Lyle McDonald Interview: Protein and Muscle Growth

Lyle McDonald is a physiologist and author who has spent over a decade obsessively finding ways to apply cutting-edge scientific research to sports nutrition, fat loss and muscle growth.

Q. There still seems to be a lot of debate about whether or not exercise increases the amount of protein you should eat. What do you think?

A. Debate over whether or not protein requirements are increased with exercise have been going on for nearly 40 years and I don’t think they are going to stop any time soon. As with so many topics in the area of sports nutrition, both groups advocating high protein and low protein can bring good data to the table. Of course, athletes tend to ignore the scientific debates since they invariably “know” what works.

On the one hand, studies using nitrogen balance research clearly indicate an increased protein requirement with training, at least in the initial stages. Critics will rightfully point out that the nitrogen balance method is fraught with errors and problems. For example, some of the nitrogen balance research, taken literally, would suggest gains in muscle mass that have simply never been seen in any study or in the real world.

As well, there is research suggesting that training improves protein utilization, some early work suggested that regular (aerobic) exercise decreased protein requirements, other research has shown that while there is an initial increase in protein requirements with training, this goes away fairly rapidly as the body adjusts.

An additional problem is that researchers are rarely measuring the endpoints important to athletes or coaches. Athletes aren’t interested in nitrogen balance, they are interested in performance (i.e. improvements in muscle mass, strength, power, endurance, speed, etc.) and these are rarely measured in studies.

As well, most research looks simply at skeletal muscle metabolism and there are a host of other pathways (e.g. immune system function, connective tissue synthesis and others) that require protein/amino acids that may be upregulated with athletic training. All would be expected to potentially increase protein requirements but this area has been woefully unstudied.

With newer methods of measuring protein metabolism becoming rapidly available, hopefully some of these questions can be answered with a little less controversy. I’d note tangentially that, a recent paper I just read, using a different method of estimating maintenance protein requirements for non-athletes came to the conclusion that currently recommended protein levels are too low.

What implication this has for athletic nutrition I’m not sure but newer methods may be able to answer this question a little more concretely in the future.

At this point, in lieu of better data, I tend towards the higher end of protein recommendations. I think it’s better to err on the side of slightly too much (where, at worst, protein becomes an expensive source of energy) than risking too little (where, at worst, performance, recovery, immunity, etc. is potentially compromised).

Which doesn’t mean that I think people should eat as much protein as possible. One potential issue, and this is a bigger concern for lighter athletes is that protein can make up such a large proportion of the daily calories that insufficient carbohydrate (to sustain training intensity) or fat (important for a number of processes including immune system function are shorted.

Q. A lot of mainstream nutrition experts like to criticize high-protein diets on the basis that excess protein is bad for your kidneys (amongst other things). At what level of intake does protein become excessive?

A. Well, for the most part, the whole issue with protein and kidney function has been overstated. The basic idea seems to have been a reversal of research showing that individuals with preexisting kidney damage had to reduce protein intake; this got turned around to suggest that high protein intakes caused kidney damage.

Other, observational data had found that older individuals often showed decreased kidney function (via something called glomerular filtration rate or GFR) and this was supposedly linked to high protein intake when they were younger. But it turned out to be simply a reflection of their current protein intake, that is GFR goes up and down (as a normal adaptation) with increasing or decreasing protein intake.

Older individuals, eating less protein, show a lower GFR. But this is thought to be a normal adaptation to changing protein intake, not a pathological observation.

So where does protein intake become excessive?

As mentioned above, at the point that it makes up so much of the diet that it prevents carbohydrate or fat intake from being sufficient, I’d consider that excessive. Now, it’s not unheard of for athletes (usually physique competitors such as bodybuilders or fitness/figure girls) to consume almost exclusively protein for short periods during their contest preparation. Weight class athletes trying to make weight may do the same. But these are typically short-term approaches. In terms of long-term nutritional intake, that would generally be a mistake.

Another potential issue is that high protein intakes do have to be metabolized in the liver, which produces urea and ammonia (the latter is implicated in fatigue during exercise). The point at high this becomes excessive might be considered the ‘cutoff’ point. But it’s a little tough to identify that point for everyone (and there are longer term adaptations in the liver to increased protein intake whereby metabolism is improved).

