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Arachidonic Acid In Inflammation + Beneficial Roles

Written by Aleksa Ristic, MS (Pharmacy) | Last updated:
Jonathan Ritter
Puya Yazdi
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology), Puya Yazdi, MD | Written by Aleksa Ristic, MS (Pharmacy) | Last updated:

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Arachidonic acid (AA) is important for growth and development, especially in infants. It plays a central role in the inflammatory response. AA supplements have gained popularity for their supposed benefits in strength training and bodybuilding. This post reveals the roles of arachidonic acid in health and disease and discusses the uses & safety of AA supplements.

What is Arachidonic Acid (AA)?

Arachidonic acid (AA), an omega-6 fatty acid (unsaturated fat) found in the outer layer of most cells in the body. It’s rich in the brain, liver, fat tissue, and other organs [1, 2, 3].

AA is an important part of the normal inflammatory process, which gets activated during injury or irritation. It gets converted into inflammatory molecules that help heal and restore the function of damaged tissues [1, 2, 3, 4].

Excess omega 6s are often seen as bad because they get converted to arachidonic acid, which can increase inflammation in some situations.

Most of the functions of AA is attributed to its conversion into other molecules – leukotrienes, prostaglandins, and more – through the action of enzymes (oxygenases) [5, 3].

AA is naturally produced in the body from another molecule (linoleic acid), and can also be ingested through different foods. It is most popular for its supposed effects on exercise and bodybuilding but also plays other important roles in the body such as boosting the immune response [6, 7, 8, 9].

It is vital for the development and growth of infants and is a major component in breast milk [10].

Pathways, Metabolism & Roles in Inflammation

Arachidonic acid (AA) is one of the most highly regulated fatty acids in cells. Even during extreme fat-free diets low in AA, it is difficult to reduce levels past a certain point. This compound gets released when cells are stimulated, and rapidly gets metabolized in most tissues [11].

Arachidonic acid is obtained through two main pathways. The first is internal production from shorter fatty acids like linoleic acid, which mainly occurs in the liver. The second pathway is through food, especially fish and poultry [11].

A small portion of released arachidonic acid (AA) gets converted back into fats (triglycerides and phospholipids), allowing cells to remodel their fat composition. But most of the released AA is metabolized into a variety of active compounds [11]:

  • Metabolized by COX-1 and COX-2 (cyclooxygenase) enzymes into prostaglandins
  • Converted into leukotrienes, lipoxins, and hydroxyeicosatetraenoic acids (HETE) through the action of the enzyme lipoxygenase.
  • Oxidized by P450 enzymes into eicosatrienoic acid products

Different cell types produce different active metabolites from AA. The variety of products differs based on the content and activators (agonists) within the cells.

These functions can be potent and opposite to each other. For example, prostaglandins and leukotrienes can be pro-inflammatory agents while lipoxin A4 negates the pro-inflammatory response. Certain prostaglandins can also suppress inflammation [11, 12, 13].

Prostaglandins

AA is converted into prostaglandin H2 (PGH2), which is a precursor to all four primary prostaglandins. Prostaglandins are involved in the inflammatory signaling processes and transfer of energy within cells (increase the concentration of cAMP, calcium ions, and activate G-protein coupled receptors) [4, 14, 5, 1].

These pathways involving prostaglandins are vital to initiate a defense response against foreign invaders that enter the body [4, 14].

Leukotrienes

In white blood cells, the main products of AA metabolism are leukotrienes, which are involved in inflammation [11, 12, 15].

Leukotrienes are chemical messengers that powerfully activate the immune response. Conversion of AA into leukotrienes helps activate immune cells, boost microbial defense, and control the inflammatory response [16].

Thromboxane

The main product of metabolized AA in red blood cells is thromboxane, a hormone involved in blood clots and constriction of the arteries [11, 12, 15].

Thromboxane is a member of the lipid family called eicosanoids. It is made in platelets through another compound (thromboxane synthetase) that is produced from AA (via COX enzyme). Thromboxane is involved in muscle (smooth) contractions and blood clotting, which is especially important for blocking wounds and other areas of tissue damage [17, 18].

Health Relevance

While the inflammatory response is inherently protective (against pathogens and injury), chronically high levels of inflammation correlated with many chronic conditions, such as cancer, arthritis, stroke, neurodegenerative disorders, and cardiovascular disease.

Because several AA metabolites are part of the inflammatory response, it may be important to monitor AA intake under certain conditions [4, 19].

