Arachidonic Acid: Synthesis, Function in the Body, Supplementation and Administration

It is structurally related to the saturated arachidic acid in Cupuaçu butter (L. Arachis – peanut).

Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20: 4 (ω-6).


In the chemical structure, arachidonic acid is a carboxylic acid with a chain of 20 carbons and four cis double bonds; the first double bond is found in the sixth carbon from the omega end.

Some chemical sources define ‘arachidonic acid’ to designate any of the eicosatetraenoic acids. However, almost all those written in biology, medicine, and nutrition limit the term to all-cis-5,8,11,14-eicosatetraenoic acid.


Arachidonic acid is a polyunsaturated fatty acid present in phospholipids (especially phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositides) of the membranes of body cells and is abundant in the brain, muscles, and liver.

Skeletal muscle is a particularly active site for the retention of arachidonic acid, representing approximately 10-20% of the fatty acid content of phospholipids on average.

In addition to being involved in cell signaling as a second lipid messenger involved in the regulation of signaling enzymes, such as PLC-γ isoforms, PLC-δ and PKC-α, -β and -γ, arachidonic acid is an intermediate inflammation key and can also act as a vasodilator.


Conditionally essential fatty acid

Essential fatty acids are fatty acids that humans and other animals must ingest because the body needs them for good health but can not synthesize them. Those that are not essential are non-essential fatty acids.

Arachidonic acid is not one of the essential fatty acids. However, it becomes necessary if linoleic acid is deficient or if there is an inability to convert linoleic acid into arachidonic acid.

Some mammals lack the capacity or have a minimal ability to convert linoleic acid into arachidonic acid, making it an essential part of their diets.

Since there is little or no arachidonic acid in common plants, such animals are obligate carnivores; The cat is a typical example that cannot desaturate essential fatty acids.

However, a commercial source of arachidonic acid has been obtained from the fungus Mortierella Alpina.

The synthesis and cascade in humans

Arachidonic acid is released from a molecule of phospholipids by the enzyme phospholipase A2 (PLA2), which cleaves the fatty acid, but can also be generated from DAG by the diacylglycerol lipase.

Generated for signaling purposes seems to derive from the cytosolic phospholipase group A2 IVA (cPLA2, 85 kDa). In contrast, the inflammatory arachidonic acid is caused by the action of a low molecular weight secretory PLA2 (sPLA2, 14-18 kDa).

Arachidonic acid is the precursor that is metabolized by various enzymes to a wide range of biologically and clinically essential eicosanoids and metabolites of these eicosanoids:

Cyclooxygenase-1 and -2 enzymes (i.e., prostaglandin G / H synthase 1 and 2 {PTGS1 and PTGS2) metabolize arachidonic acid to Prostaglandin G2 and prostaglandin H2, which in turn can be converted into various prostaglandins, to prostacyclin, to thromboxanes.

The 5-lipoxygenase enzyme metabolizes arachidonic acid in 5-hydroperoxycosatetraeneic acid (5-HPETE), which in turn is metabolized to several leukotrienes (i.e., leukotriene B4, leukotriene C4, leukotriene D4, and leukotriene E4, as well as acid 5 -hydroxyacetethraine (5-HETE).

The 15-lipoxygenase-1 enzymes (ALOX15 and 15-lipoxygenase-2 (ALOX15B) metabolize arachidonic acid to 15-hydroperoxicosatetraemoic acid (15-HPETE), which can then be further metabolized to 15-hydroxycosatetraenoic acid.

The enzyme 12-lipoxygenase (ALOX12) metabolizes arachidonic acid to 12-hydroperoxy eicosatetraenoic acid (12-HPETE0), which can then be metabolized to 12-hydroxy eicosatetraenoic acid (12-HETE) and hepoxilins.

Arachidonic acid is also used in the biosynthesis of anandamide.

Part of the arachidonic acid is converted to hydroxy-acetic acid (HETE) and epoxy-acetic acid (TSE) acids by the epoxygenase.

The production of these derivatives and their action in the body are collectively known as the “arachidonic acid cascade.”

Activation of PLA2

Due to the importance of PLA2 in inflammatory responses, regulation of the enzyme is essential. PLA2 is regulated by phosphorylation and calcium concentrations. A MAPK phosphorylates PLA2 in Serine-505.

When phosphorylation is combined with an influx of calcium ions, PLA2 is stimulated and can be translocated to the membrane to begin catalysis.

PLA2, in turn, is activated by binding the ligand to the receptors, which include:

  • 5-HT2 receptors.
  • MGLUR1.
  • Receptor de bFGF.
  • Receptor de IFN-α.
  • IFN-γ receptor.

In addition, any agent that increases intracellular calcium can cause the activation of some forms of PLA2.

PLC activation

Alternatively, arachidonic acid can be cleaved from phospholipids after phospholipase C (PLC) cleaves the inositol triphosphate group, producing diacylglycerol (DAG), which is subsequently cleaved by diacylglycerol lipase to produce arachidonic acid.

