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Meta-Analysis
. 2018 Dec 17;12(12):CD011906.
doi: 10.1002/14651858.CD011906.pub2.

Vitamin and mineral supplementation for maintaining cognitive function in cognitively healthy people in mid and late life

Anne Ws Rutjes  1 , David A Denton, Marcello Di Nisio, Lee-Yee Chong, Rajesh P Abraham, Aalya S Al-Assaf, John L Anderson, Muzaffar A Malik, Robin Wm Vernooij, Gabriel Martínez, Naji Tabet, Jenny McCleery
Affiliations
Meta-Analysis

Vitamin and mineral supplementation for maintaining cognitive function in cognitively healthy people in mid and late life

Anne Ws Rutjes et al. Cochrane Database Syst Rev. .

Abstract

Background: Vitamins and minerals play multiple functions within the central nervous system which may help to maintain brain health and optimal cognitive functioning. Supplementation of the diet with various vitamins and minerals has been suggested as a means of maintaining cognitive function, or even of preventing dementia, in later life.

Objectives: To evaluate the effects of vitamin and mineral supplementation on cognitive function in cognitively healthy people aged 40 years or more.

Search methods: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's (CDCIG) specialised register, as well as MEDLINE, Embase, PsycINFO, CINAHL, ClinicalTrials.gov and the WHO Portal/ICTRP from inception to 26th January 2018.

Selection criteria: We included randomised controlled trials that evaluated the cognitive effects on people aged 40 years or more of any vitamin or mineral supplements taken by mouth for at least three months.

Data collection and analysis: Study selection, data extraction, and quality assessments were done in duplicate. Vitamins were considered broadly in the categories of B vitamins, antioxidant vitamins, and combinations of both. Minerals were considered separately, where possible. If interventions and outcomes were considered sufficiently similar, then data were pooled. In order to separate short-term cognitive effects from possible longer-term effects on the trajectory of cognitive decline, data were pooled for various treatment durations from 3 months to 12 months and up to 10 years or more.

Main results: In total, we included 28 studies with more than 83,000 participants. There were some general limitations of the evidence. Most participants were enrolled in studies which were not designed primarily to assess cognition. These studies often had no baseline cognitive assessment and used only brief cognitive assessments at follow-up. Very few studies assessed the incidence of dementia. Most study reports did not mention adverse events or made only very general statements about them. Only 10 studies had a mean follow-up > 5 years. Only two studies had participants whose mean age was < 60 years at baseline. The risk of bias in the included studies was generally low, other than a risk of attrition bias for longer-term outcomes. We considered the certainty of the evidence behind almost all results to be moderate or low.We included 14 studies with 27,882 participants which compared folic acid, vitamin B12, vitamin B6, or a combination of these to placebo. The majority of participants were aged over 60 years and had a history of cardio- or cerebrovascular disease. We found that giving B vitamin supplements to cognitively healthy adults, mainly in their 60s and 70s, probably has little or no effect on global cognitive function at any time point up to 5 years (SMD values from -0.03 to 0.06) and may also have no effect at 5-10 years (SMD -0.01). There were very sparse data on adverse effects or on incidence of cognitive impairment or dementia.We included 8 studies with 47,840 participants in which the active intervention was one or more of the antioxidant vitamins: ß-carotene, vitamin C or vitamin E. Results were mixed. For overall cognitive function, there was low-certainty evidence of benefit associated with ß-carotene after a mean of 18 years of treatment (MD 0.18 TICS points, 95% CI 0.01 to 0.35) and of vitamin C after 5 years to 10 years (MD 0.46 TICS points, 95% CI 0.14 to 0.78), but not at earlier time points. From two studies which reported on dementia incidence, there was low-certainty evidence of no effect of an antioxidant vitamin combination or of vitamin E, either alone or combined with selenium. One of the included studies had been designed to look for effects on the incidence of prostate cancer; it found a statistically significant increase in prostate cancer diagnoses among men taking vitamin E.One trial with 4143 participants compared vitamin D3 (400 IU/day) and calcium supplements to placebo. We found low- to moderate-certainty evidence of no effect of vitamin D3 and calcium supplements at any time-point up to 10 years on overall cognitive function (MD after a mean of 7.8 years -0.1 MMSE points, 95% CI -0.81 to 0.61) or the incidence of dementia (HR 0.94, 95% CI 0.72 to 1.24). A pilot study with 60 participants used a higher dose of vitamin D3 (4000 IU on alternate days) and found preliminary evidence that this dose probably has no effect on cognitive function over six months.We included data from one trial of zinc and copper supplementation with 1072 participants. There was moderate-certainty evidence of little or no effect on overall cognitive function (MD 0.6 MMSE points, 95% CI -0.19 to 1.39) or on the incidence of cognitive impairment after 5 years to 10 years. A second smaller trial provided no usable data, but reported no cognitive effects of six months of supplementation with zinc gluconate.From one study with 3711 participants, there was low-certainty evidence of no effect of approximately five years of selenium supplementation on the incidence of dementia (HR 0.83, 95% CI 0.61 to 1.13).Finally, we included three trials of complex supplements (combinations of B vitamins, antioxidant vitamins, and minerals) with 6306 participants. From the one trial which assessed overall cognitive function, there was low-certainty evidence of little or no effect on the TICS (MD after a mean of 8.5 years 0.12, 95% CI -0.14 to 0.38).

