Casein Hydrolysate and Anabolic Hormones and Growth – Research Review

I want to try something a little bit different for today’s research review.  Rather than looking at a single study in the kind of obsessive detail that only I and three readers really care about, I want to look at multiple studies but in lesser detail.  Not only will this hopefully make the article a bit more relevant and readable, it will let me address more than a single topic at once.

With the sheer volume of research appearing on a weekly basis, this will at least help me to look at data in a more timely fashion.  I’d mention that, for anyone who wants an even better look at a lot of studies, you’d be well served to consider Alan Aragon’s monthly Research Review which I reviewed in the confusingly titled Alan Aragon Research Review – Product Review.

In any case, today I want to look at two recent studies which are:

  1. Deglaire et al. Hydrolyzed dietary casein as compared with the intact protein reduces postprandial peripheral, but not whole-body, uptake of nitrogen in humans. Am J Clin Nutr. (2009) 90(4):1011-22.
  2. West et. al. Elevations in ostensibly anabolic hormones with resistance exercise enhance neither training-induced muscle hypertrophy nor strength of the elbow flexors. J Appl Physiol. 2009 Nov 12.

For each study I’ll give a brief background to the topic, look at what was done and then jump straight to the conclusions with some final summing up.  As noted above, some of the detail will be left out but I figure that anyone who is that interested in the details of methodology and such will simply get ahold of the full paper and read it themselves.


Deglaire et al.  Hydrolyzed dietary casein as compared with the intact protein reduces postprandial peripheral, but not whole-body, uptake of nitrogen in humans. Am J Clin Nutr. (2009) 90(4):1011-22.

BACKGROUND: Compared with slow proteins, fast proteins are more completely extracted in the splanchnic bed but contribute less to peripheral protein accretion; however, the independent influence of absorption kinetics and the amino acid (AA) pattern of dietary protein on AA anabolism in individual tissues remains unknown. OBJECTIVE: We aimed to compare the postprandial regional utilization of proteins with similar AA profiles but different absorption kinetics by coupling clinical experiments with compartmental modeling. DESIGN: Experimental data pertaining to the intestine, blood, and urine for dietary nitrogen kinetics after a 15N-labeled intact (IC) or hydrolyzed (HC) casein meal were obtained in parallel groups of healthy adults (n = 21) and were analyzed by using a 13-compartment model to predict the cascade of dietary nitrogen absorption and regional metabolism. RESULTS: IC and HC elicited a similar whole-body postprandial retention of dietary nitrogen, but HC was associated with a faster rate of absorption than was IC, resulting in earlier and stronger hyperaminoacidemia and hyperinsulinemia. An enhancement of both catabolic (26%) and anabolic (37%) utilization of dietary nitrogen occurred in the splanchnic bed at the expense of its further peripheral availability, which reached 18% and 11% of ingested nitrogen 8 h after the IC and HC meals, respectively. CONCLUSIONS: The form of delivery of dietary AAs constituted an independent factor of modulation of their postprandial regional metabolism, with a fast supply favoring the splanchnic dietary nitrogen uptake over its peripheral anabolic use. These results question a possible effect of ingestion of protein hydrolysates on tissue nitrogen metabolism and accretion.

My Comments: Ever since the pioneering work in the 90′s on fast and slow proteins, there has been continued interest in the digestion speed of proteins and how that impacts on metabolism, performance and, of course, muscle growth. In recent years, there have been many claims made for the superiority of faster proteins to slower in terms of ‘speeding amino acids to muscle’ in terms of promoting growth.

As well, as many may note, a recent commercial product (T-nations Anaconda), who’s anabolic claims were analyzed in perhaps the most commented article on the site in Alan’s Aragon’s guest article Supplement Marketing on Steroids, has recently been released to the market.

For background, hydrolysates are simply whole proteins that have been pre-digested (through the addition of enzymes during production) to some degree.  The theory being that, due to this pre-digestion, the hydrolysate will be digested in the stomach faster, getting aminos into the bloodstream faster and, presumably, having a better effect on skeletal muscle than slower proteins.

But is it true?  Guess.

The above study examined this issue by feeding 21 subjects 2 test meals containing ~26.5 grams of either intact casein or it’s hydrolysate; the protein had been marked with radioactive nitrogen so that it’s fate after ingestion could be tracked over the next 8 hours.  The test meals also contained 96 grams of carbohydrate and 23 grams of fat; this is worth noting as adding other nutrients to fast proteins often makes them behave more like slow proteins.  I’ll spare you the methodology, sufficed to say that tracking protein after it enters the body is brutally complicated and involves a lot of modelling and various measurements of blood amino acid levels and such.

