CENTRAL

#1 MeSH descriptor Vitamin B Complex explode all trees
#2 ”vitamin b*“
#3 folic next acid in Title, Abstract or Keywords
#4 folate* in Title, Abstract or Keywords
#5 (homocyst* near/6 lower*)
#6 (homocyst* near/6 reduc*)
#7 pyridoxin*
#8 cobalamin*
#9 cyanocobalamin*
#10 pyridoxol*
#11 MeSH descriptor Vitamins this term only
#12 (vitamin* and homocyst*)
#13 multivitamin*
#14 (#1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13)
#15 MeSH descriptor Cardiovascular Diseases this term only
#16 MeSH descriptor Myocardial Ischemia explode all trees
#17 MeSH descriptor Brain Ischemia explode all trees
#18 MeSH descriptor Cerebrovascular Disorders this term only
#19 (coronary near/6 disease)
#20 angina
#21 myocardial next infarct*
#22 heart next infarct*
#23 (stroke or strokes)
#24 (cerebr* near/6 accident*)
#25 (cerebr* near/6 infarct*)
#26 (brain near/6 infarct*)
#27 apoplexy
#28 cardiovascular next disease*
#29 (cardiovascular near/6 event*)
#30 MeSH descriptor Hyperhomocysteinemia explode all trees
#31 hyperhomocyst*
#32 cva
#33 (#15 or #16 or #17 or #18 or #19 or #20 or #21 or #22 or #23 or #24 or #25)
#34 (#26 or #27 or #28 or #29 or #30 or #31 or #32)
#35 (#33 or #34)
#36 (#14 and #35)

LILACS (accessed through Biblioteca Virtual em Saúde)

((Pt ENSAYO CONTROLADO ALEATORIO OR Pt ENSAYO CLINICO CONTROLADO OR Mh ENSAYOS CONTROLADOS ALEATORIOS OR Mh DISTRIBUCIÓN ALEATORIA OR Mh METODO DOBLE CIEGO OR Mh METODO SIMPLECIEGO OR Pt ESTUDIO MULTICÉNTRICO) or ((tw ensaio or tw ensayo or tw trial) and (tw azar or tw acaso or tw placebo or tw control$ or tw aleat$ or tw random$ or (tw duplo and tw cego) or (tw doble and tw ciego) or (tw double and tw blind)) and tw clinic$)) AND NOT ((Ct ANIMALES OR Mh ANIMALES OR Ct CONEJOS OR Ct RATÓN OR MH Ratas OR MH Primates OR MH Perros OR MH Conejos OR MH Porcinos) AND NOT (Ct HUMANO AND Ct ANIMALES)) [Palavras] and MH Vitamina B 12 OR Cobamidas OR Hidroxocobalamina OR Complejo Vitamínico B OR Ácido Fólico OR Ácidos Pteroilpoliglutámicos OR Tetrahidrofolatos OR Formiltetrahidrofolatos OR Vitamina B 6 OR Piridoxal OR Fosfato de Piridoxal OR Piridoxamina OR Piridoxina OR Homocisteína OR Vitaminas or TW vitamin$ or tw cobalamin$ or tw cianocobalamin$ or tw cyanocobalam$ or tw cobamid$ or tw hidroxocobalam$ or tw Hydroxocobalam$ or ((tw complejo or tw complex$) and tw vitamin$ and tw b) or (tw acid$ and (tw folic$ or tw ptero$)) or tw Tetrahidrofolatos or tw Formiltetrahidrofolatos or (tw vitamin$ or (tw b or tw b6 or tw b12)) or tw Piridoxal or tw Pyridoxal or ((tw Fosfat$ or tw phosphate$) and (tw Piridoxal or tw pyridoxal)) or tw Piridox$ or tw Pyridox$ or tw Homocisteína or tw Homocysteine) AND (MH Enfermedades Cardiovasculares or Isquemia Miocárdica or Ex C14.280.647$ or Isquemia Encefálica or Ex C10.228.140.300.150$ or Trastornos Cerebrovasculares or hiperhomocisteinemia or Accidente Cerebrovascular or ((tw apoplexia or tw derrame or tw trastorno$ or tw accident$ or tw acidente or tw stroke$ or tw disease$ or tw enfermedad$ or tw doenca$ or tw event$ or tw infart$ or tw isquemia or tw disorder$) and (tw miocardio or tw myocard$ or tw cerebr$ or tw cardiovascul$ or tw heart or tw cardiovascul$ or tw encefal$)) or tw hyperhomocyst$ or tw hiperhomocisteinemia) [Palavras]

