Demonized N-6 Pufas Surprisingly Ergogenic: Safflower Oil More Than Doubles Swimming Endurance of Aging Mice.

Image 1: Unexpectedly ergogenic - Carthamus tinctorius L., better known as "safflower", a highly branched, herbaceous, thistle-like annual.

As a regular visitor of the SuppVersity and/or listener of SuperHumanRadio, you will be familiar with my skepticism towards fish oil supplementation as the "good for all" wonder-supplement in an athletic population. You will also be familiar with studies such as Filaire et al. (2010) which showed increased MDA (malondyaldehide) levels (and thus more, not less toxic waste) in athletes receiving 600mg of EPA and 400mg of DHA for 6 weeks. Thusly, it may not come as a total surprise that Guihua Zhang and his colleagues the National Food Research Institute and the National Institute of Vegetable and Tea Sciences in Japan found that 12 weeks on a diet containing 6% fish oil reduced endurance performance in aged mice by -20%. What may be more surprising, though, is that the vilified n6-pufas from safflower oil more than doubled the rodents' endurance performance.

Video 1: Not the swimming test performed in the study, but maybe an explanation why mouse-oil might be good for fish, but not vice versa - or have you ever seen a mouse eating a fish?

In view of the fact that the mice in the lard group suffered a similar loss in endurance performance, it should be said that the overall effect of fish oil, as well as lard, could in fact have been a null-effect. In other words, contrary to safflower oil, fish oil and lard had no beneficial effect on swimming endurance, so that an age-related decline in swimming endurance would have become obvious. After all, the average mouse-life is no longer than ~100-150 weeks, so that another 12 weeks are quite a time-span for 52 weeks old mice. On the other hand, previous studies such as Shimomura et al. (Shimomura. 1990) and Rustan (Rustan. 1993) would point toward an overall negative effect of high SFA+MUFA (lard) and high N3-PUFA (fish oil) on fatty acid oxidation in skeletal muscle and subsequently (endurance) exercise performance.

In the study, 40 male Crlj:CD-1 (ICR) mice had been randomly assigned to one out of three groups with the 6% of fatty acids of their experimental diet coming from either lard (n=13), safflower oil (n=13) or fish oil (n = 14) for 12 weeks.

Figure 1: Effect of 12 weeks on diets with 6% lard, fish oil and safflower oil on swimming endurance of aged mice (data calculated based on Zhang. 2011).

As the data in figure 1 goes to show, the fat content of the diet, i.e. low PUFA (lard), high N3-PUFA (fish oil) and high N6-PUFA (safflower oil) had a profound impact on the swimming performance of the animals. In view of the fact that we cannot completely rule out that the "negative effect" of lard and fish oil were simply due to an age-induced decline in swimming performance (cf. red box above), the most important finding of this study is however the +113% endurance increase in the safflower group, and not so much the -20% performance decreases in the other groups in swimming endurance [if you asked me, it's a pitty that there is no control group on a mixed diet]

Figure 2: Effect of 12 weeks on diets with 6% lard, fish oil and safflower oil on lactate levels pre and post endurance exercise in aged mice (data calculated based on Zhang. 2011).

As Zhang et al. point out, this increase in endurance performance cannot be explained based on increases in muscle or liver glycogen stores, because scientists measured "[s]imilar glycogen storage and plasma glucose levels in sedentary mice in the three diet groups suggest". A better explanation relates to the significant differences in the accumulation of plasma lactate following swimming (cf. figure 2), where lactate levels were "significantly lower" in the safflower oil group than in the lard (+57%) and non-significantly higher in the fish oil (+14%) group.

These results imply that the improved endurance associated with dietary safflower oil may be due, at least in part, to glycogen sparing. The working skeletal muscle is not only the major site of lactate production but is also important for utilization of lactate, which is mainly removed by oxidation. The decreased accumulation of lactate observed in aged mice fed safflower oil could be due to increased lactate oxidation and subsequent utilization as an additional energy source during swimming.

Yet the effect on accumulation or utilization of lactate was not the only difference that may have contributed to the increase in swimming performance that was observed in the safflower oil group. As the researchers point out,

the significant increase in muscle and liver CPT activities and decrease in plasma NEFA levels observed following exhaustive swimming in mice fed safflower oil implies an upregulation of fatty acid metabolism in these mice.

The absence of these effect in the lard or fish oil fed animals suggest that "the safflower oil group may have increased fatty acid utilization for energy than the other diet groups". In that, it is particularly noteworthy that we are talking about a localized increase in CPT activity and consequent fatty acid oxidation in muscle tissue. The increased liver CPT in the fish oil group, on the other hand could have contributed to an overall negative effect of fish oil consumption on endurance performance that would have been corroborated by the established suppressive effect of N3PUFAs on fatty acid synthesis (Kim. 1999; Nakatani. 2004)  and lipid oxidation (Rustan. 1993), against the backdrop of which less fatty acids became available for and subsequently oxidized in skeletal muscle.

Image 2: Biological activities of IL-6 (illustration by Prof. Dr. Heinrich)

Not directly relevant to the endurance aspect, but nevertheless interesting is another result of the study, which is the absence, respectively statistically insignificant elevation of elevations in the inflammatory maker IL-6 in the exercised (non-existent) and sedentary (non-significant) mice on the safflower oil diet. A result the anti-n6-faction in the diet-guru camp will probably find surprising and which goes against previous findings by Moon et al. (Moon. 2003) and Garcia-Escobar (Garcia-Escobar. 2010) - on the other hand, this also means that it was not the increase in IL6, which has in human studies been shown to selectively stimulate lipolysis in skeletal muscle (Wolsk. 2010), that facilitated the increase in endurance performance.

If and in what extent the reduction in plasma ferritin (fe) levels in the fish oil group (-13% sedentary; -24% exercised; both compared to lard, with slightly greater reductions compared to safflower oil) could have been an additional factor in a complex equation of substrate availability, usage and enzyme activity which could eventually explain the perfomance increases and decreases in the different groups is questionable. After all, the fe levels in the lard and safflower oil groups were virtually identical.

So, what would be the overall lesson, we can learn from the results of this study? Fish oil is poison, safflower oil liquid gold? Probably not. Yet, while it may still be questionable in how far the mouse metabolism is a good model for the human one, the inhibition of fatty acid synthesis and the increased fatty acid oxidation observed in mice as a consequence of fish oil feeding is present in humans, as well. Moreover, I assume you would agree that not everything that would be beneficial for the average sedentary borderline to morbidly obese inhabitant of the Western Hemisphere, is equally beneficial for performance-oriented athletes - or would you suggest 200 meter sprinters start swallowing statins and blood pressure medications? So, wouldn't it be remotely possible, then that a physical culturist (as I hope you would consider yourself to be one) would be much better off with a reasonable amount of those "nasty" n6-PUFAs in his/her diet to keep the fire in the mitochondrial furnace of his/her muscles in full blast? If you want to, ask your guru about it ;-)