Quick Navigation

Arachidonic acid

Arachidonic acid (AA) is a fatty acid of the omega-6 class, and is the main fatty acid of interest when referring to an omega-3:6 ratio (relative to fish oil fatty acids). It is proinflammatory and immunosupportive.

Our evidence-based analysis on arachidonic acid features 130 unique references to scientific papers.

Research analysis led by and reviewed by the Examine team.
Last Updated:

Easily stay on top of the latest nutrition research

Become an Examine Member to get access to all of the latest nutrition research:

  • Unlock information on 400+ supplements and 600+ health topics.
  • Get a monthly report summarizing studies in the health categories that matter specifically to you.
  • Access detailed breakdowns of the most important scientific studies.

Try FREE for 14 days

Research Breakdown on Arachidonic acid

1Sources and Structure


Arachidonic acid (AA) is the most biologically relevant omega-6 fatty acid, and in the lipid membrane of a cell serves as the fatty acid that is compared against the two fish oil fatty acids (EPA and DHA) in constituating an omega-3:6 ratio. Recent data suggests a daily intake of 50-250mg of arachidonic acid[2][3][4][5] with some sources estimated levels of up to 500mg daily;[6] arachidonic acid intake appears to be lower in vegetarians[7]

Dietary sources of arachidonic acid include:

  • Lean beef (460mg/kg)[8] 

  • Raw beef ribeye (460mg/kg raw, 200mg/kg cooked; 1.1% total fatty acids)[6]

  • Whole eggs (2,390mg/kg raw, 1,490mg/kg cooked; 1.9% total fatty acids)[6]

  • Chicken breast (640mg/kg raw, 400mg/kg cooked; 4.9% total fatty acids)[6]

  • Chicken thigh (1060mg/kg raw; 2.9% total fatty acids)[6]

  • Turkey breast (590mg/kg raw, 300mg/kg cooked; 3.1% total fatty acids)[6]

  • Pork loin (530mg/kg raw, 300mg/kg cooked; 2.2% total fatty acids)[6]

  • White tuna (packed in water and 330mg/kg;)[6]

  • Duck (990mg/kg)[9]

  • Kangaroo (620+/-120mg/kg)[5]

  • Emu (1,300+/-300mg/kg)[5]

  • Kidney (Lamb; 1,530+/-110mg/kg)[5]

  • Liver (Oxen; 2,940+/-640mg/kg)[5]

  • Barramundi (260+/-60mg/kg)[5]

  • Salmon (1,000+/-920mg/kg)[5]

Arachidonic acid is present in the visible fat ('grisle') of meat products at similar levels as the meat[9] and despite the above numbers it is not clear what occurs to arachidonic acid during the cooking process. Some studies note an increase in total fatty acids on a weight basis during the cooking process[10][11] while others note no significant differences (relative to other fatty acids[12]).

Arachidonic acid is found naturally occurring in the diet, mostly through animal products. If dietary arachidonic acid is not ingested, linoleic acid (the parent omega-6 fatty acid, also found in animal products) can be used to create arachidonic acid in the body

Concentrations of AA in the body follow a non-linear dose-dependent relationship with dietary linoleic acid (the parent omega-6 fatty acid)[13][14] where human diets consisting of less than 2% linoleic acid experience increases in plasma arachidonic acid when supplementing extra linoleic acid[15] but those at 6% or more ('standard' western diet) do not.[16] Conversely, dietary arachidonica acid itself dose-dependently increases plasma arachidonic acid.[17][18]

Dietary linoleic acid (the parent omega-6 fatty acid) can increase plasma arachidonic acid levels, which is how omega-6 fatty acids mediate their effects. There appears to be a limit cap in place, and supplementing arachidonic acid circumvents it and dose-dependently increases plasma arachidonic acid concentrations

Reducing arachidonic acid in the diet slightly (244% instead of 217%) increases the amount of EPA stored in the membranes of erythrocytes (from supplementation of fish oil) with no influence on DHA.[19]


Arachidonic acid is the reason for linoleic acid (dietary omega-6 fatty acid) having the status of an essential fatty acid, as the latter is required in the diet for synthesis into the former.

Additionally, arachidonic acid may be produced as a catablite of anandamide (one of the main endogenous cannabinoids acting upon the cannabinoid system, also known as arachidonoylethanolamide) via the FAAH enzyme[20][21] and may share some similar properties as anandamide such as acting upon TRPV4 receptors.[22] The endocannabinoid 2-arachidonoylglycerol can also be hydrolyzed into arachidonic acid via monoacylglycerol lipase[23] or similar esterases.[24]

Arachidonic acid may also be produced in the body via the breaking down of endocannabinoids


In aging rats and humans, there appears to be less bodily and neuronal stores of arachidonic acid (in plasma membranes)[25][26] associated with less activity of the biosynthetic enzymes that convert linoleic acid into arachidonic acid.[27]

Arachidonic acid appears to be reduced in older subjects relative to younger subjects due to less conversion of dietary linoleic acid into arachidonic acid


2.1Bioactivation of Eicosanoids

Eicosanoids are fatty acid metabolites that are derived from either arachidonic acid (if belonging to the omega-6 class) or from both eicosapentaenoic acid and docosahexaenoic acid (EPA and DHA, the two fish oil fatty acids, if belonging to the omega-3 class).

DHA, EPA, and AA all tend to be in the middle of a triglyceride backbone (at the sn-2 binding position) and are thus liberated form the membrane when the enzyme known as phospholipase A2 is activated; when this enzyme is activated (seizures,[28][29] ischemia,[30] NMDA-receptor stimulation,[31] as well and various inflammatory cytokines such as IL-1β,[32] TNF-α,[33] and PMA;[34] basically cell stressors) and due to the indiscriminatory nature of the phospholipase A2 enzyme (releasing DHA/EPA and AA with similar efficacy) the amount of eicosanoids produced are dependent on the ratio of omega3:6 fatty acids in the cell membrane.

