The Science of Why Hydrolyzed Whey Protein is BEST

Article by Stefan Burns - Updated May 2022. Join the Wild Free Organic email newsletter!

After finishing a workout, the standard recommendation is consume some protein to help build lean body mass. The faster the post-workout protein is absorbed the better, and as long as you have a healthy digestive system, this is true.

One of the latest advancements in the protein supplement industry is whey hydrolysate. Whey hydrolysate is absorbed by the body very rapidly because its whey protein peptides have been broken down into smaller chunks via hydrolysis.

Whey hydrolysate is rapidly absorbed by the body and it has been shown to improve the growth of muscle after a training stimulus as compared to other types of protein drinks.

What is Whey Protein?

Whey is a type of protein found in dairy milk, found to be highly bioavailable (1), and with cows milk 22% of the protein is whey. Casein protein makes up the remaining 78% of protein found in cows milk. It is almost exclusively cows milk that whey protein supplements are derived from.

Depending on the level of the extraction process, manufacturers make three different types of whey protein: whey concentrate, whey isolate, and whey hydrolysate.

Whey concentrate supplements are the least processed, still containing some fat, cholesterol, and lactose, with most modern whey concentrate supplements being 80-89% whey protein by weight. Whey isolate supplements are more processed, containing 90-99+% whey protein, being effectively lactose, carbohydrate, fat, and cholesterol free.

Whey hydrolysate is whey isolate that has been further processed to improve absorption by breaking down the whey protein chains into smaller pieces via enzymatic reactions. Whey isolate and whey hydrolysate are the same except whey hydrolysate has been predigested so it absorbs faster by the body.

For those looking to improve their health, have more energy, build muscle, and burn fat, what are the advantages to using hydrolyzed whey protein compared to a whey isolate or whey concentrate? Is hydrolyzed whey more anabolic than non-hydrolyzed whey protein?

To properly answer these questions, let’s examine more closely what whey hydrolysate is.

How is Whey Protein Hydrolyzed?

Whey hydrolysate is whey protein isolate which has been subjected to hydrolysis. Hydrolysis is a reaction involving the breaking of a bond in a molecule using water. In regards to protein, hydrolysis is the process of breaking down a protein into smaller peptides*. Protein hydrolysis typically occurs in the gastrointestinal tract after protein consumption (i.e. stomach and small intestine) through the use of acid and enzymes, but enzymatic protein hydrolysis can also be performed in the lab. Enzymatic protein hydrolysis, where food-grade enzymes are introduced to whey protein, is how whey protein hydrolysates are produced for the supplement industry.

In order to be absorbed by the body, all dietary protein is hydrolyzed during digestive enzymes to either free form amino acids or di- and tripeptides*.

*Note - Peptides are short chains of amino acid monomers (small molecules) linked by peptide bonds. A dipeptide is composed of two amino acids linked by peptide bonds, and likewise a tripeptide is composed of three amino acids linked together. A free form amino acid is a single amino acid molecule.

Any protein can be hydrolyzed, but typically only whey isolate is hydrolyzed to make whey hydrolysate supplements for economic reasons. There are three objective measures which can be used to determine the quality of a whey hydrolysate: percentage of hydrolysis, degree of hydrolysis, and average molecular weight.

Percentage of Hydrolysis

The percentage of hydrolysis is simply the amount of the protein which has been subjected to the hydrolysis process. A protein powder which is 50% hydrolyzed means that 50% of the protein has undergone some degree of hydrolysis, and the other 50% of the protein hasn't been hydrolyzed at all. Most whey hydrolysates which are sold are 100% whey hydrolysate, as they hydrolyze the whole batch of whey isolate at once.

Degree of Hydrolysis (DH)

Considering most whey hydrolysate supplements are 100% whey hydrolysate, the main determining factor in whether a whey hydrolysate is good or not is the degree of hydrolysis (DH). The degree of hydrolysis is the amount of hydrolysis that the protein has undergone, and this can range from no hydrolysis (DH0) to complete hydrolysis (DH100). A whey protein isolate which has a degree of hydrolysis of 10 (DH10), means that 10% of the whey protein has been successfully hydrolyzed (i.e. peptide bonds broken) to smaller di- and tripeptides and free form amino acids, and the other 90% of the whey protein isolate peptides are still tetrapeptides or larger. The higher the DH value of a hydrolyzed protein, the faster the whey protein is absorbed by the body.

