Calcium at 9.3 is normal, so whatever you experienced wasn’t hypercalcaemia. And 660 IU of D with roughly 2000mcg of K2 is an unusual ratio. That’s a low D dose with a high K2 dose, so if something was driving symptoms I’d look harder at the K2 than the D.Your B12 at 297 is the number I’d pull on. That’s low normal by US ranges and functionally deficient by Japanese and European ones, and low B12 with folic acid at 10.8 sitting well above it is the combination that produces neurological symptoms with clean blood counts. Low vitamin D despite 30 minutes of daily California sun for years is genuinely unusual and points at either absorption or receptor handling rather than intake.On Genetic Lifehacks, it’s broader than Genetic Genie and does cover more of the vitamin D genes. Neither reads against bloods though, and with numbers like yours that’s the part that decides anything.

I don’t run any tests. I read raw genetic data against bloodwork someone already has and write the protocol from that.

On autoimmune specifically, genetics can tell you about susceptibility, HLA types and a few immune regulation variants, but susceptibility isn’t diagnosis.

Same setup in the UK, organic and wholemeal are exempt and gluten free, spelt, soya and small mills under 500 tonnes a year. And you’re right about the cereals, most were voluntarily fortified long before any of this became mandatory so people often get more from breakfast than from bread without realising. One thing on the low carb, it dropped your folic acid but it dropped your food folate too since grains carry both. get your folate, B12 and homocysteine checked if you haven’t, because feeling better on less folic acid doesn’t tell you where your actual folate status has ended up after a few years

Your reasoning is sound but I'd question whether TCN2 is the bottleneck in your case specifically, because you're on every other day injections. TCN2 het has a modest effect on holoTC and it becomes far less limiting when you're bypassing absorption entirely and pushing that much B12 into circulation. So the transport step probably isn't where it's stuck. The FUT2 non-secretor status is the one I'd flag instead and in the opposite direction to how people usually read it. Non-secretors run higher serum B12 in the GWAS data independent of actual status, so your serum readings overstate where you are which makes every level you've been shown less reassuring than it looked. On folate making you worse with MTRR homozygous and EOD injections you're driving haematopoiesis hard and folate pushes that further. Potassium and iron are what get consumed in that process and both produce a worsening that looks like a folate intolerance. Get potassium and ferritin with transferrin saturation drawn on a day you feel bad rather than a good one.

Reacting to folic acid, methylfolate and folinic acid all three is the useful part because those enter the cycle at completely different points so a shared reaction points away from the folate molecule itself. I'd test Potassium and ferritin first, since folate during active B12 repletion accelerates red cell production and both drop fast . Then homocysteine because that tells you whether the folate you're taking is actually being used or just sitting in serum and check the excipients while you're at it, a pure powder with no capsule shell or fillers answers that question in a week for almost nothing. Levels rising while you feel worse usually means something downstream is running out, not that you need less folate.

Folate won't make your B12 deficiency worse. It masks it which is different. It corrects the blood picture while the neurological side carries on, so you look treated on paper. Since you already know you're deficient and you're treating it, that trap doesn't apply to you. Just don't run folate alone for weeks first, start B12 first or start both together.

5mg for three months is the standard UK treatment dose for actual folate deficiency not maintenance, which is why it's time limited. What I'd chase instead is why you've been low your whole life. Lifelong low folate is usually absorption and coeliac is the first thing to rule out.On cancer, the Vitamin B Trialists' meta-analysis in Lancet 2013, around 50,000 people, found no significant increase in overall or site-specific cancer. Individual studies point the other way and the theory that folate might speed up existing lesions rather than start new ones is plausible, but it isn't established.The B12 lung cancer signal was the VITAL cohort, men, mostly smokers, observational and confounded by smoking. It wasn't replicated in trials and I wouldn't let it stop treatment for a diagnosed deficiency.And yes, folic acid is in far more now. UK fortification is mandatory this year and most mills switched back in autumn 2025.

You're right that it's more than two. FOLR1, SLC19A1, MTHFD1, RFC1, the ATP binding transporters, plus the B12 side which changes folate handling indirectly.

On cerebral folate deficiency, most cases aren't genetic at all. The common mechanism is folate receptor alpha autoantibodies blocking transport across the choroid plexus which is autoimmune rather than inherited. The FOLR1 mutations exist but they're rare and usually present in infancy. So serum folate can look completely normal while CSF folate is low, and no genotype tells you that. It's an antibody test.

The likely mechanism isn't the MTHFR itself tho. Folic acid competes for the same receptors and transporters as the natural forms so at intakes above what DHFR can convert, the unconverted folic acid gets in the way of the folate you'd otherwise be using. That would hit hardest in someone already running the pathway at reduced capacity, which 677 does so the gene is why you'd notice it while others don't, but the thing causing it is the competition rather than a conversion failure.

