Omega-3 Fatty Acids Go to Your Brain Too
Omega-3 Fatty Acids Protect Against Alzheimer's Disease
New study shows that fish oil dramatically reduces risk in the elderly
By Lane Lenard, Ph.D.
lzheimer’s disease is a devastating disorder that slowly but surely destroys the very foundations of human consciousness: memory and higher mental functioning. Alzheimer’s is hard to diagnose and even harder to treat. Can it be prevented? No one knows for sure, but new evidence suggests that a simple dietary measure—eating fish at least once per week, or taking dietary supplements containing omega-3 fatty acids, which are found in fish oil—may dramatically reduce the risk of falling prey to this terrible disease.
If you let your imagination dive, you can almost see this sandy shoal as the surface of a human brain. The salmon heading for their spawning grounds are rich in omega-3 fatty acids, which are highly beneficial nutrients for
Currently the fourth-leading cause of death in adults, Alzheimer’s disease afflicts about 4 million people in the United States and over 15 million worldwide. The risk of Alzheimer’s rises sharply with age. In people over 65, the incidence doubles every 5 years, and by age 85, every other person has it, at least to some degree. Without effective methods for prevention and treatment, it is estimated that 14 million Americans will have Alzheimer’s by the middle of this century.
The Landscapes of Alzheimer’s Disease
The clinical landscape of Alzheimer’s disease is well known. Its beginning, typically, is a significant worsening of the common condition known as mild cognitive impairment (MCI), which usually, but not always, leads down this path. As Alzheimer’s takes over, it progresses, over a period of years, to severe mental deterioration and, ultimately, death. Owing to the slow, inexorable pace of this process and the increasing need for patient care in virtually every aspect of daily living, Alzheimer’s is a disease that can be even harder on the caregivers than it is on the patient.
Rx for a Sharp Mind: Stay Active
Much of our knowledge of the beneficial effects of omega-3 fatty acids is based on experimental studies with laboratory animals, such as mice, rats, and monkeys. There is abundant evidence that dietary deficiencies of omega-3s lead to impaired brain function and that supplementation with these compounds tends to improve the transmission of nerve impulses as well as other aspects of neuronal function.
The improvement is particularly significant in the hippocampus, the region of the brain most closely associated with learning and memory. The hippocampus is one of the few parts of the brain in which new neurons are continually being generated in human adults (the long-held belief that neurons never regenerate has turned out to be false). This has led some scientists to speculate that stimulating this regenerative process might help counteract the normal effects of aging, and perhaps the abnormal effects too, such as Alzheimer’s and other neurodegenerative diseases.
Speaking of stimulation, it’s well known that exposing laboratory mice to rich environments filled with toys, things to explore, and exercise devices makes them more active, curious, and cognitively sharp than mice kept in bare cages devoid of those amenities. The “rich” mice have better learning and memory functions than the “poor” ones, apparently because their activities stimulate the growth of hippocampal cells—an effect that occurs in old mice as well as young ones.
Researchers in Germany sought to determine whether this effect could be sustained for long periods in middle and later life. For 10 months—from the age of 10 months to 20 months (the average mouse lifespan is about 24 months)—the mice in this study lived in either a rich or a poor environment. Remarkably, the rich old mice generated five times as many new hippocampal cells as their poor old cousins. Furthermore (and not surprisingly), they easily outperformed the poor mice in learning and memory tasks.
These dramatic results jibe with what we know about the enhanced cognitive health of humans who stay physically and mentally active as they grow old. We do not know, however, whether new growth of hippocampal neurons is responsible for this effect, and it’s always dangerous to make assumptions based on mouse studies. Nonetheless, we do know that the human hippocampus is especially vulnerable to the ravages of Alzheimer’s disease, so anything that can help maintain its good health is surely worth pursuing. An important factor in that equation is omega-3 fatty acids.
- Kempermann G, Gast D, Gage FH. Neuroplasticity in old age: sustained fivefold induction of hippocampal neurogenesis by long-term environmental enrichment. Ann Neurol 2002;52:135-43.
