Effect of Nutrients, Dietary Supplements and Vitamins on Cognition: a Systematic Review and Meta-Analysis of Randomized Controlled Trials

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Abstract

Background

Observational studies have suggested that various nutrients, dietary supplements, and vitamins may delay the onset of age-associated cognitive decline and dementia. We systematically reviewed recent randomized controlled trials investigating the effect of nutritional interventions on cognitive performance in older non-demented adults.

Methods

We searched MEDLINE, CINAHL, Embase, and the Cochrane Library for articles published between 2003 and 2013. We included randomized trials of ≥ 3 months’ duration that examined the cognitive effects of a nutritional intervention in non-demented adults > 40 years of age. Meta-analyses were done when sufficient trials were available.

Results

Twenty-four trials met inclusion criteria (six omega-3 fatty acids, seven B vitamins, three vitamin E, eight other interventions). In the meta-analyses, omega-3 fatty acids showed no significant effect on Mini-Mental State Examination (MMSE) scores (four trials, mean difference 0.06, 95% CI −0.08 – 0.19) or digit span forward (three trials, mean difference −0.02, 95% CI −0.30 – 0.25), while B vitamins showed no significant effect on MMSE scores (three trials, mean difference 0.02, 95% CI −0.22 – 0.25). None of the vitamin E studies reported significant effects on cognitive outcomes. Among the other nutritional interventions, statistically significant differences between the intervention and control groups on at least one cognitive domain were found in single studies of green tea extract, Concord grape juice, chromium picolinate, beta-carotene, two different combinations of multiple vitamins, and a dietary approach developed for the control of hypertension.

Conclusions

Omega-3 fatty acids, B vitamins, and vitamin E supplementation did not affect cognition in non-demented middle-aged and older adults. Other nutritional interventions require further evaluation before their use can be advocated for the prevention of age-associated cognitive decline and dementia.

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Most cited references 62

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Vitamin E and donepezil for the treatment of mild cognitive impairment.

Ronald Petersen, Ronald Thomas, Michael Grundman … (2005)

Mild cognitive impairment is a transitional state between the cognitive changes of normal aging and early Alzheimer's disease. In a double-blind study, we evaluated subjects with the amnestic subtype of mild cognitive impairment. Subjects were randomly assigned to receive 2000 IU of vitamin E daily, 10 mg of donepezil daily, or placebo for three years. The primary outcome was clinically possible or probable Alzheimer's disease; secondary outcomes were cognition and function. A total of 769 subjects were enrolled, and possible or probable Alzheimer's disease developed in 212. The overall rate of progression from mild cognitive impairment to Alzheimer's disease was 16 percent per year. As compared with the placebo group, there were no significant differences in the probability of progression to Alzheimer's disease in the vitamin E group (hazard ratio, 1.02; 95 percent confidence interval, 0.74 to 1.41; P=0.91) or the donepezil group (hazard ratio, 0.80; 95 percent confidence interval, 0.57 to 1.13; P=0.42) during the three years of treatment. Prespecified analyses of the treatment effects at 6-month intervals showed that as compared with the placebo group, the donepezil group had a reduced likelihood of progression to Alzheimer's disease during the first 12 months of the study (P=0.04), a finding supported by the secondary outcome measures. Among carriers of one or more apolipoprotein E epsilon4 alleles, the benefit of donepezil was evident throughout the three-year follow-up. There were no significant differences in the rate of progression to Alzheimer's disease between the vitamin E and placebo groups at any point, either among all patients or among apolipoprotein E epsilon4 carriers. Vitamin E had no benefit in patients with mild cognitive impairment. Although donepezil therapy was associated with a lower rate of progression to Alzheimer's disease during the first 12 months of treatment, the rate of progression to Alzheimer's disease after three years was not lower among patients treated with donepezil than among those given placebo. Copyright 2005 Massachusetts Medical Society.

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Association of mediterranean diet with mild cognitive impairment and Alzheimer's disease: a systematic review and meta-analysis.

Michelle M Mielke, Patricia Erwin, D S Knopman … (2013)

To conduct a systematic review of all studies to determine whether there is an association between the Mediterranean diet (MeDi) and cognitive impairment. We conducted a comprehensive search of the major databases and hand-searched proceedings of major neurology, psychiatry, and dementia conferences through November 2012. Prospective cohort studies examining the MeDi with longitudinal follow-up of at least 1 year and reporting cognitive outcomes (mild cognitive impairment [MCI] or Alzheimer's disease [AD]) were included. The effect size was estimated as hazard-ratio (HR) with 95% confidence intervals (CIs) using the random-effects model. Heterogeneity was assessed using Cochran's Q-test and I2-statistic. Out of the 664 studies screened, five studies met eligibility criteria. Higher adherence to the MeDi was associated with reduced risk of MCI and AD. The subjects in the highest MeDi tertile had 33% less risk (adjusted HR = 0.67; 95% CI, 0.55-0.81; p < 0.0001) of cognitive impairment (MCI or AD) as compared to the lowest MeDi score tertile. Among cognitively normal individuals, higher adherence to the MeDi was associated with a reduced risk of MCI (HR = 0.73; 95% CI, 0.56-0.96; p = 0.02) and AD (HR = 0.64; 95% CI, 0.46-0.89; p = 0.007). There was no significant heterogeneity in the analyses. While the overall number of studies is small, pooled results suggest that a higher adherence to the MeDi is associated with a reduced risk of developing MCI and AD, and a reduced risk of progressing from MCI to AD. Further prospective-cohort studies with longer follow-up and randomized controlled trials are warranted to consolidate the evidence. Systematic review registration number: PROSPERO 2013: CRD42013003868.

