Apigenin: CD38 inhibition, NAD+ preservation and aging

Quick answer

Apigenin is a plant flavonoid found in parsley, chamomile, celery, and related foods. In cell and animal studies, apigenin inhibits CD38, an enzyme that consumes NAD+, and this may help preserve cellular NAD+ signaling. The longevity case is mechanistically interesting, but human trials have not yet shown that apigenin supplements raise NAD+, slow biological aging, or extend lifespan.

Key facts

Apigenin | is | a dietary flavone concentrated in parsley, chamomile, celery, and several herbs.
CD38 | consumes | NAD+, and CD38 activity is one proposed contributor to age-related NAD+ decline.
Apigenin | inhibits | CD38 in preclinical models, but human NAD+ supplementation trials for apigenin are still missing.
Food-first use | is | the lowest-risk approach, while supplement doses should be treated cautiously because long-term human data are limited.

For most of its existence, apigenin was a footnote. A pale-yellow flavonoid found in parsley, chamomile tea, celery, and artichokes, it was known primarily to food scientists studying plant pigments and to researchers who periodically noted its mild anti-anxiety effects in animal studies. In 2013, a team including Eduardo Chini published a paper in Diabetes showing that apigenin could inhibit an enzyme called CD38 in cells and mice. That mattered because later work linked CD38 activity to age-related NAD+ decline - a molecule involved in mitochondrial function, DNA repair, and inflammatory signaling.

Apigenin wasn’t invented as a longevity compound. It was rediscovered when researchers were looking for ways to preserve NAD+ without injecting pharmaceuticals. The fact that it is already present in common foods makes it particularly interesting, but food exposure and concentrated supplement use are not the same thing.

But the gap between “interesting in cell studies” and “proven in humans” is enormous. Here’s the honest state of the evidence.

What you’ll learn:

What CD38 is and why it may contribute to NAD+ decline with age
How apigenin inhibits CD38 and the evidence base behind it
Which foods contain meaningful apigenin, and whether supplements are necessary
The gap between preclinical promise and clinical reality

What is apigenin?

Apigenin (4′,5,7-trihydroxyflavone) is a flavone — a subclass of flavonoid compounds found widely in plants. It’s particularly concentrated in parsley, chamomile, celery, artichokes, and some herbs. In plants, apigenin contributes to pigmentation and helps defend against UV damage.

Quick definition: Apigenin is a plant flavonoid found in parsley, chamomile, and celery. In preclinical studies, it inhibits the CD38 enzyme and can help preserve cellular NAD+ levels, but direct human evidence for NAD+ or longevity benefits remains limited.

NAD+: why it matters for aging

Nicotinamide adenine dinucleotide (NAD+) is a coenzyme present in every living cell. It’s essential for:

Mitochondrial energy production (the TCA cycle and electron transport chain)
DNA repair (via PARP enzymes)
Sirtuin activity (SIRT1-7), which regulates gene expression, inflammation, and metabolism
Calcium signaling

NAD+ levels decline substantially with age in many tissues, although the size of the decline varies by tissue, species, disease state, and measurement method. This decline is linked to mitochondrial dysfunction, impaired DNA repair, reduced sirtuin activity, and increased inflammation. Addressing NAD+ decline has become one of the most active areas of longevity research.

The CD38 connection

CD38 is an enzyme present on many immune cells. One of its jobs is to degrade NAD+. As we age, CD38 levels rise substantially — largely because chronic low-grade inflammation recruits more CD38-expressing immune cells into tissues. The result is that older cells have more NAD+-destroying capacity just as their ability to synthesize NAD+ is declining.

CD38 is considered one contributor to age-related NAD+ depletion. Inhibiting CD38 is a coherent theoretical strategy to preserve NAD+ - and apigenin is one of the natural CD38 inhibitors identified in preclinical screening studies.

