Dr. Rose, M.D. (researcher)

Evan Jerkunica (writer)

Enzyme 365 Review

Review Rating:

Best for: decreasing bloating, improving digestion

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Review Summary of Enzyme 365

The more we all learn about our digestive system and the gut in general, the more we appreciate its impact on our overall wellness. When you can digest your food thoroughly, you feel better: less bloating, better absorption of nutrients and improved immunity. This is the objective behind United Natural’s Enzyme 365.

Enzymes are the protein workhorses in our bodies that function as the catalysts for biochemical reactions and metabolic responses. While our bodies produce these enzymes naturally, age and diet can reduce our ability to produce essential enzymes. That’s where supplements can help. And that’s why Enzyme 365 with its 600-milligram blend of 17 vegetarian enzymes and 200-milligram blend of three digestion-supporting herbs impresses me. It’s a GI-tract immune enhancer.

While there is some overlap with the other digestion-assisting supplements we have reviewed, Enzyme 365 is, perhaps, one of the more inclusive, premium products we have tested. United Naturals’ Enzyme 365 works by introducing a wide range of enzymes to break down the fats, proteins and carbohydrates in food. It’s this process that helps boost nutrient absorption while helping to reduce insulin resistance and spikes.

Enzyme 365 is created and manufactured in the United States by United Naturals to promote optimal digestion…and more. If you experience age-related digestion problems, suffer dietary intolerances such as those from gluten or lactose, or if you have pancreatic inflammation (pancreatitis), you may find that this enzyme-rich formula is beneficial to your digestion and general health.

What Was the Inspiration for Creating United Natural’s Enzyme 365

When I spoke with the company founder regarding another United Naturals product–Synbiotic 365–he emphasized his interest in developing products that support digestive health. As he explained, it was his girlfriend’s life-destroying digestive problems that clearly illustrated the importance of digestion in our overall health.

Enzyme 365 complements the probiotic support to the gut’s microbiome provided with Synbiotic 365. They work together for optimal digestion, with Enzyme 365 breaking down food for better nutrient availability and Synbiotic 365 promoting balanced digestive flora.

Vincent Pedre, MD, Oversees Enzyme365’s Development

Dr. Vincent Pedre is United Naturals’ Chief Wellness Officer. And while he is a “certified medical doctor, a functional medicine certified practitioner” he favors a holistic approach to medicine. Dr. Pedre takes advantage of every opportunity to combine the best of Western and Eastern medical knowledge. In this way, he oversees the development of products that meet patients’ needs and help further the advance of naturopathic healthcare.

Ingredients in Enzyme 365

Advanced Vegetarian Enzyme Blend:


This enzyme is present in large amounts in human saliva and in pancreatic secretions. It is also found in many starchy plant seeds. Amylase helps to break down complex polysaccharides (like starch and glycogen) in food into smaller, simple sugars that are easily absorbed by the body. Because it breaks down carbohydrates, it is a digestive aid. Normally amylase responds like a stress hormone during periods of psychological or physiological stress to increase the amount of sugar available to the body. Complex carbs that are not broken down by amylase get passed on to the colon where the normal bacteria there break it down, forming gas and loose stool.A

Yeast Lipase

Lipase is one of the three components of the pancreatic enzyme mixture that helps us digest food. Lipases target lipids, breaking them down into component fatty acids for absorption. Since lipids are high in caloric value, significant efforts are made to use the inhibiting effect of lipase as a means to controlling weight. This is the mechanism of action of orlistat, currently marketed for weight loss and diabetic control B. Lipase does break down lipids in food into digestible components. Therefore it is a digestive aid.

Acid Protease

There have been hundreds of different proteases described, all of which are targeted at breaking down proteins into their component amino acids. Because it breaks down protein, it is a type of digestive aid. Some are used for the treatment of certain infections such as HIV. One interesting recent application has been in the role that proteases play in cell signaling and control in epithelium. Acid proteases are more active in an acidic pH and become inactivated as the pH rises.C

Fungal Protease

While most hydrolytic proteases that are available commercially are derived from bacteria, their development into supplements has been problematic due to bacterial contamination or breakdown during processing. Fungal proteases are derived from fungi and are easily produced by removal of the mycelium by simple filtration. The fermentation process that produces these proteases can be performed in a solid state for easy processing, lowering the cost while preserving their biological advantages.D

Neutral Protease

Neutral proteases are more chemically active at a neutral pH. Their actions are similar to those of other proteases.


