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Arachidonic acid (AA)

Optimal Result: 5.5 - 19.01 %.

Arachidonic acid (AA) is a 20-carbon polyunsaturated n-6 fatty acid with 4 double bonds (20:4n6). Its double bonds contribute to cell membrane fluidity and predispose it to oxygenation. This can lead to several important metabolites which ensure a properly functioning immune system as well as regulate inflammation, brain activity, and other signaling cascades. AA’s metabolites are called eicosanoids which are signaling molecules. They can be produced via cyclooxygenases, lipoxygenase, cytochrome P450, and oxygen species-triggered reactions. These pathways yield molecules like prostaglandins, isoprostanes, thromboxane, leukotrienes, lipoxins, and epoxyeicosatrienoic acids. AA can be obtained in the diet from eggs, fish, and animal meats and fats – or produced directly from DGLA using the delta-5-desaturase enzyme. Although often vilified, adequate AA intake is needed to achieve an equilibrium between its inflammatory and resolution effects to support a healthy immune system. It is also fortified in infant formulas due to its importance in growth and development. AA plays a crucial role in regulating innate immunity and inflammation resolution. When tissues become inflamed or infected, AA metabolites (eicosanoids) amplify those inflammatory signals to recruit leukocytes, cytokines, and immune cells to aid in pathogen resistance and clearance. Following the initial inflammatory signaling, these metabolites then balance those signals by producing resolving metabolites for host protection.

References:

- Hanna VS, Hafez EAA. Synopsis of arachidonic acid metabolism: A review. Journal of advanced research. 2018;11:23-32.

- Carlson SE, Werkman SH, Peeples JM, Cooke RJ, Tolley EA. Arachidonic acid status correlates with first year growth in preterm infants. Proceedings of the National Academy of Sciences. 1993;90(3):1073-1077.

- Brenna JT. Arachidonic acid needed in infant formula when docosahexaenoic acid is present. Nutrition reviews. 2016;74(5):329-336.

- Xu Y, Qian SY. Anti-cancer activities of ω-6 polyunsaturated fatty acids. Biomedical journal. 2014;37(3):112-119.

- Kelley DS, Taylor PC, Nelson GJ, Schmidt PC, Mackey BE, Kyle D. Effects of dietary arachidonic acid on human immune response. Lipids. 1997;32(4):449-456.

- Sonnweber T, Pizzini A, Nairz M, Weiss G, Tancevski I. Arachidonic Acid Metabolites in Cardiovascular and Metabolic Diseases. International journal of molecular sciences. 2018;19(11):3285.

- Rapoport SI. Arachidonic acid and the brain. The Journal of nutrition. 2008;138(12):2515-2520.

- Peet M, Laugharne J, Mellor J, Ramchand C. Essential fatty acid deficiency in erythrocyte membranes from chronic schizophrenic patients, and the clinical effects of dietary supplementation. Prostaglandins, leukotrienes and essential fatty acids. 1996;55(1-2):71-75.

- Tallima H, El Ridi R. Arachidonic acid: physiological roles and potential health benefits–a review. Journal of advanced research. 2018;11:33-41.

- Das UN. Arachidonic acid in health and disease with focus on hypertension and diabetes mellitus: A review. Journal of advanced research. 2018;11:43-55.

What does it mean if your Arachidonic acid (AA) result is too low?

Reduced intake of animal meats and fats, or low dietary intake of omega-6 fatty acids in general, can result in lower levels of AA. Lack of vitamin and mineral cofactors for the desaturase and elongase enzymes upstream in omega-6 metabolism might contribute to lower levels. Because of important immune and inflammatory signaling which requires AA, and its role in cell membrane phospholipid metabolism, lower levels of AA do have clinical significance. Psychiatric disorders such as schizophrenia, and neurologic disorders like tardive dyskinesia, show depletion of AA in RBC membranes. Improving AA levels decreased symptoms in some patients. Monitoring levels and ensuring adequate dietary intake of AA is important in pregnant women, infants, children, and the elderly due to its importance for the development and optimization of the nervous system, skeletal muscle, and the immune system.

What does it mean if your Arachidonic acid (AA) result is too high?

Dietary intake of animal meats, fats, and eggs contribute to elevated levels. AA can also be produced from DGLA using the delta-5-desaturase enzyme, therefore high intake of omega-6 fatty acids or DGLA supplementation should be considered as a cause of elevations. AA is then metabolized to docosatetraenoic acid using the elongase enzyme. Lack of vitamin and mineral cofactors, or a SNP in elongase, may slow the enzyme and contribute to elevations. It should also be noted that omega-3 and omega-6 fatty acids compete for use of the elongase and desaturase enzymes.

Because of its role in the inflammatory cascade and ability to induce oxidative stress, AA is a relevant factor in the pathogenesis of cardiovascular and metabolic diseases such as diabetes mellitus, non-alcoholic fatty liver disease, atherosclerosis, peripheral vascular disease, and hypertension. Neuroinflammation and brain excitotoxicity is also regulated by an AA cascade. Elevations are associated with Alzheimer’s disease and mood disorders. There is also a substantial correlation between COX-catalyzed AA peroxidation and cancer development (prostate, colon, and breast).

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