The Industry of Enzymes
by Steve Myers

It is hard to corral the industry of enzymes. As catalysts, enzymes ubiquitously speed up chemical reactions on every imaginable front. Enzymes can help improve the yields of an industrial process or can help slaughter a recently eaten last meal. While biological activity universally requires the catalysm of enzymes, the market for dietary enzyme products is still relatively small, making a significant impact on just a few functional ingredient categories. How these catalysts target, act and travel in the human body greatly impacts their efficacy and usefulness. A better understanding of these detailed actions is the key to expanding the market for these products.

An enzyme is a protein produced by living cells for the purpose of regulating metabolic, biochemical reactions in living organisms. It is comprised of specially folded globular proteins and a co-enzyme (or cofactor).

The beauty of an enzyme is not only the increased reaction rate it provides, but also its uncanny ability to remain undestroyed by the reaction itself.This property, credited to the coenzyme, allows it to deliver its benefits over and over again.

An enzyme works only on a specific substance, called a substrate, which fits perfectly into the enzymes activity site. Here, the enzyme breaks it down into usable partssuch as lactose broken into glucose and galactosethen releases the parts and is ready to act on another molecule of that substrate.

For food processing, enzymes can be ideal, as they break down molecules into more usable forms while not affecting any other part of the product. For purposes of nutrition, enzymes can help digest certain foods, delivering necessary nutrients in a general sense; they can also help more quickly break down large quantities of certain foods, such as in high protein diets.

Considering their ability to break down foods, it is understandable that enzymes are often featured in digestive supplements. What most drives this supplement segment is the current state of nutrition.The body produces more than 20 enzymes for digestive use in the saliva, stomach and small intestines, while other dietary enzymes must come from plants and animals. Unbalanced dietsconsuming high levels of one nutrient area, such as protein, carbohydrates, dairy, fats, etc.are rampant in todays world. Add environmental toxins and an overabundance of highly refined, processed foods and youve got an enzymatic deficiency problem. Since people and marketing companies have realized the health benefits, there has been quite a push in research and production of digestive enzymes, reported Chris Conn, sales manager for American Laboratories. Digestive disorders such as irritable bowel syndrome, acid reflux and indigestion are common complaints of all consumer categories.

Then there is the combination of an increased aging population and the decrease of bodily enzyme levels associated with aging. Recent research has reported that as people get older, the amount of digestive enzymes produced by the pancreas and intestinal tract decreases. This may increase the risk of indigestion, acid reflux, lactose intolerance and flatulence, noted Mark Anderson, Ph.D., director of research and development for Triarco Industries. As the size of the geriatric market increases, the demand for enzyme formulations also will certainly continue to increase.

An offshoot of the digestive aid category is sports nutrition, one of the strongest niche markets for enzyme supplements. Unsurprisingly, athletes can have extreme dietsthe ratios of carbs, proteins and fats are not typical of the conventional nutrient profile. Reports of protein consumption have indicated that athletes on high protein diets may be consuming as much as one to two grams of protein per kilo of body weight, Anderson said. He added complaints of gastrointestinal distress and flatulence due to high protein consumption suddenly became more common. The reason was not all of the protein consumed was getting absorbed because there were not enough endogenous enzymes present during the transit time of the protein.

By affecting the absorption of nutrients, enzymes are also useful in weight management, another digestion-related market segment. For many people who joined the low carb craze, proteolytic enzymes can help better digest the high protein intake; while, for people with large fat and sugar intakes, amylase (for carbs) and lipase (for fats) are two popular enzymes that can help.

A non-digestion area of enzymatic supplementation is the market for anti-inflammatory products. With all of the news these days about how heart disease is possibly caused by inflammation, and with the removal of several previously accepted RX drugs and OTC remedies (i.e. Vioxx, etc.), there is little doubt that the confirmed role of enzymes in antiinflammation will be the big news, said Gabrielle Sill, marketing manager for Specialty Enzymes. This includes any inflammatory diseases and conditions, as well as general inflammatory conditions, such as those normally treated with nonsteroidal anti-inflammatory drugs (NSAIDs). Papain from papaya and bromelain from pineapples are two popular enzymes with anti-inflammatory properties. Proteolytic enzymes, or proteases, have been indicated for use in quelling the antiinflammatory aspects of diseases such as various arthritic, respiratory and cardiovascular diseases. Actions on inflammation have also placed proteases, as well as lipases, in the natural cosmetics market, especially where inflammation causes skin problems.

While the benefit of better nutrition via improved digestion of nutrients will generally help prevent many conditions and ailments, enzymes could be used to target specific molecules or reactions that lead to specific damaging events. Enzymes are good at breaking down toxins and can lessen stress on the pancreas and liver. Also, the cancer market is huge in dietary supplementation, and enzymes have been indicated in regulating cancer cell activity.

By virtue of their universal biochemical role, enzymes could really be considered and studied for beneficial effects in every aspect of human health. However, the work ahead for the enzyme market is to win better public acceptance of the efficacy and quality of enzyme supplements. In the United States enzymes are not traditional dietary supplements,

Anderson noted.Many health care professionals, including researchers, are taught that oral enzyme supplements simply do not work because they are protein and protein is digested, thus deactivated in the gut.

While this may be true for enzymes derived from animal sources, it is simply not the case for enzymes derived from plant sources. Plant enzymes have different amino acid sequences than animal-derived enzymes. A specific amino acid sequence is essential for the digestive enzyme to recognize and digest a protein, Anderson added. In fact some of the most potent digestive enzyme inhibitors known, such as starch blockers and trypsin inhibitors, are derived from plants.

