Effect of different doses of S-adenosyl-L-methionine (SAMe) on nicotinic acid-induced hyperbilirubinaemia in Gilbert's syndrome

Abstract

S-adenosyl-L-methionine (SAMe) has been shown to increase hepatocyte membrane fluidity thereby relieving signs of oestrogen-induced cholestasis. S-adenosyl-L-methionine might therefore prove effective in improving the efficiency of the transport of organic anions such as nicotinic acid (NA) and bilirubin which is impaired in Gilbert's syndrome (GS). In this study the effects on the metabolization rate of NA and bilirubin of two dosages of SAMe were evaluated in respect to placebo in ten male inpatients (mean age 24 years, range 16–31) with GS. Each patient received both SAMe (800 and 200 mg/day, respectively) and placebo treatment i.v. over a period of 10 days. The NA test (5.9 μmol/kg b.w. i.v.) was carried out in the same volunteers after each treatment. Unconjugated bilirubin (UCB) levels were significantly lower (p<0.01) after 800 mg/day SAMe than after placebo while the lower dosage of SAMe did not affect UCB values. The bilirubin time curve concentration, expressed as area under the curve (AUC), was significantly reduced (p<0.01) after 800 mg SAMe in comparison with the values obtained after placebo and 200 mg SAMe. Also plasma NA half-life was significantly reduced (p<0.01) by the higher dose of SAMe in respect to placebo and not by the lower dose.

Key Words:

• bilirubin
• bilitranslocase
• Gilbert's syndrome
• nicotinic acid
• s-adenosyl-L-methionine