title: Bioavailability and lack of toxicity of S-adenosyl-L-methionine (SAMe) in humans.
abstract: OBJECTIVE
  To determine if S-adenosyl-L-methionine (SAMe), a widely used dietary supplement with antidepressant properties, is significantly bioavailable, and whether toxic methylated compounds are produced with oral SAMe administration in humans. Serum homocysteine levels were also measured since alterations in these levels have been theorized in association with SAMe.
  
  
  METHODS
  Unblinded pharmacokinetic trial.
  
  
  METHODS
  Fifteen healthy volunteers.
  
  
  METHODS
  Clinical research unit in a psychiatric hospital.
  
  
  METHODS
  Subjects received oral SAMe for 4 weeks; the dosage was titrated over 5 days to 1600 mg/day. Serum levels of SAMe, toxic methylated compounds (methanol, formaldehyde, and formic acid), and homocysteine were measured at baseline and at weeks 2 and 4. At baseline, a structured clinical interview for axis I disorders (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) was completed to assess for any undiagnosed psychiatric disorders. Mood was rated at baseline and at weeks 2 and 4 using the Zung Depression Rating Scale, Young Mania Rating Scale, Montgomery-Asberg Depression Rating Scale, Clinical Global Impression Scale, and the Global Assessment of Function Scale.
  
  
  RESULTS
  After oral administration, SAMe levels were significantly elevated. Slight, likely insignificant, elevations in serum formaldehyde levels were detected in three subjects. No subject exhibited elevated homocysteine levels during SAMe treatment. One subject developed a transient mixed manic state with suicidal ideation within 2 weeks of starting SAMe; she recovered fully within 3 days of discontinuing the compound.
  
  
  CONCLUSIONS
  Oral dosages of 1600 mg/day of SAMe appear to be significantly bioavailable and nontoxic, at least regarding toxic methylated metabolites and homocysteine. However, the risk of mania in vulnerable individuals remains a serious concern.
authors.affiliation: Psychopharmacology Research Laboratory, Program for the Development of Natural and Novel Treatments for Bipolar Disorder, McLean Hospital, Belmont, Massachusetts, USA.yahbooboo@hotmail.com
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Gören
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Stoll
authors.forename: Karen E
authors.initials: KE
authors.lastname: Damico
authors.forename: Ingrid A
authors.initials: IA
authors.lastname: Sarmiento
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Cohen
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D001714:Bipolar Disorder / Q000139:chemically induced; D005260:Female; D005557:Formaldehyde / Q000097:blood; D005561:Formates / Q000097:blood; D006710:Homocysteine / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D012436:S-Adenosylmethionine / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D005561:Formates; D006710:Homocysteine; C030544:formic acid; D005557:Formaldehyde; D012436:S-Adenosylmethionine