Authors' conclusions: We did not find evidence that any vitamin or mineral supplementation strategy for cognitively healthy adults in mid or late life has a meaningful effect on cognitive decline or dementia, although the evidence does not permit definitive conclusions. There were very few data on supplementation starting in midlife (< 60 years); studies designed to assess cognitive outcomes tended to be too short to assess maintenance of cognitive function; longer studies often had other primary outcomes and used cognitive measures which may have lacked sensitivity. The only positive signals of effect came from studies of long-term supplementation with antioxidant vitamins. These may be the most promising for further research.

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Conflict of interest statement

Rutjes AWS: Dr. Rutjes declares partial funding by a grant for the project 'OPERAM: OPtimising therapy to prevent Avoidable hospital admissions in the Multi‐morbid elderly' supported by the European Union's Horizon 2020 research and innovation programme under the grant agreement No 6342388, and by the Swiss State Secretariat for Education, Research and Innovation (SERI) under contract number 15.0137.

Denton DA: none known

Di Nisio M: Di Nisio declares consultancy fees from Daiichi Sankyo, Bayer, and Aspen and participation to advisory boards for Daiichi Sankyo, Bayer, Pfizer outside the submitted work. M Di Nisio declares partial funding by a grant for the project 'OPERAM: OPtimising therapy to prevent Avoidable hospital admissions in the Multi‐morbid elderly' supported by the European Union's Horizon 2020 research and innovation programme under the grant agreement No 6342388, and by the Swiss State Secretariat for Education, Research and Innovation (SERI) under contract number 15.0137

Chong LY: none known

Abraham RP: none known

Al‐Assaf AS: none known

Anderson JL: none known

Malik MA: none known

Vernooij RWM: none known

Martinez G: none known

Tabet N: N Tabet reports I receive honorarium and consultation fees from the pharmaceutical industry

