Can digestive enzymes raise body temperature?

[carolm]

My list of odd reactions to supplements continues to grow. I have tried two brands of digestive enzymes. Both contain the expected enzymes: protease I, II, III and IV, amylase, lactase I and II, alpha-galactosidase, cellulase I and II, lipase I and II, phytase, sucrase, and maltase (malt diatase), plus one brand had bromelain and licorice.

Here’s the odd thing: about an hour after I take them, my face (cheeks) gets warm and reddish. No rash, no itching, no stuffy nose, no hives- just a warm face and sometimes feeling warmer in general all over. It can be a little uncomfortable but not awful.

I feel the enzymes are beneficial for me and I can see improvements in my reflux and motility, compared to my usual C-prominent and sluggish, slow emptying GI tract. I feel less tension in my gut, much less of that full, bloated feeling so I’d like to keep taking them (one to two per day seems to be enough).

I haven’t figured out what is going on that my cheeks get warm. It lasts about one hour or so.
Ideas? Should I be concerned? Some kind of thermic effect? Wild guesses are welcome.

Thanks fellow detectives,
Carol

[tex]

Hi Carol,

OK, this is a wild guess, but I'm guessing that you might have a deficiency of the aldehyde dehydrogenase 2 (ALDH2) enzyme, and I suspect that the enzyme supplements must contain a substance that promotes histamine production. Here's why I make such a speculation:

After consuming alcohol, an enzyme called alcohol dehydrogenases (ADH) converts alcohol into acetaldehyde, a toxin that is the byproduct of metabolized alcohol, which another enzyme (ALDH2) then metabolizes into a less harmful substance called acetate.

Facial flushing is a reaction that occurs in people with a deficiency in ALDH2, where alcohol is metabolized and processed up to 100 times faster than the average human. A deficiency in the ALDH2 enzyme means that acetaldehyde builds up in the body, causing flushing and other symptoms such as increased heart rate and nausea.

But ALDH2 is the same enzyme that is also responsible for processing histamine, and if you have a deficiency in the gene that helps break down alcohol, you get an alcohol flushing reaction. About 5-7% of people with alcohol flush reaction are actually missing the gene entirely. I would assume that it's very likely that the enzyme supplements probably contain substances that promote the release of histamine, because histamine is used as a trigger to activate the parietal glands in the stomach to entice them to produce gastric acid as a preparation for digesting a meal. I'm guessing that you probably have similar facial flushes after consuming alcohol. ALDH2 deficiency might tie in with the nausea issues that so many of us experience.

Taking a histamine H2-receptor antagonist, such as Pepcid AC or Zantac will blunt the flushing reaction, but there's controversy over the use of antihistamines while continuing to promote the production of histamines (or drink alcohol) as this practice does not address the problem of histamine buildup (or toxic levels of acetaldehyde that can build up from alcohol consumption) in the system. The enzyme supplement vendors would probably say that this is normal reaction and therefore nothing to be concerned with. I'm not so sure. It may suggest a genetic defect (or an MC side effect) that causes inflammation. But that's just my best guess.

Tex

[carolm]

Wow Tex! You’ve given me a lot to think about and to research. You are correct that I get a histamine reaction to alcohol- wine especially- flushed, stuffy nose, etc. I rarely drink so I don’t encounter it much.

I will look into this more. Initially I suspected a histamine type of response but really couldn’t find any sources to back that up. I didn’t mention that this did not occur the first or 2nd day I took them but was most definitely present on day 3 and 4. Then I stopped taking them for a few days and still had good effects (no reflux and a quiet gut) for another 4 days. Then my usual GI symptoms returned.

Which brings me to another pattern- anytime I try a new supplement- I’m generally ok the first 2 days but day 3-4 is when adverse effects show up. MethylGuard Plus was that way, Omega 3’s, and now digestive enzymes. B12 was the only exception in that it made me very ill within hours.
I did not have these issues with magnesium and D3....

So do enzymes or histamines build up by day 3 and I can’t get rid of them? Is this part of MTHFR 1298 methylation issues- complicated by my already high homocysteine levels?

Thank you as always Tex for sharing your knowledge. I feel like I’m so close to turning the corner to consistently better health but can’t quite put all of the pieces together.

C.

[tex]

Yes, buildups of histamine to exceed the threshold for reactions after 3 or 4 days is a common pattern when excess histamine purging is compromised. What is your MTHFR 1298 status, heterozygous or homozygous? Is this MTHFR A1298C we're talking about. I have a homozygous result, and according to my Genetic Genie interpretation,

MTHFR A1298C is involved in converting 5-methylfolate (5MTHF) to tetrahydrofolate (THF). Unlike MTHFR C677T,
the A1298C mutation does not lead to elevated homocysteine levels. This reaction helps generate BH4. BH4 is
important for the detoxification of ammonia. The gene is compromised about 70% in MTHFR A1298C (+/+)
individuals, and about 30% in people with a heterozygous (+/-) mutation.

