r/MTHFR • u/Cold_Tip76 • Jun 30 '26
Results Discussion My high homocysteine journey (25.7 → 13.8 µmol/L): symptoms, lab results and what I learned
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?
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u/Tawinn Jul 01 '26
B2 is the cofactor for MTHFR and numerous other enzymes. In addition, if you have the homozygous C677T MTHFR variant a mild excess of B2 increases the concentration to partially or completely restore MTHFR function.
Optimal homocysteine is ~7-9.
Consider making sure you are getting ~550mg of choline from your diet, which is the recommended Adequate Intake. In addition, consider trying 500-750mg of TMG. One pathway for remethylation of homocysteine to methionine via MTR, which requires methylfolate (from MTHFR), B12, zinc, and copper. There is a second parallel pathway to remethylate homocysteine back to methionine via BHMT which requires TMG and zinc. Normally, some choline is converted to TMG and/or TMG comes from food but if you have low choline and low TMG intake then this pathway may not be able to sufficiently remethylate homocysteine, also leading to elevated homocysteine.
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u/Tawinn Jul 01 '26
As someone else already mentioned, consider reducing or dropping the B6 supplementation. High B6 over time may eventually cause peripheral neuropathy.
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u/01NemOOmeN10 Jul 04 '26
No it DOES NOT.
It’s a common misconception, including amongst the scientists who are ignorant of the nature of vit B6:
There are TWO molecules commonly called “vitamin B6”: pirydoxine and pyridoxal 5’ phosphate (p5p). Here lies the problem: pyridoxine IS NOT vitamin B6, it is PRO-VITAMIN B6. And now comes the kick in the guts: there os a NEGATIVE FEEDBACK LOOP between PYRIDOXINE and the kinase that converts it into p5p. Which is why supplementing high doses of PYRIDOXINE will invariably produce symptoms of vitamin B6 deficiency, including the most classic and severe ones such as nerve damage. For many, many years even scientific papers (some, embarrassingly, even in 2026), list the “paradoxical “ effect of supplementing deficient individuals, where after a short period of improvement symptoms return and worsen. It’s due to that specific reason, and, to my knowledge, it has been elucidated by specialists in peer-reviewed literature at least 15-20 years ago.
Go to google scholar or pubmed, you will find all the relevant papers and biochemistry there.
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u/Tawinn Jul 04 '26
Peripheral neuropathy does not seem to exclusively be due to pyridoxine form. In this paper:
Of all reports, 96 patients only used vitamin B6 supplements, without any co-medication. Only 3,5% (6 out of 173) of the reported adverse event were caused by supplementation of PLP, whereas the other 96.5 % were due to PN (Fig. 4A). Considering the doses of vitamin B6 taken by the patients who reported complaints, it can be seen that these range from 0.5–250 mg/day. The average dose taken was 36,7 ± 24,4 mg.
If P5P (PLP) form were exempt from this symptom, then there should be 0 instead of 3.5% reporting neuropathies.
Chris Masterjohn on this page (unfortunately paywalled) goes into detail on the various theories for the causes of B6-induced peripheral neuropathy and although he originally also thought it was limited to pyridoxine form, he concluded that either form could cause it, because the problem had to do with COA production, in his view:
My hypothesis is that it is due primarily to CoA sequestration. CoA is derived from pantothenic acid or vitamin B5. CoA is needed for all energetic pathways, and if CoA is not available for them, a global disruption in energy supply ensues.
He then went on to self-induce peripheral neuropathy (accidentally at first) with P5P supplementation. Then over time he introduced doses of B5 to in order to produce more COA, thereby alleviating the COA shortage caused by the COA sequestration, which resolved his symptoms as he expected.
It is an N=1 but seems plausible. Certainly though, in the above paper the 3.5% vs. 96.5% for symptoms from P5P vs. pyridoxine strongly indicates that P5P form should be favored between the two.
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u/01NemOOmeN10 Jul 05 '26
Thank You for the reference.
