MTHFR, Methylfolate interested people, important research on inflammation and supplementing folate

So there are some on the forum I know such as myself who have discovered that they are homozygous for MTHFR C677T and thought that maybe we would do well to get on to some methylfolate, only to end up suspecting that it is making us worse. As I have posted previously, there is research to show that people with IBD have a significantly higher incidence of this genetic polymorphism than in the general population so it is relevant for lots of us here, even though it is not going to reach mainstream for a good while I think.

I have found the abstract of what looks like a really interesting research report
"Effect of multivitamins on plasma homocysteine in patients with the 5,10 methylenetetrahydrofolate reductase C677T homozygous state"

concluding that for this mutation
it is unnecessary to adminster high doses of folate to reduce plasma Hcy levels, and administering high doses of folate may cause pro-inflammatory and pro-proliferative effects

The research is focussed on lowering homocysteine but I of course am interested in the pro-inflammatory effects as inflammation is our enemy in UC.

The whole report costs £30, trying to find a way to get it from a library but if I cannot might buy it as I really want to know what form of vitamins they used and in what combinations.

www.spandidos-publications.com/mmr/8/2/609/abstract


ABSTRACT
"The role of hyperhomocysteinemia (HHcy) as a cardiovascular risk factor remains a matter of debate, while it correlates with folates, it demonstrates inverse correlation with plasma homocysteine (Hcy) levels and vitamin B12 levels and reduces plasma Hcy levels following supplementation with multivitamins. The purpose of this study was to demonstrate that administering multivitamins at specific doses for 90 days restores normal plasma Hcy levels in women who are homozygous for the thermolabile variant of 5,10 methylenetetrahydrofolate reductase (MTHFR C677T). We enrolled 106 healthy females aged between 30 and 42 years, who were non-smokers, non-vegetarian, normotensive and who had no history of food abuse in the previous months. Only females were enrolled in order to rule out any bias due to the variation in Hcy plasma concentrations between males and females. Patient blood sampling was performed in order to determine plasma Hcy, serum folic acid and vitamin B12 levels. Furthermore, molecular characterization of the C677T polymorphism present in the MTHFR gene, was also performed. The results of this study demonstrated that supplementation with specific multivitamins restores normal plasma Hcy levels, regardless of the MTHFR genotype. Furthermore, it is unnecessary to adminster high doses of folate to reduce plasma Hcy levels, and administering high doses of folate may cause pro-inflammatory and pro-proliferative effects."

Thanks OM, that's really helpful for following the trail and confirms that there seems to be an efficient level.

What I'd really like to see from the other study though is what inflammatory markers they measured and at what level they were affected because of our experience of methylfolate seeming to provoke the colitis
i.e. "administering high doses of folate may cause pro-inflammatory and pro-proliferative effects"
I can't see that this previous study looked at any inflammatory markers?

Supplementing anyone with mthfr wth folic acid will cause increased inflammation. One needs bioavailable folate in the form of l 5 methyltetrahydrofolate or metafolin/quadrafolic etc.

I have no doubt people gets sicker for a variety of reasons on methyl folate. They get sicker because they rev the cycles, or the feed a dysbiotic bacteria.. or because detox happens too rapidly. I felt like hammered dog poop for the first 6 weeks of lmethylfolate. I do think in the end *I* needed to push through it just so I could jumpstart my methylation and transulfation cycles.


Im just talking about your study and inflammation in my last comment.

Hi Conquer UC - I am on the trail to get the study, will buy it if I don't get hold of it as I really want to know what they used, as you say, we need to know that to put the picture of it together

Took methyl folate and methyl b12, but not b2.
Old Mike

I supplement every b vitamin including riboflavin, thiamine, niacin, pantheoic acid, biotin, cobalamin, folate and pyridoxine.

I started with just b12 and b9.

Riboflavin was not my issue. Good luck with your research.

Meanwhile have found that says low B2 definitely relevant in the c677 TT mutation (that I am)

www.ncbi.nlm.nih.gov/pubmed/15941973

Dietary intake of folate and riboflavin, MTHFR C677T genotype, and colorectal adenoma risk: a Dutch case-control study.

