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A primer on protein digestibility

Whether you’ve consumed a one-egg omelet, a 4-pound ribeye steak, or a block of tofu, the proteins in those meals will, for the most part, meet the same fate: first, they’ll be digested into amino acids and peptides in the stomach and small intestine; then, some will be used locally by intestinal cells, while most will be passed to the liver; finally, the liver will use some and pass the remainder into the bloodstream, where they can be taken up by cells throughout the body.

Although this process isn’t 100% efficient, as some amino acids are lost in fecal matter, it’s pretty close: the oro-ileal digestibility (i.e., digestibility through the GI tract) of protein tends to be around 91-95%, depending on the protein source and amount consumed — animal proteins are generally more digestible than plant proteins, but any degree of processing makes the difference largely negligible.^{[1][2][3][4][5]} It’s worth underscoring that there are practical and physiological limits to how much protein a human GI tract can process in a short time period, and any nutrient in severe excess can be harmful, but someone in good general health would likely become too uncomfortably full to consume additional protein before they even approached any physical limits in terms of stomach capacity.

Reframing the question: What is the maximal amount of protein your body can use from a single meal?

If you’re pondering how much protein you can eat in one sitting because you’re about to enter a national chicken wing eating competition, read no further. If you’re interested in knowing the optimal amount of protein intake per meal for supporting muscle protein synthesis (MPS) and muscle mass, the following is for you.

You might have come across the ”30 gram” rule, which postulates that roughly 30 grams is the maximum amount of protein that can be assimilated from a single meal, with the rest being ‘wasted’ and simply secreted from the body.^[6] The study, or studies, from which this “event horizon” of the protein world was derived is hard to pin down. It’s likely that early studies which observed increased nitrogen losses in the urine with increased protein intakes played a role. This was thought at the time to simply mean that the extra protein was wasted.^[7]

We now know that things aren’t so simple. More sophisticated ways of measuring the body’s response to ingested protein have been developed, and we now understand that eating more protein can increase both protein breakdown and protein synthesis by increasing protein turnover.^[8] Therefore the elevated levels of urinary nitrogen in the early nitrogen-balance studies didn’t simply reflect a waste of eaten protein, but an increase in protein turnover.^[8]

The notion of a “protein intake ceiling” also derives from studies on the skeletal-MPS response to consuming different levels of protein. One study in healthy young men found that eating more than 20 grams of whole-egg protein didn’t further increase MPS.^[9] Another study in younger and older people found that 90 grams of protein from 90% lean beef didn’t increase MPS any more than 30 grams did.^[10]

So, there does seem to be a ceiling in terms of the amount of protein required for maximal acute activation of MPS. However, it is important to consider a couple of points before taking this limit at face value.

First, we need to consider how the limit was determined. For example, the early in vivo studies observing increased nitrogen losses in the urine with increased protein intakes operated under a model that excluded protein turnover.

Second, we need to think about when amino acids are delivered into the bloodstream. Studies in cell culture models are commonly cited, where, for example, amino acid-starved muscle cells are given rapidly absorbed amino acids that quickly saturate their ability to synthesize new proteins. Although these types of models are valuable for understanding amino acid stimulation of protein synthesis at the cellular level, we need to think carefully about how they apply to humans outside of a lab. When we eat protein, we generally aren’t eating a fast-digesting liquid meal on an empty stomach — a common model for laboratory experiments studying acute activation of MPS. It takes time for your body to convert that juicy steak into amino acids in the bloodstream, so how do we know when we’re even bumping into the ‘limit’?

The body also tends to adjust the digestive process in response to protein. This works in part through the digestive hormone CCK, which, in addition to regulating appetite and satiety in response to food,^[11] can also slow down intestinal contractions and increase intestinal transit time in response to protein consumption.^[12][13] CCK is released when dietary protein is present, which slows down digestion in order to optimize protein absorption.^[14] The type of protein also affects digestion rate, as does the presence of dietary fat and fiber. All of these factors make it tough to determine whether the amino acids derived from, for example, the 100+ grams of protein from a ribeye steak you had at dinner will ever challenge any theoretical protein utilization ‘limit’ at the cellular level. Finally, your body doesn't use dietary protein only to make muscle, or even only to make other proteins. It also uses the nitrogen from your dietary protein’s amino acids to synthesize important non-protein molecules, including purines and pyrimidines, which are the building blocks for nucleic acids such as DNA and RNA.

So there’s a ceiling for acute activation of MPS… should we care?

For the sake of argument, let’s assume that 30 grams is the magic number here (or any other limit, since the following is more of a thought experiment).

Should we care?

Yes, if you are a protein researcher. For the rest of us, maybe in certain situations. Avoiding social events or career opportunities to avoid missing one of your 8 scheduled 30 grams of protein meals falls into the “who cares” territory. Eat protein consistently, don’t sweat missing a meal, and live your life. The reduced levels of stress hormones alone from not fretting over a meal schedule will be more anabolic than getting that 30 g shot of protein right at 3:15 pm.

