Do you need extra protease on a high-protein diet?
A routine need is not established. Two acute crossover trials studied a specific microbial protease blend in 24 healthy adults each. The pea-protein trial found some higher early amino-acid measures; the whey trial found no difference in its primary 120-minute total-amino-acid outcome, with increases in some exploratory 60-minute measures. These findings do not establish long-term clinical benefit or efficacy of the commercial product linked below.
Quick answer
Best suited for
- Readers examining acute, formulation-specific protease research and its limits; these studies do not establish a routine supplement need.
It is unlikely to help with
- Readers expecting proven long-term benefit or a guarantee of fewer digestive symptoms: the cited trials have acute, formulation-specific findings and do not establish those outcomes.
- A substitute for prescription pancreatic enzyme replacement therapy in people with a genuine enzyme deficiency — see the EPI guide for that distinct, medically-managed situation.
What to compare on the label
- Activity unit — Look for HUT (Hemoglobin Unit on a Tyrosine basis) at the labeled serving size.
- Underlying need — Consider whether there's an actual diagnosed deficiency (EPI) versus a general high-protein-diet rationale — the evidence base differs sharply between the two.
Where to find it
Microbiome Plus+ — Pro Digestive Enzyme Blend
Microbiome Plus+ Pro Digestive Enzyme Blend is a multi-ingredient capsule rather than a protease-only product. Its current manufacturer label (serving size: one veggie capsule) lists a Makzyme-Pro blend of fungal protease (Aspergillus oryzae) and three Lactobacillus species at 2500 HUT per 400 mg, plus bromelain, papain, fungal lipase, lactase and alpha-galactosidase. The Lactobacillus species are probiotic bacteria, not enzymes, and the HUT figure is declared for the blend as a whole, not for the protease alone. This is not the protease mixture studied in the trials on this page, and no routine need, muscle or immune benefit is established here. This is label information, not our laboratory testing. It is not a substitute for prescription pancreatic enzyme therapy; check the manufacturer's page for current directions, cautions and price.
View product →Enzyax is a Microbiome Plus affiliate through the Awin network and earns a commission on qualifying purchases made through this link. The link goes to the manufacturer's own product page, which shows current price and directions.
Also available on Amazon
Nature's Sunshine — Nature's Sunshine Protease Plus
The manufacturer lists protease, beet root fiber and trace mineral concentrate. This is a purchase option, not the proprietary BIO-CAT mixture studied in the cited trials. No equivalence, immune benefit, independent testing or personal dose recommendation is established here.
View on Amazon →As an Amazon Associate, Enzyax earns from qualifying purchases.
What the body already does
Normal protein digestion involves stomach enzymes and pancreatic proteases released into the small intestine. This physiology is different from proving that adding a supplement improves health or digestive symptoms.
What the randomized trials actually found
Paulussen et al. (2024) tested a proprietary blend with pea protein in 24 healthy adults. Total amino-acid concentrations and some early 0–2-hour exposure measures were higher with the blend; effects were not the same for every amino acid or time window. The trial also measured acute gastrointestinal symptoms and appetite, without a gastrointestinal-symptom advantage.
Huang et al. (2025) tested the blend with whey protein in 24 healthy adults. The primary outcome, 120-minute incremental area under the curve for total amino acids, did not differ from placebo. In exploratory post-hoc 60-minute analyses, essential and branched-chain amino-acid exposure was higher, but total amino acids and leucine were not significantly different. Some appetite ratings and ghrelin differed, while later meal energy intake and gastrointestinal tolerance did not establish a clinical benefit.
Both were single-meal experiments funded by BIO-CAT, with company-affiliated investigators. They did not test long-term changes in muscle health or routine supplement need, and did not test the Nature’s Sunshine retail product linked on this page.
Where the supplement claim gets thinner
The cited research does not establish a need for routine added protease in healthy adults on high-protein diets. Outcomes differ by amino-acid group and time window, and the whey trial’s primary outcome was negative. Acute blood measures, appetite ratings and single-meal observations do not establish longer-term health or digestive benefit.
This doesn't mean protease supplements do nothing for everyone — people with a genuine underlying deficiency have a real, medically-managed need for enzyme replacement. But that's a different population and a different product category (prescription PERT) than an over-the-counter protease capsule marketed to healthy high-protein eaters.
Our editorial position
We classify this use case as limited evidence because the cited trials are small, acute and formulation-specific. The primary and exploratory outcomes must be distinguished; the trials do not establish efficacy of the retail product or long-term routine benefit.
- If you suspect an actual enzyme deficiency rather than just a high-protein diet, that's a medical question — see the exocrine pancreatic insufficiency guide.
Sources: NIDDK — Your Digestive System & How it Works; Paulussen et al. (2024), "Acute Microbial Protease Supplementation Increases Net Postprandial Plasma Amino Acid Concentrations After Pea Protein Ingestion in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Trial" — PubMed 38467279 (Industry-funded (BIO-CAT, Inc.)); Huang et al. (2025), "Acute Effects of Oral Microbial Protease Co-ingestion with Whey Protein on Postprandial Plasma Amino Acid Concentrations, Appetite, and Satiety in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled, Crossover Clinical Trial" — PubMed 40675336 (Industry-funded (BIO-CAT, Inc.); some authors are company-affiliated). Last reviewed: July 29, 2026.