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PHARMACOLOGICAL ACTIVITIES - TOXICOLOGY - DRUG INTERACTIONS

Essential Fatty Acids

Toxicity for essential fatty acids has not been documented in dogs and cats when administered orally in
therapeutic doses. The LD values for essential fatty acids have not been determined.
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Some species of fish may contain significant levels of methylmercury, polychlorinated biphenyls (PCBs), or
other environmental contaminants (Mozaffarian & Rimm, 2006). In general, larger predatory fish, such as
TOXICOLOGY swordfish (Xiphias gladius), tend to contain the highest levels of these contaminants. However, several

independent laboratory analyses in the U.S. have found commercially available omega-3 fatty acid supplements
to be free of contaminants (ConsumerLab, 2005; Melanson et al., 2005). The absence of methylmercury in
omega-3 fatty acid supplements can be explained by the fact that mercury accumulates in the muscle, rather than
the fat of fish (Kris et al., 2002). Fish body oils contain lower levels of PCBs and other fat-soluble contaminants
than fish liver oils. Additionally, fish oils that have been more highly refined and deodorized also contain
lower levels of PCBs (Hilbert et al., 1998). Pyrrolizidine alkaloids, potentially hepatotoxic and carcinogenic
compounds, are found in various parts of the borage plant. Supplements containing borage oil should use
products that are certified free of pyrrolizidine alkaloids (Hendler & Rorvik, 2001).

DRUG Validated interactions studies do not exist for essential fatty acid preparations.
INTERACTIONS A literature search identified only three case reports presenting bleeding events or changes in
laboratory results in human patients taking fish oil and anticoagulant medication (Jalili & Dehpour,
2007; McClaskey & Michalets, 2007; Buckley et al., 2004) such as aspirin, clopidogrel, dalteparin,
dipyridamole, enoxaparin, heparin, ticlopidine, and warfarin. However, one small study found that
3 g/day or 6 g/day of fish oil did not affect International Normalized Ratio (INR) values in ten
patients on warfarin over a 4-week period (Bender et al., 1998). Gamma-linolenic acid supplements,
such as evening primrose oil or borage seed oil, may increase the risk of seizures in people on
phenothiazines, such as chlorpromazine (Vaddadi, 1981).
Studies suggest that the combined use of statins and omega-3 fatty acids improves cardiovascular
protection and reduces the cardiovascular disease-related mortality rate (Villalobos et al., 2010).
Omega-3 fatty acids do not interfere with the actions of chemotherapy and may potentiate the
effect of some chemotherapeutic agents such as epothilone, 5-fluorouracil and cyclophosphamide
(Wynter et al., 2004).

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