Table 2.
Clinical studies dealing with vitamin B12 and Alzheimer’s disease. RCT: randomized controlled trial. MCI: mild cognitive impairment. SAM: S-adenosyl methionine. NAC: N-acetyl cysteine. ALCAR: acetyl-L-carnitine.
| Author | Year | Type of Study/Duration/n | Main Finding |
|---|---|---|---|
| Chen et al. [197] |
2021 | RCT/6 months/intervention group (n = 51) and placebo group (n = 50) | Supplementation of folic acid and vitamin B12 had a beneficial therapeutic effect in AD patients who were not on a folic acid-fortified diet |
| Guzman-Martinez et al. [196] |
2021 | RCT/24 weeks/82 mild to moderate AD patients | The nutraceutical BrainUp-10®, containing vitamin B12, produces a significant improvement in apathy, ameliorating neuropsychiatric distress of patients |
| Rasmussen [193] |
2019 | RCT/24 + 12 months/311 patients with prodromal AD | Fortasyn Connect, a multi-nutrient combination containing vitamin B12, may show benefit on domains of cognition affected by AD |
| Vakilian et al. [191] |
2017 | Clinical trial | Vitamin B12 in combination with antipsychotic drugs is able to reduce and induce the expression of pro- and anti-inflammatory cytokines in AD patients |
| Zhang et al. [185] |
2017 | Meta-Analysis/until 7 May 2015/4 studies included | Data on vitamin B-induced improvement in cognition by reducing homocysteine levels are conflicting and should be addressed in further studies |
| Remington et al. [189] |
2016 | RCT/12 months/24 individuals diagnosed with AD | Over the duration of nutraceutical formulation (folate, alpha-tocopherol, vitamin B12, SAM, NAC, ALCAR) supplementation behavioral and psychological symptoms of dementia as well as baseline cognitive performance were maintained |
| Remington et al. [188] |
2015 | Clinical trial/3- or 6-months intervention + 6 months open-label extension/106 individuals with AD | The results of this trial extended phase I studies showing maintained or improved cognitive performance and mood/behavior after supplementation of nutraceutical formulation (folate, alpha-tocopherol, vitamin B12, SAM, NAC, ALCAR) in AD patients |
| Rommer et al. [192] |
2016 | Clinical trial/3 months/healthy control (n = 15), AD or MCI (n = 16), supplemented AD or MCI (n = 17) | Supplementation of vitamins B1, B6, B12 and folic acid for three months resulted in decreased levels of carbonyl proteins, which negatively correlated with MMSE in AD/MCI patients |
| Shen et al. [179] |
2015 | Meta-Analysis/up to January 2014/68 studies included | Higher homocysteine and lower folic acid and vitamin B12 levels in AD patients than healthy individuals |
| Lopes da Silva et al. [180] |
2014 | Meta-Analysis/literature published after 1990/more than five publications for a specific nutrient | Significantly lower plasma levels of vitamin B12 were found in AD patients. |
| Cornelli [190] |
2010 | Clinical trial/6 months/52 moderate AD patients already being treated with 5 mg donepezil per day for at least two months | Treatment with formula F (Carnosine, vitamins B1, B2, B3, B6, B9, B12, C, E, Coenzyme Q10, β-carotene, selenium, L-cysteine, Ginkgo biloba) decreased oxidative stress and homocysteine levels and improved MMSE II scores significantly |
| Remington et al. [187] |
2009 | RCT/9 months/12 institutionalized patients diagnosed with moderate-stage to later-stage AD | Supplementation of a vitamin/nutraceutical formulation containing folate, vitamin B12, alpha-tocopherol, S-adenosyl methionine (SAM), N-acetyl cysteine (NAC), acetyl-L-carnitine (ALCAR) seems to delay the decline in cognition, mood, and daily function |
| Chan et al. [186] |
2008 | Clinical trial/12 months/14 community-dwelling individuals with early-stage AD | Treatment with a vitamin/nutraceutical formulation (folate, vitamin B12, alpha-tocopherol, SAM, NAC, ALCAR) resulted in improved cognitive performance |
| Aisen et al. [184] |
2008 | RCT/18 months/intervention group (n = 202) and placebo group (n = 138) of AD patients | Daily supplementation of folate, vitamin B6 and B12 for 18 months was effective in reducing homocysteine levels, but not in slowing cognitive decline in individuals with mild to moderate AD |
| Sun et al. [183] |
2007 | RCT/26 weeks/89 patients with mild to moderate AD and normal folic acid and vitamin B12 concentrations | Multivitamin supplement including vitamins B12, B6 and folic acid reduced concentrations of homocysteine but had no statistically significant beneficial effects on cognition compared to placebo treatment |
| Aisen et al. [182] |
2003 | Clinical trial/8 weeks/69 subjects with AD, including 33 with standard multivitamin supplements | This open-label trial shows high-dose, combined vitamin B12 and B6 supplementation to reduce homocysteine levels in AD patients |
| Teunissen et al. [181] |
2003 | Clinical trial/one-point/neurological patients (AD: n = 34; Parkinson’s disease: n = 46; other cognitive disorders: n = 47) and healthy controls (n = 61) | Compared to healthy individuals the median vitamin B12 concentration was decreased in all neurological patients |