{"product_id":"apigenin-50mg-cd38-inhibitor-for-nmn-nad-stacks","title":"Apigenin 50mg + BioPerine | CD38 Inhibitor for NMN, NAD+ \u0026 Sirtuin Stacks","description":"\u003ch2\u003eThe 30-second answer\u003c\/h2\u003e\n\u003cp\u003eApigenin is a flavonoid found in chamomile, parsley, and celery. It has a single mechanism that puts it in serious longevity protocols: it \u003cstrong\u003einhibits CD38\u003c\/strong\u003e, the membrane glycohydrolase that consumes NAD\u003csup\u003e+\u003c\/sup\u003e and whose tissue activity rises several-fold with age (Camacho-Pereira et al., \u003cem\u003eCell Metabolism\u003c\/em\u003e 2016; Chini et al., \u003cem\u003eCell Metabolism\u003c\/em\u003e 2020). NAD\u003csup\u003e+\u003c\/sup\u003e precursors like \u003ca href=\"\/products\/pure-nmn-500mg-60-capsules-30-day-supply\"\u003eNMN\u003c\/a\u003e, \u003ca href=\"\/products\/nmn-1000mg-double-strength-60-capsules-30-day-supply\"\u003edouble-strength NMN\u003c\/a\u003e, and \u003ca href=\"\/products\/new-nad-hard-capsules-daily-nad-boost-for-energy-longevity\"\u003eNR\u003c\/a\u003e raise NAD\u003csup\u003e+\u003c\/sup\u003e from the production side. Apigenin slows the leak on the consumption side. Both sides need to work, which is why apigenin is the third leg of the canonical Sinclair-style NMN stack — a precursor (NMN\/NR), a methyl donor (\u003ca href=\"\/products\/tmg-1000mg-trimethylglycine-methyl-donor-for-nmn-nad-stacks\"\u003eTMG\u003c\/a\u003e), and a CD38 inhibitor (apigenin). Apigenin also contributes mild senolytic activity (Yousefzadeh et al., \u003cem\u003eEBioMedicine\u003c\/em\u003e 2018) and SASP suppression, and it modulates GABA\u003csub\u003eA\u003c\/sub\u003e receptors (Salgueiro et al., \u003cem\u003ePharmacol Biochem Behav\u003c\/em\u003e 1997) — which is why some users notice a calmer baseline and improved sleep within the first weeks. Each capsule pairs 50 mg of 98%-standardized apigenin with 5 mg of BioPerine\u003csup\u003e®\u003c\/sup\u003e, the piperine extract that solves apigenin's first-pass-metabolism problem.\u003c\/p\u003e\n\n\u003ch2\u003eWhy a flavonoid ended up in NAD\u003csup\u003e+\u003c\/sup\u003e research\u003c\/h2\u003e\n\u003cp\u003eTissue NAD\u003csup\u003e+\u003c\/sup\u003e falls roughly 50% between ages 20 and 60 (Massudi et al., \u003cem\u003ePLoS ONE\u003c\/em\u003e 2012). Two forces drive that decline. The body makes less of it as the salvage pathway slows, and it \u003cem\u003edestroys more of it\u003c\/em\u003e, because CD38 — the dominant NADase in mammalian tissue — becomes more active with age. Camacho-Pereira et al. (2016) showed that CD38 expression rises in liver, adipose tissue, skeletal muscle, and spleen as mice age, and that CD38-knockout mice are protected against age-related NAD\u003csup\u003e+\u003c\/sup\u003e loss. Tarragó et al. (\u003cem\u003eCell Metabolism\u003c\/em\u003e 2018) extended this work with the first orally-active CD38 inhibitor (the experimental compound 78c), demonstrating that pharmacologically blocking CD38 in old mice raised tissue NAD\u003csup\u003e+\u003c\/sup\u003e, restored mitochondrial function, and improved exercise performance — without giving any precursor at all. The implication: precursor supply is half the equation; precursor protection is the other half.\u003c\/p\u003e\n\n\u003cp\u003eYou can't take 78c (it's not a supplement). But apigenin inhibits CD38 in the same way, with a measured IC\u003csub\u003e50\u003c\/sub\u003e in the low-micromolar range (Escande et al., \u003cem\u003eDiabetes\u003c\/em\u003e 2013) — the paper that first identified flavonoids as CD38 inhibitors and showed apigenin raised tissue NAD\u003csup\u003e+\u003c\/sup\u003e in obese mice while improving glucose tolerance. Chini's group at Mayo Clinic (now at the Kogod Center on Aging) has since published a sustained line of work mapping CD38's role in inflammaging, NAD\u003csup\u003e+\u003c\/sup\u003e homeostasis, and the metabolic syndrome — putting CD38 inhibition on the same priority list as autophagy activation and senescent-cell clearance for healthspan-focused intervention.\u003c\/p\u003e\n\n\u003cp\u003eThis is where apigenin became the third leg of the stack. NMN feeds production. TMG replaces the methyl groups consumed when nicotinamide (the breakdown product) is exported. Apigenin slows the destruction. None of the three is the precursor. They're what makes the precursor keep working at month six instead of plateauing at month two.\u003c\/p\u003e\n\n\u003ch2\u003eThe three mechanisms apigenin actually has\u003c\/h2\u003e\n\u003cp\u003eMost antioxidant flavonoids do one thing in three different cell types. Apigenin does three different things, and they reinforce each other in ways that matter for a longevity protocol.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003e1. CD38 inhibition — the NAD\u003csup\u003e+\u003c\/sup\u003e-protecting mechanism.