Bromelain is a protease derived from the stems (and other parts) of the pineapple. It is currently approved as a chemical wound cleaner (debrider) to remove dead tissue from burns. It is also used as a meat tenderizer. There are numerous medicinal uses for bromelain that have been described, from anti-inflammatory to anti-metastatic to anti-platelet.E In the context of Enzyme 365, it is a powerful proteolytic enzyme that works to break apart complex proteins into their component parts. It is therefore a digestive aid.


Cellulase, as the name implies, breaks down cellulose in the diet. Cellulose is the non-digestible fiber component that makes up plant cell walls. The breakdown of cellulose by the human body is extremely difficult, requiring significant energy. As such, the food value of cellulose is very low. Cellulose adds a lot to dietary fiber and is passed in the stool unchanged. Cellulase releases the energy hidden in cellulose, making simple sugars available to the body. Adding cellulase to this product likely helps with the absorption of simple sugars and aids in the reduction of gas and bloating.F


Lactase is a well-known enzyme that is present in the lining of the small intestine. It is necessary for the breakdown of lactose from dairy products into the components galactose and glucose. Many people lose the ability to create their own lactase, leading to lactose intolerance: bloating, gas, diarrhea, even malnutrition. Adding lactase to a supplement may help the millions of Americans who cannot digest milk or milk products. Lactase may also help with obesity and insulin resistance.G


This is a form of amylase that is normally present in the gut, specifically in the small intestine, where it breaks down complex carbohydrates into more absorbable components. Glycoamylase aids in digestion and releases glucose into the bloodstream. The free glucose also likely supports the bacteria that reside in the gut.H There are some studies that suggest that glucoamylase might increase the insulin response to rising blood sugar, potentially helping in the treatment of diabetes.I


Pectin is the jelly-like substance that holds plant cells together to create strong fibrous networks. Pectinase is a naturally occurring enzyme that breaks down pectin. Pretreatment of fruits enhances the release of nutrient-rich juices from the fruit. Most pectinase is derived from fungi. Its use has been associated with cognitive improvement related to ginseng,J immune defense related to green tea K, and testicular health related to ginseng.L


Hemicellulase is a type of cellulase, enzymes that decompose cellulose into simple sugars. Hemicellulose is one of the major components of cell walls of plants, and hemicellulase helps break it down into small sugar molecules for absorption. Hemicellulase has been used to improve the breakdown of plant-based fiber into more digestible sugar components, reducing gas formation downstream.M Phytase A phytase is a phosphatase enzyme that breaks down phytic acid, a major storage form of phosphorus in plants and seeds. Phytase helps release phosphorus from the food and makes it more available to the body. Normally, phytic acid is the major storage form of phosphorus found in seeds, grains, and legumes, and it inhibits the absorption of zinc from the diet. Phytases, through their digestion of phytic acid, help to block that inhibition and help make zinc more available to the body.N


Invertase helps to break down sucrose into inverted sugar (glucose plus fructose). This is another name for sucrase. Invertase is derived from yeast and bees and appears to reduce the spike in both blood sugar and blood insulin after consuming sugar. The insulin spike has been associated with obesity, diabetes, and metabolic syndrome, so invertase may help avoid those common conditions.O


This is another enzyme that normally lives in the surface of the upper part of the small intestine, the duodenum. Maltase helps to break down maltose to the simple sugar glucose. This enzyme has been shown to worsen the spike in blood sugar after meals rather than blocking it as does invertase. P In diabetics this may worsen blood sugar control, but in healthy adults it more likely improves energy by making glucose more available to the body.Q

