NAD+ Family

NAD+ (nicotinamide adenine dinucleotide) is the most-studied longevity coenzyme of the last fifteen years — and it’s the molecule almost every supplement on this page is trying, by one route or another, to keep at youthful levels. Nicotinamide adenine dinucleotide runs the chemistry of every living cell: it carries electrons through the mitochondrial electron-transport chain to produce ATP, it serves as the obligate substrate for the sirtuin family of longevity enzymes (SIRT1–SIRT7), and it is consumed by the DNA-repair enzyme PARP1 every time a strand break occurs. Tissue NAD+ falls roughly 50% between age 20 and age 50 and continues to decline thereafter (Massudi 2012, PLOS One; Camacho-Pereira 2016, Cell Metabolism). The collection on this page is the True Health Protocol library of every commercially available route to raising it — precursors (NMN, NR), direct liposomal NAD+, drink-format NR, and comprehensive multi-active blends — with the trial evidence and dosing rationale that informs each one.

The 60-second answer

• Why this collection exists. NAD+ falls ~50% by 50, sirtuins and PARP1 starve, mitochondrial output drops, and tissue energetics shift toward an aged phenotype. The collection covers every supplement format that addresses this: precursors (NMN, NR), direct NAD+ (liposomal capsule, ready-to-drink), and comprehensive co-formulated blends.
• The four routes to raising NAD+. (1) NMN precursor — one enzymatic step from NAD+ via NMNAT2/3, trial-validated at 250–1000mg/day (Yoshino 2021, Science; Yamaguchi 2022, Nutrients; Igarashi 2022, npj Aging). (2) NR precursor — two-step conversion via NRK1/NRK2, trial-validated at 250–1000mg (Trammell 2016, Nat Commun; Conze 2019, Sci Rep; Brakedal 2022, Cell Metab NADPARK). (3) Liposomal direct NAD+ — phospholipid-encapsulated to bypass gut hydrolysis. (4) Comprehensive blends — precursor + sirtuin activator + cofactors in one capsule for users who want the whole stack pre-assembled.
• Daily-protocol entry stack. A precursor (NMN 500–1000mg or NR 300–600mg) + Resveratrol 600mg trans-isomer for SIRT1 allosteric activation (Howitz 2003, Nature; Hubbard 2013, Science). Time of day: morning, with breakfast.
• The Sinclair-stack cofactor pair. At sustained doses ≥500mg/day NMN, two cofactors become rate-limiting: TMG 1000mg (replaces methyl groups burned clearing nicotinamide via NNMT) and Apigenin 50mg (inhibits CD38, the age-rising NADase that degrades NAD+; Tarragó 2018, Cell Metab). Without these, high-dose precursor protocols hit diminishing returns.
• Time-to-effect. Whole-blood NAD+ rises measurably within 1–2 weeks (Yamaguchi 2022); subjective energy/sleep around weeks 2–4; insulin sensitivity around weeks 8–12 (Yoshino 2021); muscle, gait, and grip-strength endpoints around 12 weeks (Igarashi 2022); compounding gains thereafter.
• Quality. Every active in this collection is HPLC-assayed for ≥98% purity (β-NMN ≥99%, NR ≥98%, trans-resveratrol ≥98%), ISO/IEC 17025 third-party tested for arsenic / cadmium / mercury / lead / microbial, and made under cGMP 21 CFR Part 111. No proprietary blends, no titanium dioxide, no synthetic dyes. Read the full quality protocol.
• Who this collection is for. Adults 30+ noticing the slow-creep aging signals (3pm energy crash, slower workout recovery, declining VO2 max, sleep that no longer fully restores) and any adult building a serious longevity protocol around the López-Otín hallmarks framework (López-Otín 2013, Cell; López-Otín 2023, Cell).
• Who it’s not for. Pregnancy/nursing, active chemotherapy, or any condition where sirtuin activation or PARP support is contraindicated by an oncologist or transplant team. Always coordinate with prescribers before starting.

On this page

1. The 60-second answer
2. Why NAD+ falls with age — the five-mechanism breakdown
3. The four routes to raising NAD+
4. The eight products — trial evidence and dosing
5. Three protocol tiers — entry, daily, advanced
6. The Sinclair-stack cofactors — TMG and Apigenin
7. Stacking with sister collections
8. Week-by-week realistic timeline
9. Drug interactions and caution flags
10. Who this collection is for — and who it isn’t
11. Quality, sourcing, and what’s not in the bottle
12. FAQ — 13 questions
13. References
14. Related collections, pages, and reading
15. Disclaimer

Why NAD+ falls with age — the five-mechanism breakdown

The age-related decline in NAD+ is not a single switch flipping off — it’s the convergence of five separate mechanisms, each addressed by a different lever in the longevity-supplement toolkit. Understanding which mechanism is doing the work in your body shapes which product format to start with.

1. NAMPT decline — the salvage-pathway bottleneck

NAMPT (nicotinamide phosphoribosyltransferase) is the rate-limiting enzyme in the NAD+ salvage pathway — it converts nicotinamide back to NMN, which is then converted to NAD+. Tissue NAMPT activity declines steadily with age (Stein 2014, EMBO J; Camacho-Pereira 2016), so the body becomes progressively less able to recycle nicotinamide back into the NAD+ pool. Lever: NMN supplementation bypasses NAMPT entirely — it enters the pathway downstream of the bottleneck and only requires NMNAT2/3 (which remain active with age) to become NAD+. This is why NMN consistently outperforms nicotinamide alone in restoration trials.