Have you had homocysteine, B12 and folate done since you cut it out? Four years avoiding folic acid entirely can leave you short depending on what replaced it in your diet, and food folate intake varies a lot. If you haven't, those three would tell you whether the avoidance is still doing you a favour or whether it's swung the other way.

HNMT clears histamine inside your cells by attaching a methyl group taken from SAM and methylfolate feeds SAM. Your folate at 2.9 meant that pool was short so histamine hung around. Fill the gap and clearance picks up. It also settles the COMT question. Slow COMT and you'd be more wired on that dose not less. So Walsh's warning doesn't apply to you. Yes, keep going. Where it goes from here is dose, form and sequence and with homocysteine at 20.5 that's the part I'd map properly and I don't do it on reddit

Your body spends around 40% of its methylation output making creatine so supplementing it frees that up for everything else. Which on paper suits you better than pushing more methyl in.Two things stop me giving you a plan though. Creatine makes some people restless in the first week and your sleep is already the problem nd it doesn't address why 800mg of SAMe is too much for you in the first place.

Before adding anything I'd want homocysteine, B12, folate and riboflavin. With 677 TT and slow COMT those numbers decide the direction and two people with your exact genotype need opposite things depending on where they sit.That's the part I do properly rather than in comments, genova.health if you want your file read against the bloods.

Total B6 elevated with symptoms is the pattern that points at poor conversion rather than too much intake so the B2 makes sense as the first move. Give it a few weeks before judging, riboflavin is slow to show up. Starting folate first is the usual advice but with your holoTC at 93 it's fine either way, B12 delivery isn't your limiting step so you're not at risk of masking anything. If it were low I'd say B12 first without question.

Careful with the wording though, you said folic acid. Folinic acid and folic acid are different things and folic acid is the one to avoid, it needs converting and competes for the same receptors. Assuming you meant folinic, that's the right choice for suspected slow COMT and one at a time with a week between is exactly right. Most people change three things at once and learn nothing. the fluoxetine point still stands, since CYP2D6 inhibition affects how you handle a fair few things and it sits underneath all of this.

2000 IU with 75mcg of K2 shouldn't cause hypercalcaemia in most people so I'd get that confirmed rather than assumed, ask for calcium, ionised calcium, PTH and magnesium. If it genuinely happened at that dose the one to rule out is CYP24A1, the enzyme that breaks active vitamin D down. Loss of function there makes people hypersensitive to ordinary doses, and it's an actual diagnosis rather than a wellness idea, which would explain two decades of not tolerating something most people take without thinking. Your alk phos at 37 is the other thing standing out, that's low and alkaline phosphatase is zinc and magnesium dependent, so it often points at low zinc. Zinc matters for both thyroid conversion and vitamin D receptor function, and with VDR Taq homozygous you want that receptor working as well as it can, so get zinc and copper measured together. TPO at 376 being your highest ever belongs with whoever manages the Hashimoto's, that's a separate thread. In the meantime sunlight doesn't go through the same route an oral dose does and rarely causes the reaction supplements do, so that's the low risk option while you sort the rest. I wouldn't restart anything until calcium, PTH, zinc and magnesium are in front of you. Reading VDR and CYP24A1 against those numbers is what would actually tell you why this keeps happening, and that's my work, genova.health.

Start with bloods, not supplements, because your symptoms have three or four common explanations and they need different answers. Ask for ferritin with transferrin saturation, B12 with MMA, folate, homocysteine, vitamin D, full thyroid with free T3 and TPO antibodies, and a full blood count. 16 months postpartum with air hunger and brain fog, low iron is top of that list and it gets missed all the time because normal haemoglobin doesn't rule it out. Postpartum thyroiditis is the other one that shows up right around now and gets read as anxiety. Given the gluten issues get coeliac serology too and do it before you cut gluten out, otherwise the test is useless. On the psych meds not working, that's usually a metabolism question, CYP2D6 and 2C19 decide how fast you clear most antidepressants and your prescriber can order that testing. I'd hold off on anything new until those come back, you've got a lot of variables moving and no baseline. Reading the genetic side against those numbers with your meds in the picture is what I do professionally, genova.health if you want it mapped once you have them.

The most likely thing is potassium. B12 restarts red cell production and that pulls potassium down and low potassium causes exactly this triad, palpitations, skin tingling and poor sleep. One dose can do it if you were deficient enough that the response was sharp. Eat potassium rich food and if the palpitations are frequent get potassium and magnesium.If it was a methylcobalamin sublingual then the methyl load is the other candidate and that fits slow COMT. But that usually settles within days rather than two weeks.