Beneficial Roles of Arachidonic Acid

Human Studies

1) Infant Development

Arachidonic acid (AA) is essential for infant development and is found at consistent levels in breast milk. Breast milk is vital for infants because the amount of AA naturally supplemented (through production and diet) is less than their bodies require. AA has been added into infant formulas in developed countries for a number of years now (since 2001 in the US) [10].

Even before birth, AA is supplemented to the fetus through the placenta. A study involving 2474 women found that the average concentration of AA in breast milk is 0.47%. AA is important for infant growth, brain development, and health [10, 20].

Vision

A meta-analysis (19 studies of 1949 infants total) evaluated the effects of long-chain unsaturated fatty acids (LCPUFA) supplementation (which includes arachidonic acid) in infant formulas on vision. They concluded that supplementation of infant formulas improves vision (visual acuity) in infants [21].

Growth

Two studies evaluated the use of different infant formulas on preterm (194) or low birth weight infants. In both studies, the authors concluded that AA supplementation (along with docosahexaenoic acid) enhanced growth and weight-gain, without any side effects [10, 22].

AA also plays a role in the hormonal regulation of bone formation in developing infants. During development, eicosanoids produced by AA relay signals that balance calcium and phosphate levels which are required for building bones [10].

Another product of AA, prostaglandin PGE2, is a strong regulator of cartilage formation. It also promotes bone formation by increasing the production of a protein (insulin-like growth factor), which powerfully stimulates the growth of bones, cartilage, and muscles. Although at high levels PGE2 may actually reduce bone formation (animal and cell studies) [10].

Brain Function

The human brain contains 60% fat which requires AA for its growth and function. AA is the most abundant fatty acid in the brain and rapidly accumulates during development [10, 23].

Using brain cells, researchers concluded that AA promotes cell survival and enhances the growth of neurons [10, 23, 24].

Immune System

AA may potentially play a role in maintaining the health of infants through its effects on the immune system. Compounds (eicosanoids) produced by AA regulate the inflammatory response [10, 25, 26].

2) Physical Performance

Arachidonic acid supplementation (1 g/day) increased energy levels (anaerobic capacity) and reduced inflammation but had no significant effects on muscle mass or strength in 31 resistance-trained males [27].

In another study, 30 strength-trained males were supplemented with AA (1.5 g/day) or a placebo for 8 weeks. In the AA group, there was an increase in lean body mass, upper-body strength, and peak power. The authors concluded that more long-term studies should be conducted with AA supplementation [6].

A common assertion of AA supplementation is that it causes muscle inflammation, but a study involving 20 healthy males showed this is not always the case. Additionally, AA supplementation (1.5 g/day) for four weeks had positive effects on the development and fat levels of muscles [28].

3) Anti-Parasitic Defence

Two studies evaluated the effectiveness and safety of arachidonic acid (AA) in the treatment of parasites (Schistosoma mansoni) in 334 otherwise healthy school children in Egypt.

When supplemented with AA (10 mg/kg per day for 15 days) alone, a moderate number of the students were cured (65% and 30%) [29, 8].

But when AA supplementation was combined with an anti-parasitic drug (praziquantel), cure rates significantly improved (91% and 72%). The cure rates were higher than with praziquantel alone (85% and 45%) [29, 8].

Animal Studies

The following studies were conducted only on animal models, and their results may not translate to humans.

4) Brain Protection

Arachidonic acid and its products are involved in a wide array of functions in the brain, including signal transmission, neurotransmitter release, brain cell (neuronal) gene expression, blood flow to the brain, sleep/wake cycle, and appetite [30, 10].

Abnormal metabolism of AA is implicated in a number of brain and psychological disorders such as epilepsy, stroke, Alzheimer’s, Parkinson’s, schizophrenia, and mood disorders (based on animal and cell studies) [30, 10].

5) Liver Protection

Supplementation with an oil rich in arachidonic acid significantly reduced liver damage in ethanol-treated rats [31].

Limitations and Caveats

While the evidence outlining the importance of arachidonic acid for infant development is strong, studies covering physical performance and other aspects are limited. As a naturally occurring component, AA plays a role in muscle function and endurance, but the effects of supplementation are inconclusive.

Health Risks & Precautions

Although there is no consensus on whether high AA intake increases inflammation, certain populations may want to be cautious in their consumption [19, 4].

One review paper said arachidonic acid does not increase the concentration of inflammatory markers and may even reduce inflammation. However, there is also evidence suggesting omega-6 fatty acids negate the anti-inflammatory effect of omega-3 fatty acids. One AA metabolite, PGE2, is involved in both pro-inflammatory and anti-inflammatory responses [19, 32].

