Bioavailability and Lack of Toxicity of
S-Adenosyl-L-Methionine (SAMe) in Humans

Goren JL, Stoll AL, Damico KE, Sarmiento IA, Cohen BM.
Psychopharmacology Research Laboratory,
Program for the Development of Natural
and Novel Treatments for Bipolar Disorder,
McLean Hospital, Belmont,
the Department of Psychiatry,
Harvard Medical School,
and the School of Pharmacy,
Northeastern University,
Boston, Massachusetts.
Pharmacotherapy. 2004 Nov;24(11):1501-1507


Study 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. Design. Unblinded pharmacokinetic trial. Subjects. Fifteen healthy volunteers. Setting. Clinical research unit in a psychiatric hospital. Intervention. 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. Measurements and Main 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. Conclusion. 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.

SAMe mania
Natural drugs
SAMe: efficacy
SAMe: mechanisms

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