Third Arachidonic Acid Study PUBLISHED

William Llewellyn
Third Arachidonic Acid Study PUBLISHED
The third placebo-controlled study on Arachidonic Acid (ARA) supplementation in resistance-trained subjects has just been published (1). For those unfamiliar, ARA is a polyunsaturated fatty acid from the omega-6 family. It is considered the most important of its class, and is involved in various aspects of cognitive, cardiovascular, immune, and metabolic health. More on topic, it is also needed for muscle repair and growth. Full disclosure, my company introduced the first ARA supplement (X-FACTOR™) back in 2003, and funded the first two human trials on it. However, we were not involved in this latest study. This was the result of a collaboration between researchers at several places including the University of Auckland, Deakin University, and the University of Newcastle.

Study Design:

This investigation involved 19 young active male participants, aged 18–35 years. As part of the inclusion criteria, all subjects were resistance trained for a minimum of 1 year prior. They were each given either 1,500 mg of arachidonic acid, or an identical-looking placebo, daily for 4 weeks. The men were instructed to continue their normal training and dietary regimens, with a few minor adjustments for testing procedures. Blood samples and skeletal muscle biopsies (vastus lateralis) were taken at baseline, and compared to measures at 4 weeks. Body composition was examined, though with the short duration used, the effects of ARA supplementation on tissue fatty acid profile and inflammation appeared to be the primary focus of the study. The main findings are reviewed below.

1. Enriched ARA Levels.

This may seem obvious, but an important part of understanding how arachidonic acid works is investigating its disposition in the body. For instance, muscle is already a major site of ARA storage. Can this be further enriched? It is always possible that a supplement will not be absorbed or utilized as expected. As we learned from this paper though, ARA supplementation does significantly increase ARA levels in both plasma and muscle. In plasma, ARA levels increased ~2-fold, to 16.24% of total fatty acids. In muscle, ARA increased from 11.93% to 14.60% of total fatty acids. Both were unchanged in the subjects given a placebo.

2. Enhanced Myogenic Gene Expression.

Four weeks is too short to expect much by way of measurable body composition changes with arachidonic acid. We always recommend about twice that time. However, it is probably long enough to see changes in the underlying anabolic machinery that drives muscle growth. In this study, researchers examined two key Myogenic Regulatory Factors (MRFs), myogenin and MyoD. These regulatory factors are elevated by resistance training, and closely involved in the repair and adaptation of skeletal muscle (4). The study found the expression of both myogenic regulatory factors to be significantly elevated by arachidonic acid. In the case of myogenin, there was a 1.34-fold increase in the subjects taking ARA compared to baseline. For MyoD, the increase was even more profound; 1.5-fold. For those taking placebo, the fold change in both MRFs was a nonsignificant .56. These results may be important to helping us understand not just the if, but how supplemental ARA influences training adaptations. Tissue ARA levels with supplementation

3. No/Reduced Inflammation.

Arachidonic acid is a substrate used by the body to make eicosanoids, which are involved in inflammation. This has lead to a popular misconception; ARA supplementation must promote inflammation. Numerous other studies have examined this, and come to similar conclusions. It doesn’t. Inflammation is a tightly regulated biological response, that is not simply initiated by consuming ARA. However, the misconception persists. Leaving almost no stone unturned, the Auckland study addresses this in extensive detail by looking for changes in a wide range of immune cell surface markers (ITGAM, ELANE, CEACAM8, CD68, CD163, CD206) and inflammatory cytokines (IL1B, IL6, CCL2, TNF), at both the systemic and local level. The result: there was no evidence of elevated inflammation with ARA supplementation in any marker tested, at either the systemic or tissue level. In fact, there was a modest reduction in blood monocyte counts, as well as PBMC mRNA expression of (ELANE) and CD66b (CEACAM8). As the researchers pointed out,
“These changes would appear to reflect, if anything, a reduced basal systemic inflammatory response… These findings do not support the common assertion that heightened dietary intake and tissue abundance of ARA will promote chronic inflammation in otherwise healthy individuals.”

4. Improved Cholesterol Profile

Those subjects taking ARA also noticed a significant improvement in the Total Cholesterol/HDL ratio. The mean value here changed from a baseline of 3.94, to 3.66 at week 4. That is a reduction of about 7%. Comparatively, there was no change in the mean TC/HDL ratio in men taking the placebo. Not quite a main focus of the study, but an important finding. As the authors point out, this may be consistent with other studies that found higher ARA levels to be independently associated with reduced cardiovascular risk. This discussion could easily veer of in another direction, but we can see there is a lot more to this fatty acid than most realize.


It is easy to close every article like this with the requisite phrase “more research is needed”. And to be fair, it is. However, let us not forget how far we have come with this nutrient. It took nearly a decade and a half, but we now have three clinical trials on arachidonic acid supplementation by resistance-trained adults. All with favorable outcomes. Baylor University found a significant increase in peak power with 1,000mg ARA daily, along with statistically strong improvements in strength and other power variables (2). The follow up at the University of Tampa used 1,500mg/day, and reported significant increases in lean body mass, strength, and peak power (3). The Auckland study adds to what we’ve learned from these two earlier investigations. It explores the disposition of supplemental ARA, and highlights changes in underlying mechanisms that can support muscle growth. Perhaps more importantly though, it addresses a popular misconception about this nutrient in great detail. The concluding sentence in their abstract sums up the findings well.
“These data show that dietary ARA supplementation can rapidly and safely modulate plasma and muscle fatty acid profile and promote myogenic gene expression in resistance-trained men, without a risk of increasing basal systemic or intramuscular inflammation."
More research is needed on arachidonic acid, indeed. With results like these, I expect we'll see it.  

(1) Arachidonic acid supplementation modulates blood and skeletal muscle lipid profile with no effect on basal inflammation in resistance exercise trained men. James F. Markworth, Cameron J. Mitchell et al. Prostaglandins, Leukotrienes and Essential Fatty Acids 128 (2018) 74–86
(2) Effects of arachidonic acid supplementation on training adaptations in resistance-trained males. Michael D Roberts, Mike Iosia, Chad M Kerksick, et al. J Int Soc Sports Nutr. 2007; 4: 21
(3) Effects of Arachidonic Acid Supplementation on Acute Anabolic Signaling and Chronic Functional Performance and Body Composition Adaptations. Eduardo O. De Souza, Ryan P. Lowery, et al. PLoS One. 2016; 11(5): e0155153.
(4) Early myogenic responses to acute exercise before and after resistance training in young men. Marissa K Caldow, Emily E Thomas et al. Physiol Rep. 2015 Sep; 3(9): e12511.

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