Effect of dehydroepiandrosterone supplementation on fatty acid and hormone levels in patients with X-linked adrenoleucodystrophy.
OBJECTIVE
In X-linked adrenoleucodystrophy (X-ALD) the peroxisomal beta-oxidation of saturated very long-chain fatty acids (VLCFAs; carbon length > 22 atoms) is impaired. These fatty acids accumulate in blood and tissues, in particular in the nervous system, adrenal cortex and testis. 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 normal. In animal studies DHEA administration had a peroxisome proliferating effect and induced the expression of peroxisomal enzymes involved in the beta-oxidation of fatty acids.


METHODS
To study the effect of DHEA on fatty acids in X-ALD patients, we conducted a randomized double-blind study in which 14 men (age range 21-63 years) and one boy (12 years) received 50 mg of DHEA or placebo for 3 months, followed by a 1-month wash-out period, then 3 months of placebo or vice versa.


RESULTS
A significant rise was seen in the plasma levels of DHEA-S, Delta4-androstenedione and IGF-I. The elevated saturated VLCFAs in plasma and erythrocytes did not change. However, in erythrocytes significant decreases were found in the total amount of fatty acids, in C16:0, C18:0 and in C20:4omega-6, C22:5omega-6, C18:1omega-9, C20:1omega-9 and C20:3omega-9. In plasma, decreases were found for C18:1omega-9 and increases for C20:1omega-9.


CONCLUSIONS
Dehydroepiandrosterone supplementation for 3 months did not lower the elevated plasma levels of saturated very long-chain fatty acids in patients with X-linked adrenoleucodystrophy. Instead, a decrease in saturated and mono- and polyunsaturated fatty acids in erythrocytes and plasma was found. An increase of C20:1omega-9 was found in plasma only.
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000097:blood; D000284:Administration, Oral; D000326:Adrenoleukodystrophy / Q000097:blood / Q000188:drug therapy*; D000328:Adult; D000735:Androstenedione / Q000097:blood; D002648:Child; D003687:Dehydroepiandrosterone / Q000008:administration & dosage* / Q000097:blood; D004311:Double-Blind Method; D004912:Erythrocytes / Q000378:metabolism; D005227:Fatty Acids / Q000097:blood*; D005231:Fatty Acids, Unsaturated / Q000097:blood; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged
D000276:Adjuvants, Immunologic; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D007334:Insulin-Like Growth Factor I