2. CD38 amplification — the consumption side of the ledger

CD38 is an NAD-degrading enzyme (NADase) expressed on immune cells. Its activity rises ~30% per decade after age 40 due to chronic low-grade inflammaging, and it directly consumes NAD+ at increasing rates (Camacho-Pereira 2016; Tarragó 2018). The combined picture is a leaky bucket: NAMPT (the inflow tap) drips slower while CD38 (the drain) opens wider. Lever: The flavone apigenin is the most-studied small-molecule CD38 inhibitor — the Mayo Clinic group identified it as a CD38 inhibitor in a 2013 BMC Genomics screen (Escande 2013) and showed in mouse work that CD38 inhibition restores NAD+ levels independent of precursor supplementation.

3. Methylation drain — the upstream half of the cycle

NAD+ is broken down to nicotinamide; nicotinamide is methylated to N-methylnicotinamide by NNMT (using a methyl group from S-adenosylmethionine) and excreted in urine. Every dose of NMN or NR you take that becomes NAD+ that becomes nicotinamide that becomes N-methylnicotinamide costs the body a methyl group. At sustained NMN ≥500mg/day, this exceeds dietary methyl-donor supply for most users, raising plasma homocysteine and depleting SAMe (Pissios 2017, Trends Endocrinol Metab). Lever: TMG (trimethylglycine, betaine) donates three methyl groups directly into the SAMe cycle, restoring methyl-donor balance. This is the second cofactor in the canonical Sinclair / Stanfield NAD+ stack.

4. Mitochondrial DNA damage — the downstream PARP1 burn

Every time a DNA strand break occurs, PARP1 (poly-ADP-ribose polymerase) consumes NAD+ to flag and repair it. Aging tissue accumulates mtDNA damage from oxidative stress, and chronic PARP1 activation can consume up to 80% of cellular NAD+ in hyper-stressed cells (Bai 2015, Cell Metab). Lever: Reducing the upstream oxidative-damage rate — via mitochondrial-resident antioxidants (CoQ10, alpha-lipoic acid) and glutathione precursors (NAC, glycine) — reduces PARP1 burn at the source.

5. Sirtuin starvation — the readout of the whole system

The sirtuin family (SIRT1–SIRT7) are the longevity enzymes whose activity is most consequential downstream of NAD+. They’re NAD+-dependent deacetylases that regulate mitochondrial biogenesis (PGC-1α deacetylation), DNA repair (FOXO3 activation), inflammation (NF-κB suppression), and circadian metabolism (BMAL1 regulation). When NAD+ falls, sirtuins fall in lockstep — not because they’re inhibited, but because their substrate is gone. Restoring NAD+ via precursor or direct supplementation restores sirtuin activity in human muscle biopsy (Martens 2018, Nat Commun; Goh 2014, J Nutr Sci). Lever: Pair NAD+ precursor with a sirtuin activator — trans-resveratrol or pterostilbene — for the substrate-plus-activation combination that reproduces the Howitz 2003 / Hubbard 2013 SIRT1 K_m-lowering effect.

The four routes to raising NAD+ — format-by-format breakdown

Every product on this page falls into one of four format categories. Understanding the trade-offs helps you pick.

Route 1 — NMN precursor (one enzymatic step from NAD+)

β-Nicotinamide mononucleotide is the immediate precursor — one enzymatic step (via NMNAT2/3) from NAD+ itself. Oral β-NMN raises whole-blood NAD+ in 1–2 weeks (Yamaguchi 2022) and produces measurable functional endpoints at 12 weeks: Yoshino 2021 reported +25% muscle insulin sensitivity in n=25 postmenopausal prediabetic women at 250mg/day; Igarashi 2022 reported +9% gait speed and +6% grip strength in n=42 men 65+ at 250mg twice daily; Yamaguchi 2022 reported +38% whole-blood NAD+ at 250mg/day. Two SKUs in this collection: entry-tier Pure NMN 500mg for general daily use, and the cofactor-paired Longevity Stack Bundle that ships NMN 500mg with Resveratrol 600mg as the canonical substrate-plus-activator pair. Sister-collection cross-reference: NMN 1000mg Double Strength for advanced/long-term users who’ve graduated from the 500mg starting dose.

Route 2 — NR precursor (two enzymatic steps, B-vitamin-compatible)

Nicotinamide riboside is the other major precursor — converted to NMN by NRK1/NRK2 and then to NAD+ by NMNAT. Trial evidence is the most extensive of any NAD+ precursor: Trammell 2016 validated 250mg as the smallest dose to elevate human whole-blood NAD+ within 2 weeks; Conze 2019 reported +60% whole-blood NAD+ at 1000mg/day for 8 weeks in n=140; Martens 2018 reported reduced systolic blood pressure (−9 mmHg) and aortic stiffness in stage 1 hypertensive adults at 500mg twice daily for 6 weeks; Brakedal 2022 NADPARK reported NR-driven cerebral NAD+ elevation and exploratory motor improvement in early Parkinson’s disease at 1000mg/day. Two SKUs in this collection: capsule-format NR Hard Capsules with B-vitamin cofactors, and ready-to-drink Liquid NAD+ Anti-Aging Drink berry stick packs (the same NR substrate in a non-capsule format for users who don’t take pills well).

