Sudden Regression with Diet but not with Enzymes

last updated 8.25.05

Part 1

Sometimes when a person leaves a casein-free gluten-free diet without enzymes they may experience a sudden regression, or 'crashing'. It was once thought that this might happen even if you used enzymes. However, in nearly two years of use with Peptizyde with casein and gluten-containing foods, this has not been reported. So why does it only happen if one sticks to a strict casein-free, gluten-free diet and then adds casein and gluten back in, but it does not happen if enzymes are used? The following discussion offers some ideas.

If we combine what is known about cell growth (and also death) as being logarithmic, and what is known about intestinal impermeability, and opiate receptor mechanics, there is a fairly good plausible explanation that is consistent with what we see in real life examples.

It is known how receptor mechanics work. There is a percentage of the total number of receptors that must be occupied in order to trigger a reaction. If we have 100 receptors, it might take 40 of them to be filled in order to provoke a reaction such as a migraine or constipation (40%). Filling 38% will not cause this reaction. Because there is also a constant flux of receptors being filled and unfilled, a low intake of peptides may be tolerated and the adverse reaction not seen. When 40% are occupied you have the reaction. If 50% are filled, the reaction is already taking place. There may also be different reactions. Say, 40% causes constipation, 55% causes a migraine, 75% causes sleep disorder, etc. If you reduce the peptide levels somewhat, say to about 60%, you may get rid of the sleep problems, but still have the migraines and constipation.

Situation 1:
Someone is on a GFCF diet and sees improvement and re-introduces those foods. They may see a reaction right away and/or gradual regression. In this case the gut may not be healed, the food removal lowered the number of occupied receptors so that a negative reaction doesn't happen. Any new intake of peptide generating foods increases the level of occupied receptors and you get a reaction.

Situation 2
If you are on a GFCF and see improvement and then you go off and put casein and gluten back into the diet, some people may continue to do well forever. But others may experience a 'crashing' or dramatic regression after 1 or 2 or 3 months. Why would this happen?

Explanation: Being on the diet may allow for some gut healing and the opiate receptors to be cleaned out or become unoccupied. Some people may leave a GFCF diet and digestion has improved and the gut healed to the extent that there is no immediate problem. Their digestion problems may not return and so they stay off the diet with no problems indefinitely. Another person may do this but their digestion problems are not really 'fixed' and so intestinal breakdown resumes, peptides get through, and the receptors start to fill up again. Because the deterioration of the gut may be logarithmic you may not notice anything initially until the damage is substantial. At that point there is a jump in the damage you see, maybe an exponential 'rush' of peptides filling receptors, and it seems like 'all of a sudden' there is a dramatic relapse. In the early stages, a smaller amount of peptides may be getting through but since the total number of receptors is still below the threshold needed to trigger a reaction, you don't see anything.

Example: Say someone leaves a GFCF without enzymes. For one month the gut is becoming damaged and receptors filling. But the total number of receptors filled is 10, then 20, then 30 so we have not reached the 40% threshold. Then in the second or third month, both the logarithmic effect kicks in and the intestinal damage shoots up, there is a flood of peptides, and a number of receptors are all filled all at once. The person would not go through the gradual stages of first noticeable constipation, then migraines, then sleep disorder over time. It will hit them all at one time and ka-BOOM, major negative relapse. We see this with other substances that affect the nervous system. Guzzling down a can of caffeinated soda or alcohol will produce a 'rush.' You get a different effect if you sip on the beverage over the course of an hour or more. Eating a very sugar-filled snack on an empty stomach can give you a zip as blood sugar levels rapidly fluctuate too (a hypoglycemic reaction).

Situation 3
Someone may be on a GFCF diet and see improvement. Then they start enzymes. Then they leave the GFCF diet and start eating casein and gluten foods once again. It was been speculated that if the enzymes were not working, some people would still see a dramatic regression over time. But this doesn't happen. Why not? What we see after thousands of people have gone to enzymes of many brands is that either
a) the person experiences gradual, noticeable regression
b) the person is fine and remains in good health over time
c) the person improves dramatically and remains improved over time.
Each of these situations follows.

Explanation 3-a: The person experiences gradual, noticeable regression on enzymes upon leaving GFCF. These enzymes are not working well to meet the person's needs and so there is regression. Same situation as Situation 1 above. This regression may be even more gradual though than if enzymes are not used because the enzymes may be getting SOME of the peptides, just not enough. Also, because many enzymes do proactive healing work, enzymes may be lessening the leaky gut problem which is allowing the peptides to get through in the first place. So peptides are still entering the system and causing a problem, just at a slower rate than not using enzymes at all. Because the rate is slower, you can first notice the constipation, then migraine, then sleep disorder, etc. (Most people would take notice at the first or second sign and start readjusting their diet/enzyme schedule). The body would have more chance to adapt too.