MEDLINE

1 exp Vitamin B Complex/
2 vitamin b.tw.
3 folic acid.tw.
4 folate$.tw.
5 ((homocystein$ or homocystin$) adj3 (low$ or reduc$)).tw.
6 pyridoxin$.tw.
7 cobalamin$.tw.
8 cyanocobalamin$.tw.
9 pyridoxol$.tw.
10 Vitamins/
11 or/1‐10
12 Cardiovascular Diseases/
13 exp Myocardial Ischemia/
14 exp Brain Ischemia/
15 Cerebrovascular Disorders/
16 (coronary adj3 disease$).tw.
17 angina.tw.
18 myocardial infarct$.tw.
19 heart infarct$.tw.
20 heart attack$.tw.
21 (stroke or strokes).tw.
22 (cerebr$ adj3 (accident$ or infarct$)).tw.
23 (brain adj3 infarct$).tw.
24 apoplexy.tw.
25 (cardiovascular adj2 (disease$ or event$)).tw.
26 Hyperhomocysteinemia/
27 hyperhomocyst?in?emi$.tw.
28 or/12‐27
29 11 and 28
30 randomized controlled trial.pt.
31 controlled clinical trial.pt.
32 Randomized controlled trials/
33 random allocation/
34 double blind method/
35 single‐blind method/
36 or/30‐35
37 exp animal/ not humans/
38 36 not 37
39 clinical trial.pt.
40 exp Clinical Trials as Topic/
41 (clin$ adj25 trial$).ti,ab.
42 ((singl$ or doubl$ or trebl$ or tripl$) adj (blind$ or mask$)).ti,ab.
43 placebos/
44 placebo$.ti,ab.
45 random$.ti,ab.
46 research design/
47 or/39‐46
48 47 not 37
49 38 or 48
50 49 and 29

Embase

1 exp Vitamin B Group/
2 vitamin b.tw.
3 folic acid.tw.
4 folate$.tw.
5 ((homocystein$ or homocystin$) adj3 (low$ or reduc$)).tw.
6 pyridoxin$.tw.
7 cobalamin$.tw.
8 cyanocobalamin$.tw.
9 pyridoxol$.tw.
10 Vitamins/
11 or/1‐10
12 Cardiovascular Diseases/
13 exp ischaemic heart disease/
14 exp Coronary Artery Disease/
15 exp Brain Ischemia/
16 cerebrovascular disease/
17 stroke/
18 cerebrovascular accident/
19 (coronary adj3 disease$).tw.
20 angina.tw.
21 myocardial infarct$.tw.
22 heart infarct$.tw.
23 heart attack$.tw.
24 (stroke or strokes).tw.
25 (cerebr$ adj3 (accident$ or infarct$)).tw.
26 (brain adj3 infarct$).tw.
27 apoplexy.tw.
28 (cardiovascular adj2 (disease$ or event$)).tw.
29 Hyperhomocysteinemia/
30 hyperhomocyst?in?emi$.tw.
31 or/12‐30
32 11 and 31
33 controlled clinical trial/
34 random$.tw.
35 randomized controlled trial/
36 follow‐up.tw.
37 double blind procedure/
38 placebo$.tw.
39 placebo/
40 factorial$.ti,ab.
41 (crossover$ or cross‐over$).ti,ab.
42 (double$ adj blind$).ti,ab.
43 (singl$ adj blind$).ti,ab.
44 assign$.ti,ab.
45 allocat$.ti,ab.
46 volunteer$.ti,ab.
47 Crossover Procedure/
48 Single Blind Procedure/
49 or/33‐48
50 32 and 49

