A Mixture of Oleic, Erucic and Conjugated Linoleic Acids Modulates Cerebrospinal Fluid Inflammatory Markers and Improve Somatosensorial Evoked Potential in X-linked Adrenoleukodystrophy Female Carriers

J Inherit Metab Dis. 2012 Sep;35(5):899-907. doi: 10.1007/s10545-011-9432-3. Epub 2011 Dec 22.

Abstract

X-linked adrenoleukodystrophy is a rare inherited demyelinating disorder characterized by an abnormal accumulation of very long chain fatty acids, mainly hexacosanoic acid (26:0), due to a mutation of the gene encoding for a peroxisomal membrane protein. The only available, and partially effective, therapeutic treatment consists of dietary intake of a 4:1 mixture of triolein and trierucin, called Lorenzo's oil (LO), targeted to inhibit the elongation of docosanoic acid (22:0) to 26:0. In this study we tested whether, besides inhibiting elongation, an enhancement of peroxisomal beta oxidation induced by conjugated linoleic acid (CLA), will improve somatosensory evoked potentials and modify inflammatory markers in adrenoleukodystrophy females carriers. We enrolled five heterozygous women. They received a mixture of LO (40 g/day) with CLA (5 g/day) for 2 months. The therapeutic efficacy was evaluated by the means of plasma levels of 26:0, 26:0/22:0 ratio, modification of cerebrospinal fluid (CSF) inflammatory markers and somatosensory evoked potentials. Changes of fatty acid profile, and in particular CLA incorporation, were also evaluated in CSF and plasma. The results showed that CLA promptly passes the blood brain barrier and the mixture was able to lower both 26:0 and 26:0/22:0 ratio in plasma. The mixture improved somatosensory evoked potentials, which were previously found unchanged or worsened with dietary LO alone, and reduced IL-6 levels in CSF in three out of five patients. Our data suggest that the synergic activity of CLA and LO, by enhancing peroxisomal beta-oxidation and preventing 26:0 formation, improves the somatosensory evoked potentials and reduces neuroinflammation.

MeSH terms

  • Adrenoleukodystrophy / cerebrospinal fluid*
  • Adrenoleukodystrophy / drug therapy*
  • Adrenoleukodystrophy / metabolism
  • Adrenoleukodystrophy / physiopathology
  • Biomarkers / metabolism
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism
  • Drug Combinations
  • Erucic Acids / therapeutic use*
  • Evoked Potentials, Somatosensory / drug effects*
  • Fatty Acids / metabolism
  • Female
  • Heterozygote
  • Humans
  • Inflammation / cerebrospinal fluid
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation Mediators / cerebrospinal fluid*
  • Interleukin-6 / metabolism
  • Linoleic Acids, Conjugated / therapeutic use*
  • Lipid Metabolism / drug effects
  • Middle Aged
  • Oleic Acid / therapeutic use*
  • Oxidation-Reduction / drug effects
  • Triolein / therapeutic use

Substances

  • Biomarkers
  • Drug Combinations
  • Erucic Acids
  • Fatty Acids
  • Inflammation Mediators
  • Interleukin-6
  • Linoleic Acids, Conjugated
  • Lorenzo's oil
  • erucic acid
  • Triolein
  • Oleic Acid