Route 3 — Direct liposomal NAD+

Free oral NAD+ is largely degraded in the stomach and gut to nicotinamide before absorption. Liposomal phospholipid encapsulation protects the molecule through gastric pH and delivers it intact to the enterocyte for absorption, then through the lymphatic system. Two SKUs in this collection use this route: Liposomal NAD+ Ultimate 1000mg — a 10-active phospholipid formula combining direct NAD+ with NMN, CoQ10, PQQ, resveratrol, quercetin, B-complex, and antioxidants in one capsule for users who want one-bottle simplicity; and NAD+ Daily Boost — direct NAD+ paired with trans-resveratrol in a daily-dose hard capsule for substrate-plus-SIRT1-activator users who prefer the streamlined two-active format.

Route 4 — Comprehensive co-formulated blends

Multi-active formulas pre-assemble the NAD+ pathway with the most-studied cofactors so users don’t have to stack four bottles. Two SKUs in this collection sit here: NAD+ 5-in-1 Complete Mitochondrial Formula — NMN as the precursor backbone plus CoQ10 (electron-transport-chain cofactor), B-complex (methylation cofactor floor), and antioxidants (PARP-burn-reducer); and the drink-mix NAD+ 1000mg Pure Focus Formula — NR with resveratrol (SIRT1 activator), PQQ (mitochondrial-biogenesis activator), and quercetin (CD38 inhibitor / senolytic flavonoid) in a once-daily berry drink for cognitive-focus users.

The eight products — trial evidence and dosing

Per-product breakdown ordered by route. Every dose listed is the dose that appears on this product’s panel (not a generic recommendation), and every trial citation is the specific human RCT or mechanism paper that informed the formulation.

Pure NMN 500mg — the entry-tier precursor

500mg β-NMN per capsule, ≥99% purity by HPLC, β-isomer-only (the active form — α-NMN is biologically inert), no proprietary blend. Trial-grade validation at 250mg/day from Yoshino 2021 and Yamaguchi 2022. The 500mg dose is the most-studied entry tier in the broader NMN literature and the cleanest single-dose option in the catalog. Use as: 1 capsule with breakfast, daily. Pair with Resveratrol 600mg for SIRT1 activation; pair with TMG 1000mg at sustained use ≥4 weeks for methylation buffering.

Longevity Stack Bundle — the canonical NMN + Resveratrol pair

Co-shipped: NMN 500mg β-NMN ≥99% + Trans-Resveratrol 600mg ≥98% trans-isomer (the active form — cis-resveratrol does not allosterically activate SIRT1). This is the substrate-plus-activator pair that reproduces the Howitz 2003 / Hubbard 2013 K_m-lowering effect: resveratrol binds an allosteric site on SIRT1 that lowers the enzyme’s K_m for its acetyl-lysine substrate ~5-fold, increasing turnover even at the same NAD+ concentration. Trial evidence for the pair: Timmers 2011, Cell Metab (n=11 obese men, +9% mitochondrial respiration, +9% sleeping metabolic rate at 150mg resveratrol); Goh 2014 (n=10 T2DM, SIRT1 protein +3.6× at 500mg twice daily). Use as: 1 NMN capsule + 1 Resveratrol capsule with breakfast, daily. Sub-sum-of-parts pricing vs. buying the components separately.

Nicotinamide Riboside (NR) Hard Capsules — the patented precursor

NR (Niagen-class substrate) with B-vitamin cofactors (B3, B6, B12, folate) for full methylation cycle support. NR is the most clinically studied NAD+ precursor — Trammell 2016 first validated 250mg as the lowest dose to detectably raise whole-blood NAD+ in humans; Conze 2019 reported +60% whole-blood NAD+ at 1000mg over 8 weeks in n=140; Martens 2018 showed cardiovascular endpoints at 500mg twice daily; Brakedal 2022 demonstrated cerebral NAD+ elevation. Use as: 1–2 capsules with breakfast, daily, depending on dose tier. Co-formulated B-vitamins partially address the methylation drain that builds with sustained precursor use, though TMG remains useful at high doses.

Liquid NAD+ Anti-Aging Drink — ready-to-drink NR berry stick packs

Same NR substrate as the capsule SKU, in a once-daily berry stick pack format. For users who don’t take capsules well, want flavor variety, or prefer a drink format for travel and morning routine integration. Trial backing carries over from the NR capsule literature above. Use as: 1 stick pack stirred into 8oz water, morning, daily.

Liposomal NAD+ Ultimate 1000mg — the 10-active phospholipid formula

Direct NAD+ in a phosphatidylcholine liposomal carrier (protects through gastric pH for intact absorption) plus nine supporting actives: NMN (precursor backbone), CoQ10 (electron-transport-chain cofactor; Mortensen 2014, Q-SYMBIO), PQQ (mitochondrial-biogenesis activator; Harris 2013), trans-resveratrol (SIRT1 activator), quercetin (senolytic flavonoid + CD38 inhibitor), B-complex (methylation floor), and a defined antioxidant blend. The one-capsule format trades dose-per-active flexibility for one-bottle simplicity. Use as: 1–2 capsules with breakfast, daily.

