Table A1.
Characteristics of included studies on vitamins.
| Reference/Register Number | Study Design/Population of Study | No. of Participants | Mean Age ± SD, Years | Sex 
|
|---|---|---|---|---|
| Vitamin B12 + Folic acid vs. Placebo | ||||
| Kwok T. et al. [42] CUHK_CCT00373 |
RCT (placebo-controlled)/People ≥65 yr with MCI and elevated levels of serum homocysteine ≥10 µmol/L | IG: n = 138; CG: n = 141 |
IG: 76.9 ± 5.4; CG: 78.0 ± 5.3 |
IG: 63.1%; CG: 56.1% |
| Vitamin B12 + Folic acid vs. Placebo | ||||
| Walker J. et al. [38] NCT00214682 |
RCT/Community-dwelling adults between 60–74 yr with elevated psychological distress (Kessler Distress 10-scale; score >15) | IG: n = 447; CG: n = 453 |
IG: 65.92 ± 4.3; CG: 65.97 ± 4.18 |
IG: 40.5%; CG: 39.1% |
| Vitamin B12 + Folic acid vs. Conventional treatment | ||||
| Jiang B. et al. [48] | RCT/Patients with vascular cognitive impairment-no dementia (VCIND), complicated with hyperhomocystinemia | IG: n = 60; CG: n = 60 |
Average age ±SD, years: 63 ± 1.87 |
Total, %: 65% |
| Vitamin B12 + Folic acid vs. Placebo | ||||
| Chen H. et al. [39] ChiCTR-IOR-16009731 |
RCT (single-blind, placebo-controlled, single-center, parallel-group)/Patients >45 yr diagnosed clinically as probable AD and in a stable condition (MoCA less than 22) | IG: n = 60; CG: n = 60 |
IG: 68.58 ± 7.29; CG: 68.02 ± 8.34 |
IG: 50%; CG: 43.33% |
| Vitamin B12 vs. Placebo | ||||
| Dangour A. et al. [43] ISRCTN54195799 |
RCT (double-blind, placebo-controlled)/People ≥75 yr with MMSE ≥ 24 and moderate vitamin B12 deficiency (serum vitamin B12 concentrations 107–210 pmol/L) and absence of anemia | IG: n = 99; CG: n = 102 |
IG: 79.9 ± 3.5; CG: 80.1 ± 3.7 |
IG: 46.5%; CG: 47.1% |
| Folic acid vs. Placebo | ||||
| Ma F. et al. [46] | RCT (single blind experimental design)/People ≥65 yr with MCI | IG: n = 84; CG: n = 84 |
IG: 73.71 ± 2.57; CG: 73.52 ± 3.03 |
IG: 32.14%; CG: 30.95% |
| Folic acid + DHA vs. Placebo | ||||
| Li M. et al. [41] Chi-CTR-IOR-16008351 |
RCT (double-blind, placebo-controlled, two-center)/Elderly with MCI ≥60 yr and absence of mental disorders | IG1: n = 60; IG2: n = 60; IG3: n = 60; CG: n = 60 |
IG1: 70.33 ± 7.7; IG2: 70.20 ± 6.13; IG3: 71.55 ± 6.62; CG: 70.38 ± 6.73 |
IG1: 40%; IG2: 40%; IG3: 40%; CG: 45% |
| Folic acid vs. Placebo | ||||
| Ma F. et al. [45] ChiCTR-TRC-13003227 |
RCT (single-center)/Chinese adults ≥65 yr with MCI who are unexposed to folic acid fortification | IG: n = 90; CG: n = 90 |
IG: 74.82 ± 2.75; CG: 74.63 ± 3.21 |
IG: 36.25%; CG: 34.18% |
| Folic acid vs. Conventional treatment | ||||
| Ma F. et al. [47] ChiCTR-TRC-13003227 |
RCT (single-center)/Chinese adults ≥65 yr with MCI | IG: n = 90; CG: n = 90 |
IG: 74.82 ± 2.75; CG: 74.63 ± 3.21 |
IG: 43.33%; CG: 42.22% |
| Folic acid + Donepezil vs. Placebo + Donepezil | ||||
| Chen H. et al. [37] ChiCTR-TRC-13003246 |
RCT (single-center, single-blind)/Patients with a new diagnosis of possible AD of mild or moderate severity (defined as an MMSE total score between 3 and 26) and currently being treated with Donepezil | IG: n = 61; CG: n = 60 |
