. Increasing insulin sensitivity also has a significant effect on a number of other physiological functions including an increase in glucose and fatty acid uptake by muscle cells (Goodpaster et al. 2003); directing nutrients to muscle cells for oxidation (energy production) rather than fat storage, improving overall body composition and providing more fuel for muscle during exercise.

So omega-3 supplementation can activate the body’s muscle making systems and improve body composition?

Well, yes. A randomized double-blind study on 44 middle aged men and women supplemented either 4 g/day omega-3 fatty acids providing 1,600 mg/day EPA and 800 mg/day DHA, or 4 g/day safflower oil for 6-weeks revealed omega-3 fatty acid supplementation significantly increased fat free mass (body mass minus fat mass), significantly reduced fat mass, and had a tendency to reduce body fat percentage (Noreen et al. 2010).

These studies highlight a mechanism that eludes omega-3 fatty acid supplementation can significantly improve body composition. Stemming from the anti-inflammatory capacity of both EPA and DHA, omega-3 fatty acids can increase insulin sensitivity which has a knock on effect on muscle anabolism in the presence of dietary carbohydrate and protein (typical of a post-workout meal/supplement) and repartitioning of energy to muscle instead of fat which ultimately results in fat loss. These initial findings require further exploration in more rigorous studies with more participants and in a more controlled setting; although the science is clearly there to be disproved.

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References

Gingras, A., White, P., Chouinard, P., Julien, P., Davis, T., Dombrowski, L.,... & Thivierge, M. (2007). Long-chain omega-3 fatty acids regulate bovine whole-body protein metabolism by promoting muscle insulin signalling to the Akt-mTOR-S6K1 pathway and insulin sensitivity. Journal of Physiology, 579, 269.

Goodpaster, B., Katsiaras, A., & Kelley, D. (2003). Enhanced fat oxidation through physical activity is associated with improvements in insulin sensitivity in obesity. Diabetes, 52, 2191 – 2197.

Noreen, E., Sass, M., Crowe, M., Pabon, V., Brandauer, J., & Averill, L. (2010). Effects of supplemental fish oil on resting metabolic rate, body composition, and salivary cortisol in healthy adults. Journal of the International Society of Sports Nutrition, 7, 31.

Smith, G., Atherton, P., Reeds, D., Mohammed, B., Rankin, D., Rennie, M., & Mittendorfer, B. (2011b). Dietary omega-3 fatty acid supplementation increases the rate of muscle protein synthesis on older adults: a randomized controlled trial. American Journal of Clinical Nutrition, 93, 402.

Smith, G., Atherton, P., Reeds, D., Mohammed, B., Rankin, D., Rennie, M., & Mittendorfer, B. (2011a). Omega-3 polyunsaturated fatty acids augment the muscle protein anabolic response to hyperaminoacidemiahyperinsulinemia in health young and middle aged men and women. Clinical Science (London), 121, 267.

Tsitouras, P., Gucciardo, F., Salbe, A., Heward, C., & Harman, S. (2008). High omega-3 fat intakes improves insulin sensitivity and reduces CRP and IL6, but does not affect other endocrine axes in healthy older adults. Hormonal Metabolism Research, 40, 199.

Wagenmakers, A. (1999). Tracers to investigate protein and amino acid metabolism in human subjects. The Proceedings of the Nutrition Society, 58, 987.

Young Oh, D., Talukdar, S., Bae, E., Imamura, T., Morinaga, H., Fan, W., Olefsky, J. (2010). GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin sensitizing effects. Cell, 142, 687.

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UnknownBio: Matt holds a BSc (Honours) degree in Sport & Exercise Science, an MSc in Nutrition Science. Through his own Performance Nutrition business, Nutrition Condition, he delivers frequent Health & Wellbeing Workshops to corporate and personal clients advising on how best to develop a sound, scientifically structured nutrition programme free from fads and marketing bias. Nutrition Condition also delivers Performance Nutrition services to professional athletes.

Matt can be contacted on matt@nutritioncondition.com or at www.nutritioncondition.co.uk

For regular updates follow Matt on Twitter @mattNCUK.

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BCAAs for Bodybuilders: Just the Science, Part 2 (Meal Frequency)

In part one of looking at what part BCAAs play in bodybuilders’ diets, I discussed what BCAAs are, their unique role in protein synthesis, as well as what foods they are contained in and in what percentages. On a gram per gram basis, you would get more than double the amount of BCAAs for your money if you opt for a high quality whey protein isolate than if you were to purchase isolated BCAA; as well as the benefit of all the other essential and non-essential amino acids. As such, I see no use for BCAAs unless they prove to be beneficial despite a sufficient protein intake.

