Some Things Fishy: Oxidized Fish Oil Totally Benign!?Plus: The Inflammatory Side of EPA and Peroxide & Alkenal Levels in Commercial Fish and Vegetable Oils.
Highly oxidizable? Yes! Dangerous? Surprisingly not!
A pros pos "highly oxidizable", the argument that polyunsaturated fatty acids (PUFAs) are readily oxidized not only in your body, but even at the shelves of your nutrition store, is one of the few possible caveats of fish oils supplementation even fish oil enthusiasts will acknowledge. After all previous animal studies have shown that diets rich (5%) in rancid (=oxidized) fish oils lead to increases in thiobarbituric acid-reactive substances (TBARS) levels and elevate liver specific transaminases, as well as the alkaline phosphatase (ALP) levels in the plasma of rats (detrimental effects which can by the way be ameliorated by taurine supplementation, cf. Hwang. 2000). The results of a recent study by Inger Ottestad and colleagues from Norway may thusly surprise the "pro-fish oil"-faction about as much as they surprised me (Ottestad. 2011): The ingestion of 8g of oxidized (peroxide value: 18mEq/kg; ansidine value: 9) fish oil (1.6g EPA+DHA) did not have any unfavorable short term-effects in previously healthy individuals.
|Figure 1: Serum (left, 8-iso on secondary axes was measured in urine) and erythrocyte (right, GPx on secondary axes) markers of oxidative stress in 68 healthy subjects who were randomly assigned to ingest 8g of "fresh" fish oil, oxidized fish oil or high oleic-acid sunflower oil per day for before (pre) and after (post) the 7 week intervention (data adapted from Ottestad. 2011)
|Figure 2: Changes in n-3 and n-6 levels and the n-6/n-3 ratio (small graph) in the course of the study period (data calculated based on Ottestad. 2011)
[a]fter 3 and 7 weeks of intervention, the plasma level of EPA, docosapentaenoic acid and DHA were significantly increased in both fish oil groups compared to the HOSO group, but no significant difference in EPA, doc-osapentaenoic acid and DHA between the FO and oxFO groups was observed.The scientists are thusly right to conclude that their results do not support the often-heard hypothesis that higher intakes n-3 long-chain fatty acids could increase in vivo lipid peroxidation and more importantly, that ...
[...] the content of hydroperoxides in fish oil supplements, even with a PV that exceeds the European Pharmacopeia for marine n-3 oils, does not apparently influence the plasma level of n-3 FA.With regards to the obvious differences to previous animal studies, the scientists state that secondary oxidation of hydroperoxides, which are then absorbed in the intestine has until now been observed in animal and cell studies. In view of the relative short duration of the study and the reliance on healthy subjects, it is also questionable whether identical results would have been achieved, when sick patients (the usual customer group at least for the pharma-grade n-3 supplements) had been treated with the same product for years.
Oxidized fats in fish oil and beyond
It is also worth mentioning that Ottestad et al. are not sure, whether their "aritifically oxidized" fish oil (oxidation was achieved by sparkling pure oxygen through the oil for 20 min twice a day for 21 d) was an appropriate model for commercially available (oxidized) fish oils. After all, there could be major differences in the composition of the oxidation products, when the oils go rancid over months or get damaged by heat etc. While I obviously cannot answer this question without setting up my own lab, I can however tell you that another recent study by Halvorsen et al. who examined the peroxide and alkenal (one of the major products of secondary oxidation) content of fish and vegetable oils, found average peroxide levels in 33 commercially available fish oil products (mean PV: 3.61mEq/kg) that were ~500% below the ones of the oxidized fish oil (18mEq/kg) in the Ottestad study.
|Figure 3: Mean peroxide and alkenal values of 33 commercially available fish and 35 vegetable oils (Halvorsen. 2011).
|Figure 4: Peroxide (PV in mEq/kg) and alkenal (in nM/ml) levels in fresh vegetable oils and after being heated for 25 minutes at 225°C in an oven (data adapted from Halvorsen. 2011); solid red line - maximal peroxide value for olive oils, dotted red line - maximal peroxide values for fish oils as suggested by Turner et al. (Turner. 2006)
|Image 3: Extra virgin olive oils (EVOOs) have generally higher peroxide values than the cheap refined stuff, and yet, EVOOs and not refined oils have been shown to exhibit numerous health benefits.
|Image 4: Not all Omega-3 are created equal. We know for some time that DHA (not EPA) is what your brain needs and a recent study from Norway suggest that eicosapentaenoic acid (EPA) is actually pro- not anti-inflammatory at a cellular level. It may yet well be that this in turn triggers a beneficial hormetic response which would support my "fish oil = exercise in a pill hypothesis"
While I am not quite sure what to make of these observations, these results stand in line with previous studies reporting differential effects of EPA vs. DHA rich fish-oils, where across the board, the DHA appeared to be the major driving force of the beneficial health effects people hope to be getting from their fish oil caps (e.g. brain health, Engström. 2009).