Known about my MTHFR gene for a while but never really done anything about it.

For about 10 years my heart rate has sat higher than I would like.

The other week I took some methylfolate and it corrected it, which has blown my mind. Is it due to my inability to absorb folate properly that my heart beats faster? Has anyone else experienced this?

Also I had a wicked headache afterwards which has prevented me from taking any more. Could it be that methylfolate didn't actually suit me?

Last week I took 15mg of methylfolate and got a runny nose and some physical anxiety. However, mentally I was basically teleported back to my pre-morbid state. This lasted for a few days after. I then a couple days ago I tried again at 5mg and felt great, but am experiencing terrible insomnia ever since. Strangely, I am very energized during the day and have read the same from many others. I do not find this energy to hypomanic in the slightest aside from the greatly reduced need for sleep. I'm not entirely sure how reduced my sleep is because I have taken steps to pharmacologically ensure some at least 5 hours as I wait for this to pass. I'm thoroughly impressed if not a bit overwhelmed by how effective this has been otherwise, though. Next time I'll trial 500mcg and work my way up in weekly increments.

Thought I'd share in case others have had similar experiences or have thoughts to share.

Hey folks, I wanted to post here since the MTHFR/B12 subs helped me understand this issue and without it I wouldn't even suggest it to my doc.

As the title states, I came back compound heterozygous with the MTHFR mutation. My understanding is that it means functionally the enzymes are working at 40-60% efficiency. This finding is well supported, and my doc and I decided I will start taking the proper B vitamins/cofactors, Vitamin D + K2, and magnesium glycinate.

Before I share my issues, I wanted to share some noteworthy results:

Abnormal:

• Homocysteine 16.2 umol/L — elevated (May 2026)
• RBC Folate 382 ng/mL — below normal (Jun 2026)
• MMA 307 nmol/L — elevated (May 2026)
• RBC Magnesium 3.7 mg/dL — below normal (May 2026)
• Vitamin D 29 ng/mL — below optimal (May 2026)

Confirmed diagnoses

• UARS confirmed on gold-standard in-lab PSG (Oct 2022) — arousal index 26.2/hr, sleep efficiency 67.4%, never treated
• LPR confirmed independently by GI (Dec 2024) and ENT (Mar 2026) — cobblestoning on scope
• EAEC detected on PCR stool test (Dec 2024) — never confirmed cleared
• Compound heterozygous MTHFR — C677T + A1298C (Jun 2026)
• Chronic inactive gastritis on biopsy (Nov 2024)
• Two nasal surgeries — zero symptomatic improvement

I know this community is for MTHFR specifically so I may be out of scope here, but I have a hard time believing all of this stems from a functional B12 deficiency, especially seeing my RBC folate and other blood labs relatively normal. My doctor is not thinking it's an autoimmune thing i.e. pernicious anemia. I am curious if it's low stomach acid / SIBO (glucose test pending!)

As for symptoms, I have a whole bunch, I'll limit to top contenders

1. Chronic fatigue / unrefreshing sleep
2. Morning brain fog
3. Extreme shortness of breath despite no structural issue / asthma
4. Autonomic like symptoms i.e. cold feet, sweaty hands, difficulty with balance and walking straight (mild, nothing crazy)
5. Chronic inflammation of airway, particularly nose. (I assume it's pepsin from LPR)
6. Slow gut motility
7. Acne in weird places like shoulders, back, forearms

What would you do in my shoes?

I have been tested only for MTHFR, but i would like to have a full genetic test. Do you know an online test to order and send back, without asking my doctors ?

Folinic Acid is what I take. I don't know why this took me forever to find out.

I primarily take Source Natural's pills, but I recently came across iHerb's folinic acid liquid drops for around $12 for 750 servings (660mcg per drop) and that is so much cheaper than Seeking Health and Source Naturals too. Them being drops also would absorb more effectively too.

For those of you who rely on folinic acid I figured I'd share because it's a huge cost savings.

Hope this helps someone!

I just got my Ancestry test results back and some things really stood out to me:
• Slow COMT (AA)
• Slow MAOA (TT)
• MTHFR A1298C (one copy)
I've struggled with anxiety, depression, and OCD for as long as I can remember. About 5 years ago I started Zoloft, and it's been helpful and keeps me stable for the most part, but I still deal with so many symptoms daily.
Seeing these DNA results makes so much sense and honestly feels validating. I'm still waiting on my MyHeritage results so I can combine both Ancestry + MyHeritage for more complete data.
There's SO much information out there about these genes, methylation, supplements, etc. and I feel so lost trying to figure out what actually matters for me.
Has anyone else had similar results? Any advice on where to even start?

