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Arachidonic Acid (An Overview)

Updated: Aug 15, 2023

Evidence-Based. Scientifically Reviewed by Michael Sharpe, MSc and Dr. Michael Tamber, MD.


Arachidonic acid (also known as ARA and AA) is a polyunsaturated omega-6 fatty acid. Its structure is similar to that of saturated arachidic acid. Although it gets its name from the Latin word arachis (which stands for peanut).


Arachidonic acid stimulates skeletal muscle tissue repair and development by converting to prostaglandin PGF2α during and after physical activity.


PGF2α (similarly to leucine, hydroxy-methylbutyric acid (HMB), and phosphatidic acids) increases muscle protein synthesis via the Akt/mTOR anabolic pathway.



What Is It?

Arachidonic acid is a polyunsaturated fatty acid that is prevalent in the brain, muscles, and liver and is found in the phospholipids of cell membranes.


Skeletal muscle is a very active location for arachidonic acid retention, often contributing for 10-20% of the phospholipid fatty acid concentration. (1)


Arachidonic acid is a crucial inflammatory intermediary and may also serve as a vasodilator, in addition to being engaged in cellular signalling as a lipid second messenger implicated in the regulation of enzymes such as PLC-γ, PLC-δ, and PKC-α, PKC-β, and PKC-γ isoforms. (2)


Its chemical structure is a carboxylic acid having a 20-carbon chain and four cis-double bonds, with the first double bond occurring at the sixth carbon from the omega end.


arachidonic acid supplement tablets

A Conditionally Essential Fatty Acid

The fatty acid arachidonic acid is not classified as an essential fatty acid.


However, if there is a linoleic acid deficit or an inability to convert linoleic acid to arachidonic acid, it then becomes essential, classifying it as conditionally essential.


Because dietary linoleic acid has no effect on arachidonic acid levels in plasma/serum or erythrocytes, it's unclear if humans can convert linoleic acid to arachidonic acid. (3)



How It Works

Arachidonic acid has a wide range of effects within the body, especially considering it is a precursor to many other signalling molecules which have their own unique set of biological functions. The following list is the known derivatives of ARA.


  • prostaglandin G2 and prostaglandin H2, which may convert to various other prostaglandins, to prostacyclin, and thromboxanes

  • 5-hydroperoxyeicosatetraenoic acid (5-HPETE), which may convert to various leukotrienes as well as 5-hydroxyeicosatetraenoic acid (5-HETE) and may be further metabolised

  • 15-hydroperoxyeicosatetraenoic acid (15-HPETE), which may convert to 15-hydroxyeicosatetraenoic acid (15-HETE) and lipoxins

  • 12-hydroperoxyeicosatetraenoic acid (12-HPETE), which can convert to 12-hydroxyeicosatetraenoic acid (12-HETE) and to hepoxilins

  • anandamide

  • hydroxyeicosatetraenoic acids (HETEs)

  • epoxyeicosatrienoic acids (EETs)


The "arachidonic acid cascade" is the name given to the process of making these derivatives and their effects on the body.


Arachidonic acid signalling molecules synthesis diagram
Arachidonic Acid Signalling Molecules Diagram

Resistance exercise causes muscular inflammation, which is an important component of muscle development and repair. PGE2 and PGF2α are two prostaglandins released by arachidonic acid.


  • According to preliminary research involving skeletal muscle fibres, PGE2 increases protein breakdown whereas PGF2α increases protein synthesis. (4)

  • PGF2α has also been shown to promote the development of skeletal muscle fibres. (5)



Anti-Inflammatory Drugs Reduce the Effects

After exercise, using non-steroidal anti-inflammatory drugs (NSAIDs) reduces muscle protein synthesis by reducing the increase in PGF2α. (6, 7)


There is mixed evidence for this though, as some studies show a positive effect of NSAIDs on muscle growth due to inhibiting or reducing inflammation post exercise. (8, 9)


Regardless of a positive or negative effect, this research shows that arachidonic acid derived prostaglandins play a key role in the adaptive response to resistance exercise.


If inhibiting prostaglandin production diminishes resistance training adaptations in young adults, it's possible that increasing prostaglandin synthesis increases resistance training adaptations.


Arachidonic Acid Increases Inflammation

Essentially, arachidonic acid works mainly via the increase in PGE2 and PGF2α.


These two prostaglandins increase inflammation, especially post-exercise, which causes an increase in protein synthesis and a decrease in protein breakdown, promoting muscle growth.


