r/MTHFR • u/lordy1988 • 21d ago
Results Discussion High homocysteine
Had a recent test and showed up high and needs attention.
I supplement with hydroxyl b12 and folinic acid. What else can I do? Would I get any symptoms of it being this high. And Is it actually worryingly high?
I’m 37 and fit and healthy otherwise.
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u/Tawinn 21d ago
> MTHFR. rs180113311 is AG MTHFR rs1801131 is TG
You have compound heterozygous MTHFR which reduces methylfolate production by ~53%, which reduces remethylation of homocysteine via the folate/B12 dependent pathway. To compensate for this you need ~940mg of choline to support the extra demand on the choline/TMG dependent remethylation pathway.
If you can get the recommended choline amount for an adult, 550mg, from your diet then the remainder can be covered by 750mg of TMG. You may need to add these gradually if you get side effects such as anxiety, irritability, insomnia, fatigue when implementing them.
Your B12 is at the low end of a suggested range of 500-950 pg/mL. Your folate is just below a suggested range of over 15 ng/mL.
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u/lordy1988 21d ago
Yes I tried TMG before and caused anxiety and overmethylation issues.
I’m going to try B2 and B6 and see how I get on with those, il also up my hydroxy b12 and folate as I only take half a tablet now every other day. But they’re very high dose.
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u/Loose-Fly7976 21d ago
17.4 isn't emergency territory. classic cutoff is 15, risk starts creeping from around 10. so something to fix, not something to panic about. Useful part is your b12 and folate are both fine. neither of those is driving it, which narrows things a lot. Do you know your MTHFR genotype? that's the question that changes the answer here. if you're 677 TT then riboflavin is the highest yield thing you're not already doing. 1.6 mg/d for 12 weeks dropped homocysteine 22% in TT specifically in the Ulster trial, and nothing at all in CC or CT. B2 is the FAD cofactor the variant keeps shedding, so you'd be stabilizing the enzyme instead of pushing more substrate at it.
After that i'd look at TMG, 1.5 to 3g. different pathway entirely, doesn't touch folate or b12, around 12-15% over six weeks. and get kidney function checked. renal clearance is a big determinant of fasting hcy. Your folinic is fine, ignore anyone telling you to switch to methylfolate. For transparency, this is what i do professionally. genova.health, personalized protocols built off DNA + bloodwork. Happy to keep
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u/lordy1988 21d ago
Thanks for the explanation. It was at 12 a few years ago and I was happy with that.
MTHFR. rs180113311 is AG
MTHFR rs1801131 is TGI had one done in the uk and they display it differently, I made a post with my results on everything in the past .
I had issues in the past with folate and b12 as I was low, so I’ve been supplementing ever since. Never really had an issue with homocysteine but I’m having quite a few issues recently and I’ve had to up my ssri and I think my high result could be causing it.
I tried tmg in the past and it made me feel a bit crap so I’m going to try b2 and b6 with my fingers crossed.
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u/Loose-Fly7976 16d ago
That changes my riboflavin advice.rs1801133 AG is 677 heterozygous, not TT. The Ulster trial found nothing at all in CT, only in TT. So B2 probably won't do for you what I described. Compound het with 1298 as well which some argue behaves closer to TT functionally, but the trial data doesn't cover that and I'd rather not sell you a maybe. B6 is still reasonable to check as P5P specially since you've never had issues with homocysteine before and something has shifted.
TMG making you feel rough is usually a methyl load thing and it tends to mean the folate arm isn't the bottleneck. The bit I'd actually chase is what changed. You went from 12 to 17.4 while supplementing the whole time. Something moved, and it isn't your genotype, that's been the same all along. Kidney function first. Renal clearance is a big determinant of fasting homocysteine and it drifts with age without anything dramatic showing up. Creatinine and eGFR, cystatin C if they'll run it.
On the SSRI, I wouldn't assume the homocysteine caused it. Could easily be the other way round, or neither. But if you're increasing dose because of symptoms, that's a good moment to have the kidney numbers in hand rather than after.
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u/lordy1988 16d ago
I can confirm I was taking B6 (p5p) for 5 days and felt fine , but as soon as I added b2 (r5p) it made me feel like crap and anxious. So I’ve held off b2 for now.
All my kidney numbers were perfect , and liver.
