NMN 1000+

NAD+ declines with age. NMN 1000+ addresses the decline at its source — and the pathways that determine what your body does with the NAD+ it makes.*

NAD+ (nicotinamide adenine dinucleotide) is not one thing — it is the central currency of cellular energy metabolism, the required cofactor for PARP-mediated DNA repair, the substrate for sirtuin longevity enzymes, and a critical signaling molecule across virtually every tissue in the body. Its decline with age — measurable in blood, muscle, and brain — is recognized as one of the most significant shifts in the biochemistry of aging.*

NMN (nicotinamide mononucleotide) is a direct precursor to NAD+ through the salvage biosynthesis pathway — and the most clinically validated approach to supporting NAD+ levels through oral supplementation. At 1,000 mg per serving, NMN 1000+ delivers NMN at the dose tier used in published human clinical trials demonstrating meaningful NAD+ elevation.*

Three synergistic supporting ingredients — TMG for methylation balance, pterostilbene for sirtuin activation and antioxidant defense, and apigenin for CD38-mediated NAD+ conservation — complete a multi-pathway NAD+ support system that addresses not just synthesis but utilization and preservation of NAD+ simultaneously.*

KEY SUPPORTED BENEFITS

NMN 1000+ is formulated to support:*

• Healthy NAD+ levels — the primary coenzyme for cellular energy, DNA repair, and longevity signaling*
• Mitochondrial energy production and cellular metabolic efficiency*
• Healthy sirtuin enzyme activity — the longevity signaling proteins dependent on NAD+*
• Healthy DNA repair processes — PARP enzyme activity requires NAD+ as a substrate*
• Balanced methylation pathways and healthy homocysteine metabolism*
• Cellular resilience and oxidative stress defense*
• Cognitive vitality and neurological energy metabolism*
• Healthy AMPK and metabolic signaling balance*

THE FOUR-PATHWAY NAD+ SUPPORT SYSTEM

• Direct NAD+ Precursor → NMN 1,000 mg (salvage pathway · doubles circulating NAD+ in 14 days)
• Methylation Balance → TMG 500 mg (methyl donor · homocysteine support · NAD+ cycling)
•  Sirtuin Activation & Antioxidant Defense → Pterostilbene 50 mg (superior bioavailability ·
•  SIRT1/3 activation) CD38 Inhibition & NAD+ Conservation → Apigenin 50 mg (reduces NAD+ enzymatic degradation)

THE SCIENCE OF NAD+ DECLINE

Why NAD+ Falls and Why It Matters

NAD+ levels in human tissues decline measurably with age — estimated reductions of 40–60% between young adulthood and later life in key tissues including skeletal muscle, liver, and brain. This decline is driven by three converging processes:

Reduced biosynthesis: The enzyme NAMPT (nicotinamide phosphoribosyltransferase) — the rate-limiting enzyme in the NMN salvage pathway — declines with age, slowing the conversion of NAM to NMN and NMN to NAD+.*

Increased consumption: Age-associated inflammatory signaling, DNA damage accumulation, and metabolic stress all increase the demand on PARP enzymes (which consume NAD+ for DNA repair) and CD38 (an NAD+ glycohydrolase that increases dramatically with inflammaging).*

Declining precursor availability: Dietary NMN content is low (~1 mg/100g food), making supplementation the only practical approach to meaningfully supporting precursor availability.*

The consequence of declining NAD+ is not a single outcome — it affects every biological process that NAD+ participates in: electron transport chain efficiency, mitochondrial function, DNA repair capacity, sirtuin longevity signaling, and cellular stress responses.*

THE FORMULA

NMN (β-Nicotinamide Mononucleotide)

Dose: 1,000 mg Role: Direct NAD+ Precursor — Salvage Pathway NAD+ Synthesis Support

NMN is a nucleotide derived from ribose and nicotinamide — the direct immediate precursor to NAD+ in the salvage biosynthesis pathway. Following oral ingestion, NMN is absorbed in the small intestine via the Slc12a8 transporter and converted to NAD+ intracellularly through NMNAT (nicotinamide mononucleotide adenylyltransferase) enzymes.*

The 2025 evidence picture for NMN:*

Landmark 2025 Nature Metabolism head-to-head trial (Christen et al., n=65 healthy adults): NMN at 1 gram daily for 14 days significantly doubled circulating NAD+ levels versus placebo — equivalent in magnitude to NR at the same dose, and significantly superior to niacinamide (NAM) which produced no significant effect.* This is the most rigorous published head-to-head comparison of NAD+ precursors in humans to date.*