McCleery J: none known

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Forest plot of comparison: 1 B vitamins versus control, outcome: 1.1 Overall cognitive functioning.
4
4
Forest plot of comparison: 2 Antioxidants versus control, outcome: 2.1 Overall cognitive functioning.
5
5
Forest plot of comparison: 2 Antioxidants versus control, outcome: 2.2 Episodic memory.
1.1
1.1. Analysis
Comparison 1 B vitamins versus control, Outcome 1 Overall cognitive functioning.
1.2
1.2. Analysis
Comparison 1 B vitamins versus control, Outcome 2 Episodic memory.
1.3
1.3. Analysis
Comparison 1 B vitamins versus control, Outcome 3 Executive function.
1.4
1.4. Analysis
Comparison 1 B vitamins versus control, Outcome 4 Speed of processing.
1.5
1.5. Analysis
Comparison 1 B vitamins versus control, Outcome 5 Incidence of MCI or dementia.
1.6
1.6. Analysis
Comparison 1 B vitamins versus control, Outcome 6 All‐cause mortality.
2.1
2.1. Analysis
Comparison 2 Antioxidants versus control, Outcome 1 Overall cognitive functioning.
2.2
2.2. Analysis
Comparison 2 Antioxidants versus control, Outcome 2 Episodic memory.
2.3
2.3. Analysis
Comparison 2 Antioxidants versus control, Outcome 3 Executive function.
2.4
2.4. Analysis
Comparison 2 Antioxidants versus control, Outcome 4 Incidence of dementia.
2.5
2.5. Analysis
Comparison 2 Antioxidants versus control, Outcome 5 All‐cause mortality.
3.1
3.1. Analysis
Comparison 3 Vitamin D3 versus placebo, Outcome 1 Overall cognitive functioning.
3.2
3.2. Analysis
Comparison 3 Vitamin D3 versus placebo, Outcome 2 Episodic memory.
3.3
3.3. Analysis
Comparison 3 Vitamin D3 versus placebo, Outcome 3 Executive function.
3.4
3.4. Analysis
Comparison 3 Vitamin D3 versus placebo, Outcome 4 Speed of processing.
3.5
3.5. Analysis
Comparison 3 Vitamin D3 versus placebo, Outcome 5 Incident MCI.
3.6
3.6. Analysis
Comparison 3 Vitamin D3 versus placebo, Outcome 6 Incident all‐cause dementia.
4.1
4.1. Analysis
Comparison 4 Zinc + copper versus placebo, Outcome 1 Overall cognitive functioning.
4.2
4.2. Analysis
Comparison 4 Zinc + copper versus placebo, Outcome 2 Episodic memory.
4.3
4.3. Analysis
Comparison 4 Zinc + copper versus placebo, Outcome 3 Executive function.
5.1
5.1. Analysis
Comparison 5 Complex multivitamin versus control, Outcome 1 Overall cognitive functioning.
5.2
5.2. Analysis
Comparison 5 Complex multivitamin versus control, Outcome 2 Episodic memory.
5.3
5.3. Analysis
Comparison 5 Complex multivitamin versus control, Outcome 3 Executive function.
5.4
5.4. Analysis
Comparison 5 Complex multivitamin versus control, Outcome 4 Speed of processing.
See this image and copyright information in PMC

