Something Fishy: Leucine-Rich Protein + Fish Oil Supplement Boosts White Blood Cell EPA Content and Immune Response

Regular readers of the SuppVersity, as well as people who religiously follow Carl Lenore's Super Human Radio and happened to listen to my 1st appearance on the show, will know that I am generally skeptic about the usefulness of unwarranted high dose (>1-2g of combined EPA + DHA) fish oil supplementation. This is not because I think fish oil is poison, but rather out of my awareness that its pharmacological effects have more similarity to those of a drug than to those of a "common food" (including possible side effects).

Now, a group of scientists from the Netherlands and the United Kingdom published the results of a study (Faber. 2011) which found another interesting stone from the fragmented mosaic our current understanding of the effects and nutritional interactions of fish oil, in general, and EPA, in particular, resembles. While the aim of the study, which was to quantify the incorporation of EPA and DHA into white blood cells, was nothing new, the nutritional supplement they used for this purpose, a mixture of 2.4 g EPA, 1.2 g DHA, 39.7 g protein (including 4.4 g L-leucine), and 5.6 g oligosaccharides was innovative and the results were astounding. After 1 week of 2x200ml of what the scientists label a "medical food" (beware there is probably somebody patenting the formula already ;-), ...

[... from 0.5% at baseline] the percentage of EPA [in white blood cell phospholipids] rose to 2.8% (P < 0.001). Additionally, the production of proinflammatory cytokines in LPS-stimulated whole blood cultures was significantly increased within 1 wk.

It appears that the addition of protein has a positive influence on the incorporation of EPA into white blood cells, which, in turn, boosts the natural immune response to lipopolysaccharides stimulation. This, however, brings me back to my initial comment about "pharmacological" effects of fish oil: While for a cancer patient with lowered immunity, the consumption of the "medical food" or, what I would consider equivalent, a combination of whey + fish oil, would unquestionably be beneficial - but what about someone with allergies or even auto-immune issues? I assume you would agree that to further boost an immune system that is already running havoc does not seem to be a good idea!? In the end, and here I do not mind repeating myself, it again all comes back to considering who you are and what your current medical and nutritional condition is, before you start taking a supplement of which the whole Internet community seems to believe that its the healthiest (if not the only healthy) fat on earth...

Omega 3 Attenuates Exercise Induced Rise in Inflammatory Markers, BUT is This Necessarily a Good Thing?

I want to take the results of a recent study (Bakhtyar. 2011) published in the Clinical Journal of Sport Medicine as an opportunity to readdress the question of whether or not the Omega 3 induced suppression of inflammation must be considered a good or a bad thing, both in view of athletic performance, as well from a health and longevity perspective.

Those of you, who listened to my interview on Carl Lenore's Super Human Radio show, will know that my understanding of "inflammation" is somewhat different from the mass market "explanation" of "a fire that causes damage". To be precise inflammation, or what scientists generally measure, is the release of signals (inflammatory markers) that tell immune cells to do their jobs. So, saying that inflammation is the root of all disease would be like saying that someone who calls the firefighters is to blame for the fire - but I am digressing from the topic at hand...

After administering 1.5g/day of an omega 3 supplement (experimental group) to every third of 45 previously untrained volunteers, Bakhtyar et al. found the subjects' "inflammatory" response to eccentric exercise to be modified:

The experimental group showed less elevation in TNF-α and PGE₂ immediately, 24, and 48 hours after exercise, when compared with the other groups. Significantly less elevation was shown in the concentration of IL-6, CK, and Mb for the experimental group at 24 and 48 hours after exercise. The experimental group also demonstrated a significant trend toward reduction in the plasma concentration of LDH immediately, 24, and 48 hours after the exercise program.

Now, what does this tell us about the training effect and health outcomes of the exercise regimen?

• With inflammation being a not yet fully understood prerequisite for muscular repair and hypertrophy, it would warrant further investigations like muscle biopsies and consistent training regimens with continuously monitored strength and muscle gains to conclude that omega 3 supplementation is beneficial in terms of physical performance.
• In view of the conclusions Pedersen draws in a recent review (Pedersen. 2011) of the role of exercise induced myokines, i.e. inflammatory markers released by muscles (myo- = muscle-), in chronic disease, blunting of muscular IL-6 release, which has been linked to muscular AMPK activation, increased glucose uptake and fat oxidation, omega 3 supplementation is probably counter-indicated in a health oriented exercise regimen, anyway.

I hope more scientists such as Pedersen will begin to question the current "anti-inflammatory" paradigm, so that major players in the medial landscape will be forced to take on their findings and stop portraying long chain polyunsaturated fatty acids in general and fish oil in particular as the savior of the fat and diabetic. Instead they should encourage people to finally get their asses off their sofas to induce exactly that amount of healthy, exercise-induced inflammation omega 3 supplementation appeared to suppress in the aforementioned study.