Alpha Galactosidase

This is an enzyme that is used most often to treat or prevent intestinal gas and is the active ingredient in Beano. Alpha-galactosidase breaks off the simple sugars attached to fats (glycolipids) or proteins (glycoproteins) that we eat in our diet, making those sugars available for energy. Since the enzyme breaks down glycoproteins and glycolipids, those foods are not available to gut bacteria to form gas.R As an aside, this enzyme might be deficient in Parkinson’s Disease.S


This a type of hemicellulase and helps to break down the polysaccharide xylan into xylose. Xylan is described as the third-most common biopolymer on Earth, present in the cell walls of virtually every green plant. Xylanase contributes to the breakdown of the cellulose cell wall structure of plant materials into smaller sugars. It is used as a pretreatment of wheat to improve dough handling in bread and improves the nutritional value of foods derived from plant materials. It is widely used in the preparation of livestock feed to improve the digestibility and energy gained from foods.T There is also evidence that it reduces oxidative stress in the liver, at least in zebrafish.U

Beta Glucanase

Glucanases are a family of enzymes that break down complex carbohydrates through the process of hydrolysis. They are used extensively in the process of making wine to break down yeasts and polysaccharides. One type of beta glucanase is cellulase (described above). Most of the research around beta glucanase relates to pretreatment of animal food to increase their growth and vitality, probably related to its ability to break down non-digestible plant materials.V, W

Digestive Support Blend:

Deglycyrrhizinated licorice root extract

Licorice is a perennial legume grown mostly in the Middle East and the US. It is used as a flavoring and a sweetener, and has been used since ancient times by herbalists for treatment of GI disorders. It has antioxidant and anti-inflammatory properties, and some claim anti-tumor effects as well. One component of licorice, glycyrrhizin, has been removed for this preparation, presumably to reduce the potential side effects of hypertension and edema.

Recent studies with licorice have explored its effects in neurocognitive disorders. A recent study by Cho showed that three varieties of licorice were effective in reducing the neurocognitive decline seen in a mouse model of inflammation-induced cognitive dysfunction.X Jung et al found that licorice root extracts helped reduce alcohol-related liver disease, also through its anti-oxidative and anti-inflammatory properties.Y Yang published a review of all of the purported pharmacologic effects of licorice. Licorice has been shown by several authors to interfere with several medications and to have estrogenic (anti-testosterone) effects.Z

Fennel seed extract

Fennel is a flavoring herb that is grown largely along the shores of the Mediterranean, although it is now grown more globally. A member of the carrot family, it is rich in protein, dietary fiber, B vitamins and several dietary minerals, especially calcium, iron, magnesium and manganese. Fennel seed has antioxidant propertiesAA and has been used to treat infantile colic.AB

Peppermint leaf extract

In this context, peppermint is likely used mostly for its flavor. Some investigators have evaluated the anti-oxidant properties of peppermint,AC although at higher doses it becomes a mucosal irritant. A recent study by Meamarbashi showed that peppermint oil extract improved the exercise performance, blood pressure, and pulmonary function of 12 healthy young athletes.AD Another study showed in vitro activity of peppermint against HIV, inhibiting its infectivity.AE

Other Ingredients:

  • Hypromellose
  • This inert, semi-synthetic polymer often used as a controlled-delivery capsule.

  • Rice Flour
  • Used as filler and flow agent to increase shelf life.

  • Vegetable Magnesium Sterate
  • Additional filler that also has lubricating properties.

  • Silica
  • This is a natural, essential mineral important for normal growth and development that also facilitates the absorption of other minerals

Enzyme 365 Allergen Data

United Naturals reports that very few consumers will experience an allergic reaction to any of the ingredients in Enzyme 365. One potential exception is the rice flour. Although only a small amount is present, if you have an allergy to rice, you should be aware of the potential for an allergic reaction.

Enzyme 365 is appropriate for vegetarians as the ingredients are 100% free of animal products. And as with all United Naturals supplements, the ingredients are carefully sourced and the final product is manufactured in the United States.

How Should I Take Enzyme365?

Recommended Dosage: The daily serving of Enzyme 365 is two (2) capsules. I’d suggest selecting your two largest meals of the day and taking one (1) capsule with each meal. United Naturals, however, does note that you may take a second capsule with a particularly large (heavy) meal.

