Next, it is now commonly acknowledged that elevated high-sensitivity C-reactive protein (hs CRP), a selective marker of intra-arterial inflammation, is a robust risk factor for CVD. Research on the potential for fish oil to lower this cardiospecific parameter has produced mixed results. One study found that atorvastatin (Lipitor), but not fish oil, reduced hs-CRP in obese, at-risk subjects.19 In other research, omega-3 supplements did not reduce hs-CRP in healthy subjects.20 Another set of findings showed that EPA/DHA reduced hs-CRP in patients on dialysis, a population known to be at higher risk for inflammation and CVD.21
Finally, fish oil has a less equivocal effect on other inflammatory mediators, specifically such cytokines as tumor necrosis factor-alpha, elevations of which are hallmarks of chronic congestive heart failure (CHF). Studies show improvement in cytokine levels in CHF patients taking EPA/DHA, with corresponding improvements in clinical outcomes.9
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Prevention of restenosis. Accelerated restenosis following angioplasty or stenting is one of the thorniest problems in medicine, associated with numerous failed strategies. Because of fish oil’s acknowledged antiatherosclerotic effects, it became a likely candidate for restenosis prevention. Early meta-analyses showed modest benefit and provided reason to be hopeful.22 Unfortunately, the Coronary Angioplasty Restenosis Trial demonstrated no reduction in restenosis rates with 5 g/day of Omacor, a precursor to Lovaza.23
Other benefits. Ancillary benefits of fish-oil supplementation are thought to be considerable. Therapeutic effects have been investigated, with various degrees of evidence, in such diverse conditions as bipolar disorder, depression, dementia, psychosis, certain cancers (including breast, colon, and prostate) cancer cachexia, rheumatoid arthritis, cystic fibrosis, inflammatory bowel disease, dysmenorrhea, IgA nephropathy, systemic lupus, asthma, chronic obstructive pulmonary disease, psoriasis, eczema, dry eye, macular degeneration, pre-eclampsia, and prevention of organ-transplant rejection.24
With regard to fish oil’s role in secondary prevention of CVD, studies suggest potential amelioration of depression in heart attack survivors who take omega-3s. Depression is a known comorbidity following MI. It is also a negative prognostic, so, if proven, fish oil’s antidepressant effects would be a valuable ancillary benefit.
A recent trial compared fish oil plus sertraline with sertraline alone in a group of post-MI patients. Mood improved in all the patients, but no difference was seen in depression scores between fish-oil-supplemented patients vs. controls.
“Whether higher doses of EPA, DHA, or sertraline, a longer duration of treatment, or the use of omega-3 as monotherapy can improve depression in patients with stable heart disease remains to be determined,” the authors concluded.25
Adverse effects and contraindications
The most commonly observed adverse effects of omega-3 PUFA supplementation are nausea, GI upset, and “fishy” burp. These problems can sometimes be ameliorated through the use of flavored, emulsified omega-3 formulations that are palatable even to children. Alternatively, enteric-coated forms of fish oil are designed to dissolve distal to the stomach, reducing the potential for oily reflux.
Because of fish oil’s antiplatelet effects, concerns have been raised over the possibility that higher intakes will lead to an increase hemorrhagic complications. However, a comprehensive review concluded that no increased risk of clinically significant bleeding was noted with omega-3 PUFA doses of up to 7 g of combined DHA and EPA per day, even when coupled with antiplatelet therapy or warfarin.26 Results may vary in clinical practice, and such clotting disorders as Von Willebrand disease or thrombocytopenia may pose relative contraindications to high-dose fish-oil supplementation.
A recent study explored fish-oil supplements’ synergy with aspirin and clopidogrel in post-stenosis patients. Resistance to platelet inhibition was overcome with no concomitant increase in adverse hemorrhagic events.27
To prevent excessive perioperative bleeding, patients undergoing elective surgery are typically advised to forgo fish-oil supplementation for several weeks, but some studies actually support a role for fish oil in improving surgical outcomes. Some researchers have credited fish oil with offering circulatory benefits, or alternatively with modulating immunity, perhaps by blunting the exaggerated cytokine response to surgery.28
Lately, concerns have been raised over fish oil’s potential to down-regulate immunity in detrimental ways. One study observed that fish oil decreased resistance to influenza virus in a murine model,29 but the observation has not been extended to humans.
