Oxidised fish oil does not influence established markers of oxidative stress in healthy human subjects: a randomised controlled trial

Abstract

Intake of fish oil reduces the risk of CHD and CHD deaths. Marine n-3 fatty acids (FA) are susceptible to oxidation, but to our knowledge, the health effects of intake of oxidised fish oil have not previously been investigated in human subjects. The aim of the present study was to investigate markers of oxidative stress, lipid peroxidation and inflammation, and the level of plasma n-3 FA after intake of oxidised fish oil. In a double-blinded randomised controlled study, healthy subjects (aged 18-50 years, n 54) were assigned into one of three groups receiving capsules containing either 8 g/d of fish oil (1·6 g/d EPA þ DHA; n 17), 8 g/d of oxidised fish oil (1·6 g/d EPA þ DHA; n 18) or 8 g/d of high-oleic sunflower oil (n 19). Fasting blood and morning spot urine samples were collected at weeks 0, 3 and 7. No significant changes between the different groups were observed with regard to urinary 8-iso-PGF 2a ; plasma levels of 4-hydroxy-2-hexenal, 4-hydroxy-2-nonenal and a-tocopherol; serum high sensitive C-reactive protein; or activity of antioxidant enzymes in erythrocytes. A significant increase in plasma level of EPA þ DHA was observed in both fish oil groups, but no significant difference was observed between the fish oil groups. No changes in a variety of in vivo markers of oxidative stress, lipid peroxidation or inflammation were observed after daily intake of oxidised fish oil for 3 or 7 weeks, indicating that intake of oxidised fish oil may not have unfavourable short-term effects in healthy human subjects.

Response by Heydari et al to Letter Regarding Article, “Effect of Omega-3 Acid Ethyl Esters on Left Ventricular Remodeling After Acute Myocardial Infarction: The OMEGA-REMODEL Randomized Clinical Trial”

“…1 Dr. Naegele expressed concern regarding the safety of omega-3 fatty acids based on the numbers of mortality cases in the omega-3 fatty acid and placebo treatment arms. Dr. Naegele postulated that the long term cumulative effect of omega-3 fatty acids exposure may be harmful due to “lipid peroxidation” following “gradual accumulation within biological membranes.” Although, at the present time, the effects of omega-3 fatty acids on lipid peroxidation and mitochondrial glucose utilization remain unclear, 2 we do not find supportive evidence that indicate harmful effects from omega-3 fatty acids in our study. First, our study was not powered to evaluate for the outcome of patient mortality and given the small numbers of deaths (3 and 8 cases in placebo and omega-3 fatty acids groups, respectively, P=0.22), no conclusive results can be drawn regarding patient mortality.…”

Bioavailability ofn-3 fatty acids fromn-3-enriched foods and fish oil with different oxidative quality in healthy human subjects: a randomised single-meal cross-over study

“…Recent studies have reported elevated peroxide levels in commercialised fish oil capsules, which have led to some concern that regular consumption of oxidised marine oils may negatively affect human health ( 16 – 21 ) . In a previous study, we did not observe any changes in fasting plasma LC n -3 FA levels, lipids or several other oxidative stress markers after 7 weeks of consumption of oxidised compared with non-oxidised fish oil ( 22 ) . However, another study reported that the intake of less oxidised n -3 FA supplements for 30 d reduced blood lipids and blood pressure compared with highly oxidised LC n -3 FA supplements ( 23 ) .…”

Omega-3 Long-Chain Polyunsaturated Fatty Acid Content and Oxidation State of Fish Oil Supplements in New Zealand

“…The limits are also below oxidation levels seen in other ingredients or food items available to consumers, as well as the maximum limits for oxidation for seed and plant oils that are also sensitive to oxidation 6, 7 . In addition to monitoring ingredient and product quality, the accurate measurement of fatty acid content and oxidative status is fundamental to permitting the proper assessment of the biological relevance of different types of omega-3 LCPUFA-containing oils, as well as the dependence of the biological effect on the concentration and type of any oxidation products that may be present in oils, in combination with dose- and time-dependent exposure 8–10 .…”