Less familiar to laymen is the physical landscape of the disease. If the mind is not functioning as it once did, it’s not hard to understand why, once you examine brain tissue from an Alzheimer’s patient under a microscope. That is what the German neuropathologist Alois Alzheimer did to the brain of one of his patients in 1906, when she died after suffering years of worsening dementia and physical decline. Instead of the ordered array of neurons (nerve cells) characteristic of a healthy brain, he found anatomical “war zones”of plaque deposits and tangled bundles of fibers in certain regions of the brain. The types of tissue damage he observed defined the disease that now bears his name, and to this day they remain its only definitive diagnostic signs.
Plaques and Tangles Destroy Brain Function
The bundles of fibers, called neurofibrillary tangles, are the ruins of a microplumbing system designed to deliver vital nutrients as well as sodium, potassium, and calcium ions to neurons. Without the free flow of these elements, the normal electrical activity involved in neuronal function is impossible. A key element of the neurofibrillary tangles is an abnormal variety of a protein called the tau protein. Normal tau protein helps keep the microplumbing clear and the neuronal “juices” flowing, but the abnormal version seems to interfere with this protective activity.
The plaque deposits that Dr. Alzheimer saw are now known to consist of an insoluble protein called beta-amyloid, which is commonly found lying amidst the debris of dying nerve cells on the biochemical battlefield of the patient’s brain. Beta-amyloid appears to be one cause of the neurofibrillary tangles, and its presence has also been linked to reduced levels of the neurotransmitter acetylcholine, which is essential for learning and memory.
Fish Is Brain Food—and Then Some
The new data showing that fish consumption can sharply reduce the risk for Alzheimer’s disease would come as no surprise to Grandma, who never tired of reminding us that fish was “brain food,” something she probably learned from her grandmother. Numerous recent studies have now validated this folklore.
Fish—especially coldwater fish, such as salmon, tuna, herring, and mackerel—are our primary food source of omega-3 fatty acids, whose benefits for cardiovascular and cerebrovascular health are well documented. Numerous studies have shown, e.g., that laboratory animals that are fed diets rich in omega-3 fatty acids have improved neuronal function (in a variety of ways), increased levels of antioxidant enzymes, decreased levels of lipid peroxides, reduced ischemic damage to neurons, and increased cerebral blood flow; they also exhibit superior learning acquisition and memory performance compared with control animals given a standard diet.
DHA Is Particularly Beneficial
Of the various omega-3 fatty acids known to science, the one called docosahexaenoic acid (DHA) is particularly beneficial. In humans and other species, DHA is a primary component of the phospholipids that constitute neuronal cell membranes. When brains are deficient in DHA, the integrity of these membranes is compromised, and increasing our consumption of DHA restores the phospholipid levels to normal. In addition to DHA, fish oil supplies other omega-3 fatty acids, notably eicosapentaenoic acid (EPA) and the precursor to both of these molecules, alpha-linolenic acid.
Although DHA plays a vital role in normal brain function, there has been surprisingly little research on its relationship with Alzheimer’s disease. One recent study found, however, that the omega-3 fatty acid levels in the plasma phospholipids of people with Alzheimer’s were 30–40% lower than those in healthy, age-matched controls. Two prospective studies indicated that diets that are high in saturated fats and cholesterol (e.g., diets rich in meat and dairy products) increase the risk of dementia, whereas fish-rich diets may decrease this risk.
Omega-3s Reduce the Risk for Alzheimer’s Disease
New data showing the protective effects of fish consumption come from a study in Chicago of 815 randomly selected subjects, aged 65 to 94 years, who were followed for an average of 3.9 years between 1993 and 2000 after completing a dietary questionnaire. Alzheimer’s disease was subsequently diagnosed in 131 of the subjects, and fish consumption was found to be inversely associated with the risk for this disease. When the data were corrected for the effects of age, sex, race, educational level, and certain genetic and other factors, it turned out that those who ate fish one to three times per month had a 40% lower relative risk of Alzheimer’s disease than those who never ate fish, and those who ate fish once per week had a 60% lower risk. Eating fish two or more times per week did not confer any additional benefit.
