There are four main proteolytic enzymes used by DCs. Two are animal based, and two are vegetable based.
Chymotrypsin is a proteolytic enzyme crystallized from an extract of the pancreas gland of the ox. One USP unit of chymotrypsin is the activity that causes a change in the absorption of 0.0075 of a substrate solution N acetyl L tyrosine ethyl ester under conditions specified in the United States Pharmacopeia Assay.1
Trypsin is a proteolytic enzyme also crystallized from an extract of the pancreas gland of the ox. One USP unit of trypsin is the activity that causes a change in the absorption of a substrate solution of N benzoyl L arginine ethyl ester hydrochloride of 0.003 per minute, under the assay specified in the United States Pharmacopeia reference guide. 2500 USP units of trypsin may contain no more than 50 USP units of chymotrypsin.1
Papain is a purified proteolytic substance derived from carica papaya. One USP unit of papain activity is that which releases an equivalent of 1 mg of tyrosine from a casein substrate solution as described in the United States Pharmacopeia reference guide.1
There is no USP reference standard for bromelain. It is a proteolytic enzyme extracted from the pineapple. Its highest concentrations are in pineapple stems.2,3 Bromelain is not a pure substance. In addition to a proteolytic enzyme, it also contains small amounts of acid phosphatase, peroxidase, several protease inhibitors, and a small amount of organically-bound calcium.4
In preparing this article, I contacted some of he nation's leading nutritional biochemists and nutritional orthomolecular medical and chiropractic physicians. As I stated last month, the weight and activity measure of proteolytic enzymes is totally convoluted. As an example, some of the units of enzyme measurement I found included Armor units, Roggin units, National Formulary units, caseinolytic units, milligrams, micrograms, gelatin-dissolving units, milk-clotting units, and United States Pharmacopeia, or USP units, which are not equal. It is impossible to convert a USP unit of trypsin chymotrypsin, and papain to a common denominator of enzymatic activity. This is because, if you notice, the United States Pharmacopeia uses different substrate solutions to calculate their USP value for each enzyme. I did, however, find the following conversions. These will be helpful in comparing the same type of proteolytic enzyme from company to company.
Chymotrypsin 1 mg = 1,000 USP units
Trypsin 1 mg - 25,000 USP units
Papain 1 mg = 6,000 USP units
The most common measures for bromelain I found were gelatin-dissolving units and milk-clotting units. When I contacted Dr. Roger Dabba, a biochemist at the United States Pharmacopeia, he stated that there is no conversion of gelatin-dissolving units to milk-clotting units. I recommend that you look to companies who list their activity unit to weight conversion factor on the label. Thus, with some simple mathematics, this will give doctors precise comparison of milligram amounts of products that are measured with the same units of activity, as well as a ballpark idea when you are comparing products based on GDU versus MCU. Note: Although pineapple and papaya do contain proteolytic enzymes, eating these fruits will not reduce inflammation. As we have reviewed, to have a physiological effect, enzymes must be enterically coated. The consumption of pineapple and papaya will help break down any protein that is present in the stomach, and in times of injury the body does require additional protein. Thus, there is nothing wrong with instructing your patients to increase their consumption of these fruits.
In my literature search, I did not find any peer-reviewed reference papers that attempted to compare the activity of equal weights of the various proteolytic enzymes. Again, based on personal experience, I feel that the vegetable-based enzymes (bromelain and papain) that are obtained from quality conscious companies who provide assays are fairly close in their activity. However, when comparing animal-based enzymes, a milligram of chymotrypsin is much more powerful than a milligram of trypsin. It is also much more expensive. Thus, many of the combination formulas will only contain very small amounts of chymotrypsin.
To summarize dosing, there is an extreme variant of units of measurement of proteolytic enzymes and formulas various companies offer. As the amount of enzyme needed to reduce inflammation will vary depending on the nature and extent of the injury as well as the size of the individual, I recommend that you contact the director of biochemistry of the company you are dealing with for dosing advice. This person should be able to instruct you on doses that are effective (remember, label instructions on proteolytic enzymes are extremely conservative mainly due to regulatory agencies).
Below are some hypothetical examples of the dosing amounts myself and nutritional-oriented doctors will use. This is not a cookbook and varies widely, depending on the nature and extent of the injury, as well as the size, age, activity, and general health of the patient. I have included this just to give doctors a general idea of the amounts of micronutrients needed to facilitate rapid healing and to stimulate the patients to make statements like, "That stuff really helps me." This is a hypothetical example of a grade III ankle sprain of a 200 pound male. For severe sprains, I will use separate vegetable and animal-based proteolytic enzyme products.
Grade III: Bromelain 400 mg per enterically-coated tablets (with activity measurement and conversion stated on the label), three tablets four times a day on an empty stomach for the first five days; two tablets four times a day on an empty stomach for the second five days; four tablets in the morning and four at night for the third five days. Chymotrypsin 7.5 mg per enterically-coated tablet with USP activity conversion on the label, three tablets four times a day for the first five days, and two tablets four times a day for the second five days. Additional nutritional support consists of 100 mg B complex, preferably 50 mg with breakfast and 50 mg with dinner; a minimum of 2,000 mg vitamin C with a minimum of 1,000 mg bioflavonoids; one and one-half times the RDA of calcium and magnesium; with three to five times the RDA of zinc and manganese; with 100 percent of the RDA of other minerals for two to three weeks. Patients are also instructed to try to consume at least an extra 40 ounces of fluid per day and to increase their protein intake to 1 gm per pound for three weeks.
Grade II: I will use either the bromelain or chymotrypsin formula mentioned above with a dose consisting of four tablets four times per day for the first five days, with four tablets in the morning and four tablets in the evening (again on an empty stomach) for the next five days. Additional micronutrient support: a 50 mg B-complex with a minimum of 1,500 mg per day of vitamin C; 750 mg per day of bioflavonoids; with 100 percent RDA of all minerals with the exception of zinc and manganese, which are increased two to three times the RDA.
Grade I: I will use lower potency combination formulas that also contain support factors. One enterically-coated tablet will usually contain approximately 100 mg of bromelain, 75 mg of papain, and 50 mg of trypsin, along with vitamin C, bioflavonoids, and zinc. Patients will take four tablets three times per day away from food for three to five days, and this will be backed by a multivitamin, multimineral formula that contains 100 percent of the RDA of all minerals with a B-complex of at least 10-25 mg, and vitamin C of 500 mg.
Should you have any questions concerning specific dosing protocols, feel free to contact me at my office.
- United States Pharmacopeia/National Formulary, USP 22/NF 17, 1990. The United States Pharmacopeia Convention, Inc., Rockville, Maryland 20852.
- Taussig S, et al: Hiroshima Journal of Medical Science, 24(2): September 1975.
- Miller J, et al: The administration of bromelain orally in the treatment of inflammation and edema. Exp. Med. Surg, 22(4): 1964.
- Taussig S: The mechanism of the physiological action of bromelain. Medical Hypothesis, Vol 6, 1980.
G. Douglas Andersen, D.C.
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