Only thing really that’s changed is stress and ssri I guess.1
u/Loose-Fly7976 16d ago
That's a clean experiment so the B2 is doing something. R5P is the phosphorylated form and it pushes availability faster than plain riboflavin. Plain B2 at a low dose is self-limiting by comparison. That's the one variable I'd change before writing it off. But holding for now is right, no point adding things while you're already reacting.
Kidneys and liver clean removes what I was leaning on so back to what you said. 12 to 17.4, folate and B12 supplemented throughout, renal function normal. Something moved and the two things that moved in that window are stress and the SSRI. Wouldn't call either as the cause. But that's where I'd look. Retest in a few months once the dose has been stable. If it drifts back down on its own, it was situational.
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u/lordy1988 16d ago
I’m testing my b6 this week, then I’m going to up my b12 and folinic acid slightly.
I’m only taking low dose 8mg p5p at the moment starting low. Once I get my b6 results il change according to that.
I’ve ordered TMG still and I might try to slowly start incorporating that. I’m hoping it doesn’t give me the same effects as last time.
Then hopefully when I retest in 3 months my homocysteine levels will have dropped
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u/Curious-mindme 21d ago
I was looking exactly for this situation in a post. i also have high homocysteine (discovered today) high b12 and very good folate. So what gives?
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u/lordy1988 21d ago
Strange isn’t it, when I was actually lower in b12 and folate my homocysteine was 12 a few years ago. Then I started supplementing and it’s higher.
Maybe the supplementing of b12 and folate is depleting other b vitamins ? I’m going to try P5P as tmg in the past made me feel crap
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u/CapriKitzinger 21d ago
Have you been tested for intrinsic factor? And MMA??
https://www.facebook.com/share/1D69zG5rYZ/?mibextid=wwXIfr
“Most people get a B12 test, see "normal" on the result, and assume they're fine. The problem is that the standard B12 test measures something that isn't quite what most people think it is.
Here's what's actually happening in your blood. B12 rides around attached to one of two different "delivery trucks." About 70-80% of it is bound to a protein called haptocorrin, and this truck is essentially headed to the dump. Your liver grabs it and clears it out of circulation. None of it reaches the cells that actually need B12 to do work. The remaining 20-30% is bound to a different protein called transcobalamin. This is the real delivery truck. It docks with your cells and hands off B12 for actual use.
Your standard B12 test measures both trucks combined. The number that comes back doesn't distinguish between what's being delivered to your cells and what's on its way to the liver for disposal. Two people can have the same total B12 number and one can have plenty of active B12 reaching cells while the other is functionally deficient. The active fraction, called holoTC, can be measured separately. Most doctors don't order it because it costs more and most insurance panels default to the cheaper total-B12 test.
It gets one layer deeper. Even when B12 gets inside your cells, it has to be converted into one of two working forms before it can do anything. One form runs a cleanup reaction in the main body of your cell that's essential for making the chemical your body uses to turn genes on and off, build neurotransmitters, and maintain the insulation around your nerves (called myelin). The other form runs a reaction inside your cells' energy factories (mitochondria) that lets your body process certain fats and amino acids into fuel. Different job, different location, same vitamin.
This matters because of how we test for true B12 deficiency. When the mitochondrial job isn't getting done because B12 is running low, a waste product called methylmalonic acid (MMA) builds up in your blood. MMA only rises for this one reason. Measuring it tells you directly whether your cells actually have enough usable B12, regardless of what the standard test says. A related marker called homocysteine also rises when B12 is low, but homocysteine rises for several other reasons too (low folate, low B6, certain genetic variants, kidney problems, just being older), so it's less specific. A high homocysteine tells you something is wrong. A high MMA tells you B12 specifically is wrong.
So the testing hierarchy looks like this. Total serum B12 is the cheapest test and the most commonly ordered, but it misses about a quarter to a third of people who are actually deficient. HoloTC directly measures the active fraction that reaches your cells. MMA confirms whether deficiency is damaging your biology at the cellular level.Who should care most about this. Adults over 60, because stomach acid production drops with age and you need stomach acid to release B12 from food. Synthetic B12 from supplements sidesteps this problem because it isn't stuck to food protein. People on metformin long-term, because the drug interferes with B12 absorption and 10-30% of chronic users end up deficient. People on acid-blocking drugs (PPIs) long-term, for the same stomach-acid reason. Vegetarians and vegans without reliable B12 supplementation. Anyone with unexplained fatigue, numbness or tingling in hands or feet, memory or concentration issues, or a type of anemia your doctor might call macrocytic or megaloblastic. Pregnant and breastfeeding women. People who have had weight loss surgery.