IG: 68.10 ± 8.50; CG: 67.63 ± 7.92 |
IG: 54.10%; CG: 46.67% |
| Vitamin B1 (Benfotiamine) vs. Placebo | ||||
| Gibson G.E. et al. [40] NCT02292238 |
RCT (placebo-controlled, Phase IIa, double blind)/Amyloid positive patients ≥60 yr with amnestic MCI or mild dementia due to AD and MMSE > 21 | IG: n = 34; CG: n = 36 |
IG: 75.74 ± 6.91; CG: 75.81 ± 7.19 |
IG: 32.4%; CG: 50% |
| Vitamin B1 (Thiamin) vs. Non Intervention | ||||
| Lu R. et al. [49] ChiCTR-IPR-17012210 |
RCT (single-center)/adults with end-stage kidney disease and cognitive impairment (MoCA score <26) | IG: n = 25; CG: n = 25 |
IG: 66.16 ± 7.61; CG: 69.00 ± 10.80 |
IG: 72%; CG: 76% |
| (Vitamin B12+ Vitamin B6 + Vitamin B2+ Folic acid) vs. Placebo | ||||
| Moore K. et al. [44] | RCT/Generally healthy older adults ≥70 yr | IG: n = 124; CG: n = 125 |
IG: 77.9 ± 4.2; CG: 78.2 ± 4.7 |
IG: 48.5%; CG: 41.1% |
| Vitamin B12 vs. Vitamin C | ||||
| Vijayakumar T.M. et al. [50] CTRI No: REF/2016/02/010726 |
RCT (double-blind, parallel-group)/Postmenopausal women (50–75 yr) with mild to moderate cognitive dysfunction | IG: n = 28; CG: n = 28 |
IG: 57.56 ± 7.72; CG: 55.88 ± 6.01 |
IG: 0%; CG: 0% |
| High Dose Vitamin D2 vs. Placebo | ||||
| Stein M. et al. [52] ACTRN12606000324516 |
RCT (double-blind)/Community-dwelling participants ≥60 yr with mild-moderate AD (MMSE score 12–24) | IG: n = 16; CG: n = 16 |
Median age [IQR],yr: IG: 75 [64.5–80] CG: 79 [74.5–82] |
IG: 43.75%; CG: 50% |
| Vitamin D3 vs. Placebo | ||||
| Anweiler C. et al. [55] | Retrospective pre-post cohort study/Elderly outpatients visiting a memory clinic without recent vitamin D supplementation and without prescription of antidementia drugs | IG: n = 20; CG: n = 24 |
Median age [IQR],yr: IG: 81.9 [13.2] CG: 75.9 [15.0] |
IG: 45%; CG: 45.8% |
| Vitamin D3 (2000 IU/d) vs. Vitamin D3 (800 IU/d) | ||||
| Schietzel S. et al. [60] NCT00599807 |
RCT (double-blind)/Community-dwelling older adults ≥60 yr with an MMSE ≥ 24 at baseline undergoing elective surgery for unilateral total knee replacement due to severe osteoarthritis | IG: n = 137; CG: n = 136 |
IG: 70.2 ± 6.8; CG: 70.5 ± 6.0 |
IG: 49.6%; CG: 43.4% |
| Vitamin D3 vs. Placebo | ||||
| Aspell N. et al. [51] NCT02804841 |
RCT (placebo-controlled, double-blind)/Patients ≥60 yr without cognitive impairment (MMSE < 23) and with measured serum vitamin D <125 mmol/L. | IG: n = 30; CG: n = 29 |
68.5 ± 4.9 | 46.7% |
| Vitamin D + Exercise programs vs. Exercise programs | ||||
| Lee Y. et al. [56] KCT0002490 |
Non-equivalent, control-group experimental study (Pre-test-post-test design)/Adults >65 yr with serum vitamin D levels <20 ng/mL | IG: n = 46; CG: n = 48 |
IG: 77.8 ± 6.0; CG: 76.9 ± 6.5 |
IG: 21.74%; CG: 18.75% |
| Vitamine D3 vs. No supplementation | ||||
| Bischoff-Ferrari H. et al. [58] NCT01745263 |
RCT (placebo-controlled, double-blind, 2 × 2 × 2 factorial)/Adults ≥70 yr without major health problems in the 5 yr prior to enrollment and MMSE ≥ 24 | IG: n = 1076; CG: n = 1081 |
IG: 75 ± 4.5; CG: 74.9 ± 4.4 |
IG: 38%; CG: 38.6% |