Web of Science

# 11 TS=(#10 and (random* or blind* or placebo* or comparative or comparison or prospective or controlled or trial or evaluation or rct))
# 10 #7 or #8 or #9
# 9 TS=(#6 and (”cerebrovascular accident*“ or hyperhomocyst*))
# 8 TS=(#6 and (angina or stroke or strokes or cva or infarction*))
# 7 TS=(#6 and (cardiovascular or myocardial or coronary or cardiac or ”heart disease*“))
# 6 #1 or #2 or #3 or #4 or #5
# 5 TS=(homocyst* same (lower* or reduc*))
# 4 TS=(vitamin* and homocyst*)
# 3 TS=folate*
# 2 TS=”vitamin B“
# 1 TS=(pyridoxin* or cobalamin* or cyanocobalamin* or pyridoxol* or ”folic acid“)

CENTRAL

#1 MeSH descriptor Vitamin B Complex explode all trees
#2 (vitamin b)
#3 folic acid
#4 folate*
#5 ((homocystein* or homocystin*) near/3 (low* or reduc*))
#6 (pyridoxin*)
#7 (cobalamin*)
#8 (cyanocobalamin*)
#9 (pyridoxol*)
#10 MeSH descriptor Vitamins, this term only
#11 (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10)
#12 MeSH descriptor Cardiovascular Diseases, this term only
#13 MeSH descriptor Myocardial Ischemia explode all trees
#14 MeSH descriptor Brain Ischemia explode all trees
#15 MeSH descriptor Cerebrovascular Disorders, this term only
#16 (coronary near/3 disease*)
#17 (angina)
#18 (myocardial infarct*)
#19 (heart infarct*)
#20 (heart attack*)
#21 (stroke or strokes)
#22 (cerebr* near/3 (accident* or infarct*))
#23 (brain near/3 infarct*)
#24 (apoplexy)
#25 (cardiovascular near/2 (disease* or event*))
#26 MeSH descriptor Hyperhomocysteinemia, this term only
#27 hyperhomocyst?in?emi*
#28 (#12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27)
#29 (#11 AND #28)

MEDLINE

1 exp Vitamin B Complex/
2 vitamin b.tw.
3 folic acid.tw.
4 folate$.tw.
5 ((homocystein$ or homocystin$) adj3 (low$ or reduc$)).tw.
6 pyridoxin$.tw.
7 cobalamin$.tw.
8 cyanocobalamin$.tw.
9 pyridoxol$.tw.
10 Vitamins/
11 or/1‐10
12 Cardiovascular Diseases/
13 exp Myocardial Ischemia/
14 exp Brain Ischemia/
15 Cerebrovascular Disorders/
16 (coronary adj3 disease$).tw.
17 angina.tw.
18 myocardial infarct$.tw.
19 heart infarct$.tw.
20 heart attack$.tw.
21 (stroke or strokes).tw.
22 (cerebr$ adj3 (accident$ or infarct$)).tw.
23 (brain adj3 infarct$).tw.
24 apoplexy.tw.
25 (cardiovascular adj2 (disease$ or event$)).tw.
26 Hyperhomocysteinemia/
27 hyperhomocyst?in?emi$.tw.
28 or/12‐27
29 11 and 28
30 randomized controlled trial.pt.
31 controlled clinical trial.pt.
32 randomized.ab.
33 placebo.ab.
34 drug therapy.fs.
35 randomly.ab.
36 trial.ab.
37 groups.ab.
38 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37
39 exp animals/ not humans.sh. (3663238)
40 38 not 39
41 29 and 40
42 (200808* or 200809* or 20081* or 2009* or 2010* or 2011* or 2012*).ed.
43 41 and 42

