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Enzymes: Catalysts for Change

Enzymes pervade every part of life: They are in the toothpaste used first thing in the morning and in the contact solution used last thing at night. They were even in the first amoeba that cleaved to begin the evolution of man. Enzymes, in essence, are biological catalysts that speed up the rate of chemical reactions in cellswithout enzymes, no biological activity would occur. They are made up of two parts specifically folded, globular proteins and either a coenzyme or cofactorthat help enzymes return to their original state after catalyzing reactions.

Applications

In the nutritional world, enzymes are important not only for supplements, but also for food and beverage applications. Enzyme companies are always coming up with new applications to make a healthier food and beverage, beyond offering enzymes that deal with the ramifications of enzyme deficiency. For example, Bagsvaerd, Denmarkbased Novozymes recently launched Lipozyme TL IM, a lipase enzyme that aids in making bakery shortenings and margarines and which produces an optimum ratio of omega-3-to-omega-6.1

And in a collaboration between DuPont Central Research and Development facility in Wilmington, Del., and St. Louis-based The Solae Co., the companies are looking at ways to change the properties of soy protein to improve its flavor and solubility in beverages, meat products and baked goods.

Also on the soy front, Forsyth, Mo.-based National Enzyme Co.s Isolase, derived from Trichoderma longibrachiatum, has been seen in clinical trials to increase the bioavailability of isoflavones in soy products.2 Isolase also enhances the bioavailability of plant polyphenols.

While the popularity of supplemental enzymes is growing, the role of enzymes in food and beverage processing is more significant in terms of straight volume, said Philip Ronsivalli, sales manager for Kennesaw, Ga.-based Deerland Enzymes. The reasons for this include cost savings (like reducing energy costs by enhancing bread dough machine-ability), functionality (creating various syrups from starch) and consistency due to the fact that enzyme action can be controlled by the manufacturer, whether when making potable alcohol or better-tasting tomato sauce.

At Deerland, enzymes are being used to bolster one of the latest crazeslow-carb living. The companys Glucozyme, derived from Aspergillus niger var, is used to reduce the carbohydrate content in beer by producing fermentable sugars from starch.

Enzyme applications in the food industry are quite numerous since proteins, carbohydrates and fats need modification before being used in other food items. For instance, milk products have been using enzyme modification for texture and flavor for many years, as well as being modified for those suffering from lactose intolerance.

Lactose, a sugar found in milk, is a fermentable substrate. In lactose-intolerant people, lactose ferments within the large intestine in those people who have an insufficient expression of lactase enzyme on the intestinal mucosa to ferment this disaccharide to its absorbable, simple hexose sugars: glucose and galactose.3 Over the years, the science behind lactase has grown. Symptoms of lactose intolerance can be prevented by reducing the intake of lactosecontaining products or through using lactose-hydrolyzing agents.4 And in a study out of Beijing, healthy adults with a history of lactose intolerance who were given exogenous lactase experienced significantly decreased lactose malabsorption and milk intolerance symptoms.5

Another well-known enzyme aid has been alpha-galactosidase, the enzyme behind GlaxoSmithKlines Beano. Because bacterial fermentation of carbohydrates produces intestinal gas, Beano has been seen to diminish intestinal gas production by enhancing the breakdown of certain carbohydrates before they reach the lower intestine.6 Another condition helped through alpha-galactosidase supplementation is Fabry diseasean inherited disorder caused by a deficiency of the alphagalactosidase, which leads to fat storage and an increased risk of cardiovascular problems. In particular, supplementation may lead to a reduction of pain caused by the disease7 and an increase in patients sense of well-being.8

Taking supplemental enzymes also reduces the stress on the body to produce enzymes for digestion. I think the digestive category is the fastest growing and is most widely known and accepted as a condition where enzymes help, said Rohit Medhekar, Ph.D., director of research and development with National Enzyme Co.

Examples of how enzymes help maintain healthy digestion include a study showing pancreatic lipase reduces bloating, gas and fullness after a high-fat meal.9 Bromelain, extracted from the stems of pineapples, has been indicated as an anti-diarrhea agent,10 as have lactase, maltase and sucrase.11

People who consume a large amount of a particular type of food (for example, those on a low-carb, high-protein diet) may be advised to select a formulation that aids in digestion of specific macronutrients. For example, Triarcos Aminogen is a protease that helps the body absorb amino acids from a protein source,12 ultimately reducing or eliminating some of the common side effects of high-protein dieting, such as bloating, gas, constipation and indigestion. Athletes on high-protein diets may be consuming as much as 1 g to 2 g of protein per kilogram of body weight, said Mark Anderson, Ph.D., Triarcos director of research and development. Large amounts of protein reach the lower intestine where the protein is fermented and causes these problems.

