Antioxidants Against Alzheimer's, Redux

Summarized by Robert W. Griffith, MD
March 12, 2004

Introduction

Antioxidants are known to scavenge free radicals such as those that may be responsible for some of the neuronal damage of Alzheimer disease. Neurons are particularly vulnerable to free-radical damage, and this may account for the changes seen in the aging brain as well as in some types of dementia.

Several epidemiological studies have shown lower risks of Alzheimer disease in people taking more dietary antioxidants, but a recent study showed no such association between dementia and antioxidant vitamin intake, either dietary or supplemental.¹ The publication of a new study in Archives of Neurology, where vitamin C and E supplements were tested in both a prevalence and incidence design, throws more light on the topic.

Method

The study enrolled 5092 elderly residents of Cache County, Utah, USA, in 1995. The average age was 75, and 60% of the participants were female. Genotyping was done for apolipoprotein E (APOE) and a multistage screening for prevalent cases of dementia. This was termed 'wave I'. Three years later the screening was repeated in order to diagnose incident cases of dementia - 'wave II'.

The screening methods were based on interviews that included the modified Mini-Mental State Examination and the Dementia Questionnaire. Further examinations included extensive physical and neurological exams, interviews with a geriatric psychiatrist and neuropsychologist. A consensus panel was used to reach a final diagnosis. A total of 4740 subjects had sufficient data to allow determination of their cognitive status.

The initial assessment included an interview about suspected risk factors for dementia. It covered education, occupation, medical history, tobacco and alcohol use, and medications taken. Specific questions dealt with vitamin supplements. Participants were classified as vitamin E users (more than 400 IU daily), vitamin C users (at least 500 mg ascorbic acid daily), multivitamin users (taking vitamin E and/or C in lower daily doses), and vitamin B users (taking a formulation of B-complex vitamins).

Results

In wave I, there were 355 people (7.5%) with prevalent dementia; of these, 200 (56%) had Alzheimer disease. At the end of wave II there were 3227 survivors 'at risk'; 185 (5.7%) had dementia, of whom 104 (56%) had Alzheimer disease.

Over 97% of the participants gave sufficient information to allow them to be classified according to their supplement use. Roughly 17% were vitamin E or C supplement users, almost all of them (97%) for more than 2 years; these subjects were more likely to be female, younger, better educated, and in better general health than the rest.

Prevalence Analysis: Before adjustment for age, sex, years of education, APOE status, and general health, the use of vitamin E, vitamin C, and multivitamins were all associated with a reduced risk of Alzheimer disease. After making these adjustments, however, the association was only significant for the use of vitamin E and multivitamins. When analysis of the combined use of vitamins was done, a very strong association was found between a lower risk of Alzheimer disease and the combined use of vitamin E and vitamin C, with or without the use of multivitamins (odds ratio 0.22; 95% CI 0.05 to 0.60).

Incidence Analysis: The results here were similar to those for the prevalence analysis. The incidence of Alzheimer disease was reduced with vitamin E and multivitamins in combination, and more markedly so with the use of vitamin E and vitamin C together (odds ratio 0.36; 95% CI 0.09 to 0.99). Adjustment of these analyses for age, sex, or APOE status did not affect the results.

There was no evidence in these analyses of a protective effect in users of vitamin E or vitamin C supplements alone, with multivitamins alone, or with B-complex vitamin supplements.

Comment

This study suggests that antioxidant vitamins, specifically the combination of vitamin E and C supplements, may prevent Alzheimer disease. Although the study included both prevalence and incidence analyses, the authors point out that 'formal proof of such an effect can only come from randomized prevention trials'.

The authors of the study provide a rationale for the superior action of the two vitamins in combination. They speculate that, as vitamin C is water soluble and rapidly eliminated, its effect is limited to the reduction of the oxidized lipid-soluble vitamin E.

It must be noted that the current recommended daily allowance for vitamin E is 22 IU (15 mg), while that for vitamin C (ascorbic acid) is 75-90 mg.² Multivitamin preparations usually contain these amounts, whereas individual vitamin supplements commonly contain up to 1000 IU of vitamin E and 500-1000 mg of vitamin C.

The publication of this study will doubtless lead many patients to ask their doctors about the merits and risks of taking large doses of vitamins E and C, i.e. well above the recommended daily allowance. We have, on these pages, generally supported the concept that eating a vitamin-rich diet is superior to taking supplements. However, the results of this study are quite compelling. And doses up to those considered relevant (400 IU of vitamin E, 500 mg of ascorbic acid) are highly unlikely to be accompanied by any health risk, while they may well do good, if taken together.

Source

• Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements. PP. Zandi, JC. Anthony, AS. Khachaturian,  et al., Arch Neurol, 2004, vol. 61, pp. 82--88

Footnotes
1. Antioxidant vitamin intake and risk of Alzheimer disease. JA. Luchsinger, MX. Tang, S. Shea, R. Mayeux, Arch Neurol, 2003, vol. 60, pp. 203--208
2. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium and Carotenoids.  Institute of Medicine, Washington, DC: National Academic Press, 2000

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