2023 GeroScience RCT (Yi et al., n=80, multicenter, double-blind, placebo-controlled): NMN supplementation was safe and well-tolerated across dose ranges; higher doses produced dose-dependent increases in blood NAD+ levels over 60 days.*

2023 Advances in Nutrition safety and efficacy review (Song et al.): Confirmed NMN consistently elevates blood NAD+ across completed human clinical trials, with a well-established short-term safety profile at doses up to 1,250 mg/day.*

2022 placebo-controlled RCT (healthy older men, Fukamizu et al.): NMN was safe and well-tolerated; significantly increased blood NAD+ and NAD+ metabolite concentrations over 12 weeks.*

Important evidence context for practitioners: While NMN's ability to raise circulating NAD+ levels is now well-established across multiple human trials, translating elevated blood NAD+ into measurable clinical outcomes — muscle function, physical performance, metabolic improvements — has been inconsistent. A 2025 meta-analysis of 10 RCTs found no statistically significant benefit for muscle mass, strength, or physical function in older adults. A 2024 systematic review found mixed results for glucose and lipid metabolism outcomes. Whether elevated blood NAD+ meaningfully increases tissue NAD+ in critical organs (particularly skeletal muscle and brain) in humans requires further investigation. Practitioners should frame this evidence context appropriately when discussing NMN with patients.*

At 1,000 mg, NMN 1000+ delivers NMN at the dose used in the Christen et al. 2025 Nature Metabolism trial — the dose confirmed to double circulating NAD+.*

TMG (Trimethylglycine / Betaine Anhydrous)

Dose: 500 mg Role: Methylation Balance, Homocysteine Support & NAD+ Cycling

TMG (trimethylglycine, also known as betaine) is a naturally occurring methyl donor found in beets, spinach, and quinoa — and one of the most clinically important supporting ingredients for NMN supplementation.

Why TMG matters alongside NMN: The salvage pathway that converts NAM to NMN to NAD+ generates nicotinamide (NAM) as a byproduct of sirtuin activity and PARP enzyme function. NAM must be recycled back through the NAMPT enzyme to re-enter the NAD+ cycle. This recycling process involves methylation — specifically, methylation of NAM to methylnicotinamide (MeNAM) before urinary excretion. High-dose NMN supplementation can increase the demand on methyl donors, potentially contributing to methyl group depletion over time.*

TMG provides a steady supply of methyl groups through the betaine-homocysteine methyltransferase (BHMT) pathway — supporting balanced methylation, healthy homocysteine metabolism, and the methyl donor availability that underpins the full efficiency of the NAD+ cycle.*

Pterostilbene

Dose: 50 mg Role: Sirtuin Activation, Antioxidant Defense & NAD+ Pathway Support

Pterostilbene is a naturally occurring dimethylated analog of resveratrol found in blueberries and grape leaves — with two methyl groups in place of resveratrol's hydroxyl groups that dramatically improve its oral bioavailability and metabolic stability.*

Bioavailability advantage: Pterostilbene achieves approximately 80% oral bioavailability compared to resveratrol's 20–40% in most human studies — making it meaningfully more available to reach cellular targets at supplemental doses.*

NAD+ pathway synergy: Pterostilbene supports sirtuin enzyme activity — particularly SIRT1 and SIRT3 — the NAD+-dependent longevity enzymes that regulate mitochondrial biogenesis, DNA repair signaling, metabolic efficiency, and inflammatory response balance. By supporting sirtuin activation, pterostilbene amplifies the downstream biological value of the NAD+ that NMN 1000+ supports synthesizing.

Apigenin

Dose: 50 mg Role: CD38 Inhibition, NAD+ Conservation & Neuroprotection

Apigenin is a dietary flavonoid found in parsley, chamomile, and celery — and a selective inhibitor of CD38, the primary enzyme responsible for NAD+ degradation in aging tissues.*

The CD38 problem: CD38 is an NAD+ glycohydrolase — an enzyme that cleaves and consumes NAD+ as part of its normal function. In younger tissues, CD38 activity is moderate and balanced against NAD+ synthesis. With age and inflammation, CD38 expression increases dramatically — driven by the inflammaging process — consuming NAD+ faster than the salvage pathway can replace it. Some research suggests CD38 upregulation with age is as significant a driver of NAD+ decline as reduced NAMPT activity.*

Apigenin's CD38 inhibitory activity was first characterized in the published literature by Escande et al. in the Journal of Molecular Biology (2013) — establishing apigenin as one of the most potent natural CD38 inhibitors available. By slowing CD38-mediated NAD+ consumption, apigenin helps conserve the NAD+ that NMN synthesis supports, creating a more favorable NAD+ balance rather than simply increasing input without addressing the output side.

