Unlocking the enzyme market

Enzymes used for food-processing aids are buoyant but enzymes that confer health benefits have been slow to win over both scientists and consumers. Mark J Tallon, PhD, unveils new research that may change all that

Although the enzyme market is full of CEO opinions on enzyme supplementation, very few studies are reported within trade media. If the enzyme market is to grow, the applications and real science of enzymes must penetrate down from raw-ingredients suppliers, product developers, and marketing and sales teams to the end consumer. Recent cutting-edge research may just provide the fuse to potentially the biggest ingredient boom in a decade or more.

A gluten for punishment
According to a report from Mintel, gluten-free products captured approximately $450 million in retail sales in 2004.1 More than one million Europeans are thought to suffer from celiac disease, a permanent intolerance to the wheat-gluten proteins and the related proteins in barley and rye.2 Ingestion of these proteins by genetically susceptible individuals (celiac-disease sufferers) causes abnormalities of the small intestine, culminating in flat intestinal mucosa and producing a large variety of symptoms including failure to thrive, malnutrition, diarrhoea and anaemia.3

From gluten-free formulations to exercise recovery, enzymes find their moment
There is strong evidence that celiac disease is a T-cell-mediated immune disease. In a recent study, Dutch researchers assess-ed a proteolytic enzyme extracted from the fungus Aspergillus niger. 3The gluten-derived T-cell epitopes (causing negative allergic response in celiac sufferers) are proline rich and thereby highly resistant to proteolytic degradation within the gastrointestinal tract.

Conventional oral supplementation with prolyl oligopeptidases has limitations as they are irreversibly inactivated by pepsin and acidic pH, both present in the stomach.3
As a consequence, these enzymes fail to degrade gluten before it reaches the small intestine, the site where gluten induces inflammation, leading to celiac disease or exacerbation of symptoms in sufferers.

A newly identified prolyl endoprotease from Aspergillus niger addresses this. Gluten was treated with A. niger prolyl endoprotease and shown to work optimally at 4-5 pH, and remains stable at 2 pH. The upshot here is that this natural extract is completely resistant to digestion with pepsin. Moreover, the A. niger-derived enzyme efficiently degraded all T-cell epitopes as well as intact gluten molecules. On average, the endoprotease from A. niger degraded gluten peptides 60 times faster than traditionally used prolyl oligopeptidase.3

Together, these results indicate that the enzyme from A. niger efficiently degrades gluten proteins and may provide an oral supplement to reduce gluten immune response in celiac patients and gluten-susceptible individuals.

Enzymatic beauty
Nutritional therapy is critical for healing wounds in people with severe malnutrition, metabolic deficiencies and, in some cases, post-surgical trauma. Many oral supplements are marketed to surgical patients for decreasing edema and bruising. Proteolytic enzymes have been reported to moderate the inflammatory cycle and as such may enhance the healing process. The goal of one recent study was to examine the effects of an oral enzyme supplement on soft-tissue healing times.4

Twenty-six normal, healthy volunteers were recruited into a randomised, crossover, placebo-controlled, clinical trial consisting of two phases, each lasting 21 days. In phase I, subjects were subjected to a 3mm forearm skin biopsy and randomly received a placebo or oral supplement (four capsules per day for seven days). After a two-week washout period, a second biopsy was performed to start phase II, with each subject receiving the respective placebo or supplement capsules. Digital photographs were taken during wound healing in both phases and analyzed for wound areas (in square millimeters) and perimeters (in millimeters).4

On the basis of wound surface areas, subjects had improved wound healing, and five subjects did not respond or responded only slightly to the supplement treatment. The healing time of the subjects responding to supplement-treated wounds was 15 +/- 2.2 days, compared with 18 +/- 2.5 days for the placebo group. The 17 per cent acceleration of wound-healing time was significant. In subjects responding to oral supplements, less redness in the wounds was observed that might have been associated with less inflammation.

The results demonstrated that oral supplementation with protease enzymes accelerated soft-tissue wound healing in 77 per cent of normal, healthy subjects studied. This validated observations that this enzyme supplement can successfully modulate wound-healing, and suggests that patients with minor soft-tissue wounds, including those recovering from cosmetic surgery, may benefit from enzymes.