The many derivatives of ARA may also contribute to the effects seen, though this is unclear and does not have enough scientific study to conclude anything.



Its Effects

There are some known or theorised effects of arachidonic acid, mostly in regards to muscle development, brain health, and Alzheimers.


In Alzheimers

Studies on arachidonic acid and Alzheimer's disease have yielded mixed results.


One study suggesting that ARA and its metabolites are linked to the onset of Alzheimer's disease, while other research suggests that supplementing arachidonic acid during the early stages of the disease may be effective in reducing symptoms and slowing its progression. (10, 11)


More research on arachidonic acid supplementation for Alzheimer's sufferers is required.


In the Brain

Arachidonic acid is one of the most prevalent fatty acids in the brain, and it is comparable to docosahexaenoic acid in terms of quantity (DHA).


About 20% of the brains fatty-acid composition is made up of these two. (12)


It's also essential for brain health, it aids in the fluidity of hippocampus cell membranes, among other things.


It also activates peroxisome proliferator-activated receptor gamma, which protects the brain from oxidative stress. (13, 14)



Syntaxin-3 (STX-3) is a protein involved in neuron development and repair that is activated by ARA. It is also important in the development of the nervous system at a young age. (15)


Infants given supplementary arachidonic acid for 17 weeks showed considerable increases in IQ, the simultaneous supplementation of arachidonic acid and DHA enhances this effect. (16)


The altered metabolism of ARA in adulthood may have a role in neuropsychiatric illnesses including Alzheimer's and bipolar disorder. (17)


In Bodybuilding

Arachidonic acid may stimulate muscle growth and development via PGE2 and PGF2α. It may increase protein synthesis and reduce protein breakdown. (18)


Those who engage in weight exercise may benefit from ARA supplementation since it increases lean body mass, muscular strength, and power, according to one study.


Dosage

There is still inadequate research to indicate an appropriate amount of arachidonic acid supplementation, however it is often taken at a dosage of roughly 2,000 mg 45 minutes before a workout, according to anecdotal evidence.


It's unclear if this is the best dosage or whether the time is crucial.


Due to the limited research on this supplement, I don't recommend you take arachidonic acid. There is minimal study on its short term and long term safety, as well as possible interactions.



Adverse Effects

Arachidonic acid supplementation in daily dosages of 1,000-1,500 mg (1-1.5 grams) for 50 days was well tolerated, with no notable adverse effects identified.


With this amount and duration of usage, many common health indices, such as kidney and liver function, serum lipids, immunity, and platelet aggregation, seem to be unaffected. (19, 20, 21)


Additionally, greater levels of arachidonic acid in muscle tissue may be linked to enhanced insulin sensitivity. (22)


Therefore, supplementing healthy individuals with arachidonic acid seems to pose neither toxicity or major safety concern. However, there is limited research and minimal information on the long-term safety of ARA.


In Active People

While studies in sedentary adults have shown no changes in resting inflammatory markers at dosages up to 1,500 mg (1.5 grams) daily, active people may react differently.


Young males consuming 1,000 mg (1 gram) a day of arachidonic acid for 50 days in conjunction with resistance exercise showed a substantial decrease in resting inflammation (as measured by the marker IL-6) in one research.


Interestingly, this shows that rather than being pro-inflammatory, taking arachidonic acid while doing resistance exercise may help to regulate and decrease systemic inflammation. (23)



In Your Diet

Higher levels of EPA and DHA (omega-3 fats), as well as the omega-6 arachidonic acid, were shown to have a considerably lower risk of heart disease in a meta-analysis searching for links between heart disease risk and specific fatty acids. (24)


The health effects of dietary omega-6 fats, particularly arachidonic acid, have also been positively reviewed by an American Heart Association scientific recommendation.


This vital fatty acid should not be restricted, according to the organisation. (25)


In fact, the article suggests that people get at least 5-10% of their calories from omega-6 fats, such as arachidonic acid, in their diet.


It implies that dietary ARA is not a risk factor for heart disease and may help maintain a healthy metabolism and lower the risk of heart disease.


Maintaining adequate quantities of omega-3 and omega-6 fatty acids in the diet is thus suggested for optimum health.


Is It Safe?

Arachidonic acid is not carcinogenic, and studies suggest that dietary levels are not linked to cancer risk (either positively or negatively).


However, ARA is still required for the inflammatory and cell development processes, which are disrupted in a variety of diseases, including cancer. (26, 27, 28, 29)


As a result, the safety of arachidonic acid supplementation in individuals with cancer, inflammatory illness, or other diseases is uncertain, and supplementation is not advised.


