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Meta-Analysis
. 2018 Nov 1;11(11):CD011905.
doi: 10.1002/14651858.CD011905.pub2.

Vitamin and mineral supplementation for preventing dementia or delaying cognitive decline in people with mild cognitive impairment

Jenny McCleery  1 , Rajesh P Abraham, David A Denton, Anne Ws Rutjes, Lee-Yee Chong, Aalya S Al-Assaf, Daniel J Griffith, Shireen Rafeeq, Hakan Yaman, Muzaffar A Malik, Marcello Di Nisio, Gabriel Martínez, Robin Wm Vernooij, Naji Tabet
Affiliations
Meta-Analysis

Vitamin and mineral supplementation for preventing dementia or delaying cognitive decline in people with mild cognitive impairment

Jenny McCleery et al. Cochrane Database Syst Rev. .

Abstract

Background: Vitamins and minerals have many functions in the nervous system which are important for brain health. It has been suggested that various different vitamin and mineral supplements might be useful in maintaining cognitive function and delaying the onset of dementia. In this review, we sought to examine the evidence for this in people who already had mild cognitive impairment (MCI).

Objectives: To evaluate the effects of vitamin and mineral supplementation on cognitive function and the incidence of dementia in people with mild cognitive impairment.

Search methods: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's (CDCIG) specialised register, as well as MEDLINE, Embase, PsycINFO, CENTRAL, CINAHL, LILACs, Web of Science Core Collection, ClinicalTrials.gov, and the WHO Portal/ICTRP, from inception to 25 January 2018.

Selection criteria: We included randomised or quasi-randomised, placebo-controlled trials which evaluated orally administered vitamin or mineral supplements in participants with a diagnosis of mild cognitive impairment and which assessed the incidence of dementia or cognitive outcomes, or both. We were interested in studies applicable to the general population of older people and therefore excluded studies in which participants had severe vitamin or mineral deficiencies.

Data collection and analysis: We sought data on our primary outcomes of dementia incidence and overall cognitive function and on secondary outcomes of episodic memory, executive function, speed of processing, quality of life, functional performance, clinical global impression, adverse events, and mortality. We conducted data collection and analysis according to standard Cochrane systematic review methods. We assessed the risk of bias of included studies using the Cochrane 'Risk of bias' assessment tool. We grouped vitamins and minerals according to their putative mechanism of action and, where we considered it to be clinically appropriate, we pooled data using random-effects methods. We used GRADE methods to assess the overall quality of evidence for each comparison and outcome.

Main results: We included five trials with 879 participants which investigated B vitamin supplements. In four trials, the intervention was a combination of vitamins B6, B12, and folic acid; in one, it was folic acid only. Doses varied. We considered there to be some risks of performance and attrition bias and of selective outcome reporting among these trials. Our primary efficacy outcomes were the incidence of dementia and scores on measures of overall cognitive function. None of the trials reported the incidence of dementia and the evidence on overall cognitive function was of very low-quality. There was probably little or no effect of B vitamins taken for six to 24 months on episodic memory, executive function, speed of processing, or quality of life. The evidence on our other secondary clinical outcomes, including harms, was very sparse or very low-quality. There was evidence from one study that there may be a slower rate of brain atrophy over two years in participants taking B vitamins. The same study reported subgroup analyses based on the level of serum homocysteine (tHcy) at baseline and found evidence that B vitamins may improve episodic memory in those with tHcy above the median at baseline.We included one trial (n = 516) of vitamin E supplementation. Vitamin E was given as 1000 IU of alpha-tocopherol twice daily. We considered this trial to be at risk of attrition and selective reporting bias. There was probably no effect of vitamin E on the probability of progression from MCI to Alzheimer's dementia over three years (HR 1.02; 95% CI 0.74 to 1.41; n = 516; 1 study, moderate-quality evidence). There was also no evidence of an effect at intermediate time points. The available data did not allow us to conduct analyses, but the authors reported no significant effect of three years of supplementation with vitamin E on overall cognitive function, episodic memory, speed of processing, clinical global impression, functional performance, adverse events, or mortality (five deaths in each group). We considered this to be low-quality evidence.We included one trial (n = 256) of combined vitamin E and vitamin C supplementation and one trial (n = 26) of supplementation with chromium picolinate. In both cases, there was a single eligible cognitive outcome, but we considered the evidence to be very low-quality and so could not be sure of any effects.

