Enzymes are biological catalysts. A catalyst is defined as a substance that increases the rate of a chemical reaction without itself undergoing any change. Enzymes catalyze most chemical reactions that take place within living beings. For example, in the body there are about 21 enzymes involved in the conversion of a molecule of glucose to carbon dioxide and water, accompanied by release of energy. Without these enzymes metabolism would stop and so would life. Enzymes are capable of enormous rate enhancement of chemical reactions that take place in biological systems. They can accelerate the rate of a reaction from anywhere between a thousand-fold to a billion-fold, and this rate enhancement is necessary to sustain life.

Background
The word enzyme has its roots in Greek, literally meaning “in yeast.” Enzymes were first discovered in 1833 by Anselme Payen and Jean Persoz when they found that an alcohol precipitate of malt extract contained a thermolabile substance, which converted starch into sugar. During the early days many similarities were discovered between the action of enzymes and that of yeast. This led to much controversy between Louis Pasteur, who believed that fermentation was inseparable from living cells, and Justus Freiherr von Liebig, who proposed that these processes were the result of chemical action. Eventually Liebig was proved right by Eduard Buchner, who was successful in fermentation using cell-free extracts of yeast.

The study of enzymes did not progress much further until about the 1920s when enzyme purification was possible, which led to the crystallization of the first enzyme, urease. Following these developments, John Howard Northrop and co-workers were able to isolate and crystallize proteolytic enzymes, which provided conclusive evidence that enzymes were proteins that are active outside of cells. The size of an enzyme can vary anywhere from a few hundred to a few thousand amino acids. Most enzymes are only active in water and are very specific toward their substrate, which means that they will speed up only one type of reaction and are ineffective toward other systems. This specificity can be elegantly explained by the lock and key analogy, where substrate fits in the enzyme active site like a lock fitting its key. Enzymes are very delicate and small changes in pH or temperature or ionic strength can deactivate them. Sometimes even mechanical shock can render them inactive. This fragility is inherent to most proteins but especially to enzymes, since their 3-D (three-dimensional) structure or tertiary structure plays an important role in their activity. Figure 1 (previous page) illustrates a 3-D rendering of an enzyme.

Since the discovery of enzymes in 1833 they have found applications in various industries. Today they are widely used in food processing and industrial applications, including household cleaning supplies like laundry detergents. The use of enzymes not only speeds up industrial processes but also makes them cheaper thereby reducing the price of consumer goods. An even more interesting application of enzymes is in the dietary supplement field.

Dietary Supplement Enzymes
The dietary supplement arena for enzymes may be broadly categorized into two fields: digestive and systemic applications. Most everyone has heard of products such as Lactaid and Beano. These products contain the digestive enzymes lactase and a-galactosidase respectively. People who are lactose intolerant have a deficiency of the enzyme lactase and hence have to depend on exogenous sources of that enzyme. Similarly, several people are deficient in the main digestive enzymes like proteases, lipases and carbohydrases and hence cannot properly digest food. This can lead to various digestive maladies such as constipation, bloating and gas, which most Americans consider normal digestion. The truth is, digestion is not supposed to create discomfort.

Additionally, most food products people eat currently are highly refined and processed. Modern food processing techniques not only reduce the nutrient content of food but also kill all the enzymes that are present in raw food. This presents an unusual burden on the body’s digestive system on top of which is the problem of overeating and excessive fats and carbohydrates in the diet. Since most people are reluctant to change dietary habits, the best solution to this problem is taking an enzyme supplement that contains all the digestive enzymes to properly digest food. Taking an enzyme supplement with food can relieve many of the problems associated with digestion.

The second major category of enzymes sold as dietary supplements is systemic in application. Most of the enzymes considered for systemic use are those that break down proteins (proteolytics), and can help various conditions related to inflammation. There is a plethora of research available that delineates the absorption and mechanism of action of proteases on the various systems in the body involved in inflammation. Current research has shown that proteases that possess fibrinolytic activity could help people with high blood pressure and other cardiovascular problems. Additional recent research also predicts that enzymes could help people with various gastrointestinal diseases like celiac sprue and irritable bowel syndrome (IBS).

Formulation Challenges
In the dietary supplement field the main challenge to providing a quality enzyme supplement is the formulation. The formulation of an enzyme supplement presents various difficulties and only an experienced manufacturer can produce a good product. One of the most important aspects of formulation is the activity of the enzymes in the supplement. The quantity of enzymes in a product should always be listed in activity units and not in weight. (Listing the enzyme activity in terms of weight of a product is the same as somebody asking you your IQ and you telling them your weight.) The quantity of enzymes in milligrams means nothing unless the corresponding activity is also mentioned.

The manufacturer of an enzyme supplement should also be able to guarantee the activity of enzymes in the supplement for the shelf life on the bottle. This entails performing assays on enzymes in the product at various stages in the manufacturing process. This requires an enormous amount of expertise and any enzymologist will say that the behavior of enzymes in an assay can very well depend on the weather.

Another aspect of formulation is the dosage. The dosage for each person will vary with the type and quantity of food; and the best way for someone to figure out their dosage is by using a quality enzyme supplement that will deliver the same enzyme activity in each capsule.

Consumer Awareness of Enzymes
Another hurdle in the use of enzymes as dietary supplements is the general awareness about this subject. The field of enzymes seems esoteric to most people and many times it is not an easy subject to explain. In addition, there is the attitude prevalent among most Americans that some discomfort with meals is a normal way of life. Despite this, consumer awareness levels are growing at a tremendous rate. As more research and information is presented to the public, more people are realizing the enormous benefits enzymes offer.

As a manufacturer or distributor of enzymes, the most important thing that can be done to increase consumer awareness is to educate. Everyone in the supply chain must know the importance of enzymes, from the sales staff at the manufacturing company to the retail store clerk.

Although most of the general public has not heard of digestive enzyme supplements, the awareness level is growing and so are the sales of enzyme supplements. In 2001 the U.S. nutrition industry reached $53 billion sales, $2 billion of which were in the specialty category where enzymes are classified. How much of that is in enzymes sales, no one can say for sure. However, it is known that enzyme sales have been increasing steadily over the past few years showing no signs of slowing down. In almost every trade journal that lists predictions for the growth in particular types of supplements, digestive products are listed in the top 10. In addition, enzyme therapies have been proposed as a possible area of study by the NIH’s National Center for Complementary & Alternative Medicine (NCCAM). The publicity from such a study could greatly increase the demand for enzyme products.

Who Buys Enzyme Products?
One way to evaluate the potential market for enzyme supplements is to look at the percentage of the population that might purchase this type of product. Statistics vary, but estimates indicate that 20-75 million people in the U.S. suffer from some sort of digestive disorder on a regular basis. In a report in the June 2000 issue of Digestive Diseases and Sciences, researchers studying the effects of the fat substitute, olestra, coincidently discovered that pre-existing digestive symptoms were reported in the month prior to the study in approximately 41% of the study respondents. Because of the stressful lifestyles consumers lead today, as well as the large quantity and poor quality of the food that is eaten, problems with digestion are a logical consequence. This creates an enormous market, as people are seeking better ways to combat gastrointestinal problems that can range from being frustrating and embarrassing to debilitating.

The enzyme market is taking off and research is allowing for new applications in all areas of science. In the very near future we are going to see enzymes become as common in the medicine cabinet as calcium is today.

About the author:
Rohit Medhekar is technical resources manager for National Enzyme Company, Forsyth, MO. He can be reached at 800-825-8545; Fax: 417-546-6433; rohit_medhekar@nationalenzymecompany.com; Website: www.nationalenzymecompany.com.