Update of

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Abbasi 2013 {published data only}
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ACTRN12607000321448 {published data only}
    1. ACTRN12607000321448. Vitamin D and Cognition Trial [Vitamin D and Cognition Trial (VITA‐D). 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]. anzctr.org.au/Trial/Registration/TrialReview.aspx?id=82086 (first received 13 June 2007).
Alavi 2014 {published data only}
    1. Alavi N, Elmadfa I, Djazayery A, Barekatain M, Aghaye G, Djalali M, et al. The effect of antioxidant vitamins E and C on cognitive performance of the elderly with mild cognitive impairment in Isfahan, Iran: a double‐blind, randomized, placebo‐controlled trial. European Journal of Nutrition 2014;53:1255‐62. - PubMed
Almeida 2010 {published data only}
    1. Almeida OP, Marsh K, Alfonso H, Flicker L, Davis TM, Hankey GJ. B‐vitamins reduce the long‐term risk of depression after stroke: the VITATOPS‐DEP trial. Annals of Neurology 2010;68:503‐10. - PubMed
Anonymous 2003 {published and unpublished data}
    1. Anonymous. Effect of vitamins and aspirin on markers of platelet activation, oxidative stress and homocysteine in people at high risk of dementia. Journal of Internal Medicine 2003;354:67‐75. - PubMed
Arwert 2003 {published data only}
    1. Arwert LI, Deijen JB, Drent ML. Effects of an oral mixture containing glycine, glutamine and niacin on memory, GH and IGF‐I secretion in middle‐aged and elderly subjects. Nutritional Neuroscience 2003;6:269‐75. - PubMed
Benton 1995 {published data only}
    1. Benton D, Fordy J, Haller J. The impact of long‐term vitamin supplementation on cognitive functioning. Psychopharmacology 1995;117:298‐305. - PubMed
Bryan 2002 {published data only}
    1. Bryan J, Calvaresi E, Hughes D. Short‐term folate, vitamin B‐12 or vitamin B‐6 supplementation slightly affects memory performance but not mood in women of various ages. Journal of Nutrition 2002;132:1345‐56. - PubMed
Chan 2010 {published data only}
    1. Chan A, Remington R, Kotyla E, Lepore A, Zemianek J, Shea TB. A vitamin/nutriceutical formulation improves memory and cognitive performance in community‐dwelling adults without dementia. Journal of Nutrition, Health & Aging 2010;14:224‐30. - PubMed
Cheng 2016 {published data only}
    1. Cheng D, Kong H, Pang W, Yang H, Lu H, Huang C, et al. B vitamin supplementation improves cognitive function in the middle aged and elderly with hyperhomocysteinaemia. Nutritional Neuroscience 2016;19(10):461‐6. - PubMed
Chew 2015 {published data only}
    1. Chew EY, Clemons TE, Agrón E, Launer LJ, Grodstein F, Bernstein PS, et al. Effect of Omega‐3 fatty acids, Lutein/Zeaxanthin, or other nutrient supplementation on cognitive function: the AREDS2 randomized clinical trial. JAMA 2015;314(8):791‐801. [DOI: 10.1001/jama.2015.9677] - DOI - PMC - PubMed
Corless 1987 {published data only}
    1. Corless D, Ellis M, Dawson E, Fraser F, Evans S, Perry JD, et al. Using activities of daily living assessments to measure the effectiveness of vitamin D supplements in elderly long‐stay patients. British Journal of Occupational Therapy 1987;50:60‐2.
De Jager 2012 {published data only}
    1. Jager CA, Oulhaj A, Jacoby R, Refsum H, Smith AD. Cognitive and clinical outcomes of homocysteine‐lowering B‐vitamin treatment in mild cognitive impairment: a randomized controlled trial. International Journal of Geriatric Psychiatry 2012;27:592‐600. - PubMed
    1. Douaud G, Refsum H, Jager CA, Jacoby R, Nichols TE, Smith SM, et al. Preventing Alzheimer's disease‐related gray matter atrophy by B‐vitamin treatment. PNAS Proceedings of the National Academy of Sciences of the United States of America 2013;110:9523‐8. - PMC - PubMed
    1. Smith AD, Smith SM, Jager CA, Whitbread P, Johnston C, Agacinski G, et al. Homocysteine‐lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLOS One 2010;5:e12244. - PMC - PubMed
Dhesi 2004 {published data only}
    1. Dhesi J, Jackson S, Bearne L, Moniz C, Hurley M, Swift CG, et al. Vitamin D supplementation improves neuromuscular function in older people who fall. Age and Ageing 2004;33(6):589‐95. - PubMed
Flicker 2011 {published data only}
    1. Flicker L, Greenop K, Almeida O, Beer C, Hill K, Nowson C, et al. Effect of vitamin d supplementation on cognitive function in older adults with mild cognitive impairment ‐ a randomized trial. Journal of bone and mineral research 2011;26(1 suppl):S244. [DOI: 10.1111/j.1741-6612.2010.00523a.x] - DOI
Ford 2008 {published data only}
    1. Ford AH, Flicker L, Thomas J, Norman P, Jamrozik K, Almeida OP. Vitamins B12, B6, and folic acid for onset of depressive symptoms in older men: results from a 2‐year placebo‐controlled randomized trial. Journal of Clinical Psychiatry 2008;69:1203‐9. - PubMed
