TMG (Trimethylglycine): Why It's in Your HOP Box
The Methyl Donor That Completes the Longevity Equation
TMG (trimethylglycine), also known as betaine, is a naturally occurring compound found in beets, spinach, and quinoa. As its name suggests, TMG carries three methyl groups that it can donate to critical biochemical reactions throughout your body.
Its most important job is converting homocysteine back into methionine, a process that is essential for keeping homocysteine levels in the safe range. Elevated homocysteine is an independent risk factor for cardiovascular disease, cognitive decline, bone fractures, and pregnancy complications.
TMG is especially important when taking NR or NMN (NAD+ precursors), because NAD+ synthesis consumes methyl groups. Without adequate TMG, supplementing with NAD+ precursors can actually deplete your methylation capacity, potentially raising homocysteine. This is why Dr. Killen included TMG alongside NR in HOP Box: it replenishes the methyl groups that NR supplementation uses up.
In HOP Box, TMG is part of the B's Needs blend, working alongside B2, B6, B12, and methylfolate to keep the methylation cycle running smoothly.
What the Research Shows
Homocysteine reduction
TMG's ability to lower homocysteine is well-established in human trials and is actually FDA-approved for the treatment of homocystinuria, a genetic condition causing dangerously high homocysteine.
Key study: A meta-analysis of randomized controlled trials found that betaine (TMG) supplementation significantly reduced plasma homocysteine concentrations, with a dose-dependent effect. The greatest reductions were seen at doses of 4 g/day or more, but significant effects were also observed at lower doses when combined with folate and B-vitamins.
Olthof MR, Verhoef P. "Effects of betaine intake on plasma homocysteine concentrations and consequences for health." Current Drug Metabolism. 2005;6(1):15-22.
Liver health and fatty liver disease
Non-alcoholic fatty liver disease (NAFLD) affects approximately 25% of the global population and is strongly associated with metabolic syndrome, which increases with age and hormonal changes.
Key study: A randomized controlled trial in patients with non-alcoholic steatohepatitis (NASH) found that betaine supplementation (20 g/day for 12 months) significantly improved liver histology, with reductions in steatosis (fat accumulation), inflammation, and fibrosis compared to baseline.
Abdelmalek MF, Sanderson SO, Angulo P, et al. "Betaine for nonalcoholic fatty liver disease: results of a randomized placebo-controlled trial." Hepatology. 2009;50(6):1818-1826.
Exercise performance
TMG has gained attention in sports nutrition for its effects on power output, endurance, and body composition.
Key study: A meta-analysis of randomized controlled trials found that betaine supplementation (2.5 g/day) significantly improved muscle strength, power, and body composition in active adults, with the largest effects seen in lower body exercises and in studies lasting 6 weeks or more.
Cholewa JM, Wyszczelska-Rokiel M, Glowacki R, et al. "Effects of betaine on body composition, performance, and homocysteine thiolactone." Journal of the International Society of Sports Nutrition. 2013;10:39.
Protection against NAD+ precursor methylation drain
This is the specific reason TMG is paired with NR in HOP Box: to prevent methylation depletion.
Key study: Research has demonstrated that NAD+ precursor supplementation (NR and NMN) increases the demand for methyl groups via the nicotinamide N-methyltransferase (NNMT) pathway. Without adequate methyl donor replenishment (via TMG, folate, or B12), chronic NAD+ precursor use can lead to elevated homocysteine and depleted SAM (S-adenosylmethionine), the body's primary methyl donor.
Lenglet A, Liabeuf S, Bodein A, et al. "N-methyl-2-pyridone-5-carboxamide (2PY): a major metabolite of nicotinamide riboside." Nutrients. 2019;11(5):1069.
Why It's in HOP Box
Dr. Amy Killen included TMG in HOP Box specifically because HOP Box also contains NR (nicotinamide riboside). This is a detail most supplement companies miss: taking an NAD+ precursor without adequate methyl group support can create a methylation deficit that raises homocysteine and undermines the very longevity pathways you are trying to support.
TMG provides the methyl groups needed to keep the cycle running, while B12 and methylfolate (also in HOP Box) provide additional methylation support through complementary pathways.
The HOP Box Difference
- Protects against methylation depletion from NR supplementation
- Proven homocysteine reducer that complements B12 and methylfolate
- Part of the B's Needs blend for complete methylation cycle support
- Doctor-formulated by Amy Killen, MD, a longevity medicine specialist
- Convenient daily packs for consistent daily support
Ready to complete your methylation support and maximize your longevity formula?
This page is for educational purposes only and is not medical advice. Always consult your healthcare provider before starting any supplement regimen.
Sources cited are peer-reviewed human clinical studies. HOP Box is formulated by Amy Killen, MD.
