• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To register, simply click the Register button at the top right.

MTHFR, folic acid, vit D and detoriation


Senior Member
A friend of mine is really sick so I'm posting this for her. She has tested positive for MTHFR mutation but this was in the 90's and she doesn't know what kind she has. Her doctor then gave her folic acid but she noticed no effect. Now she's tried adding folic acid again and is getting worse. She doesn't know what's causing it.

Is everyone with a MTHFR mutation supposed to avoid folic acid? Can that explain her symptoms? Here is her story:

"Have defective gene MTHFR (don't know which type). Have taken b12 in the form of oral cyanokobalamin, 1 mg, since mthfr problems were discovered, ca 17 years ago. Never tried injections. Only tried higher dose, 2 mg, when first diagnosed. Then another doctor lowered to 1 mg when bloodwork came out normal. Also was first prescribed folic acid, but only took that until bloodtests were normal, then stopped altogether, as per same doctor. So only 1 mg oral cyanokobalamin för 15+ years.

Have severe insomnia. Have been sleeping w/ help of half a dozen sleep medications for many years. Especially when I crash, my sleep gets worse (both harder to fall asleep, harder to stay asleep, impossible to fall asleep again if awakened, worse circadian rhythm etc). Have solved this with temporary overmedication and more strict pacing. This has always worked. Of course, have unrefreshing sleep.

Was found to have vitamin D deficiency, have taken 10.000ie daily for ca 16 months. After 2-3 months, I noticed better mood (although already on 120mg Cymbalta for many years) and better sleep overall, but esp falling asleap easier and sooner.

April 1st, I started taking folic acid. I remembered that the doctor who diagnosed my mthfr gene in the 90's prescribed not only b12, but also folic acid, so I started supplementing that with Solgar's folic acid, 400mcg. A few months before that, I had also started taking 100mg Q10 and 500 mg Acetyl-L-Carnitine

The last month I have had severe sleep problems. My sleep behaves exactly as it did before vit d, only worse in all areas. Have not had insomnia this bad for ca 8 years.

Also, my husband told me today that I have seemed depressed for the last two months. Am housebound/bedridden, and have experienced progressive worsening for 21 years, so ascribed that to normal turn for the worse cycle with a side of grieving. And also, not sleeping is a sure way to depression.

Other sympyoms that have been exacerbated are numbness and coldness in hands/feet, and serious cognitive impairment to the point of not understanding normal conversations.

Have had sleep problems of this caliber for three weeks. My problems center around the following: Circadian rhythm back to my old normal, i e sleep arrives at about 06 am. If I go to sleap earlier than that, with the help of my "horse tranquilizors", I wake up after 4 hours and have to take another round of most of my sleeping pills, and then get another 4h. This may sound much to some, but it makes me suicidal. My body needs min.10h or my symptoms flare up ridiculously. Even if I fall asleep at six, I only get 8 h. This did not start in conjunction with any outside event, but was still quite sudden. And a week ago, I stopped taking anything that I have only taken in 2015.

Re being suicidal. I am not being overly dramatic. The same thing happened eight years ago, when I had recently moved, didn't have a doctor, and hence no sleeping pills. My insomnia got bad enough that I had to seek psyciatric help. With the deterioration of my ME since then, I break down sooner. My safety margins are close to zero. I have had a clinical depression, and this feels much more compartmentalized. Sleep sucks, but other than that I'm normal. But when I wake up too soon after already overdosing to fall asleep at all, I feel despondent. I dream of taking 30 pills and be done with it. Not that I want to die, or would actually kill myself, but because the desperation for sleep is larger than anything.

It would seem this is not my normal cycle of deterioration. Have since learned of others who got insomnia from both Q10 and ALC. And that people with the mthfr gene mutation cannot digest folic acid. Instead, they get b12 deplored. That would explain the cognitive impairment. But regarding the insomnia, it feels like my body can't get to the D3. Could thw folic acid block uptake of D3?

The sleeping pills I take are, except for 800mg magnesium, an ibuprofen and a Tylenol: 10 mg Zolpidem, 3 mg fast acting melatonin and sometimes an additional slow release of 3 mg, 25 mg propiomazine (antihistamine), and 10 mg mianserin (precursor of mirtazapin and a tetracyclic antidepressant).

Can taking a folic acid with a mthfr mutation for 5+ months do this? Have you heard of similar occasions? Do you have any input? Would greatly appreciate any additional help! Love, Anja from Sweden"
MTHFR mutations aren't a diagnosis or a disease. They're just common variations. Some are pretty mild, and if folate levels test as normal, there shouldn't be a problem, and supplementing is unnecessary.