Given the controversy that surrounds their use on top of a sufficient protein intake, I examined the limited human trials on the very matter and came to the conclusion that BCAAs would seem to make little, if any, difference in the presence of sufficient protein. In the absence of sufficient human data looking at body composition endpoints, these conclusions are somewhat speculative. However, my personal observations support my contention that they provide no benefit to those hoping for more muscle and less fat.

As I feel that the available human data doesn’t sufficiently answer the main question behind this article series, I will dig a little deeper and see if more mechanistic and theoretical arguments shed any more light on this matter. I will spend this post looking at the issue of meal frequency and how it pertains to maximising anabolism, as it will lay the foundations for the discussion in the third and final part, in which I will dissect the claims made about between-meal BCAA dosing strategies, and their use whilst dieting.

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Maximising anabolism: the role of leucine in muscle protein synthesis.

 To quote myself from my protein requirements article:

“The amount of muscle tissue in the human body remains fairly stable over time. However these tissues are undergoing a continuous process of breakdown and resynthesis; these processes are referred to as protein turnover. The amount of muscle mass a person has depends on the long-term relationship between muscle protein breakdown and synthesis. For example, if muscle protein synthesis exceeds breakdown, there will be an increase in the amount of that protein. Protein turnover is mediated by several factors including hormones (testosterone, growth hormone, thyroid, insulin, glucagon & cortisol), caloric intake, amino acid/protein availability and training. The largest factors that influence skeletal muscle metabolism are eating and training… This may lead one to assume that the simple act of eating a load of protein will lead to gains in muscle mass. However, this isn’t the case due to a process called diurnal cycling, whereby net protein synthesis following a meal is matched by an increased protein breakdown when food is not being consumed… diurnal cycling tends to keep the body at a stable amount of muscle mass. However, when [resistance] exercise is introduced, it basically “forces” the body to store more protein (assuming sufficient protein and overall caloric intake that is).”

As such, it would appear that maximising daily dietary-induced muscle protein synthesis (MPS) would yield the greatest benefit in terms of maximising the potential for muscle gain. Theoretically, it seems that maximising the anabolic response via eating, revolves around the leucine content of a protein containing meal, and the frequency of which such meal is eaten (i.e. meal frequency; technically protein frequency).

Of the three BCAAs, it is leucine that plays the major role in initiating MPS via the stimulation of the biochemical sensor named the ‘mammalian target of rapamycin’ (mTOR). Relating to the ingestion of protein, a threshold amount of leucine of 2-3 g (~ roughly 0.05g/kg body weight) is thought to exist so that changes in plasma leucine concentrations maximally stimulate MPS. Intakes above this threshold (~8 g leucine) do not appear to have any further stimulatory effects on MPS. From table 1 (in part 1), this would translate to 25-37.5 g of leucine-rich protein sources (e.g. whey, eggs and meat). It is worth highlighting that these hypotheses were developed using rodent models based on acute human data by Paddon-Jones et al. and Tipton et al.. However these notions do have some solid grounding, with more recent human data seeming to support them. This would also seem to be where the ‘broscience’ myth of being only able to absorb 30g (or other random amount) of protein came from. If this were the case, then you wouldn’t be reading this today.

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Frequency of meal/protein ingestion

Now that we know roughly how much protein is needed at each meal in order to optimise MPS, the question remains of how frequently you need to eat to maxmimise MPS, with the hope setting yourself up for maximal muscle gains.

Before we get into that, I want to quash the myth that eating more frequently helps someone to stay lean/lose more body fat by “stoking’ the metabolic fire” or whatever other silly reason is given. It makes no difference how many meals are consumed as long as total kcals (and macros) remain the same. Though the digestion of food requires energy (Thermic effect of food; TEF), TEF is directly proportional to the macronutrient content of a meal. For example, it would take twice the amount of energy to digest a 1000 kcal meal than if you were to eat only half of that meal. Therefore, you can see why splitting food intake into more meals will have no impact whatsoever on metabolic rate. As such, strictly speaking of fat loss, the optimal meal frequency is the one that suits an individual most in terms of hunger, routine, practicality etc.

Now that I’ve got that out of the way, meal frequency gets a little more complicated when talking of muscle gain; at least in theory. It would appear that increasing the frequency of which these maxmimal stimulations of MPS occur (i.e. increased meal frequency) is beneficial for those looking to build muscle. Therefore, logic would dictate that one should eat threshold amounts of protein as frequently as possible if the aim were to maximise MPS within a given 24 hour period. Unfortunately, things aren’t that simple.

Data from rodent and human amino acid infusion studies have demonstrated that MPS lasts for approximately two hours before returning to baseline, despite elevated amino acid levels in the blood. More recently, data from Layne Norton’s lab has shown that consuming a complete meal delays and extends its effects on MPS to roughly three hours, peaking at 45-90 minutes.  It therefore appears that there is a refractory response to protein synthesis (i.e. MPS decreases despite the presence of the initiating stimulus, amino acids) and that once MPS is maximally stimulated following a protein containing meal, further stimulation will not occur by simply ingesting more protein.

