Vitamin D3 engages the vitamin D receptor (VDR) in energy-demanding tissues such as skeletal muscle, where VDR signaling up-regulates mitochondrial biogenesis and oxidative phosphorylation. In human and animal models, fluctuating vitamin D status directly altered mitochondrial respiration and ATP-linked oxygen consumption, indicating that adequate D3 can make the “downstream engine” that uses NADH more efficient [1]. This matters for NMN products because NMN elevates cellular NAD⁺—via an intestinal NMN uptake route mediated by the transporter SLC12A8—thereby supplying substrate for mitochondrial redox reactions and NAD-dependent enzymes [2]. Beyond respiration, D3 also activates the NAD⁺-dependent deacetylase SIRT1 through VDR–SIRT1 cross-talk, increasing demand for and utilization of NAD⁺ in pathways tied to metabolic resilience and stress responses; NMN can reinforce this signaling by maintaining the NAD⁺ pool that SIRT1 consumes [3]. In short, D3 helps optimize the mitochondrial and sirtuin “use” side of the equation, while NMN supports the “supply” side—together targeting complementary control points in cellular energetics.

1. Salles J., et al. Vitamin D status modulates mitochondrial oxidative capacities in skeletal muscle. Communications Biology (2022).
   https://www.nature.com/articles/s42003-022-04246-3
   
2. Grozio A., et al. Slc12a8 is a nicotinamide mononucleotide transporter. Nature Metabolism (2019).
   https://www.nature.com/articles/s42255-018-0009-4
   
3. García-Martínez J.M., et al. Vitamin D induces SIRT1 activation (mechanistic study of VDR-driven SIRT1 activation). eLife (2023).
   https://elifesciences.org/articles/86913
   

Nicotinamide riboside (NR)—provided here as the hydrogen malate salt—feeds directly into the NRK→NMNAT pathway to rebuild cellular NAD⁺. In a randomized, placebo-controlled human trial, 6 weeks of oral NR (~1 g/day) was well tolerated and raised blood-cell NAD⁺ by ~60%, with NAAD increases confirming pathway engagement [1]. By restoring the NAD⁺ pool, NR supports mitochondrial redox reactions and NAD-dependent enzymes (e.g., sirtuins and PARPs) that modulate bioenergetics, inflammation, and stress responses; a 2023 top-journal review concludes that human trials consistently show robust NAD⁺ boosting with population-dependent downstream effects [2]. Clinically, a 2024 double-blind randomized trial in peripheral artery disease reported that 6 months of NR improved 6-minute-walk distance versus placebo, with larger gains in adherent participants, indicating a functional translation of NAD⁺ repletion in ischemic muscle [3]. In short, NR increases the “supply” of NAD⁺ that powers mitochondrial metabolism and repair systems, while the malate salt serves formulation purposes without changing the active NR moiety.

1. Martens C.R., et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD⁺ in healthy adults. Nature Communications (2018).
   https://www.nature.com/articles/s41467-018-03421-7
   
2. Damgaard M.V., et al. What is really known about the effects of nicotinamide riboside supplementation in humans? Science Advances (2023).
   https://pmc.ncbi.nlm.nih.gov/articles/PMC10361580/
   
3. McDermott M.M., et al. Nicotinamide riboside for peripheral artery disease: the NICE randomized clinical trial. Nature Communications (2024).
   https://www.nature.com/articles/s41467-024-49092-5
   

Quercetin—delivered here as a phospholipid phytosome complex for improved uptake—acts on the “preserve” side of NAD metabolism by inhibiting the NAD-consuming enzyme CD38. Contemporary Nature-portfolio work summarizes that quercetin binds CD38 and, at micromolar levels, reduces its NADase activity with a dose-dependent rise in intracellular NAD⁺, thereby lessening NAD⁺ loss to degradation [1]. This mechanism complements NAD-precursor products (e.g., NMN/NR), which raise supply: in aged immune cells, combining a CD38 inhibitor with an NAD precursor restored NAD⁺ levels and mitochondrial fitness, translating to functional recovery in vivo [2]. Earlier Cell Metabolism research confirms the principle that pharmacologic CD38 inhibition reverses tissue NAD⁺ decline and improves metabolic performance in aging models, underscoring why a CD38-modulating flavonoid like quercetin can be synergistic inside NAD formulations [3].

