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Cytochrome P450 and Histamine/Mast Cell Issues

Discussion in 'Hypersensitivity and Intolerance' started by Old Bones, Jul 24, 2016.

  1. Old Bones

    Old Bones Senior Member

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    I've been studying the website of Alison Vickery, an Australian Certified Health Coach whose practice involves helping patients with histamine/mast cell issues and chronic fatigue syndrome.
    http://alisonvickery.com.au/living-health-clinic/

    Alison provides a list of supplements, two of which I've tried only briefly (quercetin and DAO). So far, I haven't been able to find a medical practitioner who can help determine whether I have a DAO deficiency (in which case quercetin is unlikely to be helpful), or mast cell activation (in which case a DAO enzyme is unlikely to be helpful). Here's the segment of her article I'm wondering about:

    "Cytochrome P450 (CYP450) is a group of enzymes that convert substances, including medications and supplements. There is a high degree of variability in these enzymes. Only 50% of the population has a “normal” enzyme. It is important to know your own personal CYP450 profile. 23andMe® does not provide this profile. Some substances increase the function, some reduce the function, and some have no effect whatsoever. One of the primary reasons that people experience adverse reactions to medications and supplements is if they are a “poor metaboliser” of the CYP450 enzyme used to convert the supplement. For example, if you are a poor metaboliser of CYP2D6 then both quercetin and luteolin may be toxic to you whereas Pycnogenol®, which is not metabolised by CYP2D6, will not."

    I've looked into CYP450 testing, and it appears to be available in Canada for $1045 (Ouch!).
    http://www.pharmacy.ca/ptmain.shtml

    Cyrex Labs also includes CYP450 testing in its Array 5, although it doesn't specify CYP2D6 which appears to be involved in metabolizing both quercetin and luteolin. I'm not a scientist, and won't even pretend to know what all this means.
    https://www.cyrexlabs.com/CyrexTestsArrays/tabid/136/Default.aspx

    I'm just wondering . . . has anyone with mast cell/histamine issues had CYP450 testing, and if so, was it helpful?
     
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  2. MeSci

    MeSci ME/CFS since 1995; activity level 6?

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  3. Gemini

    Gemini Senior Member

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    In the US, Genelex offers a comprehensive panel of CYP450 tests:

    http://www.genelex.com/pharmacogenetic-tests
     
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  4. Gingergrrl

    Gingergrrl Senior Member

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    I promise I am not stalking you @Old Bones but everything you posted today is of great interest to me LOL. I have read Alison Vickery's website in the past but found that most of the foods that she lists as safe for MCAS would literally kill me. So I am not sure where she gets her info from.

    I have taken Quercetin and Daosin for over a year and both have been very helpful for me. I take plain Quercetin, Quercetin + Vit C, and NeuroProtek which contains some Quercetin. I used to take "Daosin" but the product was discontinued and I switched to a new form of Daosin called "Histamine block."

    This is interesting b/c I am a poor metabolizer of the CYP2D6 pathway per 23andMe yet I have no problem whatsoever with Quercetin or Luteolin (which is in NeuroProtek.) No idea why but wanted to share in case this helped you or anyone else.
     
  5. ahmo

    ahmo Senior Member

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    I've listened to numerous experts in webinars referring to Cyrex. Seems well respected. Whether it will give you anything more to work with, rather than just dealing with your symptoms, is another question. I've had good results adding natural antihistamines and mast cell stabilizers. Without testing, and with no help from an MD.

    Do you know of lowhistaminechef.com? More mast cell info.
     
  6. Old Bones

    Old Bones Senior Member

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    @Gingergrrl Thanks for your insight. You're right -- there are so many conflicting lists regarding safe foods for MCAS, one must be careful. I've been able to determine many of the worst choices for me based on severe reactions (eg. my face swelling up like a bright red balloon). But, I haven't had much success in reducing my baseline level of discomfort.

    So far, I've haven't been able to source a high-potency DAO supplement in Canada. My first order of Seeking Health "Histamine Block" from the US arrived a couple of days ago. Today, I spent some time in a sunny vehicle, and didn't feel as ill as I usually do in this situation. So, perhaps the DAO is helping.