\u003c\/strong\u003e Apigenin binds CD38's active site and slows the enzymatic consumption of NAD\u003csup\u003e+\u003c\/sup\u003e. The net effect in the Escande 2013 obese-mouse model was a measurable rise in tissue NAD\u003csup\u003e+\u003c\/sup\u003e levels, with the largest gains in liver and adipose tissue (the two tissues where CD38 expression is highest). This is the mechanism that puts apigenin alongside NMN and TMG in the canonical Sinclair-style stack — and it's the reason apigenin is dosed continuously rather than in pulses (CD38 is constitutively active; the inhibition needs to be steady-state).\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003e2. Mild senolytic activity.\u003c\/strong\u003e Apigenin selectively triggers apoptosis in some senescent cells. Per the Yousefzadeh 2018 head-to-head screen, it is weaker than \u003ca href=\"\/products\/fisetin-500mg-senolytic-flavonoid-for-cellular-cleanup\"\u003efisetin\u003c\/a\u003e or \u003ca href=\"\/products\/quercetin-500mg-senolytic-flavonoid-natural-antihistamine\"\u003equercetin\u003c\/a\u003e per milligram — it would not be the supplement to choose if senolysis were the only goal — but it adds a low-grade clearing mechanism on top of its primary CD38 work. Some advanced protocols stack all three flavonoids rather than choose one, taking advantage of partially-overlapping but non-identical target profiles.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003e3. SASP suppression and anti-inflammatory action.\u003c\/strong\u003e Even when apigenin doesn't kill a senescent cell outright, it reduces the Senescence-Associated Secretory Phenotype — the cocktail of inflammatory cytokines (IL-6, IL-8, TNF-α, CXCL chemokines) that senescent cells release into surrounding tissue. Perrott et al. (\u003cem\u003eGeroScience\u003c\/em\u003e 2017) showed apigenin suppressed SASP transcription in pre-adipocyte models without requiring senolysis. For NAD\u003csup\u003e+\u003c\/sup\u003e-protocol users this matters because chronic low-grade inflammation is one of the things that \u003cem\u003eactivates\u003c\/em\u003e CD38 in the first place (Chini et al., \u003cem\u003eNat Metab\u003c\/em\u003e 2024 review on inflammaging). Apigenin closes that loop: less SASP → less inflammation → less CD38 activation → more NAD\u003csup\u003e+\u003c\/sup\u003e retained.\u003c\/p\u003e\n\n\u003cp\u003eThere is a fourth mechanism that's not part of the longevity argument but explains a common subjective report: \u003cstrong\u003eapigenin is the active sleep\/calming compound in chamomile\u003c\/strong\u003e. It binds GABA\u003csub\u003eA\u003c\/sub\u003e receptors as a partial agonist (Salgueiro 1997; Avallone et al., \u003cem\u003eBiochem Pharmacol\u003c\/em\u003e 2000) — the same family of receptors targeted by benzodiazepines, but with much weaker affinity. This is why a strong cup of chamomile tea relaxes you, and why some apigenin-supplement users report falling asleep faster and waking less in the first 1–3 weeks. If sleep quality is one of your goals, dose in the evening; if NAD\u003csup\u003e+\u003c\/sup\u003e protection is the only goal, dose in the morning with the rest of your stack.\u003c\/p\u003e\n\n\u003ch2\u003eWhere this sits in the longevity-protocol stack\u003c\/h2\u003e\n\u003cp\u003eThe most useful way to think about apigenin is in terms of what it pairs with, because it has very limited reason to be a standalone purchase.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eIf you take a NAD\u003csup\u003e+\u003c\/sup\u003e precursor\u003c\/strong\u003e — \u003ca href=\"\/products\/pure-nmn-500mg-60-capsules-30-day-supply\"\u003ePure NMN 500mg\u003c\/a\u003e, \u003ca href=\"\/products\/nmn-1000mg-double-strength-60-capsules-30-day-supply\"\u003eNMN 1000mg\u003c\/a\u003e, \u003ca href=\"\/products\/new-nad-hard-capsules-daily-nad-boost-for-energy-longevity\"\u003eNR Hard Capsules\u003c\/a\u003e, \u003ca href=\"\/products\/liposomal-nad-ultimate-1000mg\"\u003eLiposomal NAD+ Ultimate\u003c\/a\u003e, \u003ca href=\"\/products\/zoone-nad-1000mg-pure-focus-formula\"\u003eNAD+ Pure Focus\u003c\/a\u003e, or the \u003ca href=\"\/products\/liquid-nad-anti-aging-drink-advanced-cellular-rejuvenation\"\u003eLiquid NAD+ stick packs\u003c\/a\u003e — apigenin is the highest-value addition you can make for protecting what the precursor produces. The two co-additions that the longevity-clinic literature converges on are TMG (replaces methyl groups burned during nicotinamide clearance) and apigenin (slows CD38). One protects the upstream cycle. The other protects the downstream one.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eIf you also run a senolytic protocol\u003c\/strong\u003e — typically \u003ca href=\"\/products\/fisetin-500mg-senolytic-flavonoid-for-cellular-cleanup\"\u003eFisetin 500mg\u003c\/a\u003e in monthly pulses, or \u003ca href=\"\/products\/quercetin-500mg-senolytic-flavonoid-natural-antihistamine\"\u003eQuercetin 500mg\u003c\/a\u003e daily — apigenin's daily SASP suppression complements both. Fisetin clears senescent cells in 2-day high-dose pulses; apigenin reduces the day-to-day inflammatory output of any cells that aren't being cleared in this cycle. That's the case for stacking all three flavonoids rather than choosing one.