Table 1 Summary of characteristics of RCTs included in the systematic review
First Author (Year) Country | Participants | Baseline levels of serum Hcy a (µmol/L) | Characteristics of Participants | Intervention | Treatment Duration | ||
|---|---|---|---|---|---|---|---|
N(IG/CG) ITT | Mean Age a (years) (IG/CG) | Male (n/%) (IG/CG) | |||||
Fei Ma (2019) China [28] | 120 MCI patients aged ≥ 65 years with no terminal illness or mental disorders, recruited from communities | 20.6 ± 2.2 | 60/60 | 69.2 ± 2.5/ 68.5 ± 3.9 | 21(35.0)/ 22(36.7) | folic acid 800 µg and vitamin B12 25 µg/day | 6 months |
Kwok Timothy (2019) China [29] | 279 MCI outpatients aged ≥ 65 years | 13.8 ± 3.2 | 138/141 | 76.9 ± 5.4/ 78.0 ± 5.3 | 87(63.1)/ 79(56.1) | folic acid 400 µg and vitamin B12 500 µg/day | 24 months |
Fei Ma (2017) China [30] | 180 MCI patients aged ≥ 65 years with no terminal illness or mental disorders, recruited from communities | 12.9 ± 4.4 | 90/90 | 74.8 ± 2.8/ 74.6 ± 3.2 | 39(43.3)/ 38(42.2) | folic acid 400 µg/day | 24 months |
Kwok Timothy (2017) China [34] | 271 diabetic non-demented outpatients aged ≥ 70 years | 16.8 ± 5.7 | 137/134 | 74.7 ± 4.0/ 75.8 ± 4.2 | 82(59.9)/ 76(56.7) | vitamin B12 1000 µg/day | 27 months |
Cheng D (2016) China [35] | 104 elderly volunteers aged ≥ 55 years, recruited from communities or nursing homes | 20.0 ± 5.6 | 57/47 | 74.3 ± 9.6/ 72.5 ± 7.0 | 27(47.4)/ 23(48.9) | folic acid 800 µg, vitamin B6 10 mg and vitamin B12 25 µg/day | 14 weeks |
Dangour AD (2015) United Kingdom [36] | 201 healthy volunteers aged ≥ 75 years | 16.1 ± 4.3 | 99/102 | 79.9 ± 3.5/ 80.1 ± 3.7 | 46(46.5)/ 23(48.9) | vitamin B12 1 mg/day | 12 months |
van der Zwaluw NL (2014) Netherlands [37] | 856 elderly participants aged ≥ 65 years with no dementia | 14.2 ± 2.5 | 425/431 | 72.6 ± 5.7/ 72.6 ± 5.8 | 244(57.0)/ 255(59.0) | folic acid 400 µg and vitamin B12 500 µg/day | 24 months |
Hankey GJ (2013) Australia [26] | 2214 patients with stroke or transient ischemic attack, MMSE ≥ 24 | 14.3 ± 8.5 | 1110/1104 | 63.6 ± 11.8 b | 1491(67.3) | folic acid 2 mg, vitamin B6 25 mg and vitamin B12 500 µg/day | 3.4 years |
Walker JG (2012) Australia [38] | 900 elderly adults aged 60 ~ 74 years, recruited from communities | 9.7 ± 2.7 | 447/453 | 65.9 ± 4.3/ 66.0 ± 4.2 | 181(40.5)/ 177(39.1) | folic acid 400 µg and vitamin B12 100 µg/day | 24 months |
de Jager CA (2012) United Kingdom [39] | 266 MCI patients aged ≥ 70 years | 11.5 ± 4.5 | 133/133 | 76.8 ± 5.1/ 76.7 ± 4.8 | 40(36.4)/ 40(35.4) | folic acid 0.8 mg, vitamin B12 0.5 mg and vitamin B6 20 mg/day | 24 months |
Ford AH (2010) Australia [40] | 299 community-dwelling elderly men aged ≥ 75 years with hypertension | 13.6 ± 5.3 | 150/149 | 79.3 ± 2.8/ 78.7 ± 2.7 | 150(100)/ 149(100) | folic acid 2 mg, vitamin B12 0.4 mg and vitamin B6 25 mg/day | 24 months |
van Uffelen JG (2008) Netherlands [41] | 179 MCI patients aged 70 ~ 80 years, recruited from communities | NR | 90/89 | 75.4 ± 2.8/ 74.9 ± 3.0 | 44(56.4)/ 41(55.4) | folic acid 5 mg, vitamin B12 0.4 mg and vitamin B6 50 mg/day | 12 months |
Durga J (2007) Netherlands [42] | 819 men and post-menopausal women aged 50 ~ 70 years | 12.9 ± 2.4 | 406/413 | 60 ± 5/ 60 ± 6 | 294(72)/ 292(70) | folic acid 0.8 mg/day | 3 years |
McMahon JA (2006) New Zealand [43] | 276 healthy participants aged ≥ 65 years | 16.6 ± 4.9 | 138/138 | 73.6 ± 5.8/ 73.4 ± 5.7 | 80(63.0)/ 61(48.4) | folic acid 1 mg, vitamin B12 0.5 mg and vitamin B6 10 mg/day | 2 years |
Eussen SJ (2006) Netherlands [44] | 131 elderly people aged ≥ 70 years with mild vitamin B12 deficiency | 15.2 ± 5.1 | 66/65 | 83 ± 6/ 82 ± 5 | 49(74.2)/ 51(78.5) | folic acid 0.4 mg, vitamin B12 1 mg/day | 6 months |
Stott DJ (2005) United Kingdom [45] | 47 elderly people aged ≥ 65 years with ischemic vascular disease | 16.7 ± 6.5 | 23/24 | 72.6 ± 6.4/ 72.8 ± 5.4 | 12(52.2)/ 14(58.3) | folic acid 2.5 mg, vitamin B12 0.5 mg and vitamin B6 25 mg/day | 3 months |
Lewerin C (2005) Sweden [46] | 195 community-dwelling participants | 17.2 ± 5.2 | 126/69 | 75.7 ± 4.7/ 75.6 ± 4.0 | 48(38.1)/ 30(43.5) | folic acid 0.8 mg, vitamin B12 0.5 mg and vitamin B6 3 mg/day | 4 months |
Hvas AM (2004) Denmark [47] | 140 elderly people with plasma methylmalonic acid 0.40 ~ 2.00µmol/L | 13.2 c | 70/70 | 75/74 c | 20(28.6)/ 22(31.4) | vitamin B12 1 mg/week | 1 month |
Garcia A (2004) Canada [48] | 24 community-dwelling participants aged ≥ 65 years, with an increased plasma methylmalonic acid and MMSE ≥ 24 | 12.2 ± 4.0 | 12/12 | 76/76 c | 5(22.7) b | vitamin B12 1 mg/month | 6 months |
Janet Bryan (2002) Australis [49] | 40 healthy older women aged 65 ~ 92 years, who did not smoke, were not pregnant or lactating | NR | 19/21 | 74.1 ± 5.75 b | 0(0)/ 0(0) | folic acid 750 µg/day | 5 weeks |
Fioravanti M (1998) Italy [50] | 30 elderly patients aged 70 ~ 90 years, with memory complaints, MMSE score 16 ~ 24 and serum folate < 3 ng/ml, recruited from homes or communities | NR | 16/14 | 80.3 ± 5.8/ 80.2 ± 5.5 | 4(25)/ 1(7.1) | folic acid 15 mg/day | 2 months |