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S-adenosylmethionine (sam, same) is a methyl donor that is present in all living organisms. It has been used in the treatment of liver disease. Deficiencies of transmethylation processes, such as those involving SAM, have been postulated as being involved in the production of folic acid-preventable neural tube defects; however, coadministration of SAM with valproic acid in pregnant rats has not been shown to decrease the incidence of valproate-associated neural tube defects in the offspring.1 Culture of rat embryos in 0.05 mM SAM did not lead to abnormal development.2 Reproductive testing has been performed with the sulphate-p-toluene sulphonate salt of SAM.3 Doses of up to 400 mg/kg/d subcutaneously or intravenously in male and female rats did not produce adverse effects on fertility or reproductive performance. Doses of up to 40 mg/kg/d intravenously in pregnant rabbits and 400 mg/kg/d in pregnant rats did not produce abnormalities of embryofetal development, and in rats did not produce neonatal toxicity when given during lactation.
SAM has been administered to humans in the treatment of liver disease. Effectiveness of this treatment for cholestasis of pregnancy was reported by one group of clinicians after 800 mg/d given for two weeks by mouth or intravenously.4-6 The treatment was during the last trimester of pregnancy and neonatal outcome information was not given. By contrast, another group found no effectiveness of 900 mg/d intravenously for 20 days in pregnant women with cholestasis.7 Infant follow-up to three months of age was reported to be without evidence of adverse effects.
In cultured rat Leydig cells, 1.4 mM SAM increases LH/hCG binding sites and potentiates testosterone synthesis.8 An Italian study, read in abstract, used 800 mg/d for eight months in men with infertility and reported an increase in sperm motility.9 No control treatments were used and an improvement in fertility was not mentioned. v
1. Ubeda-Martin N, et al. [Morphological changes induced by valproate and its administration concomitant with folinic acid or S-adenosylmethionine in pregnant rats]. Nutr Hosp 1998;13:41-49. English abstract.
2. Seyoum G, Persaud TV. In vitro effect of S-adenosyl methionine on ethanol embryopathy in the rat. Exp Toxicol Pathol 1994;46:177-181.
3. Cozens DD, et al. Reproductive toxicity studies of ademetionine. Arzneimittelforschung 1988;38:1625-1629.
4. Frezza M, et al. Reversal of intrahepatic cholestasis of pregnancy in women after high dose S-adenosyl-L-methionine administration. Hepatology 1984;4:274-278.
5. Frezza M, et al. Prevention of S-adenosylmethionine of estrogen-induced hepatobiliary toxicity in susceptible women. Am J Gastroenterol 1988;83:1098-1102.
6. Frezza M, et al. S-Adenosylmethionine for the treatment of intrahepatic cholestasis of pregnancy. Results of a controlled clinical trial. Hepatogastroenterology 1990;379(Suppl 2):122-125.
7. Ribalta J, et al. S-Adenosyl-L-methionine in the treatment of patients with intrahepatic cholestasis of pregnancy: A randomized, double-blind, placebo-controlled study with negative results. Hepatology 1991;13:1084-1089.
8. Papadopoulos V, et al. Effects of the transmethylation inhibitor S-adenosyl-homocysteine and of the methyl donor S-adenosyl-methionine on rat Leydig cell function in vitro. J Steroid Biochem 1987;26:93-98.
9. Piacentino R, et al. [Preliminary study of the use of S adenosyl methionine in the management of male sterility]. Minerva Ginecol 1991;43:191-193. English abstract.
Copyright 2000 Reproductive Toxicology Center; used with permission.