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.
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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.
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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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AA/EPA, Akkermansia muciniphila, Alloprevotella, Alpha Gliadin IgG, Amylase/Protease Inhibitors IgG, Anti-Actin IgG, Anti-LPS IgA, Anti-Zonulin IgG, Arachidonic acid (AA), Bacillus coagulans, Bacteroides, Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacterium lactis, Clostridium, Clotridiales Incertae Sedis IV, Copper to Zinc Ratio, Eggerthella lenta, Escherichia coli Nissle, Faecalibacterium, Farinins IgG, Gamma Gliadin IgG, Globulins IgG, Lactobacillus animalis, Lactobacillus paracasei, Linoleic acid (LA), LMW Glutenin IgG, Omega Gliadin IgG, Oscillospira, Porphyromonas gingivalis, Pseudobutyrivibrio, Streptococcus, Total Omega-6, Tyzzerella