Vitamin B12 Improves Pain Score, Quality of Life, and Neurophysiological Indices of Neuropathy in Patients with Diabetic Neuropathy

by | Jun 21, 2021 | 2021, Diabetes, Pancreatic Health, Vitamin B12, Vitamins

 Written by Angeline A. De Leon, Staff Writer. In subjects with deficient levels of vitamin B12, methylcobalamin (a form of vitamin B12) intake for one year produced significant improvement on neuropathy tests, pain scores, and self-reported quality of life.

vitamins B12Diabetic neuropathy (DN), a type of nerve damage that commonly affects the legs and feet, is prevalent in nearly 20% of diabetic patients at the time of diagnosis 1. Antiglycemic therapy aimed at strict glycemic control is the most popular approach to DN treatment, though research suggests its effects on DN progression are modest 2. Over 50% of patients with type 2 diabetes are reported to suffer from vitamin B12 deficiency 3, which has been implicated in the development of neurological disorders which resemble or may accelerate DN 4. Vitamin B12 deficiency in diabetic patients is largely attributed to metformin, an anti-diabetic medication known to reduce vitamin B12 uptake and cause vitamin B12 deficiency 5. Based on such evidence, the American Diabetes Association (ADA) advises close monitoring of vitamin B12 levels in patients with DN receiving metformin treatment 6. The effects of vitamin B12 intake in patients with DN are reported to be positive 7 but as vitamin B12 supplementation was combined with other supplements or used together with glycemic control in these studies, the pure effect of vitamin B12 in DN patients is yet unknown. Therefore, in a 2021 study 8 published in Nutrients, investigators sought to examine the clinical impact of normalizing vitamin B12 levels in diabetic patients with DN.

A prospective randomized, double-blind, placebo-controlled trial was carried out in a group of 90 diabetic patients with generalized neuropathy (mean age = 63 years) who had stable glycemic control and were receiving metformin treatment (for at least the last four years). Patients were also confirmed to have low vitamin B12 levels (less than 400 pmol/L). Subjects were randomly assigned to receive 1000 µg of methylcobalamin (form of vitamin B12) or an identical placebo once daily for 12 months. Neuropathy tests were performed at baseline and at 12-month follow-up and included measurement of sural nerve conduction velocity (SNCV), sural nerve action potential amplitude (SNAP), and vibration perception threshold (VPT), along with a number of cardiovascular autonomic reflex tests (CARTs). Sudomotor function was also assessed by using the SUDOSCAN device to measure electrochemical skin conductance in the hands (ESCH) and feet (ECSF). Finally, patients were administered the Michigan Neuropathy Screening Instrument Questionnaire (MNSIQ) and Examination (MNSIE), Diabetes Quality of Life Questionnaire (DQoL), and PAINDetect questionnaire prior to and following the 12-month intervention.

As expected, supplementation was associated with significant increases in vitamin B12 levels over the course of the study (from 232.0 +/- 71.8 to 776.7 +/- 242.3 pmol/L for the treatment group, p < 0.0001). At the end of 12 months, the vitamin B12 group also demonstrated significant improvements in VPT (p < 0.001), MNSIQ (p = 0.002), QoL (p < 0.0001), pain score (p < 0.000), SNCV (p < 0.0001), SNAP (p < 0.0001), and ECSF (p = 0.014). Improvements in CARTs and MNSIE were apparent, but not statistically significant. By comparison, for the control group, significant reductions were seen in MNSIQ (p = 0.017), SNCV (p = 0.0045), SNAP (p < 0.0001), and pain score (p < 0.0001) at the conclusion of the study.

As the first known study on the pure effect of vitamin B12 on DN, the present trial provides compelling evidence for the benefits of vitamin B12 supplementation on psychological and neurophysiological parameters in DN patients. In subjects with deficient levels of vitamin B12, methylcobalamin intake for one year produced significant improvement on neuropathy tests, pain scores, and self-reported quality of life, while control subjects showed an opposite trend. Based on this data, researchers suggest that vitamin B12 supplementation may be advisable for DN patients with vitamin B12 levels below 400 pmol/L. Key limitations of the trial relate to its limited generalizability, as the entire sample population was Caucasian, and its failure to examine the effects of supplementation in regards to the different types of DN.

Source: Didangelos T, Karlafti E, Kotzakioulafi E, et al. Vitamin B12 supplementation in diabetic neuropathy: a 1-year randomized, double-blind, placebo-controlled trial. Nutrients. 2021; 13: 395. DOI: 10.3390/nu13020395.

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

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Posted June 21, 2021.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

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