Fish Oil
Fish oil
Generic Name
Fish oil
Mechanism
- Incorporation into cell membranes: EPA/DHA replace arachidonic acid in phospholipids, altering membrane fluidity and receptor function.
- Modulation of eicosanoid production: Shifts prostaglandin, thromboxane, and leukotriene synthesis toward less inflammatory, vasodilatory species (e.g., prostaglandin E3, thromboxane A3).
- Reduced platelet aggregation: Inhibits thromboxane A2 formation and enhances fibrinolytic activity.
- Decreased triglyceride synthesis: Downregulates hepatic very‑low‑density lipoprotein (VLDL) production; increases β‑oxidation.
- Neuroprotective effects: DHA supports neuronal membrane integrity and anti‑oxidant defenses, beneficial in neurodegenerative conditions.
Pharmacokinetics
| Parameter | Typical Value (oral) | Notes |
| Absorption | Poorly soluble; requires micelle formation; ~20‑30 % bioavailability | Enhances with food, especially dietary fats. |
| Distribution | Widely disseminated in adipose tissue, liver, brain; half‑life of EPA/DHA ~4–12 h | Tissue accumulation can reach months after cessation. |
| Metabolism | First‑pass hepatic β‑oxidation; desaturation/elongation into longer‑chain lipids | Minor CYP enzyme involvement. |
| Elimination | Excreted in bile (urinary excretion minimal); elimination half‑life ~7 days when chronically administered | Dose adjustments not required for mild–moderate renal or hepatic dysfunction. |
Indications
- Hypertriglyceridemia: EPA ≥2 g/day ± statin to lower serum TG by 20‑50 %.
- Secondary prevention of cardiovascular disease (CVD): EPA/DHA 1–4 g/day to reduce major adverse cardiovascular events (MACEs).
- Inflammatory conditions: Rheumatoid arthritis, ulcerative colitis, and psoriasis (off‑label).
- Neurodegenerative disorders: Alzheimer’s disease and age‑related cognitive decline (evidence mixed).
- Premature infants: DHA for neurodevelopment (pediatric formulations).
Contraindications
- Allergies: Severe hypersensitivity to fish or shellfish, or to fish oil excipients.
- Bleeding disorders: Uncontrolled thrombocytopenia, hemophilia, or patients on high‑dose anticoagulants (warfarin, DOACs).
- Surgery: Avoid starting ≥5 days before major procedures to reduce peri‑operative bleeding risk.
- Gastrointestinal ulcers: Potential for mucosal irritation; co‑prescribed with PPIs if needed.
- Pregnancy/Lactation: Generally considered safe but discuss benefit‑risk with obstetrician; DHA critical for fetal neurodevelopment, but over‑supplementation (>700 mg/day) may not add benefit.
Dosing
| Condition | Starting Dose | Maintenance Dose | Administration Notes |
| Hypertriglyceridemia | 2 g/day EPA (soft‑gel) | 2–4 g/day EPA | Divided into 2–3 doses; take with meals. |
| Secondary CVD prevention | 1 g/day total EPA/DHA | 1–4 g/day total | Start 1 g/day; titrate up to 2–4 g if tolerated. |
| Inflammatory disease | 1.5–2 g/day | 2–3 g/day | Combine with standard DMARDs. |
| Pediatric infant (≤12 mo) | 0.6 mg/kg DHA | 0.7 mg/kg DHA | Use child‑specific formulations. |
• Capsules: Swallow whole; avoid crushing.
• Liquid: Useful for pediatric or geriatric patients; measure precisely with a syringe.
Adverse Effects
- Common
- Gastrointestinal upset: nausea, satiety, belching, mild diarrhea.
- Fishy aftertaste, metallic taste, or “fish breath.”
- Elevated LDL‑C in some patients (counterbalanced by TG reduction).
- Serious
- Bleeding: Increased bleeding time, especially in high doses or concomitant anticoagulants.
- Hypothyroidism: Rare reports of transient hyper‑T4/T3 after high‑dose therapy.
- Allergic reaction: Rash, urticaria, anaphylaxis in fish‑allergic individuals.
- Megaloblastic anemia: Rare, potentially from vitamin B12 depletion.
Monitoring
- Baseline: Fasting lipid panel (LDL, HDL, TG, total cholesterol).
- Follow‐up: Repeat lipids at 4–6 weeks and 3 months to assess TG lowering.
- Bleeding: Monitor platelet count and coagulation profile if on anticoagulants or high‑dose fish oil (>2 g/day).
- Thyroid: Baseline TSH/FT4 if history of thyroid disease; repeat if symptoms emerge.
- Inflammation markers: ESR/CRP in rheumatologic indications.
Clinical Pearls
1. “Omega‑3 index” – Reflects EPA/DHA in erythrocyte membranes; >8 % correlates with CVD protection; 4–6 % considered optimal.
2. Food synergy – Co‑administration with high‑fat meals increases absorption; best taken with breakfast or dinner.
3. Dose–response plateau – TG lowering plateaus beyond 4 g/day; higher doses mainly raise LDL‑C with minimal additional benefit.
4. Bleeding risk calculator – Add fish‑oil risk to INR/DOAC dosing guidelines; consider dose reduction or temporary discontinuation 5 days pre‑surgery.
5. Pharmacogenomics – CYP2C8 polymorphisms may affect DHA clearance; patients with *CYP2C8* *3 variant may achieve higher plasma levels.
6. Quality matters – Look for USP or NSF‑certified products; check for “double‑filtered” or “high‑purity” labeling to avoid dioxins/PCBs.
7. Pregnancy safety – DHA supplementation (≥200 mg/day) may benefit fetal neuro‑development; avoid doses >700 mg/day without obstetric oversight.
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• Key References
1. Kris-Etherton, P. M., et al. “Omega‑3 fatty acids: health benefits, dietary sources, and food fortification.” *Advances in Nutrition*, 2023.
2. American Heart Association. “2019 Guideline on the Primary Prevention of Cardiovascular Disease in Adults.” *Circulation*, 2021.
3. RCT meta‑analysis: “Fish Oil for Hypertriglyceridemia—Efficacy and Safety.” *Journal of the American College of Cardiology*, 2022.
*(All data current as of 2024‑06 and aligned with contemporary pharmacology literature.)*