Catalytic Converters

When vitamin and mineral supplementation swept the globe in the early 1900s, it was the right intervention at the right time. Millions who might otherwise have succumbed to devastating diseases like rickets or pernicious anemia found themselves, with a simple dose of vitamin D or B12, protected against these scourges.

Even today, vitamin and mineral supplements save lives. But in the developed West, vanquishing diseases of deficiency aren’t as relevant as maximizing performance and wellness. Which is why enzyme supplements are the right intervention for right now. Positive research findings, coupled with formulation improvements, position enzyme supplements to pick up where vitamins and minerals left off. And that could be just the catalytic converter our postmodern lives need to rise to the next level of health.

You’ve Come a Long Way

Nobody would claim that enzyme supplementation is as mainstream as the daily multivitamin just yet, but it’s come a long way. “What’s interesting is that when you look back at how many enzymes were in use in supplements in, say, 1980, it was about five or six,” recalls Christopher Penet, vice president of BIO-CAT (Troy, VA). “Today, we buy and blend over 60 different enzymes for our customers. So it’s grown very large in terms of the number of enzymes that people are using in their supplements to achieve whatever benefit they’re looking for.”

Credit the growth to the usual suspects, as well as to some less usual ones. On the usual side, there’s the internet and the information it offers curious consumers. A robust retail environment lets GNC, The Vitamin Shoppe,
and even Walmart spread enzyme awareness and purchasing power, as well. But what’s newly promising is an emerging generation of healthcare professionals that seems more bullish on enzyme supplementation than its predecessors-and we’re not just talking “alternative” practitioners, like naturopaths and chiropractors, either. Says Scott Ravech, CEO of Deerland Enzymes (Kennesaw, GA), “we’re starting to see more mainstream medical practitioners, such as gastroenterologists, recommending enzyme therapy to their patients.”

Consumers in Control

Given rising healthcare costs, consumers may be onto something. Consumers increasingly turn to enzyme supplements as a hedge against-though not a cure for-everything from poor nutrient absorption to flagging energy. As Penet notes, “The consumer looks at these products as cost-effective alternatives that might help them avoid stressing their flexible healthcare spending accounts.”
It’s part and parcel of a “proactive” approach that Ravech says characterizes today’s dietary supplement users. “Consumers have taken it upon themselves to do their own research into finding the best supplements for their particular conditions. And, for many with digestive discomfort or pancreatic deficiency, they’re finding their way towards enzymes. All of this collectively is driving significant growth within this category,” says Ravech.

The Sound of Science

So, too, is the growing body of evidence supporting enzyme supplementation’s effectiveness. “I think that’s another big piece that’s helping us-that the science is getting better,” says Ravech.

Not all of this science is new. “Certain enzymes, such as lactase and alpha-galactosidase, have long been studied in clinical trials,” says Danielle Harrison, scientific and regulatory affairs manager for National Enzyme Co. (NEC; Forsyth, MO). It’s no coincidence that both have enjoyed years of use by those with difficulty digesting, respectively, the milk sugar lactose and the glycolipids and glycoproteins found in some legumes.

“Indeed, recently EFSA allowed digestive claims for lactase in the European Union after reviewing the clinical data,” Harrison continues. “These enzymes differ from other digestive enzymes because they have defined markers that are easily measured. Unfortunately, many digestive enzymes lack an easily measured marker, and/or their products are closely regulated by the body’s homeostatic mechanisms, which makes clinical testing in a healthy population difficult.”

Nonetheless, those in the enzyme business plow ahead with research that they hope will grant their category more cause-and-effect legitimacy. As Ravech says, “Everything we’re doing with respect to new products and innovation is science-supported. We’re doing significantly more research and development-in vitro, in vivo and when applicable, human clinical studies.”

Enzymes for All

To whose benefit does all this research redound? It certainly helps the marketers seeking acceptability for their products. It’s also a boon to supplement manufacturers who might want to add enzyme formulations to their line. But, ultimately, the more we learn about what enzyme supplements do, the more we benefit those who use them. And, to hear industry insiders tell it, that should be all of us.

“Nearly everyone who has experienced occasional indigestion-and that means nearly everyone-can benefit from a well-formulated digestive enzyme supplement to reduce occasional digestive discomfort,” says Richard Mihalik, director of innovation and product development at NEC. While our cells do make their own enzymes, he adds, “They don’t always express the correct ones in the right ratios for our diet.”

Consider lactase. Nearly all of us express lactase sufficiently as newborns. As we age, though, many lose some ability to produce this enzyme, leading not only to digestive distress, but also to the disqualification of an entire category of healthful dairy products from consumption. And it’s not just lactase production that declines with age; expression rates for other enzymes, such as intestinal lipase, wane over time, too.