NAD+ Daily Boost — direct NAD+ + Trans-Resveratrol

Two-active hard capsule pairing direct NAD+ (substrate) with trans-resveratrol (SIRT1 allosteric activator). Streamlined for users who want the substrate-plus-activator combination without the rest of the comprehensive-blend stack. The trans-isomer-specific resveratrol reproduces the K_m-lowering effect documented by Howitz and Hubbard. Use as: 1–2 capsules with breakfast, daily.

NAD+ 5-in-1 Complete Mitochondrial Formula — the comprehensive capsule

NMN as precursor backbone, plus CoQ10 (cellular energy / electron-transport-chain cofactor), B-complex (methylation cofactor floor), an antioxidant blend (PARP-burn-reducer), and a skin-supportive layer (Pro-collagen amino acid co-factors). Designed for users who want a turnkey NAD+ + mitochondrial + antioxidant capsule rather than building a five-bottle stack. Use as: 1–2 capsules with breakfast, daily.

NAD+ 1000mg Pure Focus Formula — the cognitive-focus drink mix

Once-daily berry drink with NR (precursor backbone), trans-resveratrol (SIRT1 activator), PQQ (mitochondrial biogenesis), and quercetin (CD38 inhibitor / NF-κB suppressor / senolytic flavonoid). Drink-format positioning aimed at users for whom the cognitive-focus / 3pm-energy benefit is the dominant goal. Use as: 1 stick pack in 8oz water, morning, daily.

Three protocol tiers — entry, daily, advanced

The eight products in this collection let you build three protocol tiers depending on goal, sophistication, and budget. Pick the tier that matches your current state, not the most-aggressive one.

Tier 1 — Entry (one product, 8–12 weeks)

Goal: confirm you respond to NAD+ precursor before stacking. Best for first-time NAD+ users, anyone uncertain whether this category will work for them, or budget-conscious users.

• Single SKU pick: Pure NMN 500mg — or, if you don’t take capsules well, Liquid NAD+ Anti-Aging Drink.
• Schedule: 1 dose with breakfast, daily, for 12 weeks.
• What to track: 3pm energy, sleep recovery, workout PRs (subjective); fasting insulin, HOMA-IR (objective, at 12 weeks).
• If responsive: graduate to Tier 2.
• If non-responsive: check upstream basics (vitamin D, ferritin, B12, hypothyroid, sleep apnea, protein floor) before assuming the precursor itself is failing — see Getting Started for the differential list.

Tier 2 — Daily Stack (precursor + activator, ~12 weeks to compound)

Goal: substrate plus allosteric SIRT1 activation in the canonical Sinclair-stack pair. Best for confirmed responders to Tier 1, anyone with a serious daily longevity intent, or users 40+ where the NAD+ decline is mechanistically pronounced.

• Two SKUs: Longevity Stack Bundle (NMN 500mg + Resveratrol 600mg) — the easiest path; or any combination of separately purchased NMN, NR, Liposomal NAD+, NAD+ Drink Mix, or NAD+ Daily Boost + Resveratrol 600mg if buying components separately.
• Schedule: 1 dose of each with breakfast (fat-containing meal — resveratrol is fat-soluble), daily.
• What to track: subjective markers continue; objective markers expand to include hs-CRP, homocysteine, fasting glucose at 12 weeks. Resistance-training PRs and grip strength are useful endpoints (Igarashi 2022 endpoint set).

Tier 3 — Advanced (Sinclair stack with cofactors, sustained use)

Goal: comprehensive NAD+ pathway support including the upstream methylation buffer and the downstream CD38 inhibitor — the canonical advanced longevity protocol. Best for sustained users 6+ months in, anyone running NMN ≥1000mg/day, or anyone targeting the full sirtuin / autophagy / PARP-modulation downstream cascade. Note: This tier introduces products that are not in this collection but are tagged into Longevity Essentials — methylation buffer (TMG) and CD38 inhibitor (Apigenin).

• NAD+ collection picks: Longevity Stack Bundle (or NMN 1000mg Double Strength + Resveratrol 600mg for the high-dose tier).
• Cofactor adds: TMG 1000mg (methylation buffer) + Apigenin 50mg (CD38 inhibitor) + Magnesium Glycinate 400mg (NAMPT/SAMe-cycle/Mg-ATP cofactor).
• Optional fourth-pillar mitochondrial layer: Urolithin A 500mg (mitophagy — clears damaged mitochondria so the new NAD+ has functional destinations to power) + PQQ 20mg (PGC-1α biogenesis — builds new mitochondria) + CoQ10 400mg (electron-transport cofactor for the working mitochondria the NAD+ is feeding).
• Schedule: morning — NMN + Resveratrol + TMG + Apigenin + Magnesium (1 cap) + the mitochondrial layer if running it; evening — Magnesium 1 cap, 60–90 minutes before bed (split-dose Mg covers both NAMPT/SAMe daytime burn and GABA-A sleep architecture).
• What to track: full annual lab panel (CMP, A1C, lipid + ApoB + Lp(a), fasting insulin, HOMA-IR, hs-CRP, homocysteine, TSH/T3/T4, 25(OH)D, B12, ferritin, RBC magnesium); advanced biomarkers if budget allows (epigenetic age, NAD+ assay, VO2 max, grip strength, DEXA).

