The global supplement industry is going to reach $278 billion by 2024. The regulation and scientific evidence for many of the biggest sellers is sparse. Muscle Protein Synthesis (MPS) and its expression from dietary intervention is our main concern today. What I want to know is the dosage of protein/amino acid combination necessary to induce MPS most effectively and efficiently, particularly before/during/after exercise, but I’ll try to summarize every piece worth noting.
The Tiniest Bit of Prep
Protein in muscles undergoes constant changes and restructuring through the breakdown of existing protein and incorporation of new proteins. If there exists a net positive amount of protein synthesis vs breakdown, muscular hypertrophy occurs, and in the instance of breakdown being greater than synthesis, atrophy occurs. This is crude, but my Dear Reader should not expect anything else from a Crude Man.
And We’re Off
Exercise causes acute changes in amino acid metabolism that is catabolic. However, this catabolism doesn’t immediately devolve into muscular atrophy, and there is a sequence of changes in metabolism that result in an anabolic recovery state following the bout of exercise. More specifically, endurance exercise seems to inhibit MPS and results in a net negative balance proportional to the duration and intensity of the activity. Resistance exercise, in contrast, also results in an increase of protein breakdown, but increases protein synthesis, which endurance exercise does not. RE leaves skeletal muscle in a negative nitrogen balance, i.e. negative amino acid balance, similarly to EE until a refeed of energy and protein. The rate of protein synthesis increases following this meal (any meal, really) and the rate of breakdown does as well, albeit to a lesser extent, i.e. a net positive.
PJ Atherton and K Smith found that nutrient driven increases in MPS are transient, usually around 1.5 hours in duration (more on this later), while Resistance Exercise (RE) in addition to adequate feeding increases the window to >24 hours. This means eating a protein-rich diet is good, but eating a protein-rich diet while pumping that sweet, sweet iron is better. But my Dear Reader already knew that.
All of this can be found here from Norton and Layman. We’re going to come back to their journal entry after we take a short field trip.
If One Were Rich
From the International Society of Sports Nutrition and a boatload of authors, we have this compilation of the latest on Protein and Exercise. For our purposes, I will cherry-pick because I think it’s well above 10,000 words.
- It appears that ingesting 1.4-2.0 grams of protein per kilogram of body weight per day has a net positive effect on muscle mass in the exercising individual. That’s 101. Don’t eat the low-protein diet prescribed by WebMD, unless my Dear Reader wants to be Trevor Reznik for Halloween. And this study shows that the international requirement value for leucine is far too low.
- 3.0g/kg/d or greater has particularly beneficial effects on lean body mass and total body composition in resistance trained individuals. However, it could possibly hinder endurance athletes, but who cares about them? We want big arms and powerful glutes. And so but well then how about protein, isn’t it bad for the kidneys? This has not been proven beyond subjects with existing chronic kidney disease.
- Acute protein doses should contain 700-3000mg (we’ll discuss this further) of leucine with a balanced array of all Essential Amino Acids (EAA). This means eat animal proteins.
- The optimal time period for intake of protein peri-workout is a matter of individual preference. We already discovered earlier that resistance training induces a window of 24+ hours of enhanced MPS, so the “anabolic window” is a bro-science/bodybuilding myth. The window is essentially the gap between workouts.
- Rapidly digested proteins and supplements with high levels of EAA and adequate leucine are highly beneficial and most potent for MPS.
- Quality of protein matters and whole sources, i.e. animal proteins, are going to have the best bioavailability of amino acids, especially EAA.
One notable finding substantiates what we all intuitively know: protein supplementation doesn’t seem to be anywhere near as important as total protein intake, i.e. if one isn’t eating a protein-rich diet, supplementation is mostly a waste of dollars. In trainees who are ingesting the recommended daily allowance of protein, 1.4-2.0g/kg/d, protein supplements don’t seem to have a positive effect on strength, especially if they’re new to RE. Supplementation of whey, egg white, etc. doesn’t have a statistically significant effect unless the (experienced) resistance trainee is eating a diet of >2.0g/kg of protein.
The rest of this is for those who eat enough protein.
Essential amino acid supplementation was shown by Børsheim et al. to provide a stronger effect on MPS than non-essential amino acid (NEAA) supplementation. Moreover, the effect of EAA is a dose-dependent response. Six grams of EAA was doubly effective over 3g of EAA + 3g of NEAA. This study showed that approximately 10g of EAA is potentially the optimal dose to maximize MPS.
Essential amino acids are a group of nine (out of 20 total amino acids) that the body needs to receive exogenously because they cannot be synthesized de novo, i.e. on our own. Inside of that group is a subgroup called branched-chain amino acids (leucine, isoleucine, and valine), of which I’m sure my Dear Reader has heard.
