DHA + lutein prevents cognitive decline
BOSTON, MASSACHUSETTS. Cognitive decline and dementia are common among the elderly. It is estimated that 10% of people aged 65 years and 33% of individuals aged 85 years suffer from cognitive impairment, more specifically, a reduced ability to learn and remember. There is considerable evidence that both DHA (docosahexaenoic acid), a major component of fish oils, and lutein, a common dietary carotenoid, are essential for brain health. There is also evidence that lutein tends to accumulate in the macula (a small area of the retina essential for clear, detailed vision) and thereby helps prevent the initiation and progression of age-related macular degeneration. Now researchers at the Center on Aging at Tufts University report that supplementing with DHA + lutein is effective in preventing cognitive decline.

Their double-blind clinical trial involved 49 women (aged 60 to 80 years) who were randomized to receive DHA (800 mg/day), lutein (12 mg/day), DHA + lutein, or placebo. The study participants had blood samples drawn at enrolment and were subjected to a battery of cognitive tests (verbal fluency, memory, processing speed, and accuracy) at enrolment and after 4 months of supplementation. Diet was monitored with food frequency questionnaires at enrolment and at 2 and 4 months to ensure that there were no confounding changes in dietary intake. All cognitive outcomes were also adjusted for age and level of education.

At the end of the study, the researchers observed that participants who had taken DHA + lutein scored significantly higher on tests involving different aspects of memory. Thus, the DHA + lutein group improved in efficiency, learning shopping lists or lists of words with fewer trials, on average, after supplementation. All three supplement groups improved significantly on the verbal fluency test. It was also noted that DHA supplementation resulted in an increased uptake of lutein by the macula. The researchers conclude that supplementation with DHA and lutein significantly improves cognitive function in the elderly.
Johnson, EJ, et al. Cognitive findings of an exploratory trial of docosahexaenoic acid and lutein supplementation in older women. Nutritional Neuroscience, Vol. 11, No. 2, 2008, pp. 75-83

DHA may help protect against Alzheimer's disease
NEW ORLEANS, LOUISIANA. DHA (docosahexaenoic acid), a major component of fish oils, is an absolute requirement for the development of the human central nervous system and the continuous maintenance of brain cell function. DHA is an important part of the plasma membranes of nerve (neuronal) cells and is essential in the maintenance of their fluidity and integrity. It is also involved in the generation of certain metabolites (docosanoids) of which the most important is neuroprotection D1 or NPD1. Both DHA and NPD1 are involved in ensuring membrane stability and fluidity and inhibiting the activation of inflammatory signaling mediators such as cyclooxygenase-2 (COX-2). NPD1 is also beneficial in preventing excessive oxidative stress from degrading DHA. Furthermore, a recent clinical trial concluded that supplementation with DHA and lutein significantly improved cognitive abilities in elderly people.

Unfortunately, as DHA is a highly unsaturated fatty acid, it is subject to lipid peroxidation which, in turn, is associated with retinal and neurological dysfunction and visual and cognitive decline. The free radical initiated oxidation of DHA is also believed to be one of the first steps in the cascade of events (brain cell membrane instability and neural cell dysfunction) leading to Alzheimer's disease with the characteristic formation of amyloid plaques. On the other hand, the DHA metabolite, NPD1 has been found to be neuroprotective by inhibiting oxidative stress, cell death, and inflammation-triggered neuronal decline while promoting brain cell survival and maximizing cognitive function throughout the human lifespan.
Lukiw, WJ and Bazan, NG. Docosahexaenoic acid and the aging brain. Journal of Nutrition, Vol. 138, 2008, pp. 2510-14

Editor's comment: There is no question that DHA is crucial for the development and maintenance of the central nervous system and its neuronal cells. This article further suggests that an adequate DHA supply may also help prevent cognitive decline and progression of Alzheimer's disease. However, since DHA is easily oxidized its intake should always be accompanied by supplementation with vitamin E (gamma-tocopherol) and its regenerator, vitamin C.

