In the US, the benefits people link to NMN + TMG come mostly from NMN trials, not from the pair. Small human studies show NMN raises blood NAD+, and some found better walking distance or muscle insulin sensitivity. TMG is studied for homocysteine at gram doses. No published trial has tested NMN + TMG together.
Blood NAD+: The Most Consistent Result
NMN is sold to support NAD+, so the first question is simple: does it raise NAD+ in people? Three of the trials reviewed here measured it, and all three saw an increase.
In a 60-day randomized, double-blind, placebo-controlled trial of 80 healthy middle-aged adults, blood NAD rose significantly in all NMN groups (300, 600 or 900 mg once daily) at day 30 and day 60. Levels were highest at 600 and 900 mg (Yi 2023).
In healthy older men, 250 mg a day for 6 or 12 weeks significantly raised blood NAD+ and its metabolites (Igarashi 2022). In an 8-week open-label study, 11 healthy middle-aged Japanese men took two 125 mg capsules once daily before breakfast. NAD+ in their blood mononuclear cells increased (Yamaguchi 2024).
A higher NAD+ reading shows that a marker moved. On its own, it is not a health outcome. For dose context, see our guide on how much NMN per day trials used.
Walking and Physical Performance: Small, Mixed Signals
In the Yi trial, six-minute walking distance improved versus placebo in all NMN groups at day 30 and day 60 (Yi 2023). This is a practical, everyday measure, which makes it one of the more interesting findings.
Older men taking 250 mg a day showed nominally significant improvements in gait speed and a left grip test. The authors said these results "should be validated in larger studies." Body composition did not change (Igarashi 2022).
A 6-week trial gave 48 recreationally trained runners 300, 600 or 1,200 mg NMN a day while they trained 5-6 times a week. Oxygen uptake, %VO2max and power at ventilatory thresholds rose more in the 600 and 1,200 mg groups than in the control group. VO2max itself and peak power did not change (Liao 2021).
The honest reading: some measures moved, some did not, and each signal comes from one small study.
Insulin Sensitivity: One Group, One Measure
A 10-week randomized, placebo-controlled, double-blind trial gave 250 mg NMN daily to postmenopausal women with prediabetes who were overweight or obese. Muscle insulin sensitivity, measured by clamp, and muscle insulin signaling increased after NMN but not after placebo (Yoshino 2021).
In healthy middle-aged adults, HOMA-IR, a measure of insulin resistance, did not differ from placebo (Yi 2023). So this result applies to one population and one lab method. It does not show that NMN changes blood sugar in the general public.
What TMG Adds, and Why 250 mg Is Not a Trial Dose
The case for the pairing is about methyl groups. The enzyme NNMT uses SAM (S-adenosylmethionine) as a methyl donor to turn nicotinamide (NAM) into methylnicotinamide. That step produces SAH, a precursor of homocysteine (Li 2024). TMG (betaine) works mainly as an osmolyte and a methyl donor. As a methyl donor, it acts in the methionine cycle, mostly in the liver and kidneys. Low methyl intake is linked to higher homocysteine and lower SAM (Craig 2004). Betaine donates methyl groups to homocysteine to form methionine (Zeisel 2003).
The rationale runs like this: NMN yields NAM, NAM methylation draws on methyl groups, and TMG supplies them. That is a mechanistic rationale, not a proven clinical benefit. No published human trial has tested NMN + TMG against NMN alone. Our article on NMN and TMG together covers the pairing in more depth.
TMG's own human data come from gram doses. Usual dietary intake is roughly 0.5-2 g a day. In healthy adults, 1.5, 3 and 6 g a day for 6 weeks lowered fasting homocysteine by 12%, 15% and 20% versus placebo (Olthof 2003). A meta-analysis of 5 trials using at least 4 g a day found homocysteine fell by 1.23 µmol/L (McRae 2013). A larger 2022 meta-analysis also found that betaine raised total cholesterol by 14.12 mg/dL and LDL by 10.26 mg/dL (Ashtary-Larky 2022).
Each 2-capsule serving of AgeAura Pure NMN + TMG NAD+ Complex provides 500 mg NMN and 250 mg TMG. It also has 100 mg trans-resveratrol, 150 mg quercetin, 50 mg apigenin, 1 mg spermidine and 400 mcg DFE folate as L-5-MTHF. That 250 mg of TMG is far below the tested amounts, and below even usual dietary intake. No trial tested 250 mg. So do not expect it to lower homocysteine, and do not assume the cholesterol finding applies to it either.
What the Trials Did NOT Show
- No lifespan data. None of these trials measured how long people live.
- Small samples. The trials enrolled 10 to 80 people.
- Short durations. They ranged from single doses to 12 weeks.