Leucine was shown to be imperative to muscle protein turnover as early as 1975, by Buse and Reid. Moreover, this study showed that the other branched-chain amino acids (BCAA), isoleucine and valine, proved ineffective for inducing protein synthesis in rats when they were used individually. This is important, as it shows leucine is the Prime Mover. Another 1975 study by Fulks et al. showed that BCAA were particularly beneficial for synthesizing proteins and reducing degradation of proteins in rat diaphragms. They also found that isoleucine and valine showed an ability to inhibit degradation and promote synthesis when paired. So, it seems, the BCAA are the three best friends that anyone could have. Perhaps we’ll find some human subjects soon.
We now return to our regular program, Norton and Layman.
Of the nine essential amino acids, only six are relevant in the amino acid metabolism of skeletal muscle. And since I’m a superficial ignoramus, that’s all I care about. The six are glutamate, aspartate, asparagines, leucine, isoleucine, and valine. Leucine, according to Layman, seems to be unique in its ability to boost MPS, work with insulin signaling, and promote alanine and glutamine production. This is all relative to the intracellular concentration of leucine. Through these functions, it also seems to have a regulatory effect on blood glucose homeostasis.
The wording is weird on this and I can’t seem to find any clarification (it’s possible I didn’t look very hard because I don’t care), but it is made out as if the branched-chain aminotransferase (BCAT) enzyme in the liver is inhibited by the ingestion of leucine, and the effect of this inhibition is the allowance of more leucine to pass through the liver into skeletal muscle. That would create a flood-like effect every time leucine is consumed, and one would assume BCAT would only increase in activity after leucine ingestion. Anyway, the BCAA that are ingested reach the blood almost untouched from the form in which they are ingested, so the level of BCAA in the blood is directly proportional to dietary intake. Exercise only increases the release of leucine from the liver and gut into skeletal tissue.
A test of rats who underwent a 2h exhaustive run on a treadmill vs fasted, unexercised rats presented a 25 percent decrease in MPS. The exhausted rats were refueled with either a glucose and sucrose electrolyte drink or a complete meal containing protein (or leucine). The former increased blood glucose, insulin concentrations, and muscle glycogen, but didn’t improve MPS at all. The latter, protein or leucine, brought the rats back to full MPS within an hour. Skeletal muscle remains in a net negative protein balance until protein or leucine is ingested.
OK, So What Do I Need?
A study done by Katsanos et al. took four groups, two young and two old, and gave them drinks containing 6.7g of EAA with either 26 or 41 percent leucine, about 1742 or 2747mg of leucine, respectively. MPS was improved in all instances except for the old people who received the 26 percent (i.e. 1742mg) solution of leucine. It was not potent enough to kick them into MPS. This is not surprising, as we know, the older population does not absorb protein as efficiently as young folk. This means that my Dear Geriatric Reader needs to consume a lot of high-quality protein (i.e. animal sources and potent supplementation when necessary).
This study showed that spiking a whey supplement with 3g of leucine proved more effective at inducing MPS than drinking an isocaloric milk protein. This comprehensive study used five solutions on a group of trainees. 25g of whey with 3g of leucine (W25), 6.25g of whey with .75g of leucine (W6), 6.25g of whey with 3.0g of leucine (W6+Low-Leu), 6.25g of whey with 5.0g of leucine (W6+High-Leu), and 6.25g of whey with isoleucine, valine, and 5.0g of leucine. For some reason they didn’t name the last solution as they did with the others, making the study quite confusing to read. Anyway, MPS was elevated in all groups in a 0-1.5h interval post-exercise, but in the 1.5-4.5h interval, the W6 and W6+High-Leu had the highest elevations of MPS. This means a high-concentration of leucine in protein supplementation can be just as effective as a much larger dose of total protein while being much more efficient (i.e. smaller, more concentrated dose).
So, the data prove to us that we need a dose high enough to induce MPS and keep us there for a while. From all of the studies above, it’s safe to deduce that we need at least 2.5-3g of leucine, but need an adequate amount of isoleucine and valine, as they work synergistically with leucine. I see a question arising because the gap for older folks when ingesting protein was over 1g of leucine in the Katsanos study, is it possible to induce MPS with only ~2g of leucine? Uh, perhaps, but the best estimates from all the people interpreting the studies are such that 2.5-3.0g is the safest bet.
Most BCAA supplements have a 2:1:1 ratio, meaning 8g would give us 4g of leucine, 2g of isoleucine, and 2g of valine. Anywhere between five and 10g of BCAA before and after workouts would be adequate based on the studies cited. Then, we go home and eat steak again.
