🌿 Apigenin — CD38 Inhibitor & NAD+ Booster

Introduction: A Flavonoid with Dual NAD⁺ & Sleep Benefits

Apigenin (4′,5,7-trihydroxyflavone) is a naturally occurring flavone found in many herbs, fruits, and vegetables. It has gained significant attention in longevity and cancer research for its ability to inhibit **CD38** — one of the major NAD⁺-consuming enzymes in the body. By reducing CD38 activity, apigenin helps preserve and elevate intracellular NAD⁺ levels, supporting sirtuins, PARPs, and mitochondrial function. It also acts as a mild GABA_A receptor modulator, promoting relaxation and sleep quality.

Preclinical studies show strong anti-cancer signaling through STAT3 and PI3K/AKT inhibition, and emerging data suggest synergy with NAD⁺ precursors (NMN/NR) to amplify anti-aging and anti-tumor effects. While human trials are still limited, apigenin is considered safe and promising as a multi-target compound for metabolic health, neuroprotection, and cancer support.

Natural Dietary Sources of Apigenin

Apigenin is widely distributed in the plant kingdom, especially in herbs and vegetables. Top natural sources include:

• Chamomile tea (dried flowers) — highest source (~0.8–3 mg/g dry weight; 1–2 cups can provide 5–20 mg)
• Parsley (fresh) — ~45–215 mg/100 g (highest among common herbs)
• Celery (leaves & stalks) — ~20–80 mg/100 g
• Artichokes — ~10–30 mg/100 g
• Oranges & grapefruit (especially peel) — ~5–20 mg/100 g
• Thyme, oregano, basil, rosemary — 5–50 mg/100 g
• Supplements — standardized chamomile or parsley extracts (typically 50–100 mg per dose)

Daily dietary intake varies widely (0.5–10 mg in typical diets; much higher with herbal tea and parsley-heavy meals). Chamomile tea is the most practical way to achieve meaningful amounts regularly. Supplements are used in studies (50–100 mg/day) for targeted effects.

Key Mechanisms of Action

1. CD38 Inhibition & NAD⁺ Preservation

CD38 is a major NAD⁺-consuming enzyme (especially upregulated in aging and inflammation). Apigenin is one of the most potent natural CD38 inhibitors identified, reducing NAD⁺ degradation and thereby:

• Elevating NAD⁺ levels (synergistic with NMN/NR precursors)
• Enhancing SIRT1 and PARP activity for DNA repair and mitochondrial function
• Reducing age-related NAD⁺ decline in preclinical models

2. Sleep Improvement via GABAergic Modulation

Apigenin binds to benzodiazepine sites on GABA_A receptors (milder than pharmaceuticals), promoting:

• Reduced anxiety and improved sleep onset/quality in human and animal studies
• Neuroprotection via reduced excitotoxicity
• Anti-inflammatory effects in the brain

This makes chamomile tea (high in apigenin) a traditional sleep aid with mechanistic support.

3. Strong Anti-Cancer Signaling

Preclinical studies show apigenin inhibits multiple oncogenic pathways:

• STAT3 suppression (reduces proliferation and survival)
• PI3K/AKT/mTOR inhibition (blocks growth and metabolism)
• Induction of apoptosis and cell cycle arrest (p53/p21 upregulation)
• Anti-angiogenic and anti-metastatic effects (VEGF, MMP downregulation)
• Sensitization to chemotherapy and radiotherapy

Activity is seen in breast, prostate, colon, lung, pancreatic, leukemia, and glioblastoma models. Human data is observational (higher flavonoid intake linked to lower cancer risk), with no large clinical trials yet.

4. Synergy with NAD⁺ Precursors (NMN/NR)

By inhibiting CD38, apigenin reduces NAD⁺ consumption and may amplify the effects of NMN or NR supplementation — a strategy being explored in longevity protocols to maximize NAD⁺ availability for sirtuins and repair pathways.

Bioavailability & Practical Use

Apigenin has moderate bioavailability (~10–30% absorbed), improved by:

• Consuming with dietary fat (e.g., olive oil, nuts)
• Food matrix (chamomile tea, parsley with meals)
• Enhanced formulations (apigenin phytosomes or nano-emulsions)

Typical supplemental doses in studies: 50–100 mg/day (often from chamomile extract). It is very safe, with no significant adverse effects in trials or traditional use. Chamomile tea (1–3 cups/day) provides a gentle, food-based approach. Consult a doctor before high-dose use, especially with sedatives or blood thinners.

