- After 25 years of clinical practice in methylation medicine, I can tell you the same mistakes recur. Not because people aren't trying. But because the information available online is either dangerously oversimplified, biochemically incorrect, or written by someone who has never had to sit with a patient experiencing the consequences of getting this wrong. These five mistakes are the ones I see most frequently — in patients who come to me after years of trial and error, in practitioners who are doing their best with incomplete training, and in the endless lists of protocols that circulate on MTHFR forums and Facebook groups. If you recognise yourself in any of these, you are not alone. And more importantly, there is a clear, mechanistically sound way to do this better. Mistake 1: Taking Folic Acid Instead of Methylfolate This is the most common — and potentially the most consequential — mistake in MTHFR management. It seems logical on the surface. MTHFR affects folate metabolism. Folic acid is a form of folate. Therefore, take folic acid. The problem is that folic acid is not folate. It is a synthetic, oxidised form of folate that does not occur in nature and requires a multi-step enzymatic conversion before your body can use it. Here is the biochemical reality: Folic acid must first be converted to dihydrofolate (DHF), then to tetrahydrofolate (THF), and finally — via MTHFR — to 5-methyltetrahydrofolate (5-MTHF), the active form your cells require. The critical bottleneck is an enzyme called DHFR (dihydrofolate reductase), which performs the first conversion step. DHFR has notoriously low activity in humans — far lower than in most other mammals. Even in people without MTHFR variants, this conversion is sluggish. In people with MTHFR variants, the entire downstream pathway is already compromised. The result: unmetabolised folic acid (UMFA) accumulates in the bloodstream. This is not a theoretical concern. Research has identified UMFA as clinically problematic for several reasons:

Quick reference, so nobody has to dig through old posts. FREE, always The Archive (135 graded answers), the Fertility course, the weekly live Q&A (Thursday 8 pm UK), and posting and commenting in the community. PREMIUM: $29/month or $290/year All live Q&A recordings, sending your questions in ahead of the live, and anonymised case discussions. The annual plan includes the MTHFR Clinician Guide ($59). Want individual guidance? Private consultations are at mthfrdoctor.square.site. Current prices hold until 15 November 2026. Education, not medical advice. I am not your treating physician; keep working with your own doctor. Dr Jean-Marc

My labs came back as this: the 4 markers. Can you tell me what your thoughts are?

New Paid Tier in the Methylation Hub - Paid tier opens tomorrow: recorded sessions plus direct messaging for broad recommendations, not treatment - One-on-one sessions possibly in the future - Priced at 29 USD a month to start, for the first 50 people; annual is 290 USD, saving 2 months' worth - Annual Members get the MTHFR clinician guide (currently 59 USD) free, plus its upcoming upgraded version - Fertility Unasked Questions answered, and Archive foundations content stay free; implementation content moves to paid Over Methylation - Symptoms within days of starting: anxiety, feeling wired, insomnia, palpitations, headaches, irritability - Excess methyl groups build SAME; byproduct SAR inhibits COMT, so dopamine accumulates, worse with slow COMT genetics - Labs: normal homocysteine, high B12 and high folate - Management: pause methyl donors, test potassium to rule out hypokalemia, switch to hydroxy B12, restart methyl folate low and slow Methyl Trapping - Methionine synthase lacks enough B12, so 5-MTHF gets stuck, and homocysteine rises - Labs: normal or high serum folate, high homocysteine, low or low normal active B12, elevated methylmalonic acid - - RBC folate preferred over serum folate - Management: give B12 first, restart methyl folate after a couple of weeks, retest homocysteine Key Takeaways - The difference is B12: one needs B12, the other needs fewer methyl donors - Treat labs combined with genetics, not the MTHFR genotype alone (e.g. homozygous 677, up to 70% slower) - Prefer hydroxy or hydroxy plus adenosylcobalamin over methyl B12 where possible - You can send questions for the next live via DMs or post in the methylation group Q&A section

Saturday recording is here. Today I discussed a case in the order of the Archive, going through the different modules. Case study: 38-year-old woman, wired, anxious, disrupted sleep after starting methylfolate She is Compound Heterozygous: one copy of C677T and one copy of A1298C Your questions are welcome!