Arachidonic Acid Trip

TAGS: Arachidonic Acid, ARA, inflammation, muscle growth, Scott Stevenson

Smarter than Mother Nature?

Those of you who read my column here at elitefts™ know that I’ve likened bodybuilding training to an “unnatural act,” an otherwise “unproductive” expenditure of energy intended mainly to produce muscle growth. Nutritionally, similar “anabolic tricks” can be played by consuming pre-digested, high-tech protein and carbohydrate supplements just before, during and/or after exercise (peri-workout recovery supplementation), even though the autonomic nervous system is hardly geared toward digestive processes (1).

But are we really outsmarting Mother Nature in these instances? Like building up a callus or getting a good tan after repeated UV exposure, muscle hypertrophy can be considered a kind of protective adaptation that guards against future muscular overload. Truth be told, I’m impressed that even while the sympathetic nervous system is primed for fight, flight or fright during a brutal workout, the mechanisms to respond anabolically to essential amino acids are still on immediate standby. Our bodies are exquisitely designed to improvise and adapt when it comes to stress and vital nutrients.

More or Less Inflammation?

Skeletal muscle remodeling—the growth adaptation we set in motion in the gym—involves inflammation. Thus, it makes sense that if we could hyper accelerate inflammation, we might also get more muscle growth. (Get “swole” to get “swoler,” so to speak.) The question we’ll address in this two-part article series will be in the context of dietary supplementation with arachidonic acid. Can (and should) we amplify the inflammatory response as a way to trick our muscles into greater growth?

Anyone who has pushed his limits in the gym knows inflammation quite well, particularly in the form of delayed onset muscle soreness [DOMS (2)]. Some of you may have even resorted to non-steroidal anti-inflammatory drugs to limit DOMS (3, 4). Gym veterans also know that too much is too much; there is a point of diminishing returns when recovery is inadequate. Overdo your training (over-inflame, so to speak) and you risk overtraining (and under recovering).

bodybuilding ARA on stage scott stevenson 090814

In this context, even avoiding pro-inflammatory foods has been cautioned against during periods of heavy activity and stress (5). Similarly, it’s also been suspected that peri-workout recovery supplementation (RS) may foster greater muscular gains by reducing DOMS-associated muscle damage (6, 7). Additionally, recovery supplementation (especially if it contains carbohydrates) may blunt the cortisol response to exercise, thus limiting the effects of cortisol on protein degradation and facilitating greater muscle growth (8–11).

There is a paradox here, though. By reducing cortisol peri-workout [negating its anti-inflammatory actions (1, 12)], one would hypothetically also be fostering inflammation. (How is it that RS may reduce DOMS and be “anti-inflammatory” in that sense but also be pro-inflammatory by reducing cortisol?)

Chronically elevated cortisol is also a known indicator of excessive training stress [i.e. overtraining (13, 14)], and higher cortisol is associated with poor strength performance (15, 16) and reduced training-induced muscle gains (17). Perhaps elevating cortisol in the face of overtraining is a mechanism to limit excessive inflammation (i.e. an intelligent means of governing aspects of the adaptive (muscle growth) process that aren’t immediately necessary)? Could it be that when faced with the “grow or die” mandate, our bodies choose not to grow and instead to live to fight another day? (Smart choice if you ask me…)

So do we best optimize the stress response by promoting inflammation or limiting it? As you can see from the above, just mindlessly putting the “pedal to the metal” when it comes to training, and thus inflammation, may not be the wisest strategy.

One particular dietary supplement, arachidonic acid (ARA), is noted for its inflammatory actions and thus offers to us a means to potentially increase the resistance exercise related inflammation and the ensuing muscle gains (18). In the rest of this article, we’ll take a closer look at ARA from the “ground up” as a mediator of cellular signaling (including inflammation). Part two will get into the “nitty gritty” of how ARA affects muscle growth and metabolism, particularly what this may mean for muscle and strength gains.

What Is ARA?

The body can derive ARA from linoleic acid (LA), an “omega-6” (i.e. w-6; see below) fatty acid that is essential in our diet [19 (an EFA that our bodies can't produce)]. [By the way, LA is not to be confused with alpha-linolenic acid, a w-3 EFA found in plants like flax (20).] LA can be converted to the w-6 fatty acid gamma linolenic acid [GLA (21)], which has anti-inflammatory actions (22) en route to the formation of our friend arachidonic acid.