1. Yusri K., et al. The role of NAD⁺ metabolism and its modulation of mitochondria in aging and disease. npj Metabolic Health and Disease (2025).
   https://www.nature.com/articles/s44324-025-00067-0
   
2. Hope H.C., et al. Age-associated NAD decline drives CAR-T cell failure (CD38 inhibitor + NMN restores function). Nature Cancer (2025).
   https://www.nature.com/articles/s43018-025-00982-7
   
3. Tarragó M.G., et al. A potent and specific CD38 inhibitor ameliorates age-related metabolic dysfunction by reversing tissue NAD⁺ decline. Cell Metabolism (2018).
   https://www.sciencedirect.com/science/article/pii/S1550413118301943
   

Resveratrol is a calorie-restriction–mimicking polyphenol that improves mitochondrial efficiency and stress-response signaling. In mammals, its benefits depend on the NAD⁺-dependent deacetylase SIRT1: when SIRT1 is disrupted, resveratrol no longer enhances AMPK activity or mitochondrial function, underscoring a SIRT1-centric mechanism tied to cellular energetics [1]. Mechanistically, resveratrol competitively inhibits cAMP-degrading phosphodiesterases, elevating cAMP→Epac1→Ca²⁺ to activate AMPK; AMPK in turn drives the NAMPT salvage pathway, supporting intracellular NAD⁺ availability and promoting PGC-1α–linked mitochondrial biogenesis [2].
Within NAD products, resveratrol acts on the “use and recycle” side—activating SIRT1 and supporting endogenous NAD⁺ salvage—while NMN/NR expand the NAD⁺ pool. This complementary strategy is clinically relevant: a 2024 double-blind trial in peripheral artery disease tested NR with or without resveratrol and observed improved 6-minute-walk performance versus placebo, illustrating translational benefits when NAD⁺ repletion is paired with a sirtuin-targeting polyphenol [3].

1. Price N.L., et al. SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metabolism (2012).
   https://www.cell.com/cell-metabolism/fulltext/S155041311200143X
   
2. Park S.-J., et al. Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell (2012).
   https://www.sciencedirect.com/science/article/pii/S009286741200030X
   
3. McDermott M.M., et al. Nicotinamide riboside for peripheral artery disease: the NICE randomized clinical trial. Nature Communications (2024).
   https://www.nature.com/articles/s41467-024-49092-5
   

Shilajit is a fulvic-acid and dibenzo-α-pyrone–rich phytocomplex used to support cellular energy and tissue resilience. In a double-blind, placebo-controlled human study, 8 weeks of purified shilajit (500 mg/day) attenuated fatigue-induced strength decline and lowered serum hydroxyproline, consistent with reduced connective-tissue breakdown JISSN, 2019. An open-label randomized trial in older adults with hypertension found 30 days of shilajit (500 mg twice daily) significantly decreased oxidative-stress markers (e.g., MDA, ox-LDL) while increasing endogenous antioxidants (SOD, GSH) Indian J Physiol Pharmacol, 2023. Human skeletal-muscle transcriptomics further show up-regulation of extracellular-matrix genes linked to repair and mechanotransduction after 8 weeks of supplementation J Med Food, 2016.
Within an NAD product, shilajit works on the “utilization and resilience” side of bioenergetics: by lowering oxidative stress and supporting mitochondrial performance in muscle, it helps maintain efficient redox throughput and tissue recovery—complementing NMN/NR, which expand the cellular NAD⁺ pool. In practice, the pairing targets both supply (NAD⁺ repletion) and use (mitochondrial ATP generation and stress-response efficiency), a strategy supported by the human performance and antioxidant findings above JISSN, 2019; Indian J Physiol Pharmacol, 2023; J Med Food, 2016.

Fisetin is a flavonol with senotherapeutic activity—selectively reducing senescent cell burden and dampening SASP cytokines that drive chronic, sterile inflammation. In landmark work, intermittent fisetin administration in aged and progeroid mice decreased senescent cell markers, improved tissue function, and extended healthspan, supporting translation to humans. A recent state-of-the-science review further consolidates evidence for fisetin’s senolytic actions across organs and age-related conditions.
(EBioMedicine, 2018;
Mechanisms of Ageing & Development, 2024)

Aging-related NAD⁺ decline is driven not only by reduced synthesis but also by increased consumption—especially via the NADase CD38, which is up-regulated by inflammatory signaling. By clearing senescent cells and suppressing SASP, fisetin acts on the “preserve & normalize demand” side of NAD⁺ metabolism, potentially easing CD38-mediated drain. Pairing fisetin with NAD⁺ precursors (e.g., NMN/NR) therefore targets complementary control points: precursors rebuild the NAD⁺ pool (“supply”), while fisetin helps maintain a lower-inflammation, lower-CD38 environment so that NAD⁺ is utilized more efficiently in mitochondria and sirtuin-dependent repair pathways.
(AJP-Cell Physiology, 2022)

1. Yousefzadeh MJ, et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine (2018).
2. Tavenier J, et al. Fisetin as a senotherapeutic agent: evidence & emerging applications. Mechanisms of Ageing & Development (2024).
3. Zeidler JD, et al. The CD38 glycohydrolase and the NAD sink: implications for aging. Am. J. Physiol. Cell Physiol. (2022).