Before Starting: As with all supplements, please consult your physician or healthcare provider before taking this product–especially if you are on medication. And if you are under 18, please consult a pediatrician before taking this product. Further, if long-term use of this or any supplement is planned, you should discuss the benefits and any potential side effects with your physician.

Does United Naturals Offer a Money-Back Guarantee on Enzyme 365?

United Naturals offers a 100% money-back guarantee on Enzyme 365–valid for 60 days after receiving the product. If you have any questions or issues, live support is available during regular business hours Monday through Friday, from 9AM to 5PM Eastern. You can reach United Naturals by calling 844-794-7728.

Are There Any Reported Enzyme 365 Scams?

I have not seen any reports of scams or serious problems associated with United Naturals or Enzyme 365. That said, I always suggest that to be safe as well as assured of getting fresh, untampered bottles, buy directly from the manufacturer or a reputable retailer. In every case, please do your own research.

Are There Any Product Complaints?

Actually the comments and opinions of consumers are quite positive. While Enzyme 365 is among the higher-priced supplements in its class, those people taking the product are pleased with the results. Some people who don’t have significant digestive problems report that they don’t necessarily take Enzyme365 daily. Rather, they reserve use for those times when having especially large or heavy meals.

Because Enzyme 365 works by breaking down fats, proteins and carbohydrates, there is always the possibility of occasional bloating, cramps, nausea and diarrhea or constipation. If you are particularly prone to any of these side effects, you may want to start slowly.

Does United Naturals Have Good Customer Support?

I have personally tested United Naturals’ support resources and been pleased with the company’s responsiveness. When I’ve called after hours and left a message, I receive a call back early the next day. That’s a less than 24-hour response and, I think, perfectly reasonable.

Where You Can Purchase United Naturals Enzyme 365

If you want the best deals on Enzyme 365–including special offers and multiple bottle discounts–I suggest that you go over to United Naturals and buy direct. It’s also ensures that you are buying the freshest, unopened and untampered product.

Review Rating:

Best for: Optimal Digestion, Nutrient Absorption and Gut-Related Immune System

Click here to buy direct (best price)