The science behind apigenin

Mechanisms

CD38 inhibition: apigenin inhibits CD38 with relatively low IC50 in preclinical assays, making it one of the more interesting natural inhibitors identified in screening studies.
NAD+ preservation: in cell and animal studies, apigenin can raise cellular or tissue NAD+ levels, consistent with reduced NAD+ degradation.
Anti-inflammatory effects: apigenin inhibits NF-κB signaling and reduces pro-inflammatory cytokines, addressing inflammaging — a mechanism it shares with other flavonoids like quercetin and polyphenols such as resveratrol.
Antioxidant activity: scavenges reactive oxygen species and upregulates endogenous antioxidant defenses.
GABAergic effects: apigenin binds to GABA-A receptor benzodiazepine sites, explaining its mild anti-anxiety and sedative effects (this is why chamomile tea is calming).
Cell cycle and apoptosis: in cancer cell studies, apigenin induces apoptosis in transformed cells while sparing healthy cells — though this is preclinical.

What the evidence actually shows

Preclinical (cells and mice): apigenin can raise NAD+, improve metabolic readouts, reduce inflammatory signaling, and show anti-cancer activity in model systems. These results are promising, but they do not prove human longevity benefit.
Human clinical trials on aging endpoints: essentially absent. As of 2026, no published randomized trial has tested apigenin supplementation specifically for NAD+ levels, biological age, or longevity endpoints in humans.
Human trials on related endpoints: small studies on chamomile (which contains apigenin) have shown modest effects on anxiety, sleep, and inflammatory markers, but chamomile contains many other compounds.
Safety: apigenin-containing foods are generally low-risk for most people. Concentrated supplements have far less long-term safety evidence and may interact with medications.

The honest summary: apigenin is a biologically plausible, mechanistically interesting longevity compound with strong preclinical data and essentially no human aging trials yet. Anyone claiming otherwise is selling something.

Apigenin and biological aging

If NAD+ preservation meaningfully affects aging biology, then interventions that slow its decline could influence multiple hallmarks of aging:

Mitochondrial function: NAD+ is essential for the TCA cycle; preserving it supports energy production.
DNA repair: PARP enzymes consume NAD+ to fix DNA damage — more NAD+ means more repair capacity.
Sirtuin activity: sirtuins are NAD+-dependent and regulate stress response, metabolism, and inflammation.
Chronic inflammation: apigenin may reduce inflammatory signaling in preclinical models, adding a second possible mechanism beyond NAD+ preservation.

Apigenin’s proposed dual action — NAD+ preservation via CD38 inhibition plus independent anti-inflammatory effects — makes it theoretically attractive. But theoretical attraction and measurable benefit are very different things.

6 ways to approach apigenin

1. Start with food, not capsules

Meaningful apigenin intake may be achievable through diet, though food composition varies widely by cultivar, processing, and preparation:

Food	Apigenin content
Dried parsley	~45 mg/g
Fresh parsley	~215 mg per 100 g
Dried chamomile flowers	~3-5 mg/g
Celery	~3-5 mg per 100 g
Artichokes	~7-8 mg per 100 g

Chamomile tea plus culinary parsley can provide apigenin without supplements, but the absorbed amount is variable.

2. Consider bioavailability carefully

Oral apigenin bioavailability appears low and variable because of poor water solubility, intestinal metabolism, and conversion by gut microbes. Liposomal formulations, phospholipid complexes, and other delivery systems may improve absorption, but clinical data comparing forms is limited.

3. If supplementing, start low

Typical supplement doses range from 50 to 500 mg/day. Some longevity protocols use 50-100 mg/day as a conservative starting point, but these protocols are not validated for NAD+ preservation in humans. Higher doses are not clearly more effective and should not be assumed safer.

4. Don’t expect acute effects

Apigenin’s longevity-related effects are mechanistic and gradual. Unlike sleep or anxiety effects from chamomile, which can be felt within hours, any impact on NAD+ levels or inflammation is likely to be slow and subtle.

5. Pair with NAD+ precursor strategies if desired

Some protocols combine proposed CD38 inhibition (apigenin) with NAD+ precursor supplementation (NMN or NR). The logic is complementary: precursors aim to raise synthesis, while CD38 inhibitors aim to slow degradation. This is speculative but mechanistically coherent.

6. Watch for drug interactions

Apigenin can:

Enhance sedative effects of medications (it binds benzodiazepine sites on GABA receptors)
Inhibit CYP450 enzymes in the liver, potentially altering drug metabolism
Have mild estrogenic effects at high doses

Caution with sedatives, blood thinners, and hormone-sensitive conditions.