The Sinclair-stack cofactors — TMG and Apigenin

Two cofactors come up so often in advanced NAD+ protocols that they deserve their own section. Neither is a precursor — both are protective layers around the precursor. Both live in Longevity Essentials rather than this NAD+ collection because their tag taxonomy is broader (CD38, methylation, sirtuin pairing).

TMG — the upstream half of the cycle

The mechanism: NAD+ → nicotinamide → (NNMT methylation, costs SAMe) → N-methylnicotinamide → urinary excretion. Every dose of NMN/NR you absorb that becomes NAD+ that becomes nicotinamide costs the body a methyl group. At sustained NMN ≥500mg/day this can elevate plasma homocysteine and deplete SAMe (Pissios 2017). TMG (trimethylglycine) donates three methyl groups directly into the SAMe cycle (via betaine-homocysteine methyltransferase), restoring methyl-donor balance. Add at week 4–6 of a Tier 2/3 protocol or anytime NMN dose escalates above 500mg/day. Standard dose: 1000mg morning.

Apigenin — the downstream half of the cycle

The mechanism: CD38 is an NADase whose activity rises ~30%/decade after 40 due to inflammaging (Camacho-Pereira 2016). Pumping more precursor in while CD38 is shredding the output is partly self-defeating. Apigenin 50mg is the most-studied small-molecule CD38 inhibitor (Escande 2013; Tarragó 2018). Sourced at 98% from chamomile concentrate with BioPerine for absorption (food sources are largely impractical — you’d need 50–150 cups of chamomile tea for one 50mg dose). Standard dose: 50mg morning, with breakfast.

The complete Sinclair / Stanfield NAD+ stack therefore reads: NMN (precursor, salvage-pathway bypass) + Resveratrol or Pterostilbene (SIRT1 allosteric activator) + TMG (methylation buffer, upstream protection) + Apigenin (CD38 inhibitor, downstream protection) + Magnesium Glycinate (NAMPT cofactor, sleep architecture, Vitamin D activation). These five together — not any subset of three — are what canonical advanced protocols converge on.

Stacking with sister collections

NAD+ supplementation never lives alone in a serious protocol. Eight directional stacks the catalog supports:

• NAD+ × Mitochondrial Renewal. NAD+ feeds the mitochondria; mitochondrial renewal makes sure the mitochondria the NAD+ is feeding are new and functional. Add Urolithin A (mitophagy — clears the broken ones), PQQ (biogenesis — builds new ones), and CoQ10 (electron-transport cofactor for the working ones). Pumping NAD+ into a cell with half-broken mitochondria mostly produces reactive oxygen species rather than ATP.
• NAD+ × Cardiovascular Longevity. The Martens 2018 finding (NR 500mg twice daily → −9 mmHg systolic in stage 1 hypertension) is the entry point. Add CoQ10 400mg for endothelial function (Q-SYMBIO heart-failure trial), Taurine 1000mg for vascular tone, Omega-3 2000mg for ApoB/Lp(a) and inflammation.
• NAD+ × Metabolic. AMPK and sirtuins are the two master nutrient-sensing arms of metabolic longevity. Add Berberine 500mg with the largest carbohydrate meals for AMPK activation; add Alpha-Lipoic Acid 600mg for the universal antioxidant cycle that recycles glutathione and vitamin C. The Yoshino 2021 Science paper anchored NMN at 250mg/day to +25% muscle insulin sensitivity in postmenopausal prediabetics — this is the metabolic stack’s clinical anchor.
• NAD+ × Senolytics. Senescent cells (the “zombies”) consume NAD+ via CD38 over-expression and SASP-driven chronic PARP activation. Monthly senolytic pulses (Quercetin + Fisetin, two days, once monthly) reduce the NAD+-burning cell population at the source. Fisetin 500mg + Quercetin 500mg together cover the most-studied senolytic flavonoid pair.
• NAD+ × Antioxidants. Reducing oxidative damage at the source reduces PARP1 burn and preserves NAD+ for sirtuin / mitochondrial work. Glutathione 500mg + NAC 600mg + Glycine 1500mg form the GlyNAC pair (Sekhar 2021, Antioxidants; Kumar 2022) that restores tissue glutathione status while raising NAD+.
• NAD+ × Foundational Health. The mineral and vitamin floor (Vitamin D3 + K2, Magnesium Glycinate, Omega-3) determines whether the NAD+ stack functions at all — NAMPT is Mg-dependent, the SAMe cycle TMG supports is Mg-dependent, and Vitamin D activation is Mg-dependent. Roughly two-thirds of US adults sit below the magnesium RDA.
• NAD+ × Beauty & Anti-Aging. Sirtuin activation downstream of NAD+ supports fibroblast COL1A1 expression and dermal mitochondrial function. Add Marine Collagen Peptides 5000mg + Liposomal Vitamin C 1000mg + Hyaluronic Acid 200mg for the skin-from-within layer.
• NAD+ × Fertility. The oocyte carries ~100,000 mitochondria; the sperm tail is essentially a mitochondrial engine. Pre-conception NAD+/CoQ10/PQQ stacks address the oxidative-reproductive-aging axis — see the dedicated Fertility collection for the trial-validated 60–90 day pretreatment protocol.

