Also Known As:
Arachidonic Acid
AA |
Variations:
|
Related Items:
|
Type:
Lipid/Fatty Acid |
|
What is Arachadonic Acid/Arachidonic Acid?
Some chemistry sources define 'arachadonic acid' to designate any of the eicosatetraenoic
acids. However, almost all writings in biology, medicine and nutrition limit
the use the term 'arachidonic acid' to all-cis 5,8,11,14-eicosatetraenoic acid.
Eicosatetraenoic acid designates any straight chain 20:4 fatty acid. There
are two isomers, both of them essential fatty acids, that are of particular
interest:
* all-cis 5,8,11,14-eicosatetraenoic acid is an w-6 fatty acid with the trivial
name arachidonic acid. It is formed by a desaturation of dihomo-gamma-linolenic
acid 20:4 w-6.
* all-cis 8,11,14,17-eicosatetraenoic acid is an w-3 fatty acid. It is an intermediary
between stearidonic acid (18:4 ?-3) and eicosapentaenoic acid (EPA, 20:5 w-3)
Some chemistry sources define 'arachadonic acid' to designate any of the eicosatetraenoic
acids. However, almost all writings in biology, medicine and nutrition limit
the use the term 'arachidonic acid' to all-cis 5,8,11,14-eicosatetraenoic acid.
What Are The Benefits of Arachadonic Acid/Arachidonic
Acid?
AA – Root Trigger of Hypertrophy by William Llewellyn
So we have one proposed mechanism contributing to the localization of the growth
response: receptor modulation. But how exactly does this modulation come about,
and are other things involved too? Perhaps we should go back to the root. We
need to see what is going on in your muscles during exercise, and how physiological
changes during this window will shape growth in the hours and days to follow.
It all begins with the damage caused to muscle fibers during resistance exercise.
The coinciding cell disruption causes the release of phospholipase A2, which
is responsible for liberating fatty acids from cell membranes. The main target
of phospholipase A2 here is the polyunsaturated fatty acid arachidonic acid
(AA), which is the most biologically active fatty acid towards skeletal muscle
growth. Via the conversion of AA to prostaglandins (PGE2 and PGF2alpha), AA
release will regulate protein synthesis and breakdown rates in local tissues,
shifting them in favor of growth[i] [ii] [iii]. It is the first trigger in a
very long and complex anabolic cascade.
Muscle growth involves more than just protein synthesis, however. For true
hypertrophy to occur, immature satellite (stem) cells called myoblasts must
be able to differentiate and fuse with mature muscle fibers. The process involves
several steps. First, myoblasts are formed through cell proliferation, and stay
stored on the outside of the cell. These mononucleated myoblasts will differentiate
and fuse, forming a multinucleated immature cell (with several nuclei). This
is usually referred to as a nascent myotube, and is the biological target of
most molecules that effect muscle cell fusion. Immature myotubes then fuse with
mature muscle cells, increasing myonuclear number and cell size. The myotubes
will then continue to increase in size through normal protein accretion (protein
synthesis). Through this, the growth and strengthening of the muscle fiber is
achieved. Studies with PGF2alpha have shown this prostaglandin to strongly support
hypertrophy at the second level of fusion, affecting the already formed nascent
myotube by increasing its number of nuclei[iv]. This is a sufficient mechanism
to support hypertrophy, and we must remember it is but one, and isolated to
one (albeit a primary) metabolite of arachidonic acid. There are yet still other
things at play.
AA and the AR
Although the link between arachidonic acid and muscle growth is well established,
if, and how much, the AA cascade is directly involved with another specific
aspect of the anabolic response, androgen receptor proliferation and local testosterone
sensitivity in the muscles, has not (yet) been. However, there is support for
the suspicion that there is a link, beyond the mere coincidence that both AA
release and AR density increase during productive workouts. It lies in the examination
of androgen receptor concentrations in other tissues. The first is a study on
the drug flufenamic acid, which blocks inflammation by preventing arachidonic
acid from converting to prostaglandins[v]. This drug was shown to markedly suppressed
AR density and transcription in prostate cancer cells, which points to a directly
related mechanism. However, because of speculation concerning other modes of
action, a definitive conclusion was not made. Not long after, another study
of interest was published, however. This one looked at the effects of essential
fatty acids on gene expression in mice liver[vi]. After a diet rich in AA, androgen
receptor concentrations were shown to increase more than 2.5 fold over control
values. Yet another investigation took place about a year later. It was a follow
up to the first investigation on flufenamic acid, which used more specific drugs[vii].