Here’s what the study found.  Over the time course studied (8 hours after ingestion), the hydrolyzed casein product showed greater losses from digestion (that is, less was absorbed).  As well, a greater amount of the hydrolysate was oxidized for energy through deamination (a process by which the amino group is stripped off the carbon backbone).  Finally, a larger amount of the casein hydrolysate was used by the splanchnic bed (gut and intestines) with significantly less of the total protein reaching the bloodstream or peripheral tissues (muscles).

To quote the researchers:

Despite similar overall net postprandial protein utilization, our results indicate important differences in metabolic partitioning and kinetics between protein sources characterized by a preferential utilization of dietary nitrogen by for splanchnic protein syntheses after HC [hydrolyzed casein] ingestion at the expense of the incorporation into peripheral tissues.

Translating that into English: hydrolyzed casein is digested more poorly, gets burned for energy to a greater degree and gets used more by the gut than intact casein; the end result of this is that hydrolyzed casein provides LESS amino acids to skeletal muscle after ingestion than intact casein protein.

So not only is the claim that hydrolysates are better at providing aminos faster to skeletal muscle wrong, the reality is actually exactly reversed: intact casein is better for providing aminos to the muscle.  I’d note that other studies have found this as well: in one, intact protein provided MORE branched-chain amino acids into the bloodstream than a hydrolyzed form.

I’d add to this that, as I discussed in The Protein Book, other data supports the idea that slower proteins may actually be superior to faster proteins for muscle growth; in one set of studies, for example, milk protein (a mix of slow and fast proteins) resulted in greater hypertophy than soy (a fast protein) over 8 weeks of training and supplementation.  As well hydrolyzed proteins tend to taste like bleach; it’s no coincidence that Anaconda has to come with a separate flavoring intensifier: hydrolysates are gag-inducing.  They can’t be consumed straight.

Summing up: Hydrolysates are not only not superior to intact protein in terms of providing amino acids to skeletal muscle, they are distinctly inferior.  Their fast digestion speed leads to greater digestive losses, more oxidation via deamination and provides less amino acids to skeletal muscle.  That’s on top of tasting like vomit.  Or at least making you want to.


West et. al. Elevations in ostensibly anabolic hormones with resistance exercise enhance neither training-induced muscle hypertrophy nor strength of the elbow flexors. J Appl Physiol. 2009 Nov 12.

The aim of our study was to determine whether resistance exercise-induced elevations in endogenous hormones enhance muscle strength and hypertrophy with training. Twelve healthy young men (21.8 +/- 1.2 y, BMI = 23.1 +/- 0.6 kg(.)m(-2)) independently trained their elbow flexors for 15 weeks on separate days and under different hormonal milieu. In one training condition, participants performed isolated arm curl exercise designed to maintain basal hormone concentrations (low hormone, LH); in the other training condition, participants performed identical arm exercise to the LH condition followed immediately by a high volume of leg resistance exercise to elicit a large increase in endogenous hormones (High Hormone, HH). There was no elevation in serum growth hormone (GH), insulin-like growth factor (IGF-1) or testosterone after the LH protocol, but significant (P < 0.001) elevations in these hormones immediately and 15 and 30 min after the HH protocol. The hormone responses elicited by each respective exercise protocol late in the training period were similar to the response elicited early in the training period indicating that a divergent post-exercise hormone response was maintained over the training period. Muscle cross-sectional area increased by 12% in LH and 10% in HH (P < 0.001) with no difference between conditions (condition x training interaction, P = 0.25). Similarly, type I (P < 0.01) and type II (P < 0.001) muscle fiber CSA increased with training with no effect of hormone elevation in the HH condition. Strength increased in both arms but the increase was not different between the LH and HH conditions. We conclude that exposure of loaded muscle to acute exercise-induced elevations in endogenous anabolic hormones enhances neither muscle hypertrophy nor strength with resistance training in young men. Key words: testosterone, growth hormone, IGF-1, anabolism.

My Comments: For several decades now, there has been intense focus on the acute hormonal response to training.  This started back in the 80′s where researchers, interested in growth did a rather cursory examination of elite powerlifters and bodybuilders, made some assumptions about muscle size, made some even bigger assumptions about how they trained, and then proceeded to reach some staggeringly poor conclusions.

Basically, what they observed was that bodybuilders were bigger than powerlifters, which is debatable in the first place.  They also observed that powerlifters typically used low reps and long rest periods and bodybuilders (remember: this was the Arnold era) trained with high reps and short rest periods.  Thus they concluded that high reps and short rest stimulated muscle growth and went looking for reasons why this was the case.  I’d note that this is not really how you’re supposed to do science: you don’t reach your conclusion and go find reasons why it’s right.  You test hypotheses and draw your conclusions from that.  But I digress.

