High Dose Omega-3 for Fat Loss? With 90% Lower Body Fat EPA Takes The Lead, DHA Second, ALA Distant Third... in Rats on Cornstarch or High Fat + High Sugar Diets

For Neo in the Matrix (courtesy of Warner Bros.) the choice was comparably easy. He had only two pills! You, however got to chose between ALA, EPA, DHA and, believe it or not, taking no pill at all!

I guess, those of you who are curious about the whereabouts of "your's truly" Adelfo Cerame Jr. will be disappointed to hear that he is currently so overwhelmed with clients and other duties that we have decided to turn the weekly contest prep series into a bi-weekly one.

Since this was more or less a last-minute decision, I just picked the next best study from my "interesting finds" folder and ... it turns out to be one of your, yet certainly not my favorite topics: Omega-3 fatty acids! That I am still skeptic about the usefulness, let alone necessity of respective supplements, does yet not change mean that I am deliberately ignoring interesting research on the unquestionable beneficial effects they have on lazy couch-potatoes and respective rodent models.

ALA, EPA, DHA - different acronyms, different effects?

Speaking of rodents, the soon-to-be published study by Hemant Poudyal, Sunil K. Panchal, Leigh C. Ward and Lindsay Brown from the Universities of Queensland and Southern Queensland in Australia unquestionably belongs into this latter category of "interesting rodent research on the benefits omega-3 fatty acids" (Pudyal. 2012). In order to differentiate the effects of alpha linoleic acid (ALA), the short(er)-chain brother to the long-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) people often falsely refer to as "fish oil" (while fish oil contains them, the average fish oil cap has ~40% EPA/DHA or 400mg in a 1g gel cap), the scientists assigned 96 male Wistar rats (9–10 weeks old) randomly to one out of 8 different diets containing

Carbohydrate, fat and protein content (rel. to total energy)

• corn starch,
• corn starch +1.1g/d ALA-rich chia oil,
• corn starch +0.7g/d EPA,
• corn starch +0.8g/d DHA, or
• high-carbohydrate, high-fat, 
• high carbohydrate, high-fat +0.7g/d ALA-rich chia oil 
• high-carbohydrate, high-fat +0.7g/d EPA oil and 
• high-carbohydrate, high-fat+0.6g/d DHA oil

The n-3 PUFA supplemented diets were prepared by adding 3% of the oil replacing an equivalent amount of water in the diet. n-3 PUFA supplemented diets were administered for 8 weeks starting 8 weeks after the initiation of the corn starch or high-carbohydrate, high-fat diet. The drinking water in all high-carbohydrate, high-fat fed groups was augmented with 25% fructose for the duration of the study.

Profound anti-obesity effects of EPA and DHA

Over the course of the 8-week supplementation period the researchers took daily measurements of body weight, food and water intakes. They performed two oral glucose (OGTT) and insulin tolerance tests (ITT) before and after the 16 weeks trial and measured the body composition by Dual-energy X-ray absorptiometric (DXA).

Figure 1: Body composition, lipid profile, glucose management (left to right) in rodents after 8 weeks on chia seed oil (ALA), EPA and DHA supplemented diets (date expressed relative to cornstarch non-supplemented control; calculated based on Poudyal. 2012)

If you take a look at my plot of the data, you may be surprised about the significance of the results. While it has to be said that even the "normal" control diet was not exactly what I would deem healthy (even for a rodent), it is nevertheless astonishing how pronounced the anti-obesity effects actually were.

Downstream benefits on organ health, ...

Figure 2: Contrary to what we have seen in previous studies (see TTA+fish oil), the high doses of the different omega-3s (HED ~20-30g!) had no effect negative effects on either the transaminase (ALT, AST), lactate dehydrogenase (LDH), alkaline phosphatease (ALP) or bilirubin values or the histology (histologies of hepatcytes not shown) of the liver of the rodents (data based on Poudyal. 2012)

Compared to the effects of the high doses of long-chain omega-3s the ALA treatment had a comparatively low impact on the adiposity. This could partly be a result of the fact that the omega-3 fatty acid metabolism in skeletal muscle and adipose tissue appears to be specific. While EPA and DHA
accumulated readily in these organs, when they were directly supplemented, the provision of ALA did not increase the contents of long-chain omega-3 fatty acids in either body fat or skeletal muscle tissue.

On the other hand, all omega-3 fatty acids showed beneficial effects on heart and liver the function of which had already been compromised by the 8 weeks on the extreme high carbohydrate or high sugar + high fat diet (reduced cardiac fibrosis, hepatic steatosis and inflammation in both the heart and the liver). In that, both, both, the improvements in body composition, as well as organ health, were more pronounced in the low-fat diet compared to the high-carbohydrate, high-fat diet.

... but negative effects on glucose management

Against that background it is actually surprising that none of the omega-3 fatty acids actually did what they are often hailed for: Neither ALA, nor EPA or DHA did improve the profoundly reduced glucose tolerance of the carb-o-holic rodents. On the contrary,...

