TTA + Fish Oil Revisited - Increased Intramuscular Omega-3 Levels Compromise Heart and Skeletal Muscle Performance: -40% Endurance & -54% Total Work Capacity in 9 Weeks

Image 1: It is hilarious this picture was probably shot and (ab-)used to propagate the unhealthy message that you could never get enough omega-3 fatty acids from your diet, because that would mean you had to eat such nasty stuff as fish - pah, better pop some pills, I mean we are in the 21st century right!?

I guess you will remember my previous blogpost,  "TTA + Fish Oil - Fat Burning Superfats or Hepatoxic Pro-Oxidants?", on the 2012 study by Vigerust et al. which did show that TTA could ameliorate the hepatoxic side effects of fish oil, which, when it is administered in amounts higher than 1-2g per day over an extended time period, begins to accumulate in the liver (see also "Too Much of a Good(?) Thing: When Fish Oil Starts Clogging Your Arteries and Fattening Up Your Liver"). Moreover, the addition of ~912.4mg (human equivalent) TTA to the "long-term fish oil = fatty liver"-equation turned produced a pretty potent fat burning and anti-obesity stack. Based on previous reports on the unwanted side effects of TTA-based fatburners in the past, I deliberately selected the subtitle "Why You Better Avoid Large Amounts of Omega-3 and Tetradecylthioacetic Acid in the Long Run" and explicitly cautioned against the (over-)use of this fat loss combo for an extended period of time - as one of the most recent article in the journal Lipids in Health and Disease suggests, more than rightly so (Strand. 2012)!

TTA a can save your liver, but it will exasperate the shift of n-3 into your heart

Image 2 (Knuuti. 2008): a globally, well-perfused and (top) a compromised heart with a maximum perfusion of 1.3 ml/g/min (bottom)

As the data the scientists from the Haukeland University Hospital in Bergen, Norway, collected clearly suggest. A similar combination of fish oil and TTA of which Vigerust et al. found that it ramps up fatty acid oxidation in the liver and clears your most important detoxification organ from long-chain polyunsaturated fatty acid junk (not or incompletely oxidized omega-3s) fails to elicit similar effect in the heart of 8-10 weeks old male Wistar rats, who were kept for 50(!) weeks on one the following four 25% fat diets which differed only in terms of their individual fatty acid composition:

• control diet - 23% lard, 2% soybean oil
• TTA - 0.375% TTA, 22.6% lard, 2%
• fish oil - 10.4% fish oil (42% EPA / 21% DHA), 12.6% lard
• TTA & FO - 0.375% TTA, 10.4% FO, 12.2% lard, 2% soy

With both, fish oil and TTA being potent peroxisome-proliferator receptor (PPAR) agonists the scientists were mainly interested in the long-term effects of this touted "anti-diabesity" (i.e. countering diabetes and obesity) agents on the deposition and distribution of different fatty acids in various tissues. A special focus was on the heart and the downstream effects of fatty acid metabolism and myocardial function and performance.

N-3 accumulation in the heart? Wait that's a good thing, right? NO!

For the laymen who has been bamboozled by the fish oil craze this may initially sound counterintuitive, but the profound accumulation of omega-3 fatty acids in the myocardium (heart) of the rodents (see figure 1) is about as bad as it can get for the critters heart health.

Figure 1: PUFA composition (wt%) in heart of rats after 50 weeks of diet administration (Strand. 2012)

Similar to what we have seen for Zinc (cf. "Zinc: 15mg Are Plenty - After 120 Days Rodents on Diets Containing 2xRDA of Zinc Develop Metabolic Syndrome") and alpha lipoic acid (cf. "Lean & Muscular With Alpha Lipoic Acid? You Could Be Just as Lean, But More Muscular W/out 'Nutrient Repartitioner'!"), the PPAR-agonists fish oil and TTA, both of which have been shown to exert beneficial effects in certain sick (as of yet still sub-)groups of the population, like diabetics (e.g. Khalid. 2011) and patients with dilated cardiomyopathy (e.g. Nodari. 2011), exert diametrically opposed effects in a rodent model that is probably more accurate for the average healthy human being than his/her sedentary, obese and metabolically deranged peers.

Keep away from your obese neighbors' supplement stash, damn it!

Independent analyses such as a 2009 paper by Dijkstra et al. do not support the commonly held conviction that fish oil or a higher intake of omega-3 fatty acids was beneficial for the general non-diabetic public anyway (Dijkstra. 2009). And it does not take all too long to find numerous reports of in parts serious side effects from the consumption of high-dosed TTA-based fat-burners in the archives of popular fitness and bodydbuilding boards, before the respective supplement producers got scared and pulled them voluntarily and under the pre-text that they had found more effective formulations off the market.

Figure 2: Enzyme activity (nmol/min/mg) in heart of rats after 50 weeks of diet administration (based on Strand. 2012)

Probably a smart move if you look at the combined increases in enzymes that oxidize (ACOX) and enzymes that synthesize and store  fatty acids (FAS and GKAT) in the heart muscles of the rodents in figure 2. Together the synergy of increased storage and increased oxidation could create a perfect storm, which due to the overall "limited capacity of heart to metabolize the poorly oxidizable n-3 PUFA compared to SFA [...] might altogether indicate a reduction in cardiac efficiency" (Strand. 2012).

