Brain Food: It’s Not About Fish Anymore
Brain Food: It’s Not About Fish Anymore
Abstract & Commentary
Synopsis: High intake of vitamins C and E in food (not supplements) is associated with reduced risk of Alzheimer’s disease.
Source: Engelhart MJ, et al. JAMA. 2002;287:3223-3229.
The Rotterdam study is a longitudinal study of healthy elderly in The Netherlands. The current report is based on 5395 subjects who were recruited between 1990-1993 and followed until 1999. Engelhart and colleagues hypothesized that dietary antioxidants might reduce the risk of dementia.
The assessment of dementia occurred as follows: if a subject had a Mini-Mental State Examination (MMSE) score of 26 or less or a Geriatric Mental State Schedule (GMS) of 1 or more, he/she was administered the Cambridge Examination of Mental Disorders in the Elderly (CAMDEX) and an interview. If dementia was suspected based on the CAMDEX, the subject was evaluated by a neurologist and a neuropsychologist, and usually had magnetic resonance imaging of the brain. Dietary intake was evaluated both by checklist and by interview with a dietician. The checklist included questions about all foods and drinks consumed in the previous year, dietary supplements, and prescribed diets. The interview used an extensive, validated, semiquantitative food-frequency questionnaire. Engelhart et al were looking for intake of the following antioxidants: beta carotene, flavonoids, vitamin C, and vitamin E. Daily dietary intake of these antioxidants was calculated in mgs. Careful assessment of total and saturated fat also was done. Engelhart et al also obtained demographic, socioeconomic, and lifestyle data, as well as ultrasonography of the carotid arteries.
The mean age at baseline was 67.7 years, and 595 of the participants were women. Twenty-three percent were current smokers, 12% used antioxidative supplements, and 28% carried at least 1 APOE*4 allele.
Intake of flavonoids, but not of beta carotene, vitamin C, and vitamin E, was significantly associated with higher MMSE scores at baseline. Subjects were followed for an average of 6 years, during which 197 participants developed dementia (146 of these had Alzheimer’s disease [AD]). After adjustment for a wide range of relevant confounders (age, gender, education, smoking, body mass intake, and carotid plaques, among others) high intake of dietary vitamin C and vitamin E were associated with reduced risk of AD. Supplements, beta carotene, and flavonoids were not related to the risk of AD at follow-up (though flavonoids intake was related to MMSE scores at baseline). For smokers, high intake of beta carotene and flavonoids was associated with reduced risk of AD. For participants with at least 1 APOE*4 allele, higher intake of all but flavonoids was associated with somewhat lower risk of AD.
Comment by Barbara A. Phillips, MD, MSPH
AD increases with age, and is the fourth leading cause of death in adults. It is more common in women than in men. Loss of memory, inability to reason, and gradual changes in behavior are the classic symptoms. The Alzheimer’s patient will eventually die from this disease—usually within 8 years of symptom onset.1 The emotional and fiscal toll of AD in countries with long life expectancies is staggering.
Apolipoprotein E (APOE) is a plasma protein involved in the transport of cholesterol. It is encoded by a gene on chromosome 19. Some 34-65% of individuals with AD carry the APOE *4 allele, but it is present in only approximately 24-31% of the nonaffected adult population. The risk of AD increases and the age of onset decreases with the number of APOE epsilon*4 alleles.2 Oxidative stress has been felt to be one possible mechanism by which the genetic risk conferred by presence of the APOE allele might be potentiated. Previous work has addressed the issue of antioxidants and the risk of AD3-5 but has produced conflicting results. In the same issue of JAMA as the current study, a back-to-back article found that dietary, but not supplemental vitamin E reduced the risk of AD in older adults with the APOE*4 allele,6 and an editorial7 pointed out that there might be a biologic difference between "nutritional phenomena" of real food vs. vitamin content alone. In other words (I think), you have to eat food (not take supplements) to have the best chance of getting the benefits of nutrients.
But what the heck are flavonoids? These articles leave us pretty much on our own to figure this out, so I went to the internet. According to one web site, "Both pine bark and grape seed extract are rich in a group of flavonoids called proanthocyanidins, or condensed tannins. Researchers have identified about 250 different proanthocyanidins in plants and, as a group, they constitute one of 12 subcategories of flavonoids. Some 4000 flavonoids have been identified, and they are part of an even larger class of chemicals known as polyphenols."8 Thus, pine bark, grape seed, and green tea are 3 of the more common dietary sources of flavonoids. However, since there are more than 4000 flavonoids in plants, and only a few of them in tablets, the reason that food might confer more benefit than does taking supplements begins to become clearer.
Dr. Phillips, Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington, KY, is Associate Editor of Internal Medicine Alert.
References
1. www.ncbi.nlm.nih.gov/cgi-bin/SCIENCE96/nph-gene?AD4.
2. www.faseb.org/genetics/ashg/policy/pol-21.htm.
3. Morris MC, et al. Alzheimer Dis Assoc Disor. 1998;12: 121-126.
4. Masaki KH, et al. Neurology. 2000;54:1265-1272.
5. Commenges D, et al. Eur J Epidemiol. 2000;16: 357-363.
6. Morris MC, et al. JAMA. 2002;287:3230-3237.
7. Foley DJ, White LR. JAMA. 2002;287:3261-3262.
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