Effect of dehydroepiandrosterone supplementation on fatty acid and hormone levels in patients with X-linked adrenoleucodystrophy

Clin Endocrinol (Oxf). 2003 Oct;59(4):459-66. doi: 10.1046/j.1365-2265.2003.01868.x.


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.

Patients and design: 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / blood
  • Administration, Oral
  • Adrenoleukodystrophy / blood
  • Adrenoleukodystrophy / drug therapy*
  • Adult
  • Androstenedione / blood
  • Child
  • Dehydroepiandrosterone / administration & dosage*
  • Dehydroepiandrosterone / blood
  • Double-Blind Method
  • Erythrocytes / metabolism
  • Fatty Acids / blood*
  • Fatty Acids, Unsaturated / blood
  • Humans
  • Insulin-Like Growth Factor I / analysis
  • Male
  • Middle Aged


  • Adjuvants, Immunologic
  • Fatty Acids
  • Fatty Acids, Unsaturated
  • Androstenedione
  • Dehydroepiandrosterone
  • Insulin-Like Growth Factor I