I’m B12, Vitamin D, Potassium and Magnesium deficient (and most likely Iron). My PC is kinda “condition shaming” me. I’m telling him, to be engaged enough to help me figure what’s going on with these conditions, because the MCAS clinic rejected me for a tryptase level of 15. It falls back on him.   My PCP is saying “we have to tackle, what we know. And we Know you need Potassium, Magnesium, B12 and Vitamin D.

That makes sense to me, but when I have extreme sensitivities to them, the question is how without just suffering through taking them like I am now?

…I’m taking Potassium Gluconate powder three times a week, the histamine builds, I’m in a horrific flare, I stop the Potassium Gluconate for 4 days or so, until the histamine inflammation goes own…

…I’m taking Magnesium Malate powder three times a week, on the alternate days of taking the Potassium, the histamine inflammation, cog fog and muscle and joint pain builds, I’m in a horrific flare, I stop the Magnesium Malate for 7 to  10 days or so, until the histamine inflammation goes own…

…Oh and Hell No, on Methylated B12!  I could only find Hydroxy B12 and it was 5000mg, so I thought, “just take a scant to try”…DUMB! The “scant” ended up being the upper of 250mg and took at least three to four days before I wasn’t an anxious, panicked, quivering mass of flesh, calling on God, prayer lines and whoever I could think of.

(It seems my 3am Adrenalin and Cortisol wake-ups were also worse for some reason?)

I know vitamins and minerals have co-factors. (partners) that either assist in issuing through the body  or helping increasing and making them more bioavailable or creating or causing a depletion.

The doctors don’t understand and basically say in so many words, “you don’t want to get well, you just want to wallow and complain . “   What I’m trying to avoid is the further “Wack-a-mole” situation for me.

My next step is taking my DNA tests….if I ever get it back… in hopes he or she is knowledgeable about this and will listen.

I have to at least try to build my deficiencies. I’m having blood labs drawn in a week or so. And I definitely can’t stack supps.

 Does anyone have knowledge and experience in trying to slowly build their deficiencies? 

Has anyone found that alternating co-factors had benefit in adding co-factors and are still alive to tell about it?

Thans

 

If you're already deep in MTHFR stuff, COMT is an enzyme worth knowing — it clears dopamine and adrenaline after they've fired.

The pattern that got me thinking about this: someone's on a totally normal-looking routine — methylated B multivitamin, their usual two coffees, a vitamin C packet — and over a few months they're more anxious, sleeping worse, and can't shake a bad mood after a stressful afternoon. Everyone wants to know which one to cut. Usually it's not one.

Coffee's catechols and high-dose vitamin C both compete with dopamine for the same spot on COMT. Methylated B's raise SAMe, which is COMT's fuel — more fuel sounds good, but if the enzyme's already slow, it just means more for it to handle. None of these is a big deal by itself. On someone with slow COMT (Met/Met on rs4680), all three at once is a different story than on someone with the fast version.

If you're Met/Met and this sounds familiar, the two things that actually moved the needle for the case I'm describing: cutting back the coffee and vitamin C to more normal amounts, and adding magnesium, which COMT needs structurally to work at all (not just "good for you" — it's part of the enzyme's active site).

I've been trying to figure this out for almost 3 years and I honestly feel like I'm going in circles.

My symptoms are:

• severe fatigue (especially mornings)
• brain fog
• low appetite
• anxiety/adrenaline feeling when I wake up
• more anxiety overall
• tingling in my hands and feet
• gas and bloating and burping
• histamine intolerance symptoms

I've already ruled out a few common things:

• Thyroid is normal (TSH + FT4)
• No diabetes
• Kidney and liver function are normal

Here's where I get confused...

Labs (NO B12 or folate supplementation at the time)

• Homocysteine: 12.5 µmol/L
• Serum B12: 1475 pmol/L
• Holotranscobalamin: 500 pmol/L
• MMA: Normal
• RBC folate: 2564 nmol/L
• Vitamin B6 (PLP): 100 nmol/L
• Ferritin: 140 µg/L
• Serum iron: 43 µmol/L
• Vitamin D: 105 nmol/L
• MCV: fluctuates between normal and Elevated (macrocytosis)
• Cortisol**: 3 (low)**

Has anyone here seen a case like this or have any ideas about what mechanism could explain it?

I'm genuinely stuck, so I'd really appreciate any thoughts.

https://preview.redd.it/u5pfvsshjtah1.png?width=708&format=png&auto=webp&s=0b5539657ab6d28e90b50464c4ad1bc619b17d65

Doubling my normal dose of B12 and Folate seems to make me feel better in almost every way but I notice two negatives. I get more swelling in my lower legs and I get more cramping in my feet and calves. Adding extra Potassium on top of what I normally take makes the cramping worse and causes my lips to start cracking.

