Methylation and B-12 questions

TM · Post by TM » Wed Nov 22, 2017 1:59 am

Hi Everyone,

I posted a success story yesterday, and now that I’m making some serious progress, all sorts of additional questions are popping up. Most recently I‘ve been trying to understand Histamine Intolerance, Mast Cell Disorders and Methylation. But it seems that the more I read, the more complicated, confusing and overlapping these issues become.

I received my 23 and me results a few months ago, but have so far only downloaded the “Genetic Genie” results. (See below). I see that there are also options for deciphering additional genes. Does anyone have any tips on where to start and which programs are best?

These are my results from Genetic Genie:

Homozygous mutations:
MAO A R297R rs6323 TT +/+

Heterozygous and MTHFR mutations:
MTHFR C677T rs1801133 AG +/-
MTHFR A1298C rs1801131 GT +/-
MTHFR 03 P39P rs2066470 GG -/-
VDR Bsm
VDR Taq
MTRR A66G
MTRR K350A
MTRR A664A
BHMT-02
BHMT-08
CBS A360A

Do these results suggest methylation or other problems? I thought they might, but wasn’t sure whether the facts had successfully penetrated my brain fog, or whether I was misinterpreting. In any event I added Thorne Methylated B-Complex and Methyl Guard to the P5P I’d been taking, and since late September my daily supplemental B Totals from all 3 have been:

B6-P5P: 80 mg (Pure Encapsulations=50 mg, Thorne 30.4)
B12: Methylcobalamin: 1.6 mg
Folate: L-5 methyltetrahydfrofolate: 1.6 mg
Thiamin HCL: 110 mg
Riboflavin: 10 mg
Niacin/Niacinamide: 10/130 mg

Various posts here seem to recommend differing amounts of these, so I’m not clear on how much (if any) I should be taking—especially after a B-12 test last week.

In June 2014 Folate was >22 ng/mL (Reference Range is >/=5.9 ng/mL)
B-12 was 821 pg/mL (Reference Range is 180-914 ng/L)

On 11/14/2017 Folate was >23 ng/mL
B-12 was >1,500 pg/mL

So now I’m really confused!! Should I be concerned? Does this mean no B vitamins needed? When both are supplemented equally, is it unusual for B-12 to rise so much more than folate? Does any of this suggest something obvious or require further investigation?

I’ve had high blood sugar for years—even when I was on a long-term very low carb diet. However my A1C is not elevated. It’s been about 5.2 for at least the last 10 or 20 years. I now think the insulin resistance might be due in part to long-term magnesium deficiency. I’ve taken 1400 mg of magnesium glycinate (recommended based on ExaTest results) for about 5 years, and 400-1200 mg (citrate) for a decade before that. But it wasn’t until I began using topical magnesium oil this year that I’ve had significant relief from chronic, debilitating leg and muscle cramps. And my blood sugar also began to improve, despite eating way more carbs than in the past. Its still slightly elevated though.

Any suggestions will be much appreciated.

Thanks!!!

Happy Thanksgiving to all!

Post by **tex** » Wed Nov 22, 2017 9:47 am

Your results are somewhat similar to mine except for the P39P and I have some others. If I were you, I would be taking the Methyl-Guard Plus.

The C677T mutation is associated with a general set of problems: elevated homocysteine, increase in heart disease, increased stroke, increased deep vein thrombosis, peripheral neuropathy, placental vascular problems (stillbirth), preeclampsia, neural tube defects, cleft lip.

The A1298C mutation is assoicated with a second set of problems: depression, anxiety, irritable bowel syndrome, fibromyalgia, chronic fatigue, migraines, dementia, nerve pain, schizophrenia, parkinson's, tetrahydrobiopterin (BH4) problems.

I have no idea what the MTHFR P39P mutation does, since I don't have it. But the others (above) I do have, and I also have some of the symptoms (including a stroke last spring and a diagnosis of Parkinson's 8 years ago).

If you're taking B-12, your levels will test high until your body fully metabolizes them and your levels stabilize. You need to stop taking a B-12 supplement about a week before the blood draw for the test to provide an accurate result.

