Ingredient Guide

TMG Supplement Explained: The Methyl Donor Paired With NMN

Trimethylglycine (TMG), also called betaine or betaine anhydrous, is a methyl donor from beets and whole grains. What it does in the methionine cycle, what human studies found, and why it sits beside NMN in Enhanced NMN.

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Methyl Donor Found in Beets Non-Stimulant
In Our Products

TMG on the Label

Exactly how much TMG is in our product, straight from the label.

Synchronicity Health product containing TMG
Enhanced NMNPer serving of 2 capsules, with NMN 750 mg, resveratrol 200 mg, pterostilbene 100 mg and vitamin B12 750 mcg200 mg

How to use it (label directions): two capsules in the morning, with or without food. Each bottle holds 30 servings. How this compares with research doses: studies that lowered homocysteine used 1.5 to 6 g of TMG a day, and typical diets supply about 0.5 to 2 g a day. The 200 mg in Enhanced NMN is a small supporting amount of methyl donor alongside NMN, not a homocysteine-lowering dose. Use it as directed on the label.

Start Here

A Small Molecule With a Big Job

TMG (trimethylglycine) is the amino acid glycine with three methyl groups attached. It is the same compound as betaine, named after the sugar beet where it was first found. Your body makes some from choline, and you also get it from food: wheat germ and bran, spinach, beets and shellfish are rich sources.

TMG has two main jobs. It helps cells hold water and keep their volume steady under stress, and it donates methyl groups, the small chemical tags the body uses to build and regulate hundreds of molecules. That second job is why we include it in Enhanced NMN, alongside NMN, resveratrol and pterostilbene.

Tip: TMG, betaine and betaine anhydrous are the same molecule; "anhydrous" means the powder has no water bound to it. Betaine HCl is a different salt form sold as a digestive aid.

How It Works

How TMG Works

Methyl Donor in the Methionine Cycle

In the liver and kidneys, an enzyme called BHMT moves one methyl group from TMG onto homocysteine, turning it back into the amino acid methionine. Methionine then becomes SAMe, the main methyl donor for reactions that range from making creatine and phospholipids to regulating genes. When SAMe gives up its methyl group it becomes homocysteine again, and the cycle repeats. Folate and vitamin B12 run a second route through the same cycle.

Cell Hydration

TMG is also an osmolyte: it helps cells, especially in the kidneys, liver and muscles, keep their water balance and shape when conditions around them change. This is one reason it has been studied in athletes.

Why Pair It With NMN?

NMN is a precursor the body uses to make NAD+. As NAD+ is used and recycled, the body clears extra nicotinamide by attaching a methyl group to it. Pairing an NAD+ precursor with a methyl donor such as TMG is a common approach meant to support that demand. The reasoning is sound biochemistry, but the combination has not been tested in a human trial.

How TMG feeds the methionine cycle TMG donates a methyl group that turns homocysteine back into methionine in the liver and kidneys. Methionine becomes SAMe, the main methyl donor for many reactions, which then returns to homocysteine. Enhanced NMN provides 200 mg of TMG with 750 mg of NMN. How TMG feeds the methionine cycle Methionine cycle TMG (BETAINE) Gives up one methyl group METHIONINE Made from homocysteine SAMe Main methyl donor for many reactions HOMOCYSTEINE Left after SAMe gives up its methyl ENHANCED NMN, PER 2-CAPSULE SERVING 200 mg TMG with 750 mg NMN, resveratrol, pterostilbene and B12
How TMG supplies methyl groups to the methionine cycle. Diagram by Synchronicity Health.
The Evidence

What Human Studies Found

Homocysteine

In a 6 week trial of 76 healthy adults, 1.5, 3 or 6 g of betaine a day lowered fasting homocysteine by 12, 15 and 20 percent compared with placebo, and a smaller rise in homocysteine after a methionine test drink was already visible on the first day. A meta-analysis of five randomized trials in healthy adults, using at least 4 g a day for 6 to 24 weeks, found an average drop of 1.23 micromoles per liter.

Training and Body Composition

In a 15 day trial of 24 active young men, daily betaine improved squat endurance and the quality of repetitions, but did not change vertical jump, bench throw or cycle sprint power. A 2014 review describes several possible mechanisms, including support for creatine synthesis and cell hydration, and notes that the long-term effects in people are still unclear.