Grape seed extract (GSE) is rich in oligomeric proanthocyanidins (OPCs) that support vascular and metabolic health through antioxidant and anti-inflammatory actions. A recent systematic review and meta-analysis of controlled human trials found GSE supplementation produced modest, dose- and duration-dependent reductions in diastolic blood pressure and heart rate, with heterogeneous effects on flow-mediated dilation across studies Pharmacological Research, 2022. In a double-blind randomized trial in patients with NAFLD, 520 mg/day of GSE for 8 weeks significantly improved insulin resistance, atherogenic lipids, and both systolic and diastolic blood pressure, while reducing hepatic steatosis severity BMC Complementary Medicine & Therapies, 2024. Mechanistically, a Nature-portfolio study identified procyanidin C1—an OPC from GSE—as a senotherapeutic that reduces the pro-inflammatory SASP at low concentrations and clears senescent cells at higher concentrations, improving healthspan in mice Nature Metabolism, 2021.

In NAD-focused products, GSE acts on the “preserve and enable” side of cellular energetics. By lowering oxidative stress and senescent-cell/SASP burden (via OPCs such as procyanidin C1), GSE helps normalize inflammatory signaling that otherwise increases NAD⁺ consumption and strains mitochondrial redox processes. When paired with NAD-precursors (e.g., NMN/NR) that rebuild the NAD⁺ pool, GSE’s vascular and anti-inflammatory effects can support more efficient mitochondrial respiration and sirtuin-dependent repair—targeting complementary control points in the NAD⁺ supply-and-use cycle.

1. Foshati S., et al. The effect of grape seed extract on FMD, blood pressure and heart rate: systematic review & meta-analysis. Pharmacological Research (2022).
2. Ghanbari P., et al. GSE improves metabolic risk factors and blood pressure in NAFLD: randomized double-blind trial. BMC Complementary Medicine & Therapies (2024).
3. Zhu Y., et al. Procyanidin C1 from grape seed is senotherapeutic and extends murine healthspan. Nature Metabolism (2021).

Rose hip concentrates vitamin C, phenolic acids, flavonoids, and galactolipids that help counter oxidative stress and low-grade inflammation, supporting metabolic and vascular health [1].In a randomized, double-blind trial in pre-obese adults, daily rose-hip extract reduced abdominal visceral fat compared with placebo[2].

In NAD-focused products, rose hip acts on the “preserve & enable” side: by tempering inflammatory signaling and oxidative stress, it helps limit excess, inflammation-driven NAD⁺ consumption—much of which is mediated by the NADase CD38—so NMN/NR-driven NAD⁺ repletion is utilized more efficiently by mitochondria and sirtuin pathways[3].

1. 
   Review of Rosa canina bioactives and antioxidant/anti-inflammatory effects. (Authoritative overview).
   Link
   ↩︎
   
2. 
   Nagatomo A., et al. Daily rose-hip extract decreases abdominal visceral fat in pre-obese subjects: randomized, double-blind, placebo-controlled trial. Diabetes, Metabolic Syndrome and Obesity (2015).
   Link
   ↩︎
   
3. 
   Zeidler J.D., et al. CD38 as a major NAD sink: implications for aging and disease. American Journal of Physiology – Cell Physiology (2022).
   Link
   ↩︎
   

Turmeric concentrates curcuminoids and turmerone-rich volatiles that modulate redox and inflammatory signaling. Contemporary mechanistic reviews show curcumin activates the Nrf2–ARE antioxidant program and supports mitochondrial function/biogenesis, improving cellular stress tolerance [1]. Translationally, umbrella/meta-analyses of randomized trials report benefits for symptomatic osteoarthritis and related inflammatory endpoints, consistent with improved function and pain reduction [2].

In NAD-focused products, turmeric acts on the “preserve & enable” side of metabolism. By reducing low-grade inflammation and oxidative stress, it helps limit pathologic NAD⁺ consumption driven by the NADase CD38—a key sink upregulated by inflammatory signaling—so that NMN/NR-mediated NAD⁺ repletion is utilized more efficiently by mitochondria and sirtuin pathways [3].