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eIf your primary goal is sleep\u003c\/strong\u003e — and you're already on a precursor — apigenin in the evening, paired with \u003ca href=\"\/products\/magnesium-glycinate-400mg-sleep-and-nad-methylation\"\u003eMagnesium Glycinate\u003c\/a\u003e and \u003ca href=\"\/products\/glycine-1500mg-glynac-partner-glutathione-sleep-longevity\"\u003eGlycine\u003c\/a\u003e, gives you the GABAergic calming layer on top of the longevity rationale. This is the dual-purpose protocol some users prefer.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eWhat apigenin is NOT.\u003c\/strong\u003e It is not a precursor. Taking apigenin alone, without a precursor, will not raise NAD\u003csup\u003e+\u003c\/sup\u003e meaningfully — you need substrate for the salvage pathway. Apigenin's job is to slow loss; you still need to feed input. It's also not a stimulant or an energy product; the calming effect is the only thing you may notice subjectively.\u003c\/p\u003e\n\n\u003ch2\u003eWhat's in the bottle\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eApigenin (98% pure):\u003c\/strong\u003e 50 mg per capsule, extracted from chamomile flower (\u003cem\u003eMatricaria chamomilla\u003c\/em\u003e) — the natural source with the highest apigenin density. Parsley, celery, and artichoke contain it too, in much smaller amounts.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eBioPerine\u003csup\u003e®\u003c\/sup\u003e (black pepper extract, standardized to 95% piperine):\u003c\/strong\u003e 5 mg per capsule. Apigenin's bioavailability is the limiting factor in every flavonoid supplement. Piperine inhibits the gut UDP-glucuronosyltransferases (UGTs) and CYP3A4 that would otherwise metabolize apigenin in the gut wall before it reaches systemic circulation, raising blood AUC several-fold (Atal et al., \u003cem\u003eJ Pharmacol Exp Ther\u003c\/em\u003e 1985, the foundational piperine bioenhancer paper; Bhardwaj et al., \u003cem\u003eJ Pharmacol Exp Ther\u003c\/em\u003e 2002).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003e60 vegetarian HPMC capsules per bottle:\u003c\/strong\u003e a 2-month supply at the standard 1-capsule daily dose, or a 1-month supply at the higher 2-capsule dose used in some longevity-clinic protocols.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eFree of:\u003c\/strong\u003e gluten, soy, dairy, GMO, magnesium stearate, titanium dioxide, artificial colors, and synthetic flow agents.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2\u003eThe bioavailability problem (and why every cheap apigenin capsule is mostly water)\u003c\/h2\u003e\n\u003cp\u003eApigenin without an absorption enhancer is a frustrating molecule. Free apigenin is poorly soluble in water, and what does dissolve is rapidly conjugated by gut UGTs into apigenin-glucuronide and apigenin-sulfate before it ever reaches the portal circulation. Plasma free-apigenin levels after a 50 mg unenhanced dose are typically below the threshold needed for measurable CD38 inhibition in tissue. Imran et al. (\u003cem\u003eFood Chem\u003c\/em\u003e 2020 review) put the unenhanced bioavailability fraction in the low single-digit percent range.\u003c\/p\u003e\n\n\u003cp\u003eThe two interventions that work in published research:\u003c\/p\u003e\n\u003col\u003e\n\u003cli\u003e\n\u003cstrong\u003ePiperine co-administration.\u003c\/strong\u003e The Atal\/Bhardwaj line of work shows piperine inhibits both intestinal UGT activity and the CYP3A4-mediated first-pass metabolism that destroys apigenin. The 5 mg BioPerine in each capsule is the same dose used in published bioenhancer studies for curcumin, resveratrol, and other low-bioavailability polyphenols.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eFat-meal pairing.\u003c\/strong\u003e Apigenin is fat-soluble; absorption rises substantially when taken with a meal containing 5+ grams of fat (eggs, avocado, olive oil, full-fat yogurt). The combination of piperine + dietary fat is what closes the bioavailability gap that an unenhanced capsule fails to address.\u003c\/li\u003e\n\u003c\/ol\u003e\n\u003cp\u003eThis is why the dose comparison matters. A 100 mg apigenin capsule with no piperine and no food can deliver less to your tissues than a 50 mg apigenin + BioPerine capsule taken with breakfast. The label dose is not what reaches CD38 — the absorbed dose is.\u003c\/p\u003e\n\n\u003ch2\u003eDose curve: 25 mg \/ 50 mg \/ 100 mg \/ advanced\u003c\/h2\u003e\n\u003cp\u003e\u003cstrong\u003e25 mg (sub-therapeutic for CD38 work).\u003c\/strong\u003e Common in multivitamins and \"longevity blend\" caps. The plasma levels reached at this dose with no enhancer are likely below the IC\u003csub\u003e50\u003c\/sub\u003e for CD38 inhibition in tissue. Useful as part of a polyphenol matrix, not useful as a CD38 strategy on its own.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003e50 mg + piperine (our default).\u003c\/strong\u003e The dose-equivalent that, with bioavailability enhancement and a fat-meal, plausibly reaches the low-micromolar plasma concentrations associated with CD38 inhibition in the Escande 2013 mouse model. The dose most longevity-protocol practitioners use for daily NAD\u003csup\u003e+\u003c\/sup\u003e protection.