High-dose folic acid and its effect on early stage diabetic foot ulcer wound healing

High-dose folic acid (HDFA; vitamin B9)-5 mg, given daily, has not been evaluated as a treatment to improve early stage-diabetic foot ulcer (ES-DFU) wound healing. However, HDFA has been demonstrated to correct: (a) endothelial dysfunction and decreased nitric oxide (NO) bioavailability, associated with type-2 diabetes mellitus (T2DM); and (b) hyperhomocysteinemia (HHcy) that may promote impaired DFU-wound healing. Measures of wound area (cm² ) reduction (wound closure; WC), over a 4-week period (4 W-WC), greater than 50% of the wound area, have been reported as a robust indicator of the potential for DFU-wound healing. By using this model, we examined the effectiveness of a wound treatment in promoting progressive healing and complete wound closure for the chronic, nonhealing DFU-wound. To investigate this possible relationship between HDFA and ES-DFU wound healing, a retrospective cohort study of medical records, between November 2018 and April 2019, was performed for Veterans with T2DM and ES-DFUs following treatment with HDFA. During the study period 29 (n = 29) Veterans with ES-DFU wounds who received HDFA treatment were identified. Medical record reviews of this retrospective cohort of ES-DFU Veterans receiving HDFA report 90% (26/29) experiencing complete DFU-wound closure during the study period. Of the 29 Veterans with ES-DFUs receiving HDFA, the medical records of nine (30%), with healed wounds, provided documentation suitable for 4 W-WC, pre- and post-HDFA treatment study comparisons. This study documents significant (P < .05) improvements comparing 4 W-WC values for standard treatment for Veterans with poorly progressing, worsening or stagnating ES-DFU-wounds to those for the same subjects following HDFA treatment. These observations suggest that chronic ES-DFUs treated with HDFA may experience significantly improved wound closure and complete healing (re-epithelialization) when compared with standard treatments without HDFA. With validation from RCTs, HDFA may be established as an effective treatment to promote wound healing and closure for nonhealing ES-DFUs.