Omega-3 (EPA/DHA) vs Vitamin D3

Mechanism

EPA and DHA incorporate into cell membrane phospholipids, modulating membrane fluidity and lipid raft signaling. EPA competitively inhibits arachidonic acid conversion via COX-2 and 5-LOX, reducing pro-inflammatory eicosanoids (PGE2, LTB4) while generating anti-inflammatory resolvins and protectins. DHA is critical for neuronal membrane integrity, modulating BDNF expression and synaptic plasticity via Nrf2 and NF-kB pathways.

Standard Dosing

2-4g combined EPA/DHA daily (targeting 2:1 EPA:DHA ratio for inflammation; 1:1 for cognitive)

Timing

With meals containing fat for absorption. Split dose AM/PM.

Cycle Duration

ongoing

Side Effects

• Fishy burps/aftertaste
• Mild GI upset
• Loose stools at high doses
• Potential increased LDL in some individuals

Contraindications

• Active bleeding disorders
• Scheduled surgery (discontinue 2 weeks prior)
• Fish/shellfish allergy (use algal-derived)

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Mechanism

Vitamin D3 (cholecalciferol) is hydroxylated in the liver to 25(OH)D (calcidiol), then in the kidneys to 1,25(OH)2D (calcitriol), the active hormone. Calcitriol binds the nuclear vitamin D receptor (VDR), forming a heterodimer with RXR that regulates >1000 genes. Key actions: upregulation of intestinal calcium/phosphorus absorption (TRPV6, calbindin), modulation of innate immunity (cathelicidin LL-37 antimicrobial peptide production), suppression of adaptive immune overactivation (Th1/Th17 to Treg shift), regulation of PTH and osteocalcin for bone mineralization, and modulation of insulin secretion from beta cells.

Standard Dosing

5000 IU daily (125 mcg)

Timing

With largest fat-containing meal of the day (fat-soluble). Morning preferred.

Cycle Duration

ongoing (lifelong for most people in northern latitudes)

Side Effects

• Hypercalcemia at excessive doses (>10,000 IU/day long-term without monitoring)
• Nausea/vomiting (toxicity)
• Kidney stones (with excessive calcium)
• Metallic taste (toxicity sign)

Contraindications

• Hypercalcemia
• Granulomatous diseases (sarcoidosis, some lymphomas — unregulated 1-alpha hydroxylase conversion)
• Primary hyperparathyroidism (without monitoring)
• Williams syndrome

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