In The Protein Book, I recommend a maximum of 3.0 grams per kilogram of bodyweight (roughly 1.4 grams per pound) of protein as a habitual intake for strength athletes, this can go up a bit during dieting of course. For endurance athletes, there’s little reason to go over 2.0 grams per kilogram of bodyweight (a little higher when dieting) which is about 0.9 grams per pound.

Q. There are lots of different ways to estimate the amount of protein you should eat, from using a percentage of total calorie intake through to basing it on lean body mass. In your view, what’s the best way to calculate your protein requirements?

A. Well, fundamentally I disagree with using percentages to set up a diet. The problem is that may or may not have any actual relevance to nutritional requirements. Consider for example a protein intake of 150 grams per day (600 calories) on a total caloric intake of 600 calories, 2000 calories, or 5000 calories. In this case, protein makes up 100%, 30%, or 12% of the total although it’s the identical protein intake. Basically, percentage recommendations are only valid within an assumed caloric intake and I find those assumptions to be incorrect in many cases.

Rather, I prefer to set nutrient intake recommendations relative to some aspect of body weight. Fundamentally, given that fat cells don’t use much protein (they actually do synthesize a lot of different chemicals and hormones), it probably makes the most sense to relate protein recommendations to lean body mass. However, this adds an extra problem of getting an accurate measurement of lean body mass (body fat estimation being problematic for a variety of reasons).

Which makes total body weight a potentially better (easier in any case) measurement to use. I’d also note that, so far as I can tell, most of the research in this area uses total body weight as how protein recommendations are set.

Now, for lean athletes, the difference between total body mass and lean body mass (LBM) isn’t very different. That is, an athlete at 10% body fat has a LBM that is 90% of his total mass.

But consider an average female who may have 22% body fat, or a very overfat athlete at 30% body fat. As body fat goes up, the relationship between lean body mass and total body mass start to become very skewed.

So, basically, there’s a problem with all of the methods. To make things a bit easier (because of the problems getting an accurate measurement of body fat percentage), I generally recommend using total body weight to set protein intake but only with the understanding that this will tend to overestimate true protein requirements as body fat percentage goes up.

Females, who often have problems fitting in sufficient carbs and fat in the first place due to lowered caloric requirements should scale protein intake back a bit since, at any given body weight, they will typically carry more body fat. There is also some research indicating that women need less protein than men although most of the research is on endurance training.

Fatter male athletes should do the same, scaling back their total protein intake to take into account their higher body fat percentage.

Q. So how do women’s protein requirements differ to those of men?

A. Well, at least one factor that I mentioned previously has to do with body fat percentage. At any given body weight, a woman will typically have a higher body fat percentage than a man. Which means that they are carrying less lean body mass. Assuming that true protein requirements scale more with lean body mass than with total body weight, that would tend to suggest lowered protein requirements.

Additionally, a somewhat under-appreciated fact is that women’s fuel/nutrient use changes during their menstrual cycle. During certain periods they tend to use more fat for fuel, during others they tend to use more carbohydrate (in my experience, they also tend to be more prone to low blood sugar, especially on low/lowered carbohydrate diets during this period).

Studies examining fuel use during endurance training have found that, during the parts of their cycle that they use more fat for fuel, women also use less protein (measured by leucine oxidation) than men. You get the same effect in men if you inject them with estrogen, they burn more fat for fuel and oxidize less leucine. So, at least with regards to endurance training, it seems that women don’t need as much protein as men, at least during certain parts of their menstrual cycle.

A bigger question, probably more relevant to your readers is whether this also holds for resistance training. Unfortunately, there is little to no direct data.

One study found that changes in the menstrual cycle had no impact on connective tissue synthesis following resistance training. This might suggest that female hormones don’t have the same impact on skeletal muscle protein synthesis during resistance training; again it hasn’t been measured directly to my knowledge.

However, from a more basic physiological standpoint, the simple fact is that women won’t put on muscle as quickly as a man. Muscle magazine claims notwithstanding, an average male trainee would be doing stunningly to put on 20-25 pounds of lean body mass in a year (about 0.5 pounds per week). And that’s only in the first year of training.

Given that she probably has 1/10th the testosterone level, a woman might only put on half of that, maybe 10-12 pounds in a year. That would tend to suggest that protein requirements aren’t going to be as high. The body simply can’t synthesize protein fast enough in a non-steroid using female.