Fish, but not Fish Oil Supplements Reduce Breast Cancer & All-Cause Mortality Risk in Women

This is another piece of information which came up in the course of my recent research into the latest studies on fish oil supplementation: Capped fish oil, obviously, is very different from the "real deal" fish... you know that stuff that is swimming in the ocean and does not come in convenient 1 gram caps; that stuff that stinks like fish and is not molecularly distilled or filtered, ...

Researchers from the University of California (Petterson. 2010) recently found that...

Women with higher intakes of EPA and DHA from food had an approximate 25% reduced risk of additional breast cancer events [tertile 2: HR = 0.74 (95% CI = 0.58-0.94); tertile 3: HR = 0.72 (95% CI = 0.57-0.90)] compared with the lowest tertile of intake. Women with higher intakes of EPA and DHA from food had a dose-dependent reduced risk of all-cause mortality [tertile 2: HR = 0.75 (95% CI = 0.55-1.04); tertile 3: HR = 0.59 (95% CI = 0.43-0.82)]. EPA and DHA intake from fish oil supplements was not associated with breast cancer outcomes. The investigation indicates that marine fatty acids from food are associated with reduced risk of additional breast cancer events and all-cause mortality.

Of course, this again is one of those epidemiological studies, I, myself tend to criticize from time to time. Nevertheless, I find it very intriguing that, whenever we switch from natural to artificial versions of foodstuff, good things lose their value - or even become detrimental for your health.

High Dose Fish Oil NOT Effective in Promoting Weight Loss on a Professionally Monitored Weight Loss Regimen

Those of you who visit the SuppVersity pretty regularly will have noticed that I am reluctant to buy into all the hype about omega-3 fatty acids and the myriad of purported health benefits of high dose fish oil supplementation. According to the results of a very recent study published in the Journal of the American Society for Nutrition (DeFina. 2010) my doubts appear to be legitimate.

Table 1: Mean change in adiposity measures in the omega-3 supplement and placebo groups

The scientist investigated the effect of 3.0 g eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) at a 5:1 ratio (EPA:DHA) [standard fish oil caps usually have a ratio of 3:2 and you would have to take about 10 caps to get to that amount of EPA + DHA combined] on the weight loss of 128 obese and overweight individuals. Although fish oil treated individuals tended to lose a few more grams of body fat (cf. Table 1), this effect was no statistically significant, so that the researchers consequentially conclude:

No significant weight-reduction benefit was seen with the addition of omega-3 fatty acid supplementation in this weightloss study with lifestyle intervention. Overall, the participants in both arms lost .5% of their body weight, which was considered clinically significant in prior trials of diet, exercise, or medication.

A final word, before you throw away your fish oil supplies: There is one thing, which to my mind could have changed the outcome of the study considerably and that would be the use of a standard or even better a high DHA fish oil preparation. I've been following this discussion for quite some time now and whenever there were negative effects associated with fish oil supplementation, i.e. blocking the immune system, downregulation of the HPTA, etc. these were related to the highly anti-inflammatory EPA content of the oils. So, if you insist on taking your fish oil. Look for a brand that has a low EPA:DHA ratio and do not forget that for hard training athletes on low carb diets the "bad" saturated fats are "essential", as well.

Omega-3 Fatty Acids PRO(!)-Inflammatory in Athletes

Although I am aware of the magnitude of studies providing evidence for the positive effects of omega-3 fatty acids in general and EPA and DHA, in particular. I think you should be aware that research on its effects in athletes (as the general effect of anti-oxidants on healthy people) are less unequivocal than those on positive effects on your average pre-diabetic fatso.

In a very recent study, scientists from the Unité de Formation en Sciences et Techniques des Activités Physiques et Sportives in France (Filaire. 2010) found that judo athletes who took a standardized omega-3 supplement (600 mg EPA and 400 mg DHA) for 6 weeks had significantly increased stress markers compared to placebo:

Significant interaction effects between supplementation and time on resting MDA [malondyaldehide] concentrations and Rmax were found (p = .03 and p = .04, respectively), with elevated values in the n-3 LCPUFA group after supplementation and no change in the placebo group's levels. The authors observed a significantly greater NO and oxidative-stress increase with exercise (MDA, Rmax, CDmax, and NO) in the n-3 LCPUFA group than with placebo.

I've also read reports from (recreational) athletes all over the Internet claiming that whenever their PUFA supplementation goes beyond 1-2g per day, they start feeling drowsy, lose energy, recover slower and show other signs typically associated with increased inflammation. Feel free to use the comment function to let us know how fish oil or other omega3 sources make you feel.