Average Molecular Weight (AMW)

Related to the DH is the average molecular weight (AMW) of hydrolyzed whey. Molecular weights are measure in daltons (Da) and kilodaltons (kDa). Just as a whey hydrolysate with a high DH will have more di- and tripeptides and free form amino acids than a whey hydrolysate with a low DH, a more completely hydrolyzed protein will how a lower average molecular weight for the protein chains. This is important, because even if all the protein chains haven’t been completely hydrolyzed, any amount they have broken down is an improvement and will allow them to absorb faster.

Free form amino acids and di- and tripeptides have lower molecular weights than intact proteins, so the lower the average molecular weight of a whey hydrolysate, the faster it can be digested and absorbed into the blood stream. It is necessary to analyze the AMW of hydrolyzed protein supplements (if possible) because free form amino acids which have the lowest molecular weights are not as anabolic as di- and tri-peptides as they are directly absorbed by the gut at a greater rate and regulated by the liver to a much greater degree (2). Di- and tripeptides have a much easier time passing directly into the bloodstream than free form amino acids due to how they are transported (3). A low average molecular weight and a low free form amino acid percentage ensures that a hydrolyzed protein product is high in di- and tripeptides and not cheaper free-form amino acids.

To sum up, a DH30 whey hydrolysate will have a lower average MW than a DH10 whey hydrolysate.

As the DH increases, the protein which is being hydrolyzed becomes more and more bitter, and the broken protein molecules are reduced in molecular weight. A DH100 whey hydrolysate would be nearly impossible to manufacture. A typical 100% whey hydrolysate has a DH value ranging from 1-9%. A DH10 or greater is considered a high DH value, and the best protein hydrolysate supplements max out at ~DH30. If you are curious as to the degree of hydrolysis of a specific whey hydrolysate supplement, request a product specification sheet from the producer, as this information is usually not advertised.

Whey Hydrolysate Digestion

When it comes to the muscle building effects of any protein, four specific qualities must be analyzed to determine the protein’s impact on anabolism. These qualities are:

Rate of gastric Emptying
Gastrointestinal Absorption
Amino Acid Profile - Muscle Protein Synthesis
Insulin Response

The faster protein is able to exit the stomach into the small intestine for absorption, the better it is in acutely increasing circulating free form amino acids and di- and tripeptides in the bloodstream. More efficient gastrointestinal absorption also allows more protein fractions to enter into the bloodstream, creating a more anabolic environment. The level of muscle protein synthesis which is stimulated by a protein is important, and the ability of a protein to increase insulin secretion upon consumption also is important in creating an anabolic muscle building environment.

Hydrolyzed Whey has a Faster Rate of Gastric Emptying

Whey hydrolysate solutions empty with a half-time rate of 17 ± 6 minutes (4). The half-time rate is the time required by the stomach to empty 50% of the ingested meal. For reference, a standard glucose solution, which has a very fast rate of gastric emptying, has a half-time rate of 9.5 ± 1 minute and milk protein, which has a slow rate of gastric emptying, has a half-time rate of 26.5 ± 10.0 minutes (4). When it comes to quickly creating an anabolic state by delivering whey protein peptides into the blood stream, the faster the rate of gastric emptying, the better.

Hydrolyzed Whey is More Efficiently Absorbed

Whey hydrolysate is able to be absorbed by the body more rapidly than intact proteins, such as whey protein concentrate and isolate, thus quickening nutrient delivery to muscle tissues. Dipeptides and tripeptides, and less-so free form amino acids, are absorbed extremely rapidly since they are already broken down and can pass through the intestinal wall passively or via transporters. Peptides larger than tripeptides, such as tetrapeptides, cannot be directly absorbed by the body unless they undergo further digestion into smaller peptides or free form amino acids.

Studies (5, 6, 7) strongly suggest that ingestion of a protein hydrolysate results in a less efficient uptake by the splanchnic bed. The splanchnic bed is comprised of the tissues of the liver, stomach, intestines, pancreas, and spleen, and they have their own nutrient requirements. For the purpose of building muscle, the more proteins can avoid being absorbed by the splanchnic bed and flow into the blood stream, the better. With whey hydrolysate the acute increase of amino acids entering into the blood stream is greater than with protein isolate or concentrate, which should help with triggering muscle protein synthesis higher and build more muscle.