Alzheimer’s Disease

In a mouse model with Alzheimer’s disease, food with 2% arachidonic acid resulted in higher levels of amyloid plaques in their brains [33].

However, a review of preliminary research suggested AA supplementation might be helpful for Alzheimer’s patients in combination with cognitive therapy [34].

Side Effects

Arachidonic acid (AA) supplementation does not seem to cause any side effects or adverse events. In all the clinical studies mentioned, there have been no reports of any unexpected effects on any of the participants [8, 35, 7, 36].

More long-term studies need to be conducted on humans to evaluate the long-term safety of AA supplementation.

Arachidonic Acid Deficiency

Arachidonic acid deficiency in preterm infants can exacerbate after birth while they are rapidly growing. This may lead to fragile and weakened vessels that could damage the central nervous system [37, 10].

Additionally, AA deficiency may compromise the immune response of infants. In a study on healthy preterm infants, AA levels were significantly lower than in term infants. Preterm infants also had significantly fewer immune cells (leukocytes and T-cells) [38, 10].

Several other studies found that both children and adults with learning disorders including ADHD, dyslexia, and autism have abnormally low blood levels of AA. The “normal range” for control subjects in one of the studies was 10.79 (wt%) versus 10.06 (wt%) in individuals with ADHD [39, 40, 41, 42, 10].

A meta-analysis of pooled data from blood samples found that AA concentrations were lower than normal in individuals with learning and developmental disorders. Their data also suggest that AA deficiency may only truly occur in children, whereas in adults the body can resist large fluctuations [43, 10].

Genetics

A study evaluated 229 participants with diabetes/metabolic syndrome and compared individuals of European-American and African-American descent. It was concluded that rs174537, an SNP near the FADS1 gene is most strongly associated with AA levels [44, 45].

Individuals homozygous for the minor allele had significantly lower AA levels than individuals homozygous to the major allele [44].

Another study involving 520 children from different European countries concluded that a genetic variation in FADS1 (minor allele rs174546) influences AA levels in the body [46].

Foods and Supplementation

Arachidonic acid supplements have not been approved by the FDA for medical use. In general, regulatory bodies aren’t assuring the quality, safety, and efficacy of supplements. Speak with your doctor before supplementing.

Foods

AA can be found at high levels in the visible fat of meat products, especially in pork fat (180 mg per 100 g fat) and the highest level of AA in lean meat was duck (99 mg per 100 g). Meats, in general, are a great source of AA [47].

Diets high in lean beef (500 g) significantly increased the concentration of AA in the blood compared to diets with less lean beef (30-100 g). Other good protein sources of AA are eggs and turkey breast [48].

For infants, breast milk (and formula) is the essential source of arachidonic acid [10].

Powder and Capsules

There are arachidonic acid supplementation products available online for purchase. Most of these are directed towards individuals who are bodybuilding and want fitness improvement.

Due to questionable effectiveness and unknown long-term safety, we do not recommend AA supplements.

Dosage

Since arachidonic acid supplements are not approved by the FDA for any condition, there is no official dose. Users and supplement manufacturers have established unofficial doses based on trial and error. Discuss with your doctor if AA may be useful as a complementary approach in your case and which dose you should take.

In the studies mentioned above, male athletes received about 1-1.5 grams per day of arachidonic supplementation with benefits in their performance [6, 27, 28].

However, inflammation-prone individuals may want to limit their intake of AA.

Reviews & User Experiences

The opinions expressed in this section are solely from the users who may or may not have a medical background. SelfHacked does not endorse any specific product, service, or treatment. Do not consider user experiences as medical advice. Never delay or disregard seeking professional medical advice because of something you have read on SelfHacked.

One user reported that arachidonic supplementation allows them to gain more muscle, although they did feel more sore than usual.

Another user reported that they became very sore 4 days later, but it was a feeling of soreness after a powerful workout. They mention it is a good supplement for trained athletes who want a little extra gain. After they took it for 3-4 weeks, the positives began to wear off and found it was useful to cycle on and off.

Other users did not feel any extra soreness and reported that they felt extra power during their workouts.

About the Author

Aleksa Ristic

Aleksa Ristic

MS (Pharmacy)
Aleksa received his MS in Pharmacy from the University of Belgrade, his master thesis focusing on protein sources in plant-based diets. 
Aleksa is passionate about herbal pharmacy, nutrition, and functional medicine. He found a way to merge his two biggest passions—writing and health—and use them for noble purposes. His mission is to bridge the gap between science and everyday life, helping readers improve their health and feel better.

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