Also on the protein front, researchers from Stanford University and the University of Oslo in Norway reported peptidase, an enzyme that breaks down proteins, may have promise in the treatment of celiac disease, an autoimmune disease characterized by the inability to digest gluten, a protein found in wheat, rye and barley products. Researchers found that gliadin, a part of gluten responsible for celiac disease, could be broken down by peptidase.13

Animal-derived enzymes have attributes that fit well in supporting digestive health. Both porcine animals and humans have stomachs that are typically at a 1 pH to 3 pH to help start our natural digestion process, said Kenny Soejoto, executive vice president of American Laboratories Inc. in Omaha, Neb., makers of fungal-, plant- and animalderived enzymes, such as Pancreatin USP and Pepsin FCC products. [Enzymes derived from animals, such as] pancreatic enzymes are naturally broad-based (protease, amylase, lipase, etc.) and can be utilized in various pH ranges and with our natural body temperature.

Reportedly, the body uses enzymes first and foremost during digestionand will steal enzymes from the immune system to get the job done, if need be. In fact, a condition known as digestive leukocytosis, in which the level of the immune systems white blood cells increase, is seen immediately after eating a cooked, processed meal in which not enough enzymes were derived from the food.

It only stands to reason, then, that instead of reaching for the nearest NSAID (nonsteroidal anti-inflammatory drug, such as aspirin or ibuprofen) the next time a bug comes biting, an enzyme supplement might be a better alternative. Papain, in doses of .33 mg/kg and .75 mg/kg, was found to exert strong anti-inflammatory activity and was comparable to butadion and indomethacin, two NSAIDs.14 In addition, the enzyme bromelain was found to reduce symptoms of both rheumatoid and osteoarthritis. In a study of joint health in subjects without arthritis but experiencing mild acute knee pains, 400 mg/d significantly reduced physical symptoms and improved general well-being.15

Wobenzyme, a combination of trypsin, papain, bromelain and chymotrypsin, is the enzyme many in the industry credit to bringing attention to enzymes non-digestive benefits. (The preparation is produced by Mugos-Pharma in Germany.) Supplementation with Wobenzyme was found to have a positive effect on the inflammatory process, including aiding with heart health via atherogenic benefits.16

Other enzymes are showing promise in inflammatory conditions such as arthritis, respiratory and heart health. In the inflammatoryprone region of cartilage, the protease seaprose has been seen to increase proteoglycan synthesisa factor in cartilage repair in arthritis.17 And, in respiratory health, researchers out of the University of Milan found a pharmacokinetic synergism between seaprose and the antibiotic erythromycin that allows erythromycin to penetrate bronchial secretion more easily and in higher amounts, performing a sterilizing action with therapeutic advantages.18

In terms of heart health, a study out of Italy showed seaprose was shown to be effective and well tolerated in the treatment of patients with inflammatory venous diseaseswhich affects the circulatory system.19

Another promising enzyme is nattokinase found in natto, a soybeanderived cheese. In a rat model out of Kobe, Japan, it was shown to have heart-healthy effects to a greater extent than plasmin or elastase, enzymes that help break up blood clots.20 And in a situation where people were at high risk for developing blood clotsflying for extended periods of timenattokinase was seen to help. In a study out of Italy, a propriety blend of the enzyme and maritime French pine bark (as Pycnogenol, as Aidans Flite Tabs from Aidan in Tempe, Ariz.) reduced thrombotic events in those taking the supplement and traveling on long flights.21

Digestive-related products are still the most popular place youll find enzymes, but systemic enzymes for inflammation is a growing area, Ronsivalli said.

For the manufacturer using enzymes in a non-digestive manner, it is important to keep in mind too much of a good thing. On one hand, the proteolytic enzymes are the ultimate anti-inflammatory agent, so filling up an anti-inflammatory supplement with other anti-inflammatory nutrients would ultimately weaken the enzymes overall potential effectiveness, said Troy Aupperle, president of Enzymology Research in Miltona, Minn. On the other hand, enzymes generally assist in speeding up the breakdown and assimilation of those nutrients, making them more effective. So, either way it would be a win-win situation.

