SUMMARY: We believe ProHydrolase is a scam. The sole published study shows little to no difference when using ProHydrolase. The other problem with enzymes such as ProHydrolase is that they probably don't work as consumers expect. They are designed to work at a specific pH and can be slow by taking up to 90 minutes to reach peak efficacy. Not many people make a protein shake then let it sit around for an hour and a half to get the full benefit. We found many brands not using the correct dosage of ProHydrolase as well as brands not disclosing the dosage of ProHydrolase at all. We found a few brands using ProHydrolase on other proteins that we have not been able to find public studies on, like Casein and Pea. To date, we can only find one public human clinical trial done on Whey protein.
What is ProHydrolase by Deerland Enzymes?
ProHydrolase by Deerland Enzymes is a digestive enzyme that aims to break down protein into a more bioavailable form. ProHydrolase is probably the second most popular protein enzyme in use after Aminogen, which is probably the first and most popular protein enzyme. ProHydrolase claims to have two human clinical trials but we can only find one published publicly which is what we will be basing this review off.
The Study ...and the Problem with Enzymes
ProHydrolase recently published a study they have conducted on whey protein linked here. This seems like an extremely robust robust study, looking at 10 males. Participants consumed either 250 mg of Prohydrolase + 26 g of whey protein, 26 g whey alone, or non-nutritive control. Blood samples were tested at 30-, 60-, 90-, 120-, and 180-min post-exercise. Protein synthesis was similarly analyzed. Deerland Enzymes' clinical trial neglects to mention how long ProHydrolase was given to work before it was studied which will be important to our discussion later. This study was conducted by Lipscomb University, in Nashville, TN in conjunction with Kennesaw State University in Kennesaw, GA. Unfortunately, the study results don't seem very positive...
Area under the curve amino acid analysis revealed no differences between ProHydrolase + Whey and Whey
The study concludes "Area under the curve amino acid analysis revealed no differences between ProHydrolase + Whey and Whey" and we see similar results with muscle protein synthesis. Their website claims ProHydrolase can "Increase total amino acids in the blood by 20%" but we aren't sure where this claim is coming from? This is the only public study we can find and this study at least very much does not support that claim.
The other issue is that this study highlights potential "Future work investigating protease supplementation with other protein types (e.g., casein, pea, soy)". How are brands already using ProHydrolase on casein and pea if there is no human clinical data backing this up?
As Nutraingredients summarized:
There were also no differences observed between the Whey + ProHydrolase group and the whey only group for a range of signaling proteins, including AKT, mTOR, p70S6K, JNK, ERK 1/2, p38, and NFKB.
The Problem With Enzymes
The problem with enzymes no one talks about is that they only function at a specific pH and can take a really long time to work. For a quick high school refresher (we forgot as well): The pH of pure water is around 7 and the pH of the acid in your stomach is around 2.5. Pepsin is an enzyme which breaks down protein in the stomach and is most active in acidic environments between pH 1.5 to 2.5. This makes perfect sense, it exists in your stomach and as such works in a highly acidic. Pepsin also becomes completely inactive in a pH above 6.5. So it you put pepsin in your protein shake and mixed with water...it would do nothing at all to help you until you drank it and put it in an acidic envirment.
ProHydrolase is an enzyme similar to Pepsin. We cant find any public data on Deerland Enzymes testing the ideal pH of ProHydrolase but we can find data on the ingredients that make it up to help give you a decent idea. According to Creative Enzymes which sells Bromaline: The optimum pH of the enzyme is 7.1. This is reinforced by a PubMed study saying : "The optimum temperature and pH for activity was 50 ° C and pH 7.0". If we look at the other ingredient, Bacillus subtilis, according to SciAlert: " it appeared that the pH of 5.5 treatment was higher than other treatments" This means that ProHydrolase works while it is in your shaker cup with water but we cant find evidence that it would continue to work once you drink it. It also means, ideally you would want to warm the water up to 50c which is 122F. Quite hot! According to refrence.com the average temperature of tap water is 50F, which is 72F cooler the the optimal temperature! This alone isn't necessarily a problem but the other issue is that enzymes don't work instantly. The ProHydrolase website says:
ProHydrolase degrades 99% of the peptides in whey protein responsible for gastrointestinal discomfort within 90 minutes.