The information provided does not replace professional medical advice. Consult your healthcare provider before starting any supplementation.

How to track anti-inflammatory and metabolic markers

Because apigenin’s main claims are around NAD+, inflammation, and metabolism, consider tracking:

Metric	How to measure	Target direction
hs-CRP	Blood test	Lower (under 1.0 mg/L)
Fasting glucose and HbA1c	Blood test	Stable or lower
Sleep quality	Wearable (deep sleep %, HRV)	Improving
Perceived stress and anxiety	Validated scale	Lower
Biological age	PhenoAge or SuperAge	Stable or lower

Direct NAD+ measurement is becoming available but is expensive and clinically unvalidated for dietary intervention monitoring.

How SuperAge helps with NAD+ era interventions

NAD+ precursors, CD38 inhibitors, and sirtuin activators all claim to affect biological aging. The question is always: can you actually see it in your body? SuperAge provides measurable benchmarks:

Biological age trajectory

By integrating multiple Apple Health data streams into a single biological age estimate updated continuously, SuperAge lets you see whether interventions are correlating with real physiological change — not just marketing promises.

HRV, RHR, and sleep architecture

Three of the most sensitive markers of autonomic and inflammatory state. If apigenin (or any NAD+ intervention) is doing something meaningful, these markers are among the first to move.

Trends, not snapshots

Single-day measurements are noisy. SuperAge’s focus on multi-week trends filters out noise and shows the signal.

Frequently asked questions

Does apigenin really raise NAD+ in humans?

In cell and animal studies, yes. In humans, there is currently no published trial directly measuring NAD+ changes with oral apigenin supplementation. The human evidence is indirect.

How much chamomile tea do I need?

A cup of well-steeped chamomile tea may contain 1-10 mg of apigenin depending on preparation. Several cups per day could approach low-end supplement doses, though absorption from tea is variable.

Is apigenin as good as NMN or NR?

These are different strategies. NMN/NR provide NAD+ precursors; apigenin may slow NAD+ degradation. They address different sides of the NAD+ equation and may be complementary, though human head-to-head data is lacking.

Can apigenin help with anxiety or sleep?

Possibly. Chamomile has modest clinical evidence for sleep quality and anxiety-related outcomes, and apigenin may contribute through GABA-A receptor activity. But chamomile contains many compounds, so the human effect cannot be attributed to apigenin alone.

Is it safe to take long-term?

Apigenin has a long history of dietary consumption, but supplement-level doses over years have not been studied rigorously. Conservative dosing, medication checks, and periodic reassessment are reasonable.

Key takeaways

Apigenin inhibits CD38 in preclinical models, which may help preserve cellular NAD+ — a molecule central to mitochondrial function and aging.
Evidence is promising in cells and animals but clinical trials in humans on longevity endpoints are absent.
Food sources matter: parsley, chamomile, celery, and artichokes provide meaningful apigenin without supplements.
Bioavailability is limited, and supplement formulations vary.
It’s one lever, not the whole story: exercise, sleep, and diet remain the dominant drivers of NAD+ and biological age.

Start tracking your aging trajectory today

Supplement trends come and go. What matters is whether your actual physiology is moving in a healthier direction.

Ready to take control? Download SuperAge and start tracking your biological age while you experiment with interventions like apigenin.

References

Escande C. 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.
Camacho-Pereira J. et al. — CD38 dictates age-related NAD decline and mitochondrial dysfunction through an SIRT3-dependent mechanism. Cell Metabolism, 2016.
Chini C. C. S. et al. — The pharmacology of CD38/NADase: an emerging target in cancer and diseases of aging. Trends in Pharmacological Sciences, 2018.
Covarrubias A. J. et al. — NAD+ metabolism and its roles in cellular processes during aging. Nature Reviews Molecular Cell Biology, 2021.
Salehi B. et al. — The therapeutic potential of apigenin. International Journal of Molecular Sciences, 2019.
Kazemi A. et al. — Effects of chamomile on sleep: a systematic review and meta-analysis of clinical trials. Complementary Therapies in Medicine, 2024.

Last updated: 2026-06-06. This article is regularly reviewed to ensure accuracy.