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003e100 mg (advanced).\u003c\/strong\u003e Two capsules daily, used in some clinical longevity protocols for users with measured low NAD\u003csup\u003e+\u003c\/sup\u003e or for pairing with a high-dose NMN protocol (1000+ mg). Splitting morning and evening helps maintain plasma levels across the 24-hour cycle, since apigenin's plasma half-life is roughly 90 minutes (Gradolatto et al., \u003cem\u003eDrug Metab Dispos\u003c\/em\u003e 2005).\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003e200+ mg (research, not recommended for daily use).\u003c\/strong\u003e Doses above 200 mg have been used in short-term cancer-cell pharmacology research but exceed what's been studied for daily longevity-protocol use. There is no published evidence that going higher gives more CD38 inhibition once the IC\u003csub\u003e50\u003c\/sub\u003e is cleared.\u003c\/p\u003e\n\n\u003ch2\u003eWeek-by-week expectation timeline\u003c\/h2\u003e\n\u003cp\u003e\u003cstrong\u003eDays 1–7.\u003c\/strong\u003e The most-reported subjective change is calmer baseline and slightly improved sleep onset (the GABA\u003csub\u003eA\u003c\/sub\u003e partial-agonist effect). No measurable NAD\u003csup\u003e+\u003c\/sup\u003e change yet — CD38 inhibition takes longer to translate into tissue-level NAD\u003csup\u003e+\u003c\/sup\u003e rise.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eWeeks 2–4.\u003c\/strong\u003e SASP suppression begins to register at the bloodwork level. Users with elevated baseline CRP often see a modest decline (no published RCT in humans for this specific endpoint with apigenin alone — this is extrapolation from pre-adipocyte data plus broader flavonoid trials).\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eWeeks 4–8.\u003c\/strong\u003e If you're on a precursor + apigenin combination, this is the window where the \"plateau\" some people hit on precursor-alone tends to reverse. Subjectively this looks like the morning energy and recovery returning to where they were at month two of the precursor.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eMonths 2–6.\u003c\/strong\u003e The compounding window. CD38 protection is a steady-state mechanism — its benefit is a slope, not a step. Tissue NAD\u003csup\u003e+\u003c\/sup\u003e trajectory at month six on precursor + apigenin + TMG is meaningfully different from precursor alone.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eYear 1+.\u003c\/strong\u003e The horizon at which the inflammaging argument applies. Lower CD38 activity, combined with reduced SASP, plausibly slows the chronic-inflammation feedback loop that drives many age-related declines. Bloodwork (hsCRP, IL-6 if your provider runs it) is the place this shows up.\u003c\/p\u003e\n\n\u003ch2\u003eHow to take it\u003c\/h2\u003e\n\u003cp\u003e\u003cstrong\u003eDefault protocol (NAD\u003csup\u003e+\u003c\/sup\u003e-stack pairing):\u003c\/strong\u003e 1 capsule (50 mg) in the morning with breakfast, alongside your \u003ca href=\"\/products\/pure-nmn-500mg-60-capsules-30-day-supply\"\u003eNMN\u003c\/a\u003e, \u003ca href=\"\/products\/new-nad-hard-capsules-daily-nad-boost-for-energy-longevity\"\u003eNR\u003c\/a\u003e, or NAD\u003csup\u003e+\u003c\/sup\u003e precursor. Take it with a meal containing some fat (eggs, avocado, olive oil) — this matters more than most users realize.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eHigher protocol (advanced longevity stack):\u003c\/strong\u003e 2 capsules (100 mg) daily, taken together in the morning or split morning and evening. Some longevity clinics use this dose for users with measured low NAD\u003csup\u003e+\u003c\/sup\u003e or with a high-dose precursor protocol (NMN 1000 mg+).\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eSleep-priority protocol:\u003c\/strong\u003e 1 capsule (50 mg) in the evening with dinner. Trades the morning NAD\u003csup\u003e+\u003c\/sup\u003e-window logic for the GABAergic calming benefit. Stacks well with \u003ca href=\"\/products\/magnesium-glycinate-400mg-sleep-and-nad-methylation\"\u003eMagnesium Glycinate\u003c\/a\u003e and \u003ca href=\"\/products\/glycine-1500mg-glynac-partner-glutathione-sleep-longevity\"\u003eGlycine\u003c\/a\u003e.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eStacking note.\u003c\/strong\u003e Apigenin pairs cleanly with NMN, NR, liposomal NAD\u003csup\u003e+\u003c\/sup\u003e, TMG, fisetin, quercetin, \u003ca href=\"\/products\/spermidine-10mg-wheat-germ-extract\"\u003espermidine\u003c\/a\u003e, \u003ca href=\"\/products\/resveratrol-600mg-60-capsules-30-day-supply\"\u003eresveratrol\u003c\/a\u003e, and the foundational stack. There is no need to cycle apigenin — CD38 is constitutively active; the inhibition needs to be continuous to be useful.\u003c\/p\u003e\n\n\u003ch2\u003eStack pairings (with mechanism rationale)\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003e+ \u003ca href=\"\/products\/pure-nmn-500mg-60-capsules-30-day-supply\"\u003eNMN\u003c\/a\u003e or \u003ca href=\"\/products\/new-nad-hard-capsules-daily-nad-boost-for-energy-longevity\"\u003eNR\u003c\/a\u003e:\u003c\/strong\u003e the canonical pairing. Precursor raises NAD\u003csup\u003e+\u003c\/sup\u003e; apigenin slows the consumption. Always co-dose.