Embase

1 exp Vitamin B Complex/
2 vitamin b.tw.
3 folic acid.tw.
4 folate$.tw.
5 ((homocystein$ or homocystin$) adj3 (low$ or reduc$)).tw.
6 pyridoxin$.tw.
7 cobalamin$.tw.
8 cyanocobalamin$.tw.
9 pyridoxol$.tw.
10 Vitamins/
11 or/1‐10
12 Cardiovascular Diseases/
13 exp Myocardial Ischemia/
14 exp Brain Ischemia/
15 Cerebrovascular Disorders/
16 (coronary adj3 disease$).tw.
17 angina.tw.
18 myocardial infarct$.tw.
19 heart infarct$.tw.
20 heart attack$.tw.
21 (stroke or strokes).tw.
22 (cerebr$ adj3 (accident$ or infarct$)).tw.
23 (brain adj3 infarct$).tw.
24 apoplexy.tw.
25 (cardiovascular adj2 (disease$ or event$)).tw.
26 Hyperhomocysteinemia/
27 hyperhomocyst?in?emi$.tw.
28 or/12‐27
29 11 and 28
30 random$.tw.
31 factorial$.tw.
32 crossover$.tw.
33 cross over$.tw.
34 cross‐over$.tw.
35 placebo$.tw.
36 (doubl$ adj blind$).tw.
37 (singl$ adj blind$).tw.
38 assign$.tw.
39 allocat$.tw.
40 volunteer$.tw.
41 crossover procedure/
42 double blind procedure/
43 randomized controlled trial/
44 single blind procedure/
45 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44
46 (animal/ or nonhuman/) not human/
47 45 not 46
48 29 and 47
49 (200808* or 200809* or 20081* or 2009* or 2010* or 2011* or 2012*).dd.
50 48 and 49

Web of Science

#24 #23 AND #22
#23 Topic=((random* or blind* or allocat* or assign* or trial* or placebo* or crossover* or cross‐over*))
#22 #21 AND #9
#21 #20 OR #19 OR #18 OR #17 OR #16 OR #15 OR #14 OR #13 OR #12 OR #11
#20 Topic=(hyperhomocyst$in$emi*)
#19 Topic=((cardiovascular near/2 (disease* or event*)))
#18 Topic=(apoplexy)
#17 Topic=((brain near/3 infarct*))
#16 Topic=((cerebr* near/3 (accident* or infarct*)))
#15 Topic=((stroke or strokes))
#14 Topic=(heart attack*)
#13 Topic=(heart infarct*)
#12 Topic=(myocardial infarct*)
#11 Topic=(angina)
#10 Topic=((coronary near/3 disease*))
#9 #8 OR #7 OR #6 OR #5 OR #4 OR #3 OR #2 OR #1
#8 Topic=(pyridoxol*)
#7 Topic=(cyanocobalamin*)
#6 Topic=(cobalamin*)
#5 Topic=(pyridoxin*)
#4 Topic=(((homocystein*) near/3 (low$ or reduc*))) OR Topic=(((homocystin*) near/3 (low or reduc*)))
#3 Topic=(folate*)
#2 Topic=("folic acid")
#1 Topic=("vitamin b")

CENTRAL

#1 MeSH descriptor Vitamin B Complex explode all trees
#2 (vitamin b)
#3 folic acid
#4 folate*
#5 ((homocystein* or homocystin*) near/3 (low* or reduc*))
#6 (pyridoxin*)
#7 (cobalamin*)
#8 (cyanocobalamin*)
#9 (pyridoxol*)
#10 MeSH descriptor Vitamins, this term only
#11 (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10)
#12 MeSH descriptor Cardiovascular Diseases, this term only
#13 MeSH descriptor Myocardial Ischemia explode all trees
#14 MeSH descriptor Brain Ischemia explode all trees
#15 MeSH descriptor Cerebrovascular Disorders, this term only
#16 (coronary near/3 disease*)
#17 (angina)
#18 (myocardial infarct*)
#19 (heart infarct*)
#20 (heart attack*)
#21 (stroke or strokes)
#22 (cerebr* near/3 (accident* or infarct*))
#23 (brain near/3 infarct*)
#24 (apoplexy)
#25 (cardiovascular near/2 (disease* or event*))
#26 MeSH descriptor Hyperhomocysteinemia, this term only
#27 hyperhomocyst?in?emi*
#28 (#12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27)
#29 (#11 AND #28)

