NMN and TMG together: why, how much and what does the research say? (2026)

If you take NMN, you will quickly come across the advice to add TMG. On forums and longevity podcasts it sounds almost like a rule. But where does that advice come from, how much TMG would you take, and what has actually been studied? This article explains it step by step: no hype, just the biochemistry, the studies and an honest conclusion.

Short answer

• Why: NMN is converted into NAD⁺ in the body. When NAD⁺ is used, nicotinamide is released. The body clears part of it through the enzyme NNMT, and that costs methyl groups. TMG (trimethylglycine, also called betaine) is a methyl donor. The idea is that TMG replenishes those methyl groups.
• Evidence: the pathway itself is well described. A human study showed that just 100 mg of nicotinamide briefly raises homocysteine and lowers betaine levels. There is no controlled study yet comparing NMN + TMG with NMN alone.
• Dosage: there is no scientifically established ratio. A common, cautious practice is roughly the same to twice as much TMG as NMN, for example 250–500 mg NMN with 500–1,000 mg TMG per day.
• Safety: TMG at these amounts is well tolerated. At higher doses (from about 4 grams per day) LDL cholesterol may rise slightly.
• Conclusion: combining NMN with TMG is biochemically logical and low-threshold, but not a proven must. It is a precautionary choice, not a miracle combination.

What are NMN and TMG again?

NMN (nicotinamide mononucleotide) is a direct precursor of NAD⁺, a coenzyme involved in energy processes in every cell and in enzymes such as sirtuins and PARPs. NAD⁺ levels decline with age, which is why NMN gets so much attention in longevity. Read more in How does NMN work?.

TMG (trimethylglycine) is known in the scientific literature as betaine. It occurs naturally in beets, spinach and whole grains. TMG carries three methyl groups and can donate one in the so-called BHMT pathway, which converts homocysteine into methionine. More background on What is TMG?.

Why take TMG with NMN? The NNMT pathway explained

The reason to take TMG with NMN comes down to one enzyme: NNMT (nicotinamide N-methyltransferase). This is how the pathway works:

1. NMN is converted into NAD⁺ in the body.
2. Enzymes that use NAD⁺ (sirtuins, PARPs, CD38) break it down, releasing nicotinamide.
3. Part of that nicotinamide is recycled to make new NAD⁺. Another part is cleared via NNMT.
4. NNMT attaches a methyl group to nicotinamide. That methyl group comes from SAMe, the body’s main methyl donor. This produces 1-methylnicotinamide (1-MNA), which is later excreted in urine.
5. What remains of SAMe becomes homocysteine.
6. Homocysteine is converted back into methionine, either via folate and vitamin B12, or via the BHMT pathway with betaine (TMG) as the methyl donor.

In short: the more nicotinamide the body has to clear via NNMT, the more methyl groups it costs. TMG can help top up that supply. That is the logic behind the combination.

What does the research say?

The biochemical pathway is well described. Direct evidence for the NMN + TMG combination in humans does not exist yet. This is where things stand:

Study	What was studied	What it shows
Sun et al., 2012, Hypertension Research	Single 100 mg dose of nicotinamide in 46 adults, blood after 5 hours	1-MNA rose sharply, homocysteine rose (significantly in people with normal blood pressure), betaine fell
Olthof et al., 2003	1.5, 3 and 6 g betaine per day, 6 weeks	Fasting homocysteine 12%, 15% and 20% lower than placebo
McRae, 2013 (meta-analysis)	5 RCTs, ≥ 4 g betaine per day	Homocysteine on average 1.23 µmol/L lower
Zawieja et al., 2021 (meta-analysis)	Betaine supplementation	Total and LDL cholesterol may rise slightly, mainly at high doses
Jawaria et al., 2025, Biomolecules	Review on NNMT	NNMT consumes SAMe and produces homocysteine; mainly preclinical data
NMN + TMG together	—	No controlled human study found that tests the combination

The study by Sun and colleagues is the most interesting piece of the puzzle. They used nicotinamide, not NMN. Still, it shows that a form of vitamin B3 engages the methylation system within hours and uses up betaine. Whether that matters at common NMN doses in the long term has not been studied.

How much TMG should you take with NMN?

There is no scientifically established ratio between NMN and TMG. What you see online, such as a 1:1 or 1:2 ratio, is a rule of thumb, not a research finding. There are, however, some reference points:

Reference point	Amount	Source
Common practice	TMG roughly equal to or double your NMN dose	Practical rule of thumb, not studied
Using the bundle	1–2 NMN capsules (250–500 mg) + 1–2 TMG capsules (500–1,000 mg) per day	Every Day Better label
EU health claim for betaine	1.5 g per day contributes to normal homocysteine metabolism	EU register of health claims
Doses studied	1.5–6 g betaine per day	Olthof 2003, McRae 2013
Watch out	From about 4 g per day LDL cholesterol may rise slightly	Zawieja 2021

For most people taking 250–500 mg of NMN, 500–1,000 mg of TMG is a logical, cautious choice. That is well below the doses at which effects on cholesterol were seen. More details in NMN dosage and TMG dosage.

Who benefits more or less from TMG with NMN?

