Overall, our results provide no evidence for a beneficial effect of multivitamin and multimineral supplementation on cognitive function in the majority of men and women 65 years and over living in the community. This result is consistent with all previous studies in non-selected elderly populations [2
] apart from the retracted Canadian study [13
]. In the present study the doses of the vitamins and minerals in the supplement ranged from 50–210% of the UK reference nutrient intakea
i.e. levels which could be achieved by a well-balanced diet. Several other studies have used higher doses, particularly of B vitamins [2
] or antioxidant vitamins [5
] but none of these found a beneficial effect. We considered the possibility that the participants in the present study were unusually well nourished but found no evidence to support this, as the proportion of participants aged 75 years and over classified as at increased risk of micronutrient deficiency was similar to those in an earlier cross-sectional survey in the area [19
]; in addition we excluded subjects who had been taking dietary supplements prior to the study who were more likely to have had better dietary intake and nutritional status [20
The cognitive function tests used in the present study assessed only short term memory and executive function, so we cannot rule out the possibility of effects in other cognitive domains such attention and concentration. We selected the two tests used in the present study as they could be carried out by telephone at follow-up, but future studies should include a wider range of tests of different cognitive domains. We also cannot exclude the possibility of effects of nutrients such as selenium or n-3 polyunsaturated fatty acids, which were not included in the supplements used.
For the subgroups defined on the basis of age or nutritional risk, there was weak evidence for a beneficial effect in verbal fluency but not in the digit span forward test. Digit span forward is a test of attention and immediate memory involving a relatively familiar task which may be performed relatively well even in advanced cognitive decline, while verbal fluency tests speed of processing and information retrieval which are sensitive to the difficulty in generating words characteristic of Alzheimer's disease [21
]. The possibility that those at increased risk of nutritional deficiency may benefit from supplements is supported by the FACIT study of men and women aged 50–70 y with elevated homocysteine in whom there were significant effects on global cognitive function, though for specific cognitive domains the effects were seen in memory (assessed by recall of 15 common words) and information processing speed (assessed by letter-digit substitution) but not in verbal fluency (assessed by asking the subjects to name as many animals as possible in one minute) or in sensorimotor speed or complex speed [9
]. The possibility of a beneficial effect in higher risk subjects is also supported by the study of Dutch care home residents with a BMI less than 25 kg/m2
and median age of 83 y which found beneficial effects of multivitamins and multiminerals in a test of short-term memory and one of two tests of category fluency [12
]. The clinical significance of the differences in the verbal fluency test scores between supplemented and placebo groups seen in the present study is difficult to estimate as the tests are not widely used in clinical practice, but data from a cross-sectional study of Canadian adults suggest that the rate of decline in performance on this test is of the order of one point per 3 years [22
]. By this estimate the difference of 2 points observed between the supplemented and placebo groups in the present study would be equivalent to the decline seen over 6 years of normal aging and could therefore represent a clinically useful effect.
A limitation of this study is that we classified participants as being at increased risk of nutritional deficiency using a simple risk questionnaire rather than by measuring their actual nutritional status from blood samples. The nutrition assessment questionnaire used had previously been validated by comparison with blood measures of nutrient status in 398 community-living men and women aged 75 and over, in whom the odds ratios (95% CI) for deficiency of iron, folate, vitamin C and vitamin D in those identified at risk by the questionnaire were 3.8 (2.0, 6.9); 5.1 (2.3; 11.3); 5.7 (3.1, 10.4) and 4.3 (1.9, 9.4) respectively [16
]. Better definition of subjects at nutritional risk could be useful in assessing whether the effect seen in those identified as being at nutritional risk in this study is a real effect.
In summary, we found no evidence for a beneficial effect of multivitamin and multimineral supplementation on two tests of cognitive function in tests in the total sample of participants, but cannot exclude the possibility of beneficial effects in those at higher risk of nutritional deficiency. In view of the high social and economic costs of cognitive decline and the low cost of nutritional supplementation, further intervention studies in older people, particularly those at increased risk of nutritional deficiency, are still warranted.