Eicosanoids are signalling molecules derived from long chain fatty acids, and the eicosanoids from arachidonic acid are liberated by the same enzyme that liberates the fish oil fatty acids. This is the stage that determines which eicosanoids will be used in cell signalling, and is the mechanism underlying the importance of a dietary ratio of omega3:6 fatty acids (as the eicosanoids released into a cell reflect the membrane ratio)

Similar to the fish oil fatty acids, arachidonic acid can follow one of three pathways after it is liberated from the membrane. It can go into:

  • A COX-dependent pathway to produce PGH2 (the parent prostaglandin, and all prostaglandins are derived from this pathway); prostaglandins are signalling molecules with a pentacyclic structure (pentagon) in their fatty acid side-chain

  • A LOX-dependent pathway to produce lipoxins and leukotrienes

  • A P450 pathway, which can be further subject to either the epoxygenase enzyme (to produce epoxyeicosatrienoic acids or EETs) or the hydroxylase enzyme (to produce hydroxysaeicosatrienoic acids or HETEs)

Arachidonic acid can take one of three pathways after being liberated; the COX pathway (for prostaglandins), the LOX pathway (lipoxins and leukotrienes), or one of the two routes of the P450 pathway to make EETs or HETEs. All these classes of signalling molecules are known as omega-6 eicosanoids


After being liberated from the cell membrane by phospholipase A2, arachidonic acid is converted to Prostaglandin H2 (PGH2) via the Prostaglandin Endoperoxide H Synthases 1 and 2 (alternate names for the cyclooxygenase enzymes COX1 and COX2) and this process uses O2 to convert arachidonic acid to the unstable peroxide intermediate of PGG2 which then passively reconfigures into PGH2;[35] PGH2 serves as a parent intermediate for all other AA-derived prostaglandins (a subset of eicosanoid).[36] This first stage of eicosanoid synthesis is one of the reason for the antiinflammatory and antiplatelet effects of COX inhibitors (such as aspirin) which prevent AA eicosanoids from being made by reducing PGH2 production.[37][38][39]

In regards to the enzymes that mediate this conversion, COX2 is the inducable form that can be activated in response to inflammatory stressors in as little as 2-6 hours in a variety of cells[40][41][42] although it may be expressed at basal conditions in some cells (brain,[43] testes,[44] and the kidney cells known as macula densa[45]) while COX1 is just generally expressed in all cells;[46] it is due to this variation that COX2 is referred to as the inducible variant and COX1 the constitutive variant.

Arachidonic acid (AA) is liberated from the cell membrane by phospholipase A2, and then is converted into PGH2 (a prostaglandin) via one of the two COX enzymes. Inhibiting this stage inhibits production of all AA-derived eicosanoids, and after PGH2 is synthesized then it can branch out to other eicosanoids

PGH2 can be converted to Prostaglandin D2 via the enzyme prostaglandin D synthase (in the presence of sulfhydryl compounds)[47] and PDG2 is most well known to signal via the DP2 receptor (initially discovered on T cells and named CRTh2[48][49] and also referred to as GRP44[50] and coupled to a Gi or G12 protein[51]). In this sense and via signalling through its receptor, PGD2 is biologically active.

PGD2 can be converted to PGF2α which can bind to its own receptor (PGF2α receptor)[52] as well as the DP2 receptor, albeit 3.5-fold weaker than PGD2.[53] An isomer of PGF2α known as 9α,11β-PGF2 can also be produced from PGD2[54][55] and is equivalent in potency on the DP2 receptor.[54]

PGH2 can be converted to the prostaglandin D2, which is one of the few metabolic 'branches' of prostaglandins. After conversion into PGD2, further metabolism into 9α,11β-PGF2 and PGF2α can occur and these three molecules all possess similar effects

PGH2 (parent prostaglandin) can also be converted into prostaglandin E2 (PGE2) via the enzyme PGE synthase (of which there are a few, the membrane bound ones mPGES-1 and mPGES-2 and the cytosolic one cPGES[56]), and further metabolism of PGE2 results in PGF2. Interestingly, selective inhibition of the inducible enzyme (mPGES-1) appears to attenuate production of PGE2 without affecting concentrations of other prostaglandins downstream of PGH2[57][58][59] while indiscriminately suppressing COX enzymes suppresses all prostaglandins, and inhibiting PGE2 production causes a slight recompensation and increase in PGI2 levels (via COX2).[60][51]

PGE2 tends to be involved in pain as they are expressed in sensory neurons,[56] inflammation,[61] and potentially muscle loss.[62]

There are four receptors for prostaglandin E2 named EP1-4, which are all G-protein coupled receptors. EP1 is coupled to the Gq/11 protein and its activation can increase activity of phospholipase C (producing IP3 and diacylglycerol and thus activating PKC). The EP2 and EP4 receptors are both coupled to the Gs protein and activate adenyl cyclase (creatine cAMP and activating PKA).[63][56][64] EP3 receptors appear to be a tad more complex (being spliced into alpha, beta, and gamma variants; EP, EP, and EP) but are all coupled to Gi which suppresses the activity of adenyl cyclase (and thus opposes EP2 and EP4) except EP is coupled to both Gi and Gs proteins (inhibiting and activating adenyl cylase).[56][65][66]

The group of enzymes known as PGE synthases, but particularly mPGES-1, converts the parent prostaglandin into PGE2 which serves a role in promoting inflammation and pain perception. PGE2 activates the prostaglandin E receptors (EP1-4)

PGH2 (parent prostaglandin) may be subject to the enzyme prostacyclin synthase and be converted into the metabolite known as prostacyclin or PGI2, which can be further converted into 6-keto-PGF1α (and then converted to the urinary metabolite known as 2,3-dinor-6-keto Prostaglandin F1α). PGI2 is known to activate the I prostanoid receptor (PI)[67][51] which is expressed in the endothelium, kidneys, platelets, and brain.[51]

Prostacyclin production attenuates the pro-platelet function of thromboxanes (next section).[68]

PGH2 can be converted to PGI2, which is also called prostacyclin, and then this prostaglandin signals via the PI receptor

Somewhat unrelated to the prostaglandin class but still derived from the parent prostaglandin, when PGH2 is subject to the enzyme known as thromboxane synthase it is converted into Thromboxane A2. Thromboxane A2 (TxA2) signals through the the T prostanoid receptors (TP) which is a G-protein coupled receptor with two splice variants (TPα and TPβ) coupled to Gq, G12/13