NMN 1000+ AND CARDIO NAD+ — HOW THEY WORK TOGETHER

Both formulas support NAD+ status through different mechanisms — and they are complementary rather than duplicative.

NMN 1000+ provides NMN as a direct precursor — increasing the substrate available for NAD+ synthesis through the salvage pathway. The CD38 inhibition via apigenin and methylation support via TMG address the conservation and cycling of that NAD+.*

Cardio NAD+ provides NAD3® — a dual-mechanism ingredient that works by both supporting NAD+ synthesis from precursors AND inhibiting the enzymatic activity that degrades NAD+, plus a copper(I)-niacin complex that supports the NAD+/NADH ratio directly. Cardio NAD+ also provides additional cardiometabolic, vascular, and lipid support benefits through its eight-ingredient cardiovascular formula.*

For practitioners: NMN 1000+ is the dedicated high-dose precursor formula for patients where maximum NAD+ precursor supply is the priority. Cardio NAD+ is the cardiovascular longevity formula that includes NAD+ support as one of eight parallel mechanisms. Using both together provides precursor supply (NMN) alongside enzymatic support and cardiovascular longevity benefits (Cardio NAD+) — a comprehensive NAD+ strategy.*

 

References

1. Mills, K. F., et al. (2016). Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Cell Metabolism.
2. Imai, S., & Guarente, L. (2014). NAD+ and sirtuins in aging and disease. Trends in Cell Biology.
3. Craig, S. A. (2004). Betaine in human nutrition. American Journal of Clinical Nutrition.
4. Zhao, X., et al. (2018). TMG alleviates mitochondrial stress by supporting methylation. Cell Reports.
5. Hoffman, J. R., et al. (2009). Betaine supplementation and exercise performance. Journal of the International Society of Sports Nutrition.
6. Remsberg, C. M., et al. (2008). Pharmacokinetics and metabolism of pterostilbene. Life Sciences.
7. Rimando, A. M., et al. (2005). Pterostilbene as an antioxidant. Journal of Agricultural and Food Chemistry.
8. McCormack, D., & McFadden, D. (2013). Pterostilbene and cancer. Antioxidants & Redox Signaling.
9. Chini, C., et al. (2017). CD38 as a regulator of cellular NAD+ homeostasis. Nature Metabolism.
10. Escande, C., et al. (2013). Apigenin and CD38 inhibition. Journal of Molecular Biology.
11. Nabavi, S. F., et al. (2015). Neuroprotective effects of apigenin. Current Neurovascular Research.

Additional Key References on  NAD

• Song, Qin et al. “The Safety and Antiaging Effects of Nicotinamide Mononucleotide in Human Clinical Trials: an Update.” Advances in nutrition (Bethesda, Md.) vol. 14,6 (2023): 1416-1435. doi:10.1016/j.advnut.2023.08.008
• Yi, Lin et al. “The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial.” GeroScience vol. 45,1 (2023): 29-43. doi:10.1007/s11357-022-00705-1
• Soma, Mounica, and Satya Kumar Lalam. “The role of nicotinamide mononucleotide (NMN) in anti-aging, longevity, and its potential for treating chronic conditions.” Molecular biology reports vol. 49,10 (2022): 9737-9748. doi:10.1007/s11033-022-07459-1
• Wei, Zisong et al. “Nicotinamide mononucleotide: An emerging nutraceutical against cardiac aging?.” Current opinion in pharmacology vol. 60 (2021): 291-297. doi:10.1016/j.coph.2021.08.006
• Rahman, Sajid Ur et al. “Role and Potential Mechanisms of Nicotinamide Mononucleotide in Aging.” Aging and disease vol. 15,2 565-583. 1 Apr. 2024, doi:10.14336/AD.2023.0519-1
• Fukamizu, Yuichiro et al. “Safety evaluation of β-nicotinamide mononucleotide oral administration in healthy adult men and women.” Scientific reports vol. 12,1 14442. 24 Aug. 2022, doi:10.1038/s41598-022-18272-y