[1] Avendaño-Briseño K.A., et al. Antioxidant effect of curcumin and its impact on mitochondria. Antioxidants (2025). Link↩︎
 • 
[2] Bideshki M.V., et al. The efficacy of curcumin in relieving osteoarthritis: an umbrella meta-analysis of RCTs. Rheumatology (2024). Link↩︎
 • 
[3] Zeidler J.D., et al. The CD38 glycohydrolase and the NAD sink: implications for aging and disease. Am J Physiol Cell Physiol (2022). Link↩︎

Acai concentrates anthocyanins and other polyphenols that modulate redox and inflammatory pathways, with clinical and preclinical evidence for antioxidant, anti-inflammatory, and cardiometabolic support; recent comprehensive reviews summarize improvements in biomarkers under metabolic and exercise stress and delineate mechanisms across tissues [1] [2].

In NAD-focused products, acai acts on the “preserve & enable” side: by dampening low-grade inflammation and oxidative stress, it helps restrain inflammation-induced NAD⁺ consumption driven by the NADase CD38, so NMN/NR-mediated NAD⁺ repletion can be utilized more efficiently by mitochondria and sirtuin-dependent repair pathways [3].

[1] Laurindo L.F., et al. Açaí (Euterpe oleracea Mart.) in Health and Disease: A Critical Review. Nutrients (2023). Link↩︎
 • 
[2] da Silveira J.T., et al. An integrative review of Açaí (Euterpe oleracea and E. edulis): composition, bioactivity and applications. Food Research International (2023). Link↩︎
 • 
[3] Zeidler J.D., et al. The CD38 glycohydrolase and the NAD sink: implications for aging and disease. Am J Physiol Cell Physiol (2022). Link↩︎

Green tea leaf extract concentrates catechins—especially EGCG—that modulate redox and inflammatory pathways and support vascular–metabolic health. Contemporary reviews detail EGCG’s actions on AMPK–SIRT1–PGC-1α signaling, mitochondrial protection, and NF-κB/Nrf2 balance, explaining benefits observed across tissues [1]. Clinically, a 2024 grade-assessed meta-analysis of randomized trials found green tea extract reduced body mass/BMI/body-fat percentage and lipid peroxidation (MDA) while increasing total antioxidant capacity and adiponectin—consistent with improved metabolic stress handling [2].

In NAD-focused products, green tea acts on the “preserve & enable” side: by damping low-grade inflammation and oxidative stress, it helps restrain pathological NAD⁺ consumption driven by the NADase CD38. That preserves the pool rebuilt by precursors (NMN/NR), allowing more efficient mitochondrial respiration and sirtuin-dependent repair when NAD⁺ supply rises [3].

[1] Mokra D., et al. EGCG: molecular pathways and disease modulation—mechanistic review. Open-access review (2022). Link↩︎
 • 
[2] Asbaghi O., et al. Green tea extract and body composition, adipokines, and oxidative stress: grade-assessed systematic review & dose–response meta-analysis of RCTs. Br J Nutr (2024). Link↩︎
 • 
[3] Zeidler J.D., et al. The CD38 glycohydrolase and the NAD sink: implications for aging and disease. Am J Physiol Cell Physiol (2022). Link↩︎

Piperine is a well-characterized bioenhancer that increases oral exposure of co-ingested actives by inhibiting intestinal/hepatic CYP3A4 and UGT enzymes, reducing P-glycoprotein (P-gp) efflux, and modulating membrane permeability—mechanisms repeatedly documented in contemporary pharmacology reviews [1]. In humans, pairing piperine with polyphenols such as resveratrol has increased physiological bioefficacy (e.g., cerebral blood-flow responses) and has been explored in dose-ranging pharmacokinetic trials, underscoring its translational role as an absorption enhancer [2] [3].

In NAD-focused products, black pepper extract primarily acts on the “delivery” side: by improving intestinal uptake and limiting first-pass loss, it can raise systemic exposure to co-actives used alongside NAD precursors (e.g., resveratrol or quercetin that engage SIRT1/AMPK pathways), helping the formulation translate an increased NAD⁺ supply (from NMN/NR) into more efficient downstream signaling and mitochondrial use; because piperine modulates drug-metabolizing enzymes and P-gp, formulators should also consider medication interactions and appropriate dosing [1].

[1] Tripathi A.K., et al. Molecular and pharmacological aspects of piperine as a bioenhancer (CYP3A4/P-gp/UGT mechanisms). Beni-Suef Univ. J. Basic & Appl. Sci. (2022). Link↩︎
 • 
[2] Wightman E.L., et al. Resveratrol with or without piperine in healthy adults: cerebral blood-flow and cognitive endpoints (randomized, double-blind, crossover). Br. J. Nutr. (2014). Link↩︎
 • 
[3] Bailey H.H., et al. Resveratrol plus piperine: randomized, double-blind, dose-ranging pilot pharmacokinetics in humans. Cancer Prev. Res. (2021). Link↩︎