Vitamin and mineral supplementation for preventing dementia or delaying cognitive decline in people with mild cognitive impairment
Open accessAbstract
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 re
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B vitamin supplementation for 6 to 24 months has no beneficial effect on cognition in people with mild cognitive impairment.
“Cochrane reviews found no evidence for beneficial effects on cognition of those with mild cognitive impairment of supplementation with B vitamins for 6 to 24 months150”
From Dementia prevention, intervention, and care: 2020 report of the Lancet Commission (2020) · cites this paper as [150]
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- "executive function*".ti,ab. 92. Executive Function/ 81 Vitamin and mineral supplementation for preventing dementia or delaying cognitive decline in people with mild cognitive impairment (Review) Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. (Continued) 93. Attention/ 94. (speed adj2 processing).ti,ab. 95. "episodic memory".ti,ab. 96. Memory, Episodic/ 97. or/84-96 98. 83 and 97
- "vitamin* supple*".ti,ab. 52. "diet* supplement*".ti,ab. 53. calcium.ti,ab. 54. iron.ti,ab. 55. iron/ 56. zinc.ti,ab. 57. zinc/ 58. sodium.ti,ab. 59. sodium/ 60. potassium.ti,ab. 61. citrate potassium/ or potassium/ or 83 Vitamin and mineral supplementation for preventing dementia or delaying cognitive decline in people with mild cognitive impairment (Review) Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. (Continued) clavulanate potassium/ or diclofenac potas- sium/ 62. phosphorus.ti,ab. 63. phosphorus/ 64. magnesium.ti,ab. 65. magnesium/ 66. chloride.ti,ab. 67. chloride/ 68. sulphur.ti,ab. 69. mangansese.ti,ab. 70. cobalt.ti,ab. 71. cobalt/ 72. selenium.ti,ab. 73. selenium/ 74. copper.ti,ab. 75. copper/ 76. iodine.ti,ab. 77. fluoride.ti,ab. 78. fluoride/ 79. or/1-78 80. aging/ 81. aged/ 82. middle aged/ 83. mild cognitive impairment/ 84. "mild cognitive impairment".ti,ab. 85. MCI.ti,ab. 86. AAMI.ti,ab. 87. ACMI.ti,ab. 88. ARCD.ti,ab. 89. CIND.ti,ab.
- "randomi?ed control* trial".ab. 30. "random allocation".ab. 31. "controlled clinical trial".ti,ab. 32. or/22-31 33. exp Vitamins/ 34. exp Dietary Supplements/ 35. vitamin*.ti,ab. 36. mineral*.ti,ab. 37. calcium.ti,ab. 38. Calcium/ 39. exp Ascorbic Acid/ 40. exp Folic Acid/ 41. "folic acid".ti,ab. 42. cholecalciferol.ti,ab. 43. ergocalciferol.ti,ab. 44. toxiferol.ti,ab. 45. retinol.ti,ab. 46. retinal.ti,ab. 47. "retinoic acid".ti,ab. 48. "beta-carotene".ti,ab. 49. "alpha-carotene".ti,ab. 50. "gamma-carotene".ti,ab. 51. "beta-cryptoanthin".ti,ab. 52. thiamine.ti,ab. 53. riboflavin.ti,ab. 54. niacin.ti,ab. 55. nicotinamide.ti,ab. 56. pantothenic.ti,ab. 57. pyridoxine.ti,ab. 58. pyridoxal.ti,ab. 59. pyridoxamine.ti,ab. 60. biotin.ti,ab. 61. "folic acid".ti,ab. 62. cyanocobalamin.ti,ab. 86 Vitamin and mineral supplementation for preventing dementia or delaying cognitive decline in people with mild cognitive impairment (Review) Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. (Continued) 63. methylcobalamin.ti,ab. 64. "l-ascorbic acid".ti,ab. 65. "ascorbic acid".ti,ab. 66. ascorbate.ti,ab. 67. phylloquinone.ti,ab. 68. phytomeadione.ti,ab. 69. phytonadine.ti,ab.
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- Authors
- McCleery, J., Abraham, R. P., Denton, D. A., Rutjes, A. W., Chong, L.-Y., Al-Assaf, A. S., Griffith, D. J., Rafeeq, S., Yaman, H., Malik, M. A., Di Nisio, M., Martínez, G., Vernooij, R. W., & Tabet, N.
- Affiliations
- Oxford Health NHS Foundation Trust (GB)
- Surrey and Borders Partnership NHS Foundation Trust (GB)
- Sussex Partnership NHS Foundation Trust (GB)
- University of Bern (CH)
- Cochrane (GB)
- National Institute for Health and Care Research (GB)
- University Hospitals Birmingham NHS Foundation Trust (GB)
- Central Park Medical College; Community Medicine; Central Park Housing Scheme, Ferozepur Road, Kahna Nau Lahore Punjab Pakistan 53100
- Akdeniz University (TR)
- Brighton and Sussex Medical School (GB)
- University "G. D'Annunzio" of Chieti-Pescara; Department of Medicine and Ageing Sciences; Via dei Vestini 31 Chieti Scalo Italy 66013
- Universidad de Antofagasta (CL)
- Iberoamerican Cochrane Centre (ES)
- ORCID
- Venue
- Cochrane Database of Systematic Reviews
- Publisher
- Wiley
- Published
- 2018-11-01
- Volume
- 2019
- Issue
- 2
- Pages
- CD011905-CD011905
- ISSN
- 1361-6137 (ISSN-L)
- 1465-1858
- PMC
- PMC6378925
- OpenAlex
- W2172507466
- Cited by
- 162
- References
- 204
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 17 · 2023: 32 · 2022: 22 · 2021: 29 · 2020: 20 · 2019: 16 · 2018: 3 · 2017: 3 · 2015: 2
- FWCI
- 2.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cochrane Database of Systematic Reviews (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Sussex Research Online (University of Sussex) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Figshare (submittedVersion)
- University of Brighton Repository (University of Brighton) (submittedVersion, other-oa)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- National Institute for Health and Care Research (13/89/22)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
- Keywords
- vitamin and mineral supplementation, mild cognitive impairment, dementia prevention, cognitive decline, B vitamins, folic acid, vitamin B6, vitamin B12, cognitive function, episodic memory, executive function, processing speed, quality of life, functional performance, older adults, dementia incidence, adverse events, mortality, attrition bias, selective outcome reporting, risk of bias, quality of evidence
- MeSH terms
- Aged, Aged, 80 and over, Ascorbic Acid, Cognition, Cognition Disorders, Dementia, Humans, Middle Aged, Mortality, Picolinic Acids, Quality of Life, Trace Elements, Vitamin B Complex, Vitamins, Randomized Controlled Trials as Topic, Dietary Supplements, alpha-Tocopherol, Executive Function, Memory, Episodic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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