Arachidonic acid, inflammation, and muscle protein synthesis

From the perspective of the “No Pain, No Gain” paradigm, the concept is simple: a training stimulus that does not cause localized inflammation and soreness will not produce optimal muscle growth. So, what is the role of arachidonic acid in muscle inflammation?

Well, to begin with, arachidonic acid (AA, 20:4n-6) is an essential Omega-6 polyunsaturated fatty acid that is abundant in the membrane phospholipids of skeletal muscle. It is also the body’s basic component for producing prostaglandins, which are known to have several physiological roles, including close involvement in inflammation.

Recent evidence suggests that the prostaglandin isomer PGF2a has a powerful ability to stimulate muscle growth. As such, arachidonic acid is a regulator of localized muscle inflammation and may be a central nutrient controlling the intensity of the anabolic/tissue-rebuilding response to weight training.

Although the concept (and sensation) of post-exercise inflammation is familiar to many of us, the basic aspects of post-workout inflammation are actually somewhat more complex. In short, arachidonic acid is a very important compound because of its widespread role in cell signaling that leads to growth.

The mechanism of action of arachidonic acid

To rewind a little, there are certain signal-transduction pathways that are initiated within skeletal muscle through the binding of exercise-sensitive hormones (such as GH and/or IGF-1) to complementary receptors. Scientists explain that these pathways regulate the expression of contractile proteins and induce the assembly of ribosomal machinery, thereby increasing the rate of fractional protein synthesis. These are, of course, events indicative of muscle growth.

So, where does arachidonic acid fit into all this molecular biology talk?… Well, the following list chronologically describes what happens to arachidonic acid after a muscle is damaged by training:

• Cytosolic phospholipase A2 (or cPLA2, an intramuscular enzyme) is activated.
• cPLA2 causes the release of arachidonic acid into the cytoplasm (or inner portion) of the muscle cell.
• Another enzyme, cyclooxygenase-2 (COX-2), catalyzes the multi-step synthesis of prostaglandins (i.e., PGE2, PGF2a), which leak out of the cell and initiate several physiological events (i.e., vasodilation and inflammation).
• Prostaglandins (specifically the PGF2a isomer) also bind to prostanoid receptors in skeletal muscle and are proposed to initiate the signal-transduction cascades that lead to muscle growth.

In this scenario, arachidonic acid and the PGF2a isomer have been shown to facilitate ribosomal assembly in smooth muscle tissue by activating downstream proteins of the phosphoinositide 3-kinase complex.

Keep in mind that ribosomes synthesize contractile proteins in skeletal muscle using the information provided by messenger RNA transcripts. Although this may seem relatively insignificant, PGF2a signaling is mechanistically similar to the IGF-1 signaling cascade, which definitely induces skeletal muscle hypertrophy.

What does science say about this?

A classic study conducted by Dr. Todd Trappe at Ball State University (2) examined the effects on whole-body protein synthesis in 24 men who received the maximum over-the-counter doses of specific COX-2 inhibitors, including ibuprofen (1,200 mg/day), acetaminophen (4,000 mg/day), or a placebo after completing 10–14 sets of 10 leg extensions (eccentric phase only) at 120% of each participant’s concentric one-repetition maximum.

These inhibitors break down arachidonic acid for prostaglandin biosynthesis.

Interestingly, intramuscular protein-synthesis rates during the 24 hours after exercise increased by 76% in the placebo group, while protein synthesis remained unchanged in the two groups that received ibuprofen or acetaminophen.

Similarly, a 24-hour post-exercise elevation in intramuscular PGF2a levels was observed in the placebo group (+77%) compared with the ibuprofen (-1%) and acetaminophen (-14%) groups, which broke down arachidonic acid for prostaglandin biosynthesis.

This study appeared to provide the first compelling evidence of the involvement of arachidonic acid and PGF2a in muscle protein synthesis and therefore gained acceptance in sports circles that promote muscle hypertrophy as one of the anabolic pathways that is not always recognized.

On the other hand, a recent study conducted at Baylor University (3) demonstrated that arachidonic acid supplementation favorably reduced a circulating pro-inflammatory cytokine (interleukin-6) associated with cardiovascular disease and muscle protein breakdown, while also causing an upward trend in resting PGF2a and PGE2 levels (which are apparently anabolic, to say the least).

Sources

• (1)- Journal of Biol Chem. 274:12925-12932, 1999: A potential role for extracellular signal-regulated kinases in prostaglandin F2alpha-induced protein synthesis in smooth muscle cells.
• (2)- American Journal of Physiol Endocrinol Metab. 282:E551-556, 2002: Effect of ibuprofen and acetaminophen on postexercise muscle protein synthesis.
• (3)- Nutrition and Preventive Health Research, Baylor University, Waco, TX 76798-7313: