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

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.

Natural history of a cohort of ABCD1 variant female carriers

“…Our results, whilst limited by the sample size, provide preliminary bases for future studies but also allow a hypothesis that clinical progression is probably due to a peculiar vulnerability of the peroxisomal system to cellular aging, resulting in dying‐back axonal degeneration. These findings thus lead to a reconsideration of the clinical approach to this condition, providing early diagnosis and possibly appropriate therapeutic options . Moreover, the ABCD1 heterozygous state should be considered as a suitable paradigm to explore the contribution of peroxisomes in neurodegeneration pathways.…”

Dietary Conjugated Linoleic Acid-Enriched Cheeses Influence the Levels of Circulating n-3 Highly Unsaturated Fatty Acids in Humans

“…The activation of PPAR-α with the inhibition of DNL and the increase of the n-3 HUFA score may, at least in part, explain the anti-neuroinflammatory effects exerted by CLA in X-linked adrenoleucodystrophy, a genetic disorder characterized by an impaired peroxisomal beta-oxidation [ 58 , 59 ], confirming that PPAR-α activation can also play an important role in the prevention of neurodegenerative pathologies [ 60 , 61 ]. The development of innovative systems in livestock breeding aimed at increasing milk CLA content would produce dairy products rich in CLA, which, if included into a balanced diet, may contribute to the prevention of some of the major chronic pathologies [ 62 ].…”

Sheep cheese naturally enriched in α-linolenic, conjugated linoleic and vaccenic acids improves the lipid profile and reduces anandamide in the plasma of hypercholesterolaemic subjects

“…Details of the methodology regarding the characterisation of conjugated diene unsaturated fatty acids in both reference and biological samples have been published (38) . Measurements of SFA and further confirmation of trans-monoenes and CLA isomers were obtained by GC and silver ion HPLC as described in Cappa et al (40) and Ip et al (41) . Determination of anandamide (AEA) and 2-arachidonoylglycerol, the HPUFA n-6:n-3 ratio and the n-3 HPUFA score were performed as described in Piscitelli et al (42) and Stark (43) .…”