EnZymAid

[Guest guest]

Hi, my name is Ilene Buchholz and I am coordinating

Kirkman Laboratories Professional Division in San

Diego. It was suggested that I respond to some of the

questions and concerns that have been asked regarding

the use of digestive enzymes, specifically EnZymAid.

My intent is to clarify some concerns that may exist

about possible reactions to this formulation.

The question was asked if EnZymAid “could lead to

serious bladder problems” as had been reported

occurring with another formula. I would like to share

that the mechanism of action of enzymes specifically

occurs in the gastrointestinal tract, not having

direct impact in the urinary system. It is difficult

to link serious bladder problems with the use of ANY

enzyme formulation and I would caution the linking of

these two.

Regarding the concerns relating to “regression” of

symptoms when taking EnZymAid; the following may be of

some help. Jon Pangborn, Ph.D. wrote a well-documented

article entitled “EnZymAid and Dietary Peptides” which

provides some understanding and explanation of this

situation. Trust this is of help.

Ilene Buchholz, R.N.

EnZymAid and Dietary Peptides

Jon B. Pangborn, Ph.D., F.A.I.C.

Consultant to Kirkman Laboratories

Dec. 2000

BACKGROUND

In 1980, Drs. O. Trygstad, K. Reichelt and others

published initial findings that psychiatric cases,

including autistic individuals, present notably

elevated levels of unusual peptides in their urine.1

Since that time, Reichelt and others have confirmed

and expanded these findings and have identified

particular peptides in autistics as having dietary

origin. 2,3,4,5,6 Examination of these peptides by

amino acid sequencing has shown them to be

“exorphins”, or opiate-acting peptides.4,7,8,9,10

Passage of such peptides into human blood has been

documented.11,12 Specific examples of exorphins are

beta-casomorphins (from casein in dairy products), and

gliadorphin and gluteomorphin (from gluten foods:

wheat, oats, rye, barley). 7,8,9,12 On observational

grounds, Jaak Panksepp predicted this neurochemical

theory of autism in 1979 13, and it is an extension of

deWied’s pioneering work on abnormal neuropeptides and

psychopathology. 14,15

Abnormal intestinal permeability in autistic children

has been confirmed16, allowing a pathway for uptake of

exorphin peptides. That these peptides alter neuronal

development in the CNS is also documented.17,18 Not

only is there an opiate-like effect, but brain cell

growth and structure is adversely affected by these

peptides. Hence, removal of the peptides does not

immediately reverse the condition; rather, gradual

corrections must be hoped for. In addition to

dietary-source exorphins, internally-generated

(endogenous) endorphin excesses with associated

immunoreactivity has been described in a type of

autism (Rett’s syndrome).19 Thus, removal of the

dietary source of the offending peptides is not

expected to immediately reverse the autistic

condition; instead, a gradual healing process might be

achieved. Nevertheless, removal of the offending

exorphin peptides can have some short-term, observable

benefits in many autistics such as behavioral

improvement, better eye contact and the beginnings of

improved (or recovered) vocalization.

POSSIBLE INITIAL RESPONSES TO EnZymAid

EnZymAid is designed to digest dietary proteins and

peptides, and this function begins in the stomach.

(EnZymAid is not destroyed by normal stomach acidity.)

With improved digestion, three previously on-going,

improper processes may be temporarily accentuated.

First, the exposure to dietary opiate peptides is

decreased or eliminated. This usually brings about a

period of opiate withdrawal, which may last 5 to 10

days or longer in some cases. During this period, the

individual typically becomes irritable, may tantrum,

or may present increased levels of inappropriate

behavior. Cravings for discontinued foods may occur.

At the same time, reduction of undigested dietary

peptides from the gastrointestinal tract can

discontinue a food supply that may have fostered the

growth of dysbiotic, possibly pathogenic flora in the

gut. Intestinal dysbiosis is commonly presented by

autistics and may include yeast/fungi overgrowth,

parasites and unusual or pathogenic bacteria. This,

together with increased permeability of the gut wall

allows for increased toxic burden in autism. A

temporary result of using EnZymAid can be die-off of

such flora with consequent release of even more

toxins. The die-off period usually does not last more

than two to three weeks but may continue longer with

persistent, adaptable dysbiotic strains.

