The Neuroprotective Effects of Omega-3 Fats: Biological Mechanisms
Several recent studies suggest higher intake and blood levels of omega-3 fatty acids may help to reduce the risk of age-related cognitive decline, dementia and Alzheimer's disease.1-5 Three of four epidemiological studies suggest a protective effect for omega-3 fatty acids in this regard.6 The major dietary sources of these fatty acids are fish and shellfish from both salt water and fresh water.
DHA is 22 carbons long and has six double bonds, the first of which occurs between carbons three and four, from the omega end (the methyl end) of the fatty acid chain. It is the most prominent fatty acid in the brain, retina and spermatozoa and is necessary for vision, cognition and sperm motility. The neurons and synaptosomes of the cerebral cortex are especially rich in DHA, where it is incorporated into the membrane phospholipid structure. The brains of Alzheimer's patients have been shown to contain a lower content of DHA in the gray matter of the frontal lobe and the hippocampus than do the brains of patients without Alzheimer's disease. The brains of Alzheimer's patients also demonstrate a build up of amyloid-protein complex and an inflammatory component.7
The Framingham Heart Study showed that people with plasma phosphatidylcholine DHA in the top quartile of values had a significantly lower risk (47 percent) of developing all-cause dementia than did those in the bottom quartile. Also found was a significantly greater protection obtained from consuming 2.9 servings of fish per week than from consuming only 1.3 servings of fish per week, on average.7
Several mechanisms have been proposed to explain how omega-3 fats can reduce nerve cell degeneration associated with these conditions. Omega-3 fatty acids are known to provide anti-inflammatory effects due to their conversion to anti-inflammatory eicosanoids within the body. The eicosanoids formed from omega-3 fatty acids also improve blood flow by dilating vessels and decreasing platelet stickiness (anti-thrombotic), and provide other benefits associated with cardiovascular health, such as improving endothelial function and lowering triglyceride blood levels. All of these effects also are associated with prevention of cognitive decline, largely via preserved blood flow circulation to brain tissue (lower risk of cerebrovascular disease).
However, omega-3 fatty acids also play a direct role in nerve cell structure and function. Eicosapentaenoic acid (EPA) and docsahexaenoic acid (DHA) have been shown to improve the composition of nerve cell membranes, and stimulate the development, regeneration and function of nerve cells by stimulating synaptic plasticity and increasing neurotransmission, as well as increasing memory abilities. In short, long-chain omega-3 fatty acids are structural components of neuronal and other cell membranes, affecting membrane fluidity, nerve transmission and nerve cell function in a positive way. They also modulate the production of eicosanoids and inflammatory cytokines, and help preserve blood flow to the brain.
There is also the suggestion that oxidative stress (from oxygen and other free radicals), significantly contributes to neuronal damage seen in cases of cognitive impairment and Alzheimer's disease, by depleting the brain of vulnerable highly unsaturated fatty acids (e.g., EPA and DHA). Some researchers suggest that by replenishing brain cells with EPA and DHA via higher intake levels, individuals may help protect themselves against cognitive decline to a significant degree.8-11
The epidemiological and experimental studies suggest omega-3 fatty acids can reduce the risk of cognitive decline. The April 2007 issue of the American Journal of Clinical Nutrition featured the findings of two large prospective studies that evaluated intake of omega-3 fatty acids and subsequent risk of cognitive decline, dementia and Alzheimer's disease in older human subjects. Taken together, the findings of Beydoun, et al., and van Gelder, et al., indicate that a moderate intake of EPA and DHA is strongly associated with reduced risk of cognitive decline.9,10
The ARIC Study
The ARIC Study analyzed plasma fatty acids in cholesterol esters and phospholipids in Caucasians residing in Minneapolis, from 1987 to 1989. From 1990 to 1992 and from 1996 to 1998, three neurophysiological tests were administered. Effectively, this study examined the association between plasma fatty acids and cognitive decline in adults ages 50 to 65 at baseline, and conducted a subgroup analysis. A striking finding among the 2,251 subjects was that higher levels of omega-3 fatty acids were associated with reduced risk of decline in verbal fluency, particularly in hypertensive and dyslipedemic subjects, whose tissues are exposed to greater oxidative stress from these conditions. In contrast, the risk of global cognitive decline increased with elevated palmitic acid (a saturated fat) and in subjects with higher levels of arachidonic acid (an omega-6 fatty acid found in meat and dairy products).9 It should be noted that palmitic acid is a saturated fat that is highly associated with thrombosis and the elevation of LDL cholesterol, both of which can lead to atherosclerosis obstruction, increasing the tendency to develop dementia.11
The Zutphen Elderly Study
The Zutphen Elderly Study collected data on fish consumption of 210 male participants, ages 70 to 89 in 1990, and analyzed data on cognitive functioning collected in 1990 and 1995. Intake of EPA and DHA was calculated for each participant. Results showed that fish consumers had significantly less five-year subsequent cognitive decline than did non-fish consumers, and a linear trend (dose-dependent trend) was observed for the relation between the intake of EPA/DHA and cognitive decline. More specifically, the results showed that elderly men who consumed an average of approximately 400 mg per day of omega-3 fatty acids from EPA and DHA had significantly less cognitive decline over the five-year period than did those consuming an average of approximately 20 mg per day of omega-3 fatty acids.