Recipients that activate this path include:

  • Receptor A1.
  • Receptor D2.
  • Adrenergic receptor α-2.
  • Receptor 5-HT1.

Phospholipase C can also be activated by MAP kinase. Activators of this pathway include PDGF and FGF.

In the body

Muscle development:

Arachidonic acid promotes the repair and growth of skeletal muscle tissue by conversion to prostaglandin PGF2alpha during and after physical exercise.

PGF2alpha promotes the synthesis of muscle proteins by signaling through the Akt / mTOR pathway, similar to leucine, β-hydroxy-β-methyl butyric acid, and phosphatidic acid.

Due to the association with the maintenance of muscle tissue, arachidonic acid supplements are being used by some bodybuilders to improve the effects of training.

A study in the “Journal of the International Society of Sports Nutrition” published in November 2007 found that after 25 days, there was evidence of reduced inflammation in people who were taking arachidonic acid supplements but did not increase muscle strength or growth.


Arachidonic acid is one of the most abundant fatty acids in the brain and is present in amounts similar to docosahexaenoic acid (DHA). Both represent approximately 20% of their rich acid content.

Like docosahexaenoic acid, neurological health depends on sufficient levels of arachidonic acid. Arachidonic acid helps maintain the fluidity of the hippocampal cell membrane.

It also helps protect the brain from oxidative stress by activating the gamma receptor activated by the peroxisome proliferator.

Arachidonic acid also activates syntaxin-3 (STX-3), a protein involved in the growth and repair of neurons.

He is also involved in early neurological development.

A study funded by the US National Institute of Child Health and Human Development. In the US, infants (18 months) who received supplemental arachidonic acid for 17 weeks showed significant improvements in intelligence, as measured by the Mental Development Index.

The simultaneous administration of arachidonic acid reinforces this effect with docosahexaenoic acid.

In adults, the altered metabolism of arachidonic acid may contribute to neuropsychiatric disorders, such as Alzheimer’s disease and bipolar disorder.

There is evidence of significant alterations in converting arachidonic acid to other bioactive molecules (overexpression or changes in the cascade of the arachidonic acid enzyme) under these conditions.

Alzheimer disease:

Studies on arachidonic acid and the pathogenesis of Alzheimer’s disease are mixed, with a survey of arachidonic acid and its metabolites suggesting that they are associated with the onset of Alzheimer’s disease.

While another study suggests that arachidonic acid supplementation during the early stages of this disease may effectively reduce symptoms and slow the progression of the disease.

Additional studies on administering arachidonic acid supplements for patients with Alzheimer’s are needed.

Another study indicates that air pollution is the source of inflammation and the metabolites of arachidonic acid promote inflammation to signal the immune system to cell damage.

Bodybuilding supplement:

Arachidonic acid is marketed as an anabolic bodybuilding supplement in various products. It has been shown that arachidonic acid supplementation (1,500 mg/day for eight weeks) increases lean body mass, strength, and anaerobic power inexperienced men trained in resistance.

This was demonstrated in a placebo-controlled study at the University of Tampa. Thirty men (20.4 ± 2.1 years old) took arachidonic acid or a placebo for eight weeks and participated in a controlled resistance training program.

After eight weeks, lean body mass (LBM for its acronym in English) had increased significantly, and to a greater extent, in the group of arachidonic acid (1.62kg) versus placebo (0.09kg) (p <0, 05).

The change in muscle thickness was also more significant in the arachidonic acid group (0.47 cm) than in the placebo group (0.25 cm) (p <0.05).

The anaerobic power of Wingate increased to a greater extent in the arachidonic acid group (723.01 to 800.66 W) versus placebo (738.75 to 766.51 W).

Finally, the change in total strength was significantly more significant in the arachidonic acid group (109.92 pounds) compared to the placebo (75.78 pounds).

These results suggest supplementation with arachidonic acid can positively increase skeletal muscle strength and hypertrophy adaptations in men trained in resistance.

A previous clinical study that examined the effects of 1,000 mg/day of arachidonic acid for 50 days found supplements to improve anaerobic capacity and exercise performance in men.

During this study, a significant effect of group-time interaction was observed in the relative maximum power of Wingate (AA: 1.2 ± 0.5, P: -0.2 ± 0.2 W • kg-1, p = 0.015).

Statistical trends were also observed in 1RM bench press (AA: 11.0 ± 6.2, P: 8.0 ± 8.0 kg, p = 0.20), average Wingate power (AA: 37.9 ± 10.0, P: 17.0 ± 24.0 W, p = 0.16), and the total work of Wingate (AA: 1292 ± 1206; P: 510 ± 1249 J, p = 0.087).

During resistance training, supplementation with arachidonic acid promoted significant increases in relative maximum potency with other performance-related variables that approach significance.

These findings support the use of arachidonic acid as an ergogenic.