Thromboxane A2 is best known for being produced in activated platelets from when the platelet is stimulated and arachidonic acid is released[68] and its suppression by COX inhibitors (namely aspirin) underlies the antiplatelet effects of COX inhibition.[69]

Thromboxane A2 is a metabolite of the parent prostaglandin (PGH2) that acts upon the T prostanoid receptors, it is most well known to being very pro-platelet formation and exacerbating blood clotting (and inhibition of Thromboxane A2 underlies the antiplatelet benefits of aspirin)

2.3Epoxy/Hydroxyeicosatrienoic Acids

Epoxyeicosatrienoic acids (EETs) are eicosanoid metabolites that are produced when arachidonic acid is subject to the P450 pathway and then immediately subject to the epoxygenase enzyme; hydroxyeicosatrienoic acids (HETEs) are also metabolites of the P450 pathway, but subject to a hydroxylase enzyme instead of the epoxygenase enzyme.

The HETEs include mostly 19-HETE and 20-HETE.

The EETs include 5,6-EET (converted to 5,6-DHET via the soluble epoxide hydroxylase enzyme), 8,9-EET (also converted, but to 8.9-DHET), 11,12-EET (into 11,12-DHET), and 14,15-EET (14,15-DHET).

The P450 pathway mediates both EET and HETE synthesis


In the LOX pathway (to confirm, prostaglandins are due to the COX pathway and both EETs and HETEs due to the P450 pathway) the major eicosanoid metabolites are the leukotrienes. Arachidonic acid is directly converted by the LOX enzyme into the novel metabolite 5-hydroperoxyeicosatrienoic acid (5-HPETE) which is then converted into Leukotriene A4.

Leukotriene A4 can take one of two routes, either conversion into Leukotriene B4 (LTB4) via the addition of a water group, or conversion into Leukotriene C4 via glutathione S-transferase. If it is converted into the C4 metabolite, it can be further converted into Leukotriene D4 and then Leukotriene E4.

Leukotrienes may be made near the nucleus.[70]

The LOX pathway tends to mediate leukotriene synthesis



240-720mg arachidonic acid to elderly persons for 4 weeks was able to increase plasma membrane arachidonic acid concentration (at 2 weeks with no further effect at 4 weeks) but urinary metabolites and serum PGE2 and lipoxin A4 were not significantly influenced.[71]

Arachidonic acid supplementation at rest does not necessarily increase plasma level of eicosanoid metabolites despite an increase in arachidonic acid stores



Autism spectrum disorders is a neurological condition associated with impaired social functioning and communication. Arachidonic acid has been investigated as, as well as DHA from fish oil, AA is critical for neuronal development in neonates[72] and disturbances in polyunsaturated fatty acid metabolism have been associated with autism disorders[73][74] (somewhat unreliably[75]).

Supplementation of 240mg AA and 240mg DHA (with 0.96mg astaxanthin as antioxidant) over 16 weeks in 13 patients with autism (half the dose if aged 6-10yrs) failed to find any reduction in scores on the SRS and ABC rating scales for autism although there was improvement in the subscales of social withdrawal (ABC) and communication (SRS) although the percentage of patients experiencing a 50% reduction in symptoms was not significantly different than placebo.[76]

Very limited evidence to support the role of arachidonic acid and fish oil DHA in the attenuation of autism symptoms, but there is a small bit of promise in aiding social symptoms that requires larger future trials

4.2Memory and Learning

Phospholipase A2 activation has been noted to promote neurite outgrowth following neuronal injury[77] and axon elongation.[77][78] The aforementioned implications eicosanoids (of both arachidonic acid and fish oil origin, mostly DHA) and arachidonic acid has been noted to promote neurite outgrowth via the 5-LOX pathway with maximal efficacy around 100µM[79][80] although at higher concentrations (10mM) this same pathway is neurotoxic via excessive oxidation (prevented with Vitamin E).[79] The neurite outgrowth may be related to acting upon calcium channels.[81]

In the body, arachidonic acid has a role in promoting neuronal development and elongation although unnaturally high concentrations of arachidonic acid appear cytotoxic

It has been noted that, in rats, the activity of the enzymes that convert linoleic acid into arachidonic acid are reduced with aging[27] and in aged rats supplementation of arachidonic acid to the diet appears to promote cognition[82][83][84] which has been replicated in otherwise healthy elderly men with 240mg AA (via 600mg triglycerides) as assessed by P300 amplitude and latency.[85]

Due to less production of arachidonic acid during the aging process, supplemental arachidonic acid may have a cognitive enhancing role in older persons (not clear if this would also extend to youth, seems unlikely)


Activation of phospholipase A2 has been implicated in being a link between immune cells and demyelination of neurons[86] possibly via COX dependent mechanisms, as celecoxib (COX2 inhibitor) has been noted to improve neuronal healing rates.[87] This implicates eicosanoids of both omega-3 and omega-6 origin.[88]

5Cardiovascular Health

5.1Blood Flow

Arachidonic acid (4.28% of the rat diet) appears to fully reverse the age-related increase in vasoconstriction induced by phenylephrine in rats by an endothelial-dependent means and is able to slightly augment an acetylcholine-induced vasorelaxation effect; there was no apparent benefit to young rats.[89] When tested in aged (65yrs average) humans, 240mg arachidonic acid paired with 240mg DHA (one of the fish oil fatty acids) for three months was able to improve coronary blood flow in periods of hyperemia but not at rest.[1]

Arachidonic acid supplementation in older ages may be cardioprotective by promoting blood flow, although human evidence at this point is time is fairly weak

6Skeletal Muscle and Performance


Arachidonic acid is thought to be important for skeletal muscle metabolism as the phospholipids in the membrane of the sarcoplasm are thought to be reflective of the diet,[90][91] training itself appears to alter phospholipid content of the muscle (independent of muscle fiber composition[92] and associated with a lower omega6:3 ratio[92][93]) and eicosanoids from arachidonic acid interact with muscle protein synthesis via their receptors.