No Risk – 60 day money back guarantee

Full Reference List

  1. Duchemin AM, Steinberg BA, Marks DR, Vanover K, Klatt M. A small randomized pilot study of a workplace mindfulness-based intervention for surgical intensive care unit personnel: effects on salivary α-amylase levels. Journal of occupational and environmental medicine/American College of Occupational and Environmental Medicine. 2015 Apr;57(4):393.
  2. Shirai K, Tanaka M, Fujita T, Fujii Y, Shimomasuda M, Sakai S, Samukawa Y. Reduction of Excessive Visceral Fat and Safety with 52-Week Administration of Lipase Inhibitor Orlistat in Japanese: Long-Term Clinical Study. Advances in therapy. 2019 Jan 1;36(1):217-31.
  3. Schepis A, Barker A, Srinivasan Y, Balouch E, Zheng Y, Lam I, Clay H, Hsiao CD, Coughlin SR. Protease signaling regulates apical cell extrusion, cell contacts, and proliferation in epithelia. J Cell Biol. 2018 Mar 5;217(3):1097-112. https://www.ncbi.nlm.nih.gov/pubmed/29301867
  4. de Souza PM, Bittencourt ML, Caprara CC, et al. A biotechnology perspective of fungal proteases. Braz J Microbiol. 2015;46(2):337–346. Published 2015 Jun 1. doi:10.1590/S1517-838246220140359 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4507524/
  5. Maurer HR. Bromelain: biochemistry, pharmacology and medical use. Cellular and Molecular Life Sciences CMLS. 2001 Aug 1;58(9):1234-45. https://www.ncbi.nlm.nih.gov/pubmed/11577981
  6. Elghandour MM, Kholif AE, Marquez-Molina O, Vazquez-Armijo JF, Puniya AK, Salem AZ. Influence of individual or mixed cellulase and xylanase mixture on in vitro rumen gas production kinetics of total mixed rations with different maize silage and concentrate ratios. Turkish Journal of Veterinary and Animal Sciences. 2015 Aug 20;39(4):435-42.
  7. Abaturov AY, Stepanov YM, Nikulina AA. Treatment of lactase deficiency in children’s obesity with genotype c/c 13910 of lactase gene. Wiadomosci lekarskie (Warsaw, Poland: 1960). 2019;72(1):17-21.
  8. Yin D, Yin X, Wang X, Lei Z, Wang M, Guo Y, Aggrey SE, Nie W, Yuan J. Supplementation of amylase combined with glucoamylase or protease changes intestinal microbiota diversity and benefits for broilers fed a diet of newly harvested corn. Journal of animal science and biotechnology. 2018 Dec;9(1):24.
  9. Lundquist I, Panagiotidis GE, Salehi AL. Islet acid glucan-1, 4-alpha-glucosidase: a putative key enzyme in nutrient-stimulated insulin secretion. Endocrinology. 1996 Apr 1;137(4):1219-25. https://www.ncbi.nlm.nih.gov/pubmed/8625892
  10. Ju S, Jang J, Kim M, Jeong G, Seo H, Woo Y, Lee SK, Oh J, Kim JS. Oral administration of hydrolyzed red ginseng extract improves learning and memory capability in cognitive-decline models. The FASEB Journal. 2016 Apr;30(1_supplement):1176-24.
  11. Chang B, Kim T, Kim S. Polysaccharides from pectinase digests of green tea enhances host immune defence through toll-like receptor 4. Food and agricultural immunology. 2018 Jan 1;29(1):870-85. https://www.tandfonline.com/doi/full/10.1080/09540105.2018.1494139
  12. Kopalli SR, Cha KM, Lee SH, Ryu JH, Hwang SY, Jeong MS, Sung JH, Kim SK. Pectinase-treated Panax ginseng protects against chronic intermittent heat stress-induced testicular damage by modulating hormonal and spermatogenesis-related molecular expression in rats. Journal of ginseng research. 2017 Oct 1;41(4):578-88. https://www.ncbi.nlm.nih.gov/pubmed/29021707
  13. Chun J, Pochapin M. Gastric Diospyrobezoar Dissolution with Ingestion of Diet Soda and Cellulase Enzyme Supplement. ACG case reports journal. 2017;4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519403/
  14. Brnić M, Hurrell RF, Songré-Ouattara LT, Diawara B, Kalmogho-Zan A, Tapsoba C, Zeder C, Wegmüller R. Effect of phytase on zinc absorption from a millet-based porridge fed to young Burkinabe children. European journal of clinical nutrition. 2017 Jan;71(1):137.
  15. M Laue C, Ballance S, Knutsen SH, Papazova E, Soeth E, Pannenbeckers A, Schrezenmeir J. Glycemic response to low sugar apple juice treated with invertase, glucose oxidase and catalase. European journal of clinical nutrition. 2019 Apr 10:1.
