title: The safety and efficacy of oral docosahexaenoic acid supplementation for the treatment of primary sclerosing cholangitis - a pilot study.
abstract: BACKGROUND
  Primary sclerosing cholangitis (PSC) is characterised by progressive inflammatory and fibrotic destruction of the biliary ducts. There are no effective medical therapies and presently high dose ursodeoxycholic acid is no longer recommended due to significant adverse events in a recent clinical trial. Cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction is associated with PSC in both children and adults. Since CFTR dysfunction leads to altered fatty acid metabolism, specifically reduced docosahexaenoic acid (DHA), we hypothesised that DHA supplementation might be an effective therapy for patients with PSC.
  
  
  OBJECTIVE
  To determine the safety and efficacy of oral DHA supplementation for the treatment of PSC.
  
  
  METHODS
  We conducted a 12 month open-label pilot study to evaluate safety of oral DHA and its effects on serum alkaline phosphatase as a primary outcome measure in 23 patients with PSC. DHA was administered orally at 800 mg twice per day. Secondary outcomes included changes in other liver function tests and fibrosis biomarkers.
  
  
  RESULTS
  A 1.7-fold increase in serum DHA levels was observed with supplementation. The mean alkaline phosphatase level (±S.E.) at baseline was 357.8 ± 37.1 IU compared to 297.1 ± 23.7 IU (P < 0.05) after 12 months of treatment. There were no changes in other liver function tests and fibrosis biomarkers. No adverse events were reported.
  
  
  CONCLUSIONS
  Oral DHA supplementation is associated with an increase in serum DHA levels and a significant decline in alkaline phosphatase levels in patients with PSC. These data support the need for a rigorous trial of DHA therapy in PSC.
authors: Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors: C R
authors: CR
authors: Martin
authors: P G
authors: PG
authors: Blanco
authors: J C
authors: JC
authors: Keach
authors: J L
authors: JL
authors: Petz
authors: M M
authors: MM
authors: Zaman
authors: K R
authors: KR
authors: Bhaskar
authors: J E
authors: JE
authors: Cluette-Brown
authors: S
authors: S
authors: Gautam
authors: S
authors: S
authors: Sheth
authors: N H
authors: NH
authors: Afdhal
authors: K D
authors: KD
authors: Lindor
authors: S D
authors: SD
authors: Freedman
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D001652:Bile Ducts / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D015209:Cholangitis, Sclerosing / Q000188:drug therapy*; D019587:Dietary Supplements / Q000009:adverse effects*; D004281:Docosahexaenoic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects
chemical_list: D015415:Biomarkers; D004281:Docosahexaenoic Acids; D000469:Alkaline Phosphatase