TMG (Trimethylglycine / Betaine)

The verdict

Is TMG worth taking?

TMG is simultaneously one of the most underrated compounds in the longevity stack and one of the most misunderstood. Its primary standalone application is homocysteine reduction, where a 2024 meta-analysis confirmed 4 g daily meaningfully reduces cardiovascular risk markers. Its second, increasingly recognized role is as an essential methyl donor partner to NMN supplementation: the NAD+ biosynthesis pathway consumes methyl groups, and sustained NMN supplementation without methyl group replenishment can elevate homocysteine over time. TMG solves this directly and cheaply. It is also found in meaningful quantities in beets and spinach, making it one of the more accessible food-first compounds in this category.

What it does

What TMG does in the body

Homocysteine reduction through methyl donation to the homocysteine remethylation pathway, cardiovascular risk marker improvement, methyl group replenishment for those using NAD+ precursors, and potential performance enhancement through osmolyte activity at higher doses. TMG donates one of its three methyl groups in the remethylation of homocysteine to methionine, directly lowering plasma homocysteine levels independently of folate or B12 status, which makes it useful in populations with MTHFR variants.

The evidence

What the research actually shows

Moderate and consistent for homocysteine reduction. A 2003 study found 1.5 to 6 g daily TMG reduced homocysteine by 12 to 20% in a dose-dependent manner. A 2024 review and meta-analysis confirmed 4 g TMG daily produces positive cardiovascular marker effects through homocysteine reduction though lipids are a genuine caveat rather than a clean result: a dedicated meta-analysis found betaine moderately raises total cholesterol, and 6 g daily raised total cholesterol by around 8% and LDL by around 11% against placebo. Athletic performance evidence is present in some trials but less consistent, with a 2018 meta-analysis finding small but statistically significant improvements in body composition markers with TMG supplementation alongside training.

Food first

Getting TMG from food

Beetroot is the richest common dietary source of betaine (up to 300 mg per 100 g). Spinach, quinoa, wheat germ, and shellfish (especially shrimp) contain meaningful betaine. A diet regularly including beets and spinach provides a real but lower dose of TMG than supplemental doses used in the cardiovascular and NMN-pairing contexts.

What the guide adds

The part that is not on this page

Everything above is the assessment. What the guide adds for TMG is the protocol:

• Optimal Form
• Bioavailability
• Purity Red Flags
• Stack With / Avoid

147 entries across nine categories, every one graded against the clinical literature the same way.

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About the author

Who graded this

Daniel Edlund is a Le Cordon Bleu-trained private chef in Los Angeles, a certified personal trainer and strength coach, and an internationally licensed massage therapist. Thirty years of strength training and fifteen years cooking in private estate kitchens. He is the author of The Complete Supplement Guide, which grades 147 entries against the clinical literature, and of The EASY Way to Organic Cooking, first published in 2013.

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This page is information, not medical advice. Supplements interact with prescription medication and with each other, and the right answer depends on your own bloodwork and history. Talk to your doctor before starting anything, particularly if you are pregnant, nursing, managing a health condition, or already taking medication.

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All 147 entries, graded →