This is further reinforced by the Kaged Muscle website which says that it takes 15-20 minutes to even start:
As a matter of fact, if you don’t drink RE-KAGED within 15-20 minutes of mixing you will start to taste the flavor get bitter like hydrolyzed whey protein.
So if your the type of person to make a protein shake then immediately drink it, you are probably getting no benefit from ProHydrolase. In order to get the full benefit of ProHydrolase you would presumably need to make a protein shake in water, then let it sit for an hour and a half, even better would be if you did that and kept it in the oven at 122F. It really seems like supplement brands using prohydrolase should disclose this and provide directions! I would imagine most people, like ourselves, simply make and instantly drink a protein shake which does not allow proper time or conditions for ProHydrolase to work.
Is ProHydrolase safe?
ProHydrolase is probably safe. We can find no public safety data on the safety of ProHydrolase specifically but the two ingredients composing ProHydrolase are decently well studied. Bacillus subtilis is Generally Recognized as Safe (GRAS). Ananas comosus / Bromelain although tested in a variety of folk medicine and research models for its possible efficacy against diseases, the only approved clinical application to date for bromelain was issued in 2012 by the European Medicines Agency for a topical medication called NexoBrid used to remove dead tissue in severe skin burns. As an ingredient, it is used in cosmetics, as a topical medication, and as a meat tenderizer. Even though it is probably safe, be sure to look out of any side effects which we have listed below. We would ideally like to see some public safety data on ProHydrolase as a whole.
What are the side effects of ProHydrolase?
We can find no public study on the side effects of ProHydrolase so we have broken down the side effects of the two ingredients (Bacillus subtilis and Ananas comosus) per WedMD.
Bacillus subtilis - An increase in stomach gas or bloating may occur. If this effect persists or worsens, notify your doctor or pharmacist promptly. Tell your doctor right away if any of these unlikely but serious side effects occur: signs of infection (such as high fever, chills, persistent cough).
Ananas comosus / Bromelain - Bromelain can raise the risk of bleeding. Make sure to stop taking it at least two weeks before surgery. Check with a doctor before using bromelain if you have any health conditions, such as a bleeding disorder, asthma, heart problems, liver or kidney disease, or stomach ulcers. Bromelain can cause stomach upset, diarrhea, vomiting, rapid heartbeat, and heavy menstrual periods. It can trigger reactions in people with allergies to pineapples, certain pollens, carrots, celery, rye and wheat flour, latex, bee venom, and other substances.
What is ProHydrolase made of?
ProHydrolase is a protease Enzyme Blend made from Bacillus subtilis and Ananas comosus. They claims 200mg has 70,000 HUT.
Per the Food Chemical Codex, a HUT is: one unit of proteolytic activity is defined as that amount of enzyme that produces a hydrolysate whose absorbance at 275nm is the same as that of a solution containing 1.10μg/mL of tyrosine in 0.006N hydrochloric acid in 1 minute under the conditions of the assay (pH 4.7 and 40°C). The quantity of the solubilized hemoglobin substrate in the filtrate is determined spectrophotometrically.
One of the best tests to gauge substantiation and research is how comfortable do the sports nutrition brands using this ingredient feel making the claims themselves. When buying a branded ingredient, typically a sports nutrition brand will sign a non-disclosure as well as indemnify the ingredient manufacturer, this means the brands hold the branded ingredient manufacturer harmless for any claims they make. With a non-disclosure agreement, the sports nutrition brands “know how the sausage is made” and ultimately they will be responsible and potentially sued for the claims the ingredient allows. If the data substantiating a claim isn’t strong, many wont risk it, although some often will to get ahead in this market. We took and did a break down of the claims of the major ProHydrolase brand partners from Stack3d, Amazon and Walmart. According to the publicly quoted and recently public ProHydrolase study, Deerland Enzymes tested with a dosage of 250mg for 26g of protein. On their website it says a slightly higher amount is preferred, “at a dose of 10mg per gram of whey protein isolate consumed”. We will also compare the formulations and see who is dosing ProHydrolase correctly and what brands are using a lower, non-clinically substantiated dose.