With more complete digestion of dietary protein comes

a more normal amount of free-form essential and

protein amino acids. In some individuals, this can

lead to a third effect if there is an underlying

problem with transport and metabolism of amino acids.

An example of such a problem is malabsorption of the

essential amino acid tryptophan which can lead to an

increase in indolylacroylylglycine (“IAG”). IAG itself

is not known to be harmful, but dysregulation of

tryptophan metabolism can be, and unconjugated (not

detoxified) indoleacrylic acid can be harmful.

So, an initial period of adverse response to digestive

aids can occur in some autistics. And, if this problem

period continues beyond two or three weeks, please

consult the doctor who is attending the autistic

individual. Clinical laboratory tests can be

informative in cases of prolonged problems – a

comprehensive stool analysis (such as Great Smokies

Diagnostic Lab CDSA), an amino acid analysis (24-hour

urine preferred but fasting plasma is OK), and a food

allergy workup. (Food allergies can cause inflammation

of the intestinal mucosa and worsening of the

responses described above.)

LIMITING ADVERSE RESPONSES

EnZymAid (or any digestive enzyme) is not a substitute

for an elimination diet: removal of casein sources

(dairy products, goat too) and gluten/gliadin sources

(wheat, oats, rye, barley, triticale, spelt, kamut,

etc.) Progressive removal of such foods from the diet

followed by introduction of EnZymAid stages the

removal of dietary opioids and can lessen the

intensity of the withdrawal (which is then extended

over a longer period of time). Not all autistics have

a casein or gluten exorphin problem, and a trial

avoidance period (30 days) followed by reintroduction

of casein/gluten can often show need for such an

exclusion. Note that food allergy tests which measure

immunologic response to casein or gluten via IgE or

IgG levels do not apply to exorphin chemistry. A

negative IgE or IgG to these foods does not tell the

tale.

A stool analysis with bacteriology and mycology

performed ahead of dietary therapy and EnZymAid can

also lessen effects if the analysis leads to early

rectification of bowel flora. Getting the bad bugs

wiped out and replaced with beneficial probiotics

(Kirkman Pro-Bio Gold, Pro-Culture Gold) just ahead of

dietary therapy, or along with it (but before starting

EnZymAid) is a good idea. This also stages the

responses and gets the die-off (or most of it) over

with before EnZymAid is introduced.

Often, an amino acid analysis, when done up front with

the stool analysis, can forewarn of metabolism

problems. This, however, is not foolproof because

dietary restrictions plus use of EnZymAid can

significantly alter the amino acid picture. If adverse

response to EnZymAid persists beyond three weeks, then

an amino acid analysis and a food-allergy workup are

advisable through your doctor.

COMMONLY ASKED QUESTIONS, ANSWERS

1. Q. Can I reduce the gluten and casein foods in my

child’s diet and use EnZymAid to take care of the

rest? A. No, not a good idea. You’d be depending on

EnZymAid to contact all the gluten and casein

molecules that were eaten and to digest all of it

quantitatively. Remember the casomorphin and

gliadorphin exorphins are active as false

neurotransmitters at micro-quantities.

2. Q. I completely control my child’s diet and he/she

gets zero casein and gluten. Why do I need to use

EnZymAid at all? A. Four reasons: (1) Food that you

buy, even “ingredient” foods, may contain unlabelled

casein/gluten; (2) It is not proved that offending

exorphins come only from traditionally-recognized

casein/gluten foods, (3) As your child develops,

attends remedial programs or is out of direct care,

dietary mistakes will occur; (4) Autistics as a group

are typically deficient in zinc, the activator of most

digestive peptidase enzymes and EnZymAid can partially

compensate for this likely deficit in digestive

capability. (Zinc supple-mentation, away from meals,

is also recommended if an element analysis of blood

cells or hair shows need. Rectification of zinc levels

can take considerable time in autism.)