Week-by-week realistic timeline

If 12 weeks at full dose feels like nothing, run the upstream-basics differential before assuming the NAD+ category itself failed: Vitamin D <30 ng/mL, ferritin <30, B12 <400, undiagnosed hypothyroid (TSH >3.0 with subclinical T3/T4), undiagnosed sleep apnea, protein floor <0.8g/lb bodyweight. NAD+ supplementation amplifies the energy a body that’s otherwise correctly fueled can produce — it can’t paper over a missing upstream input.

Drug interactions and caution flags

• Warfarin / apixaban / rivaroxaban (anticoagulants). Resveratrol has mild antiplatelet activity. Monitor INR if combining with an NMN+Resveratrol bundle; coordinate with the prescriber, particularly around procedures that require holding anticoagulation.
• Statins. CoQ10 (in 5-in-1 / Liposomal NAD+ Ultimate) is a clinically appropriate co-supplement — statins deplete endogenous CoQ10 (Marcoff 2007), so this combination is supportive rather than antagonistic.
• Active chemotherapy. NAD+ precursors and sirtuin activators have complex effects on cancer-cell energetics that depend on tumor type and regimen — coordinate with the treating oncologist before starting any NAD+ product. Some chemotherapy protocols deliberately pursue NAD+ depletion (Chini 2018).
• Diabetes / metformin. NAD+ + sirtuin activation may improve insulin sensitivity (Yoshino 2021), which can require dose-adjustment of glucose-lowering medications. Monitor glucose closely in the first 4–8 weeks; coordinate with the prescriber.
• Surgery (elective). Hold resveratrol-containing products for 1 week before any procedure that requires anticoagulation pause; standard supplement-pause protocols apply.
• Pregnancy / nursing. Trial data are inadequate. Avoid until weaning unless coordinated with an OB/MFM team.
• Transplant immunosuppression. Resveratrol and quercetin both inhibit CYP3A4 and may raise tacrolimus / cyclosporine levels — coordinate with the transplant team.
• Apigenin + grapefruit-class drugs. Apigenin shares CYP3A4-inhibitory characteristics with grapefruit; the 50mg dose is small but combine cautiously with high-CYP3A4-substrate medications (some statins, some calcium channel blockers).
• Methylation-sensitive psychiatric medication. TMG is generally safe but at high doses can shift methylation balance; users on SSRIs, SNRIs, or MAO inhibitors should add TMG slowly and watch for over-methylation symptoms (anxiety, insomnia).

Who this collection is for — and who it isn’t

This collection is for you if:

• You’re 30+ and noticing the slow-creep aging signals: 3pm energy crash, slower workout recovery, declining VO2 max, sleep that no longer fully restores.
• You’re building a serious longevity protocol around the López-Otín hallmarks framework and want the NAD+ pillar covered.
• You’re already running foundational supplements (Vitamin D + K2, Magnesium, Omega-3, Multivitamin floor) and have addressed upstream basics (sleep, training, protein floor).
• You’re responsive to caffeine but want energy that comes from cellular metabolism rather than adenosine-receptor antagonism.
• You’re post-menopausal or peri-menopausal — the Yoshino 2021 trial population was specifically prediabetic postmenopausal women, and that’s where some of the strongest insulin-sensitivity evidence sits.
• You’re 50+ and the “feels like I’m running on lower power than I used to” subjective experience is the dominant complaint.

This collection is not for you if:

• You’re pregnant or nursing.
• You’re in active chemotherapy or radiation without oncology team coordination.
• You’ve had a solid-organ transplant and are on tacrolimus/cyclosporine without transplant-team coordination.
• You’re hoping for a Day-1 stimulant-like effect — this is a 12-week-and-then-compounding category, not an energy-drink alternative.
• You haven’t addressed sleep, training, and protein floor — the upstream variance is larger than the supplement effect at that point.
• You’re under 25 and otherwise healthy — endogenous NAD+ is still high, the marginal benefit is small, and the literature is largely in older populations.

Quality, sourcing, and what’s not in the bottle

Every active in this collection is held to the True Health Protocol quality floor. See the full quality protocol for the master document; the collection-specific summary:

• HPLC purity assay: β-NMN ≥99% (β-isomer-only — α-NMN is biologically inert), NR ≥98%, trans-resveratrol ≥98% trans-isomer (cis-isomer does not allosterically activate SIRT1), apigenin 98% from chamomile concentrate, TMG 1000mg pharma-grade sugar-beet betaine anhydrous. Every Certificate of Analysis includes the assay number and lot date.
• Heavy-metal and microbial testing: ISO/IEC 17025 third-party laboratory, every lot, for arsenic / cadmium / mercury / lead and microbial limits per USP <2021> / <2022>.
• Manufacturing standard: cGMP-registered facilities, 21 CFR Part 111. Ingredient sourcing detail.
• What’s NOT in the bottle: no proprietary blends (every dose is on the panel), no titanium dioxide (the 2022 EFSA reclassification triggered our reformulation cycle), no synthetic dyes, no magnesium stearate where avoidable, no soy (where labeled soy-free), 24-month shelf life from manufacture date, lot-and-expiry on every bottle.
• Storage: NMN and NR are oxidation-sensitive — keep tightly capped, away from heat/humidity, and finished within the printed expiry window. The drink-format SKUs (Liquid NAD+, Pure Focus Drink Mix) are individually foil-sealed for the same reason.

FAQ — 13 questions

Should I take NMN or NR? They both raise NAD+ — does it matter which?

