NMN and TMG: Why They Are Often Taken Together

NMN and TMG are often taken together because of methylation. NMN is a building block your cells turn into NAD+, and as NAD+ is used, the body clears extra nicotinamide by attaching a methyl group to it. TMG (trimethylglycine, also called betaine) is a methyl donor, so it is added to help cover that demand. Studies so far have tested the two separately, so the pairing rests on how the body handles nicotinamide.

Key Takeaways

• The liver clears excess nicotinamide by methylating it into compounds such as N1-methylnicotinamide, which leave the body in urine (NIH ODS).
• In 10 healthy men, single NMN doses of 100 to 500 mg raised two methylated breakdown products of nicotinamide in step with the dose (Irie et al., 2020).
• In a small study, a 300 mg dose of nicotinamide lowered blood betaine and raised homocysteine within 3 hours, a sign that clearing it draws on methyl donors (Sun et al., 2017).
• Betaine trials in healthy adults have used 1.5 to 6 g a day, and food supplies roughly 0.5 to 2 g a day (Olthof et al., 2003).
• Vitamin B12 and folate are the other methyl helpers, needed to turn homocysteine back into methionine (NIH ODS).

What NMN and TMG Each Do

NMN (nicotinamide mononucleotide) is a niacin-like compound and a direct building block of NAD+, the coenzyme that more than 400 enzymes in the body need to work (NIH ODS). People take it to support NAD+ levels; our guide to how NAD+ is made walks through the pathway.

TMG (trimethylglycine) is the amino acid glycine with three methyl groups attached. It is the same compound as betaine, and the richest food sources measured include wheat bran, wheat germ, spinach and shrimp (Zeisel et al., 2003). In the body it acts as a methyl donor, handing off one of those methyl groups (Sun et al., 2017). Our guide to betaine anhydrous and TMG covers it on its own.

NMN vs TMG at a glance

	NMN	TMG (betaine)
What it is	A niacin-like building block of NAD+	Glycine with three methyl groups
Main role	Supports NAD+ levels for cellular energy	Donates methyl groups
Amounts studied	300 to 900 mg a day for 60 days	1.5 to 6 g a day for 6 weeks
In food	The body also makes NAD+ from niacin in food	About 0.5 to 2 g a day from a typical diet
Why together	NMN raises the nicotinamide the liver has to methylate; TMG adds to the methyl supply

Why TMG Is Paired With NMN: Methylation and Nicotinamide

Methylation means moving a methyl group, a small carbon unit, from one molecule to another. One of its uses is tagging nicotinamide so it can leave the body:

Step	What happens
1. NMN becomes NAD+	Cells use NMN to make NAD+, which powers hundreds of enzymes
2. Nicotinamide is left over	Nicotinamide is part of the NMN and NAD+ molecule, and any excess has to be handled
3. The liver adds a methyl group	Excess nicotinamide becomes N1-methylnicotinamide and related compounds, which leave in urine
4. Methyl donors are drawn on	The methyl group has to come from somewhere; betaine (TMG) is one source

The NIH describes step 3: the liver methylates excess niacin compounds to N1-methylnicotinamide and N1-methyl-2-pyridone-5-carboxamide, which are excreted in urine (NIH ODS). TMG is added to NMN formulas as a simple way to support the methyl supply that this step uses.

What Studies Have Measured

NMN is broken down through methylated products

In a Japanese study, 10 healthy men took single doses of 100, 250 and 500 mg of NMN. Two methylated nicotinamide breakdown products in the blood, known as 2-Py and 4-Py, rose in step with the dose. The authors concluded that a single oral dose was safe and effectively metabolized (Irie et al., 2020).

Clearing nicotinamide uses up betaine

In a small study, 30 adults were split into three groups of 10 and given water, 300 mg of nicotinic acid or 300 mg of nicotinamide. Three hours after nicotinamide, N1-methylnicotinamide was far higher than in the water group, blood betaine was about 24 percent lower and homocysteine had risen. The authors concluded that breaking down nicotinamide consumes more betaine than breaking down nicotinic acid (Sun et al., 2017). It used plain nicotinamide, not NMN, but it shows the methyl link behind the pairing.

NMN on its own

In a 60-day randomized trial, 80 healthy adults aged 40 to 65 took a placebo or 300, 600 or 900 mg of NMN a day. Blood NAD rose in all three NMN groups, with 600 mg giving higher levels than 300 mg and 900 mg adding little beyond 600 mg. The 600 and 900 mg groups also walked farther in a 6-minute walk test, and the authors reported NMN was safe and well tolerated up to 900 mg a day (Yi et al., 2023). See NMN supplement benefits for more of the human research.

What has not been tested yet

These studies looked at NMN, nicotinamide and betaine one at a time; a trial comparing NMN with and without TMG is the next step. The pairing comes from well-described chemistry, which is why many NMN formulas include TMG as a small, sensible addition. For what human trials of NMN on its own have found, see our guide to whether NMN works.

How Much TMG With NMN?

There is no official ratio. What we do know is the range that has been studied. In a 6-week trial, 76 healthy adults took a placebo or 1.5, 3 or 6 g of betaine a day, and fasting homocysteine came out 12, 15 and 20 percent lower than placebo, showing that betaine in the range of normal dietary intake feeds methylation (Olthof et al., 2003). The same paper puts typical intake from food at about 0.5 to 2 g a day.

NMN formulas usually add a few hundred milligrams of TMG on top of what your diet gives. Our Enhanced NMN pairs 750 mg of NMN with 200 mg of TMG per 2 capsules. For NMN amounts on their own, see our NMN dosage guide. For more on TMG as a supplement on its own, see our guide to TMG benefits. If you also take creatine, our guide to TMG and creatine explains how the two connect and whether to take both.