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Dietary intake of antioxidants and risk of Alzheimer disease.

Marianne J. Engelhart (2002)

Laboratory findings have suggested that oxidative stress may contribute to the pathogenesis of Alzheimer disease. Therefore, the risk of Alzheimer disease might be reduced by intake of antioxidants that counteract the detrimental effects of oxidative stress. To determine whether dietary intake of antioxidants is related to risk of Alzheimer disease. The Rotterdam Study, a population-based, prospective cohort study conducted in the Netherlands. A total of 5395 participants who, at baseline (1990-1993), were aged at least 55 years, free of dementia, and noninstitutionalized and had reliable dietary assessment. Participants were reexamined in 1993-1994 and 1997-1999 and were continuously monitored for incident dementia. Incidence of Alzheimer disease, based on Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) criteria and National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer Disease and Related Disorders Association (NINCDS-ADRDA) criteria, associated with dietary intake of beta carotene, flavonoids, vitamin C, and vitamin E. After a mean follow-up of 6 years, 197 participants developed dementia, of whom 146 had Alzheimer disease. When adjustments were made for age, sex, baseline Mini-Mental State Examination score, alcohol intake, education, smoking habits, pack-years of smoking, body mass index, total energy intake, presence of carotid plaques, and use of antioxidative supplements, high intake of vitamin C and vitamin E was associated with lower risk of Alzheimer disease (rate ratios [RRs] per 1-SD increase in intake were 0.82 [95% confidence interval [CI], 0.68-0.99] and 0.82 [95% CI, 0.66-1.00], respectively). Among current smokers, this relationship was most pronounced (RRs, 0.65 [95% CI, 0.37-1.14] and 0.58 [95% CI, 0.30-1.12], respectively) and also was present for intake of beta carotene (RR, 0.49 [95% CI, 0.27-0.92]) and flavonoids (RR, 0.54 [95% CI, 0.31-0.96]). The associations did not vary by education or apolipoprotein E genotype. High dietary intake of vitamin C and vitamin E may lower the risk of Alzheimer disease.

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Author and article information

Journal

Journal ID (nlm-ta): Can Geriatr J

Journal ID (iso-abbrev): Can Geriatr J

Title: Canadian Geriatrics Journal

Publisher: Canadian Geriatrics Society

ISSN (Electronic): 1925-8348

Publication date Collection: December 2015

Publication date (Electronic): 23 December 2015

Volume: 18

Issue: 4

Pages: 231-245

Affiliations

[1 ]Department of Physiology and Pharmacology, Faculty of Medicine, University of Calgary, Calgary, AB;

[2 ]Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, AB;

[3 ]Brenda Stafford Foundation Chair in Geriatric Medicine, Faculty of Medicine, University of Calgary, Calgary, AB;

[4 ]Departments of Medicine, Clinical Neurosciences and Community Health Sciences, Faculty of Medicine, University of Calgary, Calgary, AB;

[5 ]Alberta Seniors Health Strategic Clinical Network, Alberta Health Services, Calgary, AB

Author notes

Correspondence to: David B. Hogan, MD, HSC-3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada, E-mail: dhogan@ 123456ucalgary.ca

Article

Publisher ID: cgj-18-231

DOI: 10.5770/cgj.18.189

PMC ID: 4696451

PubMed ID: 26740832

SO-VID: 5b51de71-b2e6-46e1-ae2e-123f23b4d558

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial No-Derivative license ( http://creativecommons.org/licenses/by-nc-nd/2.5/ca/), which permits unrestricted non-commercial use and distribution, provided the original work is properly cited.

Effect of Nutrients, Dietary Supplements and Vitamins on Cognition: a Systematic Review and Meta-Analysis of Randomized Controlled Trials

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Abstract

Background

Methods

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Conclusions

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Karger: Neurology and Neuroscience

Most cited references 62

Vitamin E and donepezil for the treatment of mild cognitive impairment.

Association of mediterranean diet with mild cognitive impairment and Alzheimer's disease: a systematic review and meta-analysis.

Dietary intake of antioxidants and risk of Alzheimer disease.

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