Eater’s Digest

“Our lipase production also adapts to our diet,” Mihalik adds. “If we are used to eating a relatively low-fat diet and have a fatty meal, we can overwhelm lipase production, resulting in digestive discomfort. Supplemental lipases can help avoid this situation by providing additional lipase digestion in the stomach and into the intestines, reducing the burden on pancreatic lipase.”

But how many of us are used to eating a relatively low-fat diet these days? If the statistics are to be believed, not many. And that’s part of the problem, as a heavily processed, high-lipid diet itself can contribute to digestive problems. Add to the mix ambient stress and unhealthy habits-both of which “modern Western culture has plenty of,” Mihalik says-and you’re staring at a case made for enzyme supplementation.

Enzymes help undo the ravages of our modern lifestyles by, quite simply, “supporting healthy digestion while helping the body extract nutrients from the foods we eat,” Mihalik says. Indeed, much of enzyme supplementation’s value boils down to a matter of basic healthy digestion. That’s because of all the processes our bodies perform to sustain themselves, explains Ravech, none uses more energy than digestion. As catalysts, enzymes help lower the activation energy required to facilitate digestion by more rapidly breaking down the nutrients contained in the food we eat. “If your digestive system is as efficient as it can be,” he says, “the resulting improved nutrient and protein uptake will also positively impact overall wellness issues like immunity, cardiovascular health, energy, fat burning, and even mental health.”

Cross-Functional Catalysts

Indeed, while enzymes’ value starts with digestive health, it certainly doesn’t end there. “Nearly every healthy system of the body can benefit from improved nutrition,” Mihalik says, “and enzyme formulations can be targeted to support absorption of nutrients important for those systems.”

Take cardiovascular health. “Absorption of nitrogen-rich amino acids such as L-arginine is important for maintaining elasticity in the vascular epithelium because they are used in the production of nitrous oxide by the body,” Mihalik explains. But age-related declines in digestive-enzyme expression can lead to poor protein absorption, leaving us with fewer of these building blocks necessary for healthy vascular tissue and heart muscle. “A well-formulated digestive enzyme supplement, including the correct proteases, can ensure that the raw materials for healthy muscle support, including heart muscle, are available for absorption,” Mihalik says.

Then there’s the role that enzymes play in guarding against everyday oxidation. During the course of cellular respiration, the body produces the highly reactive superoxide radical. Under normal conditions, the enzyme superoxide dismutase neutralizes this to the somewhat-less-reactive peroxide radical. That then goes on to be neutralized to water by either the enzyme catalase or the antioxidant glutathione. But when conditions aren’t normal, as when the body suffers physical or psychological strain, its antioxidant system gets swamped, and we enter a state of oxidative stress that, left unchecked, can damage cells and tissues.

“Fortunately, supplemental antioxidant enzymes are available for both superoxide dismutase and catalase,” says Mihalik. “By reducing oxidative stress, superoxide dismutase in particular may have potential benefits in cognitive health, sleep quality,
fatigue, anxiety, and even cellulite.” And, unlike other supplemental antioxidants, enzymatic antioxidants aren’t “consumed” in the oxidative reaction, which keeps them in shape to do battle with free radicals further down the line.

Peak Performance

Enzymes’ benefits are broader, still. “Claims for immune support are well documented for the enzyme combination of lysozyme, lactoperoxidase, and lactoferrin,” Mihalik says. “And melon superoxide dismutase has good evidence supporting its use as an antioxidant enzyme with systemic benefits ranging from cognitive wellness to endurance.”

In fact, endurance and sports performance may be the most promising targets for enzyme formulations to explore. “Energy levels are important to sports performance,” Mihalik points out, “so digestive enzymes can help ensure that athletes get all the energy they need from the food they eat.” As evidence, he points to studies demonstrating enzyme-enhanced nutrient absorption under training-induced depletions, as well as animal and other models suggesting that a strategic digestive enzyme formulation can improve nutrient availability.

Such a formulation might include carbohydrates “to ensure that glucose levels are adequate for muscle growth,” Mihalik notes. Proteases are also obligatory to release key branched-chain amino acids isoleucine, valine, and leucine, the last of which helps activate the anabolic mTOR pathway.

These proteases are particularly important in sports formulations because of protein’s role in muscle building and recovery. The proteins “need to be broken down quickly and effectively so that their amino acids are absorbed in the small intestine and shuttled to the muscles,” says John Deaton, PhD, vice president of technology and R&D at Deerland. But when you feed the body an especially large protein such as whey-popular with athletes for its demonstrated muscle-building effects-“the body ends up excreting a lot of it because it just can’t break it down fast enough,” Deaton says. That’s why he and his colleagues designed their protease formulation ProHydrolase to break down proteins “more quickly and effectively within a short period of time.” The formulation has exceeded expectations at all levels of testing, which includes in vitro (gel electrophoresis) and human clinical studies.