    I was surprised to hear of your awareness of being a poor metabolizer of the CYP2D6 pathway, since Alison Vickery states "23andME does not provide this profile". Perhaps her website is not as good a resource for accurate and uptodate information as I thought. Thanks for reminding me of the need to apply a wise degree of skepticism when reading health advice on-line.
     
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  7. Old Bones

    Old Bones Senior Member

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    @ahmo Which natural antihistamines and mast cell stabilizers have you found to be most helpful? Yes, I am aware of the low histamine chef website. Thanks.
     
  8. alicec

    alicec Senior Member

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    I can't help with the mast cell apsects of your question but can offer some info about CYPs.

    There are many CYP enzymes with varying roles in phase I detox and other activities such as synthesis and catabolism of steroids. They are divided into families and subfamilies with about a dozen members of families 1,2,and 3 being responsible for drug metabolism.

    I had a quick look at Alison Vickery's website. It's got some useful information - maybe the problem lies sometimes in over simplification.

    The genetics of CYPs are complicated and it is often combinations of SNPs, or deletions and duplications that determine things like overall drug metabolism.

    So she is quite right in saying that many of the sites which analyse 23 and me results are not very helpful in predicting your drug metabolism status.

    Promethease doesn't do a bad job so if you have 23 and me data you could try running it through that site. It would be an inexpensive way of maybe getting an idea if you have serious CYP problems.

    I'm not sure what she means about 23 and me not collecting data on CYP2D6. It certainly did on the previous chip but I think this is one of the complicated genes.

    She is saying more specialised testing and interpretation of CYPs is necessary and I'm inclined to agree. If I had adverse drug responses I would certainly get one of these tests.

    This is the test she uses. It looks for variants in genes encoding the enzymes CYP2C9, CYP2C19, CYP2D6, CYP3A5, CYP1A2, CYP3A4, VKORC1 and the drug transporter SLCO1B1. Cost is AUD149.

    This is pretty comprehensive since these CYP enzymes are responsible for the vast majority of drug metabolism.

    The Canadian test you linked seems to look only at CYP2C9, 2C19 and 2D6. These are important, being responsible for 12.8, 6.8 and 20% respectively of metabolism of clinically used drugs. But 3A4/5 is responsible for 30.2% and CYP1A2 for 8.9%. So the test seems fairly expensive and maybe not as comprehensive as you would like.

    The Cyrex test is not what you are looking for. It is looking for autoantibodies to CYP protein, not at the genetic variability of various CYP genes.

    I couldn't access the site of the American test so can't comment.

    Here is a review of CYPs and drug metabolism. It is fairly heavy going but you can just look at the figures and tables which give valuable information on which CYPs do what and what is known about the genetic variants.

    Fig 1 is a pie chart showing the breakup of drug metabolism among the various CYPs. This is where I got the percentage figures I quoted above.
     
  9. Old Bones

    Old Bones Senior Member

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    @alicec Thanks for your detailed post regarding CYP genetic testing. I took a look at the myDNA test, but alas, it is not available to those outside Australia. Nevertheless, the website does provide much valuable information to help me determine what tests I can access that would provide the "biggest bang for the buck".
     
  10. Gingergrrl

    Gingergrrl Senior Member

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    @Old Bones, the food lists are completely conflicting and initially drove me crazy and about a year ago, my daughter laid them all out side by side and made a list of which foods were deemed safe on ALL lists and which were deemed unsafe by ALL lists and then all the ones that conflicted. My MCAS doc said to choose one list and stick with it, so I have been following the SIGHI diet for over one year and overall, it is a very close match to what I tolerate.

    My understanding is that Daosin is only effective if taken right before you eat food and would have no effect on non-food reactions like sunlight. Whereas the other H1 or mast cell stabilizers can affect all reactions. When I take my second set of meds and am not eating food, I skip the Daosin for this reason. But I could be wrong so as usual, do not quote me on anything! I loved the original Daosin by Swanson and hoping it is back on the market some day b/c the histamine block contains fillers that I try to avoid (but am taking anyway for now b/c no alternative.)

