Effect of Dehydroepiandrosterone (DHEA) Supplementation on Fatty Acid and Hormone Levels in Patients with X-linked Adrenoleukodystrophy
In X-linked adrenoleukodystrophy (X-ALD) the peroxisomal ß-oxidation of saturated very long chain fatty acids (VLCFA-carbon length >22 atoms) is impaired. These fatty acids accumulate in blood and tissues, in particular in the nervous system, adrenal cortex and testes. Most patients have a primary adrenocortical insufficiency with low levels of Cortisol and dehydroepiandrosterone (DHEA) and its sulphate ester (DHEA-S) collectively called DHEA(S). Surprisingly, very low plasma levels of DHEA(S) may be found when plasma Cortisol and ACTH levels are still normal (Assies et al 1998). In animal studies DHEA-administration had a peroxisome proliferator effect and induced the expression of peroxisomal enzymes involved in the ß-oxidation of fatty acids (Waxman,1996, Depreter et al.). To study the effect of DHEA on fatty acids in X-ALD patients we conducted a randomised double blind study in which fourteen men, age range 21-63 years and one boy (12 year), received 50 mg of DHEA or placebo for 3 months, followed by a one month wash-out period, then 3 month of placebo or vice versa.