What happens when you take choline with vitamin b12?
The body has two parallel routes for recycling homocysteine back into methionine. Most people are familiar with the first: methionine synthase, which uses 5-methylfolate as a methyl donor and methylcobalamin (vitamin B12) as a cofactor. The second route is less famous but just as important: betaine-homocysteine methyltransferase (BHMT), which uses betaine - the oxidation product of choline - as the methyl donor. BHMT operates mainly in the liver and kidneys.
The two pathways are complementary. When folate and B12 are abundant, methionine synthase carries most of the load. When folate or B12 is low, the BHMT pathway takes over - provided enough choline (and therefore betaine) is available. This is why dietary choline and betaine intake correlate with lower homocysteine, especially in people with marginal folate or B12 status.
Why is this important?
Methylation is one of the most fundamental reactions in the body. It produces S-adenosylmethionine (SAMe), the universal methyl donor used to make phospholipids (phosphatidylcholine), neurotransmitters (dopamine, serotonin metabolism), creatine, and to silence or activate genes through DNA methylation.
If methylation falters, homocysteine rises, SAMe falls, and a cascade of consequences follows: vascular endothelial dysfunction, impaired liver function (because phosphatidylcholine is required to export fat from the liver as VLDL), reduced neurotransmitter synthesis, and altered gene expression. Choline deficiency itself causes fatty liver and muscle damage in controlled feeding studies.
Pairing choline with vitamin B12 covers both methylation pathways. Observational data show that the relationship between choline intake and homocysteine is strongest in people with low folate and B12 status - exactly the people who benefit most from the alternative pathway. For older adults, vegans (who tend to be low in both B12 and choline since the richest choline foods are eggs, liver, and meat), and people on metformin or PPIs, the pair is especially relevant.
What should you do?
Choline does not yet have an RDA, but the NIH Adequate Intake (AI) is 425 mg/day for women and 550 mg/day for men (450 mg/day in pregnancy, 550 mg/day in lactation). Most multivitamins contain little or no choline, so dietary intake matters: two large eggs supply roughly 300 mg, and 100 g of cooked beef liver provides over 400 mg.
For vitamin B12, aim for at least the RDA of 2.4 mcg, though supplement doses of 100-1000 mcg are commonly recommended for adults over 50, vegans, and people on metformin or acid-suppressing drugs.
If your diet is low in eggs, liver, and meat, consider a choline supplement: choline bitartrate, citicoline (CDP-choline), alpha-GPC, or phosphatidylcholine, typically 250-500 mg/day. Pair it with a B-complex or multivitamin that supplies B12 (and folate). Take with food.
Very high choline doses (above 3.5 g/day, the tolerable upper level) can cause a fishy body odor, sweating, low blood pressure, and GI upset. Stay within recommended ranges.
Which specific products are affected?
Dedicated choline supplements include Jarrow Citicoline, Now Foods Choline Bitartrate, Designs for Health PhosphatidylCholine, and Alpha Brain (which contains alpha-GPC). Some prenatal vitamins (such as Ritual Prenatal, Needed Prenatal, FullWell) include 100-300 mg choline because the requirement rises in pregnancy and most prenatal formulas historically underdelivered it.
Standard B-complex and multivitamin products usually supply B12 but not meaningful choline. Liver-support and methylation-support formulas (Designs for Health Homocysteine Supreme, Thorne MediClear) often combine choline, betaine (TMG), B12, and folate.
The bottom line
Choline and vitamin B12 power the two parallel pathways that keep methylation running. Aim for 425-550 mg/day of choline from eggs, liver, fish, and soy (or a supplement if needed) and pair it with 2.4-1000 mcg of B12 in a daily B-complex or multivitamin. This combination is particularly important during pregnancy, in older adults, and for anyone who eats little animal food.