Commence the Ruffling of Feathers
The only reason I really took the time to write all of the crap above is so that I could disparage a bunch of supplement companies… with science. Before we move on, our necessary dose of 2.5-3.0 grams of leucine is equivalent to 2500-3000 milligrams. I hope that didn’t have to be said, but public education never ceases to amaze me.
Nutrilite – The Prince of Trash
This is Amway’s protein product. It’s not good. The nutrition label says one serving is 10g of protein, made up by 830mg of leucine, 490mg isoleucine, and 500mg valine. It stacks up at $54 for 36 servings. I’d expect nothing less (or should I say more?) from a glorified pyramid scheme. I place Shakeology (1450-1700mg of leucine, 780-940mg of isoleucine, and 810-960mg of valine), Isagenix, and Herbalife in the same category as Nutrilite. I combed the internet for a while trying to find the amino acid profiles for Herbalife and Isagenix to no avail. Herbalife has articles written about amino acid profiles on their website, so I know they are at least tangentially aware of the importance. If that large of a company isn’t willing to post their profile, it can’t be good.
Paleoethics – The Queen of Garbage
Here is its nutrition label. It has 18g of protein, 799mg of leucine, 391mg of isoleucine, and 30.1mg of valine. $39.99 for 25 servings. I don’t even know what to say about 30mg of valine, and if I’m at a loss for words, it’s really bad.
Advocare – The King of Shit
Here is the label for Post-Workout Recovery. It has 12g of protein – 200mg leucine, 100mg of isoleucine, and 100mg valine. I guess it has the 2:1:1 ratio… so it’s got that going for it, which is nice. Advocare is identical to the other MLM Princes of Trash above but on a whole other level. Did I mention that it’s $79.99 for 25 servings? In case my Dear Reader hasn’t done the math, it would take about 13 servings, 26 scoops, just to get our recommended dose of leucine… That’s half the container. But Max, Drew Brees takes it! I thoroughly discussed in my CrossFit article why our training shouldn’t mirror the freaks. What I don’t understand is why Advocare’s Muscle Gain supplement, which is much higher in protein and assuredly has a better amino acid profile, wouldn’t have its breakdown on the label while the Post-Workout Recovery does. I would do the opposite if I were a logical conman.
All of these products beg the question, are the doctors and dietitians involved in creating and marketing these products ignorant of the current literature, or are they willfully conning the masses into paying for a product they know we’ll never research?
The Good, Not the Bad, nor the Ugly
I didn’t spend a ton of time on this because I believe supplements are the least important pillar of health. If my Dear Reader is lifting, eating enough, resting well, and meditating between eight and 24 hours per day, supplements can prove beneficial. Moreover, the main thesis of this blog is Muscle Protein Synthesis, so I better provide something pragmatic. These are a few supplements that do exactly what they are intended to do and comport with the recent literature that we discussed above.
Dymatize ISO 100 – The Archbishop
This is our commercial product. It’s good, throws 2.7g of leucine and 25g of protein right in the consumer’s face, and I respect the confidence. It is currently $49.99 for 3 lb/43 servings on Amazon.
NOW Whey Isolate – The Cardinal
The Dutch Chocolate, 5 lb tub is selling on Amazon for $56.99. That’s 69 (nice) delicious servings of exactly 25g of protein, 2909mg of leucine, 1591mg isoleucine, and 1671mg of valine. With 8oz of milk, it doesn’t get much better than this.
Barbell Medicine Whey Rx – The Pope
This product was created by Jordan Feigenbaum of Barbell Medicine, of which he is the founder and Head Doctor. He and his Barbell Medicine comrade Austin Baraki, MD, are quite insightful, strong, and aware of the current literature. It would be treasonous negligence if my Dear Reader didn’t check out their articles and videos. His 30-serving tub of 20g of protein, 3g of leucine, 1.5g of isoleucine, and 1.5g of valine is currently on sale for $39.99. I hope it still is at the time of my Dear Reader’s purchase. Not only is it the most potent protein on the market, it’s a small business and the highest quality with the shortest ingredients label.
A Post Scriptum
It isn’t a protein supplement, but I prefer to take the watermelon Peri Rx supplement Dr. Feigenbaum created. It’s a bit lighter, 8g of BCAA at a 2:1:1 ratio with lots of other performance ingredients we’ll likely discuss at some point, and tastes great with an Ultra Red Monster. I will let my Dear Reader know that I am fully aware of the irony of labeling Jordan Feigenbaum the Pope. As I leave you to navigate the field of protein supplements, please consider the fact that your dumb.
Until next time,
“Well, that about does her, wraps her all up… I guess that’s the way the whole darned human comedy keeps perpetuatin’ itself, down through the generations, westward the wagons, across the sands of time until we– aw, look at me, I’m ramblin’ again. Well, I hope you folks enjoyed yourselves. Catch ya later on down the trail.” – The Stranger