Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled Trial

Aim: To investigate the effect of normalizing vitamin B12 (B12) levels with oral B12 (methylcobalamin) 1000 μg/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...

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Main Authors: Triantafyllos Didangelos, Eleni Karlafti, Evangelia Kotzakioulafi, Eleni Margariti, Parthena Giannoulaki, Georgios Batanis, Solomon Tesfaye, Kοnstantinos Kantartzis
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/13/2/395
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author Triantafyllos Didangelos
Eleni Karlafti
Evangelia Kotzakioulafi
Eleni Margariti
Parthena Giannoulaki
Georgios Batanis
Solomon Tesfaye
Kοnstantinos Kantartzis
author_facet Triantafyllos Didangelos
Eleni Karlafti
Evangelia Kotzakioulafi
Eleni Margariti
Parthena Giannoulaki
Georgios Batanis
Solomon Tesfaye
Kοnstantinos Kantartzis
author_sort Triantafyllos Didangelos
collection DOAJ
description Aim: To investigate the effect of normalizing vitamin B12 (B12) levels with oral B12 (methylcobalamin) 1000 μg/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 ± 71.8 at baseline to 776.7 ± 242.3 pmol/L at follow-up, <i>p</i> < 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 (<i>p</i> < 0.001, <i>p</i> = 0.002, <i>p</i> < 0.0001, <i>p</i> < 0.000, <i>p</i> < 0.0001, <i>p</i> < 0.0001, and <i>p</i> = 0.014, respectively), whereas CARTS and MNSIE improved but not significantly. MCR, MNSIQ, SNCV, SNAP, and pain score significantly deteriorated in the control group (<i>p</i> = 0.025, <i>p</i> = 0.017, <i>p</i> = 0.045, <i>p</i> < 0.0001, and <i>p</i> < 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.
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spelling doaj.art-655f53aa69b44b55869e5f657093cd272023-12-03T14:54:29ZengMDPI AGNutrients2072-66432021-01-0113239510.3390/nu13020395Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled TrialTriantafyllos Didangelos0Eleni Karlafti1Evangelia Kotzakioulafi2Eleni Margariti3Parthena Giannoulaki4Georgios Batanis5Solomon Tesfaye6Kοnstantinos Kantartzis7Diabetes Center, 1st Propaedeutic Department of Internal Medicine, Medical School, “AHEPA” Hospital, Aristotle University of Thessaloniki, 54621 Thessaloniki, GreeceDiabetes Center, 1st Propaedeutic Department of Internal Medicine, Medical School, “AHEPA” Hospital, Aristotle University of Thessaloniki, 54621 Thessaloniki, GreeceDiabetes Center, 1st Propaedeutic Department of Internal Medicine, Medical School, “AHEPA” Hospital, Aristotle University of Thessaloniki, 54621 Thessaloniki, GreeceDiabetes Center, 1st Propaedeutic Department of Internal Medicine, Medical School, “AHEPA” Hospital, Aristotle University of Thessaloniki, 54621 Thessaloniki, GreeceDepartment of Nutrition and Dietetics, University General Hospital of Thessaloniki ‘’AHEPA’’, 54621 Thessaloniki, GreeceDiabetes Center, 1st Propaedeutic Department of Internal Medicine, Medical School, “AHEPA” Hospital, Aristotle University of Thessaloniki, 54621 Thessaloniki, GreeceDiabetes Research Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF, UKDepartment of Internal Medicine IV, Division of Endocrinology, Diabetology and Nephrology, University of Tübingen, 72076 Tübingen, GermanyAim: To investigate the effect of normalizing vitamin B12 (B12) levels with oral B12 (methylcobalamin) 1000 μg/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 ± 71.8 at baseline to 776.7 ± 242.3 pmol/L at follow-up, <i>p</i> < 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 (<i>p</i> < 0.001, <i>p</i> = 0.002, <i>p</i> < 0.0001, <i>p</i> < 0.000, <i>p</i> < 0.0001, <i>p</i> < 0.0001, and <i>p</i> = 0.014, respectively), whereas CARTS and MNSIE improved but not significantly. MCR, MNSIQ, SNCV, SNAP, and pain score significantly deteriorated in the control group (<i>p</i> = 0.025, <i>p</i> = 0.017, <i>p</i> = 0.045, <i>p</i> < 0.0001, and <i>p</i> < 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.https://www.mdpi.com/2072-6643/13/2/395diabetic neuropathyvitamin B12SUDOSCANmetformindiabetic footdiabetes mellitus
spellingShingle Triantafyllos Didangelos
Eleni Karlafti
Evangelia Kotzakioulafi
Eleni Margariti
Parthena Giannoulaki
Georgios Batanis
Solomon Tesfaye
Kοnstantinos Kantartzis
Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled Trial
Nutrients
diabetic neuropathy
vitamin B12
SUDOSCAN
metformin
diabetic foot
diabetes mellitus
title Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled Trial
title_full Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled Trial
title_fullStr Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled Trial
title_full_unstemmed Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled Trial
title_short Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled Trial
title_sort vitamin b12 supplementation in diabetic neuropathy a 1 year randomized double blind placebo controlled trial
topic diabetic neuropathy
vitamin B12
SUDOSCAN
metformin
diabetic foot
diabetes mellitus
url https://www.mdpi.com/2072-6643/13/2/395
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