Most people arrive at methylation from the wrong end. They have a genetic result, usually MTHFR, and look for a supplement to match it. Bloods are the more useful starting point, because they tell you what is happening now rather than what has been possible since birth. Below are the six patterns I see most often in clinic and the first thing I reach for in each. Some look similar on paper but lead somewhere quite different. 1- High homocysteine, low red cell folate Suggests: not enough raw material. Where I start: 5-MTHF or folinic acid, plus B12. 2- High homocysteine, low active B12 or raised MMA Suggests: a missing cofactor. Where I start: methylcobalamin or hydroxocobalamin. 3- High homocysteine, folate and B12 already corrected Suggests: a blockage further down the pathway. Where I start: B6 as P5P, serine, glycine, betaine. 4- Low SAM, low methionine, low protein intake Suggests: not enough starting material. Where I start: dietary protein and methionine adequacy. 5- Low SAM to SAH ratio, normal homocysteine (specialist testing, not on a standard panel) Suggests: a manufacturing or clearance problem. Where I start: check kidney function, then consider SAMe. 6- Low choline intake Suggests: methylation traffic being diverted elsewhere. Where I start: choline or phosphatidylcholine. Why the last two matter more than people expect The SAM-to-SAH ratio is the one nobody measures. SAM is the molecule that carries methyl groups around your body; SAH is what is left after one has been delivered. SAH is a potent blocker of almost every methylation reaction there is, so a person can have plenty of SAM and still methylate poorly if the SAH is not clearing. Kidney function is the usual reason it does not. Choline is the quiet one. Building phosphatidylcholine consumes three SAM molecules for every molecule made, and it accounts for a large share of all the methylation traffic in the liver. A low-choline diet pulls methyl groups away from everything else and pushes homocysteine up in a way the B vitamin picture alone will not explain.

I am polishing a special presentation I did for Fountain Life back in September and will be happy to share it with you.