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Arachidonic Acid and Bipolar Disorder


Arachidonic acid mnemonic

Arachidonic Acid, an omega-6 polyunsaturated fatty acid (PUFA), is one of the most abundant fatty acids in the brain.  Its name derives from “peanut”, although peanuts do not contain arachidonic acid. 


A genetic propensity to higher levels of arachidonic acid has been linked with a lower risk for bipolar disorder. Arachidonic acid turnover may be overactive in mania (Rapoport & Bosetti, 2002). Lithium and mood stabilizing antiepileptics (carbamazepine, valproate, lamotrigine)—but not non-mood stabilizing antiepileptics—downregulate arachidonic acid turnover (Rapoport, 2014).


Arachidonic acid omega 3 PUFA fatty acid

A potential role for PUFAs in bipolar disorder has been focused on omega-3 PUFAs such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). It now appears that decreased arachidonic acid, an omega-6 PUFA, is a potential causal risk factor for bipolar disorder (Stacey & Benyamin, et al (2024).


The fatty acid desaturase (FADS1/2/3) gene cluster is a robust bipolar disorder risk locus that encodes enzymes that convert linoleic acid into arachidonic acid. The association of dysregulated arachidonic acid synthesis appears to be specific for bipolar disorder, not extending to related disorders like schizophrenia or unipolar depression. 

 

Arachidonic acid is considered essential for infant brain development. Arachidonic acid can be sourced directly from meats, eggs, and seafood or indirectly synthesized from dietary linoleic acid (e.g., nuts, seeds, oils) via the FADS1/2/3 genes. Infants lack the ability to synthesize arachidonic acid so are reliant on human milk or formula. Stacey & Benyamin (2024) hypothesized a cross-generational effect—if lower levels of arachidonic acid in human milk drive bipolar risk, then the mother's genotype at the FADS1/2/3 cluster would be more important than the genotype of the infant. 


Research is needed to assess a potential role for arachidonic acid supplementation in prevention and/or treatment of bipolar disorder, particularly in individuals who carry bipolar disorder risk alleles at the FADS1/2/3 cluster. Currently there is insufficient data to recommend arachidonic supplementation for mental health purposes. 


Arachidonic acid supplements are used by bodybuilders to increase inflammation, which is involved in muscle hypertrophy. Arachidonic acid is metabolized to both proinflammatory and anti-inflammatory eicosanoids.  Although increased dietary arachidonic acid intake does not appear to influence basal inflammation, the acute inflammatory response to exercise stress is transiently increased following supplementation with arachidonic acid 1,500 mg/day (Markworth et al, 2018). 


High arachidonic acid level stimulates mucin production in the gallbladder and is thought to promote gallstone formation. 


Check out this masterful biochem mnemonics video (not mine):





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