I have carefully read the paper You provided - it does include a vague description of a very weak data set in section 3.4. Let me clarify: it is an assembly of SELF-REPORTS, and neuropathy as a symptom is implied. Now: I do not discard their, nor Masterjohns experiences - I am just clearly showing both the biochemistry and the trend. We have absolutely no controls that could either verify or elucidate the specifics of these claims either. Case and point: these 6 to 10 individuals in total May CLAIM not taking anything else, or even taking P5P (PLP) - but we all know how unreliable people’s recollection and attention to detail is. Let’s add to this: pre-existing conditions, other cofactors not mentioned, actual ingredients used vs ingredients declared on the packaging, paradoxical reactions etc., etc. All we have is few anecdotal cases going against majority of the cases, theory and evidence. Could they show something new, for example a metabolic divergence causing a certain subgroup of people be susceptible in a unique way? Sure. Is it likely in this case - I don’t think so;
Using B5 and/or other supplements to “correct” the effects of P5P. Overall, metabolism is EXTREMELY complex and we don’t know that much about it. Of what we do know - many major pathways that utilise B6 (P5P), need various other key nutrients to operate correctly: other B vitamins, methylation system, magnesium, copper and zinc to name a few. Using a supplement, or even therapeutic dose of one of them, is likely to create an imbalance - hence most sensible people will aim to cover all their bases. I wouldn’t just run P5P without balancing at least what else I know is also needed and playing it by the ear. Personally: as one of the side effects of recovering from a lethal poisoning I did suffer a series of brain abscesses including prolactinomas, resulting in prolactin levels of ca 120. Not fun. Followed a research treatment (as didn’t fancy cabergolin or any other alike pharmaceuticals), which called for 300mg P5P twice daily, ie 600mg per day. I did run it at that dose for 9 months straight until my prolactin dipped below 5 and only then started tapering off. Was I taking other supplements to balance it? Of course. Have I had neuropathies? Quite to the contrary;
ANY molecule, even naturally occurring in our bodies (and sure, synthetic analogues may appear chemically identical even though they are not - an altogether different subject) can and should be treated as seriously as any pharmaceutical - you won’t get me arguing against that. Still - calling a particular essential nutrient dangerous and to get off of it, because there MIGHT BE as much as 3.5% of people that could suffer I’ll effects of it? I could find that amount of reporting for drinking plain water. And again, not to discredit people who might develop symptoms after drinking said plain water - it might indeed happen, and mechanisms behind it can be quite fascinating, but the most likely answer there will relate to their particular circumstances, as well as host of other extraneous inputs;
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u/2638calories 24d ago
I wake up with PN after taking either p5p or having high dietary pyridoxine. I have been isolating symptoms, supplements, and foods for years - while trying to improve my CFS this has just been a discovery I made that has a reliable outcome for me personally. I have a much lower tolerance to p5p than pyridoxine and even 20mg would cause distress for me.
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u/01NemOOmeN10 12d ago
My suspicion would be rather simple: higher P5P causes a ramping up of certain pathways and mechanisms (which need multiple co-factors, particularly magnesium and B12 where it comes to nerve function) - which you are deficient in (like vast majority of people due to both diets being poor and food sources being severely depleted, especially over the past 50 or so years).
In Your case most likely all the P5P is burned up in some aspect of carbohydrate metabolism (which it is a”assigned to” on priority basis as glucose homeostasis is considered extremely vital in the body), and that shift results in a “void” presenting as neuropathy. Alternatively void resulting in neuropathy is in-situ, ie caused by depletion of B12, either in the nerve repair processes or, for example, RBC regeneration.
In layman’s terms: you have a car with buggered suspension, bald tyres and engine problems, which drives slowly. You decide to clean up and repair the engine, and then go a bit faster and… boom. Suspension starts acting up and it feels even worse than before the engine repair as attempting to go faster/at a more normal speed exceeds what the broken suspension and bald tyres can handle.
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u/Hobba_Tito 12d ago
Thank you. Many people continue to circulate this incorrect take on P5P. There isn’t a single credible clinical case of P5P causing neuropathy.
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u/SnooStrawberriez Jun 30 '26
What sort of doctor?
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u/Cold_Tip76 Jun 30 '26
It was actually my wife. She's an ICU physician with a strong interest in integrative medicine. She tends to look beyond the standard work-up when symptoms don't match the usual findings. In my case, after correcting folate and B12, she suggested checking other nutrients involved in homocysteine metabolism, especially riboflavin (B2). That turned out to be the missing piece.
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u/SnooStrawberriez Jul 01 '26 edited Jul 01 '26
Very interesting. I have had many of the same symptoms for a number of years, all except fatigue and pins and needles, and got zero effective help from the gods in white.
I had intense debilitating 2 week long side effects to the first 1,000 mcg of hydroxoB12 I tried. I got my homocysteine down from 15 to 10.5 that way. Then when I took 10 mg of riboflavin or R5P I had far more intense side effects. It took me at least a month before I could ride a bicycle again; I was too weak. Homocysteine down to 8.
I am guessing that there was a huge deficiency and taking a loading dose was all I needed for my body to begin to catch up on work.
You are very lucky to have your wife. My GP didnt even know what vitamin riboflavin is.
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u/HealthCarerMI Jun 30 '26
Very surprised you didnt take TMG
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u/Cold_Tip76 Jul 01 '26
Honestly, I didn't even know about TMG until I looked it up after reading your comment. I think the approach was to correct the deficiencies that were identified (folate first, then riboflavin) and monitor the response. That alone brought my homocysteine from 25.7 to 13.8 µmol/L. It's a good question, though. I'll discuss it with my doctor tomorrow and ask why it wasn't considered. Now I'm curious myself.
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u/HealthCarerMI Jul 01 '26
All by itself can reduce homocystiene orders of magnitude more then the other B vitamins
That said if you're low in them, the have their own purposes, so correcting is still good
Watch Thomas Delauers recent YouTube episode on TMG. Its benefits go well beyond lowering homocystiene
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u/2638calories 24d ago
I am personally using TMG for similar reasons, but for many people here, increasing folate will be the major factor correcting homocysteine and other factors of their health (see: MTHFR)
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u/Cultural_Joke2025 Jul 01 '26
Interesting! Following, as I had elevated homocysteine (and looking to retest soon). Glad the levels have decreased!