At present, the American Heart Association recommends the consumption of fish (preferably fatty fish) at least twice per week, a recommendation that is compatible with the results of the Zutphen Elderly Study. To achieve 400 mg per day of EPA and DHA, one would have to consume six servings per week of lean fish (average serving size 140 gm or about 5 ounces) or one serving per week of fatty fish, such as mackerel or herring.10 One also can achieve this level of intake by consuming a mere 20 gm of Chinook salmon (less than 1 ounce) or 100 gm of cod (a little more than 3.5 ounces). As such, two to three servings of fish per week would supply approximately 380 mg of EPA/DHA per day, on average.7
A number of epidemiological studies and experimental studies suggest higher intake levels, brain levels and blood levels of EPA and DHA may help preserve cognitive function as we age, and reduce risk of dementia and Alzheimer's disease. A number of biological mechanisms have been proposed to explain the protective effects of EPA and DHA in regard to these neurodegenerative conditions.
More recently, two prospective studies involving older and elderly humans (the ARIC and Zutphen Elderly Studies) have shown a strong correlation between higher plasma and intake levels of EPA and DHA, and subsequent decreased cognitive decline. The Zutphen Elderly Study highlighted the fact that an average daily intake of 400 mg of EPA and DHA appears to be a significant threshold level at which a marked protective effect is observed. Some experts suggest that people who are allergic to fish and/or shellfish, and those who cannot or will not obtain sufficient intake of fish, should consume 1,000 mg per day of fish oil from supplementation.7 A supplement containing fish oil and flaxseed oil also may be a consideration, providing the total amount of EPA and DHA reaches a minimum threshold intake value of 400 mg per day.
Health practitioners should keep this information and dosage levels in mind when making recommendations about specific essential fatty-acid supplement products to their patients.
- Conquer JA, Tierney MC, Zecevic J, et al. Fatty acid analysis of blood plasma of patients with Alzheimer's disease, other types of dementia, and cognitive impairment. Lipids, 2000;35:1305-12.
- Heude B, Ducimetiere P, Berr C. Cognitive decline and fatty acid composition of erythrocyte membranes - the EVA Study. Am J Clin Nutr, 2003;77:803-8.
- Tully AM, Roche HM, Doyle R, et al. Low serum cholesteryl esterdocosahexaenoic acid levels in Alzheimer's disease: a case-control study. Br J Nutr, 2003;89:483-9.
- Kalmijn S, van Boxtel MP, Ocke M, et al. Dietary intake of fatty acids and fish in relation to cognitive performance at middle age. Neurology, 2004;62:275-80.
- Kalmign S, Feskens EJ, Launer LJ, Kromhout D. Polyunsaturated fatty acids, antioxidants, and cognitive function in very old men. Am J Epidemiol, 1997;145:33-41.
- He K, Song Y, Daviglus MI, et al. Fish consumption and incidence of stroke: a meta-analysis of cohort studies. Stroke, 2004;35:1538-42.
- Connor WE, Connor SL. The importance of fish and docosahexaenoic acid in Alzheimer's disease. Am J Clin Nutr, 2007;85:929-30.
- Brunner E. Oily fish and omega 3 fat supplements. BMJ, 2006;332:739-40.
- Beydoun MA, Kaufman JS, Satia JA, et al.. Plasma n-3 fatty acids and the risk of cognitive decline in older adults: the Atherosclerosis Risk Communities Study. Am J Clin Nutr, 2007;85:1103-11.
- Van Gelder BM, Tijuis M, Kalmijn S, Kromhout D. Fish consumption, n-3 fatty acids, and subsequent 5-y cognitive decline in elderly men: the Zutphen Elderly Study. Am J Clin Nutr, 2007;85:1142-7.
- Scientific Advisory Committee on Nutrition, Committee on Toxicity. "Advice on Fish Consumption: Benefits and Risks." Available at www.food.gov.uk/multimedia/
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