MTHFR gene defects - resources and info

I'm not 100% sure this is the right forum for this, but it'll do until someone decides there's a better one out there. This is partly stuff straight out of my head from the research I've done into MTHFR defects for my own family, and part copying of notes that our naturopath gave us when we had hubby's MTHFR polymorphism officially diagnosed.

MTHFR is a gene that affects the methylation pathway in the body. The methylation pathway does a TON of stuff, but the bit we're most interested in is its role in a) transforming various forms of folate into other forms that the body can use, and b) the effect this has on the body's detoxification pathways. If your body isn't metabolising folate how it should, it can impact a ton of different processes in the body. Hence a gene mutation can manifest in many different ways, symptoms, and disorders. These include autism spectrum disorders (one study showed 98% of autistic subjects that were tested had an MTHFR gene defect), ADHD, fibromyalgia, gluten and/or dairy intolerances and allergies, depression and other mood disorders, repeat miscarriages and other pregnancy issues, and a ton of others that I don't remember right now. www.mthfr.net has a whole list.

Standard MTHFR testing is now available through many places in many countries. I can only speak to Australia, since that's where I live. Here the test is $65 and non-Medicare rebatable, unless you or a direct relative have a history of deep vein thrombosis. As far as I know all the MTHFR specific tests only test for the two most common defects. These are C677T and A1298C. While these are the two most common, there's about 20 known locations on the MTHFR gene where a defect can occur. Thus getting a full spectrum gene analysis (such as provided by 23andme.com) can be very helpful. Full gene testing will also reveal if you have more or different polymorphisms besides MTHFR, as there's a few others that can greatly impact your health.

Gene defects can be present as either heterozygous or homozygous mutations. Genes always come in pairs. If you have a heterozygous mutation, that means you have one copy of the defective gene. If you have a homozygous mutation, then both copies of the gene are defective. How many defects you have determines how badly your methylation pathway is affected. For example, hubby has a homozygous mutation (both copies affected) at C677T. This means that his methylation pathway is functioning at about 25% of normal. The lab test we got back states that the C667T homozygous mutation is "found in 8-18% in various populations". From memory, someone with a homozygous A1298C mutation has pathways running at 10% of normal. (Given these numbers, I expect anyone with homozygous mutations at both positions would probably be dead or very, very sick.)


Types of folate
folic acid - A synthetic version of folate that's federally mandated to be added to flour and many other processed foods. Also very common in supplements. Conversion to usable folate is poor even in healthy individuals, and it can be downright toxic in someone with an impaired methylation pathway.

folate - The naturally occurring form of folate found in food. Most prevalent in leafy greens.

folinic acid - not the same thing as the synthetic version! A type of folate that's important for DNA synthesis. 3 steps away from being converted into activated folate. Depending on what type of mutation you have, it might be an idea to skip this form. In other cases it might be useful to include it, especially if you're pregnant (since you want to be turning out good DNA in the foetus). Something to discuss with a health care provider who's familiar with MTHFR mutations.

5-methyltetrahydrofolate - AKA activated folate, 5-methylTHF, methylfolate. This is the final step in the folate cycle. It's also the form that people with MTHFR mutations have the most trouble creating.

The following stuff is more or less verbatim from the naturopath's notes. My comments are in round brackets (like this).

Steps to Take When You Find You Have a Mutation
Remove Folic Acid from your diet.It's common in supplements, non-organic flours, fruit juices and breakfast cereals. Read labels carefully - folic acid is often wrongly labelled "folate", so if either of these is listed, don't eat it.

Incorporate Folate into your diet. Add lots of leafy green vegetables, eg spinach, kale, lettuce, mustard and collard greens. These are best eaten raw as folate is a heat sensitive vitamin and breaks down quickly when cooked. So either eat them raw or add during the last few minutes of cooking. (I find green smoothies the best way to get a lot of greens in our diet, since we're both salad haters.)