But again, there’s not really any direct data on this. At least one paper (written by Jeff Volek and Cassandra Forsythe) actually argues that, due to the differences in fuel utilization by women, they should consume more protein and fat and less carbohydrate. Maybe. Or it might depend on the phase of the menstrual cycle.

At this point, I think women can probably reduce their protein intake a bit from the recommendations commonly given for men, and this is reflected in the guidelines in my Protein Book. Of course, I still basically believe that it’s better to err on the side of a little too much than too little.

However, women have another potential consideration to, err, consider. Given their generally lower body weight and tendency to restrict calories excessively, a female who fills up her daily calories with too much protein often ends up with too few calories left for carbohydrates or fat. This tends to impair the ability to train well.

Reducing daily protein intake slightly allows more “room” for the other nutrients, allowing more effective training sessions which, in the long-run, will have more benefit anyhow.

Q. Some people say you should never go for more than two hours without eating protein or else you run the risk of losing muscle. What do you think is the maximum length of time (excluding sleep) that you can leave between eating a protein-rich meal or supplement?

A. A lot of it will depend on what type of intake you’re talking about. The now infamous whey/casein study showed that casein could still be releasing amino acids into the bloodstream 8 hours after ingestion. Whey was closer to 3 hours; of course if you combine whey with fat, carbs or fiber, it slows down too. A small intake of something like an essential amino acid supplement will peak and go back down rapidly while whole food meals will generally maintain an anabolic state for 5-6 hours or so.

So I’d say 5 hours is about the maximum to go between meals.

Interestingly, there are various lines of emerging research (including one very recent direct study published in abstract form only) suggesting that eating too frequently could be detrimental from the standpoint of muscle mass gains.

Q. The idea that eating too frequently impairs gains in muscle mass is certainly one that flies in the face of conventional wisdom. What’s the theory behind it?

A. Some interesting research has come out of some recent amino acid infusion studies and I want to note upfront that it is extremely speculative at this point how this applies to normal meal feeding.

As a quick note of introduction, recent studies have essentially demonstrated beyond a shadow of a doubt that it is amino acids themselves that stimulate protein synthesis (with the BCAA and leucine specifically playing the primary role). Which makes a certain sort of sense when you think about it.

In any case, what the studies did was this: infused amino acids at a high level and measured protein synthesis. What they found was bizarre: initially protein synthesis went up considerably. Then, after two hours, protein synthesis started to go down. What’s interesting is that protein synthesis went down despite the maintenance of high blood amino acid levels.

As well, the researchers found increased levels of urea production (a waste product of amino acid metabolism) suggesting that the continuing influx of amino acids was simply being burnt off.

The researchers suggested that the skeletal muscle had become “desensitized” to the effect of amino acids in terms of stimulating protein synthesis. Which also suggested that allowing blood amino acids to decrease again would be necessary to “resensitize” it to the effect of amino acids.

Interestingly, this is quite similar to the pattern observed in the now famous Boirie casein/whey study. While whey protein spiked amino acid levels and promoted whole-body protein synthesis, it also increased amino acid oxidation. Perhaps this was due to the muscle being “full” and having become desensitized to the amino acid levels, causing the rest to be oxidized off.

I’d also note that Layne Norton (a natural pro-bodybuilder who is doing his PhD work in protein metabolism) has apparently shown the same with protein feeding in rats. To my knowledge, this hasn’t yet been shown for protein feeding in humans.

However, bodybuilders typically try to eat protein frequently with the goal of maintaining nearly constant blood amino acid levels and the above research suggests that this may not be the best idea.

Rather, spiking amino acid levels (to promote protein synthesis) and then allowing them to decrease again (by not eating more protein too frequently) may turn out to be a better pattern for mass gains. Another possibility is that by alternating very fast acting proteins (which generate a quick spike followed by a drop) between whole-food meals may turn out to be superior.

I’d note that, from the standpoint of preventing muscle loss on a diet, it would appear that this is the best eating pattern, maintaining low levels of amino acids throughout the day reliably inhibits protein breakdown. But it may not be ideal for stimulating protein synthesis.

In this regards, a recent paper (not yet published in full unfortunately, I’ve only seen an expanded abstract) out of Norway compared three versus six meals in bodybuilders put on a slight caloric surplus and a training program. Contrary to what you’d expect, the three meal per day group actually gained more weight, more muscle mass, but also more body fat.