Arachidonic acid signals for muscle protein sythesis via a COX-2 dependent pathway (suggesting prostaglandins are involved)[94] which is associated with increases in both prostaglandin E2 (PGE2) and PGF(2α),[94][95][96][97] although incubation with isolated PGE2 or PGF(2α) doesn't appear to fully replicate the hypertrophic effects of arachidonic acid.[94] PGE2 and PGF(2α) are also induced by exercise (specifically, a stretching of muscle cells in vitro[98]) and has been noted both in serum[99][100] and intramuscularly (four-fold, from 0.95+/-0.26ng/mL to 3.97+/-0.75ng/mL[101]) of exercising subjects, which are normalized within an hour after working out.[101] The ability of the stretch reflex to increase concentrations of PGE2 and PGF(2α)[98] may merely be due to stretching increasing the activity of COX2.[98][102]

It should be noted that supplementation of 1,500mg arachidonic acid (relative to a control diet containing 200mg) for 49 days has been noted to increase PGE2 secretion from stimulated immune cells (by 50-100%) in otherwise healthy young men,[103] but the relevance to skeletal muscle of this study is not known. This study also noted that, without stimulation, there were no significant differences between groups.[103] Elsewhere, a trend to increase serum PGE2 concentrations has been noted at rest in trained men given 1,000mg arachidonic acid for 50 days.[104]

Arachidonic acid, via the eicosanoids known as PGF(2α) and PGE2, stimulate muscle protein synthesis. They are produced from arachidonic acid, but normally do not form their respective muscle building eicosanoids until the cell is stimulated by a stressor (such as the stretch reflex on a muscle cell) which then induce their production

The receptor for PGF(2α) (FP receptor) appears to be upregulated by COX1 inhibitors (acetaminophen used in this study)[62] and enhanced signalling of PGF(2α) is thought to underlie the improvement in muscle protein synthesis seen in older individuals with antiinflammatory drugs. Supplementation of arachidonic acid does not appear to affect the amount of FP receptors in youth;[105] while exercise itself can increase EP3 receptor content neither COX1 inhibitors[62] nor arachidonic acid[105] appear to further influence it.

However, usage of COX2 inhibitors (in youth) have been found to abolish the exercise-induced increase of PGF(2α) (Ibuprofen and Acetaminophen)[105][106] as well as PGE2,[106] which is thought to be due to conversion from PGH2 into these metabolites being reliant on COX2 activity.

Due to the production of these eicosanoids being dependent on the COX2 enzyme, inhibiting this enzyme is thought to reduce the anabolic effects of exercise when taken prior to

Arachidonic acid (as well as EPA from fish oil) have not been noted to impair glucose uptake into isolated muscle cells and 10μM of fatty acid is able to attenuate saturated fat-induced insulin resistance;[107] a phenomena seen with saturated fats of 18 carbon chains or longer[108] that doesn't appear to apply to polyunsaturated fatty acids of equal chain length[109][110] and is likely related to increasing intracellular ceramides[111] that impair Akt signalling[112][113] and reduce GLUT4-mediated glucose uptake from insulin.[111]

Arachidonic acid and omega-3 polyunsaturated fats are both associated with improved insulin sensitivity of muscle cells, which may be secondary to reducing the levels of saturated fats in the lipid membrane and thus reducing intracellular ceramide concentrations. It is possible that this is not related to eicosanoids or the omega-3:6 ratio

6.2Exercise Interactions

Exercise is known to release vasoactive metabolites which induce blood vessel relaxation of which alongside some common vasodilatory agents (nitric oxide, adenosine, hydrogen ions) prostanoids are also released.[114] Arachidonic acid levels in serum are acutely suppressed by exercise (normalized within a few minutes) and there were increases in a few eicosanoids of arachidonic acid including 11,12-DHET, 14,15-DHET, 8,9-DHET, and 14,15-EET when cycling at 80% VO2 max acutely[115] and higher 2,3-dinor-6-keto Prostaglandin F1α urinary concentrations (indicative of higher PGI2 and 6-keto-PGF1α concentrations) have been noted at rest after 4 weeks of training in previously untrained youth.[116]


In 31 trained males subject to a standardized weight lifting program and diet (500kcal excess with 2g/kg protein) given either 1g arachidonic acid daily or placebo, supplementation over 50 days appeared to increase peak power (7.1%) and average power (3.6%) on a Wingate test but failed to positively influence muscle mass or weight lifting measures of power (bench press and leg press).[104]

7Bone Metabolism and the Skeleton


Prostaglandin F2 alpha (PGF2α) is able to postively influence bone growth via acting as a mitogen on osteoclasts.[117]

8Inflammation and Immunology


In patients of rheumatoid arthritis, a reduction of dietary arachidonic acid (from 171mg to 49mg; eicosapentaenoic acid nonsignificantly increased) and linoleic acid (from 12.7g to 7.9g) is able to reduce pain symptoms of rheumatoid arthritis (14%) and was able to improve the efficacy of fish oil supplementation from 17% to 31-37%.[19]

Limiting dietary intake of arachidonic acid appears to aid in symptoms of rheumatoid arthritis and appears to augment the efficacy of fish oil supplementation

9Interactions with Hormones


Both total and free testosterone appear to be unaffected following 50 days supplementation of arachidonic acid in resistance trained men.[104]


In resistance trained males given 1,000mg arachidonic acid for 50 days, there was no detectable difference in cortisol concentrations relative to placebo.[104]

10Interactions with the Lungs


Prostaglandin D2 (PGD2) is a potent bronchoconstrictor, which is slightly more potent than its related prostaglandin PGF2α (3.5-fold) and much more potent than histamine itself (10.2-fold).[53][55] 

It is thought that signalling through the DP-1 and DP-2 receptors mediate the pro-asthmatic effects of these prostaglandins as those are the receptors best known to respond[118] and abolishing this receptor genetically is associated with reduced airway inflammation.[48]

