Vitamin D

Rationale. Vitamin D is actually a hormone with effects on:

• Immune regulation (relevant to ME/CFS immune dysfunction)
• Muscle function
• Mood
• Bone health
• Potential TRPM3 regulation (speculative): The vitamin D receptor (VDR) is a nuclear transcription factor; VDR response elements have been identified in the promoter regions of multiple TRPM genes. If VDR drives TRPM3 expression, chronic vitamin D deficiency could reduce TRPM3 protein abundance in immune cells, compounding functional channelopathy. This provides a second, channel-specific rationale for vitamin D monitoring in ME/CFS beyond the general immune and musculoskeletal effects. (Certainty: 0.30; VDR-TRPM regulatory link is inferred from VDR binding site analysis; not yet measured in ME/CFS patients.)

Deficiency is common in ME/CFS patients (often housebound with limited sun exposure).

Evidence. Moderate for general health; limited ME/CFS-specific data.

Target Levels. Controversy exists:

• Conventional: 30–50 ng/mL (75–125 nmol/L)
• Some ME/CFS practitioners target: 50–80 ng/mL
• Toxicity typically \(\\>\) 150 ng/mL

Dosing.

• Maintenance: 1000–2000 IU daily
• Deficiency correction: 5000–10,000 IU daily for 8–12 weeks, then retest
• Take with fat-containing meal

Cofactors. Vitamin D requires cofactors for proper function:

• Magnesium: Required for vitamin D activation
• Vitamin K2: Directs calcium to bones (away from arteries)
• Vitamin A: Balances vitamin D effects

Energy Profile. Category B (energy-neutral). Immune regulatory and gene expression effects operate through nuclear receptor signaling with minimal direct energy cost. Long half-life means infrequent dosing keeps metabolic processing burden low. No direct energy provision.