  16. P Ibrahim MA, Yunusa I, Kabir N, Ali Baba S, Yushau AM, Ibrahim SS, Bello ZI, Suleiman SH, Isah MB. In vivo maltase and sucrase inhibitory activities of five underutilized Nigerian edible fruits. Mediterranean Journal of Nutrition and Metabolism. 2016 Jan 1;9(1):37-45.2
  17. Nichols BL, Baker SS, Quezada-Calvillo R. Metabolic impacts of maltase deficiencies. Journal of pediatric gastroenterology and nutrition. 2018 Jun 1;66:S24-9.
  18. Tuck CJ, Taylor KM, Gibson PR, Barrett JS, Muir JG. Increasing Symptoms in Irritable Bowel Symptoms With Ingestion of Galacto-Oligosaccharides Are Mitigated by α-Galactosidase Treatment. The American journal of gastroenterology. 2018 Jan;113(1):124. https://www.ncbi.nlm.nih.gov/pubmed/28809383
  19. Alcalay RN, Wolf P, Levy OA, Kang UJ, Waters C, Fahn S, Ford B, Kuo SH, Vanegas N, Shah H, Liong C. Alpha galactosidase A activity in Parkinson’s disease. Neurobiology of disease. 2018 Apr 1;112:85-90.
  20. Cho JH, Park JH, Lee DH, Lee JM, Song TH, Kim IH. Effects of xylanase supplementation on growth performance, digestibility, fecal gas emission, and meat quality in growing–finishing pigs. Canadian Journal of Animal Science. 2016 Aug 4;97(1):95-100. https://www.nrcresearchpress.com/doi/full/10.1139/cjas-2015-0198#.XXJX9ShKiUk
  21. Lin YS, Saputra F, Chen YC, Hu SY. Dietary administration of Bacillus amyloliquefaciens R8 reduces hepatic oxidative stress and enhances nutrient metabolism and immunity against Aeromonas hydrophila and Streptococcus agalactiae in zebrafish (Danio rerio). Fish & shellfish immunology. 2019 Mar 1;86:410-9.
  22. Ferreira LG, Endrighi M, Lisenko KG, de Oliveira MR, Damasceno MR, Claudino JA, Gutierres PG, Peconick AP, Saad FM, Zangeronimo MG. Oat beta-glucan as a dietary supplement for dogs. PloS one. 2018 Jul 31;13(7):e0201133.
  23. Clarke LC, Sweeney T, Curley E, Gath V, Duffy SK, Vigors S, Rajauria G, O’Doherty JV. Effect of β-glucanase and β-xylanase enzyme supplemented barley diets on nutrient digestibility, growth performance and expression of intestinal nutrient transporter genes in finisher pigs. Animal Feed Science and Technology. 2018 Apr 1;238:98-110.
  24. Cho MJ, Kim JH, Park CH, Lee AY, Shin YS, Lee JH, Park CG, Cho EJ. Comparison of the effect of three licorice varieties on cognitive improvement via an amelioration of neuroinflammation in lipopolysaccharide-induced mice. Nutrition research and practice. 2018 Jun 1;12(3):191-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974064/
  25. Jung JC, Lee YH, Kim SH, Kim KJ, Kim KM, Oh S, Jung YS. Hepatoprotective effect of licorice, the root of Glycyrrhiza uralensis Fischer, in alcohol-induced fatty liver disease. BMC complementary and alternative medicine. 2015 Dec;16(1):19. https://www.ncbi.nlm.nih.gov/pubmed/26801973
  26. Yang R, Wang LQ, Yuan BC, Liu Y. The pharmacological activities of licorice. Planta medica. 2015 Dec;81(18):1654-69. https://www.ncbi.nlm.nih.gov/pubmed/26366756
  27. Oktay M, Gülçin İ, Küfrevioğlu Öİ. Determination of in vitro antioxidant activity of fennel (Foeniculum vulgare) seed extracts. LWT-Food Science and Technology. 2003 Mar 1;36(2):263-71. https://eurekamag.com/research/003/706/003706345.php
  28. Alexandrovich I, Rakovitskaya O, Kolmo E, Sidorova T, Shushunov S. The effect of fennel (Foeniculum vulgare) seed oil emulsion in infantile colic: a randomized, placebo-controlled study. Alternative therapies in health and medicine. 2003 Jul 1;9(4):58. https://www.ncbi.nlm.nih.gov/pubmed/12868253
  29. Sroka Z, Fecka I, Cisowski W. Antiradical and anti-H2O2 properties of polyphenolic compounds from an aqueous peppermint extract. Zeitschrift für Naturforschung C. 2005 Dec 1;60(11-12):826-32.
  30. Meamarbashi A, Rajabi A. The effects of peppermint on exercise performance. Journal of the International Society of Sports Nutrition. 2013 Dec;10(1):15.
  31. Geuenich S, Goffinet C, Venzke S, Nolkemper S, Baumann I, Plinkert P, Reichling J, Keppler OT. Aqueous extracts from peppermint, sage and lemon balm leaves display potent anti-HIV-1 activity by increasing the virion density. Retrovirology. 2008 Dec;5(1):27.

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