In particular, you’ll see ARA designated as polyunsaturated (20:4), w-6 polyunsaturated fatty acid (PUFA). It’s considered polyunsaturated because at multiple (“poly”) places along the 20 carbon long molecule (four, in fact), ARA is not saturated (“unsaturated”) with hydrogen. (There are double bonds at those places instead.) It’s considered w-6 because the first of these double bonds is at the sixth position from the “omega” end of the fatty acid molecule. (FYI, these are cis double bonds as opposed to the trans isomer configuration that you might have heard of in the context of the heart unhealthy trans fats.)

bodybuilding side pose scott stevenson ARA 090814

What Does ARA Do?

Well, from the figure below, you can see that ARA is found in cell membrane fats (phospholipids and diacylglycerol) and is the starting material for quite a few molecules, particularly those called eicosanoids. [There are a number of different classes of eicosanoids including prostaglandins, leukotrienes, and lipoxins (23).] Eicosanoids are locally acting signaling molecules [affecting the cells of their origin as well as surrounding cells (20)] that can be derived from both w-3 fatty acids (yes, as in omega-3 fatty acids found in fish oil) and our w-6 buddy ARA. Eicosanoids are formed in response to a number of stresses (including exercise) and have a plethora of effects on blood flow, inflammatory responses, immune responses, and even important signals in our brains (24). In this context, you might consider ARA as the starting material for its own specific set of (generally pro-inflammatory) eicosanoids because of its particular molecular structure.

Does ARA Have Competition?

An important thing to note here is that the fish oil-derived w-3 eicosapentanoic acid (EPA) as well as the ARA precursor GLA are both anti-inflammatory and actually compete with ARA for two enzymes of eicosanoid production (cycloxygenase and lipoxygenase). Using the building material analogy, these enzymes are the construction workers who have produced eicosanoids based upon the starting material (w-3 or w-6 fatty acid). Give these workers a relative abundance of either w-3 or w-6 fatty acids and the resulting eicosanoids (and effects on inflammation) will reflect this.

So normally, we have interplay among [predominantly but not entirely (25)] pro-inflammatory ARA and the anti-inflammatory fatty acid precursors (including GLA, EPA and DHA, another w-3 found in fish oil). A particular instance of this competition is EPA’s ability to inhibit the conversion of ARA into the pro-inflammatory eicosanoids prostaglandin E2 (PGE2) and leukotriene B4 [LTB4 (26)]. Additionally, w-3 PUFAs (from both flax and fish oil) will decrease ARA content in the cell membrane and ARA metabolite production in a dose-dependent fashion (27). On the other hand, adding ARA to your diet may essentially undo the (anti-inflammatory) eiconsanoid-related benefits that one typically derives from fish oil supplementation (28).

Is ARA Healthy?

The health conscious may want to take particular note of ARA’s potential antagonism of the fish oil derived omega-3s DHA and EPA actions [e.g. anti-tumor effects (29–31)]. DHA actually inhibits COX enzyme-derived prostaglandin synthesis (32), meaning that it shares a mechanism of action with non-steroidal anti-inflammatories (NSAIDs), which may also reduce cancer risk (33, 34) To be fair though, not all ARA-derived eicosanoids are inflammatory in nature (25), and ARA intake does not seem to increase cancer risk (35).

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Figure 1: Overview of various eicosanoids derived from arachidonic acid. Figure based on various sources (25, 36–40).

ARA As A Pro-Inflammatory Anabolic?

In summary, supplemental ARA means more “worker bees” signing up for production of pro-inflammatory eicosanoids whereas w-3 PUFA consumption generally has the opposite effect. The interplay here is “dose-dependent” depending on your diet and supplementation. It’s possible that adding ARA to your diet may counteract the eicosanoid-related benefits of fish oil.

The complexity portrayed in the figure above prompts our original question—can we trick Mother Nature and promote greater muscle growth simply by supplying more ARA (via diet or supplementation)? Or are the eicosanoid-based signaling mechanisms just too intelligent to be so outwitted by such a simple tactic? In part two, we’ll dig even deeper.

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