The major findings on brain arachidonic acid (AA, omega-6) and docosahexaenoic acid (DHA, omega-3) are:
- Ca. 5% of daily dietary AA and DHA are converted to make prostaglandins in the brain. Converted AA and DHA are rapidly replaced by serum AA and DHA.
- Brain DHA and AA metabolisms are independent.
- AA and DHA are rapidly circulated into phospholipids (R2 on the diagram) on the endoplasmic reticulum, move to the cytoplasmic membrane (see diagram, gray and white strands) removed by phospholipase A2 in synapses, converted to prostaglandins, leukotrienes, etc., or recycled to phospholipids. Enzymes that catalyze these reactions are usually different for DHA and for AA.
- Drugs used to treat bipolar disorder (lithium, carbamazepine, valproic acid, lamotrigine) lower AA conversion in rats, but do not affect DHA conversion.
- Experimentally induced brain inflammation or neurotoxicity increases AA conversion, but not DHA conversion to prostaglandins.
- An omega-3 fatty acid deficient diet also increases AA, but not DHA conversion.
- More AA is converted in Alzheimer’s patients. This is consistent with increased inflammation and neurotoxicity in postmortem examinations.
- Mice that have been genetically manipulated to eliminate alpha-synuclein, a protein implicated in Parkinson’s disease, also show an increase in AA conversion and a decrease in DHA conversion.
Interpretation: Inflammation in the brain is separate from the rest of the body, but is the foundation of many brain disorders, including Alzheimer’s disease, bipolar disorder and Parkinson’s disease. In these disorders, arachidonic acid is rapidly converted into inflammatory prostaglandins and leukotrienes. Drugs that reduce symptoms, reduce AA conversion.
A diet rich in omega-3 DHA and reduced omega-6 arachidonic acid reduces the symptoms of these diseases -- an anti-inflammatory diet and lifestyle should be the first line of defense against brain/mental disorders.
Rapoport SI. 2008. Brain arachidonic and docosahexaenoic acid cascades are selectively altered by drugs, diet and disease. Prostaglandins Leukot Essent Fatty Acids. Oct 28. [Epub ahead of print]