Anabolic response to protein ingestion has no upper limit in humans

While this might sound like good evidence to support increasing your protein intake to build more muscle, it doesn't take into account the adverse effects of protein intake above the RDA of ~0.8g/kg of healthy body weight, unless you're over 65.

> The adverse effects associated with long-term high protein/high meat intake in humans were (a) disorders of bone and calcium homeostasis, (b) disorders of renal function, (c) increased cancer risk, (d) disorders of liver function, and (e) precipitated progression of coronary artery disease.

- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4045293/

High protein intake is associated with elevated levels of IGF-1, and "High IGF-1 levels increased the relationship between mortality and high protein":

> Respondents aged 50–65 reporting high protein intake had a 75% increase in overall mortality and a 4-fold increase in cancer death risk during the following 18 years. These associations were either abolished or attenuated if the proteins were plant derived. Conversely, high protein intake was associated with reduced cancer and overall mortality in respondents over 65, but a 5-fold increase in diabetes mortality across all ages.

> These results suggest that low protein intake during middle age followed by moderate to high protein consumption in old adults may optimize healthspan and longevity.

- https://www.cell.com/fulltext/S1550-4131(14)00062-X

Also important to note that one of the authors of the OP article is an employee of FrieslandCampina, the world's largest dairy co-operative and one of the top 5 dairy companies in the world.

Wow, I've only read the abstract so far but this basically goes against all conventional research on this topic AFAIK. I read probably ~50 papers on this topic (maximal protein dosing) and emailed a few researchers about it as I was writing a book. I believe the saturation point for a relative dose for a single meal is generally held to be ~0.25g per kg of bodyweight. Of course, there are some obvious observable issues with this belief given that there are people who practice intermittent fasting and have no issues building muscle, so it'll be really interesting to see if this study replicates

EDIT: After skimming the paper, I don't see anything immediately wrong with it. But there are some important nuances to note: the subjects were all fasted and given milk protein (casein in milk protein is known to take longer to absorb than pure whey protein which is a popular choice for these studies), and the measurements were made after an hour of exercise. This would skew the results towards more protein sensitivity than in normal settings where a person is pretty much always somewhat well-fed and not always eating after exercise. This is still encouraging because the results for post-exercise protein metabolism have still indicated a much lower limit than a 100g dose. Their report that oxidation rates didn't increase significantly is also notable since the belief has generally been that excess protein is oxidized and burned for energy instead of being incorporated into muscle. However, it would've been nice for them to include a 50g group as well to see if the dose-response relationship was really still linear between 25-50-100

Ultimately, this result seems encouraging for increasing post-exercise protein consumption for muscle gain, but we shouldn't discount the fact that the subjects were fasted before exercise. It would be interesting to see this study prolonged over the course of a day with further protein ingestions to see if the area-under-the-curve of muscle protein synthesis would eventually equalize in both groups, or if the larger immediately-post-exercise dose made a lasting difference. Existing research seems to not indicate such an "anabolic window". I might speculate that there is a daily limit for protein ingestion, but it doesn't matter if you hit that limit in one meal or five. That said, I have previously come across a paper that found medium-sized, spaced out doses to be more effective than infrequent large doses and overly frequent small doses, so there's still more to discover here

Apologies for only linking to the abstract. PDF can be found here: https://www.cell.com/cell-reports-medicine/pdfExtended/S2666...

This validates the approach of eating a ludicrous quantity of protein after working out.

I’ve been weight training consistently for more than a decade, keep up to date on the science, and I don’t find this that surprising.

mTOR is stimulated by a rising plasma concentration of leucine. It can only be stimulated to a certain extent at a given time (known as the “muscle full” effect), but if the leucine level remains chronically elevated until after the refractory period, it makes sense that another bout would trigger.

You can even see in their results that the smaller protein feeding produced a larger percentage-wise incorporation of that protein into muscle protein (17% vs 13%). If the subjects consumed that 25g four times across the 12 hours, I imagine they would have produced a larger net accumulation of muscle protein than the 100g group. This is because each discrete feeding could produce other anabolic effects, such as stimulating the release of insulin.

You can also see that the 25g dosing was insufficient to saturate even short-term muscle protein synthesis rates from figure 6C. Based on that graph, I’d guess that about a 40g bolus would have been sufficient.

So, no groundbreaking practical implications, IMO. Single bolus is still suboptimal, just maybe less suboptimal than the researchers thought. When evaluating practical implications, it is also worth noting that most humans do not fast after consuming a single protein shake, or after consuming four protein shakes. Our diets are typically a little more complex and varied than that.

Really surprising stuff (to me). I'm coming from the prior that large amounts of protein ingestion in one sitting are "wasted" and do not contribute much above a certain moderate amount. This is obviously only a single study, but it at least opened me up more to the possibility that this is wrong.

Some important limitations as listed in the paper:

- Study only assessed a short-term assessment window (~12 hr), and the researchers speculate that metabolic changes over time might skew these results:

"it is possible that the metabolic response to protein ingestion is modified over time. For example, it could be speculated that amino acid oxidation may increase in response to frequent, prolonged epi- sodes of hyperaminoacidemia or that large postprandial protein gains are compensated for by upregulation of amino acid oxida- tion in a subsequent fasted state"

- Study was with healthy young men after a bout of whole-body resistance exercise. May not extrapolate to other populations or conditions (i.e. at rest).

- Other study "limitations" point out that they were conservative in their conclusions, and the results of eating large amounts of protein at one time may be even stronger than stated in the paper.

Still, very interesting stuff.

"Anabolic response to protein ingestion has no upper limit in humans - according to a single paper, that might not replicate and be full of methodology errors and/or conflicts of interest, time will tell..."

Here's a better title, before people start jumping to conclusion about how this "invalidates conventional research" or how they'll start following this, etc.

Just to be clear, 100g is a large dose, but far from being able to assert there's "no upper limit"

> we show that the ingestion of 100 g protein results in a greater and more prolonged (>12 h) anabolic response when compared to the ingestion of 25 g protein

So the 25g protein group didn't consume any more protein/meal within 12h post-workout after their 25g protein meal? This seems like a hole in the study.

>100 g protein results in a greater and more prolonged (>12 h) anabolic response when compared to the ingestion of 25 g protein.

What does this even mean? Are subjects taking 100g and 25g of protein a day? Or 200g and 100g over 2 meals?

Oh this is very cool. It seems like the takeaway for body builders is “you don’t actually have to time protein ingestion super carefully?”

bros were right.

Now, find a way to trigger that without excercise @ win your Nobel prize.

Before anybody intervenes, I want to say that excercise is stupid activity and that gorillas don't excercise that much. Try wrestle with one.