How much you gain from extra TMG depends on what you already get and how the rest of your methylation runs:

• More reason to combine: you take NMN daily and long term, you eat few betaine- and choline-rich foods (beets, spinach, whole grains, eggs), or you want a cautious, complete routine.
• Less reason: you take NMN occasionally or at a low dose, or you already eat plenty of the foods above.
• Measure instead of guess: homocysteine can be measured through your doctor or a blood test service. A baseline and a follow-up after a few months tell you more than any rule of thumb.

Side effects and safety of NMN with TMG

In studies of healthy adults, NMN was well tolerated at up to about 1,250 mg per day for several weeks. TMG at doses up to a few grams per day rarely causes complaints; occasionally these are digestive upset, nausea or headache. The main point of attention with TMG is the slight rise in LDL cholesterol at higher doses.

Do you take medication, are you pregnant or breastfeeding, or do you have a medical condition? Talk to a doctor or pharmacist first. See also NMN side effects and TMG side effects.

In practice: how to combine NMN and TMG

1. Start low: begin with 1 NMN capsule (250 mg) and 1 TMG capsule (500 mg) per day.
2. Take them together: most people take both in the morning, with or after breakfast.
3. Build up gradually: after a few weeks you can move to 2 + 2 capsules if that suits you.
4. Keep it simple: fixed moments work better than complicated schedules.
5. Combine with lifestyle: sleep, exercise and a varied diet remain the foundation.

Want to go beyond NMN + TMG? GlyNAC targets glutathione, a different pathway. How the three fit together is explained in NMN, TMG and GlyNAC: the longevity stack.

The NMN and TMG bundle from Every Day Better

Want both in one go? The NMN and TMG bundle contains 60 vegan NMN capsules of 250 mg and 60 vegan TMG capsules of 500 mg, for 30 to 60 days. The NMN is independently tested by Intertek at 99.5–99.63% purity (HPLC); you can find the reports on our NMN certificates page. The bundle costs €67, cheaper than buying separately (€51 + €21.50).

Frequently asked questions about NMN and TMG

Do you need to take TMG with NMN?

No, it is not required. It is a precaution: NMN can cost methyl groups via NNMT and TMG can replenish them. No study has yet shown that the combination works better than NMN alone.

How much TMG should you take with 250 mg of NMN?

A common, cautious choice is 250–500 mg of TMG. With 500 mg of NMN, 500–1,000 mg of TMG makes sense. There is no fixed, studied ratio.

What is NNMT and why does it matter for NMN?

NNMT (nicotinamide N-methyltransferase) is an enzyme that clears excess nicotinamide by attaching a methyl group to it. That methyl group comes from SAMe. As a result, a lot of nicotinamide can put a load on the methylation system.

Does NMN raise homocysteine?

This has barely been studied for NMN itself. A study with 100 mg of nicotinamide showed a short-term rise in homocysteine. If you want certainty, have your homocysteine measured.

Is TMG the same as betaine?

Yes. TMG (trimethylglycine) and betaine (betaine anhydrous) are the same substance. Betaine HCl is a different form, mainly used as a stomach acid supplement. See TMG vs betaine.

When should you take NMN and TMG?

Most people take both in the morning, with or after breakfast. Taking them consistently matters more than the exact moment.

Does NMN with TMG have side effects?

At common doses both are usually well tolerated. TMG can occasionally cause digestive upset and, at high doses (from about 4 g per day), slightly raise LDL cholesterol.

Can you get TMG from food?

Yes. Beets, spinach, quinoa and whole wheat contain betaine. Your body also makes it from choline, found in eggs among other foods.

Conclusion

Combining NMN with TMG is biochemically logical: the breakdown of NAD⁺ releases nicotinamide, and clearing it via NNMT costs methyl groups that TMG can replenish. Direct evidence that the combination works better than NMN alone is still missing. For anyone taking NMN daily, a modest dose of TMG (roughly equal to or twice the NMN dose) is a low-threshold precautionary choice. Do not expect miracles, and measure your homocysteine if you want to be sure.

Sources

• Sun W-P et al. (2012). Effect of an oral nicotinamide load on homocysteine, betaine and 1-methylnicotinamide in normotensive and hypertensive adults. Hypertension Research 35(2):180–185. Link
• Jawaria et al. (2025). Nicotinamide N-Methyltransferase in Cardiovascular Diseases. Biomolecules 15(9):1281. Link
• Olthof MR et al. (2003). Low dose betaine supplementation leads to immediate and long term lowering of plasma homocysteine in healthy men and women. Journal of Nutrition 133(12):4135–4138.
• McRae MP (2013). Betaine supplementation decreases plasma homocysteine in healthy adult participants: a meta-analysis. Journal of Chiropractic Medicine 12(1):20–25.
• Zawieja E et al. (2021). Betaine supplementation moderately increases total cholesterol levels: a systematic review and meta-analysis. Journal of Dietary Supplements 18(1):105–117.
• Fukamizu Y et al. (2022). Safety evaluation of β-nicotinamide mononucleotide oral administration in healthy adult men and women. Scientific Reports 12:14442.

This article is intended for information purposes only and does not constitute medical advice. Supplements are not a substitute for a varied and balanced diet and a healthy lifestyle. In case of doubt, medication use, pregnancy, or underlying conditions, always consult a doctor before starting new supplements.