Basic question on Homocysteine

[PeterPositive]

Hello everyone. I've been lurking for some time reading a lot, it's a great resource! Thanks to everyone.

After the digging into the methylation problems, I have "some back-to-basics" questions.
When it comes to homocysteine values I see two schools of thought. The more generic doctors don't seem overly concerned with high Hcy values, e.g. in the range of 15 - 25 pmol/L, in fact they define this range as "mild".

Other doctors instead are highly concerned with any value > 9-10pmol/L and say that anything above 6-7 should be addressed.

In my case I was found with 98 pmol/L back in 2011, I started supplementing with the usual methyl-B12, B complex, folic acid and in one year it came down to ~13. Problem is I seem to be stuck there, no matter how much coenzymated Bs, SAM-e, I take, the value doesn't go down any further.

Questions:
Is a value of 13 really that bad? I am 40, no smoking and drinking, healthy diet.
Is it normal that the regular B vitamin therapy works up to a point and then stops?

My ND suggested to check for mthfr mutations. I live in Italy, while I can probably find a lab near here to test that I see people here tend to use more comprehensive panels that look for many other related mutations. Can you recommend an international lab that can offer a more comprehensive test to check for methylation issues?

Thanks in advance.

 

[PeterPositive]

Also, one more question. My serum level of B12 are at the top of the scale (900+). I see lots of people here using megadoses of various B12 forms, are you concerned about the serum levels at all? Or one can keep taking high B12 doses even when the serum level is already high?

Thanks

 

[Snow Leopard]

I wouldn't worry about it too much.

But if you want to try something, then here are my suggestions: Based on personal experience (I can't tolerate high doses of Folic acid), I would try swapping the folic acid for an equivalent effective dose of folinic acid. Or you could try Rich Van Konynenburg's 'Methylation protocol' (results are not guaranteed though).

 

[PeterPositive]

Thanks Snow Leopard,
as regards folic acid, I not using megadoses. I take a regular 400mcg of Methyl Folate (Jarrows) and there's another 200mcg of folic acid in the active B complex I am taking.

Is the folinic acid better than methyl folate? In terms of absorption I mean.

cheers

 

[Valentijn]

My ND suggested to check for mthfr mutations. I live in Italy, while I can probably find a lab near here to test that I see people here tend to use more comprehensive panels that look for many other related mutations. Can you recommend an international lab that can offer a more comprehensive test to check for methylation issues?

From Europe, it costs about US$200 to get genetic testing from 23andMe, with shipping included. They test most of the relevant methylation SNPs, and quite a few other things as well. In total, they give results for about 960,000 SNPs.

 

[PeterPositive]

Thank you Valentijn,
I was looking into testing with 23andMe and I noticed comments by other people as regards the accuracy. It looks like there're still some reliabilty problems in testing saliva vs blood. Am I correct?

I also noticed some comments about the fact that 23andMe don't include certain SNPs that might be relevant to the methylation cycle. Does this make sense? What is your experience?

Cheers

 

[Valentijn]

Thank you Valentijn,
I was looking into testing with 23andMe and I noticed comments by other people as regards the accuracy. It looks like there're still some reliabilty problems in testing saliva vs blood. Am I correct?

I also noticed some comments about the fact that 23andMe don't include certain SNPs that might be relevant to the methylation cycle. Does this make sense? What is your experience?

I think the accuracy is supposed to be about 99%. I have found two SNPs (while looking at thousands), which 23andMe reports incorrectly for everyone.

It might not include a couple SNPs relevant to the methylation cycle, but it includes dozens of additional SNPs relevant to the methyl cycle, compared to the Yasko panel, and nearly 1 million SNPs, some of which might be relevant to other conditions. Some lists of 23andMe SNPs relevant to methylation are at:
http://forums.phoenixrising.me/index.php?threads/interesting-mtr-variations.24572/
http://forums.phoenixrising.me/index.php?threads/interesting-mtrr-variations.24551/
http://forums.phoenixrising.me/index.php?threads/interesting-mthfr-variations.24543/
And so on.

 

[PeterPositive]

Thanks again,
it's much appreciated. I'll check the links very soon. Lots of stuff to process.

 

[PeterPositive]

Just a little side question. Can you guys keep your homocysteine levels in a decent range? Or maybe you have been able to do so after finding out the SNPs and employing the right supplements?

I seem to be pretty much stuck at 14-15 no matter what, and have already excluded kidney or thyroid issues. I will see what the genetic test says.

 

[PennyIA]

I can report my own experience. I had high homocysteine levels > 14 when I had a Pulmonary embolism (blood clots in lungs, nearly died in 2004). That's part of the risk factors from having high homocysteine levels. It's worsened by other blood clotting risk factors - which include a lot of genetics reported by 23andme (I'm thinking very specifically about FVL). Most people hear 'genetics' and immediately think that they would know if it applied to them, ergo it must not. I know that's what I used to think until after I had my Pulmonary Embolism. In fact, I have two clotting conditions and lived my entire life without knowing I was at risk.