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003e+ \u003ca href=\"\/products\/tmg-1000mg-trimethylglycine-methyl-donor-for-nmn-nad-stacks\"\u003eTMG\u003c\/a\u003e:\u003c\/strong\u003e the third leg of the Sinclair-style stack. TMG donates methyl groups burned during the methylation of nicotinamide (the breakdown product of any precursor). The full triad — precursor + TMG + apigenin — is what most longevity-focused protocols converge on.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003e+ \u003ca href=\"\/products\/fisetin-500mg-senolytic-flavonoid-for-cellular-cleanup\"\u003eFisetin\u003c\/a\u003e:\u003c\/strong\u003e the senolytic complement. Fisetin pulses (typically 1500 mg\/day for 2 days, monthly) clear senescent cells; apigenin's daily SASP suppression reduces the inflammatory output between pulses.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003e+ \u003ca href=\"\/products\/quercetin-500mg-senolytic-flavonoid-natural-antihistamine\"\u003eQuercetin\u003c\/a\u003e:\u003c\/strong\u003e the most-studied senolytic in human trials. Pairs with apigenin for daily flavonoid-class coverage of CD38 (apigenin) plus broader senescence work (quercetin).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003e+ \u003ca href=\"\/products\/resveratrol-600mg-60-capsules-30-day-supply\"\u003eResveratrol\u003c\/a\u003e:\u003c\/strong\u003e the SIRT1 activator. Apigenin protects NAD\u003csup\u003e+\u003c\/sup\u003e, which sirtuins consume; resveratrol activates the consumption. Complementary, not redundant.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003e+ \u003ca href=\"\/products\/spermidine-10mg-wheat-germ-extract\"\u003eSpermidine\u003c\/a\u003e:\u003c\/strong\u003e the autophagy activator. Different cellular renewal pathway (autophagy-of-proteins vs CD38-protection-of-NAD\u003csup\u003e+\u003c\/sup\u003e) — additive, not overlapping.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003e+ \u003ca href=\"\/products\/magnesium-glycinate-400mg-sleep-and-nad-methylation\"\u003eMagnesium Glycinate\u003c\/a\u003e + \u003ca href=\"\/products\/glycine-1500mg-glynac-partner-glutathione-sleep-longevity\"\u003eGlycine\u003c\/a\u003e:\u003c\/strong\u003e the sleep stack. Apigenin's GABA\u003csub\u003eA\u003c\/sub\u003e activity layers on top of magnesium and glycine for users prioritizing sleep quality.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2\u003eForm comparison: chamomile tea vs parsley vs 50 mg vs 100 mg\u003c\/h2\u003e\n\u003cp\u003e\u003cstrong\u003eChamomile tea.\u003c\/strong\u003e A strong cup contains roughly 0.3–1 mg of free apigenin. To reach a 50 mg dose from tea you would need to drink 50–150 cups daily. Tea delivers a real calming effect at low apigenin levels; it does not deliver a CD38-relevant dose.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eParsley and celery.\u003c\/strong\u003e Parsley is the highest dietary source by weight (roughly 215 mg\/100 g dry parsley flake; 45 mg\/100 g fresh) — but you'd need to eat 100+ grams of fresh parsley daily for a 50 mg dose, and absorption from food matrix is lower than from a piperine-enhanced capsule. Useful as part of a healthy diet; not a viable replacement for a targeted CD38 protocol.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eApigenin 50 mg + piperine (this product).\u003c\/strong\u003e The dose used in longevity-protocol practice, with the bioavailability enhancement that closes the absorption gap. The default for NAD\u003csup\u003e+\u003c\/sup\u003e stacking.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eApigenin 100 mg \/ 200 mg without piperine.\u003c\/strong\u003e A higher label dose without bioavailability enhancement does not clearly outperform a lower label dose with enhancement. Read the SUPPLEMENT FACTS panel: if there's no piperine\/BioPerine and no liposomal\/phytosome carrier, the higher label dose is partially marketing.\u003c\/p\u003e\n\n\u003ch2\u003eQuality \u0026amp; sourcing\u003c\/h2\u003e\n\u003cp\u003eManufactured in a U.S. cGMP-compliant facility. Each batch is tested for identity, potency, heavy metals (lead, arsenic, cadmium, mercury), and microbial contamination. Apigenin is standardized to 98% from \u003cem\u003eMatricaria chamomilla\u003c\/em\u003e extract; the BioPerine\u003csup\u003e®\u003c\/sup\u003e is the patented form of piperine from Sabinsa Corporation, the form used in the published bioenhancer literature. Capsule shell is HPMC (vegetarian, no gelatin); no magnesium stearate, no titanium dioxide, no synthetic dyes. Per-batch certificate of analysis available on request through customer service.\u003c\/p\u003e\n\n\u003ch2\u003eWho this is for\u003c\/h2\u003e\n\u003cp\u003eApigenin is most useful for someone already running a NAD\u003csup\u003e+\u003c\/sup\u003e precursor protocol who wants the protection-side mechanism added. It's also useful for someone running a senolytic protocol who wants daily SASP suppression between fisetin pulses, and for someone whose evening routine could use a mild GABAergic layer (typically combined with magnesium and glycine). It is reasonable as a long-term, continuous addition — there's no reason to cycle it.