ProHydrolase is often under-dosed. However, the bigger issue is that frequently it is not even disclosed how much is used in a formulation so customers cant know if they are getting a full clinical dose of 10mg per gram of protein.
ProHydrolase in one serving
Protein in one serving
MET-Rx Metamyosyn Whey Protein Isolate
CytoSport Monster Blend
Kaged Muscle, Micropure Whey Protein Isolate
BPI Sports, Whey HD
|GenePro Protein Powder|
|TRIMTUF Whey Protein Isolate|
|Activ Folks Ultra-Premium 100% Whey|
|CLEAN MACHINE Clean Green Protein|
|BioPharma Scientific nanopro: vegan|
GNC AMP Wheybolic Whey
GNC AMP Wheybolic Ripped Whey Protein Powder
GNC AMP Wheybolic Alpha Whey Protein Powder
|Muscletech Iso Clear Hydrolyzed|
|MuscleTech NitroTech Iso Whey Isolate Protein Powder|
|Kaged Muscle, RE-KAGED Whey Protein Powder|
MET-Rx Metamyosyn Whey Protein IsolateWe have been pretty big fans of the legacy brand MET-Rx in the past. They made our go-to protein nearly 15 years ago. While we have moved on to new proteins, we have a soft spot in our heart for MET-Rx. Its sad for us to see them using only 50mg of ProHydrolase for 24g of protein. Keep in mind, Deerland Enzymes recommends 10mg per gram of protein. This formulation should have 240mg of ProHydrolase in it to match the clinical and Met-Rx is only giving a paltry 50mg! It seems to us like they are trying to get credit for putting the absolute least amount of enzymes in so they can put it on the label while spending as little as they can.
CytoSport Monster Blend
CytoSport is one of the larger sports nutrition brands. They are famous for their widely distributed Muscle Milk. CytoSport Monster Blend features 125mg of ProHydrolase for 25g of milk protein and whey protein. This SHOULD have 250mg of ProHydrolse to match the amount in their study. Also concerning is that the major source of protein used in this formulation is milk protein of which we can find no publicly available study showing ProHydrolate works on this protein source. Maybe the lower dose on an untested protein is whey CytoSpots chose to make no claims on ProHydrolase.
GNC AMP Wheybolic WheyEveryone is familiar with GNC and shopping their aisles was one of the reasons we started this site. AMP Wheybolic Whey is GNC's own house brand. It contains an impressive 40g of whey protein matched with a clinically correct dose of 400mg of ProHydrolase. Interestingly, despite GNC using ProHydrolase properly in the correct dosage, they make no claims by actually using it. Why include it if you arent going to tell customer what its going to do for them?
GNC AMP Wheybolic Ripped Whey Protein Powder
AMP Wheybolic Ripped Whey Protein Powder is GNC's own house brand. It contains an impressive 40g of whey protein matched with a clinically correct dose of 400mg of ProHydrolase. Interestingly, despite GNC using ProHydrolase properly in the correct dosage, they make no claims by actually using it. Why include it if you arent going to tell customer what its going to do for them?
GNC AMP Wheybolic Alpha Whey Protein PowderAMP Wheybolic Alpha Whey Protein Powder is GNC's own house brand. It contains an impressive 40g of whey protein matched with a clinically correct dose of 400mg of ProHydrolase. Interestingly, despite GNC using ProHydrolase properly in the correct dosage, they make no claims by actually using it. Why include it if you arent going to tell customer what its going to do for them?
RE-KAGED Whey Protein Powder by Kaged Muscle
We are big fans of Kris Gethin and what he is doing at Kaged Muscle. Re-Kaged Whey Protein is their formulation designed for recovery. We are happy to report, it features 280mg of ProHydrolase for 28g of protein, a clinical dose. Kaged Muscle seems to make no claims by using ProHydrolase, this product has been on the market a while so it might pre date the existence of the ProHydrolase clinical trial which just came out this year.