But without seeing the full paper, it’s impossible to know exactly what’s going on. Perhaps the three meal per group simply ate more; although the researchers attempted to account for this with statistical methods. Perhaps by allowing blood amino acid levels to drop between meals, the three meal per day group was able to better stimulate protein synthesis.

As I noted above, this is all a bit speculative until more direct research shows up.

Q. Some say that you should never eat more than 25 grams of protein in a single meal. Are they right? How much protein should you eat in each meal?

A. If you had asked me this question a year ago, I’d have given you a short and simple answer which is that it’s utter nonsense (although the number more typically thrown around is 30 grams).

However, some recent research suggests that there may be some truth to it. One odd little study examined the intake of essential amino acids (EAAs) in both young and older individuals (older individuals typically show a decreased anabolic response to protein intake which is what they were studying).

Various amounts were fed and skeletal muscle protein synthesis was measured. The young individuals showed the maximum response at 10 grams of EAA, with no further increase at 20 grams of EAA.

Now, most whole food dietary proteins are 40-50% EAA so this amounts to 20-25 grams of whole protein to maximally stimulate skeletal muscle protein synthesis. I’d note that some amino acid infusion research suggests a similar threshold effect, once amino acid concentrations go above a certain level, there is no further impact on protein synthesis.

But now we have a problem, say an athlete is consuming 6 meals per day (ignoring my response to the question about meal frequency above). That yields a maximum protein intake of 120-150 grams of protein per day. For a 70-kilogram (154-pound) athlete, that’s 1.7-2.0 grams per kilogram of body weight (roughly 0.8-0.9 grams per pound) which is actually pretty consistent with older recommendations.

But it doesn’t explain why, empirically, many athletes feel that gains are better with higher protein intakes, say 3.3 grams per kilogram of body weight (1.5 grams per pound).

It may be that, when you add training and increase overall protein turnover (synthesis and breakdown), the above values don’t hold and will have to be increased. It’s possible that only looking at skeletal muscle protein synthesis is missing some parts of the overall picture, there are other pathways important to athletes that use protein which will increase requirements. Given how EAA digest, compared to whole proteins for example, it’s also eminently possible that the digestion pattern of whole proteins makes the above research inapplicable in the first place.

Finally, it’s possible that all bodybuilders are deluding themselves about their need for higher protein intakes although it’s a little hard to dismiss 4 decades of empirical observations out of hand like that. A lot of what bodybuilders have found to work has been subsequently validated by research, this may be another of those areas.

So, to go back to your question: yes and no. There is emerging research suggesting a limitation in terms of how much protein is needed or required to maximally stimulate protein synthesis. But the numbers that come out of those measurements seem to fail the reality check in terms of what athletes have often found to work.

Q. We hear a lot about the importance of taking in protein as soon as possible after exercise. How true is this?

A. Another yes and no kind of answer. The original idea of a window of opportunity for nutrient intake actually came out of endurance research, scientists become fascinated about how to improve glycogen synthesis following training. A zillion studies were done and one factor that was important was timing, under certain conditions, how quickly you got nutrients into the system was critical in terms of overall glycogen synthesis rates.

This became a little more relevant to strength athletes when some research showed that protein plus carbs worked better than carbs alone for glycogen synthesis. More research followed, some of it found a benefit of protein, others didn’t.

Finally, researchers started looking at resistance training. Various studies examined different combinations of nutrients, often using isolated essential amino acids (EAA) with or without carbs (usually sucrose). Many found that it was absolutely crucial that nutrients be consumed following training to switch the body from a net catabolic state (breaking down more protein than it was synthesizing) to a net anabolic state (the opposite).

But these studies all suffered one huge methodological problem: they were done in the fasted state. Basically, take subjects, have them not eat overnight, bring them to the lab, train them, feed or don’t feed them and see what happens. And under those conditions, absolutely consuming post-workout nutrients is critical.

I’d note that one study, tested under the same conditions, actually found that pre-workout aminos worked better than post-workout. This makes some logical sense mind you, consuming amino before a morning fasted workout will have them in your bloodstream during and after training faster than consuming them afterwards.

But the question then became this: If you’re not training first thing in the morning fasted and have eaten a solid meal 2-3 hours before training, does this still hold?