One of the newer applications for systemic enzymes is in cosmeceutical products, since skin conditions such as psoriasis are considered inflammatory. However, as with many personal care ingredients, enzymes also offer anti-aging benefits. I feel the primary interest in enzymes for skin treatments, whether they are for facial scrubs or creams, has to do with an aging population who wants to preserve its appearance as best as possible, said Gabrielle Sill, marketing manager with Specialty Enzymes Co., based in Chino, Calif, makers of the SoftSEB line, products containing either proteases that exfoliate or lipases that condition. Enzymes remove dead skin from the surface, improving the skins overall appearance by lessening the formation of wrinkles and making the skin healthier and happier looking.

Manufacturing with Enzymes

Ten years ago, people were unaware of enzymes except for industrial uses, Sill said. When it comes to using them on a personal level, they knew very little about them, but now everyoneincluding the supplements industryis interested in them because of the multiple benefits they hold.

How does a manufacturer begin to tap into these benefits? One issue to contend with when using enzymes is employee safety. As with all proteins, there is a respiratory risk for employees who work with powdered enzymes. The body doesnt necessarily like foreign proteins, and employees working around enzymes may have the same reactions as hayfever sufferers, said Peter Moodie, sales director for New York-based Enzyme Development Corp. There is also the potential risk for more serious reactionsthe manufacturer should always review the information on the MSDS [material safety data sheets].

On a more cost-effective note, manufacturers can save money on one part of the manufacturing process when producing enzyme supplements: Enteric-coated enzyme preparations are no more effective than non-coated ones, since enzymes can withstand the lowpH environment of the stomach. Also, manufacturers should be in the know as to which enzymes work best together. Enzymes of a similar classsuch as proteasetend to work better together. In the case of human digestion, the conditions change as human digestion progresses. As one enzyme shuts down as it leaves its optimum environment, another starts up, Ronsivalli said.

Sill suggested it is important to know which companies manufacture enzymes. For instance, a company that manufactures the enzymes itself is more disposed to know the ins and outs of its enzymesfrom the science to the applications. We feel that when you deal with a manufacturer of enzymes, you are bound to get better and more complete information, Sill said. As a manufacturer, we are able to easily customize and blend formulas to clients preferences.

In the end, though, which enzyme is the one for a supplement makers needs? According to Soejoto, its imperative to know where the enzymes came from and how they were tested. In turn, manufacturers of tablets and capsules need to know if they are purchasing enzymes from a processor, manufacturer or supplier, he said. In addition, is the supplier merely just making blends or is the company actually testing and standing behind its product?

Suppliers emphasize enzymes should be purchased based on potency and not weight. According to Enzyme Development Corp. in New York, the potency of an enzyme is a measure of how much enzyme is needed to accomplish a specific action within a specified time. For instance, 1 g of lactase testing at 1,000 FCC lactase units per gram may convert 99 percent of lactose in a liter of milk at a specific temperature in 24 hours. However, lactase testing at 10,000 FCC units per gram would only need one-tenth of a gram to do the same job.

Also, a manufacturer should keep in mind there is no steadfast rule regarding what 500 mg is in terms of enzymes. Of course, 500 mg of bromelain testing at 50,000 FCC units per mg is a higher potency than the next guys product containing 500 mg of bromelain testing at 2,000 FCC units per milligram. In order for a customer not to be misled into buying a sub par product, a manufacturer should list on a supplement, food or beverage the amount and activity of the enzyme per dose.

In addition, it is important to have the enzyme tested by the same assay method as the supplier. As a buyer, it is imperative to know when the activity of the enzyme was tested and who tested it.

Having a generally recognized assay method that can be duplicated by different labs is becoming increasingly important, especially with the Food and Drug Administrations good manufacturing practices [GMPs] coming up, Moodie said. For example, theres a debate on the enzyme producer side to encourage manufacturers of bromelain-containing supplements to move from the GDU method, which can have a wide variance in testing outcomes, to the FCC unit.

Having lab tests that vary from company to company doesnt negate the fact enzymes are an integral part of the supplement industry. Soejoto stated enzymes will continue to be a growth niche market in the supplements industry. Just like a typical vitamin, such as vitamin C, a human being cannot survive without enzymes. Without enzymes, our bodies would not be able to digest the various foods we eat in order to sustain life.

Between the science and multiple applications of enzymes, the future seems bright for these catalysts. Enzymes do what they do very well, very specifically and very efficiently, and all we have to do is figure out new ways where to apply them, Ronsivalli said. I believe there is a lot of potential out there for enzymes. 

Editors note: for a full list of references to this story,

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