Here, the cyclooxygenase inhibitors celecoxib and nimesulide also suppressed
androgen receptor levels in prostate cancer cells. Again, none of these studies
may have been in skeletal muscle, but they do illustrate a strong effect in
other tissues that may (likely) carry over here.
AA, IGF-1, and PI3K
Arachidonic acid is also a known stimulator of phosphatidylinositol kinase
(PI3K)[viii]. Those familiar with the field of growth hormone research may recognize
a key study published back in 1996, which looked at PI3K, and how it related
to the protein synthesizing effects of both insulin and IGF-1[ix]. During this
investigation, incubation of epitrochlearis muscle explants from mice with IGF-1
significantly increased both inward glucose transport and protein synthesis
rates. This was an expected result given the hormone used, of course. But when
the PI3K inhibitor wortmannin was added in with the IGF-1, both of these increases
were quickly and effectively blunted. The researchers put it very succinctly
when commenting “Our results clearly demonstrated that stimulation of
PI3 kinase was indispensable for the stimulatory effect of both insulin and
IGF-1 on muscle protein synthesis.”
Exactly how AA affects PI3K and the IGF-1 signaling cascade is not entirely
known. This does appear to be one of the most complex actions of arachidonic
acid, and may involve the interaction of a number of its end products. It may
include not only the cyclooxygenase metabolites of AA (prostaglandins), but
lipoxygenase metabolite(s) as well, and perhaps involves both modulation of
IGF-1 receptor density and signaling ability, through direct and indirect means[x]
[xi] [xii] [xiii] [xiv]. Definitive studies in skeletal muscle tissue have not
been undertaken, so no exact conclusions can be drawn. What is clear, however,
is that arachidonic acid does affect this system, and likewise, should be intensifying
the growth producing signals of not only androgens, but Insulin-Like Growth
Factor 1 as well (endogenous or exogenous in origin). An in-depth examination
of the IGF-1/PI3 kinase system would entail an article all of its own.
Response Modulation
OK, so we know that arachidonic acid sits at the center of the core anabolic/hypertrophic
response. Now, here comes the bad news. Levels of this nutrient can vary depending
on a number of factors, and one of them happens to be exercise itself. A key
effect of regular training is to diminish the responsiveness of the arachidonic
acid cascade! This effect occurs via the gradual utilization of membrane-bound
arachidonic acid, and its replacement with other fatty acids. As the arachidonic
acid content is diminished, the body simply has less to use as substrate, and
becomes less able to produce prostaglandins and other active metabolites. When
this happens we seem to find it more difficult to trigger growth. It is also
one of the reasons we are so much more receptive to training when we are first
introduced to lifting, or when we hit the weights after a long period of time
off.
Both ends of this equation have been well documented, but independently of
one another. To begin with, studies with 19 sedentary middle-aged men in Sweden
in 1998 showed that moderate exercise for as little as 6 weeks would measurably
lower muscle AA content (it was largely replaced with oleic acid in this study)[xv].
On the other end of this phenomenon, we find a paper that was published about
a decade earlier, which followed a group of athletes for one full year[xvi].
This study looked at this response using PGE2 as a marker, and reported a gradual
and steady suppression of the prostaglandin system with regular exercise. The
longer the subjects were on a regular training schedule, the harder it was for
them to generate the same strong prostaglandin response (and logically other
products of AA metabolism). Thankfully, dietary intake of AA can be modified
(increased) to reverse (even exploit) this phenomenon. As you may be aware,
I have been a strong advocate of AA loading for muscle building phases or training
(Arachidonic Acid™), which is intended to increase AA levels and offer a strong
pro-anabolic effect. It is a practice I am happy to say has been very effective,
however I will save further product promotions for another time.