    It was actually my mold doctor last summer who read and interpreted my Genetic Genie results (based on 23andMe test) and told me I was a poor metabolizer of the CYP2D6 pathway. She explained that I also metabolize adrenaline or stimulating chemicals (my wording b/c I cannot recall the real terms) at 1/4 of the speed of a normal person which is why I sometimes get a very exaggerated startle response which can last for hours (although this is not happening at present.) I showed the 23andMe results to docs who had no idea what to do with it and my mold doctor was the first one who had a solid understanding and gave me some feedback. She is a gem.

    Wow, Alice, your explanation in above post was incredible and I wish I had the background to understand it! But from my experience, 23andMe does give you that data, you just need someone to interpret it for you if you lack a scientific brain like me.
     
  11. ahmo

    ahmo Senior Member

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    Rutin for antihistamine; royal jelly and mangosteen for mc. I switched from quercetin to mangosteen. My mc symptoms are relatively benign, but very real, and generally these things keep things in control.
     
  12. Old Bones

    Old Bones Senior Member

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    A very good suggestion, and one that I have considered. My problem is that histamines/other biogenic amines are not the only things I need to avoid. I'm also gluten intolerant, and should be following an autoimmune paleo diet (no grains, legumes and dairy) and also the restrictions for those with SIBO. By the time I list everything I should be avoiding, there is nothing left!

    Your understanding is consistent with what I've read -- that DAO does not have a systemic effect, but instead breaks down ingested histamine in the gastrointestinal tract. Might this mean that in the presence of leaky gut, less histamine in the GI tract would result in less getting into the blood stream/tissues throughout the body, thereby lessening the effect of non-food triggers like sunlight? My medical analysis is often quite flawed, but this doesn't stop me from trying to make connections.

    @Gingergrrl I'm so glad you have some "gems" in your medical team. I, also, am quite fortunate, although my doctors are constrained by the significant limitations of our public medical system. So far, I haven't had genetic testing. Perhaps it's time. Like you, my reactions to even minute doses of most medications are extreme, so I'm probably not metabolizing them properly.
     
    Last edited: Jul 26, 2016
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  13. Old Bones

    Old Bones Senior Member

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    @ahmo Thanks for the suggestions. By coincidence, yesterday I found some mangosteens at an Oriental market -- a first for me. At about $1.50 apiece, I don't think they're something I'll be eating regularly. But, they are delicious.
     
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  14. ahmo

    ahmo Senior Member

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    I've never tasted a mangosteen.They look beautiful.
     
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  15. Gingergrrl

    Gingergrrl Senior Member

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    I actually have never tasted a mangosteen either but they are on my list of foods to try. Am tolerating more fruits these days and today I tried champagne grapes (they are tiny!) and yellow pluots and no allergic reaction whatsoever to either. I hope to try cherries, plums, apricots, peaches, and nectarines in the future and see if any cause a reaction (all on separate days of course.)
     
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  16. Gingergrrl

    Gingergrrl Senior Member

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    I am not gluten intolerant but have avoided it for three years b/c of Hashimotos at the recommendation of my Endo and other docs. So I follow the SIGHI diet plus am gluten free. But I do eat grains, as long as they do not contain gluten or yeast, and I do eat dairy as long as it is not fermented like yogurt, etc.

    It is certainly possible and I truly have no idea!

    The gems in my medical team are the ones who are mavericks. They are not swayed by insurance companies, Big Pharma, or the prestige of a big hospital or name. They believe in a theory like ME/CFS, MCAS, mold toxicity, etc, and they believe in providing relief to their patients and testing and trying non-traditional ideas. For each doc I have found that is a true "gem", I have probably seen ten horrible doctors to find that person.

    Part of my extreme reactions to meds I am certain has to do with slow liver metabolism but part has to do with unknown food dyes, additives and fillers that I was reacting to before I realized I had MCAS. When I get a med compounded in it's purest form, the difference is really striking for me.
     
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  17. Gingergrrl

    Gingergrrl Senior Member

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    upload_2016-7-26_15-38-26.png This is a mangosteen in case anyone was curious. If I try one (if we can find one!) I will post about it @ahmo. Am still thinking about trying the supplement version as well as an additional MCAS supplement since it sounds like it has worked out so well for you and a few others.
     
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  18. ahmo

    ahmo Senior Member

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    :thumbsup::)
     
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