What kind of interaction is it?

Synergy: a documented combination effect that is stronger or more useful than either substance taken alone.

Is this interaction backed by published research?

Yes. NutriStack lists 1 citation row for the Methylfolate + Trimethylglycine pair, each linking to PubMed by PMID where available. Full sourcing methodology at https://nutristackapp.com/methodology/interactions.

Supplement × Supplement·a synergy·Moderate evidence

Methylfolate + Trimethylglycine

Q: Can I take Methylfolate and Trimethylglycine together?

Yes. The combination of Methylfolate and Trimethylglycine produces a measurable benefit. TMG and methylfolate act on parallel homocysteine remethylation routes: TMG drives the folate-independent BHMT pathway while methylfolate (with B12) drives methionine synthase. Used together they can lower homocysteine more completely than either alone.

Q: How does this affect a NutriStack Stack Score?

+2 to your Stack Score per scored synergy row.

Synergy Moderate evidence

TMG and methylfolate act on parallel homocysteine remethylation routes: TMG drives the folate-independent BHMT pathway while methylfolate (with B12) drives methionine synthase. Used together they can lower homocysteine more completely than either alone.

Supplement × Supplement

Open the interaction checker → Read the methodology

From the database

What the row says.

Every entry follows the same shape: what is happening, the mechanism, and the recommendation.

Substances

Methylfolate and Trimethylglycine

Pair type

Synergy

Evidence

Moderate

Source citations

Scope

Supplement × Supplement

Last verified

June 4, 2026

SynergyModerate evidence

What is happening. TMG and methylfolate act on parallel homocysteine remethylation routes: TMG drives the folate-independent BHMT pathway while methylfolate (with B12) drives methionine synthase. Used together they can lower homocysteine more completely than either alone.

Mechanism. Betaine supplies methyl groups via BHMT; methylfolate supplies methyl groups via 5-methyltetrahydrofolate to methionine synthase. The two converge on regenerating methionine and SAMe.

Recommendation. Reasonable to combine when targeting elevated homocysteine, ideally with adequate vitamin B12. Monitor homocysteine to confirm response and avoid over-supplementation.

Stack Score

How it moves the number.

Effect on the composite score

If both Methylfolate and Trimethylglycine are in the same stack, this pair applies +2 to your Stack Score (per scored synergy row).

The full algorithm, the clamping rules, and four worked stacks are at /methodology/stack-score.

Sources

Sources, by evidence tier.

Every claim on this page is cited. PMIDs link straight to PubMed.

Reference material

1Olthof MR, Verhoef P. Effects of betaine intake on plasma homocysteine concentrations and consequences for health. Curr Drug Metab. 2005.Needs sourceNo link

Check your full routine

One pair was the worked example.

Drop your supplements and prescriptions into NutriStack and it runs every pair at once: every interaction, synergy, timing rule, and contraindication, each linked to its primary source.

Open the interaction checker → Browse the research index