DHEA (Dehydroepiandrosterone)

Overview

Dehydroepiandrosterone (DHEA) is a steroid hormone produced primarily in the adrenal cortex (and in smaller amounts by the gonads and brain). It functions as a “pro‑hormone,” serving as a biochemical precursor that can be converted into the major sex hormones—testosterone, dihydrotestosterone (DHT), estradiol, and estrone—thereby influencing many physiological systems.

Benefits

Cognitive function: Randomized trials in older adults show modest improvements in episodic memory and mental‑speed tasks when 25–50 mg/day is administered for ≥12 weeks.
Muscle & strength: In combination with resistance training, DHEA (30–50 mg/day) modestly increases lean body mass and hand‑grip strength in older men and women, though effects are modest and dose‑dependent.
Bone health: Meta‑analyses reveal that 50 mg/day for 12–24 months can modestly increase lumbar spine BMD in post‑menopausal women, likely via conversion to estrogen.
Metabolic regulation: Small‑to‑moderate doses (25–100 mg/day) improve insulin sensitivity and reduce fasting glucose in subjects with mild insulin resistance, as demonstrated in several crossover studies.
Mood & wellbeing: DHEA supplementation (25–50 mg/day) reduces depressive scores in individuals with major depressive disorder or adrenal insufficiency, likely through neuro‑steroid modulation of GABA and NMDA receptors.
Immune & anti‑oxidant: Laboratory studies show DHEA attenuates NF‑κB‑mediated inflammation, and clinical data suggest modest reductions in IL‑6 and CRP in aging cohorts.

How It Works

Process: DHEA enters cells by passive diffusion and is then converted by specific enzymes (e.g., 3β‑hydroxysteroid dehydrogenase, 17β‑hydroxysteroid dehydrogenase) into downstream androgens (androstenedione, testosterone) and estrogens (estrone, estradiol).
Pathway: These downstream hormones bind classical nuclear receptors— androgen receptors (AR) and estrogen receptors (ERα/β)—modulating gene transcription that drives anabolic and metabolic effects. In the brain, DHEA and its sulfated form (DHEA‑S) act as neuro‑steroids: they modulate GABA_A, NMDA, and σ‑1 receptors, promoting neuro‑protective signaling and influencing mood and cognition. DHEA also interacts with the nuclear receptor PPAR‑α/γ and inhibits the NF‑κB pathway, reducing pro‑inflammatory cytokine production. Through these pathways, DHEA can influence muscle protein synthesis, bone remodeling, glucose homeostasis, and neuro-plasticity.

Dosage

General adult supplementation: 25–50 mg oral DHEA once daily is most common for healthy adults seeking modest anti‑aging or mood benefits.
Age‑related bone loss or sarcopenia: 50 mg/day (often divided into 25 mg twice daily) for 6–12 months has been used in trials.
Cognitive/ mood support: 25–40 mg/day taken in the morning to mimic the natural circadian peak; some studies use 100 mg/day for severe adrenal insufficiency under physician supervision.
Special cases: In women with menopausal symptoms, 30 mg/day is commonly used; in men aiming to preserve muscle mass, 50 mg/day combined with resistance training is standard.
Timing: Because endogenous DHEA peaks in the early morning, taking the supplement early (e.g., 7–9 a.m.) aligns with physiologic rhythms and may reduce insomnia risk.
Adjustments: Renal or hepatic impairment may require a 50 % dose reduction; elderly (> 70 y) often start at 10–25 mg to assess tolerance.

Safety & Side Effects

Common adverse effects: Acne, oily skin, and mild hirsutism (especially in women) due to androgen conversion.
Hormone‑sensitive conditions: Breast, uterine, ovarian, or prostate cancer patients should avoid DHEA because it can increase circulating estrogen/testosterone.
Pregnancy & lactation: Contraindicated; animal data and limited human data suggest potential teratogenicity.
Drug interactions: May potentiate anticoagulants (warfarin, DOACs) by altering platelet function; can reduce efficacy of insulin or oral hypoglycemics; may interact with hormone‑based therapies (e.g., oral contraceptives, hormone replacement) by altering endocrine feedback.
Metabolic concerns: High doses (> 200 mg/day) have been linked to increased LDL‑C and decreased HDL‑C in some cohorts.
Other contraindications: Active liver disease, uncontrolled hypertension, and severe psychiatric disorders (e.g., bipolar mania) are cautions. Monitoring of serum testosterone, estradiol, and lipid panel is advised after 3–6 months of use.

Chemistry

IUPAC name: 3β‑Hydroxyandrost‑5‑en‑17‑one.
Molecular formula: C₁₉H₂₈O₂; molecular weight = 286.38 g mol⁻¹.
Structure: A 19‑carbon steroid backbone (cyclopentanoperhydrophenanthrene) with a β‑hydroxyl at C‑3 and a double bond between C‑5 and C‑6 (Δ⁵‑3β‑hydroxyandrost-5-en-17-one). It is a lipophilic, weakly androgenic molecule with a logP ≈ 3.1, allowing good oral absorption. The sulfated form (DHEA‑S) contains a phosphate‑like sulfate group at C‑3, increasing water solubility and serving as a circulating reservoir. DHEA is stable at pH 5–8, but degrades under high temperature or UV light, necessitating protective packaging (e.g., amber glass) for supplements.

Sources & Quality

Natural source: Endogenously produced in the human adrenal cortex; plasma levels decline 40–80 % from ages 20 to 80 y.
Commercial production: Primarily synthesized from plant‑derived sterols (e.g., diosgenin from Mexican yam Dioscorea spp.) using a series of oxidation, reduction, and de‑hydrogenation steps yielding high‑purity DHEA (≥ 98 % by HPLC).
Extraction: Limited commercial extraction from animal adrenal glands is prohibited in many jurisdictions; most pharmaceutical‑grade DHEA is chemically synthesized.
Quality considerations: Look for USP‑ or USP‑NF‑qualified products; verification by GC‑MS or HPLC ensures absence of contaminants (e.g., heavy metals, residual solvents). Third‑party testing (e.g., NSF, Informed‑Choice) is recommended to confirm potency and to confirm that the product is free of anabolic steroids or other adulterants.

All information reflects current peer‑reviewed literature and clinical guidelines as of 2024.