Tex

TM · Post by TM » Wed Nov 22, 2017 8:29 pm

Thanks Tex. I’ll be back with a few more questions next week.

TM · Post by TM » Thu Nov 30, 2017 6:53 pm

Thanks, Tex. I ordered Methyl Guard Plus and it should be arriving any day now. In the meantime I doubled my Methyl Guard dosage from 3 to 6 caps per day, since it’s less than half the potency of the Plus version. I stopped the 50 mg of P-5-P I’d been taking, but continued with the Thorne B-complex, since it contained some Riboflavin which is absent in the original Methyl Guard. I noticed though that in another post today you said you took only one M/G Plus per day, rather than 3 per day which is the serving size listed on the container. Is that the general recommendation—just one? If so, it seems that 6 of the others was probably too many.

Along with the M/G Plus should I also be taking 50 mg of P-5-P, or any other vitamins or supplements? What about B-1 and selenium? In addition to the B’s, D3, magnesium glycinate and KCL(Rx), I’ve also started taking zinc + copper again, after my thyroid became kind of swollen and I developed a small (benign) nodule in May. Does anyone else take zinc carnosine? It was recommended a few years ago by my naturopath who had seen studies linking 32 mg of zinc from zinc carnosine to reductions in GERD symptoms. I never noticed any definitive gut changes, although it does seem to help with thyroid issues. If anyone’s interested here’s a link to a British study and to Dr’s Best version (4 caps per day) on Amazon.

https://smile.amazon.com/Doctors-Best-Z ... osine&th=1

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1856764/ :

Also seems like I’ve seen a few differing recommendations re: best zinc/copper ratio. What’s the correct amount of copper to take per 32 mg zinc daily?

I was hoping that only being heterozygous for both of those MTHFR mutations meant much less likelihood of being affected. Guess not. Makes me kind of hesitant to look much further into other genetic results, but know I’ll do so eventually. One more question now though, about the homozygous MAO A R297R rs6323 TT +/+. I’m pretty sure I have histamine and/or mast cell issues (about which I will also bombard you with questions soon) and noted the importance of DAO. Does anyone know if DAO and MAO are related, functionally?

Again, I can't thank all of you enough for the support, encouragement and wealth of information you share every day. I simply can't imagine where I'd be now without your invaluable advice.

Gabes-Apg · Post by **Gabes-Apg** » Thu Nov 30, 2017 7:09 pm

Sorry I had not replied earlier to this post.

one important thing about genetic results - you may have the gene variations but there is no way to test if the variations are 'turned on'

genetics is like injuring someone with a gun. the gun alone does not cause the injury. you need the gun, it has to be loaded with a bullet and then fired via the trigger for the injury to happen. It is the same with genetic variations, you may have them but it take epigenetics (environment, diet etc ) for the gene variations to be loaded and fired.

Zinc wise - zinc is key for multiple reasons - lilja recently posted about a study and importance of zinc for strength of valves in the digestion system etc. I personally prefer Zinc Picolinate
so far as zinc copper ratios and dosages - the only way to gauge this is via blood tests results for zinc and copper.

my experience with methylation issues linked to histamine issues (and our MC etc) taking P5P and fixing magnesium deficiency resolved my life long histamine/allergy issues. Erica had similar success and has posted about this in
i found the repost of this info at the top of the second page of this thread on the success stories area
http://perskyfarms.com/phpBB2/viewtopic ... c&start=15

have you read the posts in the mast cell and methylation section of the forum? lots of info on histamine / mast cell / methylation etc

Gabes-Apg · Post by **Gabes-Apg** » Thu Nov 30, 2017 7:18 pm

using search function i found some other discussions that you might be interested in

http://perskyfarms.com/phpBB2/viewtopic ... hlight=p5p

I also found this one that i had forgotten about - P5P helps with magnesium retention
http://perskyfarms.com/phpBB2/viewtopic ... hlight=p5p

TM · Post by TM » Fri Dec 01, 2017 8:27 pm

Gabes, thanks so much for your explanations. I’ve known about triggers, but assumed that the genes I mentioned had probably been triggered already, based on symptoms and connections I think I’m now beginning to understand. As you suggest, I’m just assuming the worst.