MEDLINE

1 exp Vitamin B Complex/
2 vitamin b.tw.
3 folic acid.tw.
4 folate$.tw.
5 ((homocystein$ or homocystin$) adj3 (low$ or reduc$)).tw.
6 pyridoxin$.tw.
7 cobalamin$.tw.
8 cyanocobalamin$.tw.
9 pyridoxol$.tw.
10 Vitamins/
11 or/1‐10
12 Cardiovascular Diseases/
13 exp Myocardial Ischemia/
14 exp Brain Ischemia/
15 Cerebrovascular Disorders/
16 (coronary adj3 disease$).tw.
17 angina.tw.
18 myocardial infarct$.tw.
19 heart infarct$.tw.
20 heart attack$.tw.
21 (stroke or strokes).tw.
22 (cerebr$ adj3 (accident$ or infarct$)).tw.
23 (brain adj3 infarct$).tw.
24 apoplexy.tw.
25 (cardiovascular adj2 (disease$ or event$)).tw.
26 Hyperhomocysteinemia/
27 hyperhomocyst?in?emi$.tw.
28 or/12‐27
29 11 and 28
30 randomized controlled trial.pt.
31 controlled clinical trial.pt.
32 randomized.ab.
33 placebo.ab.
34 drug therapy.fs.
35 randomly.ab.
36 trial.ab.
37 groups.ab.
38 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37
39 exp animals/ not humans.sh. (3663238)
40 38 not 39
41 29 and 40
42 (2012* or 2013* or 2014*).ed.
43 41 and 42

Embase

1 exp Vitamin B Complex/
2 vitamin b.tw.
3 folic acid.tw.
4 folate$.tw.
5 ((homocystein$ or homocystin$) adj3 (low$ or reduc$)).tw.
6 pyridoxin$.tw.
7 cobalamin$.tw.
8 cyanocobalamin$.tw.
9 pyridoxol$.tw.
10 Vitamins/
11 or/1‐10
12 Cardiovascular Diseases/
13 exp Myocardial Ischemia/
14 exp Brain Ischemia/
15 Cerebrovascular Disorders/
16 (coronary adj3 disease$).tw.
17 angina.tw.
18 myocardial infarct$.tw.
19 heart infarct$.tw.
20 heart attack$.tw.
21 (stroke or strokes).tw.
22 (cerebr$ adj3 (accident$ or infarct$)).tw.
23 (brain adj3 infarct$).tw.
24 apoplexy.tw.
25 (cardiovascular adj2 (disease$ or event$)).tw.
26 Hyperhomocysteinemia/
27 hyperhomocyst?in?emi$.tw.
28 or/12‐27
29 11 and 28
30 random$.tw.
31 factorial$.tw.
32 crossover$.tw.
33 cross over$.tw.
34 cross‐over$.tw.
35 placebo$.tw.
36 (doubl$ adj blind$).tw.
37 (singl$ adj blind$).tw.
38 assign$.tw.
39 allocat$.tw.
40 volunteer$.tw.
41 crossover procedure/
42 double blind procedure/
43 randomized controlled trial/
44 single blind procedure/
45 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44
46 (animal/ or nonhuman/) not human/
47 45 not 46
48 29 and 47
49 (2012* or 2013* or 2014*).dd.
50 48 and 49

Web of Science

#24 #23 AND #22
#23 Topic=((random* or blind* or allocat* or assign* or trial* or placebo* or crossover* or cross‐over*))
#22 #21 AND #9
#21 #20 OR #19 OR #18 OR #17 OR #16 OR #15 OR #14 OR #13 OR #12 OR #11
#20 Topic=(hyperhomocyst$in$emi*)
#19 Topic=((cardiovascular near/2 (disease* or event*)))
#18 Topic=(apoplexy)
#17 Topic=((brain near/3 infarct*))
#16 Topic=((cerebr* near/3 (accident* or infarct*)))
#15 Topic=((stroke or strokes))
#14 Topic=(heart attack*)
#13 Topic=(heart infarct*)
#12 Topic=(myocardial infarct*)
#11 Topic=(angina)
#10 Topic=((coronary near/3 disease*))
#9 #8 OR #7 OR #6 OR #5 OR #4 OR #3 OR #2 OR #1
#8 Topic=(pyridoxol*)
#7 Topic=(cyanocobalamin*)
#6 Topic=(cobalamin*)
#5 Topic=(pyridoxin*)
#4 Topic=(((homocystein*) near/3 (low$ or reduc*))) OR Topic=(((homocystin*) near/3 (low or reduc*)))
#3 Topic=(folate*)
#2 Topic=("folic acid")
#1 Topic=("vitamin b")

