Abstract: Nine studies compared 1354 participants randomised to either vitamin B or its derivatives with placebo or active control were identified. A total of 1102 participants were randomised to single vitamin B derivatives, placebo or active control in eight studies, and 252 participants randomised to multiple vitamin B derivatives or placebo. Monotherapy included different dose of pyridoxamine (four studies), benfotiamine (1), folic acid (1), thiamine (1), and vitamin B12 (1) while combination therapy included folic acid, vitamin B6, and vitamin B12 in one study. Treatment duration ranged from two to 36 months. Selection bias was unclear in three studies and low in the remaining six studies. Two studies reported blinding of patient, caregiver and observer and were at low risk of performance and detection bias, two studies were at high risk bias, and five studies were unclear. Attrition bias was high in one study, unclear in one study and low in seven studies. Reporting bias was high in one study, unclear in one study, and low in the remaining seven studies. Four studies funded by pharmaceutical companies were judged to be at high risk bias, three were at low risk of bias, and two were unclear. Only a single study reported a reduction in albuminuria with thiamine compared to placebo, while second study reported reduction in glomerular filtration rate (GFR) following use of combination therapy. No significant difference in the risk of all-cause mortality with pyridoxamine or combination therapy was reported. None of the vitamin B derivatives used either alone or in combination improved kidney function: increased in creatinine clearance, improved the GFR; neither were effective in controlling blood pressure significantly compared to placebo or active control. One study reported a significant median reduction in urinary albumin excretion with thiamine treatment compared to placebo. No significant difference was found between vitamin B combination therapy and control group for serious adverse events, or one or more adverse event per patient. Vitamin B therapy was reported to well-tolerated with mild side effects in studies with treatment duration of more than six months. Studies of less than six months duration did not explicitly report adverse events; they reported that the drugs were well-tolerated without any serious drug related adverse events. None of the included studies reported cardiovascular death, progression from macroalbuminuria to ESKD, progression from microalbuminuria to macroalbuminuria, regression from microalbuminuria to normoalbuminuria, doubling of SCr, and quality of life. We were not able to perform subgroup or sensitivity analyses or assess publication bias due to insufficient data. There is an absence of evidence to recommend the use of vitamin B therapy alone or combination for delaying progression of DKD. Thiamine was found to be beneficial for reduction in albuminuria in a single study; however, there was lack of any improvement in kidney function or blood pressure following the use of vitamin B preparations used alone or in combination. These findings require further confirmation given the limitations of the small number and poor quality of the available studies.

Plain-language summary: This review included nine studies with a total of 1354 participants. One study reported improvement in urinary albumin levels following use of thiamine. None of the other studies reported improvement in kidney function or reduction in urinary albumin excretion after two to 36 months monotherapy with vitamin B therapy. Vitamin B therapy was reported to well-tolerated with mild side effects in studies with treatment duration of more than six months. Studies of less than six months duration did not explicitly report adverse events; they reported that the drugs were well-tolerated without any serious drug related adverse events. All these findings require confirmation in larger studies before they can be accepted as definite.