Fish oils halt cognitive decline
BILTHOVEN, THE NETHERLANDS. Cognitive decline (memory loss and a decline in awareness and the ability to think, learn and judge) is often part of the aging process and precedes Alzheimer’s disease and dementia. Dutch researchers report that cognitive decline is substantially less among elderly men consuming a diet rich in EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), the main components of fish oil. Their study, part of the Zutphen Elderly Study, involved 210 men between the ages of 70 and 89 years when enrolled in the study in 1990. The men completed food frequency questionnaires and were tested with the Mini-Mental State Examination (MMSE) scale at enrolment and 5 years later. In 1990 24% of the participants never consumed fish, 41% consumed up to 20 grams/day (1 serving a week), and 35% consumed more than 20 grams/day (more than 1 serving a week). The daily intake of EPA + DHA among men consuming no fish at all was only 15 mg. After 5 years the MMSE score had declined by 1.2 points among the men who never consumed fish as compared to a decline of only 0.3 points in the fish consumers (a higher MMSE score indicates better cognitive functioning).

The researchers also compared the rate of cognitive decline to the calculated daily intake of EPA + DHA. They found that men with an intake of about 400 mg/day actually improved their MMSE score by 0.2 points over the 5-year evaluation period, while men who consumed only about 20 mg/day experienced an average decline of 0.9 points – a statistically significant difference of 1.1 points. An intake of 400 mg/day of EPA + DHA can be obtained through supplementation with fish oil or by consuming one serving (140 grams) of fatty fish (mackerel, herring, salmon) a week.
van Gelder, BM, et al. Fish consumption, n-3 fatty acids, and subsequent 5-y cognitive decline in elderly men. American Journal of Clinical Nutrition, Vol. 85, 2007, pp. 1142-47

DHA helps prevent Alzheimer’s disease
BOSTON, MASSACHUSETTS. Dementia is becoming increasingly common among elderly people. About 70% of all cases of the disorder are Alzheimer’s disease (AD). Advancing age, high blood plasma concentrations of homocysteine, a family history of dementia, and the presence of the apolipoprotein E epsilon-4 allele (alternative gene form) are all known risk factors for AD.

Now researchers at Tufts University report that a low blood plasma level of DHA (docosahexaenoic acid), a main component of fish oils, also increases the risk of developing AD. Their study included 899 men and women free of dementia when entering the study (Framingham Heart Study). The median age of the participants was 76 years and they were followed up for an average of 9 years. During the follow-up period, 99 (11%) of the patients developed dementia (including 71 [72%] with AD). All participants had provided blood samples at the start of the study. Analysis of these samples showed that those with high levels of DHA in the phosphatidylcholine fraction of their blood plasma had a 47% lower risk (relative) of developing dementia and a 39% lower risk of developing AD than did the participants with lower levels (after adjustment for age, gender, homocysteine level, education level, and presence of the apolipoprotein E epsilon-4 allele). The researchers estimate that the intake of DHA among participants with high plasma levels was about 180 mg/day. This amount of DHA can be obtained from eating 2-3 servings of fish per week or from supplementation with a high quality fish oil.
Schaefer, Ernst J., et al. Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease. Archives of Neurology, Vol. 63, November 2006, pp. 1545-50
Morris, Martha Clare. Docosahexaenoic acid and Alzheimer disease. Archives of Neurology, Vol. 63, November 2006, pp. 1527-28 (editorial)

Fish oil slows down progression of mild Alzheimer’s disease
STOCKHOLM, SWEDEN. There is substantial evidence that Alzheimer’s patients have significantly lower blood levels of DHA (docosahexaenoic acid), a main component of fish oil, than do normal controls. Epidemiological studies have also shown that regular fish consumption is associated with a substantially reduced risk of developing Alzheimer’s disease (AD) and dementia. Researchers at the Karolinska Institute report that supplementation with DHA-rich fish oil, while not effective in the treatment of moderate existing AD, does slow down the progression of milder forms of the disease.

Their clinical trial involved 174 patients with mild to moderate AD. The patients had a score between 15 and 30 on the Mini-Mental State Examination (a higher score indicates milder disease) and were treated with an acetylcholine esterase inhibitor (Donepezil, Galantamine or Rivastigmine) throughout the study. Participants were randomized to receive four 1-gram capsules of placebo oil (corn oil) daily or four 1-gram capsules of fish oil daily for a 6-month period. The fish oil capsules provided 1.7 grams/day of DHA and 0.6 grams/day of EPA.