I did get put on folic acid, b6, cyanocobalamin (b12) immediately. And started to get ill very shortly after that and have been ill pretty much ever since. I have SEVERAL MTHFR defects which were only discovered after I started to put together the timing of my illness, the extremely high levels of b12 in my blood (but lots of symptoms of b12 deficiency) and toxic levels of b6.

However, the folic acid, b6 & b12 DID drop my homocysteine levels into the normal range pretty quickly. The sad thing is that they seemed to have contributed to a lot of health issues because I wasn't taking the right forms of the vitamins. Once I started following the advice of a integrative md who treats methylation issues is the first time I felt like I was starting to recover.

I'd agree with the recommendation that the 23andme testing is invaluable and that it might eventually help explain the remaining high level of homocysteine you have and perhaps even help discover a way to get it lower yet.

 

[PeterPositive]

Thanks for the recommendation.

 

[alex3619]

The basis for high B12 and high homocycteine is some kind of problem with enzymes that are supposed to deal with these. The most likely causes are methylation related mutations, but not all of those may be known yet, not even with the best testing. However if no snp mutation can be found, then I would suggest looking at toxins. Metallic toxins, especially mercury, might cause similar issues, I have not looked into this much though.

I have normal B12 but higher than normal homocysteine. So far I have not found the cause, but my testing options are limited.

 

[PeterPositive]

Yes, indeed heavy metals have been mentioned to me by several doctors. I have done some tests (the classic hair analysis) which resulted in high levels of mercury, so that's also something to check. Unfortunately this is another of those topic where there's very little consensus among practitioners. E.g. the hair test can be regarded very differently depending on the doctor you speak to.

At the moment I am trying to reduce the Hg levels with anti-oxidants, vitamins and glutathione. I know there are stronger drugs to do that, but I've also read many "horror stories" about mobilizing too much Hg too quickly.

Similarly to other people here I am pretty sensitive to strong drugs and especially their side effects. Two years ago I could hardly handle small doses of B vitamins now I can take high dosages without problems, so for me the trick is to listen to the body and gradually build up the tolerance.

For example my body refuses TMG, no idea why, but I can take SAMe without problems. Hopefully the genetic test will be able to shed some more light.

Thanks!

 

[triffid113]

The basis for high B12 and high homocycteine is some kind of problem with enzymes that are supposed to deal with these. The most likely causes are methylation related mutations, but not all of those may be known yet, not even with the best testing. However if no snp mutation can be found, then I would suggest looking at toxins. Metallic toxins, especially mercury, might cause similar issues, I have not looked into this much though.

I have normal B12 but higher than normal homocysteine. So far I have not found the cause, but my testing options are limited.

Other than heavy metals, have you tried Vitamin D, antioxidants, and/or TMG? I forget what part of the cycle is dysregulated by D shortage but I think it's the P5P excretion path. TMG lowers post-prandial homocysteine and is very fast compared to B12+folate path. Free radicals dysregulate the cycle so antioxidants are important. (I cannot quantify this as I have been taking Olympic doses of antioxidants all my life). You prolly know all this, but just in case you missed one. Oh, also, zinc is a required cofactor for at least one of the methylation enzymes (I think methionine synthase). And copper is involved somewhere...witness that a copper deficiency causes the exact same neuropathy as B12 deficiency. So ability to absorb copper and zinc would be important (maybe) to methylation (idk, because maybe methylation uses so little of these that they are not a real concern except in extremes??). And absorption of copper (and potentially zinc) is less w/o youthful hormones. (Can this be totally fixed by supplementation or is it a metallothionein issue? maybe you know?). I kind get the idea you know everything there is to be known.

 

[PeterPositive]

Hi Triffid,
actually I am not entirely familiar with all of the aspects that you have mentioned, so thanks for pointing them out. I have read about the other co-factors that might get in the way of the methylation cycle but I haven't looked into them thoroughly. I am currently having a hard time processing supplements with minerals due to GI problems. Magnesium in particular is a "bad beast" for me so I try to take it from the diet more than anywhere else.

TMG is another type of supplement that I can't process. Reason unknown. I hear that people usually don't have problems with TMG while SAMe is usually more problematic. For me it's the other way around. Go figure

Is there a reliable way of measuring trace elements such as copper/zinc etc... ? I have done a few hair analysis but doctors usually say they aren't reliable and I can understand why. Are serum levels of those element of any significance?

Thanks

 

[PeterPositive]

Oh... one more question.
Does it make any sense to keep swallowing active B12 (methyl-c or adenosyl-c) when serum levels are already at the top of the scale?

Since my Hcy level is pretty much stable at ~13 no matter how much B12 I take it seems sensible to think that B12 is not making any difference and that I should probably look into other strategies... e.g. higher folate or SAMe or other cofactors etc...