Subchronic toxicity of fish oil concentrates in male and female rats.

There are an overwhelming number of reports indicating the beneficial effects of fish oil supplements in human and animal nutrition. The purpose of this study, second in a series, was to evaluate the effects, particularly those that may be harmful, of high-dose, long-term consumption of fish oil concentrates (FOC) using male and female rats. One hundred and twenty male and 120 female rats were gavaged daily with oils and oil mixtures in a volume equal to 0.5% body weight (5 mL/kg/d) for 13 weeks. The administered oils were corn oil, pure menhaden oil (MO), pure MaxEPA fish oil or different mixtures of corn oil with MO. The stability and the homogeneity of the dosing solutions were tested under study conditions. The animals received isocaloric and isonitrogenous diets throughout. Food and pure water were supplied ad libitum. At the end of the in-life phase of the study, the animals were anaesthetized with CO2 and humanely killed by exsanguination. Blood and other tissues were prepared for various clinical, histopathological and laboratory tests. Some beneficial effects of FOC, such as reduction in total serum cholesterol, in rats were confirmed. However, we also observed a significant reduction in absolute amount of serum HDL and a significant increase in relative liver and spleen weights in both sexes with the high dose of FOC. High doses of FOC (5 mL/kg/d) reduced serum iron and vitamin E concentrations. A reduction in osmotic fragility of RBC as well as an increase in RBC deformity were also observed in rats treated with high doses of FOC. These rats showed a significant overall increase in WBC count. We conclude that in rats, subchronic consumption of high levels of FOC can be beneficial but may also be harmful because of induction of clinical abnormalities including increased red cell deformity, increased relative liver and spleen weights, and reduced serum HDL, iron and vitamin E concentrations.

Effects of long-term consumption of high doses of fish oil concentrates on clinical parameters in male and female rats.

Many studies suggest that a diet supplemented with fish oil concentrates (FOCs) may provide protection against cardiovascular and other diseases. The possible harmful effects of long-term consumption of high doses of FOCs, however, have not been adequately investigated. Corn oil, fish oil (MaxEPA) and various mixtures of the oils were administered by gavage to 120 male and 120 female rats, 5 d/wk for 13 wk at the rate of 5 mL/kg/d. Although MaxEPA had no effect on prothrombin time or activated partial thromboplastin time, it caused a statistically significant diminution of the total serum cholesterol level. Correlations between relative liver and spleen weights and dose levels were positive but a negative correlation was found between dose levels and serum vitamin E concentration. In female rats, the negative correlations between dose levels and serum iron and triglyceride levels were highly significant. The pathology data showed no remarkable lesions in any of the tissues examined. Results of this study suggest that long-term consumption of high levels of FOCs in rats may reduce serum cholesterol and triglycerides and adversely affect serum iron level and relative liver weight in female rats and relative spleen weights in both sexes.