Cell study: more arachidonic acid, more muscle growth


William Llewellyn was right. About ten years ago Llewellyn came up with the theory that the fatty acid arachidonic acid might just be a key factor in muscle growth. Llewellyn launched a supplement containing arachidonic acid on the market, and financed a study which, although it didn’t discover any anabolic effects, did show that the substance enhances performance levels. But arachidonic acid probably does have an anabolic effect too, according to researchers at the University of Auckland in New Zealand.

The body converts the n-6 fatty acid linoleic acid into gamma-linolenic acid, or GLA, which is then converted into arachidonic acid. Arachidonic acid in turn is a precursor of hormone-like signal substances such as PGE2 and PGF2a. The diagram below shows how this all works.


Arachidonic acid has a bad reputation. The fatty acid, or rather, its metabolites are believed to whip up inflammation, and are therefore regarded as being responsible to the negative effects of a diet containing too much n-6 fatty acids. Llewellyn has always maintained that the story isn’t as simple as that. Some metabolites of arachidonic acid actually inhibit inflammation. [vpxsports.com January 4, 2013]

Seven years ago Llewellyn’s company Molecular Nutrition sponsored a study in which young strength athletes were given arachidonic acid. Their anaerobic capacity increased dramatically, although they didn’t become more muscular. In January 2013 a New Zealand PhD researcher James Markworth published the results of an in-vitro study which showed that Llewellyn’s theory does seem to hold water.

Markworth exposed C2C12 muscle cells to various concentrations of arachidonic acid. The higher the concentration, the thicker the muscle fibres were that the cells forms and the more muscle protein they manufactured.



Exposure to arachidonic acid inhibited the increase in the total number of muscle fibres, the figure above shows. Click on it for a larger version. Dark bars = muscle cells that were exposed to arachidonic acid.

On the right above you can see that arachidonic acid caused an increase in the number of larger muscle fibres – ones with more than five cell nuclei. That means that arachidonic acid causes muscle fibres to become bigger.

The researchers repeated their experiments with compounds that inhibit the COX-2 enzyme. COX converts arachidonic acid into PGE2. By blocking this almost all of the anabolic effect of arachidonic acid was taken away. Experiments with a non-metabolisable version of arachidonic acid produced no results either.

“The findings of the present study show that an increased availability of free arachidonic acid and subsequent metabolism by the COX-2 pathway have a net stimulatory effect on in vitro skeletal muscle cell growth”, the researchers conclude.

Am J Physiol Cell Physiol. 2013 Jan 1;304(1):C56-67. doi: 10.1152/ajpcell.00038.2012. Epub 2012 Oct 17.

Arachidonic acid supplementation enhances in vitro skeletal muscle cell growth via a COX-2-dependent pathway.

Markworth JF, Cameron-Smith D.


School of Exercise and Nutrition Science, Deakin University, Melbourne, Australia.


Arachidonic acid (AA) is the metabolic precursor to a diverse range of downstream bioactive lipid mediators. A positive or negative influence of individual eicosanoid species [e.g., prostaglandins (PGs), leukotrienes, and hydroxyeicosatetraenoic acids] has been implicated in skeletal muscle cell growth and development. The collective role of AA-derived metabolites in physiological states of skeletal muscle growth/atrophy remains unclear. The present study aimed to determine the direct effect of free AA supplementation and subsequent eicosanoid biosynthesis on skeletal myocyte growth in vitro. C2C12 (mouse) skeletal myocytes induced to differentiate with supplemental AA exhibited dose-dependent increases in the size, myonuclear content, and protein accretion of developing myotubes, independent of changes in cell density or the rate/extent of myogenic differentiation. Nonselective (indomethacin) or cyclooxygenase 2 (COX-2)-selective (NS-398) nonsteroidal anti-inflammatory drugs blunted basal myogenesis, an effect that was amplified in the presence of supplemental free AA substrate. The stimulatory effects of AA persisted in preexisting myotubes via a COX-2-dependent (NS-389-sensitive) pathway, specifically implying dependency on downstream PG biosynthesis. AA-stimulated growth was associated with markedly increased secretion of PGF(2?) and PGE(2); however, incubation of myocytes with PG-rich conditioned medium failed to mimic the effects of direct AA supplementation. In vitro AA supplementation stimulates PG release and skeletal muscle cell hypertrophy via a COX-2-dependent pathway.

PMID: 23076795 [PubMed – indexed for MEDLINE]

Source: http://www.ergo-log.com/more-arachidonic-acid-more-muscle-growth.html