Abstract

We investigated the associations between dietary intake of folate and vitamin B2, MTHFR C677T genotype, and colorectal adenomas in a Dutch case-control study. Data of cases with at least one histologically confirmed colorectal adenoma (n = 768) and controls with no history of any type of colorectal polyp (n = 709) were included. Dietary intake was assessed using a food-frequency questionnaire. Multivariable models included age and, if appropriate, dietary folate and calcium intake. The adjusted odds ratio (OR) and 95% confidence interval (CI) for the highest compared with the lowest sex-specific tertile of intake were 1.32 (95% CI, 1.01-1.73) for folate and 0.51 (95% CI, 0.36-0.73) for vitamin B2. Folate seemed to be a risk factor, especially when vitamin B2 intake was low; vitamin B2 was inversely associated with adenomas, especially with relatively high folate intake. No association was observed between MTHFR C677T genotype and colorectal adenomas. The inverse association between vitamin B2 intake and colorectal adenoma risk seemed to be more pronounced among those with the MTHFR TT genotype. We conclude that this study does not provide evidence for a decreased colorectal adenoma risk for subjects with high dietary intake of folate. It suggests, however, an inverse association between vitamin B2 and colorectal adenomas, which may be more relevant for those with the MTHFR TT genotype.

and then further research that this is probably also involved with mutations in SLC19A1, where I am hetero it would seem on the risky SNP
www.ncbi.nlm.nih.gov/pmc/articles/PMC3059778/#!po=85.2941
Variation in folate pathway genes and distal colorectal adenoma risk: a sigmoidoscopy-based case–control study

So I got hold of the full article of the abstract that I linked to in post 1 and found that the research on pro-inflammatory effects is from another study which is here (full open access)

[url]http://www.ncbi.nlm.nih.gov/pubmed/20567905[url]
The homocysteine controversy

Abstract said...
As we explain, such side effects may relate to direct adverse effects of the B-vitamin regimen (in particular, the use of high-dose folic acid) or to proinflammatory and proproliferative effects of B vitamins on advanced atherosclerotic lesions.

The research is focussed on heart rather than colon. They also cast doubt on whether C677t on the MTHFR is really the most important gene to be looked at in relation to folate's relationship with homocysteine.

Post Edited (London Lurker) : 4/15/2014 3:51:47 PM (GMT-6)

It's where much research has been focussed though PK, that's what they are saying, they are saying other genes need to be studied but heart disease/homocysteine connection has been researched greatly in conjunction with c677t with nothing really conclusive coming out of it in terms of how to reduce homocysteine and protect from inflammatory effects of folate.

did you post this paper about Riboflavin, homocysteine and MTHFR c677t?
www.clinchem.org/content/46/8/1065.full

London Lurker said...

What I'd really like to see from the other study though is what inflammatory markers they measured and at what level they were affected because of our experience of methylfolate seeming to provoke the colitis
i.e. "administering high doses of folate may cause pro-inflammatory and pro-proliferative effects"
I can't see that this previous study looked at any inflammatory markers?

As for Conquer, I hope you dont mind me chiming in on this but Conquer, has an overgrowth of a bacteria that is unique in that it can use preformed folate. So it isnt about lmethylfolate causing inflammation, instead it is about the biome being out of whack with a bit of a nasty bug.

I know they discuss snp's. I'm not saying they are not related at all. In fact quite the opposite. It's a big area of research that's for sure. Quite daunting though. But what we learn differs in many ways from all these crazy websites on mthfr etc etc. . Things like most of the snp's from 23&me and other companies are in non-coding regions - so before the gene itself, so the effect is actually unknown other than there is reported "higher incidence" based on some studies because of the snp.

23 and me no longer shows health related reports because of the FDA. Now I have to laugh at myself here as when it first came out I made a post and also made some comments about the FDA overstepping and interfering and all that and a lot of people got on my case. I find it funny that after progressing here through school that I can see why they did this and actually think in some ways it was a good decision.

I also should point out that I always thought that 23 and me was actually reading my DNA!! - and telling me that I have certain specific genetic problems based on my genes and all that jazz... but this is not the case at all. It's done via a gene chip and just points out specific snp's that "their researches" find most interesting AND the number of snp's that are cost effective for them to analyze, which goes back to the chip. In total the human genome is some 3 billion base pairs so really estimates range from 3,000,000 to 10,000,000 snp's can be present in an individual - or 1 snp per 1,000 base pairs to 1 snp per 300 base pairs. 23&me will analyze for about 1,000,000 snp's now i think.

So what the heck is a base pair? And what is a snp? and what is a coding and non-coding region? thats what I was thinking of adressing based on what I was taught as there seems to be a lot of confusion where people get their results and immediately assume they are lacking certain enzymes and stuff... which may not be the case at all.

In short - 23&me results are not really showing you have a specific "defective gene" or "faulty gene" which is producing a faulty enzyme and leading to disease via a messed up pathway. It's comparing your snp's (and not all of them that you may have) to certain specific populations or ethnic groups based on the data from the human genome project.