\u003c\/p\u003e\n\n\u003cp\u003eIt is less useful as a standalone product. Apigenin without a precursor will not raise NAD\u003csup\u003e+\u003c\/sup\u003e meaningfully; the substrate side still needs to be addressed. If you're new to longevity supplementation and choosing a single SKU, start with the precursor (NMN or NR) and add apigenin once the precursor is established.\u003c\/p\u003e\n\n\u003ch2\u003eWho should not take this\u003c\/h2\u003e\n\u003cp\u003eApigenin inhibits CYP3A4, CYP2C9, and several other liver enzymes that metabolize prescription drugs. If you take any of the following, talk to your physician before starting apigenin:\u003c\/p\u003e\n\u003cul\u003e\n\u003cli\u003eBlood thinners (warfarin, apixaban, rivaroxaban, dabigatran)\u003c\/li\u003e\n\u003cli\u003eStatins (atorvastatin, simvastatin, lovastatin in particular)\u003c\/li\u003e\n\u003cli\u003eCalcium channel blockers (amlodipine, diltiazem)\u003c\/li\u003e\n\u003cli\u003eImmunosuppressants (cyclosporine, tacrolimus)\u003c\/li\u003e\n\u003cli\u003eCertain antiarrhythmics, antifungals, and antiretrovirals\u003c\/li\u003e\n\u003cli\u003eAny medication labeled \"do not take with grapefruit\" — the interaction mechanism is similar (CYP3A4 inhibition)\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eApigenin has weak estrogenic activity in cell models. People with hormone-sensitive conditions (estrogen-receptor-positive breast cancer history, endometriosis) should consult their oncologist or gynecologist before use. Discontinue 2 weeks before any planned surgery (interaction with anesthetics is poorly studied; standard precaution).\u003c\/p\u003e\n\n\u003cp\u003eNot recommended during pregnancy or breastfeeding (insufficient safety data for supplemental doses) or for anyone under 18.\u003c\/p\u003e\n\n\u003cp\u003eChamomile-allergic individuals (Asteraceae\/Compositae family — also includes ragweed, daisies, marigolds) should avoid this product.\u003c\/p\u003e\n\n\u003ch2\u003eFrequently asked questions\u003c\/h2\u003e\n\n\u003cp\u003e\u003cstrong\u003eCan't I just drink chamomile tea?\u003c\/strong\u003e\u003cbr\u003e\nA strong cup of chamomile tea contains roughly 0.3–1 mg of apigenin. To get 50 mg from tea you would need to drink 50–150 cups daily. The supplement form delivers the dose used in research; tea delivers the calming effect of chamomile, which is real but driven by much lower apigenin levels acting on GABA\u003csub\u003eA\u003c\/sub\u003e receptors in the brain — the calming effect is dose-low, the CD38 effect needs dose-high.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eWhat's the difference between apigenin, fisetin, and quercetin?\u003c\/strong\u003e\u003cbr\u003e\nAll three are flavonoids and all three have some senolytic activity. The differences matter for what you're optimizing for. \u003cem\u003eApigenin\u003c\/em\u003e is the only one of the three with primary action on CD38, which is why it's the NAD\u003csup\u003e+\u003c\/sup\u003e-stack pairing. \u003ca href=\"\/products\/fisetin-500mg-senolytic-flavonoid-for-cellular-cleanup\"\u003e\u003cem\u003eFisetin\u003c\/em\u003e\u003c\/a\u003e is the most potent senolytic per milligram in the Yousefzadeh 2018 head-to-head and crosses into brain tissue best — choose it if cellular cleanup is your primary goal, typically dosed in monthly 2-day pulses. \u003ca href=\"\/products\/quercetin-500mg-senolytic-flavonoid-natural-antihistamine\"\u003e\u003cem\u003eQuercetin\u003c\/em\u003e\u003c\/a\u003e has the strongest human-trial evidence (it's the \"Q\" in the Mayo Clinic D+Q protocol), works synergistically with dasatinib, and adds antihistamine activity. Many users in advanced protocols take all three, each at its standard dose; the targets overlap only partially.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eWhy do I need apigenin if I'm already taking NMN?\u003c\/strong\u003e\u003cbr\u003e\nNMN raises NAD\u003csup\u003e+\u003c\/sup\u003e by feeding the production side of the cycle (the salvage pathway). Apigenin protects what NMN produces by slowing CD38, the enzyme that destroys NAD\u003csup\u003e+\u003c\/sup\u003e and whose activity rises with age. They're complementary, not redundant. The same logic applies to TMG: NMN production burns through methyl groups; TMG replaces them. NMN alone works. NMN with TMG and apigenin works longer, with less plateau at month two.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eHow long until I notice anything?\u003c\/strong\u003e\u003cbr\u003e\nApigenin's primary effects (CD38 inhibition, senolytic activity, SASP suppression) are biological — you would not feel them in the first week. The most commonly reported subjective effect is mild improvement in sleep quality and a calmer baseline within the first 1–3 weeks, which tracks with apigenin's known partial-agonist activity at GABA\u003csub\u003eA\u003c\/sub\u003e receptors. The longevity benefits accrue silently over months and are best measured at the bloodwork level (hsCRP for inflammation, NAD\u003csup\u003e+\u003c\/sup\u003e if your provider can run a blood NAD\u003csup\u003e+\u003c\/sup\u003e panel).