NMN With TMG and B Vitamins: B12 and Folate

TMG is not the only methyl helper. The body's main methyl donor is S-adenosylmethionine (SAMe), which is made from the amino acid methionine. After a methyl group is used, what is left is homocysteine, and it has to be turned back into methionine to keep the cycle going. Vitamin B12 is the cofactor for methionine synthase, the enzyme that does this, and methylcobalamin is one of its active forms (NIH ODS: Vitamin B12). Folate works in the same reaction (NIH ODS: Folate). Betaine offers a second route for the same step.

Methyl helper	Adult daily need	Where you get it
Vitamin B12	RDA 2.4 mcg; no upper limit set	Animal foods and fortified foods
Folate	RDA 400 mcg DFE	Spinach, asparagus, Brussels sprouts, legumes, liver
Betaine (TMG)	No set RDA; about 0.5 to 2 g a day from food	Wheat bran, wheat germ, spinach, shrimp

B12 is generally considered safe even at large doses because the body does not store the excess (NIH ODS). For B12 forms, see methylcobalamin vs cyanocobalamin.

Taking NMN and TMG Together

Most people tolerate this pairing well. In the 60-day trial, the 600 and 900 mg NMN groups had no adverse events, and none of the mild or moderate events elsewhere were linked to NMN (Yi et al., 2023).

• Timing: take them together in the morning, with or without food. Having them in one capsule makes this simple.
• Diet still counts: foods rich in folate and betaine, such as spinach, asparagus, wheat germ and wheat bran, add to the same methyl supply.
• Check first: if you take prescription medicine or are pregnant or breastfeeding, talk with your clinician before starting.

Who Might Choose Which

• NMN with TMG: NAD+ support with the methyl side covered in the same capsule.
• NMN on its own: for people who already take TMG separately or eat plenty of betaine-rich foods.
• NMN, TMG and B12 together: all three in one routine, which is how our Enhanced NMN is built.

For more on how NMN fits with other longevity ingredients, see NMN and resveratrol, our NMN ingredient page, our TMG ingredient page and our cellular energy guide. Our guide to pterostilbene vs resveratrol explains the other two ingredients in Enhanced NMN.

Where Our Enhanced NMN Fits

Our Enhanced NMN was built around this pairing. Each 2-capsule serving gives 750 mg of NMN, 200 mg of trimethylglycine (TMG), 200 mg of resveratrol, 100 mg of pterostilbene and 750 mcg of vitamin B12 as methylcobalamin, with ginger extract and vegan capsules as the other ingredients, made with third-party tested ingredients. Take 2 capsules in the morning, with or without food, every day.

Benefits build with consistent daily use. Months 1 to 2 can bring early changes, and 3 months and beyond is where the full benefit builds. If you are also looking at glutathione support for healthy aging, our NAC Nasal Spray gives 50 mg of N-acetylcysteine per 2 sprays.

Frequently Asked Questions

Should I take TMG with NMN?

Many people do. The body clears extra nicotinamide by methylating it, and TMG is a methyl donor, so it helps cover that demand.

Why do people take NMN and TMG together?

NMN adds to the nicotinamide your liver has to methylate before it leaves the body, and TMG supplies methyl groups.

How much TMG should I take with NMN?

There is no official ratio. NMN formulas often add a few hundred milligrams; ours pairs 200 mg of TMG with 750 mg of NMN. Betaine trials have used 1.5 to 6 g a day, and food gives about 0.5 to 2 g.

Is TMG the same as betaine?

Yes. Trimethylglycine and betaine are two names for the same compound, and betaine anhydrous is its common supplement form.

Should I take NMN with TMG and B vitamins?

Vitamin B12 and folate are needed to turn homocysteine back into methionine, so they support the same methyl cycle as TMG. Our Enhanced NMN includes 750 mcg of B12 as methylcobalamin.

When should I take NMN and TMG?

Together in the morning, with or without food, every day.

Is it safe to take NMN and TMG together?

Most people tolerate both well, and NMN was reported safe up to 900 mg a day in a 60-day trial. Check with your clinician first if you take prescription medicine.

Sources

• National Institutes of Health, Office of Dietary Supplements. Niacin: Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/Niacin-HealthProfessional/
• Irie J, Inagaki E, et al. Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men. Endocrine Journal, 2020. https://pubmed.ncbi.nlm.nih.gov/31685720/
• Sun WP, Zhai MZ, Li D, et al. Comparison of the effects of nicotinic acid and nicotinamide degradation on plasma betaine and choline levels. Clinical Nutrition, 2017. https://pubmed.ncbi.nlm.nih.gov/27567458/
• Yi L, Maier AB, Tao R, et al. The efficacy and safety of beta-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. GeroScience, 2023. https://pubmed.ncbi.nlm.nih.gov/36482258/
• Zeisel SH, Mar MH, Howe JC, Holden JM. Concentrations of choline-containing compounds and betaine in common foods. Journal of Nutrition, 2003. https://pubmed.ncbi.nlm.nih.gov/12730414/
• Olthof MR, van Vliet T, Boelsma E, Verhoef P. Low dose betaine supplementation leads to immediate and long term lowering of plasma homocysteine in healthy men and women. Journal of Nutrition, 2003. https://pubmed.ncbi.nlm.nih.gov/14652361/
• National Institutes of Health, Office of Dietary Supplements. Vitamin B12: Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/
• National Institutes of Health, Office of Dietary Supplements. Folate: Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/

These statements have not been evaluated by the Food and Drug Administration. This content is for education and is not medical advice. Our products are not intended to diagnose, treat, cure or prevent any disease. Talk with a healthcare provider before starting a new supplement if you are pregnant, breastfeeding or taking medication.