| Vitamin D3 (600 IU/d) vs. Vitamin D3 (2000 IU/d) vs. Vitamin D3 (4000 IU/d) | ||||
| Castle M. et al. [59] NCT01631292 |
RCT (double-blind)/Overweight/obese postmenopausal women with serum 25-hydroxyvitamin D <30 ng/mL | IG1: n = 15; IG2: n = 15; IG3: n = 12; |
IG1: 58 ± 6.8; IG2: 58.5 ± 5.3; IG3: 57.2 ± 5.9; |
IG1: 0%; IG2: 0%; IG3: 0%; |
| Vitamin D3 + fish oil supplements vs. Placebo | ||||
| Kang J. et al. [53] VITAL trial: NCT01169259. Two substudies:
|
Large RCT (placebo-controlled, double-blind, 2 × 2 factorial)/People >60 yr free of vascular disease and cancer | VITAL-Cog substudy: IG: n = 1710; CG: n = 1714 CTSC-Cog substudy: IG: n = 396; CG: n = 398 |
VITAL-Cog substudy: IG: 71.9 ± 5.4; CG: 71.8 ± 5.4 CTSC-Cog substudy: IG: 66.9 ± 5.2; CG: 67.3 ± 5.4 |
VITAL-Cog substudy: IG: 40.9%; CG: 41.4% CTSC-Cog substudy: IG: 48.2%; CG: 51.0% |
| Vitamin D3 + Calcium carbonate vs. Placebo | ||||
| Rossom R.C. et al. [54] | Post-hoc analysis of an RCT (double-blind, placebo-controlled)/Women ≥65 yr without cognitive impairment at baseline | IG: n = 2034; CG: n = 2109 |
IG: 70.7; CG: 70.9 |
IG: 0%; CG: 0% |
| Fortified yogurts with vitamin D3 and Calcium vs. Non-fortified yogurts | ||||
| Beauchet O. et al. [57] NCT02086409 |
RCT (Unicentre, single-blind, in 2 parallel groups)/Female ≥65 yr with hypovitaminosis D (seum 25 OHD concentration <75 nmol/L), calcemia <2.65 mmol/L and free of dementia | IG: n = 20; CG: n = 20 |
IG: 71 ± 3.7; CG: 71.5 ± 5.2 |
IG: 0%; CG: 0% |
| Vitamine E (+ selenium) vs. Placebo | ||||
| Kryscio R.J. et al. [61] NCT00040378 |
First an RCT (double-blind, 4 arm); then transformed into a cohort study/men ≥60 yr in absence of dementia | IG1: n = 1799; IG2: n = 1881; IG3: n = 1828; CG: n = 1830 |
IG1: 67.5 ± 5.2; IG2: 67.6 ± 5.3; IG3: 67.6 ± 5.3; CG: 67.3 ± 5.2 |
IG1: 100%; IG2: 100%; IG3: 100%; CG: 100% |
| Vitamin E (+ Memantine) vs. Placebo | ||||
| Dysken M. et al. [62] NCT00235716 |
RCT (double-blind, placebo-controlled, parallel-group)/People with mild to moderate AD (MMSE 12–26) currently taking AChEI | IG1: n = 152; IG2: n = 155; IG3: n = 154; CG: n = 152 |
IG1: 78.6 ± 7.2; IG2: 78.8 ± 7.2; IG3: 78.3 ± 7.0; CG: 79.4 ± 7.0 |
IG1: 96%; IG2: 96%; IG3: 97%; CG: 98% |
| Vitamin E + Vitamin C vs. Placebo | ||||
| Alavi Naeini A.M. et al. [63] | RCT (double-blind, placebo-controlled)/Elderly aged 60–75 yr with MCI and MMSE between 21–26 scores | IG: n = 127; CG: n = 129 |
IG: 66.5 ± 0.39; CG: 66.3 ± 0.38 |
IG: 49.6%; CG: 44.2% |
AD: Alzheimer’s disease; AChEI: Acetylcholinesterase inhibitor; CG: control group, DHA: docosahexaenoic acid; IG: intervention group, IG1: intervention group 1, IG2: intervention group 2, IG3: intervention group 3, [IQR]: interquartile range, IU: International unit; MCI: mild cognitive impairment; MMSE: Mini-Mental State Examination; MoCA: Montreal Cognitive Assessment; n: number of participants, RCT: randomized controlled trial, SD: standard deviation, VCIND: vascular cognitive impairment-no dementia; yr: years; 25OHD: 25-hydroxyvitamin D;/d: per day, : male.