- Industry involvement. Yi 2023 was industry co-sponsored. A trial of 1,250 mg daily for up to 4 weeks in 31 healthy adults was funded by the NMN supplier, and its authors were employed by that supplier (Fukamizu 2022).
- No combination trial. No published human trial has tested NMN + TMG against NMN alone.
- Narrow groups. The participants were healthy middle-aged adults, healthy older men, middle-aged Japanese men, trained runners and postmenopausal women with prediabetes.
Short-term tolerability looked good. In 10 healthy men, single doses of 100, 250 and 500 mg caused no significant clinical symptoms and no changes in heart rate, blood pressure or oxygen saturation over 5 hours (Irie 2020). The 1,250 mg trial found no severe adverse events. Short-term tolerability is not long-term safety data.
NMN + TMG Benefits in the US: 2026 Evidence Table
Each row shows one outcome from one study.
| Outcome | Study | Dose | Result | Caveat |
|---|---|---|---|---|
| Blood NAD | Yi 2023 | 300-900 mg/day, 60 days | Rose in all NMN groups | 80 adults; industry co-sponsored |
| Blood NAD+ | Igarashi 2022 | 250 mg/day, 6 or 12 weeks | Rose significantly | Healthy older men only |
| Mononuclear-cell NAD+ | Yamaguchi 2024 | 2 × 125 mg/day, 8 weeks | Increased | Open-label; 11 men |
| Six-minute walk | Yi 2023 | 300-900 mg/day | Improved vs placebo | Small; 60 days |
| Gait speed, grip | Igarashi 2022 | 250 mg/day | Nominal gains | Needs larger studies |
| Ventilatory thresholds | Liao 2021 | 600 or 1,200 mg/day, 6 weeks | Rose vs control | VO2max and peak power unchanged |
| Muscle insulin sensitivity | Yoshino 2021 | 250 mg/day, 10 weeks | Increased | One group of women |
| HOMA-IR | Yi 2023 | 300-900 mg/day | No difference vs placebo | Healthy adults |
| Homocysteine (TMG) | Olthof 2003 | 1.5-6 g/day, 6 weeks | Fell 12-20% | Far above 250 mg |
Who Might Reasonably Try It, and How to Judge It
A reasonable candidate is a healthy adult who is curious about NAD+ support and accepts early, modest evidence. It is a poor fit for anyone who expects dramatic changes, because the trials do not support that.
If you try it, judge it fairly. Pick a fixed period, keep your routine steady, and track something you can measure, like a regular walk. Our guide on how long NMN takes to work covers what to watch from week 1 to week 12.
According to the product page, Wellness Nest's AgeAura Pure NMN + TMG NAD+ Complex is non-GMO and comes in vegan capsules. It is made in a USA cGMP-certified partner facility, with no artificial fillers or preservatives. It lists wheat as an allergen, because its spermidine comes from wheat germ extract. The label also says it is free from gluten, soy, dairy, fish and shellfish. You can also browse the Wellness Nest best sellers.
Dietary supplements are not FDA-approved to treat, cure or prevent disease. If you are pregnant, nursing, under 18, taking medication or managing a medical condition, talk to your doctor before use. This product is not a medicine and does not replace medical care.
Frequently Asked Questions
Has the NMN + TMG combination been tested in humans?
No. No published human trial has tested NMN + TMG against NMN alone. The evidence comes from separate NMN and TMG studies, plus a methylation rationale.
Is NMN legal in dietary supplements in the US?
Yes. On September 29, 2025, the FDA responded to a Natural Products Association citizen petition and confirmed that NMN is lawful in dietary supplements (NPA). The FDA found that NMN was marketed as a supplement in the US as early as 2017.
Will 250 mg of TMG lower homocysteine?
No trial has shown that. Trials lowered homocysteine with 1.5-6 g a day (Olthof 2003), and 250 mg is below even usual dietary intake. No trial has tested 250 mg.
Was NMN well tolerated in trials?
Yes, in the short term. Yi 2023 found no safety issues at up to 900 mg daily for 60 days (Yi 2023). Igarashi 2022 found no significant harmful effect at 250 mg (Igarashi 2022). Neither trial lasted long enough to show long-term safety.
What does it cost?
One bottle costs $69.95 as a one-time purchase. Subscribe & save options include 1 bottle every 4 weeks at 15% off, or 3 every 12 weeks or 6 every 24 weeks at 14% off. The product page offers a 90-day money-back guarantee, and other Wellness Nest products are on the Wellness Nest best sellers.
About the Author
Dr. Marcus Hale — Dr. Marcus Hale is the resident health researcher behind Wellness Nest's editorial team, translating peer-reviewed sports-nutrition and longevity research into practical daily guidance for US readers.
