DHEA (Dehydroepiandrosterone) vs NMN (Nicotinamide Mononucleotide)

Mechanism

DHEA is the most abundant circulating steroid hormone, produced primarily by the adrenal zona reticularis. It serves as a precursor for both androgens (testosterone, DHT via 3beta-HSD and 17beta-HSD) and estrogens (estradiol, estrone via aromatase). DHEA-S (sulfated form) acts as a neurosteroid, positively modulating NMDA receptors and antagonizing GABA-A receptors (cognitive enhancement/alertness). It also modulates immune function (enhances Th1 immunity, IL-2 production), supports bone mineral density via estrogenic metabolites, enhances insulin sensitivity via PPAR-alpha activation, and opposes cortisol's catabolic effects (DHEA:cortisol ratio is a stress/aging biomarker).

Standard Dosing

25-50mg daily (men); 10-25mg daily (women)

Timing

Morning (mimics natural circadian peak). With food.

Cycle Duration

Ongoing under supervision with regular blood monitoring (DHEA-S, testosterone, estradiol, PSA in men)

Side Effects

• Acne (androgenic)
• Hair loss (androgenic)
• Hirsutism in women
• Mood changes (irritability, aggression)
• Deepening of voice in women (at high doses)
• Insomnia
• Oily skin

Contraindications

• Hormone-sensitive cancers (prostate, breast, ovarian)
• PCOS (may worsen androgen excess)
• Endometriosis
• Uterine fibroids
• Children/adolescents

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Mechanism

NMN is a direct biosynthetic precursor to NAD+ via the salvage pathway enzyme nicotinamide phosphoribosyltransferase (NAMPT). Elevated NAD+ activates sirtuins (SIRT1-7), PARP DNA repair enzymes, and CD38/CD157 signaling. SIRT1 activation deacetylates PGC-1alpha (mitochondrial biogenesis), FOXO transcription factors (stress resistance), and NF-kB (anti-inflammatory). NMN also enters cells via the Slc12a8 transporter, recently identified in the gut.

Standard Dosing

500-1000mg daily

Timing

Morning on empty stomach. Sublingual absorption bypasses first-pass metabolism.

Cycle Duration

ongoing

Side Effects

• Mild GI discomfort
• Flushing (rare, unlike niacin)
• Mild headache during initial use

Contraindications

• Active cancer (theoretical concern: NAD+ may fuel rapidly dividing cells)
• Pregnancy/lactation (insufficient data)
• Theoretical concern in active cancer (NAD+ fuels all rapidly dividing cells)

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