Micropure Whey Protein Isolate by Kaged Muscle
While we are big fans of Kris Gethin and what he is doing at Kaged Muscle, we are extremely disappointed in their Micropure Whey Protein Isolate. It features 25g of protein and a completely unknown amount of ProHydrolase. Is it dosed correctly? How much is actually in a serving? We have no clue whatsoever. What makes this even more disappointing is that that they DO disclose the amount on their re-kaged product. With their commitment below...we expected more.
Kaged Muscle® vendors and manufacturers commit to strict ethical, quality, and testing standards
Iso Clear Hydrolyzed by MuscletechMuscletech is one of the larger legacy brands in sports nutrition and have been around about as long as we have been working out. We typically see them at Walmart so they are very widely distributed. Iso Clear Hydrolyzed by Muscletech features 22g of protein and a clinical dose of 220mg of ProHydrolase.
MuscleTech NitroTech Iso Whey Isolate Protein Powder
Muscletech is one of the larger legacy brands in sports nutrition and have been around about as long as we have been working out. We typically see them at Walmart so they are very widely distributed. Iso Whey Isolate Protein Powder by Muscletech features 25g of protein and a clinical dose of 250mg of ProHydrolase.
BPI Sports Whey HD Ultra Premium Protein Powder
BPI Sports is a newer player on the block. We really like the clean label design utilized on their Whey HD Ultra Premium Protein Powder. However, we are very disappointed that BPI chooses not to disclose how much ProHydrolase is used in their formulation. How is the customer supposed to know if they are getting a clinical dose? Even weirder, BPI seems to be making no claims off its usage of ProHydrolase.
GenePro Protein Powder
While we were researching ProHydrolase we came across GenePro,a brand we have never heard of before. While we normally focus on branded ingredients, this is such an interesting product loaded with claims that we might do a full feature on this in the future. Unfortunately, they are only using 50mg of ProHydrolase for 30g** equivalent of whey protein, which might be 7.2g of real protein? We honesty don't know which makes us want to dive deeper on this product.
TRIMTUF Whey Protein Isolate
TRIMTUF seems to be a new player on the block and they just recently launched their Whey Protein Isolate. We are disappointed that they don't disclose how much ProHydrolase they are using in their formulation to customers can see if they are getting their value from this product. Hopefully since the product is so new, they are still able to change this and keep customers informed.
Activ Folks Ultra-Premium 100% WheyActiv Folks is a newer brand that just launched their Ultra-Premium 100% Whey. This brand proudly displays that they use ProHydrolase on their label. However, we are disappointed that they don't disclose how much ProHydrolase they are using in their formulation to customers can see if they are getting their value from this product. Why would you advertise you are using it on the front of the package then withhold from consumers how much is actually in the product?
Only Works With Whey
We are also going to highlight various brands who are using ProHydrolase in protein formulations with other proteins besides whey. The single public clinical study we have found was only tested on whey protein. The whey study mentioned other proteins an a future area of research so we believe there is currently no human clinical evidence supporting its use in other proteins.
GNC BEYOND RAW ISO-CASEIN P.M.
In its whey products GNC gives you a full clinical dose of ProHydrolase. Its upsetting to see GNC use that same ingredient on casein when we can find no public human clinical supporting that usage.
Doctor's Best Pea Protein Powder
Doctor's Best is a new player in the protein market. They feature ProHydrolase front and center, proudly on their label. They do deliver a clinically dose amount but we can find no evidence supporting ProHydrolase working with pea protein.
CLEAN MACHINE Clean Green Protein
CLEAN MACHINE Clean Green Protein features ProHydrolase in a blend of Lentein, which is a dehydrated, pulverized whole food made of a water lentil as well as pea protein. We can find no public information on ProHydrolase working with either Lentein or pea protein.
BioPharma Scientific nanopro: vegan
nanopro vegan by BioPharma Scientific is made from non-GMO American yellow pea, brown rice and chia seed and features 110mg of ProHydrolase for 14g of protein, which is under the studied amount. However, we can find no studies on ProHydrolase being effective in any of the proteins used in the formulation.