Table 1.
Clinical studies examining a potential link between vitamin B12 and cognitive performance in elderly adults without cognitive impairments or MCI patients. MCI: mild cognitive impairment. RCT: randomized controlled trial. SAM: S-adenosyl methionine. NAC: N-acetyl cysteine. ALCAR: acetyl-L-carnitine.
| Author | Year | Type of Study/Duration/n | Main Finding |
|---|---|---|---|
| Perla-Kaján et al. [164] |
2021 | RCT/2 years/intervention group (n = 95) and placebo group (n = 101) | A daily dose of folic acid, vitamin B12 and B6 ameliorates detrimental effects of paraoxonase 1 (PON1) on cognition in individuals with mild cognitive impairment |
| Li et al. [167] |
2021 | Meta-Analysis/until 1 December 2019/21 RCTs (7571 participants) | Vitamin B supplements (vitamin B12, B6, folic acid alone or in combination) show preventive efficacy on cognitive decline of elderly adults |
| Zhang et al. [166] |
2020 | Meta-Analysis/until 8 August 2019/21 observational studies (sample sizes: 155–7030) | Higher levels of vitamin B12 concentration were associated with better cognition in cross-sectional studies |
| Ma et al. [168] |
2019 | RCT/6 months/240 participants with MCI (four treatment groups) | Daily oral uptake of vitamin B12 (25 µg) in combination with folic acid (800 µg) significantly improved cognitive performance and reduced inflammatory cytokine levels in peripheral blood in MCI elderly |
| Oulhaj et al. [173] |
2016 | RCT/2 years/266 participants with MCI aged ≥70 years | The effect of vitamin B treatment on cognitive decline in MCI depends on the omega-3 fatty acid concentrations |
| Remington et al. [174] |
2015 | RCT/6 months nutraceutical formulation (NF) and placebo + 6 months extension with NF for all participants/34 individuals with MCI | Intervention with nutraceutical formulation (400 µg folic acid, 6 µg B12, 30 I.U. alpha-tocopherol, 400 mg SAM, 600 mg NAC, and 500 mg ALCAR) improved cognitive performance |
| Jernerén et al. [172] |
2015 | RCT/2 years/intervention group (n = 85) and placebo groups (n = 83) | High plasma long-chain omega-3 fatty acids are important for the beneficial effect of vitamin B treatment (folic acid, vitamin B6 and B12) on brain atrophy in MCI patients |
| Douaud et al. [171] |
2013 | RCT/2 years/intervention group (n = 80) and placebo group (n = 76) | High-dose vitamin B treatment (folic acid, vitamin B6 and B12) slow the atrophy of specific brain regions related to AD and cognitive decline in MCI patients |
| A de Jager et al. [170] |
2012 | RCT/2 years/intervention group (n = 133) and placebo group (n = 133) | Vitamins B (folic acid, vitamin B6 and B12) appear to slow cognitive and clinical decline in MCI patients, especially among participants with elevated baseline homocysteine levels |
| Ford et al. [165] |
2010 | RCT/2–8 years/299 hypertensive men ≥ 75 years | No beneficial effect of supplementation with B vitamins (B12, B6, folic acid) on cognitive function (2 years outcome) or the risk of cognitive impairment or dementia (8 years outcome) |
| Smit et al. [169] |
2010 | RCT/2 years/intervention group (n = 85) and placebo group (n = 83) | Accelerated brain atrophy in MCI patients can be slowed by treatment with B vitamins (folic acid, vitamin B6 and B12) |
| Flicker et al. [175] |
2008 | RCT/2 years/intervention group (n = 150) and placebo group (n = 149) | Reduced increase of plasma Aβ40 levels in older men treated with a combination of folate, vitamin B6 and B12 compared to placebo group |
| Frick et al. [176] |
2006 | Clinical Trial/1 month/58 patients (AD, n = 30; vascular dementia, n = 12; MCI, n = 16) | Daily supplementation of B vitamins (vitamins B1, B6, B12, folic acid) declines concentrations of homocysteine but not of neopterin in demented patients |
| An et al. [177] |
2019 | Clinical trial/2.3 years/2533 participants for longitudinal study + a subgroup of 109 MCI patients and 73 controls for DNA methylation and biochemical analyses | Significant association between inadequate dietary intake of vitamin B12 and accelerated cognitive decline, which may be mediated by affected methylation levels of specific redox-related genes |
| Van Dyck et al. [178] |
2009 | Controlled clinical trial/16 weeks/replacement group with low serum B12 levels (n = 28) and control group with normal serum B12 levels (n = 28) | Vitamin B12 replacement in dementia with low serum B12 levels resulted in significant improvements in hematologic and metabolic parameters but is unlikely to benefit cognitive or psychiatric symptoms |