Likewise, the long-term safety of ARA is unknown.


Therefore, it doesn't seem to be unsafe as it is found within the diet, but the consumption of supplementary or higher levels of arachidonic acid should be avoided to be on the safe side.



More Information

Below is more information about arachidonic acid, such as other names, functions and roles, commonly confused names, etc.


Other Names: ARA, AA

Primary Role: Exercise performance, muscle gain

Confused With: Linoleic acid (parent omega-6 fatty acid)


Things to Note

  • Supplementing with arachidonic acid does not seem to cause inflammation in healthy people, but it may counteract the anti-inflammatory benefits of omega-3 fatty acid supplementation.

  • Aspirin and other NSAIDs inhibit the cyclooxygenase enzyme, which prevents arachidonic acid from being converted to other signalling molecules.

  • Supplementation and consuming in your diet are different, although we recommend not to supplement with ARA, consuming it within your diet is essential.


Warnings

  • It is possible that arachidonic acid can exacerbate joint inflammation and pain.

  • There is limited repeated or long-term study on arachidonic acids safety.

  • Individuals with a history of inflammatory illness, who have cancer, or who are in poor health should avoid consuming arachidonic acid.



Definitions

Below are definitions and short explanations of what some of the terms in this article mean.


  • NSAIDs (non-steroidal anti-inflammatory drugs): NSAIDs are non-steroidal drugs which reduce pain, decrease fever, and in higher doses, decrease inflammation. Examples include; ibuprofen, paracetamol, naproxen, etc.

  • Prostaglandin: Prostaglandins are a class of eicosanoids that behave like hormones in animals. They regulate inflammation, blood flow, blood clotting, etc.

  • PGE2: Prostaglandin E2 (PGE2), also known as dinoprostone, is a naturally occurring prostaglandin and a mediator of inflammation. Cyclooxygenase 2 (COX2) conversion of arachidonic acid generates PGE2.

  • PGF2α: Prostaglandin F2α, pharmaceutically termed carboprost, is a naturally occurring prostaglandin and a key mediator in inflammation. Cyclooxygenase 2 (COX2) conversion of arachidonic acid generates PGF2α.

  • DHA (docosahexaenoic acid): DHA is an omega-3 fatty acid that is found in the human brain, cerebral cortex, skin, and retina.

  • EPA (eicosapentaenoic acid): EPA is an omega-3 fatty acid and is used as a prescription medicine to reduce triglyceride levels.



References

This section contains links to research, studies, and sources of information for this article, as well as authors, contributors, etc. All sources, along with the article and facts, are subjected to a series of quality, reliability, and relevance checks.

Real Muscle primarily uses high-quality sources, such as peer-reviewed publications, to back up the information in our articles. To understand more about how we fact-check and keep our information accurate, dependable, and trustworthy, read more about us.

This evidence based overview of arachidonic acid features 29 references, listed below.


1. Smith GI, Atherton P, Reeds DN, Mohammed BS, Rankin D, Rennie MJ, Mittendorfer B. Omega-3 polyunsaturated fatty acids augment the muscle protein anabolic response to hyperinsulinaemia-hyperaminoacidaemia in healthy young and middle-aged men and women. Clin Sci (Lond). (2011, Sep)

2. Baynes, John W, Marek H. Medical Biochemistry 2nd Edition. (2005)

6. Trappe TA, White F, Lambert CP, Cesar D, Hellerstein M, Evans WJ. Effect of ibuprofen and acetaminophen on postexercise muscle protein synthesis. Am J Physiol Endocrinol Metab. (2002, Mar) (Clinical Trial)

7. Trappe TA, Fluckey JD, White F, Lambert CP, Evans WJ. Skeletal muscle PGF(2)(alpha) and PGE(2) in response to eccentric resistance exercise: influence of ibuprofen acetaminophen. J Clin Endocrinol Metab. (2001, Oct) (Clinical Trial) ✔

8. Trappe TA, Carroll CC, Dickinson JM, LeMoine JK, Haus JM, Sullivan BE, Lee JD, Jemiolo B, Weinheimer EM, Hollon CJ. Influence of acetaminophen and ibuprofen on skeletal muscle adaptations to resistance exercise in older adults. Am J Physiol Regul Integr Comp Physiol. (2011, Mar) (Randomised Controlled Trial)

9. Trappe TA, Standley RA, Jemiolo B, Carroll CC, Trappe SW. Prostaglandin and myokine involvement in the cyclooxygenase-inhibiting drug enhancement of skeletal muscle adaptations to resistance exercise in older adults. Am J Physiol Regul Integr Comp Physiol. (2013, Feb) (Randomised Controlled Trial)

