Folic acid and vitamin B12 supplementation in subjects with type 2 diabetes mellitus: A multi-arm randomized controlled clinical trial

Complement Ther Med. 2020 Sep:53:102526. doi: 10.1016/j.ctim.2020.102526. Epub 2020 Jul 22.


Objective: This study was conducted to investigate and compare the effects of add-on folic acid and vitamin B12 supplementation on glycaemic control, insulin resistance and serum lipid profile in subjects with type 2 diabetes mellitus.

Study design & intervention: This study was a randomized, multi-arm, open-label clinical trial. 80 patients with type 2 diabetes and on stable oral antidiabetics were enrolled and 20 patients each were randomly allocated to one of the four groups - Group A: add-on Folic acid (5 mg/day); Group B: add-on Methylcobalamin (500 mcg/day); Group C: add-on Folic acid (5 mg/day) + Methylcobalamin (500 mcg/day) and Group D: Standard oral anti-diabetic drugs. The patients were followed up after 8 weeks.

Results: HbA1c improved significantly in Groups B and C [median changes from baseline - 1.2 % (- 13 mmol/mol) and - 1.5 % (- 16 mmol/mol) respectively, p values 0.04 and 0.02 respectively] compared to Group D. Groups B and C also showed significant improvements in plasma insulin, insulin resistance and serum adiponectin compared to Group D. Serum homocysteine declined significantly in all three groups with add-on supplementation compared to standard treatment. No improvement in the lipid profile was noted in any of the groups.

Conclusions: Add-on supplementation with vitamin B12 improved glycaemic control and insulin resistance in patients with type 2 diabetes mellitus.

Keywords: Folic acid; Type 2 diabetes mellitus; Vitamin B 12.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dietary Supplements
  • Drug Therapy, Combination
  • Folic Acid / therapeutic use*
  • Glycemic Control
  • Humans
  • Insulin Resistance
  • Lipids / blood
  • Middle Aged
  • Vitamin B 12 / therapeutic use*


  • Lipids
  • Folic Acid
  • Vitamin B 12