Why is TMG needed with NMN?

If you are a longevity enthusiast, you probably already know about nicotinamide mononucleotide (NMN) supplementation. You possibly also know about trimethylglycine (TMG) supplements. It seems that both of those should be taken together, but do you know why? 

Don't worry if you never heard about these supplements or you're in the beginning of your longevity journey. This article will explain all you need to know! 

Benefits of NMN

NMN or nicotinamide mononucleotide is a molecule used as raw material for the synthesis of nicotinamide adenine dinucleotide or NAD+. This molecule is then used for a wide range of metabolic functions, and for the production of cellular energy.

As we age, the natural production of NAD+ in our bodies decreases. We start noticing usual aging symptoms, like a lack of energy, less athletic and cognitive capability, and perhaps the development of age-related diseases. NAD+ cannot unfortunately be taken up directly by our cells, but NMN can. This is the reason NMN became a popular anti-aging supplement instead. 

There are already several scientifically proven health benefits of NMN in humans, such as:

• NMN raises NAD+ levels in blood (1),
• NMN increases muscle responsiveness and drowsiness in older age (2),
• NMN increases aerobic capacity during training (3). 

 Read more about NMN health benefits in our articles:

• 5 Benefits of Nicotinamide Mononucleotide (NMN)
• What Is Nicotinamide Mononucleotide Good For?
• When and how should you take NMN?

Do I need to take TMG with NMN?

You can take NMN without TMG if you want to, or you can take both. However, it would be a very good idea to take NMN and TMG together in any case. This is because the breakdown of NMN requires high levels of methionine, and TMG supplements might help replenish them (4). 

Explore our offer of TMG (Betaine) supplements: TMG (Betaine) - 500 mg x 120 capsules. 

On the other hand, if you decided not to take TMG supplements, you can try to naturally increase your levels of TMG, or its precursor choline. You can do this by eating more of these foods:

• beets,
• shellfish,
• spinach,
• eggs (for choline),
• animal liver (for choline) and meat in general. 

Be aware that you can generally take a much lower dose of TMG/choline through food than through supplements. 

TMG dosage with NMN

NMN was found to be safe when taken up to 1200 mg per day, for up to six weeks (3). This dose was also found to be more effective than smaller doses. TMG is safe when taken in doses of up to 15 grams per day, and the most common side effects are nausea, gastrointestinal issues, and increased levels of LDL cholesterol in the body (5). 

Since you won't take more than 1200 mg of NMN per day, and TMG supports NMN, you don't have to take more than 1200 mg of TMG per day. One of the most famous longevity researchers, dr. David Sinclair, takes 1000 mg of NMN and 500-1000 mg of TMG per day (6). 

When to take TMG with NMN?

As these two supplements work in synergy, TMG can be taken at the same time as NMN. However, as the idea is to increase the levels of TMG in your body to be available for NMN at any time, you can take them separately as well. 

The only proof we have on this topic so far comes from David Sinclair's personal research. He likes to take NMN and TMG, among other supplements, in the morning to have enough energy throughout the day. 

Dr. Sinclair emphasizes that his supplement routine is based on his personal research. Anyone who's considering such supplements should talk to a healthcare provider first.

What can't you take with NMN?

NMN supplements are generally considered safe to use (1), but there may be some cross-interactions with other supplements or medication. 

First of those would be supplements that also increase NAD+ levels, but through different molecular pathways. Those are, for example, niacin and nicotinic acid, which are both forms of vitamin B3. While increasing NAD+ through different pathways than NMN, they might decrease the efficiency of NMN. 

It was shown in animal studies that NMN can lower blood sugar and insulin levels (7, 8), which means it might interfere with some medication that lowers blood sugar. If you're already taking metformin or insulin, the addition of NMN might further reduce blood sugar levels and lead to hypoglycemia. However, there is no research on humans regarding NMN and insulin levels, so consult your doctor before you take it. 

Reference list:

1. Irie J, Inagaki E, Fujita M, Nakaya H, Mitsuishi M, Yamaguchi S, Yamashita K, Shigaki S, Ono T, Yukioka H, Okano H, Nabeshima YI, Imai SI, Yasui M, Tsubota K, Itoh H. Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men. Endocr J. 2020 Feb 28;67(2):153-160. doi: 10.1507/endocrj.EJ19-0313. 
2. Kim M, Seol J, Sato T, Fukamizu Y, Sakurai T, Okura T. Effect of 12-Week Intake of Nicotinamide Mononucleotide on Sleep Quality, Fatigue, and Physical Performance in Older Japanese Adults: A Randomized, Double-Blind Placebo-Controlled Study. Nutrients. 2022 Feb 11;14(4):755. doi: 10.3390/nu14040755.
3. Liao B, Zhao Y, Wang D, Zhang X, Hao X, Hu M. Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study. J Int Soc Sports Nutr. 2021 Jul 8;18(1):54. doi: 10.1186/s12970-021-00442-4.
4. Arumugam MK, Paal MC, Donohue TM Jr, Ganesan M, Osna NA, Kharbanda KK. Beneficial Effects of Betaine: A Comprehensive Review. Biology (Basel). 2021 May 22;10(6):456. doi: 10.3390/biology10060456.
5. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Betaine. [Updated 2017 Sep 26]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548774/
6. Ciardha, V. (2023) The Anti-Aging Supplements Dr. David Sinclair Takes Besides NMN. NMN.com
7. Yoshino J, Mills KF, Yoon MJ, Imai S. Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 2011 Oct 5;14(4):528-36. doi: 10.1016/j.cmet.2011.08.014.
8. Mills KF, Yoshida S, Stein LR, Grozio A, Kubota S, Sasaki Y, Redpath P, Migaud ME, Apte RS, Uchida K, Yoshino J, Imai SI. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metab. 2016 Dec 13;24(6):795-806. doi: 10.1016/j.cmet.2016.09.013.