Amino Acid Profile - Muscle Protein Synthesis

Increasing muscle protein synthesis (MPS) is the main reason protein powder supplements are popular, as it leads to greater muscular gains, and compared to other protein sources such as casein and soy, whey protein is the best at acutely increasing MPS (8). The amino acid profile of whey protein compared to other proteins such as soy and casein is responsible for its greater ability to increase MPS, and the 2:1:1 ratio of branched chained amino acids leucine, isoleucine, and valine found in whey protein is responsible for this (9).

Whey Hydrolysate has a Stronger Insulin Response

Whey protein has been shown to greatly stimulate insulin release once the various di- and tripeptides and free form amino acids enter the bloodstream (10), and insulin is a major contributor to muscle anabolism* under certain conditions. The one-two punch of increased muscle protein synthesis from whey protein and increased insulin levels makes whey protein a very anabolic supplement, and considering whey hydrolysate is the quickest and most efficiently absorbed whey protein available, whey hydrolysate will stimulate insulin release to a greater degree than whey isolate or concentrate.

Compared to other versions of whey protein and casein hydrolysate, whey hydrolysate increases skeletal muscle glycogen levels to a greater degree over a similar time period (11, 12). Higher muscle glycogen stores and fast absorption make whey hydrolysate a great ingredient to use in a intra-workout drink.

*Note - Insulin allows nutrients in the bloodstream, such as whey protein fractions and glucose, to enter into a muscle cell. Insulin also stimulates muscle protein synthesis and increases blood flow to muscles.

Should you Buy Whey Hydrolysate?

Whey protein hydrolysate is more effective than whey protein isolate and concentrate, but since whey protein concentrate and isolate are already highly bio-available, the increased ability of whey protein hydrolysate to be absorbed into the blood stream, increase muscle protein synthesis, and build muscle might be overplayed.

A whey hydrolysate supplement with a degree of hydrolysis of 3, which is typical for the industry, only offers a small competitive advantage over regular whey protein isolate, but the current science shows that a DH10+ whey hydrolysate definitely confers significant anabolic advantages over regular whey protein isolate or concentrate.

Whether the increased price of whey protein hydrolysate is worth the extra premium is up to you the buyer. I personally like to afford myself every advantage I can, and whey hydrolysates are not that much more expensive than standard whey isolate.

To answer the question of whether consumption of a hydrolyzed whey protein produces a more anabolic environment compared to a non-hydrolyzed whey protein, the answer is yes (13). Consumption of a high DH, low AMW whey hydrolysate supplement has significant benefits over traditional whey isolate and concentrate supplements.

Is Whey Hydrolysate Right for You?

If you are already buying a whey protein supplement for pre, peri, or post workout nutrition, I would recommend you buy whey hydrolysate instead of whey isolate or concentrate as long as the degree or hydrolysis value of the hydrolysate is 10+.

When buying a protein powder for general health reasons, such as getting sufficient protein in the diet or to have an easy meal replacement on hand, I would stick with a less allergenic plant based protein, which also adds fiber to your diet.

Lower DH (<10) whey hydrolysates still offer unique advantages over typical whey protein supplements, but the higher price per pound doesn't make low DH whey hydrolysates worth the extra cost compared to whey isolate in my opinion.

If you are mildly lactose intolerant but whey isolate consumption causes no health issues, whey hydrolysate is a great choice. Whey hydrolysate is virtually free of lactose, fat, and cholesterol, and it shouldn't cause any adverse effects. Caution is always recommended though, and if you are unsure if you can consume whey protein safely with no gastrointestinal issues please consult with your doctor or wellness practitioner.

Whey Hydrolysate Buying Recommendations

Overall, I would give whey hydrolysate a big BUY recommendation considering you buy the right type (aka DH10+, AMW & ~10,000 Da). Below I have two brands I recommend and have tried, and there are other supplement companies which sell comparable products. Armed with the knowledge provided in this article, it should now be easy to determine whether any whey hydrolysate supplement you run across is high quality and legit or a marketing gimmick.

