{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:33:17Z","timestamp":1773189197933,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,3,30]],"date-time":"2020-03-30T00:00:00Z","timestamp":1585526400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006379","name":"Office of Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006379","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Wound Repair Regeneration"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>High\u2010dose folic acid (HDFA; vitamin B9)\u20145 mg, given daily, has not been evaluated as a treatment to improve early stage\u2010diabetic foot ulcer (ES\u2010DFU) wound healing. However, HDFA has been demonstrated to correct: (a) endothelial dysfunction and decreased nitric oxide (NO) bioavailability, associated with type\u20102 diabetes mellitus (T2DM); and (b) hyperhomocysteinemia (HHcy) that may promote impaired DFU\u2010wound healing. Measures of wound area (cm<jats:sup>2<\/jats:sup>) reduction (wound closure; WC), over a 4\u2010week period (4 W\u2010WC), greater than 50% of the wound area, have been reported as a robust indicator of the potential for DFU\u2010wound 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\u2010wound. To investigate this possible relationship between HDFA and ES\u2010DFU wound healing, a retrospective cohort study of medical records, between November 2018 and April 2019, was performed for Veterans with T2DM and ES\u2010DFUs following treatment with HDFA. During the study period 29 (n = 29) Veterans with ES\u2010DFU wounds who received HDFA treatment were identified. Medical record reviews of this retrospective cohort of ES\u2010DFU Veterans receiving HDFA report 90% (26\/29) experiencing complete DFU\u2010wound closure during the study period. Of the 29 Veterans with ES\u2010DFUs receiving HDFA, the medical records of nine (30%), with healed wounds, provided documentation suitable for 4 W\u2010WC, pre\u2010 and post\u2010HDFA treatment study comparisons. This study documents significant (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.05) improvements comparing 4 W\u2010WC values for standard treatment for Veterans with poorly progressing, worsening or stagnating ES\u2010DFU\u2010wounds to those for the same subjects following HDFA treatment. These observations suggest that chronic ES\u2010DFUs treated with HDFA may experience significantly improved wound closure and complete healing (re\u2010epithelialization) 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\u2010DFUs.<\/jats:p>","DOI":"10.1111\/wrr.12804","type":"journal-article","created":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T02:38:06Z","timestamp":1583462286000},"page":"517-525","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["High\u2010dose folic acid and its effect on early stage diabetic foot ulcer wound healing"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1583-7001","authenticated-orcid":false,"suffix":"Jr","given":"Joseph V.","family":"Boykin","sequence":"first","affiliation":[{"name":"Department of Surgery\/Plastic Surgery, Hunter Holmes McGuire Department of Veterans Affairs Medical Center  Richmond Virginia USA"},{"name":"Department of Surgery\/Plastic Surgery Virginia Commonwealth University Health System  Richmond Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glenn D.","family":"Hoke","sequence":"additional","affiliation":[{"name":"Department of Surgery\/Plastic Surgery, Hunter Holmes McGuire Department of Veterans Affairs Medical Center  Richmond Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cassandra R.","family":"Driscoll","sequence":"additional","affiliation":[{"name":"Department of Surgery\/Plastic Surgery, Hunter Holmes McGuire Department of Veterans Affairs Medical Center  Richmond Virginia USA"},{"name":"Department of Surgery\/Plastic Surgery Virginia Commonwealth University Health System  Richmond Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benita S.","family":"Dharmaraj","sequence":"additional","affiliation":[{"name":"Department of Surgery\/Plastic Surgery, Hunter Holmes McGuire Department of Veterans Affairs Medical Center  Richmond Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,3,30]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1615439"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis460"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.5.1435"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2016.11.020"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1753-4887.2010.00296.x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa060900"},{"issue":"2","key":"e_1_2_9_8_1","first-page":"220","article-title":"Short\u2010term oral folic acid supplementation enhances endothelial function in patients with type 2 diabetes","volume":"18","author":"Mangoni AA","year":"2005","journal-title":"J Hypertens"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1191\/1358863x06vm664oa"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2005-2143"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/918267"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2018.03.012"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2010.12.018"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.101.13.1506"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13410-019-00744-z"},{"key":"e_1_2_9_16_1","first-page":"2479","article-title":"Folic acid improves endothelial function in coronary artery disease via mechanisms largely independent of homocysteine lowering","volume":"102","author":"Doshi SN","year":"2002","journal-title":"Circulation"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-6109(02)00207-4"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.2337\/db06-0699"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-6060(97)90105-7"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/WON.0b013e3181c68b61"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M302227200"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2004.03.019"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.612325"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2015.6329"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2014.2332"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2013.05.026"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/nutrit\/nuw053"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.4161\/15592294.2014.967584"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1177\/2326409817698994"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2018.10.001"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-015-0046-8"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/1586927"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.054718"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008469-199411000-00004"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-015-0154-5"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2006.03.026"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0124739"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.6.1879"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/wrr.12048"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.114.206599"},{"issue":"4","key":"e_1_2_9_41_1","first-page":"101","article-title":"Homocysteine: a stealth mediator of impaired wound healing","volume":"18","author":"Boykin JV","year":"2006","journal-title":"Wounds"}],"container-title":["Wound Repair and Regeneration"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/wrr.12804","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/wrr.12804","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/wrr.12804","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T15:34:29Z","timestamp":1693582469000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/wrr.12804"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,30]]},"references-count":40,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["10.1111\/wrr.12804"],"URL":"https:\/\/doi.org\/10.1111\/wrr.12804","archive":["Portico"],"relation":{},"ISSN":["1067-1927","1524-475X"],"issn-type":[{"value":"1067-1927","type":"print"},{"value":"1524-475X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,30]]},"assertion":[{"value":"2019-10-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}