Harris 2015 {published data only}
    1. Harris E, Macpherson H, Pipingas A. Improved blood biomarkers but no cognitive effects from 16 weeks of multivitamin supplementation in healthy older adults. Nutrients 2015;7:3796‐812. - PMC - PubMed
Hvas 2004 {published data only}
    1. Hvas AM, Juul S, Lauritzen L, Nexo E, Ellegaard J. No effect of vitamin B‐12 treatment on cognitive function and depression: a randomized placebo controlled study. Journal of Affective Disorders 2004;81:269‐73. - PubMed
Imaoka 2016 {published data only}
    1. Imaoka M, Higuchi Y, Todo E, Kitagwa T, Ueda T. Low‐frequency exercise and vitamin D supplementation reduce falls among institutionalized frail elderly. International Journal of Gerontology 2016;10:202‐6.
Krikorian 2010 {published data only}
    1. Krikorian R, Eliassen JC, Boespflug EL, Nash TA, Shidler MD. Improved cognitive‐cerebral function in older adults with chromium supplementation. Nutritional Neuroscience 2010;13:116‐22. - PubMed
Kwok 2017 {published data only}
    1. Kwok T, Lee J, Ma R, Wong S, Kung K, Lam A, et al. A randomized placebo controlled trial of vitamin B12 supplementation to prevent cognitive decline in older diabetic people with borderline low serum vitamin B12. Clinical Nutrition 2017;36(6):1509‐15. [DOI: 10.1016/j.clnu.2016.10.018] - DOI - PubMed
Li 2015 {published data only}
    1. Li Y, Liu S, Man Y, Li N, Zhou Y. Effects of vitamins E and C combined with beta‐carotene on cognitive function in the elderly. Experimental and Therapeutic Medicine 2015;9(4):1489‐93. - PMC - PubMed
    1. Ma A, Li Y, Han X, Sun Y. Effect of beta‐carotene, vitamin E and ascorbic acid supplementation on improving cognitive function in the old people. FASEB Journal 2007;21(6):A1072.
Liu 2015 {published data only}
    1. Liu X, Shi M, Xia F, Han J, Liu Z, Wang B, et al. The China Stroke Secondary Prevention Trial (CSSPT) protocol: a double‐blinded, randomized, controlled trial of combined folic acid and B vitamins for secondary prevention of stroke. International Journal of Stroke 2015;10:264‐8. - PubMed
Loriaux 1985 {published data only}
    1. Loriaux SM, Deijen JB, Orlebeke JF, Swart JH. The effects of nicotinic acid and xanthinol nicotinate on human memory. Psychopharmacology 1985;87:390‐5. - PubMed
Macpherson 2012 {published data only}
    1. Macpherson H, Ellis KA, Sali A, Pipingas A. Memory improvements in elderly women following 16 weeks treatment with a combined multivitamin, mineral and herbal supplement: a randomized controlled trial. Psychopharmacology 2012;220:351‐65. - PubMed
    1. Macpherson H, Pipingas A, Ellis K. Can taking a daily multivitamin improve cognitive performance in the elderly? Evidence from a steady state visually evoked potential investigation of memory in elderly women. International Journal of Psychophysiology 2010;77:239‐87.
Maniam 2004 {published data only}
    1. Maniam J, Krishnaswamy S, Mohame J. Randomized double blind placebo controlled human clinical trial investigating effect of 1200iu a‐tocopherol on lipid peroxidation, antioxidant status and cognitive function of elderly. Free Radical Biology & Medicine 2004;36:S146.
McNeill 2007 {published data only}
    1. McNeill G, Avenell A, Campbell MK, Cook JA, Hannaford PC, Kilonzo MM, et al. Effect of multivitamin and multimineral supplementation on cognitive function in men and women aged 65 years and over: a randomised controlled trial. Nutrition Journal 2007;6:10. - PMC - PubMed
Miller 2016 {published data only}
    1. Miller B, Whisner C, Johnston C. Vitamin D supplementation appears to increase plasma Aβ40 in vitamin D insufficient older adults: a pilot randomized controlled trial. Journal of Alzheimer's Disease 2016;52:843‐7. - PubMed
Murray‐Kolb 2011 {published data only}
    1. Murray‐Kolb LE, Wenger MJ, Venkatramanan S, Marquis GS, Wesley AS, Haas JD. Effects of double‐fortified salt on perceptual and cognitive performance in women. FASEB Journal 2011;25(1 suppl):238.6.
NCT00903695 {published data only}
    1. NCT00903695. MemoryXL effects on mild cognitive impairment patients [Nutriceutical effects on cognitive status in mild cognitive impairment patients]. clinicaltrials.gov/show/NCT00903695 (first received 18 May 2009).
NCT01095211 {published data only}
    1. NCT01095211. B‐vitamins treatment for improvement of cognitive function [Effect of B‐vitamins on cognitive function in elderly people]. clinicaltrials.gov/show/NCT01095211 (first received 30 March 2010).
NCT01708005 {published data only}
    1. NCT01708005. Dietary supplements, executive functions and vitamin D (DIET‐D) [Dietary supplements, executive functions and vitamin D (DIET‐D): a double‐blind randomized controlled trial]. clinicaltrials.gov/show/NCT01708005 (first received 16 October 2012).