Arachidonic acid eicosanoids appear to be pro-asthmatic

11Interactions with Aesthetics


Prostaglandin D2 (of arachidonic acid origin) and the enzyme that produces it (prostaglandin D2 synthase) are 10.8-fold higher in the scalp of men with androgenic alpoceria (receding hair line) relative to the parts of their heads with hair[50] and appears to suppress hair growth via signalling through the DP2 receptor (also known as GPR44 or CRTh2[49][119]), with the PGD2 receptor 1 not being associated with hair growth suppression and the prostaglandin 15-ΔPGJ2 also having suppressive effects.[50] Overexpression of the enzyme is able to mimic androgenic alpoceria, suggesting that the enzyme is a therapeutic target[50] and this enzyme is known to be highly responsive to androgenic signalling.[120][121]

Prostaglandin D2 and its metabolites (produced from Prostaglandin H2 via the prostaglandin D2 synthase enzyme) are increased in the balding portion of androgenic alopecia relative to the haired portion, and the enzyme itself is increased in activity by androgens. Signalling via the DP2 receptor (named after prostaglandin D2) appears to suppress hair growth

Prostaglandin F2α signalling (PGF2α; which binds to the PGF2α receptor at a concentration of 50-100nM[122]) appears to promote hair growth.[123] 

There appears to be more prostaglandin E2 (PGE2) in the sections of the head in balding men with hair relative to bald areas (2.06-fold).[50] Increasing PGE2 is thought to be one of the possible mechanisms of minoxidil in promoting hair growth.[124]

Other prostaglandins derived from arachidonic acid

12Safety and Toxicology


Arachidonic acid is known to be increase in breast milk following oral consumption (either via foods or supplementation, in a relatively dose-dependent manner[125]) although supplemental DHA (fish oil) in isolation may reduce the concentration of arachidonic acid in breast milk.[126] The increase has been quantified at 14-23% over 2-12 weeks (220mg arachidonic acid supplementation[126]) while one week of 300mg arachidonic acid being insufficient to increase concentrations significantly.[127] This apparent time delay may be due to most fatty acids coming from material stores rather than directly from the diet of the mother.[128]

Arachidonic acid concentrations in breast milk tend to correlate with the diet, with low concentrations noted in some studies[129] with lower dietary arachidonic acid intake in general[126] and higher breast milk concentrations noted in studies where the study population tends to have higher arachidonic acid intake.[130]

Arachidonic acid is known to accumulate in the breast milk of mothers, and its concentrations in breast milk appear to correlate with dietary intake.