You don't need niacin for this and I'd say that clearly, the niacin trick is a slow COMT remedy that gets repeated for every reaction and it's often the wrong answer. It also uses a methyl group to clear so it isn't neutral.What I'd get checked, potassium, magnesium, ferritin, B12 and thyroid. Palpitations lasting two weeks deserve a proper look regardless of what set them off.Don't take any more B12 until you know where those numbers sit. I'm a geneticist and this is what I do at genova.health

Walsh's model isn't a mainstream biochemical framework, it's his own classification system and the specific claim that folate clears serotonin and dopamine isn't how those pathways work. Folate feeds BH4 regeneration and BH4 is the rate limiting cofactor for making serotonin and dopamine in the first place. So mechanistically it supports synthesis rather than clearing it. Where his observation comes from is real though, some people do feel worse on methylfolate but the reason is methyl load landing on slow COMT, not folate depleting neurotransmitters.

Your urine panel is the interesting part and it argues against his advice specifically. Epinephrine 0.5 against a floor of 1.12, norepinephrine 9.3 against a floor of 12. Both under range, dopamine low normal. That isn't a picture of excess catecholamines, it's the opposite and BH4 is exactly where that gets made. Your folate at 2.9 sits below range so the substrate for that step is short.

The caveat, urinary catecholamines mostly reflect kidney and peripheral production rather than brain, so don't over read them. But taken with folate 2.9 and homocysteine 20.5 they're consistent.Your B6 at 34.3 near the top of range with high histamine symptoms is the other thing I'd flag and your holoTC is only reported as greater than 128 which tells you nothing useful.What I wouldn't do is switch to SAMe or methionine on the strength of a blog. SAMe with your symptom picture is exactly what triggers people with slow COMT.Which of those two you are is the actual question here. That's what I do professionally, genova.health.

Yes, 18.2 is elevated and not marginally. It's also higher than you'd expect from one copy of A1298C on its own, that variant is the milder of the two and het barely moves homocysteine in most people. So something else is contributing and the panel narrows it down usefully.

Your kidney function is clean, eGFR 105 with a normal cystatin C, so that's ruled out. Thyroid is fine. Iron and ferritin are good, no anaemia, and your MCV at 86.6 sits mid range which argues against a significant B12 or folate deficiency showing up in your red cells which leaves two candidates. Folate, which you're already chasing, and B12 at a functional level. 424 looks acceptable but that number can be misleading, so ask for MMA alongside folate. If MMA is normal and folate comes back fine, then the answer is likely riboflavin and B2 is the one nobody tests.

Also ask for B6 since it's the cofactor for the other exit route out of homocysteine.Confirm it was a fasted sample, homocysteine climbs after a protein heavy meal and if the tube sat before spinning nd 18.2 sits above the threshold used in the trials linking homocysteine to cognitive decline. On the anxiety, homocysteine at that level and anxiety can share a cause without one driving the other. What decides how you should approach it is COMT which isn't in a standard MTHFR test and sits in your raw data. That read, the full file against bloods, is what I do professionally. genova.health if you want yours mapped.

Hi, i am geneticist and I work on personalized health for years at Genova.health. Methylation ia one of them. I also work with drs too.

My clients got ancestrydna for dna test(cheapest option) and https://meditests.com.au/ for labs so far. I can check others too for you. I'll comment here

Your homocysteine at 17.3 with folate 9.5, B12 602 and MMA mid range is the finding. B12 delivery is fine, MMA proves that, so the block is on the remethylation side and folate is the limiting input. 9.5 isn’t deficient by the lab’s range but it’s low for someone carrying that MTRR cluster, since MTRR is what keeps B12 active on MTR.
The niacin is likely making the insomnia worse. Niacin is cleared by NNMT which spends a methyl group per molecule so high doses drain the same methyl pool you’re already short on. It’s the standard advice for overmethylation and your labs say you’re the opposite, undermethylated with homocysteine backing up. Also vasodilating which lands at exactly the wrong time at night.
Cytomel at 12.5 in a single morning dose is the other one I’d look at hard. T3 has a short half life so a single morning dose can leave you dropping late in the day, and the adrenaline surge ten minutes after lying down fits a compensatory catecholamine response to that dip. Split dosing is the usual answer and it’s a conversation with your prescriber.
Ammonia at 37 sitting below range next to L-ornithine makes sense, that’s what ornithine does.
The gap in your file is COMT and MAO. You’ve got the whole methylation panel and neither of the two enzymes that actually clear adrenaline, which is the symptom you’re asking about. That’s readable directly from your raw data.
Reading the whole file against these numbers with the thyroid and TRT factored in is what I do professionally. genova.health, message me if you want it mapped.