CENTRAL

#1 MeSH descriptor Vitamin B Complex explode all trees

#2 (vitamin b)

#3 folic acid

#4 folate*

#5 ((homocystein* or homocystin*) near/3 (low* or reduc*))

#6 (pyridoxin*)

#7 (cobalamin*)

#8 (cyanocobalamin*)

#9 (pyridoxol*)

#10 MeSH descriptor Vitamins, this term only

#11 (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10)

#12 MeSH descriptor Cardiovascular Diseases, this term only

#13 MeSH descriptor Myocardial Ischemia explode all trees

#14 MeSH descriptor Brain Ischemia explode all trees

#15 MeSH descriptor Cerebrovascular Disorders, this term only

#16 (coronary near/3 disease*)

#17 (angina)

#18 (myocardial infarct*)

#19 (heart infarct*)

#20 (heart attack*)

#21 (stroke or strokes)

#22 (cerebr* near/3 (accident* or infarct*))

#23 (brain near/3 infarct*)

#24 (apoplexy)

#25 (cardiovascular near/2 (disease* or event*))

#26 MeSH descriptor Hyperhomocysteinemia, this term only

#27 hyperhomocyst?in?emi*

#28 (#12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27)

#29 (#11 AND #28)

MEDLINE OVID

1 exp Vitamin B Complex/

2 vitamin b.tw.

3 folic acid.tw.

4 folate$.tw.

5 ((homocystein$ or homocystin$) adj3 (low$ or reduc$)).tw.

6 pyridoxin$.tw.

7 cobalamin$.tw.

8 cyanocobalamin$.tw.

9 pyridoxol$.tw.

10 Vitamins/

11 or/1‐10

12 Cardiovascular Diseases/

13 exp Myocardial Ischemia/

14 exp Brain Ischemia/

15 Cerebrovascular Disorders/

16 (coronary adj3 disease$).tw.

17 angina.tw.

18 myocardial infarct$.tw.

19 heart infarct$.tw.

20 heart attack$.tw.

21 (stroke or strokes).tw.

22 (cerebr$ adj3 (accident$ or infarct$)).tw.

23 (brain adj3 infarct$).tw.

24 apoplexy.tw.

25 (cardiovascular adj2 (disease$ or event$)).tw.

26 Hyperhomocysteinemia/

27 hyperhomocyst?in?emi$.tw.

28 or/12‐27

29 11 and 28

30 randomized controlled trial.pt.

31 controlled clinical trial.pt.

32 randomized.ab.

33 placebo.ab.

34 drug therapy.fs.

35 randomly.ab.

36 trial.ab.

37 groups.ab.

38 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37

39 exp animals/ not humans.sh. (3663238)

40 38 not 39

41 29 and 40

42 (2014* or 2015* or 2016*).ed.

43 41 and 42

Embase OVID

1 exp Vitamin B Complex/

2 vitamin b.tw.

3 folic acid.tw.

4 folate$.tw.

5 ((homocystein$ or homocystin$) adj3 (low$ or reduc$)).tw.

6 pyridoxin$.tw.

7 cobalamin$.tw.

8 cyanocobalamin$.tw.

9 pyridoxol$.tw.

10 Vitamins/

11 or/1‐10

12 Cardiovascular Diseases/

13 exp Myocardial Ischemia/

14 exp Brain Ischemia/

15 Cerebrovascular Disorders/

16 (coronary adj3 disease$).tw.

17 angina.tw.

