Can TMG and NMN Support Healthy Ageing?

Last Reviewed: 31 December 2025
Written by: Mathew Stuckey, Founder, Longevity Formulas

Quick Answer

NMN and TMG may work synergistically to support healthy ageing: NMN boosts NAD+ levels (which decline approximately 50% by age 50), whilst TMG provides the methyl groups needed to process NMN's metabolic by-products efficiently. 

Research shows NMN improves cellular energy and physical performance, whilst TMG reduces homocysteine (a cardiovascular risk marker) by 20-30%. Together, they may support energy levels, cardiovascular health, and cellular function more effectively than either supplement alone.

Typical dosing: 250-500mg NMN with 1-1.5g TMG daily, taken in the morning with food.

We also covered this topic on our youtube channel which you can view below.

Understanding NMN: The NAD+ Precursor

Nicotinamide Mononucleotide (NMN) is a compound derived from vitamin B3 (niacin), naturally present in small amounts in foods like broccoli, edamame, and avocados. Its primary function is serving as a direct precursor to Nicotinamide Adenine Dinucleotide (NAD+), a coenzyme essential for cellular energy production and DNA repair.

Why NAD+ Matters

NAD+ is critical for cellular metabolism. It drives the electron transport chain in mitochondria, producing ATP—the energy currency that powers every cellular process. NAD+ also activates sirtuins (longevity-associated proteins) and supports DNA repair enzymes called PARPs.

The challenge: NAD+ levels decline substantially with age. Research indicates approximately 50% reduction by age 50, with further decreases in subsequent decades (Nature Reviews Molecular Cell Biology, 2018). This decline is associated with reduced mitochondrial function, decreased cellular repair capacity, and various age-related changes.

How NMN Works

When you take NMN orally, it's absorbed through the small intestine and converted to NAD+ within cells. A 2020 study in Nature Communications showed that oral NMN supplementation increased blood NAD+ levels by up to 142% within hours (Yoshino et al., 2021).

What we've seen: Most users report improved energy within 2-4 weeks, but responses vary widely. Some notice changes within days, others need months. This likely reflects individual NAD+ depletion levels before starting supplementation.

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Understanding TMG: The Methylation Supporter

Trimethylglycine (TMG), also called betaine, is an amino acid derivative found naturally in beetroot, spinach, and whole grains. It functions as a methyl donor—providing methyl groups (CH3) needed for hundreds of biochemical reactions throughout the body.

The Role of Methylation

Methylation regulates gene expression, produces neurotransmitters, supports detoxification, and converts homocysteine to methionine. This last function is particularly important for cardiovascular health, as elevated homocysteine is associated with increased cardiovascular risk.

TMG provides three methyl groups per molecule, making it one of the most efficient methyl donors available. Clinical studies show TMG supplementation (1.5-6g daily) reduces homocysteine levels by 20-30% (McRae, 2013).

Our experience: We added TMG to our NMN Complex after reviewing methylation data showing NMN's NAM by-product consumes methyl groups. Customer feedback on the combined formula has been consistently better than NMN alone, though this is observational rather than clinical evidence.

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Why Combine NMN and TMG?

The synergy between NMN and TMG stems from NMN's metabolic pathway. When NMN boosts NAD+ production, it generates nicotinamide (NAM) as a by-product. To be excreted, NAM must be methylated—a process that consumes methyl groups from your body's methylation pool.

Without adequate methyl donors, sustained NMN supplementation could theoretically deplete methylation capacity, though this hasn't been clinically demonstrated to cause problems in healthy individuals.

The Theoretical Framework

TMG supplies the methyl groups needed to process NAM efficiently, theoretically allowing sustained NAD+ elevation without compromising methylation-dependent processes like homocysteine metabolism. Additionally, TMG's homocysteine-lowering effects complement NMN's cardiovascular benefits.

Important caveat: Whilst this synergy is biochemically sound, there are no published clinical trials directly comparing NMN alone versus NMN+TMG in humans. The synergy is based on metabolic pathways rather than head-to-head clinical evidence.

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What Research Shows vs. What Remains Unknown

What Research Demonstrates

NMN Studies:

• 250mg daily improved insulin sensitivity in postmenopausal women with prediabetes over 10 weeks (Yoshino et al., 2021)
• 300mg daily increased aerobic capacity in recreational runners aged 27-50 (Liao et al., 2021)
• Up to 1,250mg daily showed no adverse effects in a 12-week safety trial (Igarashi et al., 2022)

TMG Studies:

• Meta-analysis of 13 trials confirmed 1.5-6g daily reduces homocysteine by approximately 10-20% (Olthof et al., 2005)
• Safe and well-tolerated at doses up to 15g daily in clinical settings

Combined Use:

• No published trials directly testing NMN+TMG combinations exist
• The rationale is mechanistic, based on metabolic pathways

What We Don't Know

• Optimal NMN:TMG ratios for different populations
• Long-term effects (beyond 12 weeks) of combined supplementation
• Whether TMG genuinely improves NMN outcomes in practice
• Effects in younger adults (<40 years old)
• Whether dietary methyl donors (from food) are sufficient for most NMN users

Reality check: The combination is biochemically sound, but no clinical trials test NMN+TMG together. We're applying metabolic pathway knowledge to a supplement pairing that lacks direct research. Both compounds have strong safety profiles individually, which is reassuring.