Consider my response to a previous question where I pointed out that a whole-food meal will continue digesting for up to 5-6 hours, maintaining an anabolic state. If you’ve eaten a solid meal 2-3 hours before workout, you have plenty of nutrients floating around in the bloodstream. Will post-workout nutrition be as crucial?

A recent area of research has been that of during a workout nutrition, combinations of carbohydrate and amino acids or carbohydrate and protein during training maintains insulin at a higher level, cortisol at a lower level, and decreases protein breakdown. If you do that, do you need post-workout nutrients? If you consume a small carbohydrate-protein drink immediately before training, do you need the post-workout nutrients?

At this point there are more questions than answers although I deal with the topic of around workout nutrition in The Protein Book for about 35 pages.

One very interesting study did actually set out to shed some light on this. Cribb down in Australia recruited trained bodybuilders, put them on the same training program and had them consume a whey/dextrose/creatine drink either immediately before and after training or at two times of the day that weren’t around training.

So it looked at the issue very practically in that both groups consumed the extra nutrients but only one took it directly around training while the other didn’t. The pre/post group showed better lean mass gains and even a slight fat loss.

So I have to conclude that, even if the athlete has been fed, there is still some benefit to putting some amount of the day’s nutrients around training. There are other good physiological reasons (e.g. hormonal, blood flow, etc.) that support this idea as well.

Q. How are someone’s protein needs affected by dieting? Does someone who wants to lose fat need extra protein? Or is it just for people wanting more muscle?

A. It’s been known for at least 40 years that one of the primary factors affecting how well or poorly the body uses dietary protein is calorie intake. As caloric intake goes down, protein retention by the body goes down as well; as caloric intake goes up, protein retention goes up.

Tangentially, while it was usually thought that dietary carbohydrate had a greater impact than dietary fat, recent research suggests that dietary fat intake is as good and could be better from the standpoint of nitrogen retention.

In any case, what this means is that protein requirements go up while dieting. Of course, bodybuilders knew this for years but research has clearly shown that increasing protein intake on a diet has a number of benefits including increased fullness, maintenance of thermogenesis, better blood glucose control and, of course, better maintenance of lean body mass (which also means greater fat loss).

Quite in fact, I’d say that protein requirements will be higher while dieting than while bulking for this reason. When you’re eating plenty of calories, the body will use protein more effectively. When you reduce calories, some of your dietary protein will be used for energy by the body, increasing intake to compensate for this is critical to avoiding muscle loss.

Q. The idea of protein cycling for muscle growth seems to crop up every few years. For those readers who don’t know what I’m talking about, protein cycling involves zig-zagging your protein intake so that you alternate between high and low levels of dietary protein, with the goal of “tricking” your body into building muscle faster. Is this a worthwhile strategy?

A. I can still remember when this idea was first presented, I actually wrote a fairly long piece looking at the research where I argued that it was crap and my opinion hasn’t changed in the last 10 years.

The basic premise is that, with increasing protein intake, the body will increase the oxidation (burning) of amino acids. Quite in fact, at least one researcher has argued that a high apparent protein requirement in athletes is being driven by a habitually high protein intake (which increases amino acid oxidation). That is, athletes need high protein intakes because they have high protein intakes.

In any case, as the logic goes, by decreasing protein intake drastically, you downregulate these processes, such that when you increase protein intake again, the body will utilize it more effectively.

In a related vein, there’s a phenomenon called “catch-up growth” that is often seen with malnutrition whereby kids grow at a faster rate (“catching-up” with their peers) due to some of the adaptations. There is some truth to all of this mind you.

But when I looked into what little research was available, it all fell apart in my opinion. The problem essentially has to do with the lag time between when you change protein intake and how the body adapts. In humans, there is about a 7-9 day time span between when protein intake is increased and the body adapts by up- and down-regulating amino acid oxidation.

The problem is that during that time period, the body loses a massive amount of protein. That is, say you go from your habitual high protein intake and slash protein intake drastically. Your body still has all of these adaptations to the previous high protein intake and until it readapts; during that time period, nitrogen balance is just massively negative.

Now, it works the other way of course, if you go from a very low to a very high protein intake, you see this massive positive nitrogen balance for about 7-9 days until the body adapts.

