DHEA (Dehydroepiandrosterone) vs NR (Nicotinamide Riboside)

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

NR is converted to NMN by nicotinamide riboside kinases (NRK1/NRK2), then to NAD+ via the salvage pathway. Like NMN, elevated NAD+ activates sirtuins, PARPs, and CD38. NR has demonstrated ability to cross the blood-brain barrier and elevate brain NAD+ levels. It supports mitochondrial function, DNA repair, and circadian rhythm regulation through SIRT1-mediated deacetylation of BMAL1 and CLOCK proteins.

Standard Dosing

300-600mg daily

Timing

Morning with or without food.

Cycle Duration

ongoing

Side Effects

• Mild nausea
• Warmth/flushing (mild)
• GI upset
• Fatigue in some during initial days

Contraindications

• Active cancer (same theoretical NAD+ concern as NMN)
• Pregnancy/lactation
• Theoretical cancer concern shared with NMN

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