On the other hand, let’s say that you’re wondering how much whey protein isolate (a rapidly absorbed protein) to include in your post-workout protein shake. (Note: There’s a popular idea of an “anabolic window” post-training that can be taken advantage of with properly timed protein delivery, but it’s not clear whether or not that really exists. My take is that post-workout protein doesn’t hurt, and there are arguments to be made that it can be helpful). Knowing that there’s an acute limit to stimulating MPS might steer you into consuming 25-40 g protein, rather than 300. Full disclosure, if you ever try to consume 300 g of whey protein isolate at once, it’ll be a self-correcting problem. Just try to avoid being downwind from other humans for several hours if you try that experiment—unless you really don’t like the people you’re downwind from—and possibly invest in a gas mask. (I’m serious about the gas mask.)

Protein-induced flatulence jokes aside, it’s important to keep in mind that although MPS is necessary for muscle growth, it’s not sufficient. This is illustrated by the lack of concordance between acute stimulation of MPS, be it from a workout or acute protein intake or both, and long-term increases in muscle mass.^[15]

Stimulating MPS does not guarantee muscle growth, or vice versa, and consistently consuming enough high-quality protein throughout the day seems to be much more important than procuring any particular amount of protein at any given time.^[16] Although consistent consumption throughout the day is definitely a good strategy, it’s important to also keep in mind that some studies have found that, for increasing lean mass, there was little difference between one larger protein meal and several smaller ones,^[17] and another trial found that a single high-protein meal was even more effective than several smaller ones for increasing lean mass in elderly women.^[18]

Research on intermittent fasting also suggests that the body can use far more protein consumed in a short period of time than most people think, with some studies showing that the consumption of large amounts of protein over a restricted time period yielded no differences in lean mass compared to more frequent consumption.^{[19][20][21][22][23]}

It is also important to emphasize that studies on MPS are a single snapshot in time, and lean mass is something that takes weeks to months to accumulate. Taking all this together, consistent consumption of high-quality protein is the key to maximizing lean mass; the timing of protein intake, as well as the amount of protein consumed per meal, are lesser concerns.

Another important thing to keep in mind is that MPS is only one piece of the muscle growth puzzle. It is the “business end” of the process, since muscle is made of proteins, and the proteins that we ingest are broken down into amino acids — the building blocks for making these proteins. However, MPS is occurring on a constant basis, regardless of whether a muscle is growing, shrinking, or maintaining its mass. In other words, protein is necessary, but not sufficient, for adding muscle mass.

Think of it this way: if you wanted to build a bridge, would you just dump tons of steel and concrete into a river? Of course not. The materials would need to be assembled by workers into a complex structure, as drawn up in plans or blueprints. Muscle growth is analogous. Amino acids from ingested proteins are the bricks and steel, assembled to order in response to changes in gene expression, which are far more dependent on factors such as sleep, managing stress levels, and a solid nutritional approach than on ingested protein.

For a quick primer on how this works, every gene in the human genome is encoded in the DNA that resides in the nuclei of every single one of our 30 trillion^[24] or so cells. Obviously, though, every cell is not the same. Muscle cells and bone cells and fat cells are all quite different from each other in form and function. This is possible in spite of having identical genomic DNA sequences because not all genes are expressed in every cell. This is how we can have different cell types in spite of every cell having an identical genomic DNA sequence. The subset of genes expressed in any given cell out of all the collective genes encoded in our genomic DNA is what makes a muscle cell a muscle cell, and not a fat or bone cell.

Additionally, not all genes are expressed at the same time, even in the same cell type. This allows a cell to constantly adapt to environmental stimuli to maintain homeostasis. For example, gene expression in muscle cells ultimately determines whether a muscle gains mass (hypertrophies), loses mass (atrophies), or stays the same. You might have just had the most growth-stimulating resistance training workout ever, which indeed would activate genes associated with muscle growth and adaptation. If, after that “perfect” workout, you consumed alcohol to the point of intoxication every day for the next week, failed to get adequate sleep, and layered on high stress levels, no amount of protein or protein timing can save you. Your muscles would not recover, let alone adapt and grow, and if you continued to train hard with that lifestyle, there’s a good chance that you’d develop an injury. Your gene expression would be tuned more toward survival, which means that you’d be breaking down more muscle protein than you added, regardless of your protein intake at any level.

This is why the ultimate takehome from this article is that protein intake is necessary, but not sufficient for muscle growth. If lifestyle or other factors (injury, illness, etc) have tilted your gene expression towards muscle protein breakdown (through upregulating genes associated with protein turnover), no amount of protein supplementation can fix that.

To sum it up:

• There is likely a ceiling for acute stimulation of MPS, but this is more of an academic concern.
• For optimal lean mass, health, and gains, consume enough quality protein on a daily basis. Consistently.
• Supporting optimal conditions for muscle growth through good habits / overall lifestyle factors (smart training, adequate sleep, stress management, good overall nutrition, etc) is probably a better thing to focus our attention on than consumption of a precise amount of protein with strict timing, or stressing over a ‘lost’ protein consumption opportunity from the occasional missed meal.