NCT02185222 {published data only}
    1. NCT02185222. Effect of vitamin D on cognitive decline of patients with memory complaint (D‐COG) [Effect of vitamin D on cognitive decline of patients with memory complaint]. clinicaltrials.gov/show/NCT02185222 (first received 9 July 2014).
NCT02467153 {published data only}
    1. NCT02467153. Vitamin D and resistance exercise training; effects on musculoskeletal health in frail older men and women (EXVITD) [Influence of combined vitamin D supplementation and resistance exercise training on musculoskeletal health in frail older men and women (EXVITD)]. clinicaltrials.gov/show/NCT02467153 (first received 9 June 2015).
Ng 2017 {published data only}
    1. Ng T, Nyunt M, Feng L, Feng L, Niti M, Tan BY, et al. Multi‐domain lifestyle interventions reduces depressive symptoms among frail and pre‐frail older persons: randomized controlled trial. Journal of Nutrition, Health & Aging 2017;21(8):918‐26. [DOI: 10.1007/s12603-016-0867-y] - DOI - PubMed
Ong 2016 {published data only}
    1. Ong A, Weiler H, Wall M, Haddad R, Gorgui J, Daskalopoulou SS, et al. Feasibility of a clinical trial to assess the effect of dietary calcium v. supplemental calcium on vascular and bone markers in healthy postmenopausal women. British Journal of Nutrition 2016;116:104‐14. - PubMed
Pase 2015 {published data only}
    1. Pase MP, Grima N, Cockerell R, Stough C, Scholey A, Sali A, et al. The effects of long‐chain Omega‐3 fish oils and multivitamins on cognitive and cardiovascular function: a randomized, controlled clinical trial. Journal of the American College of Nutrition 2015;34:21‐31. - PubMed
Pathansali 2006 {published data only}
    1. Pathansali R, Mangoni AA, Creagh‐Brown B, Lan ZC, Ngow GL, Yuan XF, et al. Effects of folic acid supplementation on psychomotor performance and hemorheology in healthy elderly subjects. Archives of Gerontology and Geriatrics 2006;43:127‐37. - PubMed
Petersen 2005 {published data only}
    1. Petersen RC, Thomas RG, Grundman M, Bennett D, Doody R, Ferris S, et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. New England Journal of Medicine 2005;352:2379‐88, 2465. - PubMed
Pettersen 2017 {published data only}
    1. Pettersen J. Does high dose vitamin D supplementation enhance cognition?: a randomized trial in healthy adults. Experimental Gerontology 2017;90:90‐7. - PubMed
Quick 2013 {published data only}
    1. Quick M, Kiefer D. Calcium plus vitamin D supplementation and cognitive decline in women. Integrative Medicine Alert 2013;16:30‐4.
Rietsema 2014 {published data only}
    1. Rietsema WJ. Unexpected recovery of moderate cognitive impairment on treatment with oral methylcobalamin. Journal of the American Geriatrics Society 2014;62:1611‐2. - PubMed
Schietzel 2016 {published data only}
    1. Schietzel S, Brugger P, Fischer K, Meyer O, Freystaetter G, Meyer S, et al. Effect of high dose vitamin D on cognitive performance in healthy seniors ‐ a randomized controlled trial. European Geriatric Medicine 2016;7(Suppl 1):71.
Smith 1999 {published data only}
    1. Smith A, Clark R, Nutt D, Haller J, Hayward S, Perry K. Anti‐oxidant vitamins and mental performance of the elderly. Human Psychopharmacology 1999;14:459‐71.
Summers 2010 {published data only}
    1. Summers WK, Martin RL, Cunningham M, Deboynton VL, Marsh GM. Complex antioxidant blend improves memory in community‐dwelling seniors. Journal of Alzheimer's Disease 2010;19:429‐39. - PubMed
Van Uffelen 2007 {published data only}
    1. Uffelen JG, Chinapaw MJ, Hopman‐Rock M, Mechelen W. The effect of walking and vitamin B supplementation on quality of life in community‐dwelling adults with mild cognitive impairment: a randomized, controlled trial. Quality of Life Research 2007;16:1137‐46. - PMC - PubMed
    1. Uffelen JG, Chinapaw MJ, Mechelen W, Hopman‐Rock M. Walking or vitamin B for cognition in older adults with mild cognitive impairment? A randomised controlled trial. British Journal of Sports Medicine 2008;42(5):344‐51. - PubMed
Wouters‐Wesseling 2005 {published data only}
    1. Wouters‐Wesseling W, Wagenaar LW, Rozendaal M, Deijen JB, Groot LC, Bindels JG, et al. Effect of an enriched drink on cognitive function in frail elderly persons. Journals of Gerontology 2005;60A:265‐70. - PubMed

References to studies awaiting assessment

Sanchez 2011 {published data only}
    1. Sanchez H, Albala C, Lera L, Castillo JL, Verdugo R, Lavados M, et al. Comparison of two modes of vitamin B12 supplementation on neuroconduction and cognitive function among older people living in Santiago, Chile: a cluster randomized controlled trial. A study protocol. Nutrition Journal 2011;10:100. [PUBMED: 21952034] - PMC - PubMed

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