  1. ^ a b Oe H, et al. Arachidonic acid and docosahexaenoic acid supplementation increases coronary flow velocity reserve in Japanese elderly individuals. Heart. (2008)
  2. ^ Kawabata T, et al. Age-related changes of dietary intake and blood eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid levels in Japanese men and women. Prostaglandins Leukot Essent Fatty Acids. (2011)
  3. ^ Linseisen J, et al. Quantity and quality of dietary fat, carbohydrate, and fiber intake in the German EPIC cohorts. Ann Nutr Metab. (2003)
  4. ^ Sioen IA, et al. Dietary intakes and food sources of fatty acids for Belgian women, focused on n-6 and n-3 polyunsaturated fatty acids. Lipids. (2006)
  5. ^ a b c d e f g Mann NJ, et al. The arachidonic acid content of the Australian diet is lower than previously estimated. J Nutr. (1995)
  6. ^ a b c d e f g h Taber L, Chiu CH, Whelan J. Assessment of the arachidonic acid content in foods commonly consumed in the American diet. Lipids. (1998)
  7. ^ Phinney SD, et al. Reduced arachidonate in serum phospholipids and cholesteryl esters associated with vegetarian diets in humans. Am J Clin Nutr. (1990)
  8. ^ Sinclair AJ, et al. Diets rich in lean beef increase arachidonic acid and long-chain omega 3 polyunsaturated fatty acid levels in plasma phospholipids. Lipids. (1994)
  9. ^ a b Li D, et al. Contribution of meat fat to dietary arachidonic acid. Lipids. (1998)
  10. ^ Brignoli CA, Kinsella JE, Weihrauch JL. Comprehensive evaluation of fatty acids in foods. V. Unhydrogenated fats and oils. J Am Diet Assoc. (1976)
  11. ^ Anderson BA, Kinsella JA, Watt BK. Comprehensive evaluation of fatty acids in foods. II. Beef products. J Am Diet Assoc. (1975)
  12. ^ Broiling, Sex and Interrelationships with Carcass and Growth Characteristics and their Effect on the Neutral and Phospholipid Fatty Acids of the Bovine Longissimus Dorsi.
  14. ^ Renaud SC, Ruf JC, Petithory D. The positional distribution of fatty acids in palm oil and lard influences their biologic effects in rats. J Nutr. (1995)
  15. ^ James MJ, et al. Simple relationships exist between dietary linoleate and the n-6 fatty acids of human neutrophils and plasma. Am J Clin Nutr. (1993)
  16. ^ Rett BS, Whelan J. Increasing dietary linoleic acid does not increase tissue arachidonic acid content in adults consuming Western-type diets: a systematic review. Nutr Metab (Lond). (2011)
  17. ^ Whelan J, et al. Dietary arachidonate enhances tissue arachidonate levels and eicosanoid production in Syrian hamsters. J Nutr. (1993)
  18. ^ Adam O. Immediate and long range effects of the uptake of increased amounts of arachidonic acid. Clin Investig. (1992)
  19. ^ a b Adam O, et al. Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis. Rheumatol Int. (2003)
  20. ^ Khanna IK, Alexander CW. Fatty acid amide hydrolase inhibitors--progress and potential. CNS Neurol Disord Drug Targets. (2011)
  21. ^ Ahn K, McKinney MK, Cravatt BF. Enzymatic pathways that regulate endocannabinoid signaling in the nervous system. Chem Rev. (2008)
  22. ^ Watanabe H, et al. Anandamide and arachidonic acid use epoxyeicosatrienoic acids to activate TRPV4 channels. Nature. (2003)
  23. ^ Nomura DK, et al. Monoacylglycerol lipase regulates 2-arachidonoylglycerol action and arachidonic acid levels. Bioorg Med Chem Lett. (2008)
  24. ^ Ueda N. Endocannabinoid hydrolases. Prostaglandins Other Lipid Mediat. (2002)
  25. ^ Söderberg M, et al. Fatty acid composition of brain phospholipids in aging and in Alzheimer's disease. Lipids. (1991)
  26. ^ Lynch MA, Voss KL. Membrane arachidonic acid concentration correlates with age and induction of long-term potentiation in the dentate gyrus in the rat. Eur J Neurosci. (1994)
  27. ^ a b Maniongui C, et al. Age-related changes in delta 6 and delta 5 desaturase activities in rat liver microsomes. Lipids. (1993)
  28. ^ Bazan NG. Synaptic lipid signaling: significance of polyunsaturated fatty acids and platelet-activating factor. J Lipid Res. (2003)
  29. ^ Mori T, et al. Involvement of the arachidonic acid cascade in the hypersusceptibility to pentylenetetrazole-induced seizure during diazepam withdrawal. Biol Pharm Bull. (2012)
  30. ^ Sun GY, et al. Phospholipase A2 in the central nervous system: implications for neurodegenerative diseases. J Lipid Res. (2004)
  31. ^ NMDA Receptor-Stimulated Release of Arachidonic Acid: Mechanisms for the Bazan Effect.
  32. ^ Walev I, et al. Potassium regulates IL-1 beta processing via calcium-independent phospholipase A2. J Immunol. (2000)
  33. ^ Sun GY, Hu ZY. Stimulation of phospholipase A2 expression in rat cultured astrocytes by LPS, TNF alpha and IL-1 beta. Prog Brain Res. (1995)
  34. ^ Björnsdottir H, et al. Inhibition of phospholipase A(2) abrogates intracellular processing of NADPH-oxidase derived reactive oxygen species in human neutrophils. Exp Cell Res. (2013)
  35. ^ Prostaglandin Endoperoxide H Synthases (Cyclooxygenases)-1 and −2.
  36. ^ Wada M, et al. Enzymes and receptors of prostaglandin pathways with arachidonic acid-derived versus eicosapentaenoic acid-derived substrates and products. J Biol Chem. (2007)
  37. ^ Patrono C. Aspirin as an antiplatelet drug. N Engl J Med. (1994)
  38. ^ Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain.
  39. ^ Chan CC, et al. Pharmacology of a selective cyclooxygenase-2 inhibitor, L-745,337: a novel nonsteroidal anti-inflammatory agent with an ulcerogenic sparing effect in rat and nonhuman primate stomach. J Pharmacol Exp Ther. (1995)
  40. ^ Molecular cloning of human prostaglandin endoperoxide synthase type II and demonstration of expression in response to cytokines.
  41. ^ Evett GE, et al. Prostaglandin G/H synthase isoenzyme 2 expression in fibroblasts: regulation by dexamethasone, mitogens, and oncogenes. Arch Biochem Biophys. (1993)
  42. ^ Lipopolysaccharide priming of alveolar macrophages for enhanced synthesis of prostanoids involves induction of a novel prostaglandin H synthase.
  43. ^ Yamagata K, et al. Expression of a mitogen-inducible cyclooxygenase in brain neurons: regulation by synaptic activity and glucocorticoids. Neuron. (1993)
  44. ^ Wang X, et al. Inhibition of cyclooxygenase-2 activity enhances steroidogenesis and steroidogenic acute regulatory gene expression in MA-10 mouse Leydig cells. Endocrinology. (2003)
  45. ^ Cyclooxygenase-2 is associated with the macula densa of rat kidney and increases with salt restriction.
  46. ^ DeWitt DL, Meade EA. Serum and glucocorticoid regulation of gene transcription and expression of the prostaglandin H synthase-1 and prostaglandin H synthase-2 isozymes. Arch Biochem Biophys. (1993)