Get tested. Discuss with your health care provider about relevant tests that may be helpful to see how the methylation cycle, and the body as a whole, is running. RBC folate, active B12, homocysteine, thyroid function, E/LFT and haematology are a good start. Other useful tests might include zinc, B6, neurotransmitter analysis, stool analysis, or hair mineral analysis. (Hubby had all but homocysteine and the last three done, plus about half a dozen more. In this case thorough is good and getting them all done at once helped to save him from multiple blood draws. Our naturopath gave us a list of tests to order and we had to take them to a doctor to get them done - some were covered by Medicare, some not. You usually need a GP that is familiar with gene defects and/or the need for nutritional panels - any old doctor at the walk-in clinic will probably order the wrong ones, not order all the tests, and generally stuff you about. At least that's what happened to DH.)

Perform a Toxin-ectomy on Your Environment. (I'm sure most folk here are aware of how to go about this. How thorough you need to be depends on how bad your mutation is. Someone with a heterzygous C377T might be able to get away with removing the low-hanging toxin fruit from their life; whereas a person with a homozygous A1298C might need to go whole hog to give their impaired methylation pathways a chance to catch up and de-crapify their body. In any case, lowering the toxic load of your living environment is a good thing for everybody.)

Minimise pesticides and herbicides - these interfere with the methylation cycle.

Avoid processed foods. If you don't recognise words on a food label, don't buy it. (Side note: I find this much better advice than "If you can't pronounce it, don't eat it" since fellow sesquipedalists will have no trouble pronouncing things like "methyltetrahydrofolate" and "sodium lauriminodipropionate" and "cocamidopropyl hydroxysultaine".)

Avoid charcoaled foods, nitrates (found in food additives, cheeses and cured meats) and sulphites (found in sausages, cordial, dried fruit and most wines). These interfere with detoxification pathways. (A partial list of numbers to avoid: Tartrazine (106), Dyes (102, 104, 107, 110, 120, 122-124, 127-129, 131-133), Sodium benzoate (211), Sulphites (221-224), Nitrates (251,252), BHA (320), BHT (321), MSG (621), Artificial sweeteners (Aspartame, NutraSweet). Please keep in mind that I'm in Australia, so the numbers might mean something different in a different country.)

Avoid High-fructose Corn Syrup (HFCS) and trans-fats. They alter glucose metabolism, damage the liver, and affect fat breakdown.

Stay away from soft plastics that contain Bisphenol-A (BPA). They disrupt the endocrine system, especially the thyroid, which is necessary to activate the B2 that acts as a co-factor for the MTHFR enzyme. (It's probably best to avoid plastics in general, where possible, but let's face it we live in the Plastic Age and it's not always feasible. We try to stick to hard plastics where we can, and we're very slowly buying more metal and glass stuff as funds permit.)

Use the stove instead of the microwave. (We don't, our stove is old and electric and just generally horrible. Maybe next house.)

Use natural body care products that don't contain harsh chemicals, and use safe natural cleaning products. (The skin is your biggest organ and it absorbs a LOT more stuff than most people realise, so this is one to be very aware of if you suffer from any type of autoimmune disorder.)

MTHFR Resources on the Web
These were all provided to us by our naturopath. I haven't had the chance to check all of them out yet, but the ones I've gotten to are full of all sorts of useful info. It can be a bit overwhelming so I'd recommend starting with Dr Ben Lynch's stuff and branching out from there.

Dr Ben Lynch - MTHFR Resources
Dr Amy Yasko - Dr Amy Yasko
Stirling Hill - MTHFR Support
Carolyn Ledowsky - An Australian researcher
Dr Andrew Rostenberg - Beyond MTHFR
Methyl Cycle Nutrigenomics - A VERY detailed explanation of the methylation cycle
Genetic Testing at 23andMe - 23 and Me
MTHFR Gene Mutation Facebook page
MTHFR Genotype Support and Education Facebook page

If anyone has any questions feel free to ask and I'll do my best to answer them. Please keep in mind though that I'm not a medical professional in any way, shape or form - just an unusually self-educated permie with a family full of gene defects.

Thanks so much for posting this! This is very helpful.