For most users, the answer is “either works, pick the format you’ll actually take consistently.” The trial literature favors NR slightly because it’s been studied longest (Trammell 2016 was the first human bioavailability trial; multiple positive endpoint studies followed). NMN has a stronger mechanistic case (one enzymatic step from NAD+ vs two for NR; bypasses the age-declining NAMPT bottleneck) and Yoshino 2021 / Yamaguchi 2022 / Igarashi 2022 are the trials that anchor most modern protocols. If you’re a capsule-and-data person, start with NMN. If you don’t take pills well or want flavor variety, the Liquid NAD+ Drink is the same NR substrate as the capsule SKU. Read the full NMN vs NR comparison on the blog.

Why direct liposomal NAD+ instead of just taking precursor?

Free oral NAD+ is largely degraded in the stomach to nicotinamide before absorption. Liposomal phospholipid encapsulation protects the molecule through gastric pH and delivers it intact to the enterocyte for lymphatic absorption. This bypasses both the NAMPT bottleneck (age-related) and the NRK/NMNAT precursor-conversion steps. The trade-off: direct NAD+ is more expensive per dose than precursor, and the precursor route already works well for most users. Reach for direct liposomal NAD+ if you’ve plateaued on precursor or want the comprehensive 10-active formula simplicity.

I’m on warfarin. Can I take NMN + Resveratrol?

Coordinate with your prescriber before starting and monitor INR after starting. NMN itself has no documented anticoagulant activity. Resveratrol has mild antiplatelet effects that occasionally shift INR in patients on warfarin — not enough to be a hard contraindication, but enough that an extra INR check 2 weeks after starting is sensible. Hold for 1 week before any procedure that requires anticoagulation pause.

Do I need TMG and Apigenin from day one?

No. At Tier 1 / Tier 2 doses (NMN ≤500mg/day, ≤8 weeks), the methylation drain is modest and the CD38 burn is in the range that endogenous SAMe production handles. Add TMG at week 4–6 if escalating to NMN ≥1000mg/day or running sustained protocols ≥3 months. Add Apigenin if you’re 45+ (CD38 activity rises ~30%/decade after 40) or if precursor-only response has plateaued. The full Sinclair stack (precursor + activator + TMG + Apigenin + Magnesium) is the canonical advanced protocol — not the entry protocol.

What if I don’t feel anything after 4 weeks?

That’s normal. NAD+ supplementation is a 12-week-and-then-compounding category, not an energy-drink. The Yoshino 2021 endpoint was at 12 weeks. The Igarashi 2022 functional endpoints (gait speed, grip strength) were at 12 weeks. The Brakedal 2022 cerebral-NAD+ MRI signal moved at 30 days, but the symptomatic motor improvement signal was at 30+ days and exploratory at that. If 12 weeks at full dose still feels like nothing, run the upstream-basics differential (vitamin D, ferritin, B12, hypothyroid, sleep apnea, protein floor) before concluding the precursor is failing.

Is it safe to take all four routes (NMN + NR + Liposomal NAD+ + drink mix) together?

Pharmacologically, yes — they all converge on the NAD+ pool, and there’s no documented toxicity from co-administration. Practically, no — this is overkill, expensive, and the extra precursor mass largely gets methylated and excreted as N-methylnicotinamide rather than producing additional NAD+ benefit. Pick one precursor (NMN or NR) and one direct-NAD+ option (capsule or drink) at most, and put the budget into the cofactor side of the stack (TMG, Apigenin, Magnesium) where the marginal benefit is larger.

Is NMN safer than NR or vice versa?

Both have well-tolerated long-term human safety data at trial doses. NR has the larger long-term safety database (Conze 2019 8-week n=140 RCT, Brakedal 2022 12-month n=400+ Parkinson’s cohort, multiple 6–12 week endpoint studies with no significant adverse-event difference vs placebo). NMN has shorter-duration human RCTs but no signals of toxicity. The most-reported subjective complaint with either at high dose is mild flushing (similar to high-dose niacin but much milder) or transient GI upset; both are dose-responsive and resolve at lower doses.

Vegan-friendly?

NMN, NR, resveratrol, TMG, apigenin, and magnesium glycinate in this collection are all vegan-compatible. Capsule shells are vegetable cellulose. The exception within the broader stack: marine collagen (fish-derived) in the beauty layer is not vegan; bovine collagen is not vegan; if running the full longevity-plus-beauty protocol vegan, swap collagen for the precursor amino acids (glycine, proline, hyaluronic acid) and rely on liposomal vitamin C as the cofactor. The 5-in-1 NAD+ Complete Mitochondrial Formula is fully plant-derived.

Best time of day?

Morning, with a fat-containing breakfast. NAD+ rises throughout the morning are aligned with circadian SIRT1 / BMAL1 metabolic rhythm; resveratrol and CoQ10 are fat-soluble and absorbing them with a meal that contains 5–10g of fat materially raises bioavailability. Avoid late-evening dosing — raising sirtuin activity at night can interfere with sleep architecture in some users. The exception: magnesium glycinate, which is a evening cofactor pair (60–90 minutes before bed) for the NAD+ stack, not a morning component.

How does this compare to NAD+ IV drips?