An explanation for this resistance to further stimulation of MPS comes from the ‘protein stat hypothesis’, which suggests that an extracellular (outside of the muscle cell) membrane-bound sensor is influenced by relative changes in amino acid concentrations as opposed to absolute concentrations. Specifically, the change from a lower concentration of AAs to a higher one is what seems to drive MPS, meaning that this whole process needs time to “reset” before MPS can be triggered again with the next meal. It therefore seems that spacing meals and allowing blood AA levels to drop, would maximise MPS in subsequent feedings.

Based on this refractory phenomenon, in his aptly titled The Protein Book, Lyle McDonald poses two questions in the attempt to negotiate an ideal meal/protein frequency:

  1. Is it possible to eat too frequently?

  2. How long will a typical meal maintain the body in an anabolic state?

The first question is getting at how long it takes for the processes discussed above to “reset”, before a subsequent meal will max out MPS. The second question refers primarily to digestion rates (i.e. how long after a meal are nutrients (e.g. amino acids) being released into the blood stream?).

Looking at the first question, based on the available data, it would seem that 3-4 hours would theoretically be the minimum time that should pass between meals if you wish to maximise MPS in the second meal. With regards to the second question, there are plenty of data points to determine roughly how long it takes for proteins to be digested. It has been shown that even a modest meal (37g PRO, 75g CHO, 17g FAT) is still releasing nutrients in to the blood stream five hours later. Slowly digesting proteins such as casein (touted as the good old “pre-bed” source to stop you waking up with no muscles) may still be releasing AAs into the blood 7-8 hours, or more, after ingestion!

"My buddy got swole by eating every 3 hours!"

However, meals consumed by most people looking to gain muscle, often contain more protein and total nutrients than in the aforementioned studies. Therefore, taken together, a VERY conservative time limit of six hours passing between meals, during waking hours, would seem reasonable. Incidentally, these recommendations of eating every 3/4-6 hours are similar to those of Layne Norton, who advocates consuming threshold doses of protein containing meals 4-6 hours apart, interspersed with a BCAA/CHO solution with the aim of circumventing this refractory phenomenon associated with MPS (more on this in the next article!). So, eating every 3-6 hours while awake (assuming eight hours of sleep) would yield a meal frequency of roughly 3-6 meals per day.

Since I previously recommended an intake of between 2.5-3 g/kg of bodyweight for bodybuilders/strength athletes, using my body mass as an example (77 kg), this equates to a protein intake of between 192.5-231 g per day. Using the higher end as an example, at a fairly standard frequency of 3-6 meals, daily protein intake would equate to roughly 38.5-77g per meal on average. At the bottom end of this intake, 38.5 g of any high quality protein would adequately cover the upper-end of the 2-3 g leucine threshold for maximising the anabolic response to a given meal (see table 1). In theory, it would seem that splitting the intake over six meals rather than three would lead to better gains in muscle mass due to 6 vs. 3 stimulations in MPS per day. In reality things aren’t that straight forward. If it were, using this example, six stimulations of MPS per day SHOULD lead to double the rates of muscle growth than three.

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This is where things get confusing

For example, 25g of a whey protein isolate (WPI) (see part 1) would provide roughly 3g of leucine (the maximum amount likely to maximally stimulate MPS in anyone). If someone were to ingest 25g of WPI every three hours (six ingestions per day), then MPS should theoretically be maxed out in a day, with an intake of only 150g of protein. If we take a 100kg rugby player, this would provide an intake of 1.5g/kg per day of protein. This is half of the upper end of what I advocate for strength/power athletes, and is also on the low side of the already conservative values cited in research. What’s going on?

Though I’ve used somewhat of an extreme example to illustrate my point, it seems that there is more to building muscle than just hitting these leucine thresholds on a meal per meal basis. In my opinion, total protein intake is the more important variable in terms of muscle mass accrual, compared with how it is split up throughout the day; at least in terms of a typical meal frequency encountered by those who have more to worry about than prepping half a dozen Tupperware boxes per day.

To quote Lyle McDonald from The Protein Book on the matter,

“Optimizing the function of other important pathways [besides MPS] of AA metabolism would very likely raise protein requirements even further.”

Indeed, as alluded to in my article on protein requirements, increased levels of AA oxidation (likely due to intakes in excess of these leucine thresholds), may be involved in the overall “anabolic drive”, meaning there are likely to be “hidden” signaling pathways that contribute to muscle anabolism that we are not yet aware of. As such, increased AA oxidation may actually provide benefit as opposed to its traditional view as being a wasteful process. Essentially, we know that more protein is better (hence my recommendations), but science hasn't figured out the whys yet.