In this study, the total intake of omega-3 fatty acids (computed from the information provided in the questionnaire) was also inversely associated with the risk of developing Alzheimer’s disease. When the data were corrected as described above, the results showed that those persons in the top 20% of omega-3 intake had a 60% reduction in risk compared with those in the lowest 20% of intake. By this same analysis, the protective effect of DHA alone was very strong: a 70% risk reduction. By contrast, EPA had virtually no effect, but since 40% of the subjects consumed no EPA at all, the statistics were skewed, and the authors opined that higher average levels of EPA intake might show a protective effect.
Let Them Eat Fish?
Just how omega-3 fatty acids protect against the destructive effects of Alzheimer’s disease is not clear, but there is evidence that it may be through various biochemical mechanisms that inhibit the formation or deposition of beta-amyloid. In any case, the results described above might make you want to rush to the nearest fish market. And you probably should, because fish are a terrific food in many ways. Bear in mind, however, that even fish can have their downside, and eating too much of certain kinds may not be a good idea. Although they’re an excellent source of high-quality protein and healthy fats, many fish available today also contain environmental toxins, notably polychlorinated biphenyls (PCBs), which are carcinogenic, and organic mercury compounds. The latter can promote atherosclerosis, thus at least partially negating the substantial cardiovascular and neurologic benefits normally derived from eating fish.
The National Academy of Sciences now recommends that pregnant women and women who may become pregnant completely avoid eating fish with the highest levels of methylmercury, such as king mackerel, tilefish, shark, and swordfish. Other fish, including tuna, salmon, haddock, cod, pollack, and sole, may also contain mercury, but at lower levels. Local contamination of rivers and lakes may also be problematic, and even farm-raised fish may be exposed to pollution and contaminated feed.
Grandma Was Right
The omega-3 fatty acids—especially DHA and EPA—play such vital roles in many aspects of human health that they are surely among the most precious nutrients in Mother Nature’s cornucopia. As discussed in previous issues of Life Enhancement, they help prevent heart disease (a fact openly acknowledged by the American Heart Association) and perhaps cancer, they enhance our cognitive function, and, as we have now seen, they protect against the scourge of Alzheimer’s disease.*
For those reasons and more, taking daily supplements of omega-3 fatty acids is one of the best things you can do for your health—assuming, of course, that you already lead a physically and mentally active life with a sensible diet and regular exercise. Remember what Grandma also used to say: An ounce of prevention is worth a pound of cure.
- Morris MC, Evans DA, Bienias JL, et al. Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol 2003;
- Connor WE, Neuringer M, Lin DS. Dietary effects on brain fatty acid composition: the reversibility of n-3 fatty acid deficiency and turnover of docosahexaenoic acid in the brain, erythrocytes, and plasma of rhesus monkeys. J Lipid Res 1990;31:237-47.
- Anderson GJ, Connor WE, Corliss JD. Docosahexaenoic acid is the preferred dietary n-3 fatty acid for the development of the brain and retina. Pediatr Res 1990;27:89-97.
- Conquer JA, Tierney MC, Zecevic J, Bettger WJ, Fisher RH. Fatty acid analysis of blood plasma of patients with Alzheimer’s disease, other types of dementia, and cognitive impairment. Lipids 2000;35:1305-12.
- Barberger-Gateau P, Letenneur L, Deschamps V, Peres K, Dartigues JF, Renaud S. Fish, meat, and risk of dementia: cohort study. Brit Med J 2002;325:932-3.
- Kalmijn S, Launer LJ, Ott A, Witteman JC, Hofman A, Breteler MM. Dietary fat intake and the risk of incident dementia in the Rotterdam Study. Ann Neurol 1997;42:776-82.
- Friedland RP. Fish consumption and the risk of Alzheimer disease. Arch Neurol 2003;60:923-4.
- Guallar E, Sanz-Gallardo I, van’t Veer P, et al. Mercury, fish oils, and the risk of myocardial infarction. N Engl J Med 2002;347:1747-54.
- Yoshizawa K, Rimm EB, Morris JS, et al. Mercury and the risk of coronary heart disease in men. N Engl J Med 2002;347:1755-60.
Lane Lenard is a medical writer and editor who has worked for several health-related publications. He earned a doctorate in psychopharmacology and was a researcher in drug development for a major pharmaceutical company.