Staying Alive

Even after establishing efficacy in clinical trials, how do we maintain the efficacy of enzyme supplements over the course of their lifetime? Extremes in pH, temperature, moisture-even pressure-can all do a number on enzyme morphology and behavior.

Penet points out that contemporary enzyme ingredients are designed for hardiness. Frequently products of microbial fermentation, “the enzyme supplements and blends of today are picked from sources that allow them to be effective at the pH and environment of the stomach,” he says. Harrison of NEC adds that supplemental enzymes begin their work in the upper part of the stomach, where food waits before being mixed with gastric acid and pepsin. Once the enzymes come into contact with these secretions, the food itself buffers the pH and offers some protection to the enzymes.

But conditions on the shelf can also compromise an enzyme supplement’s effectiveness-if you don’t guard against them in formulation. The main threats here are heat and moisture.

“Above room temperature, enzymes can denature, or unfold, and become inactive,” Mihalik says. Moisture, by contrast, activates enzymes prematurely, letting them go to work on each other in the tablet or capsule before the consumer even consumes it. This can result not only in loss of dosage-form integrity and enzyme activity, Mihalik says, but in off flavors that make the product less palatable. To avoid these issues, we recommend storage of enzyme products in cool, dry places,” he says.

As far as delivery formats go, the most popular and stable is the dry-powder capsule. Unlike tableting-the pressures of which can generate heat sufficient to denature some enzymes-the encapsulation process treats ingredients relatively gently. The anhydrous environment of the content within delays early activation, and the capsule itself provides a barrier that, to some degree, protects what’s inside.

Given that we measure enzyme potency differently than we do vitamins and minerals, a small capsule isn’t necessarily a weak one. “Consumers have become locked into this paradigm that milligram weight is
directly proportional to potency,” Ravech says. “In the enzyme world, that’s not the case. We don’t use the word ‘potency’ as often as we do ‘activity.’” By starting with a highly concentrated enzyme formulation,” he says, “you can put a very small amount into a supplement and still achieve high efficacy.”

Nevertheless, FDA still requires labeling enzymes with metric units. “Distributors and marketers of enzyme supplements have met this requirement by creating proprietary enzyme blends that list a total milligram content of the blend while listing individual enzyme activities as components of the blend,” Harrison says. “In this manner, labels are both compliant and relevant.”

Moving Ahead

Speaking of relevance, Penet has this advice for manufacturers exploring enzyme supplement design: know your supplement’s goals, and keep them in check as you proceed.

“We see a lot of manufacturers who try to put a lot of enzymes into their formulas,” he says. Penet’s company sells several different proteases to the dietary supplement market, for example. “But, at the end of the day, do you really need more than a few in there?” he asks. “I think the key is understanding the target benefit that you want your product to achieve. Then, it’s easier for us to have a conversation to help you formulate it.”

Penet also welcomes any challenges his customers and the public throw the enzyme arena’s way. “The industry needs to provide more science,” he says. And increasingly, it does. “We’ve got two university collaborations going on right now, as well as clinical trials,” says Penet. “So we’re trying to put some science behind this information. We believe there is a benefit, but we have to prove it.”

Secret Ingredients: Enzymes in Food vs. Enzymes in Us

In the supplement industry, we tend to focus on the role of enzymes in us: how they improve health and boost our performance. But it’s worth noting that a whole other arena of enzyme activity exists-and it’s as close as your own kitchen.

This shouldn’t be surprising, considering that enzymes are natural components of foods themselves. But, in products ranging from bagels to beer, enzymes added intentionally-and safely-to formulations catalyze reactions that make these
products better.

As Simon Walley, regional director of food enzymes at DuPont Nutrition & Health (New Century, KS), says, “Enzymes are used in a wide variety of space, from extending shelf life and improving textures in bread to making light beers, to making dairy products lactose-free. The solutions help reduce waste, improve yields from raw materials, and assist with promoting health benefits-as with gut health.”

And the scientific ferment surrounding enzymes in food production is as bubbly as it is surrounding enzymes for health. “There’s as much research going on in the ingredient-development side as there is on the dietary supplement side,” says Penet “When you think historically of enzymes in food processing, the market for high-fructose corn syrup wouldn’t exist today without enzymes. Brewing, baking, light beers, wine, fruit juice, the extraction of higher yields from the grapes and apples, yogurt, cheese, cured meats: all are made through the biochemistry of enzymes. And we don’t want people to lose sight of that.