I’ve read most of the Histamine/Mast Cell/Methylation posts—multiple times—over the last year. I’ve also checked many internet sources on these topics, and read whatever studies I’ve come across. My problem is retention. I think I’m beginning to get it, but have to keep re-re-reading everything.

I’m still confused about the MAO++ variant. Is it related to DAO and histamine clearance or is MAO totally different than DAO?

I found a lot of info on DAO, including several European studies recommending DAO testing and supplementation. Unfortunately histamine Intolerance is not recognized in the U.S. Has anyone tried DAO supplementation? I didn't see much info on MAO, but haven't checked as carefully yet.

When I mentioned mast cells to my endocrinologist last May, she referred me to an allergist. Unfortunately he didn’t recognize MCAD or histamine intolerance as credible conditions. For the scratch test, I was required to stop all antihistamines for about 2 weeks prior to the appointment, but after just a few days “eczema” began to flare and quickly grew increasingly worse. After resuming loratadine and ranitidine daily, it took almost 3 weeks for itching to subside again.

So I’m wondering how safe it is to take these antihistamines on a long-term basis--I started taking them regularly last winter. I’m also wondering about dosage. I noticed a number of posts that referred to taking higher dosages than those recommended for allergy/heartburn. Is that okay?

Is there a recommended daily total intake for P-5-P from Methyl Guard Plus and other sources? Does one 50 mg cap and 15 mg from one M/G Plus sound right? Is it possible to take too much?

Thanks!!!!!!!!!!!

TM · Post by TM » Fri Dec 15, 2017 7:34 pm

I was retested after stopping (methylated) B vitamins for 11 days. Folate increased slightly to 24 ng/mL and B-12 increased from 1500 to 2000 pg/mL. I did get a small amount of B-12 in coconut milk—but less than 200 mcg. daily and that’s the only packaged food I used. Could this have caused the B-12 increase, or is there likely something else going on?

Can’t say I have a firm grasp on this at all. Does the high B-12 level suggest that help with methylation is necessary or unnecessary? Two days ago I began Methyl Guard Plus—1 daily, and 50 mg of P-5-P. (I’d previously taken 3 regular Methyl Guards + 50 mg P-5-P daily since late September). Not sure if I should be taking more—or any Methyl Guard Plus—or in addition to or instead of P-5-P. In any event, both feet are still numb. Any suggestions?

My tryptase was being tested, so I’d also stopped all antihistamines for a baseline reading. That test and the urine histamine test had to be sent out, so I don’t have the results yet. There’s no question that itching, sneezing, congestion, etc. all increased again during the hiatus, however I’m concerned about taking antihistamines continuously. Do others do this?

My PCP has requested mast cell counts (using the special stains) on my 2016 colonoscopy slides and a 2012 skin biopsy. Of course I’d be really surprised to actually learn something from any of this.

As for gut issues—all remains calm and my clothes have gotten too small!!!

With many thanks and best regards.

Post by **tex** » Fri Dec 15, 2017 10:14 pm

My brain is numb after rereading this entire thread.

It's apparent that your "B" levels really are high. So these are uncharted waters.

DAO and MAO have completely different purposes.

DAO stands for diamine oxidase. Diamine oxidase is responsible for breaking down excess (left over) histamine.

MAO stands for monoamine oxidase. Monoamine oxidase is responsible for breaking down dopamine, norepinephrine, and serotonin.

But it gets more complicated when we start using antihistamines, because antihistamines do more than just reduce allergic reactions by preventing histamine from activating histamine receptors.

Antihistamines not only minimize the activation of histamine receptors, but they also inhibit seretonin uptake. About 90 % of our seretonin is located in our enterochromaffin (EC) cells in our intestinal epithelia. Seretonin released from EC cells regulates motility in the gut, while of course in the brain, seretonin affects mood, etc. The higher the seretonin level in the gut, the faster the motility. So antihistamines can not only suppress allergic reactions, but also slow down intestinal motility.

Most pharmacists would probably tell you that long-term use of antihistamines is safe. But based on what I've written above, I would suspect that long-term use of antihistamines might eventually have consequences, as our body becomes accustomed to their use. But who knows?