Authors' conclusions: The evidence on vitamin and mineral supplements as treatments for MCI is very limited. Three years of treatment with high-dose vitamin E probably does not reduce the risk of progression to dementia, but we have no data on this outcome for other supplements. Only B vitamins have been assessed in more than one RCT. There is no evidence for beneficial effects on cognition of supplementation with B vitamins for six to 24 months. Evidence from a single study of a reduced rate of brain atrophy in participants taking vitamin B and a beneficial effect of vitamin B on episodic memory in those with higher tHcy at baseline warrants attempted replication.

PubMed Disclaimer

Conflict of interest statement

Jenny McCleery ‐ none known Rajesh P Abraham ‐ none known David A Denton ‐ none known Anne WS Rutjes ‐ none known Lee‐Yee Chong ‐ none known Aalya S Al‐Assaf ‐ none known Daniel J Griffith ‐ none known Shireen Rafeeq ‐ none known Hakan Yaman ‐ none known Muzaffar A Malik ‐ none known Marcello Di Nisio ‐ Di Nisio reports participation to Advisory Boards for Daiichi‐Sankyo, Aspen and Pfizer, and consultancy fees for Daiichi‐Sankyo and Bayer Health Care outside the submitted work. Gabriel Martínez ‐ none known Robin WM Vernooij ‐ none known Naji Tabet ‐ none known

Figures

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Study flow diagram.
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Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
4
4
Forest plot of comparison: 1 B vitamins versus placebo, outcome: 1.1 Overall cognitive function (MMSE).
5
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Forest plot of comparison: 1 B vitamins versus placebo, outcome: 1.2 Episodic memory.
6
6
Forest plot of comparison: 1 B vitamins versus placebo, outcome: 1.3 Executive function.
7
7
Forest plot of comparison: 1 B vitamins versus placebo, outcome: 1.4 Speed of processing.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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References to studies awaiting assessment

ACTRN12607000321448 {published data only}
    1. ACTRN12607000321448. Vitamin D and cognition trial/a randomised, placebo controlled trial of Vitamin D in older adults with mild cognitive impairment and low vitamin D concentration to prevent cognitive decline and delay progression of cognitive decline. www.anzctr.org.au/TrialSearch.aspx?searchTxt=12607000321448 (first received 13 Jun 2007).
    1. Flicker L, Greenop K, Almeida O, Alfonso H, Beer C, Hill K, et al. Effect of vitamin D supplementation on cognitive function in older adults with mild cognitive impairment ‐ a randomized trial. Australasian Journal on Ageing 2011;30(1):11.
    1. Torres SJ, Lautenschlager NT, Wattanapenpaiboon N, Greenop KR, Beer C, Flicker L, et al. Dietary patterns are associated with cognition among older people with mild cognitive impairment. Nutrients 2012;4(11):1542‐51. [PUBMED: 23201831] - PMC - PubMed
Jiang 2014 {published data only}
    1. Jiang B, Ding C, Yao G, Yao C, Zhang Y, Ge J, et al. Intervention effect of folic acid and vitamin B12 on vascular cognitive impairment complicated with hyperhomocysteinemia. Journal of Medical Biochemistry 2014;33(2):169‐174.
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Ma 2017 {published data only (unpublished sought but not used)}
    1. Ma F, Li Q, Zhou X, Zhao J, Song A, Li W, et al. Effects of folic acid supplementation on cognitive function and Abeta‐related biomarkers in mild cognitive impairment: a randomized controlled trial. European Journal of Nutrition 2017 Dec 18 [Epub ahead of print]. [DOI: ] - PubMed
    1. Ma F, Wu T, Zhao J, Han F, Marseglia A, Liu H, et al. Effects of 6‐month folic acid supplementation on cognitive function and blood biomarkers in mild cognitive impairment: a randomized controlled trial in China. Journals of Gerontology. Series A: Biological Sciences and Medical Sciences 2016;71(10):1376‐83. - PubMed
    1. Ma F, Wu T, Zhao J, Song A, Liu H, Xu W, et al. Folic acid supplementation improves cognitive function by reducing the levels of peripheral inflammatory cytokines in elderly Chinese subjects with MCI. Scientific Reports 2016;6(37486). [DOI: 10.1038/srep37486] - DOI - PMC - PubMed

References to ongoing studies

NCT02185222 {published data only}
    1. NCT02185222. Effect of vitamin D on cognitive decline of patients with memory complaint. clinicaltrials.gov/show/NCT02185222 2014; Vol. (first received 9 July 2014).

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