Efficacy and Safety of the Combination of Palmitoylethanolamide, Superoxide Dismutase, Alpha Lipoic Acid, Vitamins B12, B1, B6, E, Mg, Zn and Nicotinamide for 6 Months in People with Diabetic Neuropathy

Nutrients. 2024 Sep 10;16(18):3045. doi: 10.3390/nu16183045.

Abstract

Aim: To investigate the efficacy of Palmitoylethanolamide (PEA, 300 mg), Superoxide Dismutase (SOD, 70 UI), Alpha Lipoic Acid (ALA, 300 mg), vitamins B6 (1.5 mg), B1 (1.1 mg), B12 (2.5 mcg), E (7.5 mg), nicotinamide (9 mg), and minerals (Mg 30 mg, Zn 2.5 mg) in one tablet in people with Diabetic Neuropathy (DN).

Patients-methods: In the present pilot study, 73 people (age 63.0 ± 9.9 years, 37 women) with type 2 Diabetes Mellitus (DMT2) (duration 17.5 ± 7.3 years) and DN were randomly assigned to receive either the combination of ten elements (2 tablets/24 h) in the active group (n = 36) or the placebo (n = 37) for 6 months. We used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE), measured vibration perception threshold (VPT) with biothesiometer, and Cardiovascular Autonomic Reflex Tests (CARTs). Nerve function was assessed by DPN Check [sural nerve conduction velocity (SNCV) and amplitude (SNAP)]. Sudomotor function was assessed with SUDOSCAN, which measures electrochemical skin conductance in hands and feet (ESCH and ESCF). Pain score (PS) was assessed with Pain DETECT questionnaire. Quality of life was assessed by questionnaire.

Results: In the active group, there was a large improvement of pain (PS from 20.9 to 13.9, p < 0.001). There was also a significant improvement of vitamin B12 (B12) levels, MNSIQ, SNCV, VPT, and ESCF (222.1 vs. 576.3 pg/ mL, p < 0.001; 6.1 vs. 5.9, p = 0.017; 28.8 vs. 30.4, p = 0.001; 32.1 vs. 26.7, p = 0.001; and 72.2 vs. 74.8, p < 0.001 respectively). In the placebo group, neither pain (21.6 vs. 21.7, p = 0.870) or any other aforementioned parameters changed significantly, and MNSIE worsened (2.9 vs. 3.4, p < 0.001). As a result, changes from baseline to follow-up in pain, B12 levels, VPT, and MNSIQ differed significantly between the two groups (p < 0.001, 0.025, 0.009, and <0.001, respectively). CARTs, SNAP, ESCH did not significantly change in either of the two groups.

Conclusions: The combination of the ten elements in one tablet for 6 months at a daily dose of two tablets in people with DN significantly improves pain, vibration perception threshold, and B12 levels.

Keywords: diabetes mellitus type 2; diabetic neuropathy; neuropathic pain; pain; painful diabetic neuropathy; supplements; vitamin supplementation.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Amides* / administration & dosage
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetic Neuropathies* / drug therapy
  • Dietary Supplements
  • Double-Blind Method
  • Ethanolamines* / administration & dosage
  • Female
  • Humans
  • Male
  • Middle Aged
  • Niacinamide* / administration & dosage
  • Niacinamide* / therapeutic use
  • Palmitic Acids* / administration & dosage
  • Pilot Projects
  • Superoxide Dismutase*
  • Thiamine / administration & dosage
  • Thioctic Acid* / administration & dosage
  • Treatment Outcome
  • Vitamin B 12* / administration & dosage
  • Vitamin B 6* / administration & dosage
  • Vitamin E / administration & dosage
  • Zinc / administration & dosage

Substances

  • Vitamin B 12
  • palmidrol
  • Thioctic Acid
  • Vitamin B 6
  • Palmitic Acids
  • Ethanolamines
  • Superoxide Dismutase
  • Niacinamide
  • Amides
  • Zinc
  • Vitamin E
  • Thiamine

Grants and funding

The supplement: both the active (Epineuron) and the placebo, were prepared and provided to the study from Pharma Unimedis, Greece (Pharma Unimedis, Athens, Greece), which had no further involvement in the study’s planning, execution, or data analysis.