Response to Dr. Pangborn’s Letter

May 7, 2002

Dr. Pangborn;

Thank you for your input. As a result of your interpretation of the No-Fenol description, I have slightly modified the text of the No-Fenol description to clarify the meaning. I apologize for any confusion it may have caused you. I will address your concerns regarding the proposed mechanism of action of No-Fenol.

Your concerns of tyrosine oxidation by No-Fenol are groundless for several reasons. First, I have no evidence for the presence of a tyrosine-modifying activity in No-Fenol. My reference to “oxidation of phenols” does not extend to amino acids such as tyrosine. While you may classify tyrosine as a “phenol”, most researchers classify it as a non-essential amino acid. The simple fact that tyrosine contains the classic “phenol” structure of a benzene ring with a hydroxyl group (as do countless other compounds) does not necessarily imply that tyrosine is a substrate for the enzymes found in No-Fenol.

Second, enzymes have very specific functions. The metabolic enzymes involved in the sequential conversion of tyrosine to norepinephrine (tyrosine monooxygenase (EC 1.14.18.1), amino acid decarboxylase, and dopamine hydroxylase) are most likely not the enzymes involved in modification of polyphenolic compounds. Again, you may be confusing the fact that because tyrosine has a phenolic moiety as part of its structure, it is naturally a substrate for those enzymes involved in metabolizing polyphenolics. I can’t find evidence to support this conjecture, but I can certainly respect a difference in interpretation of existing research literature. While there is a plant-based enzyme often called “tyrosinase” (EC 1.10.3.1) it is limited to acting upon catechol compounds to produce benzoquinones. While there is evidence that an isoform of these enzymes can occur in certain fungal species, their stability properties indicate that they would not be viable as oral supplements, and so most likely would not be present as accompanying activities in certain fungal enzyme blends. The only other “tyrosinase” is EC 4.1.99.2, which catalyzes pyruvate formation from tyrosine, cysteine, and serine, producing a phenol in the process. This enzyme is dependent upon pyridoxal phosphate for activity, and is not found in Aspergillus species, though it may be the tyrosinase isolated from mushrooms.

Third, tyrosine oxidation occurs naturally in the body due to metabolic enzymes, in fact, one study (James, WP, et al, Clin Sci Mol Med 50:525, 1976) found that 20% of tyrosine flux was due to oxidation of tyrosine in normal human volunteers, expelled as carbon dioxide through respiration. The term “tyrosine oxidation” should not fill us with fear of dreadful consequences.

Fourth, the reactions catalyzed by No-Fenol occur in the gastrointestinal tract, not within the cells of the body. This is an important point for the lay person and you to remember. Supplemental enzymes cannot cross into the cells of our body and initiate chemical reactions. While there is evidence that oral enzymes may cross into the systemic circulaton, they still cannot enter and interact intracellularly. They perform the bulk of their work in the GI tract. IF they did enter cells and affected metabolic processes therein, perhaps we would have solutions to a number of disease states, but we don’t. IF tyrosine were somehow modified by No-Fenol or any other dietary supplement in the GI tract, the effect would be simply to limit dietary tyrosine. As tyrosine is a non-essential amino acid, meaning it is produced from other precursors within the body, any dietary deficiency of tyrosine produced by a supplement would be alleviated by simply not taking the supplement. In othe words, it would be a reversible effect.

So, how does No-Fenol work? Based on the enzyme blends in the product (xylanase, hemicellulase, phytase, and glucanase), we are working under the assumption that the benefits parents are noticing with No-Fenol are due to increased breakdown of plant fiber and complex carbohydrates comprising the plant cell wall. There are possibly additional side activities from other glycosidic enzymes at work, such as amylase and ferulic acid esterase, and we are attempting to assess the potential role of any additional enzyme activities in the benefits of No-Fenol. There is evidence in the literature that phenolic compounds may be modified such that they cannot cross cell membranes, usually through the addition of sugar moieties to the phenolic structure. Once these sugar groups are enzymatically cleaved, the phenol can then be transported within the cells, and disposed of through normal channels of detoxification. As this hypothesis does not quite match the current thinking behind this problem (i.e. sulfation, phenolsulfotransferase deficiency, etc), it may well be that the medical community will re-evaluate the underlying mechanism of phenol intolerance in autism based on the benefits observed with use of No-Fenol.

Since No-Fenol is the first enzyme product to be positioned as supporting the natural assimilation of phenolics, we are obviously still studying and analyzing its function as a digestive aid. Phenolic compounds from plant sources offer significant nutritive value as antioxidants and anticarcinogenics, and it is hoped, as our informal field-testing has indicated, that No-Fenol will allow children and adults to ingest fruits and vegetables without the negative behavioral effects often observed. After all, these kids deserve to be able to eat strawberries, blueberries, and bananas as much as any other child. As with all enzymes allowed by FDA for use in the food industry, standard toxicity testing in animals of the enzymes in No-Fenol has indicated no mutagenic, carcinogenic, or toxic side effects even at very high dosages (see references listed below for partial listing). In addition, No-Fenol is produced in strict adherence to FDA’s current Good Manufacturing Practices and meets compositional and purity requirements as defined in the Food Chemicals Codex, which is a compendium of food ingredient specifications developed in cooperation with the FDA.

I hope this explanation is satisfactory, please note the links below for more information.

Devin Houston, Ph.D.

References:

Pedersen PB, Food Addit Contam 17: 739, 2000

Bergman A, Food Addit Contam 14:389, 1997

Pico Y, J Agric Food Chem 47:1597, 1999

Coenen TM, Food Chem Toxicol 33:859, 1995

Sandberg AS, J Nutr 118:469

Pariza MW, Regul Toxicol Pharmacol 33:173, 2001

Links concerning enzyme food use and safety