Did you know…
Making creatine in your own body consumes 40 to 50 percent of the methyl groups your metabolism produces each day. Taking 3 to 5 grams of creatine as a supplement lets that budget go elsewhere: to DNA methylation, to phosphatidylcholine synthesis, to neurotransmitter production.
The biochemistry in one paragraph
The final step of endogenous creatine synthesis is catalyzed by GAMT (guanidinoacetate N-methyltransferase). Each molecule of creatine produced consumes one S-adenosylmethionine (SAM), the universal methyl donor. Estimates from Brosnan & Brosnan (2010) and McBreairty & Bertolo (2016) converge: this single reaction accounts for roughly 40 to 50 percent of the total daily transmethylation load in a healthy adult, and the corresponding methionine cost is about 1.5 to 1.7 grams per day.
What this means downstream
Every methyl group used has to be regenerated. Homocysteine, the product of every methyl-transfer reaction, is remethylated back to methionine by one of two pathways: MTR (methionine synthase, folate- and B12-dependent) or BHMT (betaine-homocysteine methyltransferase, betaine-dependent). Supplementing creatine cuts demand on both pathways at the source. The methionine you save comes with a matching reduction in downstream betaine and folate/B12 turnover.
The condition
The sparing effect assumes adequate B12 and folate. If either is limiting, the arithmetic shifts: BHMT becomes the dominant remethylation route and betaine (from choline or direct intake) becomes structurally load-bearing. In practice, checking holotranscobalamin or methylmalonic acid is more informative than serum B12 alone.
What creatine does not spare
Choline has four roles: betaine donation for BHMT (directly spared), phosphatidylcholine synthesis via PEMT in the liver (SAM-dependent, indirectly spared), phosphatidylcholine synthesis via the CDP-choline pathway (does not consume SAM, so not spared at the step itself but arbitrated against PEMT), and acetylcholine (neurotransmission). Acetylcholine sits at the end of a longer chain: freed SAM lets PEMT produce more hepatic phosphatidylcholine, some of which is catabolized back to free choline, which crosses the blood-brain barrier and feeds choline acetyltransferase. The chain exists and is worth naming, but its yield is modest and depends on PE availability, on estrogen tone (PEMT is more active in premenopausal women), and on cholinergic demand. Creatine supplementation is therefore a systemic offload of the methyl-transfer economy that reaches choline in more than one way, without substituting for dietary choline itself.
A companion note to the forthcoming right-to-creatine fiche and to the One Missing Letter argument on amino-acid triage under sufficient protein intake.