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 Creatine + Trimethylglycine pair, each linking to PubMed by PMID where available. Full sourcing methodology at https://nutristackapp.com/methodology/interactions.

Supplement × Supplement·a synergy·Emerging evidence

Creatine + Trimethylglycine

Q: Can I take Creatine and Trimethylglycine together?

Yes. The combination of Creatine and Trimethylglycine produces a measurable benefit. Endogenous creatine synthesis consumes a large share of the body's SAMe-derived methyl groups. Supplementing creatine reduces methylation demand, while TMG helps maintain SAMe supply; together they can support methylation economy and exercise outcomes.

Q: How does this affect a NutriStack Stack Score?

+2 to your Stack Score per scored synergy row.

Synergy Emerging evidence

Endogenous creatine synthesis consumes a large share of the body's SAMe-derived methyl groups. Supplementing creatine reduces methylation demand, while TMG helps maintain SAMe supply; together they can support methylation economy and exercise outcomes.

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

Creatine and Trimethylglycine

Pair type

Synergy

Evidence

Emerging

Source citations

Scope

Supplement × Supplement

Last verified

June 4, 2026

SynergyEmerging evidence

What is happening. Endogenous creatine synthesis consumes a large share of the body's SAMe-derived methyl groups. Supplementing creatine reduces methylation demand, while TMG helps maintain SAMe supply; together they can support methylation economy and exercise outcomes.

Mechanism. The guanidinoacetate-to-creatine step (GAMT) is one of the largest consumers of SAMe; betaine supports methionine/SAMe regeneration, and exogenous creatine spares this methylation burden.

Recommendation. The combination is commonly used in athletic stacks and is generally safe. There is no need to separate dosing.

Stack Score

How it moves the number.

Effect on the composite score

If both Creatine 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

1Cholewa JM, et al. Effects of betaine on body composition, performance, and homocysteine thiolactone. J Int Soc Sports Nutr. 2013.Needs sourceNo link

Check your full routine

One pair was the worked example.

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Open the interaction checker → Browse the research index