10. Zareen Amtul, Markus Uhrig, Lin Wang, Richard F. Rozmahel, Konrad Beyreuther. Detrimental effects of arachidonic acid and its metabolites in cellular and mouse models of Alzheimer's disease: structural insight. Neurobiology of Aging. (2012)

11. Schaeffer, E.L., Forlenza, O.V. & Gattaz, W.F. Phospholipase A2 activation as a therapeutic approach for cognitive enhancement in early-stage Alzheimer disease. Psychopharmacology. (2009)

13. Fukaya T, Gondaira T, Kashiyae Y, Kotani S, Ishikura Y, Fujikawa S, Kiso Y, Sakakibara M. Arachidonic acid preserves hippocampal neuron membrane fluidity in senescent rats. Neurobiol Aging. (2007, Aug)

14. Wang ZJ, Liang CL, Li GM, Yu CY, Yin M. Neuroprotective effects of arachidonic acid against oxidative stress on rat hippocampal slices. Chem Biol Interact. (2006, Nov 7)

16. Birch EE, Garfield S, Hoffman DR, Uauy R, Birch DG. A randomized controlled trial of early dietary supply of long-chain polyunsaturated fatty acids and mental development in term infants. Dev Med Child Neurol. (2000, Mar) (Clinical Trial)

17. Rapoport SI. Arachidonic acid and the brain. J Nutr. (2008, Dec)

18. Trappe TA, Liu SZ. Effects of prostaglandins and COX-inhibiting drugs on skeletal muscle adaptations to exercise. J Appl Physiol (1985). (2013, Sep) (Review)

19. Nelson GJ, Schmidt PC, Bartolini G, Kelley DS, Phinney SD, Kyle D, Silbermann S, Schaefer EJ. The effect of dietary arachidonic acid on plasma lipoprotein distributions, apoproteins, blood lipid levels, and tissue fatty acid composition in humans. Lipids. (1997, Apr) (Clinical Trial)

21. Nelson GJ, Schmidt PC, Bartolini G, Kelley DS, Kyle D. The effect of dietary arachidonic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans. Lipids. (1997, Apr) (Clinical Trial)

22. Borkman M, Storlien LH, Pan DA, Jenkins AB, Chisholm DJ, Campbell LV. The relation between insulin sensitivity and the fatty-acid composition of skeletal-muscle phospholipids. N Engl J Med. (1993, Jan 28)

23. Roberts MD, Iosia M, Kerksick CM, Taylor LW, Campbell B, Wilborn CD, Harvey T, Cooke M, Rasmussen C, Greenwood M, Wilson R, Jitomir J, Willoughby D, Kreider RB. Effects of arachidonic acid supplementation on training adaptations in resistance-trained males. J Int Soc Sports Nutr. (2007, Nov 28)

24. Chowdhury R, Warnakula S, Kunutsor S, Crowe F, Ward HA, Johnson L, Franco OH, Butterworth AS, Forouhi NG, Thompson SG, Khaw KT, Mozaffarian D, Danesh J, Di Angelantonio E. Association of dietary, circulating, and supplement fatty acids with coronary risk: a systematic review and meta-analysis. Ann Intern Med. (2014, Mar 18) (Review)

26. Astorg P. Acides gras alimentaires, cancer colorectal et cancer de la prostate: études épidémiologiques [Dietary fatty acids and colorectal and prostate cancers: epidemiological studies]. Bull Cancer. (2005, Jul) (Review) (Translated)

27. Whelan J, McEntee MF. Dietary (n-6) PUFA and intestinal tumorigenesis. J Nutr. (2004, Dec)

28. Schuurman AG, van den Brandt PA, Dorant E, Brants HA, Goldbohm RA. Association of energy and fat intake with prostate carcinoma risk: results from The Netherlands Cohort Study. Cancer. (1999, Sep 15) (Comparative Study)

29. Leitzmann MF, Stampfer MJ, Michaud DS, Augustsson K, Colditz GC, Willett WC, Giovannucci EL. Dietary intake of n-3 and n-6 fatty acids and the risk of prostate cancer. Am J Clin Nutr. (2004, Jul)

Citations with a tick indicate the information is from a trusted source.

 

The information provided in this article is not intended to replace professional medical advice, diagnosis, or treatment. Always seek the guidance of a physician or other competent professional before following advice or taking any supplement. See our terms and conditions.



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