Pain-free osteoarthritis
Osteoarthritis (OA) is the most common form of arthritis. Among US adults 30 years of age or older, symptomatic disease in the knee occurs in approximately six per cent and symptomatic hip osteoarthritis in roughly three per cent.5 Because OA is a disease whose prevalence increases with age, it will become even more prevalent in the future as the bulging cohort of baby boomers grows older. Osteoarthritis is the most common reason for total hip and total knee replacement. Because of the longevity of working careers and the substantial prevalence of osteoarthritis in middle-aged persons, OA causes a considerable burden in lost time at work and early retirement.6

The objective of one new study was to establish the efficacy of an oral enzyme therapy (ET) as compared to the non-steroidal anti-inflammatory drug diclofenac (DC) in patients with OA of the hip.7 Ninety patients presenting with painful episodes of OA of the hip were treated for six weeks in one study centre in a phase III, randomised, double-blind and parallel group trial. Primary efficacy criteria were: WOMAC dimensions pain, joint stiffness and function, and Lequesne index as multiple endpoints.

In the majority of patients, tolerability was judged in both drug groups as very good or good. This trial showed significant noninferiority from six weeks treatment with ET in patients with OA of the hip with regard to the WOMAC dimensions pain, stiffness and physical function; to Lequesne's index; to the investigator's and patients' assessments of efficacy; and to the responder rates based on pain, physical function and patient assessment of efficacy. With regard to drug tolerability, some tendencies in favour of ET were detected. However, this study showed no real difference between ET and DC 100mg/day, implying an equal benefit-risk relation between the substances. ET may well be recommended for treating patients with hip OA with signs of inflammation as indicated by a high pain level.

Exercise recovery
In a recent study, researchers from the department of health and human performance at Elon University (USA) have evaluated the capacity of protease supplementation to attenuate soft-tissue injury resulting from intense exercise.8

The study's aim was to evaluate the effects of protease supplementation on muscle soreness and performance after muscle-damaging exercise. The participants consumed two protease-containing tablets or a placebo four times a day beginning one day before exercise and lasting four days.

The enzyme group demonstrated superior recovery of contractile muscle function and diminished muscle soreness after downhill running when compared with those taking placebo. Recovery of muscle function was also enhanced. These results are the first to show that nonenterically coated (to protect from acid in gut) enzyme supplementation can facilitate muscle healing, decrease soreness and allow for faster restoration of contractile function after intense exercise.

What the future holds
The future for enzymes making a successful bid to grow into a substantial market outside of food-processing aids requires a much greater push in consumer education. Cross-market applications from health and beauty to sports nutrition could integrate dietary enzyme supplementation into their product range. Although at this time much of public perception surrounding enzyme use is for digestive health, it is clear from these studies the applications for dietary enzymes are far greater. This wider application and associated marketing will increase awareness, understanding and acceptance, which will provide the catalyst for widespread commercial success.

Mark J Tallon, PhD, is chief science officer of the London-based consultancy firm OxygeniX. www.oxygenix.com He is also co-founder of Cr-Technologies, a supplier. www.cr-technologies.net

1. Mintel Market Reports: Food Allergies and Intolerance. Mintel International Group Limited. 2005
2. Fasano A, et al. Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study. Arch Internal Med 2003;163(3): 286-92
3. Stepniak D, et al. Highly efficient gluten degradation with a newly identified prolyl endoprotease: implications for celiac disease. Am J Physiol Gastrointest Liver Physiol 2006;291(4):G621-9.
4. Brown SA, et al. Oral nutritional supplementation accelerates skin wound healing: a randomized, placebo-controlled, double-arm, crossover study. Plast Reconstr Surg 2004;114(1):237-44.
5. Felson DT, Zhang Y. An update on the epidemiology of knee and hip osteoarthritis with a view to prevention. Arthritis Rheum 1998;41:1343-55.
6. Yelin E. The economics of osteoarthritis. In: Brandt KD, Doherty M, Lohmander LS, eds. Osteoarthritis. New York: Oxford Univ Pr 1998:23-30.
7. Klein G, et al. Efficacy and tolerance of an oral enzyme combination in painful osteoarthritis of the hip. A double-blind, randomised study comparing oral enzymes with non-steroidal anti-inflammatory drugs. Clin Exp Rheumatol 2006;24(1):25-30.
8. Miller PC, Bailey SP, et al. The effects of protease supplementation on skeletal muscle function and DOMS following downhill running. J Sports Sci 2004;22(4):365-72.

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