18 myocardial infarct$.tw.

19 heart infarct$.tw.

20 heart attack$.tw.

21 (stroke or strokes).tw.

22 (cerebr$ adj3 (accident$ or infarct$)).tw.

23 (brain adj3 infarct$).tw.

24 apoplexy.tw.

25 (cardiovascular adj2 (disease$ or event$)).tw.

26 Hyperhomocysteinemia/

27 hyperhomocyst?in?emi$.tw.

28 or/12‐27

29 11 and 28

30 random$.tw.

31 factorial$.tw.

32 crossover$.tw.

33 cross over$.tw.

34 cross‐over$.tw.

35 placebo$.tw.

36 (doubl$ adj blind$).tw.

37 (singl$ adj blind$).tw.

38 assign$.tw.

39 allocat$.tw.

40 volunteer$.tw.

41 crossover procedure/

42 double blind procedure/

43 randomized controlled trial/

44 single blind procedure/

45 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44

46 (animal/ or nonhuman/) not human/

47 45 not 46

48 29 and 47

49 (2014* or 2015* or 2016*).dd.

50 48 and 49

Web of Science

#26 #25 AND #24

#25 TS=((random* or blind* or allocat* or assign* or trial* or placebo* or crossover* or cross‐over*))

#24 #23 AND #10

#23 #22 OR #21 OR #20 OR #19 OR #18 OR #17 OR #16 OR #15 OR #14 OR #13 OR #12 OR #11

#22 TS=(hyperhomocystein$emi*)

#21 TS=(hyperhomocystin$emi*)

#20 TS=(cardiovascular near/2 (disease* or event*))

#19 TS=(apoplexy)

#18 TS=((brain near/3 infarct*))

#17 TS=((cerebr* near/3 (accident* or infarct*)))

#16 TS=((stroke or strokes))

#15 TS=(heart attack*)

#14 TS=(heart infarct*)

#13 TS=(myocardial infarct*)

#12 TS=(angina)

#11 TS=((coronary near/3 disease*))

#10 #9 OR #8 OR #7 OR #6 OR #5 OR #4 OR #3 OR #2 OR #1

#9 TS=(pyridoxol*)

#8 TS=(cyanocobalamin*)

#7 TS=(cobalamin*)

#6 TS=(pyridoxin*)

#5 TS=((homocystin*) near/3 (low or reduc*))

#4 TS=((homocystein*) near/3 (low$ or reduc*))

#3 TS=(folate*)

#2 TS=("folic acid")

#1 TS=("vitamin b")

LILACS (accessed through Biblioteca Virtual em Saúde)

((Pt ENSAYO CONTROLADO ALEATORIO OR Pt ENSAYO CLINICO CONTROLADO OR Mh ENSAYOS CONTROLADOS ALEATORIOS OR Mh DISTRIBUCIÓN ALEATORIA OR Mh METODO DOBLE CIEGO OR Mh METODO SIMPLECIEGO OR Pt ESTUDIO MULTICÉNTRICO) or ((tw ensaio or tw ensayo or tw trial) and (tw azar or tw acaso or tw placebo or tw control$ or tw aleat$ or tw random$ or (tw duplo and tw cego) or (tw doble and tw ciego) or (tw double and tw blind)) and tw clinic$)) AND NOT ((Ct ANIMALES OR Mh ANIMALES OR Ct CONEJOS OR Ct RATÓN OR MH Ratas OR MH Primates OR MH Perros OR MH Conejos OR MH Porcinos) AND NOT (Ct HUMANO AND Ct ANIMALES)) [Palavras] and MH Vitamina B 12 OR Cobamidas OR Hidroxocobalamina OR Complejo Vitamínico B OR Ácido Fólico OR Ácidos Pteroilpoliglutámicos OR Tetrahidrofolatos OR Formiltetrahidrofolatos OR Vitamina B 6 OR Piridoxal OR Fosfato de Piridoxal OR Piridoxamina OR Piridoxina OR Homocisteína OR Vitaminas or TW vitamin$ or tw cobalamin$ or tw cianocobalamin$ or tw cyanocobalam$ or tw cobamid$ or tw hidroxocobalam$ or tw Hydroxocobalam$ or ((tw complejo or tw complex$) and tw vitamin$ and tw b) or (tw acid$ and (tw folic$ or tw ptero$)) or tw Tetrahidrofolatos or tw Formiltetrahidrofolatos or (tw vitamin$ or (tw b or tw b6 or tw b12)) or tw Piridoxal or tw Pyridoxal or ((tw Fosfat$ or tw phosphate$) and (tw Piridoxal or tw pyridoxal)) or tw Piridox$ or tw Pyridox$ or tw Homocisteína or tw Homocysteine) AND (MH Enfermedades Cardiovasculares or Isquemia Miocárdica or Ex C14.280.647$ or Isquemia Encefálica or Ex C10.228.140.300.150$ or Trastornos Cerebrovasculares or hiperhomocisteinemia or Accidente Cerebrovascular or ((tw apoplexia or tw derrame or tw trastorno$ or tw accident$ or tw acidente or tw stroke$ or tw disease$ or tw enfermedad$ or tw doenca$ or tw event$ or tw infart$ or tw isquemia or tw disorder$) and (tw miocardio or tw myocard$ or tw cerebr$ or tw cardiovascul$ or tw heart or tw cardiovascul$ or tw encefal$)) or tw hyperhomocyst$ or tw hiperhomocisteinemia) [Palavras]

