Arachidonic acid – Essential fatty acid with key roles in inflammation and cell signaling

History & Evolution

1909: isolation from mammal tissues by Percival Hartley | 1940: definition of four double bonds locations (Martin et al. 2016)

Unlike its name suggests (derived from the Latin, arachis, meaning peanut), arachidonic acid is not present in high amounts in peanuts. This polyunsaturated fatty acid was named in 1913 after its saturated cousin, arachidic acid, which is commonly found in peanuts and other nuts (Martin et al. 2016). In contrast, arachidonic acid is rarely found in plants, but can be produced by many animal and microbial species (Abedi and Sahari 2014).

Biosynthesis vs. dietary uptake

Arachidonic acid (C20:4, standing for 20 carbons with 4 double bonds) is available in high amounts in foods of animal origin: meats, fish, dairy products and eggs (Mann et al. 1995; Taber et al. 1998; Abedi and Sahari 2014). In humans, arachidonic acid can be synthesized by elongation and saturation of linoleic acid (C18:2), an essential fatty acid. This means that a lack of linoleic acid can hinder processes requiring arachidonic acid. However, the degradation of phospholipids by phospholipases such as PLA2 can also be a source of arachidonic acid from endogenous metabolism. Both exogenous (dietary) and endogenous arachidonic acid may be used as substrates (Brash 2001).

Arachidonic acid and cellular membranes

The role of lipids in cellular organization and signalling is gaining momentum, putting fatty acids and complex lipids at the forefront of modern biomedical research.  As a fatty acid present in phospholipids, arachidonic acid plays an important role in cellular structure. Thanks to its four cis double bonds, it contributes to the flexibility of cellular membranes which is essential for cell function, particularly in the nervous system, skeletal muscle and immune system (Rich 1993; Tallima and El Ridi 2018).

Arachidonic acid, eicosanoids and inflammation

The four cis double bonds of arachidonic acid make it particularly prone to oxidation, from which eicosanoids are derived. This family of molecules includes prostaglandins, leukotrienes, and other lipids, which act as mediators and regulators of inflammation and wound healing. They also contribute to vascular tone, lipid metabolism, epithelial barrier function, pain, and more (Dennis and Norris 2015). For this reason, lipidomics is a popular method when investigating processes such as inflammation and anti-inflammatory therapies (Mazaleuskaya et al. 2016). Recently, one of these eicosanoids (12-HETE) was identified as an enterosyne, a bioactive molecule able to control the enteric nervous system (ENS) and contribute to the gut-brain axis (Abot et al 2020).

Arachidonic acid and the brain

Arachidonic acid and other polyunsaturated fatty acids (PUFA) are essential to brain development, repair, and maintenance, and to neuron protection (Liu et al. 2015). Although results are inconclusive, studies have explored the role of arachidonic acid and eicosanoids in depression (Lin et al. 2010; Gopaldas et al. 2019), amyotrophic lateral sclerosis (ALS) (Carter et al. 2020), Alzheimer’s disease (Snowden et al. 2017; Goozee et al. 2017), Parkinson’s disease (Willkommen et al. 2018) and bipolar disorder (Rapoport 2014). Research shows arachidonic acid supplements could also have a beneficial effect on cognitive dysfunction (Kotani et al. 2006).

Arachidonic acid supplements and athletes

The effects of arachidonic acid supplements have been investigated in fields as varied as neurology, cardiology, hepatology or nutrition (Kawashima 2019). But it is athletes that probably represent the largest market for arachidonic acid supplements. However, given the role of arachidonic acid in the regulation of inflammation, there are concerns about the safety of such supplements. Supplementation of the diet with arachidonic acid may help increase lean body mass, upper-body strength and peak power in trained males (De Souza E. O. et al. 2016). Studies on the effects of arachidonic acid supplements in resistance training also showed effects on skeletal muscle and blood lipid profiles and peak power without a significant induction of inflammation signalling (Markworth et al. 2018; Roberts et al. 2007).

Arachidonic acid and COVID-19

Recent metabolomic and lipidomic investigations on the effects of the SARS-CoV-2 virus revealed a link to imbalances in arachidonic acid and eicosanoid levels (Di Wu et al. 2020; Barberis et al. 2020). Arachidonic acid was identified as a marker of the severity of the disease (Barberis et al. 2020), leading the authors to conclude that PLA2 may be a potential target for the treatment of COVID-19. The suggested anti-viral properties of arachidonic acid and related metabolites also led to their recommendation as potential therapeutics (Shoieb et al. 2020; Das 2020).

Learn more about the roles of arachidonic acid and other fatty acids in complex chronic diseases such as cancer, Alzheimer’s disease, depression, inflammatory bowel disease, multiple sclerosis and diabetes in our whitepaper “Complex chronic diseases have a common origin”.

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References

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