IV NAD+ delivers a large bolus dose subcutaneously bypassing the gut, which produces a transient ~hours-long high serum NAD+ peak. Trial evidence for IV is sparse (most published is anecdotal or industry-funded). Oral precursor produces a smaller peak but a sustained chronic elevation over weeks that’s where most of the trial-validated functional endpoints sit. Cost: oral is ~$50–$150/month; IV is typically $300–$1000/session. For sustained longevity goals, the oral protocol is the better bet; IV is occasionally useful as a one-time intensive in specific contexts (post-illness recovery, pre-event peak).

Why are there so many SKUs in this collection?

NAD+ is the most-supplemented longevity pathway in the world right now — format diversity matches user diversity. Some users want a single capsule with everything (Liposomal NAD+ Ultimate, 5-in-1 Complete). Some want maximum flexibility to titrate dose and switch precursors (Pure NMN, NR Hard Capsules). Some don’t take pills well (Liquid NAD+ Drink, Pure Focus Drink Mix). Some want the canonical bundle pre-paired (Longevity Stack Bundle). The collection covers the full grid so users don’t have to compromise on format to access the category.

Can I open the capsules and put the powder in a smoothie?

NMN and NR are stable enough to open and mix, but oxidation accelerates rapidly once the capsule is breached — mix and consume immediately. Resveratrol is the bigger problem — the capsule shell protects against oxidation and light degradation; once opened, the active begins converting from trans- to inactive cis-resveratrol within an hour. If you can’t swallow capsules, the Liquid NAD+ Drink or NAD+ Drink Mix are the right call.

Returns and refund?

30-day, no-return-required money-back. If you’ve tried any product in this collection and it didn’t work for you within 30 days of arrival, email support@truehealthprotocol.health for a refund — you don’t need to ship the bottle back. Full refund policy; our guarantee in detail.

References

1. Bai P, et al. Cell Metabolism. 2015. PARP-1 and NAD metabolism. PMID 24360282
2. Brakedal B, et al. Cell Metabolism. 2022. NADPARK trial: NR in Parkinson’s disease. PMID 35243604
3. Camacho-Pereira J, et al. Cell Metabolism. 2016. CD38 as a major regulator of NAD+ during aging. PMID 27068460
4. Chini CCS, et al. Trends Pharmacol Sci. 2018. NAD+ metabolism in cancer. PMID 28937962
5. Conze D, et al. Sci Rep. 2019. NR safety and NAD+ elevation, n=140 8-week RCT. PMID 30530937
6. Escande C, et al. Diabetes. 2013. Apigenin as CD38 inhibitor. PMID 23339328
7. Goh KP, et al. J Nutr Sci. 2014. Resveratrol and SIRT1 in T2DM. PMID 24909168
8. Harris CB, et al. J Nutr Biochem. 2013. PQQ pharmacodynamics in humans. PMID 23211660
9. Howitz KT, et al. Nature. 2003. Resveratrol activation of SIRT1. PMID 12939617
10. Hubbard BP, et al. Science. 2013. SIRT1 allosteric activation crystal structure. PMID 23471395
11. Igarashi M, et al. npj Aging. 2022. NMN 250mg twice daily, n=42 men 65+. PMID 35365707
12. Kumar P, et al. J Gerontol A Biol Sci Med Sci. 2022. GlyNAC and oxidative stress. PMID 35114078
13. López-Otín C, et al. Cell. 2013. The hallmarks of aging. PMID 23746838
14. López-Otín C, et al. Cell. 2023. Hallmarks of aging: an expanding universe. PMID 36599349
15. Marcoff L, Thompson PD. JACC. 2007. Statin-induced CoQ10 depletion. PMID 17631503
16. Martens CR, et al. Nat Commun. 2018. NR and cardiovascular endpoints. PMID 29985466
17. Massudi H, et al. PLOS One. 2012. Age-associated NAD+ decline in human tissue. PMID 22452603
18. Mortensen SA, et al. JACC Heart Fail. 2014. Q-SYMBIO: CoQ10 in chronic heart failure. PMID 25282031
19. Pissios P. Trends Endocrinol Metab. 2017. Nicotinamide N-methyltransferase. PMID 12824063
20. Sekhar RV, et al. Antioxidants. 2021. GlyNAC supplementation in older adults. PMID 34593657
21. Stein LR, Imai S. EMBO J. 2014. Specific ablation of Nampt in adult neural stem cells. PMID 22484942
22. Tarragó MG, et al. Cell Metabolism. 2018. CD38 inhibitor 78c. PMID 30002995
23. Timmers S, et al. Cell Metabolism. 2011. Resveratrol calorie-restriction mimetic effects. PMID 22106405
24. Trammell SAJ, et al. Nat Commun. 2016. NR human bioavailability and NAD+ metabolome. PMID 27721479
25. Yamaguchi S, et al. Nutrients. 2022. NMN 250mg/day in healthy adults. PMID 35624462
26. Yoshino M, et al. Science. 2021. NMN improves muscle insulin sensitivity in postmenopausal women. PMID 33888596

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Disclaimer

These statements have not been evaluated by the U.S. Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease. The information on this page is educational and reflects published peer-reviewed research; it is not medical advice. Coordinate with your prescribing physician before starting any supplement, particularly if you are pregnant, nursing, on prescription medication, or undergoing active medical treatment. Individual response varies and trial-anchored timelines describe population averages, not guarantees.