Table 2.

Interventional trials on the effects of folic acid and vitamin B12 administration and CVD risk, mortality and CKD progression.

Study	Design/Intervention	Participants, n	End Point	Follow-up, Years	Results
Xu et al., 2016 [87]	Double blind RCT: enalapril 10 mg versus enalapril 10 mg plus folic acid	15,104 (eGFR ≥ 30 mL/min). No folic acid fortification	CKD progression	4.4	Enalapril plus folic acid delayed CKD progression
House et al., 2010 [125]	Double blind RCT: folic acid 2.5 mg + Vitamin B6 25 mg + Vitamin B12 1 mg versus placebo	238 (diabetic nephropathy with eGFR > 30 mL/min). Folic acid fortification	CKD progression	2.6	Greater GFR decrease and more CVD events in treatment group
Heinz et al., 2010 [120]	Double blind RCT: folic acid 5 mg, vitamin B12 50 µg, vitamin B6 20 mg versus placebo 3 times a week	650 hemodialysis patients	All-cause mortality, cardiovascular events	2	No differences
Mann et al., 2008 [126]	Double blind RCT: folic acid 2.5 mg + vitamin B6 50 mg + vitamin B12 1 mg versus placebo	619 CKD (eGFR <60 mL/min)	All-cause mortality, cardiovascular events	5	No differences
Cianciolo et al., 2008 [11]	Open label randomized trial: 5-MTHF intravenous. three times a week versus folic acid 5 mg oral daily	314 hemodialysis patients	All-cause mortality	4.5	Less mortality risk in 5-MTHF group (independent of homocysteine)
Jamison et al., 2007 [119]	Double blind RCT (HOST): folic acid 40 mg + vitamin B6 100 mg + vitamin B12 2 mg versus placebo	2056 CKD (eGFR ≤ 30) or hemodialysis (folic acid fortification)	All-cause mortality, CKD progression	3.2	No differences
Vianna et al., 2007 [127]	Double blind RCT: folic acid 5 mg versus placebo	97 hemodialysis patients	Cardiovascular events	2	No differences
Zoungas et al., 2006 [118]	Double blind RCT (ASFAST): folic acid 15 mg versus placebo	315 CKD (eGFR < 25 mL/min), hemodialysis and peritoneal dialysis	Cardiovascular events and mortality	3.6	No differences
Righetti et al., 2006 [128]	Open prospective trial: folic acid 5 mg versus untreated	114 hemodialysis patients	Cardiovascular events	2.4	Folic acid decreases CVD events
Wrone et al., 2004 [76]	Three arms, double blind RCT: folic acid 1 mg or 5 mg or 15 mg	510 hemodialysis patients	Cardiovascular events and mortality	2	No differences
Righetti et al., 2003 [117]	Placebo-controlled, non-blinded RCT: folic acid 5, 15, 25 mg or placebo	81 hemodialysis patients	Cardiovascular mortality	1	No differences

Abbreviations: CKD, Chronic Kidney Disease; CVD, Cardiovascular Disease; eGFR, estimated Glomerular Filtration Rate; RCT, Randomized Clinical Trial.