Your tryptase test result will probably be meaningless (the result will be in the normal range) unless you were having a mast cell event (allergic reaction) at the time of the blood draw.

As to whether of not you should continue to take Methyl-Guard Plus or P-5-P or take more or less.

Again, these are uncharted waters. I've been taking either Metanx or Methyl-Guard Plus for over eight years now. I don't usually check my "B" vitamin levels, but I'm sure they're high. A few years ago (after a B-12 test that showed a result somewhere around the top end of the normal range), I asked my PCP if he thought I should stop taking it or reduce my dose, he simply said, "I wouldn't worry about it."

Tex

TM · Post by TM » Mon Dec 18, 2017 5:22 pm

Thanks for the clarifications Tex, and for indulging my numerous questions. I’m trying to make some sense of it all, but my brain is numb too!! In addition to trying to process the DAO and MAO mutation info, I’ve been reading that high B-12 levels can be a very serious cause for concern—or merely indicative of methylation problems. I’m guessing that’s it, since my most significant improvement began in October, soon after I began taking 3 Methyl Guard daily. So for now I’ll stick with one MethylGuard Plus a day, see how that goes, and try not to let myself get too crazy trying to decipher this stuff.

I knew the tryptase would be normal, but the instructions recommended a baseline reading. I also doubt I’ll get anywhere with the mast cell counts, but figured I might as well try, since my PCP offered to request them.

Thanks again Tex!

TM · Post by TM » Thu Dec 21, 2017 7:33 pm

Tex,
My serum tryptase and urine histamine were normal however the histamine to creatinine ratio was elevated. Any idea if this suggests kidney involvement?
Thanks

brandy · Post by **brandy** » Thu Dec 21, 2017 8:36 pm

Not Tex but I will take a stab in the dark. My comments are very speculative but I've read a lot about creatinine the last several months.
It is very difficult to find any information on line about what histamine to creatinine ratio defines so here is my speculations:

Elevated histamine to creatinine would mean that your creatinine score is "lowerish." Lowerish creatinine is a good thing....i.e. is representative of healthier kidneys.

Elevated histamine to creatinine ratio would also mean that your histamines are "higherish." We now that high histamines are common with MC particularly when someone is in a flare due to leaky gut. https://www.mindbodygreen.com/0-11175/e ... rance.html (not a scholarly article but I think has good info)

My wild guess is that a elevated histamine to creatinine ratio would probably be pretty common for a MCer who is in a MC flare but who has pretty healthy kidneys.

As an MCer heals (who has healthy kidneys) then their histamine to creatinine ratio should go back to normal.

Tex may have a totally different take on things.

brandy · Post by **brandy** » Thu Dec 21, 2017 8:45 pm

Going back to your question the elevated histamine to creatinine ratio would suggest that your kidney is in decent shape but your histamine output is high.

Again...speculative answer on my part.

I'm not sure if you saw my recent creatinine thread but I find the kidney ratios to be pretty confusing in general and found I would have to take a look at the definition of the numerator and the definition of the denominator to think through the meaning of the result.

Post by **tex** » Thu Dec 21, 2017 9:26 pm

Teri,

Ordinarily, an elevated histimine to creatinine ratio might mean that you have interstitial cystitis, but I believe that Brandy is correct because some of the lab markers and clinical symptoms of microscopic colitis mimic other diseases. When my MC was active, I often had the clinical symptoms of interstitial cystitis. You must have good kidneys if they can handle that much magnesium and still maintain a low creatinine score.

Tex

TM · Post by TM » Fri Dec 22, 2017 4:27 pm

Thanks guys. Brandy, your hypothesis seems totally logical, and Tex you’re right, as far as I know my kidneys have always been fine. I was Dx’d with a renal calcium leak 15 years ago, but told it did not in any way impair my kidney function, (just my bones and parathyroid). My creatine is generally between 7 & 8 and eGFR always >60—although I’ve never paid any attention to what these actually mean. Basically I did the urine testing, hoping for some (numerical) confirmation that I have histamine issues. I got the results on-line but haven’t yet heard anything more from my PCP.