Multivitamins and Cognitive Health in Adults
Multivitamin supplementation does not meaningfully improve cognitive function in healthy adults, with the exception of one recent large trial showing modest benefits in older adults, particularly those with cardiovascular disease. 1
Current Evidence on Multivitamins for Cognition
Most Recent High-Quality Evidence
The COSMOS-Mind trial (2023), the largest and most recent pragmatic trial with 2,262 participants (mean age 73 years), found that daily multivitamin-mineral (MVM) supplementation for 3 years produced statistically significant but modest improvements in global cognition (mean z-score 0.07,95% CI 0.02 to 0.12; P = 0.007) 1. The effect was most pronounced in participants with cardiovascular disease history (z-score 0.14 vs 0.06 in those without CVD history) 1. Benefits were also observed for memory and executive function 1.
However, this finding stands in contrast to the broader evidence base and requires confirmation in more diverse populations 1.
Systematic Review Evidence
A comprehensive Cochrane systematic review (2018) of 28 studies with over 83,000 participants found no evidence that vitamin or mineral supplementation strategies for cognitively healthy adults in mid or late life have meaningful effects on cognitive decline or dementia 2. The certainty of evidence was rated as moderate to low for most outcomes 2.
Meta-Analysis Findings
An earlier meta-analysis (2012) of 10 trials (n=3,200) found that multivitamins improved immediate free recall memory (SMD = 0.32; 95% CI: 0.09-0.56, p < 0.01) but not delayed recall memory or verbal fluency 3. Executive and visuospatial functions were under-researched 3.
Specific Vitamin Components
B Vitamins (B6, B12, Folic Acid)
B vitamin supplementation in cognitively healthy adults probably has little or no effect on global cognitive function at any time point up to 10 years (SMD values from -0.03 to 0.06) 2. This conclusion is based on 14 studies with 27,882 participants, mostly aged over 60 years 2.
The ESPEN guidelines (2015) explicitly state: "We do not recommend supplementation of B vitamins and/or folic acid for prevention or correction of cognitive decline in patients with dementia when there is no indication of deficiency" 4. Multiple RCTs showed that while B vitamin supplementation reduces homocysteine levels, it does not slow cognitive decline in patients with mild to moderate Alzheimer's disease 4.
Vitamin D
International expert consensus (2015) concluded that vitamin D supplementation should be given to older adults with hypovitaminosis D due to high prevalence, but this advice is not specific to cognition 4. While hypovitaminosis D increases the risk of cognitive decline, well-conducted RCTs are still needed to establish causality 4.
Antioxidant Vitamins
There was low-certainty evidence of benefit associated with β-carotene after 18 years of treatment (MD 0.18 TICS points) and vitamin C after 5-10 years (MD 0.46 TICS points), but not at earlier time points 2. However, one study found a statistically significant increase in prostate cancer diagnoses among men taking vitamin E 2.
The ESPEN guidelines (2015) state: "We do not recommend the use of vitamin E supplements in persons with dementia for prevention or correction of cognitive decline" (Grade of evidence: moderate) 4. Two studies in Alzheimer's patients (800 and 2000 IU/day) and one in MCI (2000 IU/day) showed no positive effect 4.
Other Minerals
- Vitamin D3 (400 IU/day) with calcium: No effect on cognitive function or dementia incidence over 10 years (MD -0.1 MMSE points) 2
- Zinc and copper: Little or no effect on cognitive function (MD 0.6 MMSE points) after 5-10 years 2
- Selenium: No effect on dementia incidence (HR 0.83,95% CI 0.61 to 1.13) after 5 years 2
Key Limitations and Caveats
Study Design Issues
Most participants were enrolled in studies not designed primarily to assess cognition, often lacking baseline cognitive assessments and using only brief follow-up assessments 2. Very few studies assessed dementia incidence 2. Only 10 studies had mean follow-up > 5 years, and only two had participants with mean age < 60 years at baseline 2.
Biomarker vs. Clinical Effects
One trial (2015) demonstrated that 16 weeks of multivitamin supplementation improved blood biomarkers (vitamins B6, B12, reduced homocysteine, improved lipid profile) but produced no cognitive improvements in healthy adults aged 55-65 years 5. This disconnect between biomarker normalization and clinical benefit is a critical consideration 5.
Population-Specific Considerations
The modest benefit seen in COSMOS-Mind was greater in adults with cardiovascular disease, suggesting that certain subgroups may benefit more than the general population 1. A 2007 trial found weak evidence for benefit in those aged ≥75 years and those at increased risk of micronutrient deficiency 6.
Clinical Recommendation
Do not recommend routine multivitamin supplementation specifically for cognitive health in healthy adults. The evidence is insufficient to support this practice, with only one recent trial showing modest benefits that require confirmation 1, 2.
For patients with documented vitamin deficiencies, correct the deficiency for general health reasons, but do not promise cognitive benefits. Screen older adults for hypovitaminosis D due to high prevalence, but supplementation advice is not specific to cognition 4.
Avoid vitamin E supplementation for cognitive purposes given lack of efficacy and potential harm (increased prostate cancer risk) 4, 2.
If considering multivitamins in older adults with cardiovascular disease, the COSMOS-Mind findings suggest possible modest benefit, but this requires confirmation in more diverse populations and the effect size is small 1.