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Practical Dosing Guidelines

Based on clinical research and observed safety profiles:

Starting Protocol

Week 1-4:

• NMN: 250mg daily (morning, with food)
• TMG: 1g daily (with NMN or separately)

Week 5-8:

• NMN: 500mg daily (if well-tolerated)
• TMG: 1.5g daily

Week 9+:

• NMN: 500-1,000mg daily
• TMG: 1.5-2g daily

Timing Considerations

Take NMN in the morning, as NAD+ follows circadian rhythms and supports daytime energy metabolism. TMG can be taken with NMN or split across meals. Both are better absorbed with food containing healthy fats.

Individual Variations

Some practitioners suggest a 1:2 or 1:3 ratio of NMN:TMG (e.g., 500mg NMN with 1-1.5g TMG), though this isn't evidence-based. Start conservatively and adjust based on how you feel and, ideally, blood biomarker testing.

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Safety and Side Effects

NMN Safety Profile

Clinical trials up to 1,250mg daily for 12 weeks showed no serious adverse effects. Occasional mild flushing or digestive discomfort has been reported anecdotally at higher doses (>1,000mg).

TMG Safety Profile

Well-tolerated up to 15g daily in clinical settings. Mild gastrointestinal symptoms (nausea, stomach upset) may occur at higher doses (>6g). Some individuals report a fishy body odour at very high doses due to trimethylamine production.

Important Contraindications

Consult your GP before use if you:

• Take blood pressure medications (NMN may affect vascular function)
• Have MTHFR genetic variants (affects methylation metabolism)
• Are pregnant or breastfeeding (insufficient safety data)
• Have kidney or liver conditions
• Take medications metabolised via methylation pathways

What to Monitor

If supplementing long-term, consider annual blood tests for:

• Homocysteine levels (TMG should reduce these)
• Methylmalonic acid (indicates B12 status, important for methylation)
• Liver function (both supplements are hepatically metabolised)
• Blood pressure and glucose (NMN may affect these)

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Realistic Expectations

What People Report

Based on customer feedback and online communities, common reported experiences include:

Within 2-4 weeks:

• Improved morning energy levels
• Better exercise recovery
• Clearer thinking

Within 8-12 weeks:

• Enhanced physical endurance
• Improved skin texture (anecdotal)
• More consistent energy throughout the day

What's likely placebo or confounded:

• Dramatic overnight changes
• "Anti-ageing miracles"
• Complete reversal of age-related conditions

User feedback patterns: The most credible reports describe gradual improvements over weeks, not sudden transformations. Users combining supplementation with exercise, sleep, and nutrition consistently report better outcomes than supplements alone.

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Potential Cardiovascular Benefits

Both compounds may support heart health through complementary mechanisms:

NMN's cardiovascular effects:

• Improved endothelial function (blood vessel flexibility)
• Enhanced mitochondrial energy in heart muscle
• Reduced arterial stiffness in animal studies (de Picciotto et al., 2016)

TMG's cardiovascular effects:

• Reduced homocysteine (independent cardiovascular risk factor)
• Improved lipid metabolism
• Enhanced liver function

Combined potential: The pairing may offer dual support for vascular health, though this hasn't been clinically validated in combination studies.

Who Might Benefit Most

Based on available research, these supplements may be most relevant for:

• Adults over 40 experiencing age-related energy decline
• Active individuals seeking exercise performance support
• Those with elevated homocysteine levels (TMG specifically)
• People interested in longevity-focused supplementation

Who should be cautious:

• Younger adults (<30) with no specific health concerns
• Those with genetic methylation variants (MTHFR)
• Individuals on multiple medications
• Anyone expecting dramatic anti-ageing effects

Where to Learn More

Related articles on this site:

• What is NMN? A Guide to Nicotinamide Mononucleotide
• Why Take TMG with NMN?
• How NMN Works in the Body: A Simple Guide
• Is NMN Safe to Take Daily?

Our products:

• NMN Complex (contains both NMN and TMG)
• NAD+ Boosting Supplements

Key Scientific References

1. Yoshino, J., et al. (2021). "Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women." Science, 372(6547), 1224-1229.

2. Liao, B., et al. (2021). "Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners." Journal of the International Society of Sports Nutrition, 18(1), 54.

3. McRae, M.P. (2013). "Betaine supplementation decreases plasma homocysteine in healthy adult participants: a meta-analysis." Journal of Chiropractic Medicine, 12(1), 20-25.

4. Igarashi, M., et al. (2022). "Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men." npj Aging, 8(1), 5.

5. de Picciotto, N.E., et al. (2016). "Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice." Aging Cell, 15(3), 522-530.

Final Thoughts: NMN and TMG represent a biochemically rational supplement combination for supporting healthy ageing, particularly for adults experiencing age-related NAD+ decline. However, they're not magic pills. The strongest evidence supports modest improvements in energy metabolism and cardiovascular markers when combined with healthy lifestyle habits. As with any supplement, individual responses vary, and professional medical guidance is advisable for personalised recommendations.