I may find the answer I dig through all that but I wondered if you have any info in regards to Niacin. It seems that Niacin also has a methylation cycle? If I find that I have an mutation in the MTHFR gene, is taking Niacin a problem? I've tried googling and gotten some conflicting information on whether niacin is good or bad for folks with methylation issues. I take 300mg of niacin daily to lower my cholesterol (not really high overall but my Trig is not good and the niacin is helping with that...besides, it keeps the doctor off my back about taking statins which I simply will not do). I take it in a single dose before bed so the "flush" happens while I sleep. But, now I'm wondering if this is perhaps causing me a problem? any thoughts?

Thank you for posting this! I have the mutation, I can't remember which variant, But it's the "not so bad" version. Since getting the news and adjusting my diet and fiddling around with the dosage of methylfolate (*and* adding niacin!) I feel so much better, the difference between having complete physical and mental exhaustion *all*the*time* and now being able to get things done, have normal conversations while looking people in the eye, not needing to hide in the closet from paralyzing fear.....amazing.
It's shocking how common the mutation is and pretty sad that it's not something that is tested for when people are showing symptoms. I know that if I had known about this earlier, it probably would have saved me a lot of grief physically and mentally. I'm just glad that I did find out about it, I was able to make changes AND the methylfolate is super inexpensive. (that said...if you suspect you have the mutation, get tested, don't just start dosing on the methylfolate!)

Cheers,
Eriko

eriko mukasa wrote:Since getting the news and adjusting my diet and fiddling around with the dosage of methylfolate (*and* adding niacin!) I feel so much better...

Cheers,
Eriko

So, adding niacin helped you?

Yes, I felt better on the methylfolate but not 100% better, so my doc and I increased the dosage...which made me feel better in some ways and not so good in other ways (hard to explain, sort of unbalanced) so we added niacin which kind of smoothed things out. Not to mention I am one of the nutty people who loves the niacin flush.

Tina Paxton wrote:

eriko mukasa wrote:Since getting the news and adjusting my diet and fiddling around with the dosage of methylfolate (*and* adding niacin!) I feel so much better...

Cheers,
Eriko

So, adding niacin helped you?

eriko mukasa wrote:Yes, I felt better on the methylfolate but not 100% better, so my doc and I increased the dosage...which made me feel better in some ways and not so good in other ways (hard to explain, sort of unbalanced) so we added niacin which kind of smoothed things out. Not to mention I am one of the nutty people who loves the niacin flush.

Ummm, that is interesting. I wonder in what way the niacin is smoothing out the methylfolate?

You LIKE the flush??? Wow. I prefer to sleep through the intense flush I get from 300mg. I woke up during it two nights ago...it was...intense. definitely prefer sleeping through it.

Edited to add:

I found this methylfolate side effects article that explains how Niacin reduces any excess SAM caused by taking methylfolate.

I wonder, though, since I'm not taking methylfolate, is the niacin reducing SAM too much in my body or ??? (I sure wish I had a better grasp of biochemistry!)

Like a lot of things with gene defects, the answer is "it depends". Some people will benefit from taking niacin as well, some won't, and the same person might react two completely different ways depending on what other supplements they're taking and how their system levels of other nutrients are. Dr Ben Lynch has a very general protocol on his website but it can take a lot of tweaking and you might not even need to go whole hog. For example hubby is worlds better just on N-acetyl cysteine and vitamin D, but we're adding in other things and changing doses as needed to see if we can get even more improvement. The next thing we're adding is inositol since it's been pretty well tested in anxiety and depression patients and can have good outcomes. He didn't respond well to it last time (a year or so ago), but now that his glutathione levels are higher, who knows?

I know that the B vitamins are involved in the energy making cycles of the body, but I couldn't tell you specifically how they're involved in the methylation process.

I did find this snippet in this article about potential side effects of taking too much methylfolate: "niacin binds methyl groups and also increases the breakdown of glutamate – which is the excitatory neurotransmitter." I'd take that to mean that it could have an inhibitory effect on your methyl production, but if you're having high levels of glutamates for some reason, it could be helping. Is your doctor likely to listen to your concerns if you point out the possibility of having a MTHFR defect and how the niacin may/may not be helping with regard to your methylation production? MTHFR defects can also present with various cholesterol/cardiovascular issues, so perhaps you're treating the problem a step or two up the chain rather than at its source?

Edit: punctuation