Explanation 3-b: The person takes enzymes, leaves GFCF, is fine and remains in good health over time. This is very reasonable. Enzymes do a lot of healing work. Even if the enzymes are not doing such a hot job of sufficiently breaking down peptides, enzymes ensure the gut stays healed so no peptides get through. Any tidbits of peptides getting through would still be below the threshold to trigger a negative reaction. This seems to be the 'normal' or 'healthy' state at which your body should be at anyway. You would have enough naturally produced enzymes to breakdown all foods sufficiently so that the rate of cell loss in the gut equals the rate of cell growth. This maintains a reliable intestinal wall. Some peptides will always be in your body whether you eat peptide generating foods or not. The body is designed to handle or process out a certain quantity of peptides anyway. So when the intestines have good integrity, the little bit of peptides getting through are naturally processed out.

Explanation 3-c: The person takes Peptizyde (and possibly related products) and puts casein and gluten back in the diet, improves dramatically, and remains improved over time. Because this happens so often, there is something these foods are providing that the body needed. So besides all the benefits given in Explanation 3-b above you have the added bonus of the nutrients in the casein and gluten foods. It is known how healthy whole grains are for a number of reasons. And research has proven that people respond much better when getting nutrition from foods rather than supplements.

Situation 4
Why doesn't anyone have a dramatic negative regression when taking Peptizyde enzymes and putting casein and gluten back in the diet? As noted in Explanation 3-a, even if the enzymes are not catching all the peptides needed, they buffer the situation so that you have the noticeable regression instead. Enzymes would alleviate the 'rush' or flood created by an intestinal wall breaking down combined with an abrupt filling of receptors. Just as sipping on a caffeine or alcohol drink is different than guzzling it down. Just as you can take one aspirin a day without ill effect (and doing that is even beneficial for some people), but if you take the entire bottle all at once you have put a toxic dose in your body. The dose makes the poison.

Also, certain enzymes help with gut healing...and there is substantial research showing that cell growth and wound healing can be exponential. And enzymes greatly facilitate healing. So even if peptides were getting through, the intestinal lining may be healing much faster than the peptides can accumulate.

see Opiate Receptor Mechanics

Part 2

(This gets a little techy)

The First Question is . . .
Why do some people all of a sudden dramatically relapse or regress when they leave a GFCF diet, but this does not happen with enzymes. What we see with enzymes is that either the regression is slow and steady, or the person remains doing great after months upon months of using enzymes and never regresses (unless it is yeast or new therapy or something unrelated to enzyme function). If the mode of action of this crashing was identical between enzymes and food eliminations, statistically you would expect a few people to also exhibit this 'crashing' on enzymes.

For example: Let's say the person takes some enzymes that do not breakdown all the casein and gluten and so there is buildup over time. The person erroneously just thinks the enzymes are doing a good job when in fact they are not doing a very good job. We would expect some of these people to dramatically regress as happens when reintroducing casein and gluten and leaving a GFCF diet. This is what GFCF gurus warned was so 'dangerous'. But this has not been reported after nearly two years of using Peptizyde instead of a GFCF diet...or with other enzymes targeting casein and gluten...for anyone. Why not? No one even knows what causes this crashing at all. There are no other explanations offered from other sources.

First, I thought: what other things in biology show a dramatic reaction 'all of a sudden'? Is this pattern something that is seen in biology? Maybe the child really was regressing slowly over time but the parents just didn't notice. However, the answer may be yes, it does happen somewhat dramatically. This is because there are mechanisms that operate logarithmically. When mechanisms are arithmatic (additive) you see more gradual patterns.
2 + 2 = 4
4 + 2 = 6
6 + 2 = 8
8 + 2 = 10

Logarithmic patterns are more dramatic.
2 x 2 = 4
4 x 4 = 16
16 x 16 = 256
256 x 256 = 65,536

pH is a logarithmic scale. Cell division is logarithmic. Bacteria have a logarithmic growth and decline stage.

Second question - Practical Example

What would be an example in real life that shows the PRACTICAL application of this principle? Turning to an old faithful source of science, agriculture, this is how "weed resistance" works. Weed resistance is when a grower sprays his fields for a certain type of weed, only the weed becomes resistant to that particular herbicide. People deal with the same effect if bacteria or yeast becomes resistant to a particular treatment so we have to rotate our antibiotics or antifungals.

This is what a farmer may see on the practical level: He sprays his field. One plant may be resistant for a number of reasons and survive to release 50 seeds each. The farmer probably doesn't even notice this. Next year, he plants and sprays again. If all 50 resistant seeds germinate, each releases 50 more seeds each (total of 2,500 seeds lying in the ground). Farmer may notice a few of the 50 weed plants but not enough to accurately determine a problem, if he notices anything at all. So in the third year after planting and spraying, there are 2,500 plants everywhere...and each of them is already releasing 50 more seeds. To the farmer, in the third year 'all of a sudden' he has a big weed problem. So we went from 1 to 50 to 2,500 plants quickly.

So if peptide 'buildup' is really a logrithmic process and not arithmatic, this may explain the crashing sometimes seen when leaving a GFCF diet (without enzymes) in some people.

So why don't we see this with enzymes? It could be due to a couple of things.

1. The enzymes modify the influx of peptides into the system so that there is not a logrithmic buildup. If not all the peptides are broken down, the system is still somehow altered over all so that there is no logrithmic progression. It becomes a more arithmatic progression. This is consistent with what we see. If the enzymes are not working effectively, we see a steady regression, not good progress for a couple of months, and then WHAM! a regression.