More About Arachadonic Acid/Arachidonic Acid
Arachidonic acid (AA) is an omega-6 fatty acid 20:4(w-6). It is the
counterpart to the saturated arachidic acid found in peanut oil, (L. arachis
– peanut.) Chemically, arachidonic acid is a carboxylic acid with a 20-carbon
chain and four cis double bonds; the first double bond is located at the sixth
carbon from the omega end.
Arachidonic acid (AA) is a polyunsaturated fatty acid that is present in the
phospholipids (especially phosphatidylethanolamine, phosphatidylcholine and
phosphatidylinositides) of membranes of the body's cells, and is abundant in
the brain. It is a precursor in the production of eicosanoids: the prostaglandins,
thromboxanes, prostacyclin and the leukotrienes (through enzymes including cyclooxygenase,
lipoxygenase and peroxidase). It is also used in the biosynthesis of anadamide.
The production of these derivatives, and their action in the body, are collectively
known as the arachidonic acid cascade.
Arachidonic acid is freed from phospholipid molecule by the enzyme phospholipase
A2. It is also involved in cellular signaling as a second messenger.
Arachidonic acid is one of the essential fatty acids required by most mammals.
Some mammals lack the ability to—or have a very limited capacity to—convert
linoleic acid into arachidonic acid, making it an essential part of their diet.
Since little or no arachidonic acid is found in plants, such animals are obligatory
carnivores; the cat is a common example.
In resting cells, arachidonic acid is stored within the cell membrane, esterified
to glycerol in phospholipids (Fig. 2). A receptor-dependent event, requiring
a transducing G protein, initiates phospholipid hydrolysis and releases the
fatty acid into the intracellular medium. Three enzymes may mediate this deacylation
reaction: phospholipase A2 (PLA2), phospholipase C (PLC), and phospholipase
D (PLD), whose different sites of attack on the phospholipid backbone are shown
in Fig. 2 (inset). PLA2 catalyzes the hydrolysis of phospholipids at the sn
(stereospecific numbering)-2 position. Therefore, this enzyme can release arachidonate
in a single-step reaction. By contrast, PLC and PLD do not release free arachidonic
acid directly. Rather, they generate lipid products containing arachidonate
(diacylglycerol and phosphatidic acid, respectively), which can be released
subsequently by diacylglycerol- and monoacylglycerol-lipases (Fig. 2).
Once released, free arachidonate has three possible fates: reincorporation
into phospholipids, diffusion outside the cell, and metabolism. Metabolism is
carried out by three distinct enzyme pathways expressed in neural cells: cyclooxygenase,
lipoxygenases, and cytochrome P450. Several products of these pathways act within
neurons to modulate the activities of ion channels, protein kinases, ion pumps,
and neurotransmitter uptake systems. The newly formed eicosanoids may also exit
the cell of origin and act at a distance, by binding to G-protein-coupled receptors
present on nearby neurons or glial cells. Finally, the actions of the eicosanoids
may be terminated by diffusion, uptake into phospholipids, or enzymatic degradation.
Usage Indications for Arachadonic
Acid/Arachidonic Acid
Around 1000mg of Arachidonic Acid a day for bodyweights of around 200lb. Reduce
to around 750 - 800mg a day for lighter individuals.
Side effects and ContraIndications of Arachadonic
Acid/Arachidonic Acid
With extensive monitoring of various biomarkers of health, the clinical trails
at Baylor University established not only that Arachidonic Acid is an effective performance-enhancing
supplement, but that it is safe supplement as well. Subjects taking Arachidonic Acid
noticed no negative changes in any of the markers of clinical safety, nor were
any side effects ever recorded. Furthermore, serum levels of inflammatory marker
IL-6 (interleukin-6) tended to strongly decline in the Arachidonic Acid group, which
demonstrates a potential beneficial reduction of systemic (whole-body) inflammation.
|