Generation of the allocation sequence

• Low risk of bias, if the allocation sequence was generated by a computer or random number table, drawing of lots, tossing of a coin, shuffling of cards or throwing dice.

• Unclear, if the trial was described as randomised but the method used for the allocation sequence generation was not described.

• High risk of bias, if a system involving dates, names or admittance numbers was used for the allocation of patients. These studies are known as quasi‐randomised and we excluded them from the review when assessing beneficial effects.

Allocation concealment

• Low risk of bias, if the allocation of patients involved a central independent unit, on‐site locked computer, identical‐appearing numbered drug bottles or containers prepared by an independent pharmacist or investigator, or sealed envelopes.

• Unclear, if the trial was described as randomised but the method used to conceal the allocation was not described.

• High risk of bias, if the allocation sequence was known to the investigators who assigned participants or if the study was quasi‐randomised. We excluded the latter from the review when assessing beneficial effects.

Blinding (or masking)

We assessed each trial (as low, unclear or high risk) with regard to the following levels of blinding.

• Blinding of clinician (person delivering treatment) to treatment allocation.

• Blinding of participant to treatment allocation.

• Blinding of outcome assessor to treatment allocation.

Incomplete outcome data

• Low risk of bias, if the numbers and reasons for dropouts and withdrawals in all intervention groups were described or it was specified that there were no dropouts or withdrawals.

• Unclear, if the report gave the impression that there had been no dropouts or withdrawals but this was not specifically stated.

• High risk of bias, if the number or reasons for dropouts and withdrawals were not described.

We further examined the percentage of dropouts overall in each trial and per randomisation arm and we evaluated whether intention‐to‐treat analysis was performed or could be performed from the published information.

Selective outcome reporting

• Low risk of bias, if pre‐defined or clinically relevant and reasonably expected outcomes were reported on.

• Unclear, if not all pre‐defined or clinically relevant and reasonably expected outcomes were reported on or were not reported on fully, or it was unclear whether data on these outcomes were recorded or not.

• High risk of bias, if one or more clinically relevant and reasonably expected outcomes were not reported on; data on these outcomes were likely to have been recorded.

Other bias

• Low risk of bias, the trial appeared to be free of other components that could put it at risk of bias.

• Unclear, the trial may or may not be free of other components that could put it at risk of bias.

• High risk of bias, there were other factors in the trial that could put it at risk of bias.

Overall risk of bias

We considered studies to have an overall low risk of bias if they did not have high risk of bias in any of six individual domains (random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data or selective reporting), and if a definitive risk of bias assessment could be made for the majority (at least five of six) of domains. We did not include ‘Other bias’ in our overall assessment.