But it might help to test for active folate instead of folic acid, since MTHFR mutations slow down the transformation of folic acid into active folate. Similarly, people with MTHFR mutations usually prefer to supplement active forms of folate, not folic acid.

If something is making her feel worse, she should probably stop taking it, or at least talk to a doctor about it.


But I Look So Good.
Left Coast
When I didn't have stuff for methylation balanced I was in a rage. Or crying.

I forget the docs name but there is a site about side effects. Maybe @PeterPositive knows. I'm drawing a blank in his name.


Senior Member
@minkeygirl I believe you mean Ben Lynch's article about methylfolate side effects.

Note that insomnia is on the list of side effects. There is a later article linked in that article with even more info on how to work through side effects.

That's if the folic acid is actually working. This would depend on which MTHFR mutations she has. It's possible that the folic acid is not being converted and in addition, it could even be blocking methylfolate. That would be slowing methylation, which would slow production of neurotransmitters, which would impact sleep.

In general, nobody (especially those with certain SNPs such as MTHFR and the B12 SNPs MTR and MTRR) should be taking the synthetic B vitamins, folic acid and cyanocobalamin.

Oral B12 (in any form) only absorbs 1-2%, so it's almost like taking nothing. B12 should be taken sublingually to get around stomach absorption issues. The forms hydroxycobalamin and especially methylcobalamin are more active and get into the cells better.

Folate and B12 work together. Consuming too much of one without the other creates a deficiency situation. Assuming that the folic acid is working at least somewhat, and the cyanocobalamin is barely working at all, the folic acid could be creating a deficiency in the B12. This again, would slow methylation, which would slow production of neurotransmitters and impact sleep.

Of course, neurotransmitters are also import for mental health, so the depression could be caused by this as well.

The other thing which impacts sleep is the adrenals. The delayed sleep phase you reported is typical of adrenal fatigue.

The numbness and coldness of hands and feet sound like either neuropathy or Raynaud's. That, and the cognitive impairment, could be B12 deficiency.


What I would suggest is to stop taking all of the new supplements you have added in. That would be folic acid, CoQ10 and carnitine. It does look like all of the above could cause insomnia.

Hopefully, that will get you back to your "normal" baseline after a period of time.

Then I would suggest doing research on methylation before trying more supplements. I have some beginners' videos and other documents in my signature link.

I could say more, but I don't want to overwhelm you when all you want is some decent sleep! Good luck!


Senior Member
Northcoast NSW, Australia
My terrible insomnia resolved after I'd gotten up to theraputic levels of B12.

In addition to the Lynch article from Caledonia, here are some other links to his articles re folic acid, vs folate. You might not want the pdf and vid at the moment, but very helpful for further understanding of MTHFR issues. Also in my signature, Methylation for Dummies


More articles here: http://mthfr.net/?s=folic acid

Folate Metabolism and MTHFR: An Introduction (1.21min) vid



Certified in Environmental Medicine, ATSDR
Methylation cycle issues are complicated. It really is necessary to have your SNPs determined, because they interact. I endorse what Caledonia and ahmo said, don't take cyanocobalamine. The forms and amounts of folate, B12, etc have to be correct for her specific variances. Cyanocobalamine is a cyanide plus B12 form. In a body w/o variances the cyano would be lopped off and disposed of, then a methyl would be added, converting it to methylcobalamine. MTHFR issues mean that she can't add a methyl at some point(s) in her metabolic cycle. Dr. Smith explains it like a railroad yard manager must construct the trains according to the order sheet. He can't add any cars until the next one on the order sheet shows up. Everything in the yard backs up until that car arrives. Our methyls don't show up... I have 18 methylation errors. I also have MTR and MTRR variances. I inject mB12 subQ. I don't take methylfolate because of the cascading effect of my other errors, but I do take TMG, as opposed to DMG. Because of the "Rube Goldberg Trap" like function of the methylation cycle and intertwined co-exist cycles, DMG gives me migraines. Its very complicated! I also take BH4, the short cut to glutathione production. This worked great until I got glyphosate exposures. Glyphosate is a chelator. I believe it sucked out my cobalt. I'm going to discuss that, and getting tested to determine how much I need to increase my mB12, Tuesday. My best suggestion is have her run her DNA, and get biometric testing through Dr. Yasko. :bouquet: