B vitamins may slow cognitive decline in people without dementia, but the effect is small Original paper

    In some trials, B vitamins (folate, vitamin B6, vitamin B12) slowed cognitive decline in studies lasting longer than 12 months and in people without dementia, though the effect was small and of questionable clinical significance. In other studies, only folate (but not the other B vitamins) was associated with a lower risk of dementia.

    This Study Summary was published on November 2, 2021.


    Some evidence suggests that increased homocysteine levels may contribute to cognitive decline during aging.[1] Because folate, vitamin B6, and vitamin B12 play a central role in the metabolism of homocysteine, an increased intake of these B vitamins may benefit cognition and reduce the risk of dementia.

    The study

    This systematic review and meta-analysis examined the effect of B vitamins (specifically B6, B12, and folate) on cognitive decline and dementia. In total, 95 studies with 46,175 people were analyzed, of which 25 were randomized controlled trials (RCTs), 50 were cohort studies, and 50 were cross-sectional studies. All studies focused on populations older than 50 years of age.

    In the RCTs, the investigators assessed the effect of B-vitamin supplementation on changes in cognitive function. In the observational studies, the investigators assessed the association between dietary intake and levels (in serum, plasma, or cerebrospinal fluid) of B vitamins and both dementia incidence and cognitive decline. Cognitive function was assessed using the Mini-Mental State Exam (MMSE), a common cognitive test used to assess cognitive decline and diagnose dementia.

    The results

    In the RCTs, B-vitamin supplementation improved cognition compared to a placebo. Subgroup analysis indicated that this effect was due to B vitamins slowing cognition loss, rather than increasing cognition. Additional subgroup analysis indicated that this effect of B vitamins on cognition only occurred in trials longer than 12 months in people without dementia.

    In the observational studies, folate intake was associated with a lower risk of dementia, whereas no association was found between either vitamin B12 or vitamin B6 intake and dementia. Low folate levels were associated with a higher risk of dementia and cognitive decline, whereas no association was found between vitamin B12 levels and these outcomes or between vitamin B6 and cognitive decline.


    This study found that in RCTs, the effect of B-vitamin supplementation on cognition was a relative improvement of 0.14 points on the MMSE compared to placebo. This difference is quite small, and although it is statistically significant, it is probably not clinically significant.[2]

    This Study Summary was published on November 2, 2021.


    1. ^Esther Setién-Suero, Marta Suárez-Pinilla, Paula Suárez-Pinilla, Benedicto Crespo-Facorro, Rosa Ayesa-ArriolaHomocysteine and cognition: A systematic review of 111 studiesNeurosci Biobehav Rev.(2016 Oct)
    2. ^J Scott Andrews, Urvi Desai, Noam Y Kirson, Miriam L Zichlin, Daniel E Ball, Brandy R MatthewsDisease severity and minimal clinically important differences in clinical outcome assessments for Alzheimer's disease clinical trialsAlzheimers Dement (N Y).(2019 Aug 2)