  47. ^ Urade Y, Hayaishi O. Prostaglandin D synthase: structure and function. Vitam Horm. (2000)
  48. ^ a b Pettipher R, Hansel TT. Antagonists of the prostaglandin D2 receptor CRTH2. Drug News Perspect. (2008)
  49. ^ a b Nagata K, et al. Selective expression of a novel surface molecule by human Th2 cells in vivo. J Immunol. (1999)
  50. ^ a b c d e Garza LA, et al. Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia. Sci Transl Med. (2012)
  51. ^ a b c d Prostanoids in health and disease.
  52. ^ Sales KJ, et al. Expression, localization, and signaling of prostaglandin F2 alpha receptor in human endometrial adenocarcinoma: regulation of proliferation by activation of the epidermal growth factor receptor and mitogen-activated protein kinase signaling pathways. J Clin Endocrinol Metab. (2004)
  53. ^ a b Hardy CC, et al. The bronchoconstrictor effect of inhaled prostaglandin D2 in normal and asthmatic men. N Engl J Med. (1984)
  54. ^ a b Beasley CR, et al. 9 alpha,11 beta-prostaglandin F2, a novel metabolite of prostaglandin D2 is a potent contractile agonist of human and guinea pig airways. J Clin Invest. (1987)
  55. ^ a b Bochenek G, et al. Plasma 9alpha,11beta-PGF2, a PGD2 metabolite, as a sensitive marker of mast cell activation by allergen in bronchial asthma. Thorax. (2004)
  56. ^ a b c d Kawabata A. Prostaglandin E2 and pain--an update. Biol Pharm Bull. (2011)
  57. ^ Mbalaviele G, et al. Distinction of microsomal prostaglandin E synthase-1 (mPGES-1) inhibition from cyclooxygenase-2 inhibition in cells using a novel, selective mPGES-1 inhibitor. Biochem Pharmacol. (2010)
  58. ^ Xu D, et al. MF63 {2-(6-chloro-1H-phenanthro{9,10-d}imidazol-2-yl)-isophthalonitrile}, a selective microsomal prostaglandin E synthase-1 inhibitor, relieves pyresis and pain in preclinical models of inflammation. J Pharmacol Exp Ther. (2008)
  59. ^ Bruno A, et al. Effects of AF3442 {N-(9-ethyl-9H-carbazol-3-yl)-2-(trifluoromethyl)benzamide}, a novel inhibitor of human microsomal prostaglandin E synthase-1, on prostanoid biosynthesis in human monocytes in vitro. Biochem Pharmacol. (2010)
  60. ^ Microsomal prostaglandin E synthase-1 inhibition in cardiovascular inflammatory disease.
  61. ^ Kalinski P. Regulation of immune responses by prostaglandin E2. J Immunol. (2012)
  62. ^ a b c Trappe TA, et al. 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)
  63. ^ Wang C, et al. A critical role of the cAMP sensor Epac in switching protein kinase signalling in prostaglandin E2-induced potentiation of P2X3 receptor currents in inflamed rats. J Physiol. (2007)
  64. ^ Narumiya S. Prostanoids and inflammation: a new concept arising from receptor knockout mice. J Mol Med (Berl). (2009)
  65. ^ Tober KL, et al. Possible cross-regulation of the E prostanoid receptors. Mol Carcinog. (2007)
  66. ^ Sugimoto Y, Narumiya S. Prostaglandin E receptors. J Biol Chem. (2007)
  67. ^ Hata AN, Breyer RM. Pharmacology and signaling of prostaglandin receptors: multiple roles in inflammation and immune modulation. Pharmacol Ther. (2004)
  68. ^ a b FitzGerald GA. Mechanisms of platelet activation: thromboxane A2 as an amplifying signal for other agonists. Am J Cardiol. (1991)
  69. ^ Patrono C, et al. Platelet-active drugs: the relationships among dose, effectiveness, and side effects: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. (2004)
  70. ^ Peters-Golden M, Brock TG. Intracellular compartmentalization of leukotriene synthesis: unexpected nuclear secrets. FEBS Lett. (2001)
  71. ^ Kakutani S, et al. Supplementation of arachidonic acid-enriched oil increases arachidonic acid contents in plasma phospholipids, but does not increase their metabolites and clinical parameters in Japanese healthy elderly individuals: a randomized controlled study. Lipids Health Dis. (2011)
  72. ^ Plausible explanations for effects of long chain polyunsaturated fatty acids (LCPUFA) on neonates.
  73. ^ Sliwinski S, et al. Polyunsaturated fatty acids: do they have a role in the pathophysiology of autism. Neuro Endocrinol Lett. (2006)
  74. ^ Vancassel S, et al. Plasma fatty acid levels in autistic children. Prostaglandins Leukot Essent Fatty Acids. (2001)
  75. ^ Bell JG, et al. The fatty acid compositions of erythrocyte and plasma polar lipids in children with autism, developmental delay or typically developing controls and the effect of fish oil intake. Br J Nutr. (2010)
  76. ^ Yui K, et al. Effects of large doses of arachidonic acid added to docosahexaenoic acid on social impairment in individuals with autism spectrum disorders: a double-blind, placebo-controlled, randomized trial. J Clin Psychopharmacol. (2012)
  77. ^ a b Edström A, Briggman M, Ekström PA. Phospholipase A2 activity is required for regeneration of sensory axons in cultured adult sciatic nerves. J Neurosci Res. (1996)
  78. ^ Nakamura S. Involvement of phospholipase A2 in axonal regeneration of brain noradrenergic neurones. Neuroreport. (1993)
  79. ^ a b Okuda S, Saito H, Katsuki H. Arachidonic acid: toxic and trophic effects on cultured hippocampal neurons. Neuroscience. (1994)
  80. ^ Dehaut F, et al. n-6 polyunsaturated fatty acids increase the neurite length of PC12 cells and embryonic chick motoneurons. Neurosci Lett. (1993)
  81. ^ Williams EJ, Walsh FS, Doherty P. The production of arachidonic acid can account for calcium channel activation in the second messenger pathway underlying neurite outgrowth stimulated by NCAM, N-cadherin, and L1. J Neurochem. (1994)
  82. ^ Fukaya T, et al. Arachidonic acid preserves hippocampal neuron membrane fluidity in senescent rats. Neurobiol Aging. (2007)
  83. ^ Okaichi Y, et al. Arachidonic acid improves aged rats' spatial cognition. Physiol Behav. (2005)
  84. ^ Kotani S, et al. Synaptic plasticity preserved with arachidonic acid diet in aged rats. Neurosci Res. (2003)
  85. ^ Ishikura Y, et al. Arachidonic acid supplementation decreases P300 latency and increases P300 amplitude of event-related potentials in healthy elderly men. Neuropsychobiology. (2009)
  86. ^ Martini R, et al. Interactions between Schwann cells and macrophages in injury and inherited demyelinating disease. Glia. (2008)
  87. ^ Cámara-Lemarroy CR, et al. Celecoxib accelerates functional recovery after sciatic nerve crush in the rat. J Brachial Plex Peripher Nerve Inj. (2008)
  88. ^ Camara-Lemarroy CR, et al. Arachidonic acid derivatives and their role in peripheral nerve degeneration and regeneration. ScientificWorldJournal. (2012)