\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eIs the BioPerine necessary?\u003c\/strong\u003e\u003cbr\u003e\nYes — and this is the single biggest difference between supplements in this category. Apigenin without an absorption enhancer is largely metabolized in the gut wall before it reaches circulation; published bioavailability is in the low single-digit percent range. The 5 mg of piperine (BioPerine) increases apigenin bioavailability several-fold by inhibiting the UGTs and CYP3A4 that would otherwise destroy it on the way in (Atal 1985, Bhardwaj 2002). A capsule without piperine costs less to manufacture and delivers a fraction of the dose to your blood.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eWhy not take 100 mg or 200 mg?\u003c\/strong\u003e\u003cbr\u003e\nThe published CD38-inhibition IC\u003csub\u003e50\u003c\/sub\u003e in the Escande 2013 mouse model is reached at the 50 mg + piperine + fat-meal protocol. Going higher hasn't been shown to give more CD38 inhibition once the IC\u003csub\u003e50\u003c\/sub\u003e is cleared. Some advanced longevity-clinic protocols use 100 mg (2 capsules) for users with measured low NAD\u003csup\u003e+\u003c\/sup\u003e or high-dose NMN — this is a reasonable upper bound, but more is not better past that point.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eCan I take apigenin with my evening dose if I want the sleep benefit?\u003c\/strong\u003e\u003cbr\u003e\nYes. The CD38 mechanism doesn't care what time of day you dose — it works on a steady-state basis, and apigenin's plasma half-life of ~90 minutes means you get the same daily AUC whether you take it at 8 AM or 8 PM. If sleep is your priority, evening dosing with dinner gives you the GABAergic effect close to bedtime.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eDoes apigenin compete with sirtuin activation?\u003c\/strong\u003e\u003cbr\u003e\nNo — and this confuses some people. Sirtuins (SIRT1\/3\/6 in particular) \u003cem\u003econsume\u003c\/em\u003e NAD\u003csup\u003e+\u003c\/sup\u003e; that's the whole point of feeding them with a precursor. Apigenin slows CD38, which is a different NAD\u003csup\u003e+\u003c\/sup\u003e-consuming enzyme. CD38 is wasteful (its NAD\u003csup\u003e+\u003c\/sup\u003e consumption doesn't do useful biological work for longevity-relevant tissues at age 60+); sirtuins are productive (they catalyze deacetylation and other useful reactions). Apigenin slows the wasteful consumer; resveratrol activates the productive ones. They're complementary.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eWill apigenin make me drowsy during the day?\u003c\/strong\u003e\u003cbr\u003e\nAt a 50 mg morning dose, no — the GABAergic effect is mild and is much more noticeable when the apigenin dose lands closer to a normal sleep window. If you're sensitive to sedatives generally, start at half a capsule for a few days. If you find any morning grogginess, switch to evening dosing.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eCan I open the capsule and take the powder?\u003c\/strong\u003e\u003cbr\u003e\nYou can, but apigenin is bitter and has poor solubility in water. Most users prefer to swallow the capsule with water or a small amount of fat-containing food.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eHow does apigenin compare to the Sinclair-recommended dose?\u003c\/strong\u003e\u003cbr\u003e\nDr. David Sinclair has discussed taking apigenin daily as part of his personal longevity protocol; he hasn't published a specific dose. The 50 mg + piperine + fat-meal protocol is the dose-equivalent that the underlying CD38-inhibition pharmacology supports for daily use, and it's consistent with what longevity-clinic practitioners report using.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eIs there a published human RCT showing apigenin raises NAD\u003csup\u003e+\u003c\/sup\u003e?\u003c\/strong\u003e\u003cbr\u003e\nNot yet at the human-RCT level for the CD38 → NAD\u003csup\u003e+\u003c\/sup\u003e endpoint specifically. The mechanistic evidence (CD38 IC\u003csub\u003e50\u003c\/sub\u003e in Escande 2013, NAD\u003csup\u003e+\u003c\/sup\u003e rise in obese-mouse tissue, SASP suppression in pre-adipocyte models) is solid, and the human safety profile from chamomile-extract studies is reassuring, but a placebo-controlled human NAD\u003csup\u003e+\u003c\/sup\u003e-rise trial for apigenin alone has not been published as of this writing. Most clinicians who use apigenin in protocols are extrapolating from the mechanism-of-action plus the broader CD38-inhibitor literature (including the 78c animal work) rather than from a head-to-head human trial.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eCan I cycle apigenin or do I need to take it daily?