I am wondering if it could possibly be magnesium that is being depleted by the extra B12 and Folate. Or if it could be a lack of B12 or Folate that is getting thrown off by the increase in both. What is the most likely cause if potassium makes it worse?

For almost a year I was dealing with symptoms that nobody could explain.

My main symptoms were:

• Fatigue
• Brain fog
• Difficulty concentrating
• Memory problems
• Numbness and tingling in my hands

Routine blood tests were essentially normal, so no one suspected homocysteine.

Eventually, my doctor ordered a homocysteine test, and that's when everything started to make sense.

February 2026 (before treatment)

My initial blood tests showed:

• Homocysteine: 25.7 µmol/L
• Folate: 6.69 ng/mL
• Vitamin B12: 401 pg/mL

My doctor suspected that low folate was the main cause of the elevated homocysteine.

On February I started taking:

• Methylcobalamin (Vitamin B12) – 1000 mcg/day
• Methylfolate – 1000 mcg/day
• Vitamin B6 (P5P) – 50 mg/day

April 2026

After about seven weeks, my results had improved:

• Homocysteine: 19.2 µmol/L
• Folate: 17.40 ng/mL
• Vitamin B12: 497 pg/mL

So the supplements were clearly working, but my homocysteine was still well above the optimal range.

My doctor decided to investigate further and ordered additional vitamin testing.

That's when we found something unexpected:

Vitamin B2 (Riboflavin): <2 µg/L (deficient).

Since riboflavin is an essential cofactor for the MTHFR enzyme, I started taking 100 mg/day in mid-April.

June 2026

About two months later, my blood work showed:

• Homocysteine: 13.8 µmol/L
• Folate: >24.0 ng/mL
• Vitamin B12: 533 pg/mL
• Vitamin B2 (Riboflavin): 5 µg/L (back within the normal range)

How I feel today

The improvement has been remarkable.

• My fatigue has almost disappeared.
• The brain fog is gone.
• I can concentrate properly again.
• My memory is much better.
• The numbness and tingling in my hands has completely disappeared.

Overall, I finally feel like myself again.

What I learned

This is only my personal experience, but I found something interesting.

Correcting folate, B12 and B6 reduced my homocysteine from 25.7 to 19.2 µmol/L, but it remained elevated.

The turning point was discovering that I was deficient in vitamin B2. After adding riboflavin, my homocysteine dropped further to 13.8 µmol/L, while my symptoms gradually resolved.

I'm not claiming that vitamin B2 alone was responsible—this was likely the result of correcting multiple deficiencies—but riboflavin appeared to be the missing piece that allowed my homocysteine to return to the normal range.

I wanted to share my experience because I rarely see vitamin B2 discussed when people talk about elevated homocysteine, despite its role in one-carbon metabolism.

Has anyone else here found that riboflavin was the missing piece for lowering their homocysteine?

I dont know if I have MTHFR, but my blood test said 2 ug/l folate so I took 5mg of folic acid for 4 months and felt zero difference (no bloods to confirm till next week).

So I assumed maybe I do. So I bought 1mg Methylfolate.

First few days I felt incredible?? My fatigue was better, I was able to sleep 6 hours and function fine. Usually I sleep 10 hours and im still tired.

I cant tell what it is, its so quick it surely cant be the folate deficiency getting corrected? And if its the methyl part, then that also means I have a methyl group problem?

Problem is, its also giving me a LOT of anxiety.

It feels like ive taken an ADHD med.

What is going on??

Hi everyone,
I’m completely new to this topic and would really appreciate your thoughts.
I’m 40 and was diagnosed with probable perimenopause. I started HRT (Estrogel + oral micronized progesterone), but after my estrogen dose was increased from 2 pumps to 3, I developed severe anxiety, panic attacks, intrusive thoughts and depression. Even after reducing and eventually stopping estrogen, I haven’t recovered and now I’m taking escitalopram.
Today a nutritionist suggested that I may have impaired methylation. My homocysteine is around 11 µmol/L.
My blood tests show:
Active B12: 182.6 pmol/L (above the reference range)
Folate: 18 ng/mL (also above the reference range)
She believes this could still represent a functional B12/folate problem and recommended SAM-e and TMG.
I also have the raw data from my DNA test.
Could this kind of sudden reaction be related to MTHFR or other methylation-related variants (COMT, MAOA, FUT2, etc.)?
What would you recommend checking first from my raw DNA data or blood tests?
I’m not looking for a diagnosis—just trying to understand whether I’m looking in the right direction.
Thank you.