Arachidonic acid and inflammation in the diet:

The increase in the consumption of arachidonic acid will not cause inflammation during normal metabolic conditions unless the lipid peroxidation products are mixed.

Arachidonic acid is metabolized to pro-inflammatory and anti-inflammatory eicosanoids during and after the inflammatory response.

To promote growth, arachidonic acid is also metabolized to inflammatory and anti-inflammatory eicosanoids during and after physical activity.

However, chronic inflammation due to exogenous toxins and excessive exercise should not be confused with the acute inflammation of movement and sufficient rest that requires the inflammatory response to promote the repair and growth of microtears in tissues.

However, the evidence is mixed. Some studies that provide between 840mg and 2,000mg per day to healthy individuals for up to 50 days have not shown an increase in inflammation or related metabolic activities.

However, others show that increased levels of arachidonic acid are associated with reduced pro-inflammatory IL-6 and IL-1 levels and an increase in beta anti-inflammatory tumor necrosis factors. This can result in a reduction of systemic inflammation.

Arachidonic acid still plays a central role in inflammation related to injuries and many diseased states.

How it is metabolized in the body dictates its inflammatory or anti-inflammatory activity.

Individuals suffering from joint pains or active inflammatory disease may find that increased consumption of arachidonic acid exacerbates symptoms, presumably because it becomes more easily inflammatory compounds.

Similarly, a high arachidonic acid intake is not recommended for people with inflammatory diseases or health problems.

It should be noted that although the administration of arachidonic acid supplements does not seem to have proinflammatory effects in healthy individuals, it may counteract the anti-inflammatory effects of omega-3 fatty acid supplements.

The discovery of COX enzymes and the role of eicosanoids derived from arachidonic acid in pain and inflammation led to the understanding that aspirin works by blocking COX enzymes.

COX inhibitors, called nonsteroidal anti-inflammatory drugs or NSAIDs such as ibuprofen, Celebrex, and celecoxib, also block COX enzymes, relieve pain and inflammation, and prevent heart attacks by blocking the actions of molecules derived from the body. Arachidonic acid.

However, nonsteroidal anti-inflammatory drugs can cause ulcers because they also block the formation of eicosanoids that help repair damage to the stomach and intestinal lining.

Effects of arachidonic acid supplementation on health

The administration of arachidonic acid supplements in daily doses of 1,000mg – 1,500mg for 50 days has been well-tolerated during several clinical studies, with no significant side effects reported.

All common health markers, including kidney and liver function, serum lipids, immunity, and platelet aggregation, appear to be unaffected by this level and duration of use.

In addition, higher concentrations of arachidonic acid in muscle tissue can be correlated with better insulin sensitivity. The supplementation with arachidonic acid in the diets of healthy adults seems to offer no toxicity or significant risk of safety.

Although studies analyzing the administration of arachidonic acid supplements in sedentary subjects failed to find changes in resting inflammatory markers at doses of up to 1,500 mg per day, subjects trained in strength may respond differently.

A study at Baylor University reported a significant reduction in resting inflammation (through the IL-6 marker) in young men supplementing 1,000 mg/day of arachidonic acid for 50 days in combination with resistance training.

This suggests that the administration of arachidonic acid supplements during resistance training can improve the regulation of systemic inflammation.

A meta-analysis from the University of Cambridge looking for associations between the risk of heart disease and individual fatty acids reported a significantly lower risk of heart disease with higher levels of EPA and docosahexaenoic acid (Omega-3 fats) as acid Omega-6 arachidonic.

Scientific advice from the American Heart Association has also favorably evaluated the health impact of omega-6 fats in the diet, including arachidonic acid.

The group does not recommend limiting this essential fatty acid. The document suggests that people follow a diet of at least 5-10% calories from omega-6 fats, including arachidonic acid.

It suggests that arachidonic acid in the diet is not a risk factor for heart disease and may play a role in maintaining optimal metabolism and reducing the risk of heart disease.

Therefore, it is recommended to maintain sufficient levels of intake of omega-3 and omega-6 fatty acids for optimal health.

Arachidonic acid is not carcinogenic, and studies show that the diet level is not associated (positively or negatively) with cancer risk.

However, arachidonic acid remains an integral part of the inflammatory process and cell growth, altered in many diseases, including cancer.

Therefore, the safety of administering arachidonic acid supplements in patients with cancer, inflammation, or other disease states is unknown, and supplementation is not recommended.

Administration of arachidonic acid

There is not enough evidence to recommend an ideal dose of arachidonic acid supplements, but anecdotally it is used in amounts of around 2,000mg taken 45 minutes before a workout. It is not clear if this is an optimal dose or if the time is necessary.

The ideal dose of arachidonic acid may be a dietary restriction for people with chronic inflammatory disorders, such as rheumatoid arthritis or inflammatory bowel diseases.

In inflammatory diseases, the administration of arachidonic acid supplements is probably contraindicated.