"[...] EPA and DHA supplementation increased basal blood glucose concentrations, decreased intestinal glucose absorption and maintained the blood glucose concentrations for two hours after glucose loading with normal insulin sensitivity." (Poudyal. 2012)

Interestingly, this effect was probably brought about by yet another unexpected effect the high dose (human equivalent ~20-30g) omega-3 treatment had on the sympathetic nervous system:

"These effects were accompanied by increases in sympathetic activation seen as increased heart rate and cardiac output, increased force of left ventricular contraction and increased vascular responses to noradrenaline and sodium nitroprusside as observed with the hypothalamus–pituitary– adrenal axis response to stress and low blood glucose concentrations " (Poudyal. 2012; my emphasis)

As Poudyal et al. point out, this could also explain the profound weight loss effect in the cornstarch groups, and the "relatively smaller but significant changes in [high fat + high sugar] rats that still have an abundance of fructose and fat to meet the energy requirements."

From rodents to humans, from humans to...  fishmen?

The latest on the usefulness of omega-3 supplementation for active individuals and athletes: One of the most recent reviews of the issue states: "[O]nly a few studies have evaluated the impact of omega-3 PUFA supplementation on exercise performance. It has been suggested that the ingestion of DHA of approximately 1-2 g per day, at a ratio of EPA to DHA of 2:1, may be beneficial in counteracting exercise-induced inflammation and for the overall health of an athlete. However, the human data is inconclusive as to whether omega-3 PUFA supplementation, at this dosage, is effective in attenuating the inflammatory and immunomodulatory response to exercise, and improve exercise performance." (Micleborough. 2012; my emphasis)

These (at least for me novel) effects of very high doses of EPA and DHA on the sympathetic nervous system as well as the modulatory effects of the baseline diet are certainly things to keep in mind. This is particularly true in view of the latest epidemiological data which suggests that the consumption of comparatively minuscule amounts of fish oil has a population (and thus probably diet-)dependent effect on diabetes risk  (Wallin. 2012), with

• 17% increased risk of type-2 diabetes per 0.30 g per day increment in long-chain n-3 fatty acids in US residents, and
• -2% reduced risk of type-2 diabetes per 0.30 g per day increment in long-chain n-3 fatty acids in Europeans

The same goes for the U-shaped dose-response curve, Crochemore observed in one of the most recent controlled trials in the course of which a low dose (1.5 g/d) fish oil supplement improved the body composition and fatty acid metabolism of 41 women (60.64 ± 7.82 years) with high blood pressure and diabetes mellitus, while only 1g more, i.e. 2.5g/day, did not simply yield less pronounced decreases in body mass and waist circumference, the "high" dose fish oil supplement also reduced the already highly compromised insulin sensitivity of subjects even further (Crochemore. 2012).

EPA & DHA can come to the rescue, but a healthy diet would render supplements obsolete

If I did not know that fish oil was an invention of the 1990s, I would speculate that the "fishman" in the 1954 horror blockbuster The Creature from the Black Lagoon (Universal Pictures) was a "fish oil fat loss supplementation experiment gone wrong" ;-) Or joke aside - you don't seriously consider popping 70 fish oil caps a day to get the human equivalent of the ~1g of EPA or DHA the rodents in the study consumed, do you?

Regardless of the "optimal dosage", we should not lose sight of the influence and importance of the basal diet, when we evaluate the effects of DHA and EPA on body composition, lipid metabolism and not the least glucose management. It is, for example, very unlikely that we would see anywhere similarly pronounced effects in humans who are following a whole-foods based, "paleo-esque" diet without tons of cornstarch in it (control group), or plain sugar (and 17% additional fructose) that are on top of that hilariously protein-deficient (5%-6% is - if anything - enough not to die).

If you chose grass-fed over regular butter / dairy (makes sense only for high fat dairy), eat fish once or twice a week and replace the grain-based oils in your diet with coconut and olive oil, anything that goes beyond the occasional one or two fish oil caps will probably do more harm than good. And let's be honest, you don't really believe that you would get rid of the blubber that may still be covering your abs by copying the supplementation protocol of the study at hand and taking 70 fish oil caps every day to get your 20-30g of EPA and DHA, do you?

References:

• Crochemore IC, Souza AF, de Souza AC, Rosado EL. ω-3 polyunsaturated fatty acid supplementation does not influence body composition, insulin resistance, and lipemia in women with type 2 diabetes and obesity. Nutr Clin Pract. 2012 Aug;27(4):553-60.
• Mickleborough TD. Omega-3 Polyunsaturated Fatty Acids in Physical Performance Optimization. Int J Sport Nutr Exerc Metab. 2012 Sep 4.
• Poudyal H, Panchal SK, Ward LC, Brown L. Effects of ALA, EPA and DHA in high-carbohydrate, high-fat diet-induced metabolic syndrome in rats. J Nutr Biochem. 2012 Sep 28. pii: S0955-2863(12)00207-0. .
• Wallin A, Di Giuseppe D, Orsini N, Patel PS, Forouhi NG, Wolk A. Fish consumption, dietary long-chain n-3 fatty acids, and risk of type 2 diabetes: systematic review and meta-analysis of prospective studies. Diabetes Care. 2012 Apr;35(4):918-29.