As the market for enzyme supplements continues to make progress in various areas of human health, more such products will undoubtedly be in development. For manufacturers interested in bringing an enzyme product to market, there are many important factors to consider, among which are target health areas, ingredient sourcing, formulation, potency and testing.

Various factors in the active environment can affect the nature of an enzyme. Just as each type of enzyme catalyzes one specific substrate, each also has very specific temperature and pH requirements. Anything too far below an enzymes optimum temperature causes virtual inactivity, while anything too high above can denature or destroy the enzyme. Likewise, any significant deviation from its optimum pH can also render the enzyme denatured.

These concerns are important to a manufacturer looking to produce a supplement with a specific health benefit in mind. Suppliers such as Deerland Enzymes and Specialty Enzymes provide ingredients along with detailed information about each ingredients propertieseffects of temperature and pH; inhibitors, substances that affect or limit the enzymes activity; level of use; and requirements for storage and packaging. Thus, a good supplier will save a manufacturer a good portion of the research effort required to bring an enzyme product to market.

Formulation might pose a bigger challenge. Single enzyme products or blends of a single enzyme category work well for specific needs or targeted digestion, according to Anderson, whose companys Aminogen and Carbogen products each are blends of single enzyme families. For instance, people who need help digesting high levels of consumed protein would need only proteolytic enzymes.However, most people eat a variety of foods in large quantities and would require a variety of enzymes to aid digestion. This would result in different enzyme families blended to benefit general digestion. Customization is king, said Troy Aupperle, president of Enzymology Research, noting the specific needs of consumers combined with the specific actions of various enzymes drive product formulas. The benefit of an enzyme blend is that it makes formulation easier for a manufacturer, Conn said. All they need to know is which enzymes they need, the desired potency (their label claim) and how many milligrams they need in each tablet or capsule, and the supplier can do the rest.

One of the ongoing debates in the industry is which enzyme product delivery system is ideal. The answers elusiveness owes to the specific properties and actions of each enzyme, as well as the desired product result. No one enzyme delivery system is going to address even a tiny fraction of the endless possibilities they could be used for, Aupperle said. Enteric coating enables an enzyme to pass unscathed through the stomach and into the intestines, where certain enzymes (mostly pancreatic) best perform. Still other enzymes can withstand the low pH of the stomach and require no coating. According to Anderson, the primary choices are capsules and packets because of stability issues. Fueling the debate is the introduction of new delivery systems, such as Bio-Tract from Nutraceutix Inc., which has manufactured finished enzyme products for many years and initially patented BIO-Tract for probiotic supplements. BIO-Tract technology works to deliver a tablets payload past stomach acids in order to release ingredients in the intestines, said Tim Gamble, vice president of sales and marketing for Nutraceutix. This has applications for a variety of payloads that need to reach optimal sites in the intestines regardless of the activity ranges of the ingredient or its ability to survive transit through stomach acids. He noted some enzymes, like most probiotics, benefit from protection because they can be denatured by stomach acids. Other enzymes, although hardy enough to survive and be active in the stomach, may be delivered directly to intestinal sites (prevented from being significantly active in the stomach) by BIO-Tract, thereby satisfying consumers looking for this kind of optimal delivery and the additional safety and benefits it may provide, Gamble said.

What could prove to be the most difficult aspect of producing an enzyme supplement is achieving and ensuring the enzymes activity levelthe mother of all markers of enzyme potency. Unlike vitamins, enzymes cannot be measured simply by quantity or weight. Instead, potency is measured by assaying the quantity of hydrolysis that occurs under specific conditions. This includes a range of concentration, quantity, pH, temperature and substrate. Unfortunately, the greater enzyme industry has no standardized assay. Currently, there are a lot of different [activity] units associated with each enzyme, noted Conn, adding that some companies create their own, non-standard units to defend against formula copying. There is no way to determine the actual potency of a product without testing it in a lab using a specific reference standard.

Currently, two reference standards exist for enzymesthe Committee on Food Chemicals Codex (FCC), which focuses on food grade ingredients and provides assays more generally used for microbial and plant-based enzymes; and the U.S. Pharmacopeia (USP), whose testing is generally directed more toward pharmaceutical-use enzymes and whose methodology is more often employed for assaying animal-derived enzymes.

Beyond all these steps, a manufacturer should concentrate on suppliers with many years of specialized experience in enzymes. For example, American Laboratories has 35 years, Triarco has 15 years, Deerland has 15 years, and Specialty Enzymes Co. has 20 years experience in enzymes. National Enzyme Co. has been around since 1932 and maintains an extensive information resource called Enzyme University (www.enzymeuniversity.com); while Enzyme Development Co. has been in business since 1953 and provides a comprehensive Buyers Guide to Enzymes on its Web site, www.enzymedevelopment.com.

As is the case when sourcing any dietary supplement, manufacturers should check the suppliers facilities and quality programs (GMPs, etc.) as well as request the usual certificate of analysis. Testing enzymes is a tricky enterprise, so a review and tour of a suppliers testing procedures and laboratories is also vital in finding a quality source.

Despite the challenges, the industry of enzymes is in a position to reach and benefit an increasing number of consumers; and responsible, well-educated manufacturers and suppliers will produce quality products that expand this relatively untapped market. Because nothing can ultimately compete with enzymes from an efficiency, cost and safety perspective, the real opportunity has been and will continue to be education. Aupperle said. Once a business owner or consumer understands what enzymes can do for them, its a done deal.