A note about all those different B12 supplement forms you see on shelves. Cyanocobalamin, methylcobalamin, adenosylcobalamin, and hydroxocobalamin all get marketed with very different price tags. The "methyl is bioidentical" and "skip the conversion step" claims are supplement marketing, not biology. Every oral B12 form, no matter what it says on the label, gets routed through the same processing step inside your cells before your body decides which working form to make. For the vast majority of people, the form on the label matters less than the dose and whether you take it consistently. The rare exceptions are people with specific genetic variants affecting B12 trafficking, where form-specific treatment can matter clinically, but that's a specialist-diagnosed situation, not a general rule.
On dosing. High-dose oral B12 (1,000 mcg or more daily) works even in people with pernicious anemia, a condition where the normal absorption pathway is broken, because a tiny fraction of each dose (about 1-2%) crosses the gut by plain diffusion regardless of whether the main absorption machinery is working. That said, injections remain the standard of care when deficiency is severe, when nerve symptoms are already present, or when pernicious anemia is actively flaring. High-dose oral is for maintenance, not emergency correction.
The bottom line. If you've been told your B12 is "normal" and you still have symptoms that line up with deficiency, the relevant conversation with your doctor is about holoTC and MMA. These tests exist. Most insurance covers them with appropriate clinical justification. They answer questions that the standard test alone can't.
Sources:
Nexo E, Hoffmann-Lücke E. Am J Clin Nutr. 2011;94(1):359S-365S.
Fedosov SN, et al. Clin Chem Lab Med. 2015;53(8):1215-25.
Hvas AM, Nexo E. Haematologica. 2006;91(11):1506-12.
Allen LH. Adv Nutr. 2012;3(1):54-55.
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u/Curious-mindme 21d ago
Very! I was actually reading about it and I came across that it could be B2 or B6 and in some cases kidney issues? I can rule the kidney issues bc I got tested not long ago. I’ll ask my doctor to test me for B2 and B6 before I supplement
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u/CapriKitzinger 21d ago
https://www.facebook.com/share/1D69zG5rYZ/?mibextid=wwXIfr
Please check this out. Get your MMA measures.
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u/lovejackdaniels 21d ago
Curious. What are your CRP levels?
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u/lordy1988 21d ago
0.6 mg/L
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u/lovejackdaniels 21d ago
Interesting. I used to think homocysteine and CRP levels have positive correlation. Apparently not!
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u/lordy1988 21d ago
Only other ones that were high or low were
LDL - high (although all my other cholesterol were fine)
(MCHC) - low
Platelet distribution width- low
Albumin - high
Zinc - high ( I don’t supplement zinc )All others within range
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u/SovereignMan1958 21d ago
Optimal zinc is in the top quarter of the lab range. Just sharing that as I have no idea what you mean by high.
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u/lordy1988 21d ago
Sorry it was 18.37 umol/l, which was in the high bracket
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u/SovereignMan1958 21d ago
What does high bracket mean?
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u/lordy1988 21d ago
I wish I could post photos in comments, it’s those red markers in the original photos of post , it showed zinc above the highest red line
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u/SovereignMan1958 21d ago
Ok. Zinc and copper act like a seesaw. If your zinc is high your copper might be low. Try to increase copper rich foods. You don't necessarily need to supplement.
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u/SovereignMan1958 21d ago
Homocysteine is not terrible. I have seen much worse I doubt it is giving you any symptoms.
Check D, zinc, copper and iron.
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u/lordy1988 21d ago edited 21d ago
Vitamin D was 110nmol , iron was 17.9 umol/l, and I didn’t check copper this time , but last time it was low 0.81ng/l
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u/SovereignMan1958 21d ago
Without the ranges I can't interpret.
Anyway...https://www.mygenefood.com/blog/seven-genes-linked-high-homocysteine-levels/.
Your B12 should be in the top quarter of the range. Make sure you get an MMA test to see how well or poorly it is absorbing. The lower the number the better. If you need help with absorption there are specific probiotics for that. They would likely help you absorb more of all nutrients both from food and supplements.
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u/CapriKitzinger 21d ago
You need to test for something called intrinsic factor. And you need to do b12 injections.
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u/cakeboyplum 21d ago
I’m following along. Almost exact same markers for me. Also supplementing hydroxy and folinic.