And the main focus for a while was potential differences in hormonal response to training, primarily focusing on testosterone and growth hormone (GH).  The basic study design that was followed was to compare the acute hormonal response to either 3 sets of 5 repetitions with a long rest interval (3 minutes) to sets of 10 with a 1 minute rest interval.  Repeatedly, studies showed that the first type of training boosted testosterone and the second GH.  Entire training schemes have grown out of this but there was a problem: nobody ever bothered to see if these acute (usually less than 10-15 minute) bumps in hormones actually did anything.

Nevermind that this makes little sense anyhow for a variety of reasons.  Not the least of which is that women have higher GH levels than men and get a bigger GH response to training, yet they don’t grow better.  If anything, with the known impact of testosterone on muscle growth, if there was to be any benefit to this, you’d expect the lower rep/heavy work to be superior.  Yet the researchers were arguing that it wasn’t.   There was a logic missing in the argument (not the least of which being the assumption that powerlifters had smaller muscles than bodybuilders) that seemed to get skipped over.

In addition to the science, there is a long held belief, echoed in various places (including the comments section of another contentious article I wrote titled Squats vs. Leg Press for Big Legs) that certain movements, notably squats and deadlifts, will have full-body growth stimulating properties, generally mediated through the hormonal response.

It’s not uncommon to see people recommending things like “If you want big arms, squat/train legs.” for example.  Essentially, heavy leg work is touted as being the key to overall growth.  Nevermind that the same people who make this argument will often complain about “All those guys in the gym with huge upper bodies and no legs” without realizing that the two ideas contradict one another (that is, if leg training is required for growth, how can guys get huge upper bodies without training legs).  But I digress again.

In any case, this study examined the issue directly with a somewhat confusing study design: twelve healthy young men trained their biceps on different days of the week under different training conditions.  In what they called the low-hormone condition, the biceps were trained all by themselves; no other exercise was done.  In the other called the high-hormone condition, the biceps were trained and then a large-volume of leg training was done to elevate the supposedly anabolic hormones.

Does that make sense, all subjects trained both arms, but on different days and under different conditions.  And the training was far enough apart that the hormonal response from the leg training wouldn’t have impacted the low-hormone training session.  This training was followed for 15 weeks and subjects consumed protein both before and after the training (so there was nutritional support).

Hormone levels were measured and while there was no significant change in hormones in the low-hormone situation, in the high-hormone situation, there were increases in lactate, growth hormone, free and total testosterone and IGF-1 with the peak occurring approximately 15 minutes after the leg work.

And, if the hormonal response to heavy leg training actually has any impact, what you’d expect to see is that one arm, the one trained along with the leg training, would grow better.

Did it happen? Guess.

Both maximal strength and muscle cross sectional area increased identically in both arms to the tune of a 20% vs. 19% increase in strength for low- vs. high-hormones and an increase in skeletal muscle cross sectional area of 12% vs. 10% in low- vs. high-hormones.  These differences were not statistically significant. Quoting the researchers:

Despite vast differences in hormone availability in the immediate post- exercise period, we found no differences in the increases in strength or hypertrophy in muscle exercised under low or high hormone conditions after 15 weeks of resistance training. These findings are in agreement with our hypothesis and previous work showing that exercise-induced hormone elevations do not stimulate myofibrillar protein synthesis (36) and are not necessary for hypertrophy (37). Thus, our data ((36) and present observations), when viewed collectively, lead us to conclude that local mechanisms are of far greater relevance in regulating muscle protein accretion occurring with resistance training, and that acute changes in hormones, such as GH, IGF-1, and testosterone, do not predict or in any way reflect a capacity for hypertrophy.

I don’t think it gets any clearer than that and I’d note that another recent study titled “Resistance exercise-induced increases in putative anabolic hormones do not enhance muscle protein synthesis or intracellular signalling in young men.” by the same group found the exact same thing.

Summing Up: Leg training has no magic impact on overall growth, most of which is determined locally (through mechanisms of tension and fatigue mediated by changes in local muscular metabolism).  If you want big arms, train arms.  If you want big legs, train legs.

And if folks are wondering why empirically ‘folks who train legs hard’ seem to get big compared to those who don’t, I’d offer the following explanation: folks willing to toil on heavy leg work work hard.  Folks too lazy to train legs hard often don’t.  And it’s the overall intensity of the training that is causing the difference, not the presence or absence of squats per se. Which is why guys who only hammer pecs and guns get big pecs and guns even if they couldn’t find the squat rack in the gym: the small acute hormonal responses to training are simply irrelevant to overall growth.