\u003c\/strong\u003e\u003cbr\u003e\nCD38 is constitutively active — its consumption of NAD\u003csup\u003e+\u003c\/sup\u003e happens around the clock. The inhibition needs to be continuous to be useful. There's no published rationale for cycling, and the safety data on chronic apigenin intake from chamomile tea (people drink it daily for decades) is reassuring. Daily continuous use is the standard.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eWhat about apigenin and thyroid?\u003c\/strong\u003e\u003cbr\u003e\nApigenin has been studied for weak inhibitory effects on thyroid peroxidase in cell models (Schmutzler et al. 2007). At supplemental doses this effect is unlikely to be clinically meaningful in someone with normal thyroid function. People with hypothyroidism on levothyroxine should mention apigenin to their endocrinologist; people with hyperthyroidism may consult their physician about whether apigenin's mild thyroid-modulating activity is desirable in their context.\u003c\/p\u003e\n\n\u003ch2\u003eThe science (selected references)\u003c\/h2\u003e\n\u003cp\u003eCamacho-Pereira J et al. \u003cem\u003eCD38 dictates age-related NAD decline and mitochondrial dysfunction through an SIRT3-dependent mechanism.\u003c\/em\u003e Cell Metab. 2016 Jun 14;23(6):1127-1139. — The age\/CD38\/NAD\u003csup\u003e+\u003c\/sup\u003e mechanism paper.\u003c\/p\u003e\n\n\u003cp\u003eTarragó MG et al. \u003cem\u003eA potent and specific CD38 inhibitor ameliorates age-related metabolic dysfunction by reversing tissue NAD+ decline.\u003c\/em\u003e Cell Metab. 2018 May 1;27(5):1081-1095.e10. — The 78c\/CD38-inhibition-without-precursor proof of concept.\u003c\/p\u003e\n\n\u003cp\u003eChini CCS et al. \u003cem\u003eThe pharmacology of CD38\/NADase: an emerging target in cancer and diseases of aging.\u003c\/em\u003e Trends Pharmacol Sci. 2020. — The Mayo Clinic group's CD38 review.\u003c\/p\u003e\n\n\u003cp\u003eEscande C et al. \u003cem\u003eFlavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome.\u003c\/em\u003e Diabetes. 2013 Apr;62(4):1084-93. — The apigenin\/CD38 IC\u003csub\u003e50\u003c\/sub\u003e paper and obese-mouse NAD\u003csup\u003e+\u003c\/sup\u003e-rise demonstration.\u003c\/p\u003e\n\n\u003cp\u003eYousefzadeh MJ et al. \u003cem\u003eFisetin is a senotherapeutic that extends health and lifespan.\u003c\/em\u003e EBioMedicine. 2018 Oct;36:18-28. — The flavonoid head-to-head senolytic screen.\u003c\/p\u003e\n\n\u003cp\u003ePerrott KM et al. \u003cem\u003eApigenin suppresses the senescence-associated secretory phenotype and paracrine effects on breast cancer cells.\u003c\/em\u003e GeroScience. 2017 Apr;39(2):161-173. — SASP suppression paper.\u003c\/p\u003e\n\n\u003cp\u003eMassudi H et al. \u003cem\u003eAge-associated changes in oxidative stress and NAD+ metabolism in human tissue.\u003c\/em\u003e PLoS ONE. 2012;7(7):e42357. — The ~50% NAD\u003csup\u003e+\u003c\/sup\u003e-decline curve.\u003c\/p\u003e\n\n\u003cp\u003eSalgueiro JB et al. \u003cem\u003eAnxiolytic natural and synthetic flavonoid ligands of the central benzodiazepine receptor have no effect on memory tasks in rats.\u003c\/em\u003e Pharmacol Biochem Behav. 1997. — The GABA\u003csub\u003eA\u003c\/sub\u003e receptor pharmacology.\u003c\/p\u003e\n\n\u003cp\u003eAvallone R et al. \u003cem\u003ePharmacological profile of apigenin, a flavonoid isolated from Matricaria chamomilla.\u003c\/em\u003e Biochem Pharmacol. 2000 Jun 1;59(11):1387-94. — Chamomile-derived apigenin sleep\/calming pharmacology.\u003c\/p\u003e\n\n\u003cp\u003eAtal CK et al. \u003cem\u003eBiochemical basis of enhanced drug bioavailability by piperine: evidence that piperine is a potent inhibitor of drug metabolism.\u003c\/em\u003e J Pharmacol Exp Ther. 1985 Jan;232(1):258-62. — The foundational piperine bioenhancer paper.\u003c\/p\u003e\n\n\u003cp\u003eBhardwaj RK et al. \u003cem\u003ePiperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4.\u003c\/em\u003e J Pharmacol Exp Ther. 2002 Aug;302(2):645-50. — The piperine\/CYP3A4 mechanism for first-pass-metabolism inhibition.\u003c\/p\u003e\n\n\u003cp\u003eGradolatto A et al. \u003cem\u003ePharmacokinetics and metabolism of apigenin in female and male rats after a single oral administration.\u003c\/em\u003e Drug Metab Dispos. 2005 Jan;33(1):49-54. — Apigenin plasma half-life and conjugation pharmacology.\u003c\/p\u003e\n\n\u003cp\u003eImran M et al. \u003cem\u003eApigenin as an anticancer agent.\u003c\/em\u003e Food Chem. 2020 Apr 25;308:125605. — Comprehensive apigenin pharmacology review including bioavailability.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eFDA disclaimer:\u003c\/strong\u003e These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. Consult a healthcare professional before starting any new supplement, especially if you take prescription medication or have a medical condition.\u003c\/p\u003e\n","brand":"True Health Protocol","offers":[{"title":"Default Title","offer_id":47839318507738,"sku":"THP-APIGENIN-50-60","price":27.99,"currency_code":"USD","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0814\/5158\/1658\/files\/thp_apigenin.png?v=1778047674","url":"https:\/\/truehealthprotocol.health\/products\/apigenin-50mg-cd38-inhibitor-for-nmn-nad-stacks","provider":"True Health Protocol","version":"1.0","type":"link"}