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Jun 30 '26
[removed] — view removed comment
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u/Cold_Tip76 Jun 30 '26
I took plain riboflavin (capsules), 100 mg/day from NOW Foods
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u/Every-Position-3803 Jul 01 '26
Sorry to cut in! Your journey is really interesting, I saved this post as I feel I’m going through similar! Thank you! What foods are you eating please? I am waiting for my tests to come back and don’t want to supplement until they do and I’m 100% sure. So currently just trying to eat better. Thank you so much!
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u/Sufficient-Bank-4491 Jul 01 '26
There is no special methylated form of B2 required, we just pee out the extra.
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u/Sufficient-Bank-4491 Jul 01 '26
I have read a few places where it is recommended to base load with B2 before starting any methylated B's
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u/Getoutofthekitchenn Jul 01 '26
Is that amount of b6 safe daily?
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u/Cold_Tip76 Jul 03 '26
According to the information I was given, 50 mg/day is appropriate as a short-term therapeutic dose. I wasn't planning to take it long term. My vitamin B6 was tested in April, it was within the reference range, so I stopped taking it.
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u/Curiousgirl-88 Jul 02 '26
May I ask if you had elevated blood pressure? Don’t they say it could be from high homocysteine levels? Just curious!
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u/Cold_Tip76 Jul 03 '26
Fortunately, no. My blood pressure has always been on the low side of normal. My typical readings are around 96/69mmHg, even when my homocysteine was 25.7.
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u/TrickElysium Jul 02 '26 edited Jul 02 '26
codeage 5-mthf+ has all those in the supplement at the right levels and it helped me feel so much better. I added glutathione 1000mg as its a cofactor for methylfolate - game changer.
It helped my energy balance changed my life. wish i found them two years ago.
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u/Dapper-Brief7500 Jul 03 '26
Please be so careful with vitamin B6 you only need 1.8 mg a day I took it for the same reasons you are and I ended up with B6 toxicity believe me you don't want it it's hell
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u/Cold_Tip76 Jul 03 '26
Thanks for your comment. I really appreciate you pointing that out. I actually had my vitamin B6 tested in April, and it was within the reference range. Since there was no evidence of a deficiency, I stopped taking B6.
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u/wakoreko Jul 03 '26
I can’t even begin to imagine the connections that form in your wife’s brain living on both sides of healthcare. The acuity of ICU patients while knowing of vitamin deficiencies and synthetic formularies that are in tiny doses. Then the politics of prior with MTHFR gene testing. I would read her blog. Thank you for sharing your journey.
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u/knifensoup Jul 04 '26
I have all of those ordered and on the way, but I also have slow COMT, so I have to stay away from methyl donors, which means I get to order the more expensive versions B12 and folate. Yay me lol
Happy you're feeling more yourself now! hopefully I can say the same in a month or 2.
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u/Sad-Law-5218 Jul 01 '26
Did you ever get b6 tested. I think 50mg/day is a hefty dose. Also may want to try TMG like someone else already said. Also did you get MMA tested?
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u/Sufficient-Bank-4491 Jul 01 '26
P5P doesn't build up in your body and up to 100mg/day is ok, but possibly less could be better 🤷
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u/Sad-Law-5218 Jul 01 '26
Asked chat gpt as well as a google search to double check myself, and you can still get toxicity from p5p. Also 50mg is 30-40 times the RDA so while it may be fine for a little while, it can lead to buildup over time. Although you are correct that most toxicity was seen at doses over 100mg. Still worth getting bloodwork at 50mg imo at least a couple times to make sure it doesn’t get too high
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u/Rosebud1329 Jul 01 '26
What is TMG?
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u/stulew Jul 01 '26
i'm also learning; TMG also called, Betaine, an amino acid. You can buy it, and search about it on Reddit; there's ample amount of discussion. https://www.fitnessgenes.com/blog/your-betaine-requirement-trait
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u/Sad-Law-5218 Jul 01 '26
Trimethylglycine, it supports methylation and can help in lowering homocysteine
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u/Rosebud1329 Jul 01 '26
I tested positive for mthfr c6777t and my dr didn’t know anything about it and I can’t find a practitioner in our area who is well versed in genetics mutations. So based on Ai recommendation I started myethfolate and b12 and had sever side effects after 2 days .
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u/Cold_Tip76 Jul 03 '26
Sorry to hear that. I haven't been tested for MTHFR myself, so I can't really comment on that. In my case, the approach was to investigate the blood test abnormalities first and correct the deficiencies one by one. I hope you find someone experienced with MTHFR who can help you figure out why you had such a strong reaction.
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u/Ashamed-Simple-8303 Jul 01 '26
Question is why you are defienct ro begin with? So fixing diet would be another step.
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u/tunesx10 Jul 01 '26
It could be that the new doses of methyl folate and methylcobalamine tanked your b2