Body Weight

In a 12 week trial, 6 g a day of betaine lowered homocysteine but did not change body weight, body composition or resting energy expenditure compared with placebo.

The honest summary: TMG reliably lowers homocysteine at gram doses and plays a central role in methylation. The 200 mg in Enhanced NMN is a supporting amount, and the idea that it helps balance NMN use has not been tested in people.

Compare

TMG and Other Methyl Nutrients

Several nutrients feed the same methylation system through different routes.

NutrientRole in methylationMain food sourcesIn our products
TMG (betaine)Donates a methyl group to homocysteine through BHMT, mainly in the liver and kidneysWheat bran and germ, spinach, beets, shellfishEnhanced NMN, 200 mg
FolateSupplies methyl groups through the folate routeLeafy greens, legumesNot used
Vitamin B12Cofactor that lets the folate route workAnimal foodsEnhanced NMN (750 mcg) and our B12 nasal spray
CholineConverted into betaine in the bodyEggs, liver, soybeansAlpha GPC in Clarity Nasal Spray
How To Use It

Dosage, Timing, and Stacking

Amounts Used in Studies

Homocysteine studies used 1.5 to 6 g a day, and typical diets supply about 0.5 to 2 g. Enhanced NMN provides 200 mg per serving as part of an NAD+ formula, so follow the label rather than these study amounts.

Timing

The Enhanced NMN label says two capsules in the morning, with or without food. TMG has no known timing effect of its own, so the best time to take it is the time you will remember each day. Because gram doses can cause mild digestive upset, some people take a separate TMG supplement with a meal.

Stacking

TMG already sits with NMN, resveratrol, pterostilbene and vitamin B12 in Enhanced NMN. Our Longevity Stack pairs Enhanced NMN with NAD+ Nasal Spray and Glutathione Nasal Spray. If you already take a separate high-dose TMG product, count it in your total and check with your clinician.

Read This First

Safety and Side Effects

TMG is a normal part of the diet and is generally well tolerated. At gram doses, some people notice mild digestive upset.

Points Worth Knowing

  • Cholesterol: a meta-analysis of six trials found that at least 4 g a day for six weeks or more raised total cholesterol by about 0.34 mmol/L, with no significant change in LDL, HDL or triglycerides. This is far above the 200 mg in Enhanced NMN, but worth knowing if you take a separate high-dose product.
  • Medications: TMG interacts with methylation, so anyone on medication that affects folate or homocysteine should ask a clinician before adding high doses.

Who should be cautious: speak with a qualified healthcare professional before taking TMG supplements if you are pregnant or nursing, have a kidney or liver condition, are watching your cholesterol, or take regular medication.

In Short

Key Takeaways

  • TMG (betaine) is a methyl donor that turns homocysteine back into methionine and helps cells keep their water balance.
  • Gram doses of 1.5 to 6 g a day lowered homocysteine by 12 to 20 percent in healthy adults.
  • Training studies are small and mixed; one found better squat endurance but no change in power.
  • Enhanced NMN provides 200 mg per serving, a supporting amount alongside NMN; the pairing rationale is untested in people.
  • High doses of 4 g a day or more slightly raised total cholesterol in trials.
The Bottom Line

Quiet Work, Every Day.

TMG does not announce itself. It supplies the methyl groups that keep one of the body's busiest cycles turning, which is why it earns a small, steady place next to NMN.

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Frequently Asked

TMG FAQ

What are the benefits of TMG?

TMG (trimethylglycine, or betaine) donates methyl groups that the liver uses to turn homocysteine back into methionine. In healthy adults, 1.5 to 6 g a day for 6 weeks lowered fasting homocysteine by 12 to 20 percent compared with placebo. Smaller studies have looked at training performance, with mixed results. It also helps cells hold water and keep their volume steady.

Why is TMG paired with NMN?

When the body clears extra nicotinamide, part of NAD+ turnover, it attaches a methyl group to it. Some people pair NAD+ precursors such as NMN with a methyl donor like TMG to support that demand. This is a reasonable idea based on biochemistry, but the pairing has not been tested in a human trial.

How much TMG is in Enhanced NMN?

