Clinical Question

Are vitamin and mineral supplements beneficial in preserving cognitive functioning or preventing cognitive decline in cognitively healthy adults 40 years and older?

Evidence-Based Answer

Vitamin and mineral supplementation has little to no beneficial effect on preserving cognitive functioning or preventing dementia in cognitively healthy adults 40 years and older.¹ (Strength of Recommendation: B, based on inconsistent or limited-quality patient-oriented evidence.)

Practice Pointers

In 2010, an estimated 35 million people worldwide had dementia, and the prevalence is expected to double by 2030. Modifiable risk factors for dementia include diabetes mellitus, midlife obesity and hypertension, smoking, and physical inactivity. Vitamins and minerals have recognized roles in normal functioning and development, so it has been hypothesized that dietary supplementation may prevent dementia. This Cochrane review sought to evaluate whether vitamin and mineral supplementation preserves cognitive functioning or prevents decline in cognitively healthy adults 40 years and older.¹

The Cochrane authors identified 28 randomized controlled trials involving more than 83,000 cognitively healthy participants 40 years and older. These trials compared oral vitamin and mineral supplements with either placebo or usual care for at least 12 weeks. The primary outcome was overall cognitive functioning as measured by various accepted and validated scales. Secondary outcomes included subdomain measures (i.e., episodic memory, executive functioning, and cognitive processing speed), incidence of mild cognitive impairment (MCI) or dementia, serious adverse events, and mortality. Most studies did not assess the incidence of dementia specifically or reflect performance of a baseline cognitive assessment. Ten studies had follow-up from five to 10 years, and only one study had follow-up longer than 10 years. The authors pooled study data into five supplement groups based on their theorized mechanisms of action in preventing dementia: antioxidants (vitamin C, vitamin E, and beta carotene), B vitamins, vitamin D, zinc and copper, and selenium. The review also pooled data for any combinations from these different groups.

Fourteen studies (n = 27,882) compared B vitamins (folic acid, vitamin B₆, vitamin B₁₂, or a combination) with placebo and found that, based on low- to moderate-certainty evidence, B vitamins had little to no benefit on measurements of cognitive functioning. These 14 studies evaluated supplementation over varying lengths of time using more than 30 different cognitive function scales, so standardized mean differences (SMDs) were used to describe treatment effect (SMD was defined as the difference between the groups' mean values divided by the pooled standard deviation). SMDs ranged from −0.03 to 0.06 for supplementation from three months to more than 10 years. B vitamin supplementation also did not provide a benefit in any specific subdomains of cognitive functioning, the incidence of MCI or dementia, or mortality.

Eight studies (n = 47,840) assessed antioxidants (vitamin E, vitamin C, beta carotene, or a combination) and had mixed results. Five studies showed that antioxidant supplementation over a mean of 12 months to 8.9 years had no effect on overall cognitive functioning, based on low- to moderate-certainty evidence. Three studies showed marginal improvements in cognitive functioning that are likely not clinically significant. One study (n = 74) involving adults with type 2 diabetes found that three months of vitamin E supplementation resulted in improved Mini-Mental State Examination (MMSE) scores (maximum score = 30) compared with placebo (mean difference [MD] = 1.4; 95% CI, 1.18 to 1.62). Another study (n = 1,586) found that five to 10 years of vitamin C supplementation in adults with cardiovascular disease resulted in very small improvements in cognitive functioning based on the 41-point Telephone Interview for Cognitive Status (TICS), modeled after the MMSE (MD = 0.46; 95% CI, 0.14 to 0.78).² A final study (n = 4,052) demonstrated moderate-certainty evidence of a very small benefit in overall cognitive functioning after a mean of 18 years of treatment with beta carotene, based on improvements in the TICS score (MD = 0.18; 95% CI, 0.01 to 0.35).

Regarding the subdomain of episodic memory, one study (n = 1,583) found that after 8.9 years of vitamin C supplementation, verbal memory scores (a composite score of the immediate and delayed recalls of the 10-word TICS and the East Boston Memory Test, scale not defined) improved slightly (MD = 0.14; 95% CI, 0.06 to 0.22) in women with or at risk of cardiovascular disease.³ Antioxidants had no effect on executive functioning, speed processing, incidence of dementia, or mortality. Of note, one trial that measured the incidence of dementia in patients taking vitamin E supplements was an ancillary study of a larger trial that demonstrated vitamin E supplementation had a nonsignificant increased risk of prostate cancer (P = .06; relative risk = 1.13; 99% CI, 0.95 to 1.35) after a mean 5.5 years of supplementation (n = 35,533).⁴

Vitamin D does not improve overall cognitive functioning based on the results of one study (n = 4,143) that compared the supplementation of 400 IU of vitamin D₃ with calcium carbonate vs. placebo over an average of 7.8 years. The study found MDs on the modified MMSE as measured at various follow-up times ranging from −0.2 to 0. Vitamin D also did not affect subdomains of cognitive functioning or the incidence of MCI or dementia. Likewise, trials involving zinc and copper (one study, 1,072 participants), selenium (one study, 3,711 participants), or complex multivitamins (combination of B vitamins, antioxidants, and minerals; three studies, 6,306 participants) suggested low-certainty evidence of no effect on cognitive functioning, its subdomains, or the incidence of dementia.

This Cochrane review generally supports the American Academy of Neurology 2018 practice guideline for the prevalence, prognosis, and treatment of MCI. The American Academy of Neurology recommends that patients and families be counseled that there are currently no dietary modalities effective in slowing symptomatic cognitive impairment.⁵

The practice recommendations in this activity are available at http://www.cochrane.org/CD011906.

The opinions and assertions contained herein are the private views of the authors and are not to be construed as the official policy or position of the U.S. Army, the Department of Defense, or the U.S. government.