The high DH whey hydrolysate I recommend can be purchased from True Nutrition. True Nutrition sells dozens of different types of supplement powders and pills, rigorously third party tests them, and then retails them at competitive prices. You can even create your own custom protein blend, which is basically a combination of whichever bulk powders you want in your desired ratios. They charge extra for flavors, the bags used to hold the protein, and shipping, but even after all of that you still come out ahead.

The Hydrolyzed Whey Protein Ultra Grade sold by True Nutrition is approximately the same price as Optimum Nutrition’s Platinum HydroWhey, but it’s degree of hydrolysis is clearly listed at 13%, which is exceptional, and True Nutrition’s Hydrolyzed Whey isn’t spiked with lower quality BCAA’s like Optimum Nutrition’s HydroWhey. Optimum’s brand also uses artificial sugars which disrupt gut health.

True Nutrition powders can also be blended in the factory with other protein, carbohydrate, or fat powders for a customized shake blend, and you can customize the flavoring too, which is pretty great. Create your own peri-workout drink, meal replacement, protein shake, or more!

If you don’t care about hydrolysis, then Isopure’s Unflavored Whey Isolate is a great whey protein. I give it my highest recommendation because it is easy to digest, isn’t loaded up with any junk artificial sugars or chemicals, and comes at a reasonable price. Hydrolyzed protein can give you an extra edge, but for 99% of the populace, a whey isolate is a better choice of protein and will be just as effective in building muscle and increasing strength.

Boost Testosterone and Build Muscle with Cistanche

Whey protein confers quite an advantage in maintaining and building lean body mass compared to other proteins, and if you want to make sure every gram of protein goes to proper use and to really give yourself an extra edge with strength training, I recommend trying a Cistanche and Cholesterol Protocol.

Combining the testosterone boosting herb cistanche with high cholesterol sources of food like eggs primes the body for muscular growth by providing it everything it needs to increase steroidogenesis. Combining cistanche and eggs together caused me to increase my free testosterone levels by 53% in just 30 days. You can purchase cistanche from Nootropics Depot.

References

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Matthews, David M. et al. Peptide Absorption. Gastroenterology, Volume 71, Issue 1, 151 - 161
Frenhani PB, Burini RC. [Mechanisms of absorption of amino acids and oligopeptides. Control and implications in human diet therapy]. Arq Gastroenterol. 1999;36(4):227-37.
Calbet JA, Holst JJ. Gastric emptying, gastric secretion and enterogastrone response after administration of milk proteins or their peptide hydrolysates in humans. Eur J Nutr. 2004;43(3):127-39.
Manninen AH. Protein hydrolysates in sports nutrition. Nutr Metab (Lond). 2009;6:38.
Kim W, Egan JM. The role of incretins in glucose homeostasis and diabetes treatment. Pharmacol Rev. 2008;60(4):470-512.
Paddon-jones D, Sheffield-moore M, Aarsland A, Wolfe RR, Ferrando AA. Exogenous amino acids stimulate human muscle anabolism without interfering with the response to mixed meal ingestion. Am J Physiol Endocrinol Metab. 2005;288(4):E761-7.
Tang JE, Moore DR, Kujbida GW, Tarnopolsky MA, Phillips SM. Ingestion of whey hydrolysate, casein, or soy protein isolate: effects on mixed muscle protein synthesis at rest and following resistance exercise in young men. J Appl Physiol. 2009;107(3):987-92.
Hulmi JJ, Lockwood CM, Stout JR. Effect of protein/essential amino acids and resistance training on skeletal muscle hypertrophy: A case for whey protein. Nutr Metab (Lond). 2010;7:51.
Frid AH, Nilsson M, Holst JJ, Björck IM. Effect of whey on blood glucose and insulin responses to composite breakfast and lunch meals in type 2 diabetic subjects. Am J Clin Nutr. 2005;82(1):69-75.
Morifuji M, Kanda A, Koga J, Kawanaka K, Higuchi M. Post-exercise carbohydrate plus whey protein hydrolysates supplementation increases skeletal muscle glycogen level in rats. Amino Acids. 2010;38(4):1109-15.
Kanda A, Morifuji M, Fukasawa T, et al. Dietary whey protein hydrolysates increase skeletal muscle glycogen levels via activation of glycogen synthase in mice. J Agric Food Chem. 2012;60(45):11403-8.
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