{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T19:22:37Z","timestamp":1791055357358,"version":"4.1.0"},"reference-count":86,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T00:00:00Z","timestamp":1611705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Aim: To investigate the effect of normalizing vitamin B12 (B12) levels with oral B12 (methylcobalamin) 1000 \u03bcg\/day for one year in patients with diabetic neuropathy (DN). Patients and methods: In this prospective, double-blind, placebo-controlled trial, 90 patients with type 2 diabetes on metformin for at least four years and both peripheral and autonomic DN were randomized to an active treatment group (n = 44) receiving B12 and a control group (n = 46) receiving a placebo. All patients had B12 levels less than 400 pmol\/L. Subjects underwent measurements of sural nerve conduction velocity (SNCV), sural nerve action potential (amplitude) (SNAP), and vibration perception threshold (VPT), and they performed cardiovascular autonomic reflex tests (CARTs: mean circular resultant (MCR), Valsalva test, postural index, and orthostatic hypotension). Sudomotor function was assessed with the SUDOSCAN that measures electrochemical skin conductance in hands and feet (ESCH and ESCF, respectively). We also used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE, respectively) and questionnaires to evaluate quality of life (QoL) and level of pain (pain score). Results: B12 levels increased from 232.0 \u00b1 71.8 at baseline to 776.7 \u00b1 242.3 pmol\/L at follow-up, p &lt; 0.0001, in the active group but not in the control group. VPT, MNSIQ, QoL, pain score, SNCV, SNAP, and ESCF significantly improved in the active group (p &lt; 0.001, p = 0.002, p &lt; 0.0001, p &lt; 0.000, p &lt; 0.0001, p &lt; 0.0001, and p = 0.014, respectively), whereas CARTS and MNSIE improved but not significantly. MCR, MNSIQ, SNCV, SNAP, and pain score significantly deteriorated in the control group (p = 0.025, p = 0.017, p = 0.045, p &lt; 0.0001, and p &lt; 0.0001, respectively). Conclusions: The treatment of patients with DN with 1 mg of oral methylcobalamin for twelve months increased plasma B12 levels and improved all neurophysiological parameters, sudomotor function, pain score, and QoL, but it did not improve CARTS and MNSIE.<\/jats:p>","DOI":"10.3390\/nu13020395","type":"journal-article","created":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T12:20:26Z","timestamp":1611750026000},"page":"395","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":125,"title":["Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled Trial"],"prefix":"10.3390","volume":"13","author":[{"given":"Triantafyllos","family":"Didangelos","sequence":"first","affiliation":[{"name":"Diabetes Center, 1st Propaedeutic Department of Internal Medicine, Medical School, \u201cAHEPA\u201d Hospital, Aristotle University of Thessaloniki, 54621 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7094-0338","authenticated-orcid":false,"given":"Eleni","family":"Karlafti","sequence":"additional","affiliation":[{"name":"Diabetes Center, 1st Propaedeutic Department of Internal Medicine, Medical School, \u201cAHEPA\u201d Hospital, Aristotle University of Thessaloniki, 54621 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4841-1928","authenticated-orcid":false,"given":"Evangelia","family":"Kotzakioulafi","sequence":"additional","affiliation":[{"name":"Diabetes Center, 1st Propaedeutic Department of Internal Medicine, Medical School, \u201cAHEPA\u201d Hospital, Aristotle University of Thessaloniki, 54621 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Margariti","sequence":"additional","affiliation":[{"name":"Diabetes Center, 1st Propaedeutic Department of Internal Medicine, Medical School, \u201cAHEPA\u201d Hospital, Aristotle University of Thessaloniki, 54621 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9413-6368","authenticated-orcid":false,"given":"Parthena","family":"Giannoulaki","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Dietetics, University General Hospital of Thessaloniki \u2018\u2019AHEPA\u2019\u2019, 54621 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Batanis","sequence":"additional","affiliation":[{"name":"Diabetes Center, 1st Propaedeutic Department of Internal Medicine, Medical School, \u201cAHEPA\u201d Hospital, Aristotle University of Thessaloniki, 54621 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solomon","family":"Tesfaye","sequence":"additional","affiliation":[{"name":"Diabetes Research Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0584-1138","authenticated-orcid":false,"given":"K\u03bfnstantinos","family":"Kantartzis","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IV, Division of Endocrinology, Diabetology and Nephrology, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich at the University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"German Center for Diabetes Research (DZD), 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,27]]},"reference":[{"key":"ref_1","first-page":"S40","article-title":"Vitamin B12 status and peripheral neuropathy in patients with type 2 diabetes mellitus","volume":"69","author":"Khalaf","year":"2019","journal-title":"J. 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