BH4 acts as a rate limiting factor for the production of neurotransmitters and catecholamines including serotonin,
melatonin, dopamine, norepinephrine, and epinephrine. A MTHFR A1298C + status may cause a decrease in any of
these neurotransmitters or catecholamines. BH4 is also a cofactor in the production of nitric oxide. A dysfunctional
BH4 enzyme may lead to mental/emotional and/or physical symptoms. Mercury, lead, and aluminum may act as a
drain on BH4.

Nitric oxide is apparently needed for gut homeostasis, and it's already depleted when IBDs are active.

Tex

[carolm]

The report printout I have says I have the normal or wild-type genotype for the C677T variant (c.665C>T) and am homozygous for A1268C (c.1268A>C). Like you said, my report says ‘Although this genotype may lead to reduced enzyme activity, it does not cause an increase in plasma homocysteine level and is not associated with increased risk for artherosclerotic coronary artery disease or venous thrombosis.”

This is through my functional med doc and True Health Labs.


C.

[tex]

OK, I have a correction to make — I'm heterozyous for A1298C (not homozygous). I have no idea why I wrote homozygous when I was thinking heterozygous, except for the fact that the gremlins are always alert for an opportunity to make old codgers look stupid. I'm also heterozygous for the C677T gene. When I had my homosysteine level checked a few years ago it was low normal, but maybe I should have it checked again. I do have atherosclerosis.

But to get back to your situation. With a homozygous A1268C result, that gene is compromised about 70%.

Tex

[carolm]

That’s okay Tex. It’s not like I would even know the difference. It sounds like C667A is tougher to deal with. I’m sorry you are tackling both.

I did have a cardiac calcium test run, and I had mild calcification in the right posterior artery and all others are less than mildly calcified BUT I still have a moderate chance of developing heart disease. My CRP level was high and fibrinogen, Lp-PLA and Myeloperoxidase levels are all in the ‘Intermediate risk” level— so artery and heart disease is something I need to be aware of.

So my dilemma remains the same: where can I get traction and start supplementing for some of these issues, when I start reacting 3 days in?

Do I take DAO along with digestive enzymes? Do I add a stronger anti-histamine (rather than Claritin)?
Supplement for ALDH2? All the above? Take enzymes for 2 days and take one day off, then another two days? Or every other day (THIS might be worth a try-).

I am disappointed to be spinning my wheels again but the more I go at this the more that pattern emerges so I guess I have learned something. It’s becoming clear that I’m going to have to address the probable histamine issue first or I’m not going to make headway on anything else.

I would welcome any other thoughts you might have on how to move forward.

[tex]

Some authorities claim that DAO supplements help (taken about a half an hour before meals), but their effect is only short-term, so as soon as you stop taking them, the problem will return. Certain antihistamines seem to work better than others, but this is an individual phenomenon. In the long run though, some authorities believe that antihistamines deplete DAO, making antihistamines counterproductive eventually. But this may also be an individual effect, so it may vary among users.

I know nothing about treating ALDH2 deficiencies. Apparently the most common treatment is an H2 antihistamine, but that doesn't actually address the deficiency, of course. It mostly slows down the reaction to reduce the symptoms. That might help in your situation, but it may not be a long-term solution. And some MC patients react to H2 antihistamines. I have no idea if H1 antihistamines might help for this particular problem. Every-other-day supplementation might work, depending on the level of the problem. As you say, it might be worth a try.

If you discover a long-term solution, I'm all ears. I find myself slowly becoming increasingly histamine intolerant, despite restricting (or eliminating) high-histamine foods in my diet. I've thought about asking my doc for a prescription for Gastrocrom (cromalyn sodium), but I understand it's expensive and probably wouldn't be covered by insurance (surely not without a diagnosis of mastocytosis). I probably have mastocytosis (I have red, inflamed areas on my skin that have been there for years), but I'll bet that getting a diagnosis would be a big hassle.

Tex

[carolm]

Thanks Tex- I will likely have to settle for a short-term solution for now. I might try taking a Zantac in the mornings. I’m still taking 75mg at night. (The GI doc had me on 300mg but I’ve found I could reduce it without obvious issues). Then digestive enzymes every other day to start.

I see cromolyn sodium comes in a nasal spray but I assume that’s too small a dose to be effective for wide ranging mast cell issues.

Truthfully, I learn as much from our conversations as I do from seeing my functional med doc. Although I think he is skilled, nothing beats talking to knowledgeable people who are dealing with the same disease.

I will definitely let you know if I figure out how to jump this hurdle and break my 3 day pattern.

Thanks again- you are the best!
Carol

[tex]

You're very welcome. I learn a lot from these discussions too.

Tex