3. Q. Before my child started using EnZymAid, his

urine IAG was 15. After a month on the enzyme, his

level was at 25. Why? A. Although most show a decline

in the IAG peptide with use of EnZymAid, some show an

increase. This response probably means that a lot more

free tryptophan has become available from dietary

protein. There are two reasons: i. The digestive

enzyme is working; ii. The protein content of the diet

is higher in tryptophan because meat, fish and poultry

have been substituted for dairy and grains. Also,

there is a third concern. Tryptophan may not be doing

what it’s supposed to. Either there is underlying

intestinal malabsorption (investigate pancreatic

dysfunction and allergic sensitivity to foods now in

the diet), or there is a problem in tryptophan

metabolism (check via amino acid analysis).

4. My child is in his fourth week of extreme

inappropriate behavior and irritability after starting

EnZymAid. What do I do now? A. Contact your doctor.

Continue or discontinue the enzyme per his advice.

Suggest to him that he evaluate your child for:

intestinal dysbiosis, food allergies, amino acid

metabolism disorders. Also, review your child’s diet;

is he/she really off casein and gluten?

5. A lab measured my child’s exorphin peptides (e.g.,

beta-casomorphin 7), and his levels have increased

while on EnZymAid but his behavior and functioning

have improved. What’s going on? A. The behavioral

and functional improvements are of key importance;

continue what you are doing. Stopping or changing

because of one perverse lab result has disappointed

several parents. The exorphin peptides were originally

measured as a group and individually by a procedure

called HPLC (high-performance liquid chromatography).

Not all labs do this; some use RIA (radioimmune

assay). Cross-reactivities and uncertainties currently

plague this particular analysis. Children guaranteed

by their parents to not be consuming any casein have

lab reports with high casomorphins (ditto for

gliadomorphin and gluten). We hope that with

experience and improved testing procedures that this

will be sorted out in the future.

Jon B. Pangborn, Ph.D., Ch.E.

Fellow, American Institute of Chemists

Consultant to Kirkman Laboratories

REFERENCES FOR EnZymAid AND DIETARY PEPTIDES PAPER

1. Trygstad OE, KL Reichelt et al., Brit J. Psych.

(1980) 136 p.59-72.

2. Reichelt KL et al. J.App.Nutr (1990) 42

p.—(preprint from author)

3. Reichelt KL et al. Brain Dysfunction 4 1991

p.308-319

4. Shattock P et al. Brain Dysfunction 3 (5-6) 1990

p.328-345

5. Shattock P. DAN Communication, “The Evaluation of

Urinary Profiles in Autism and Associated Disorders”

1998

6. Cade R et al. “Autism and Schizophrenia: Intestinal

Disorders”, research report for grant from M and R

Cade Foundation and from U of Florida, Gainesville

(undated, ca.1995)

7. Reichelt to Pangborn, private communication, “Amino

Acid Sequences of Exorphins Found in Autistic Urine”,

16 Aug 1995

8. Fukudome S and M.Yoshikowa FEBS (1992) 29 (1)

p107-111

9. Zioudrou C et al. J.Biol.Chem (1979) 254 (7)

p.2446-2449

10. Reichelt KL et al. Dev.Brain Dysfunct.(1994) 7

p.71-85

11. Chabance B et al. Biochimie (1998) 80 p.155-65s

12. Meisel H. Biopoly (1997) 43 p.119-128

13. Panksepp J. Trends in Neurosciences (1979) 2

p.174-177

14. DeWied D “Psychopathology as a Neuropeptide

Dysfunction” p.113-122 in J. van Ree and L.Terenius,

eds., Characteristics and Functions of Opioids,

Elsevier/North Holland Biomedical Press (1978)

15. DeWied D, Endeavor, New Science (1980) 4 154-159

(Pergamon Press)

16. D’Eufemia P et al. Acta Pediatr (1996) 65

p.1076-1079

17. Zagon IS and PJ McLaughlin Brain Research (1987)

412 p.68-72

18. Hauser KF et al. J.Comp Neurol (1989) 281 p.13-22

19. Leboyer M et al. Am J Psychiat (1994) 151 no12

p.1797-1801s

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