Each 2-capsule serving of Enhanced NMN contains 200 mg of TMG, alongside NMN 750 mg, resveratrol 200 mg, pterostilbene 100 mg and vitamin B12 750 mcg. That is well below the 1.5 to 6 g a day used in homocysteine studies and within the range people get from food.

Who should avoid taking TMG?

At high doses of 4 g a day or more, TMG raised total cholesterol slightly in trials, so people watching their cholesterol should check with a clinician before taking large amounts. Anyone who is pregnant or nursing, has a kidney or liver condition, or takes regular medication should also ask first.

Is TMG the same as creatine?

No. TMG and creatine are different molecules. TMG supplies methyl groups to the methionine cycle, which the body also uses to make creatine, so the two are related biochemically, but TMG does not replace creatine.

Is TMG the same as betaine HCl?

Not quite. TMG is betaine in its plain form. Betaine hydrochloride (betaine HCl) is a salt form sold as a digestive acid supplement, which is a different use.

What foods contain TMG?

Rich dietary sources include wheat germ and wheat bran, spinach, beets and seafood, especially shellfish. Typical diets supply roughly 0.5 to 2 g a day.

What does TMG do for the body?

TMG does two main jobs. It donates methyl groups that the liver and kidneys use to turn homocysteine back into methionine, which then becomes SAMe, the main methyl donor for many reactions. It also acts as an osmolyte, helping cells keep their water balance and volume steady.

How much TMG should I take per day?

There is no official recommended amount. Homocysteine studies used 1.5 to 6 g a day, and typical diets supply about 0.5 to 2 g. Enhanced NMN provides 200 mg per 2-capsule serving as a supporting amount alongside NMN. Follow your product label, and ask a clinician before taking gram doses.

What is the best time to take TMG?

TMG has no known timing effect of its own, so take it at a time you will remember each day. The Enhanced NMN label says two capsules in the morning, with or without food. If a separate gram-dose TMG product upsets your stomach, taking it with a meal may help.

What are the side effects of TMG?

TMG is a normal part of the diet and is generally well tolerated. At gram doses some people notice mild digestive upset. In trials, 4 g a day or more for six weeks or longer raised total cholesterol by about 0.34 mmol/L, far above the 200 mg in Enhanced NMN.

Is betaine anhydrous the same as TMG?

Yes. Betaine anhydrous is TMG (trimethylglycine) in a dry powder form with no water bound to it. Betaine HCl is a different salt form sold as a digestive acid supplement.

Should I take TMG with NMN?

Many people pair NMN with a methyl donor such as TMG, because the body attaches a methyl group to extra nicotinamide as it uses and recycles NAD+. The idea is sound biochemistry but has not been tested in a human trial. Enhanced NMN already includes 200 mg of TMG with 750 mg of NMN, so there is no need to add a separate product for that supporting amount.

Is TMG the same as glycine?

No. TMG is glycine with three methyl groups attached, which is what lets it donate methyl groups. Glycine on its own has none to give.

References

Sources

  1. Craig SA. Betaine in human nutrition. American Journal of Clinical Nutrition, 2004. PubMed 15321791
  2. Olthof MR, et al. Low dose betaine supplementation leads to immediate and long term lowering of plasma homocysteine in healthy men and women. Journal of Nutrition, 2003. PubMed 14652361
  3. McRae MP. Betaine supplementation decreases plasma homocysteine in healthy adult participants: a meta-analysis. Journal of Chiropractic Medicine, 2013. PubMed 23997720
  4. Schwab U, et al. Betaine supplementation decreases plasma homocysteine concentrations but does not affect body weight, body composition, or resting energy expenditure in human subjects. American Journal of Clinical Nutrition, 2002. PubMed 12399266
  5. Hoffman JR, et al. Effect of betaine supplementation on power performance and fatigue. Journal of the International Society of Sports Nutrition, 2009. PubMed 19250531
  6. Cholewa JM, et al. Effects of betaine on performance and body composition: a review of recent findings and potential mechanisms. Amino Acids, 2014. PubMed 24760587
  7. Zawieja EE, et al. Betaine supplementation moderately increases total cholesterol levels: a systematic review and meta-analysis. Journal of Dietary Supplements, 2021. PubMed 31809615

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure, or prevent any disease. Nothing here is medical advice. If you are pregnant, nursing, taking medication, or managing a health condition, consult a qualified healthcare professional before use.