In my mind, what this will end up doing is basically having you waste 14-18 days to end up where you started. Before you can add any new muscle mass during the period of high nitrogen balance, you have to replace what you lost during the period of very low nitrogen balance. End result: no change.

And while at least one of the proponents of this idea has argued that the downregulation of amino acid oxidation is permanent (allowing you to sustain the high net nitrogen balance), there is zero research to support that contention. And research that basically says it’s nonsensical.

Additionally, what is often forgotten in discussions of amino acid oxidation is that the body is only burning off “excess” amino acids. In fact, early research looking at protein requirements for athletes used an increase in amino acid oxidation as the indicator that protein requirements had been met or exceeded. The new protein requirement method I mentioned above is actually using an increase or decrease in amino acid oxidation rates to try and determine maintenance protein requirements.

Which is a long-winded way of saying that amino acid oxidation isn’t some inherent evil in the first place, it’s not as if the body is oxidizing off the amino acids that it needs to support protein synthesis or what have you, it’s only oxidizing off the excess that it doesn’t need.

Finally, at least one researcher (DJ Millward) has suggested that amino acid oxidation might be part of the body’s overall “anabolic drive,” with some of the byproducts of amino acid oxidation having regulatory or valuable roles in terms of promoting gains.

As one example, readers may remember a brief fascination of the supplement companies with keto-isocaproate (KIC) and beta-hydroxy-methyl-butyrate (HMB). Well, in the body, when leucine is oxidized, it produces KIC and then HMB.

If Millward is correct and amino acid oxidation actually has a stimulatory role on protein synthesis, this might explain the disconnect between some of the research suggesting that there is a limit in terms of how much protein is required to maximally stimulate protein synthesis and what athletes have found to be most effective. Perhaps the increased amino acid oxidation from the supposedly “excessive” protein intake is having a regulatory effect above and beyond what you’d expect.

Q. When it comes to supplements, the conventional wisdom is that you should take a “fast” protein (e.g. whey) after exercise and a “slow” protein (e.g. casein) before you go to bed. What do you think?

A. Well, there is certainly a good logic to taking a slowly digesting protein, which could be casein, or just whole food, or even whey combined with carbohydrate, fat, and/or fiber at bedtime from the idea of maintaining nutrient availability to support growth, recovery, etc.

I’d qualify that by stating that no research has examined the impact on anything mind you, and there was some weird stuff some years back suggesting that around the clock feeding might be negative (I’d note that this was done in a hospital setting on sick folks) with the idea that the gut needed “rest” from the process of digesting and assimilating food.

As well, some of the intermittent fasting groups have been arguing that there is something good that happens when the gut isn’t having to process food but I’ll be honest that I haven’t really looked into it in huge detail. With all of that said, the general idea is probably a sound one.

As far as the idea of a fast protein after training, I think it gets a bit more complicated. Now, I’ll say that there is no doubt in my mind that a fast protein before or during a workout is superior. This is basically a practicality thing, you don’t want slowly digesting protein sitting in your gut while you’re training unless you like seeing and/or tasting it again.

But there is some emerging research, and some theoretical speculation, that a slow or a mixed fast/slow protein following training will actually yield superior results.

For example, casein (a slow protein) has been found to be superior to soy protein (a fast protein) and some work out of Stuart Phillips’ lab suggets that a 50/50 whey/casein mix might be superior. Other recent research has found that milk generates a nice anabolic response following training; interestingly higher fat milk did better than skim milk although the dietary fat would be expected to slow the rate of digestion.

I’m personally a big fan of milk protein isolate (MPI) which contains 80% casein and 20% whey (the same proportion as found in milk itself); although it hasn’t been tested in research, I suspect that it will outperform faster proteins in terms of maximizing the anabolic response.

Of course, athletes have long simply consumed a whole food meal following training and this seems to work just as effectively assuming they are hungry enough to eat (training blunts appetite for lot of people which makes liquids superior).

At this point my feeling is that a fast protein pre- and/or during-training with a slow or mixed fast/slow protein after a workout is superior. I would note that I definitely see absolutely no reason for the current popularity of protein hydrolysates (predigested proteins). Not only are they more expensive, but they tend to be bitter tasting; most importantly, research has failed to show any significant difference in digestion speed for whey versus its hydrolysate or casein versus its hydrolysate.

Click to continue to The Protein Book