Reduced cardiac efficacy = reduced muscular efficacy

It's quite funny that we could actually have known that all along, after all, one of my favorite "holy omega-3 vs. bad omega-6" studies by K.J. Ayre and A.J. Hulbert was published in 1997 already. Ayre and Hulbert wanted to elucidate the effects of different dietary fatty acid compositions on the exercise capacity of rodents and found (way before the fish oil craze and therefore not so much to their surprise) that compared to a coconut (EFA deficient) or sesame oil (high omega-6) the n-3 enriched test diet led to a profound decrease in exercise capacity (see figure 3)

Figure 3: Endurance and total work capacity (left) and soleus and EDL fatty acid composition (right) of rats after 9 weeks on diets containing almost no essential fatty acids , a high n-6 or a high n-3 content (Ayre. 2012)

Similar to the detrimental effects on the efficacy of the heart muscle, the decreases in endurance -40% and -54% in endurance and work capacity in the n-3 group went hand in hand with profound increases in the soleus and extensor digitorum longus omega-3 content.

In view of the fact that TTA appears to increase the existing fatty acid recompositioning effects of an overload of dietary omega-3 fatty acids in the diet, and against the background that the observed negative side effects came about in no more than 9 weeks and were not reversed after 6 weeks on standard chow, it appears more than questionable if the few lbs of body fat you may be able to shed with the aforementioned TTA+fish oil double whammy over say 4-8 weeks are actually worth taking the risk of permanent or at least only slowly reversible changes in the intracellular fatty acid composition of your heart and skeletal muscle.

"And what about fish oil supplementation alone?"

Aside from the fact that the usefulness of fish oil caps in healthy individuals is questionable (Dijkstra. 2009) and anything beyond 1-2g of fish oil per day could well lead to increased not decreased oxidative damage in athletes and physical culturists (cf. "Omega-3 Fatty Acids Pro-Inflammatory in Athletes"; Filaire. 2010), you don't necessarily have to throw away your fish oil. After all, I would hope that no one here is getting 50% of his/her daily fat intake from fish oil caps - which was basically what Strand et al. fed their rodents to make sure that the shift in myocardial fatty acid levels would be profound enough. Still the Ayre study, where the n-3 content of the diets was much lower (16% of total fat intake, ~8.8g of fish oil if you consumed 2,000kcal/day), does indicate that the intramuscular changes in fatty acid composition can be profound and not without detrimental consequences even without the addition of TTA and in response to amounts of omega 3 fats of which we all know that thousand of supplement junkies still believe would be nothing but beneficial for their health.

Image 3 (woschie): What would these guys say, if everything they caught was a handful of fish oil caps? "Look! I have caught the best part of the fish. lucky me, so I don't have to take it, squeeze it and bath it in all sorts of chemicals to separate the good fats from the bad protein I would then have to process to fish meal!"

In the end, it all comes, as so often, by the way, back to two very common motifs here at the SuppVersity motif A which I have already implied in one of the subheadings is the simple truth that what has been show to work for the obese type II diabetic does not necessarily work for a healthy human being, let alone such an extraordinary specimen as you are ;-) And that does in fact segue perfectly into motif B which revolves around the notion of balance and is basically the foundation of my repetitive advice to always prefer real foods over supplements, where the latter is possible - and contrary to creatine of which even a meal-loving carnivore like myself could never get enough from his diet to see any of the scientifically well-established benefits, eating fish spending a couple of extra-bucks on grass-fed beef from time to time and simply avoiding the omega-6 laden vegetable oils will make the use of those nasty fish oil caps obsolete, anyways.

References:

1. Ayre KJ, Hulbert AJ. Dietary fatty acid profile affects endurance in rats. Lipids. 1997 Dec;32(12):1265-70.
2. Dijkstra SC, Brouwer IA, van Rooij FJ, Hofman A, Witteman JC, Geleijnse JM. Intake of very long chain n-3 fatty acids from fish and the incidence of heart failure: the Rotterdam Study. Eur J Heart Fail. 2009 Oct;11(10):922-8.
3. Filaire E, Massart A, Portier H, Rouveix M, Rosado F, Bage AS, Gobert M, Durand D. Effect of 6 Weeks of n-3 fatty-acid supplementation on oxidative stress in Judo athletes. Int J Sport Nutr Exerc Metab. 2010 Dec;20(6):496-506.
4. Khalid AM, Hafstad AD, Larsen TS, Severson DL, Boardman N, Hagve M, Berge RK, Aasum E. Cardioprotective effect of the PPAR ligand tetradecylthioacetic acid in type 2 diabetic mice. Am J Physiol Heart Circ Physiol. 2011 Jun;300(6):H2116-22. Epub 2011 Mar 18.
5. Knuuti J, Bengel FM. Technology and guidelines: Positron emission tomography and molecular imaging. Heart 2008;94:3 360-367
6. Nodari S, Triggiani M, Campia U, Manerba A, Milesi G, Cesana BM, Gheorghiade M: Dei Cas L: Effects of n-3 polyunsaturated fatty acids on left ventricular function and functional capacity in patients with dilated cardiomyopathy. J Am Coll Cardiol 2011, 57:870–879.
7. Strand E, Bjørndal B, Nygård O, Burri L, Berge C, Bohov P, Christensen BJ, Berge K, Wergedahl H, Viste A, Berge RK. Long-term treatment with the pan-PPAR agonist tetradecylthioacetic acid or fish oil is associated with increased cardiac content of n-3 fatty acids in rat. Lipids Health Dis. 2012 Jun 27;11(1):82.
8. Vigerust NF, Cacabelos D, Burri L, Berge K, Wergedahl H, Christensen B, Portero-Otin M, Viste A, Pamplona R, Berge RK, Bjørndal B. Fish oil and 3-thia fatty acid have additive effects on lipid metabolism but antagonistic effects on oxidative damage when fed to rats for 50 weeks. J Nutr Biochem. 2012 Jan 3.