# Chemical Compositional Changes in Over-Oxidized Fish Oils
## 1 Introduction  
Fish oils are a good source of the omega-3 long chain polyunsaturated fatty acids (PUFAs) (omega-3 LCPUFA), eicosapentaenoic acid (EPA), and docosahexaenoicenoic acid (DHA). The intake of EPAand DHA from the consumption of fish, or fish oils and concentrates (oils containing EPA and DHA in higher concentrations), can confer a range of health benefits, such as lowering blood pressure and reducing the risk for heart disease in adults [1,2]. Specific omega-3 LCPUFAs such as DHA also support the development of the brain and visual system of the fetus during pregnancy [3, 4, 5, 6, 7, 8]. The intake of fish oil can also impart antioxidant effects though the increased expression of antioxidant enzymes, and components in fish oil are associated with antimicrobial effects [9,10]. Given their relatively high content of polyunsaturated fatty acids, fish oils and other EPA/DHA omega-3-containing oils are susceptible to oxidation [11,12]. Fatty acid composition, antioxidant concentrations, oxidative condition(s) (for example temperature and light), and specific compositional aspects such as trace metal ions and moisture all affect the oxidation rate of edible LCPUFA-rich oils [13, 14, 15, 16]. The handling of fish oils in a correct manner during processing and employing a proper product formulation designed for the applicable storage conditions can effectively prevent oxidation during their production and shelf-life [17]. However, the uncontrolled oxidation of highly unsaturated oils will lead to the formation of an array of oxidation products. Additionally, it is expected that widely dissimilar and unique profiles of oxidation products will be present in distinct fish oils exposed to different oxidizing conditions. Quality guidelines for edible oils set by regulatory authorities exist to avoid rancid products entering the market. Producers of oils and retailers have also set voluntary quality limits through organizations such as the Global Organization for EPA and DHA Omega-3s (GOED) [18]. Industry guidelines assist in making sure products comply with the applicable quality limits set by regulatory agencies for the markets where products are sold. Before fish oil products are sold to consumers, the oxidative quality of EPA/DHA omega-3 ingredient oils and finished products is typically measured using peroxide value (PV), _para_-anisidine value (p-AV), and total oxidation number (TOTOX). Recent studies show that the large majority of ingredient oils as well as finished products found in retail stores is of acceptable quality, although further improvements in oxidative quality can be made for some retail products [19, 20, 21, 22, 23, 24, 25]. The consumption of fish oils that are mildly oxidized (i.e., close to or just above regulatory limits) has not been found to alter a range of biochemical parameters in the body [26,27]. It is when severely oxidized, rancid oils that surpass quality limits many-fold are administered to experimental animals in supra-normal doses that adverse effects have been observed [28,29]. However, it is important to understand which chemical changes occur in over-oxidized oils in order to evaluate the risk pertaining to the consumption of specific substances that may be formed during oxidation. Risks associated with specific hazardous oxidation products should be studied and discussed in the proper context regarding their occurrence in finished products, product availability to consumers, and the actual exposure, i.e., the volumes (doses) of oil that people ingest. One specific study published in 2016 that aimed at evaluating the effects of oxidized fish oil on the gestational and perinatal health of rats employed an excessively over-oxidized fish oil [28]. Daily gavage with a high dose of the rancid hoki liver oil throughout gestation led to high newborn mortality, and continued feeding of dams with the damaged oil augmented maternal insulin resistance [28].