At the end of the 6-month period all patients were switched to receive the fish oil capsules for a further 6 months. As expected, the level of DHA and EPA in blood plasma phospholipids rose substantially during fish oil supplementation – by a factor of 2.4 for DHA and a factor of 3.6 for EPA. There was no statistically significant difference in Mini-Mental State Examination (MMSE) score or the score on the cognitive part of the Alzheimer Disease Assessment Scale between the placebo group and the fish oil supplemented group after 6 and 12 months. However, in a sub-group (32 patients) with a MMSE score greater than 27 points (very mild disease) the researchers did observe a significantly slower disease progression in the fish oil group than in the placebo group. The average decline in MMSE score in the placebo group over the first 6 months was 2.5 points versus only 0.5 points in the fish oil group. The decline over the next 6 months, when both groups received fish oil capsules, averaged 0.6 points indicating that the slowing of progression persists with continuing supplementation.

It was also noteworthy that fish oil supplemented patients experienced no decline at all in the MMSE scale on sub-items – “delayed word recall” and “attention”. The fish oil supplement was well-tolerated and safe. The researchers speculate that fish oils may act beneficially in very mild AD through their anti-inflammatory effect. Recent research has shown that there may be a critical period, 2 or more years before the onset of dementia, during which inflammation is pronounced in brains of patients with mild to moderate AD.
Freund-Levi, Y, et al. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease. Archives of Neurology, Vol. 63, October 2006, pp. 1402-08

Fish oil protects against Alzheimer's disease
CHICAGO, ILLINOIS. High levels of the omega-3 fatty acid docosahexaenoic acid (DHA) are found in the more active areas of the brain including the cerebral cortex, mitochondria, synaptosomes, and synaptic vesicles. At least one epidemiologic study has shown that patients with Alzheimer's disease (AD) have significantly lower levels of omega-3 fatty acids in their plasma phospholipids than do age- matched controls. Researchers at the Rush-Presbyterian-St. Luke's Medical Center now report that older people can reduce their risk of developing AD by increasing their intake of fish and fish oil (DHA). Their study included 815 men and women over the age of 65 years who had showed no sign of AD during a thorough baseline examination. About 2 years after the examination all participants completed a 154- item food frequency questionnaire and provided information about their current use of supplements. After another 2 years all participants were again subjected to a thorough, structured neurologic clinical evaluation to establish the presence or absence of AD. A total of 131 study participants were found to have developed AD over the 3.9-year follow-up period.

The researchers found that participants who consumed fish just once a week had a 60% lower risk of developing AD than did those who rarely or never ate fish. They also observed that participants whose daily intake of DHA was about 100 mg/day had an incidence of AD which was 70% lower than those with an intake of 30 mg/day or less.

Eicosapentaenoic acid (EPA), another component of fish oil, showed no appreciable effect; however, the maximum intake was only 30 mg/day. A high total intake of omega-3 fatty acids was also strongly correlated with a reduced risk for AD. Participants with an intake of 1.6 – 4.1 grams/day had a 70% lower risk than those with an intake below 1.05 grams/day. Alpha-linolenic acid (flaxseed oil) intake was not associated with AD risk except in the case of people with the APOE-epsilon 4 allele where a high intake was strongly protective. The researchers conclude that an increased intake of fish or omega-3 fatty acids, especially DHA, can substantially reduce the risk of developing Alzheimer's disease.
Morris, MC, et al. Consumption of fish and n-3 fatty acids and risk of incident of Alzheimer's disease. Archives of Neurology, Vol. 60, July 2003, pp. 940-46
Friedland, RP. Fish consumption and the risk of Alzheimer disease. Archives of Neurology, Vol. 60, July 2003, pp. 940-46

Editor's comment: High doses of fish oils should always be accompanied by vitamins E and C in order to prevent oxidation of the oil.