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Searching for the optimal meal frequency

Since most people tend to eat their total daily protein across 3-4 meals, an important question is whether splitting an existing protein intake across an additional 2-3 meals, will provide any benefit in terms of muscular hypertrophy. In the May 2012 issue of his monthly research review, Alan Aragon (I’d abbreviate to AA but then you may mistake him for an amino acid) attempted to answer this question with a combination of limited available data as well as his own observations in the field. In this article, he states:

“Given a diet with an abundance of high-quality protein from varying sources, frequency and proportional distribution of protein doses within day are not likely to make any meaningful impact unless extremes are pushed. It’s rare for anyone with the primary goal of muscle growth to eat twice a day (or less)… It’s reasonable to hypothesize that consuming a solid, mixed, protein-rich meal every 4-6 hours while dosing BCAA between meals could result in a higher rate of muscle growth than getting all of your protein in a single meal each day. However, I see quite a grey area when [Layne] Norton’s protocol is compared with 2-3 meals containing a matched total of high-quality protein (minus the BCAA or leucine threshold dosing between meals).”

Aragon then goes out on a limb and states that:

“even in the case of an IF-type [intermittent fasting] of scenario where only one or two meals per day are consumed, I would still challenge that any meaningful compromise in muscular growth is speculative in the absence of data."

Though seemingly counter-intuitive, there is actually nothing incorrect about Aragon's claims, despite the criticisms of IF from many experts; the scientific data just isn’t there (yet).

Despite some of its questionable conclusions, according to the ISSN position stand on meal frequency, a reduced meal frequency doesn’t appear to compromise lean body mass (LBM) under hypocaloric conditions in the presence of a sufficient protein intake. That is, eating 10 times per day as opposed to once or twice per day doesn’t seem to make a difference with regards to the sparing of LBM on a diet (assuming you're getting sufficient protein that is). If it were true that maximising MPS following the protocols outlined above (i.e. total protein spread evenly across six meals per day) would result in maximal rates of muscle mass accrual, then it raises the question, ‘why doesn’t reducing meal frequency appear to have a negative effect on LBM whilst dieting?’

It is my contention that as long as sufficient amounts of high quality protein are consumed, then spreading protein intake from 3-4 meals to 6 meals is a waste of time and effort for the vast majority of people. This increase in protein frequency may be of benefit to the elite physique athlete, but I’m yet to see how this could result in more than trivial amounts of muscle mass; quantities of which are unlikely to be detected in research (especially with modern-day assessments of body composition). On a related note, I’m not certain that the concern of eating too frequently is a valid one either. The majority of bodybuilding champions eat upwards of six, sometimes 10, meals per day, and they don’t seem to be held back by it. By the same token, there are many proponents of IF who have achieved excellent improvements in body composition despite a meal frequency of perhaps 1-3 protein feeding per day. With respect to my last point, there is at least some data suggesting that going below 2 protein feedings per day might hinder muscle gains.

So, with all things considered, I think that a minimum of three protein feedings per day would be ideal and easily achievable for >99.9% of people looking to optimally gain muscle mass.

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Summary

To briefly summarise:

  • The amount of muscle mass a person has depends on the long-term relationship between muscle protein breakdown and synthesis.
  • A threshold amount of leucine of 2-3 g (~ roughly 0.05g/kg body weight) is thought to exist, with no apparent further stimulation of MPS with higher intakes.
  • This would translate to 25-37.5 g of leucine-rich protein sources.
  • Yes, you can absorb more than 30g of protein in one sitting!
  • Due to the apparent refractory nature of MPS, it would seem that eating meals spaced every 3/4-6 hours apart would optimise MPS within a 24-hour period.
  • However, it appears that there is more to muscle gain than frequently stimulating MPS; the reasons being as follows:
  1. A recommendation for higher daily amounts of protein than is likely to ‘max’ out MPS.

  2. Concept of the anabolic drive and hidden signaling pathways involved in protein turnover and AA oxidation.

  3. Real-world observations of excellent improvements in muscle mass despite theoretically ‘too high/too low’ meal frequencies.

  4. Apparent lack of effects on LBM whilst dieting with reduced meal frequencies (i.e. 1-2 meals per day).

  • It therefore seems that total protein intake is the most important variable, and how this intake is distributed, impacts body composition to a lesser degree.
  • For this reason, I don’t see any reason for meal frequency to be higher than the typical 3-4 meals per day for most people seeking optimal rates of muscle gain.
  • Though it is unknown whether moving to the ‘optimal frequency’ would be of benefit, it seems unlikely in the real world; and if so, it may only benefit the elite physique athlete looking for that 1-2% over their competition. Likewise, eating less than twice per day may compromise rates of muscle gain, however, no solid data exist to be make definitive conclusions.

I will get straight in to things in part three and discuss the issue of dosing BCAAs between meals as well as their use whilst dieting. If you’ve been paying attention in this article, you can already see where things are going…

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