Efficacy and Safety of the Combination of Superoxide Dismutase, Alpha Lipoic Acid, Vitamin B12, and Carnitine for 12 Months in Patients with Diabetic Neuropathy

Abstract

Aim: To investigate the efficacy of Superoxide Dismutase, Alpha Lipoic Acid, Acetyl L-Carnitine, and Vitamin B12 (B12) in one tablet in Diabetic Neuropathy (DN). Patients–methods: In this prospective, double-blind, placebo-controlled study, 85 patients with Diabetes Mellitus Type 2 (DMT2) were randomly assigned, either to receive the combination of four elements (active group, n = 43), or placebo (n = 42) for 12 months. We used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE), measured the vibration perception threshold (BIO), and Cardiovascular Autonomic Reflex Tests (CARTs). Nerve function was assessed by DPN Check [sural nerve conduction velocity (SNCV) and amplitude (SNAP)]. Pain (PS) and quality of life (QL) questionnaires were administered. Results: At follow-up, BIO, MNSIQ, QL, PAIN, and SNCV, SNAP, and B12 levels had significantly improved inactive group (p <0.001, p <0.001, p <0.001, p <0.001, p = 0.027, p = 0.031, and p <0.001 respectively), whereas the inplacebo group MCR (mean circular resultant) and PAIN deteriorated (p <0.001, p <0.001). The changes in MNSIQ, QL, SNCV, BIO, and PAIN differed significantly between groups (p <0.001, p <0.001, p = 0.031, p <0.001, and p <0.001 respectively). Conclusions: The combination of the four elements in one tablet for 12 months in patients with DMT2 improved all indices of peripheral neuropathy, including SNAP and SNCV, pain, and Quality of Life perception, except CARTs and MNSIE.

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

“…This is because vitamin B12 deficiency is commonly found in patients with DM2 and vitamin B12 deficiency may cause a variety of neurological disorders resembling or accelerating DN. Accordingly, several trials have investigated the effect of supplementation of B12 in DN [ 3 , 33 , 34 , 35 , 36 , 38 , 51 , 61 , 62 , 64 , 65 ]. Some of them reported favorable effects [ 3 , 33 , 36 ], but no one could prove a “pure” effect of B12 supplementation on improvements in peripheral nerve function.…”

“…The majority of the studies were performed in DM2 patients with poor glycemic control (HbA1c: 8–10%) [ 34 , 36 , 61 ] and reported concurrent decrease of HbA1c levels or/and body weight during follow-up [ 34 , 36 , 61 ]. In other studies, combinations of B12 with other supplements or agents, not solely B12, were given [ 3 , 33 , 34 , 36 , 38 , 51 , 61 , 62 , 64 , 65 ]. In addition, there was a great variation in these studies in terms of the baseline blood levels (150–450 pmol/L), dose (25–2000 μg), duration (from 12 to 24 weeks), molecular form (cyano-, methyl-, or hydroxocobalamin) [ 31 , 35 , 62 , 63 , 66 ], and mode of administration (orally or parenterally) of B12 [ 31 ], as well as the inclusion criteria of the study participants (without or with established DN, DPN, or painful DN) [ 3 , 33 , 34 , 36 , 38 , 51 , 61 , 62 , 64 , 65 ].…”

“…In these trials, B12 had been administered in a dose varying from 250 to 2000 μg when given orally and from 1000 to 2000 μg when given intramuscularly [ 35 , 63 , 67 , 68 ]. For instance, doses of 250 mcg cyanocobalamin for one year [ 51 ] and 1500 mg methylcobalamin for four months [ 33 ] led to improvements in neurophysiological parameters and a substantial increase of B12 levels. However, in our previous study, 250 mcg of cyanocobalamin for one year did not result in the normalization of B12 levels [ 51 ].…”

“…Age-specific values were applied [ 49 ]. For the clinical diagnosis of DPN, the MNSIQ and MNSIE scoring algorithm was used (result ≥2 for lower extremity examination, ≥7 for questionnaire, and ≥2.5 for MNSI examination were considered abnormal) [ 40 , 50 , 51 ]. The evaluation of quality of life status was assessed by the Diabetes Quality of Life Brief Clinical Inventory, a brief form of the questionnaire used in the Diabetes Control and Complications Trial (DCCT) trial [ 52 ].…”

“…The level of pain was evaluated with the PAINDetect questionnaire that is used for the identification of neuropathic components [ 53 ]. All measurements were performed according to international guidelines regarding patient preparation, i.e., hydration status, physical activity, and hypoglycemic events in the day before examination [ 4 , 5 , 51 ].…”