Cognitive function and fat intake
PARIS, FRANCE. Several epidemiological studies have shown that a high dietary intake of linoleic acid and a low intake of fish oils (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) are associated with cognitive impairment and an increased risk of dementia. French researchers now report that the fatty acid composition in erythrocytes (red blood cells) is an indicator of the risk of cognitive function decline (ability to learn, think and remember).

Their study involved 246 men and women (aged 63 to 74 years) who had the lipid (fatty acid) composition of their erythrocytes analyzed in 1995. All participants also underwent tests to determine their cognitive function at baseline and after a 4-year follow-up period. The researchers found that study participants with high erythrocyte levels of stearic acid (a saturated fatty acid) had a 91% higher risk of having experienced a significant decline in cognitive function over the 4 years than did participants with average levels. Participants with high levels of linoleic acid (an unsaturated omega-6 acid) had a 59% increased risk of decline while those with high levels of EPA and DHA had a 41% lower risk of experiencing cognitive decline than did those with normal levels.

The researchers suggest that the omega-3 fatty acids EPA and especially DHA help keep the membranes of brain cells more fluid while saturated and omega-6 fatty acids tend to "harden" them. They believe this and the anti-inflammatory effects of EPA and DHA are what help preserve cognitive function.
Heude, Barbara, et al. Cognitive decline and fatty acid composition of erythrocyte membranes – The EVA Study. American Journal of Clinical Nutrition, Vol. 77, April 2003, pp. 803-08

Editor's comment: Stearic acid is found in high quantities in beef, mutton, and pork while omega-6 fatty acids are abundant in vegetables oils such as safflower, sunflower, and soybean oil. The long-chain omega-3 fatty acids (EPA and DHA) are found in fatty fish and fish oils.

Dementia associated with low DHA levels
GUELPH, CANADA. Dementia now affects about 47% of the population over 80 years of age in Western countries. The incidence of Alzheimer's disease, a leading cause of dementia, is growing especially rapidly. There is no cure for Alzheimer's disease (AD) and it is not at all clear what causes it. Researchers at the University of Guelph now report that they have found low levels of long-chain polyunsaturated fatty acids, notably DHA (docosahexaenoic acid) in people suffering from AD and dementia.

The study involved 84 people (aged 80 years or older) who were given a thorough clinical evaluation. Nineteen of the people were diagnosed as having AD, 10 as having non-AD dementia, 36 were characterized as non-demented but cognitively impaired, and 19 had normal cognitive functioning. Blood samples were obtained from all participants and analyzed for fatty acids in the phospholipid phases of the plasma. The researchers observed significantly lower levels of EPA (by about 42%), DHA (by 17-33%) and total omega-3 fatty acids (by 23-28%) in the plasma phospholipids phase of the patients with AD, other dementia and cognitive impairment (non-demented) than in the normal controls. DHA is highly concentrated in the cerebral cortex and a deficiency in blood plasma is likely to translate into a deficiency in the brain.

Other research has confirmed the association between low DHA and EPA levels and impaired cognitive function. Other studies have found that fish oil supplementation improves mood, cooperation, appetite, sleep, and short-term memory in AD patients. The Guelph researchers conclude that an effort should be made to increase the intake of fish or fish oils in the population at large and the elderly in particular.
Conquer, Julie A., et al. Fatty acid analysis of blood plasma of patients with Alzheimer's disease, other types of dementia, and cognitive impairment. Lipids, Vol. 35, December 2000, pp. 1305-12

Low docosahexaenoic acid levels and Alzheimer's disease
BOSTON, MASSACHUSETTS. Docosahexaenoic acid (DHA), a major component of fish oils, is the most important fatty acid in the brain and retina and makes up more than 30% of the structural lipid (fat) in neurons. There is ample evidence that a deficiency of DHA is associated with depression, attention deficit hyperactivity disorder, and dementia. Clinical studies have shown that an increased intake of DHA may benefit patients with dyslexia and Alzheimer's disease.

