Biomarkers of response to alpha-lipoic acid ± palmitoiletanolamide treatment in patients with diabetes and symptoms of peripheral neuropathy

Endocrine. 2019 Nov;66(2):178-184. doi: 10.1007/s12020-019-01917-w. Epub 2019 Apr 4.

Abstract

Purpose: To evaluate the effect of oral alpha-lipoic acid (ALA) ± palmitoyl-ethanolamide (PEA) on neuropathic symptoms in patients with diabetic peripheral neuropathy (DPN) and to identify factors related to the efficacy of the treatment.

Methods: This is a retrospective observational pilot study evaluating 49 patients with diabetes and positive Neuropathy Symptoms Score (NSS). Clinical and biochemical variables, including NSS, were compared between untreated patients and patients treated with oral 600 mg/day ALA ± 600 mg/day PEA at baseline (first occurrence of NSS ≥ 3) and at least 2 months after baseline. Number of days between treatment initiation and symptoms' relief and related factors were also investigated.

Results: Thirty subjects were treated with ALA ± PEA and 19 subjects did not receive any specific treatment for neuropathy symptoms. Follow-up visits occurred after 98 ± 46 days. NSS significantly decreased in patients treated with ALA ± PEA (5.4 ± 1.3 at baseline vs. 1.7 ± 2.4 at follow-up, p < 0.001), but not in untreated patients (p = 0.164). Subjects treated with ALA ± PEA reported a mean time from treatment initiation to symptoms' relief of 18.4 ± 9.0 days. The number of days of treatment needed for symptoms' relief was inversely related to HDL-cholesterol levels (r = -0.503, p = 0.010) and to eGFR (r = -0.428, p = 0.033), whereas there was no significant relationship between time to symptoms' relief and age, HbA1c, lipid profile and the severity of symptoms at baseline.

Conclusions: This study documents that oral administration of ALA ± PEA helps in controlling neuropathy symptoms in diabetes. Moreover, our data show that higher HDL-c levels and better renal function are associated to a faster therapeutic effect, suggesting them as biomarkers of response to therapy with ALA ± PEA.

Keywords: Alpha-lipoic acid; Diabetic neuropathy; PEA, HDL; Palmitoiletanolamide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amides
  • Biomarkers / blood
  • Cholesterol, HDL / blood*
  • Cholesterol, LDL / blood*
  • Diabetic Neuropathies / blood
  • Diabetic Neuropathies / diagnosis
  • Diabetic Neuropathies / drug therapy*
  • Ethanolamines / therapeutic use*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Palmitic Acids / therapeutic use*
  • Pilot Projects
  • Retrospective Studies
  • Severity of Illness Index
  • Thioctic Acid / therapeutic use*
  • Treatment Outcome
  • Triglycerides / blood*

Substances

  • Amides
  • Biomarkers
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Ethanolamines
  • Palmitic Acids
  • Triglycerides
  • palmidrol
  • Thioctic Acid