  89. ^ Nakano D, et al. Effects of dietary arachidonic acid supplementation on age-related changes in endothelium-dependent vascular responses. J Nutr Sci Vitaminol (Tokyo). (2007)
  90. ^ Zhou L, Nilsson A. Sources of eicosanoid precursor fatty acid pools in tissues. J Lipid Res. (2001)
  91. ^ Ayre KJ, Hulbert AJ. Dietary fatty acid profile influences the composition of skeletal muscle phospholipids in rats. J Nutr. (1996)
  92. ^ a b Andersson A, et al. Fatty acid profile of skeletal muscle phospholipids in trained and untrained young men. Am J Physiol Endocrinol Metab. (2000)
  93. ^ Helge JW, et al. Training affects muscle phospholipid fatty acid composition in humans. J Appl Physiol. (2001)
  94. ^ a b c Markworth JF, Cameron-Smith D. Arachidonic acid supplementation enhances in vitro skeletal muscle cell growth via a COX-2-dependent pathway. Am J Physiol Cell Physiol. (2013)
  95. ^ Mo C, et al. Prostaglandin E2: from clinical applications to its potential role in bone- muscle crosstalk and myogenic differentiation. Recent Pat Biotechnol. (2012)
  96. ^ Palmer RM. Prostaglandins and the control of muscle protein synthesis and degradation. Prostaglandins Leukot Essent Fatty Acids. (1990)
  97. ^ Palmer RM, et al. The influence of changes in tension on protein synthesis and prostaglandin release in isolated rabbit muscles. Biochem J. (1983)
  98. ^ a b c Vandenburgh HH, et al. Stretch-induced prostaglandins and protein turnover in cultured skeletal muscle. Am J Physiol. (1990)
  99. ^ Nowak J, Wennmalm A. Effect of exercise on human arterial and regional venous plasma concentrations of prostaglandin E. Prostaglandins Med. (1978)
  100. ^ Demers LM, et al. Effect of prolonged exercise on plasma prostaglandin levels. Prostaglandins Med. (1981)
  101. ^ a b Karamouzis M, et al. In situ microdialysis of intramuscular prostaglandin and thromboxane in contracting skeletal muscle in humans. Acta Physiol Scand. (2001)
  102. ^ Vandenburgh HH, et al. Skeletal muscle growth is stimulated by intermittent stretch-relaxation in tissue culture. Am J Physiol. (1989)
  103. ^ a b Kelley DS, et al. Arachidonic acid supplementation enhances synthesis of eicosanoids without suppressing immune functions in young healthy men. Lipids. (1998)
  104. ^ a b c d Roberts MD, et al. Effects of arachidonic acid supplementation on training adaptations in resistance-trained males. J Int Soc Sports Nutr. (2007)
  105. ^ a b c Trappe TA, et al. Effect of ibuprofen and acetaminophen on postexercise muscle protein synthesis. Am J Physiol Endocrinol Metab. (2002)
  106. ^ a b Trappe TA, et al. Skeletal muscle PGF(2)(alpha) and PGE(2) in response to eccentric resistance exercise: influence of ibuprofen acetaminophen. J Clin Endocrinol Metab. (2001)
  107. ^ Sawada K, et al. Ameliorative effects of polyunsaturated fatty acids against palmitic acid-induced insulin resistance in L6 skeletal muscle cells. Lipids Health Dis. (2012)
  108. ^ Hommelberg PP, et al. Fatty acid-induced NF-kappaB activation and insulin resistance in skeletal muscle are chain length dependent. Am J Physiol Endocrinol Metab. (2009)
  109. ^ Dimopoulos N, et al. Differential effects of palmitate and palmitoleate on insulin action and glucose utilization in rat L6 skeletal muscle cells. Biochem J. (2006)
  110. ^ Lee JS, et al. Saturated, but not n-6 polyunsaturated, fatty acids induce insulin resistance: role of intramuscular accumulation of lipid metabolites. J Appl Physiol. (2006)
  111. ^ a b Jové M, et al. Palmitate induces tumor necrosis factor-alpha expression in C2C12 skeletal muscle cells by a mechanism involving protein kinase C and nuclear factor-kappaB activation. Endocrinology. (2006)
  112. ^ Pickersgill L, et al. Key role for ceramides in mediating insulin resistance in human muscle cells. J Biol Chem. (2007)
  113. ^ Chavez JA, et al. A role for ceramide, but not diacylglycerol, in the antagonism of insulin signal transduction by saturated fatty acids. J Biol Chem. (2003)
  114. ^ Clifford PS, Hellsten Y. Vasodilatory mechanisms in contracting skeletal muscle. J Appl Physiol. (2004)
  115. ^ Giordano RM, et al. Effects of dynamic exercise on plasma arachidonic acid epoxides and diols in human volunteers. Int J Sport Nutr Exerc Metab. (2011)
  116. ^ Stergioulas AT, Filippou DK. Effects of physical conditioning on lipids and arachidonic acid metabolites in untrained boys: a longitudinal study. Appl Physiol Nutr Metab. (2006)
  117. ^ Agas D, et al. Prostaglandin F2α: a bone remodeling mediator. J Cell Physiol. (2013)
  118. ^ Gervais FG, et al. Selective modulation of chemokinesis, degranulation, and apoptosis in eosinophils through the PGD2 receptors CRTH2 and DP. J Allergy Clin Immunol. (2001)
  119. ^ Hirai H, et al. Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2. J Exp Med. (2001)
  120. ^ Zhu H, et al. Expression and regulation of lipocalin-type prostaglandin d synthase in rat testis and epididymis. Biol Reprod. (2004)
  121. ^ Treister NS, et al. Influence of androgens on gene expression in the BALB/c mouse submandibular gland. J Dent Res. (2005)
  122. ^ Samuelsson B, et al. Prostaglandins and thromboxanes. Annu Rev Biochem. (1978)
  123. ^ Johnstone MA, Albert DM. Prostaglandin-induced hair growth. Surv Ophthalmol. (2002)
  124. ^ Kvedar JC, Baden HP, Levine L. Selective inhibition by minoxidil of prostacyclin production by cells in culture. Biochem Pharmacol. (1988)
  125. ^ Weseler AR, et al. Dietary arachidonic acid dose-dependently increases the arachidonic acid concentration in human milk. J Nutr. (2008)
  126. ^ a b c van Goor SA, et al. Human milk arachidonic acid and docosahexaenoic acid contents increase following supplementation during pregnancy and lactation. Prostaglandins Leukot Essent Fatty Acids. (2009)
  127. ^ Smit EN, et al. Effect of supplementation of arachidonic acid (AA) or a combination of AA plus docosahexaenoic acid on breastmilk fatty acid composition. Prostaglandins Leukot Essent Fatty Acids. (2000)
  128. ^ Sauerwald TU, Demmelmair H, Koletzko B. Polyunsaturated fatty acid supply with human milk. Lipids. (2001)
  129. ^ Smit EN, et al. Estimated biological variation of the mature human milk fatty acid composition. Prostaglandins Leukot Essent Fatty Acids. (2002)
  130. ^ Kuipers RS, et al. High contents of both docosahexaenoic and arachidonic acids in milk of women consuming fish from lake Kitangiri (Tanzania): targets for infant formulae close to our ancient diet. Prostaglandins Leukot Essent Fatty Acids. (2005)