Researchers at Boston University and Tufts University School of Medicine now report that they have found a clear association between low blood levels (in the phosphatidylcholine fraction of serum) of DHA and the risk of developing Alzheimer's disease. Their study involved 1188 elderly Americans (mean age of 75 years) who had blood samples drawn and analyzed for DHA in 1985. Sixteen of the participants had clinically diagnosed Alzheimer's at the time of blood sampling. The researchers noted that 11 of the 16 (69%) had DHA levels in the lower half of the DNA distribution. The remaining 1172 participants were followed for 10 years. Again the researchers noted that participants with DHA levels in the lower half of the distribution had a 67% greater risk of developing Alzheimer's disease. The researchers suggest that maintaining adequate levels of DHA through the consumption of fish or dietary supplements rich in DHA may be particularly important for the elderly.
Kyle, D.J., et al. Low serum docosahexaenoic acid is a significant risk factor for Alzheimer's dementia. Lipids, Vol. 34 (suppl), 1999, p. S245

Fish consumption slows mental decline
ROTTERDAM, THE NETHERLANDS. Dutch researchers report an intriguing association between diet and the extent and rate of cognitive impairment in older men. Their study, part of the Zutphen Elderly Study, involved almost 1000 men born between 1900 and 1920. The men's intake of various food components was assessed (by personal interviews) in 1985 and 1990 and their cognitive function was evaluated in 1990 and 1993 using the Mini-Mental State Examination scale. The MMSE scale includes questions on orientation to time and place, registration, attention and calculation, recall, language, and visual construction.

The researchers found that men with the highest intake of linoleic acid (mainly from margarine, butter, baking fats, sauces, and cheeses) had a 76% higher degree of cognitive impairment than did men with the lowest intake. This association held true even after adjusting for age, level of education, cigarette smoking, alcohol consumption, and calorie intake. The intake of omega-3 fatty acids, on the other hand, was not associated with any degree of impairment. Men with a high fish intake were less likely to be cognitively impaired than men with a low intake and their rate of decline over the period 1990-93 was half that of men rarely consuming fish. The intake of beta-carotene, flavonoids, and vitamins C and E was not associated with a greater or lesser degree of impairment. However, there was a clear correlation between a high vitamin C intake and a decline in cognitive function over the period 1990-93. Men with a high vitamin C intake were twice as likely to have experienced a decline as were men with a low intake. The researchers speculate that vitamin C may act as a pro-oxidant in the presence of free iron in the brain.
Kalmijn, S., et al. Polyunsaturated fatty acids, antioxidants, and cognitive function in very old men. American Journal of Epidemiology, Vol. 145, January 1, 1997, pp. 33-41

Fish oils help patient with Alzheimer's disease
MURRAYVILLE, VICTORIA, AUSTRALIA. Dr. Robert Peers, an Australian family physician, reports on the case of a 77-year-old farmer diagnosed with Alzheimer's disease (confirmed by a neurologist). The patient, when first admitted to a nursing home, was restless and destructive and unable to dress himself. After several months he became calmer, regained weight, and was again able to dress himself. Dr. Peers ascribes the changes to the fact that the nursing home served fish every week thus providing the patient with long-chain omega-3 fatty acids which had been missing in his previous diet. In the five years prior to being diagnosed with Alzheimer's disease (AD) the farmer had been in the habit of just frying up meat, rice and vegetables in an omega-6 vegetable oil. Dr. Peers provides a compelling scientific explanation of the reasons why a deficiency in docosahexaenoic acid (DHA), a main component of fish oil, may lead to Alzheimer's disease. He suggests that patients with AD should be queried about an excessive intake of omega-6 fatty acids (from vegetable oils and margarine) and a deficient intake of omega-3 fatty acids. If an imbalance is observed it should be treated with fish oil supplementation. He points out that DHA is quickly taken up by the brain and hypothesizes that fish oil supplementation may not only improve Alzheimer's symptoms, but may even prevent the disease from progressing further.

Two other Australian physicians, Drs. Simons and Broe, find Dr. Peers' observation interesting, but caution that considerably more research needs to be done for fish oil supplementation to be recognized as an effective treatment for AD.
Peers, Robert J. Alzheimer's disease and omega-3 fatty acids: hypothesis. Medical Journal of Australia, Vol. 153, November 5, 1990, pp. 563-64 (letter)