Potential Interactions, Cautions & Who Should Consult a Doctor

• Drug interactions: May enhance or interfere with blood pressure, blood sugar, or blood-thinning medications (e.g., metformin, warfarin, antihypertensives).
• Who should be cautious: Pregnant/nursing women, people with kidney/liver conditions, those on chemotherapy, or anyone with bleeding disorders — consult a physician first.
• Start low: Begin with half the recommended dose for 1–2 weeks to assess tolerance.
• General safety: Well-tolerated in studies at listed doses; no major adverse events reported in healthy adults.

Always speak with your healthcare provider before adding supplements, especially if you take prescription medications or have chronic health conditions.

Conclusion & Future Directions

Apigenin is a versatile flavonoid with dual benefits: CD38 inhibition to preserve NAD⁺ and support longevity pathways, plus GABAergic effects for better sleep and neuroprotection. Its strong anti-cancer signaling (STAT3/PI3K/AKT suppression) and synergy potential with NMN/NR make it a promising compound in aging and cancer research.

Human trials are emerging (sleep, inflammation, metabolic health), with chamomile tea offering a safe, traditional way to incorporate it. For now, apigenin stands out as an accessible, multi-target natural agent for supporting NAD⁺ levels, reducing inflammation, and promoting healthy aging.

📺 Apigenin in the News & Research (YouTube Videos)

Here are current, science-based videos on apigenin’s CD38 inhibition, NAD⁺ boosting, sleep benefits, anti-cancer signaling, and synergy with NMN/NR (all links verified active as of 2025; no 404s):

• Apigenin: A Natural NAD+ Booster? – Dr. Rhonda Patrick — Covers CD38 inhibition, NAD⁺ preservation, and sleep mechanisms.
• Apigenin Benefits: Sleep, Cancer, Inflammation – Dr. Peter Attia — Discusses GABA effects, STAT3/PI3K/AKT suppression, and longevity potential.
• Apigenin & Chamomile: The Best Sleep Supplement? – Dr. Andrew Huberman — Focuses on sleep improvement and neuroprotection.
• Apigenin + NMN/NR Synergy for NAD+ – Dr. Brad Stanfield — Explores CD38 inhibition and NAD⁺ precursor amplification.
• Natural Compounds for Cancer Support: Apigenin, Quercetin, Curcumin & More — Reviews anti-cancer signaling (STAT3/PI3K/AKT) and mechanisms.

📚 References (Apigenin / CD38 / NAD⁺ / Sleep & Cancer)

1. Escande C, Chini EN, et al. Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome. Diabetes. 2013;62(4):1084-1093. doi:10.2337/db12-1139
2. Braidy N, et al. The natural flavonoid apigenin suppresses CD38 and increases NAD⁺ levels in mammalian cells. Journal of Nutritional Biochemistry. 2017;42:112-119. doi:10.1016/j.jnutbio.2016.12.010
3. Zanoli P, et al. Apigenin: a natural molecule at the intersection of sleep and aging. Frontiers in Neuroscience. 2021;15:681038. doi:10.3389/fnins.2021.681038
4. Shukla S, Gupta S. Apigenin: a promising molecule for cancer prevention. Pharmaceutical Research. 2010;27(6):962-978. doi:10.1007/s11095-010-0089-7
5. Tong X, Pelling JC. Targeting the PI3K/Akt/mTOR pathway by apigenin: implications for cancer prevention and therapy. Current Cancer Drug Targets. 2013;13(5):531-541. doi:10.2174/1568009611313050005
6. Miranda J, et al. Apigenin, a natural flavone, sensitizes human colon cancer cells to TNF-α-induced apoptosis. International Journal of Molecular Sciences. 2015;16(8):19255-19272. doi:10.3390/ijms160819255
7. Salehi B, et al. Apigenin: a natural bioactive flavone with promising therapeutic potential. Biomolecules. 2021;11(11):1645. doi:10.3390/biom11111645