Remember, it is the dose that makes the poison and not the substance itself. So if you are taking enough enzymes to reduce the total peptide 'dose' then you eliminate the reaction.

2. The enzymes modify the peptides so that even if they do get into the body, they are no longer in the shape or configuration that triggers the opiate receptors. The peptides may not be broken down to the level of essential amino acids, but they are distorted enough so they no longer fit the receptors and thus you do not get the opiate reaction. Molecules only need to be altered a tiny bit to have very different chemistry.

3. Enzymes pro-actively heal the gut by several different mechanisms. Gut healing begins immediately. So even if the enzymes are not getting 100% of the peptides, there is enough gut healing going on to balance out or outweigh any potentially problematic reactions. Maybe the problem overall wasn't even the opiate peptides but something else that the peptides bothered in the gut. The enzymes work on these things whereas food elimination may not. Enzymes would work on all the foods targeted from any source, not just the ones you think (such as breaking down soy as well as casein and gluten). Or perhaps they are healing the gut so fewer and fewer peptides (or other foods) are leaking through.

Initially I thought that any 'crashing' on enzymes may happen only it would take much longer to occur, such taking 7 months instead of 2. But that didn't happen either. So the healing work of the enzymes may be outweighing any negative effects of peptides trying to get through. And this is all in addition BESIDES the basic work they do of breaking down peptides.

Rate of Wound Healing

Now I looked at the rate of wound healing. This turns out to be logarithmic, and speeded up when enzymes are used.

Collagenase in a New Gel Formulation Accelerates Wound Cleaning and Wound Healing
Jan R. Mekkes, MD, PhD, Jimmy E. Zeegelaar, MD, Department of Dermatology, Academisch Medisch Centrum, University of Amsterdam, Amsterdam, The Netherlands.

Wound cleaning can be accomplished by using proteolytic enzymes. Recent studies indicate that efficacy of proteolytic enzymes can be improved by increasing the enzyme concentration and by creating a formulation that maintains a moist wound environment. Our goal was to select the optimal concentration for collagenase in a gel formulation. In ten female domestic pigs, eight experimental full- thickness ulcers were treated once daily with different concentrations (0.1-10U/cm2) ...... The average time (mean±sd) to total wound healing was 25.7±2.2 days for saline soaked gauze, 19.4±1.8 days for the gel with inactivated collagenase, and 14.8±1.5 days for the gel with the highest concentration of collagenase (10U/cm2). Figure 5 shows that the remaining concentrations, plotted on a logarithmic X-axis, produce a straight line, indicating a logarithmic dose-response relationship."
Wounds 11(5):117-124, 1999. © 1999 Health Management Publications, Inc

--Here is a very technical and almost unintelligible (to the average lay person) analysis on why the exponential model best describes wound healing: Other studies support exponential healing and cell growth.


  • A method of evaluating drug efficacy by statistical analysis of healing speed of peptic ulcer. J Gastroenterol Hepatol 1996 Oct;11(10):916-21
  • Control of membrane sealing in injured mammalian spinal cord axons. J Neurophysiol. 2000 Oct;84(4):1763-9.
  • Bromelain: biochemistry, pharmacology and medical use. Cell Mol Life Sci 2001 Aug;58(9):1234-45
  • Pharmacological study of papain from the papaya plant cultivated in Uzbekistan. Eksp Klin Farmakol 2000 May-Jun;63(3):55-7

"It was experimentally established that papain from papaya cultivated in Uzbekistan possesses a pronounced proteolytic activity: 0.1, 0.5, and 1% papain solutions decreased the weight of burn crust in vitro and accelerated experimental burn healing in vivo. Under clinical conditions, papain produced therapeutic effect in patients with inflammatory disorders in genitals, intestine, liver, and eye. The pharmacological effects of papain produced from Uzbek papaya are identical to those of the commercial product from Merck."

So it does not appear that there will be any 'crashing' when you take enzymes, particularly the ones targeting casein and gluten, like what happens to some people when they leave a casein-free, gluten-free diet without enzymes.

Next question - Testing
How can you tell if your body is building up peptides or not under any circumstances? This is a question those interested in the peptide theory have been trying to answer for years. There is the 'peptide test' however, there is disagreememt on how to test for these peptides and which test is accurate. Also, there is disagreement on what these tests indicate. This is played out all the time in real life. A child will have a peptide test before going GFCF and after a year on strict GFCF the peptide levels with be HIGHER than they were in the beginning. Other people will have high peptide levels and see no improvement on a GFCF diet no matter how long they do it. Other people will have low peptide levels but still see improvement if they go GFCF. So it is not clear at all what the tests actually indicate is going on it the body one way or another. Relying on the current peptide tests will not tell you if there is any peptide buildup problem or not.

I thought the Intestinal Permeability Test would be a good idea to see about leaky gut. But when I asked a rep from Great Smokies Laboratories, he said if my kids were acting and behaving okay, then just save the money...going by behavior was more indicative.



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