Professional Documents
Culture Documents
Advertisement
Search
Log in
Drug Evaluation
Published: 27 October 2012
S-Adenosyl-L-Methionine
A Review of its Pharmacological Properties and Therapeutic Potential in Liver Dysfunction and Affective
Disorders in Relation to its Physiological Role in Cell Metabolism
Heather A. Friedel 1,
Karen L. Goa1 &
Paul Benfield1
Drugs
volume 38, pages 389–416 (1989)Cite this article
62 Accesses
161 Citations
6 Altmetric
Metrics details
Summary
Synopsis
S-Adenosyl-L-methionine (SAMe) is a naturally occurring molecule distributed to virtually all body tissues and
fluids. It is of fundamental importance in a number of biochemical reactions involving enzymatic
transmethylation, contributing to the synthesis, activation and/or metabolism of such compounds as hormones,
neurotransmitters, nucleic acids, proteins, phospholipids and certain drugs. The administration of a stable salt of
SAMe, either orally or parenterally, has been shown to restore normal hepatic function in the presence of
various chronic liver diseases (including alcoholic and non-alcoholic cirrhosis, oestrogen-induced and other
forms of cholestasis), to prevent or reverse hepatotoxicity due to several drugs and chemicals such as alcohol,
paracetamol (acetaminophen), steroids and lead, and to have antidepressant properties. In all of these studies
https://link.springer.com/article/10.2165%2F00003495-198938030-00004 1/32
11/30/21, 3:08 PM S-Adenosyl-L-Methionine | SpringerLink
SAMe has been very well tolerated, a finding of great potential benefit given the well-known adverse effects of
tricyclic antidepressants with which it has been compared in a few trials.
Thus, with its novel mechanisms of action and good tolerability, SAMe is an interesting new therapeutic agent
in several diverse disease conditions, but its relative value remains to be determined in appropriate comparisons
with other treatment modalities in current use.
Release of methyl groups from the SAMe molecule results in activation of the transsulphuration pathway
leading to the formation of glutathione, the main cellular antioxidant responsible for the detoxification of
various compounds, including lead and paracetamol. Thus, regulation of the transsulphuration pathway is an
important effect and one which may be responsible for its beneficial action on drug-and chemical-induced liver
disease.
The almost universal distribution of SAMe in body tissues and its complex role in metabolic processes, all of
which depend in some way on methylation reactions, complicate the complete characterisation of its effects on
cellular biochemistry. As a result the mechanism of its actions in various diverse disease states remains
speculative.
The role of SAMe in transmethylation reactions and as a precursor of sulphur-containing compounds via the
transsulphuration pathway is fundamentally important in the liver, as both pathways have been shown to be
abnormal in the presence of liver disease. In the presence of cirrhosis, methionine metabolism is decreased, and
the activities of S-adenosyl-methionine synthetase and phospholipid methyltransferase are reduced, possibly
leading to lessened production of sulphated compounds and phosphatidylcholine. Levels of the important thiol
compounds glutathione and cysteine are reduced in plasma.
Various animal models have been used to demonstrate the protective effect of SAMe against intrahepatic
cholestasis induced by a range of compounds, including oestrogen. The mechanism of action of SAMe in
oestrogen-induced cholestasis appears to be via increased enzyme activity and fluidity of liver plasma
membranes, and maintenance of phospholipid activity in bile salt transport systems. Preliminary findings of a
preventative effect of SAMe in women with oestrogen-induced cholestasis have been augmented by results of
small therapeutic trials (see below).
Acute toxicity studies in animals reveal that SAMe can prevent mortality induced by paracetamol
(acetaminophen) and acute and chronic lead poisoning. Some success has been achieved with the use of SAMe
in treating patients with lead poisoning (see below). Maintenance of glutathione stores is instrumental in the
prevention by SAMe of hepatotoxicity due to these agents.
SAMe administered to rats and baboons subjected to chronic ethanol ingestion has been shown to maintain or
prevent depletion of glutathione levels, to normalise mitochondrial enzyme activity, and to prevent production
of acetaldehyde and deposition of fat in the liver. In healthy volunteers, plasma concentrations of ethanol and
acetaldehyde were significantly lower when SAMe was ingested concomitantly with ethanol.
https://link.springer.com/article/10.2165%2F00003495-198938030-00004 2/32
11/30/21, 3:08 PM S-Adenosyl-L-Methionine | SpringerLink
SAMe has been shown in animals and humans to be distributed to the brain where it stimulates the activity of
dopaminergic and serotonergic pathways, probably through its involvement in transmethylation processes.
Levels of SAMe, and of 5-hydroxy indoleacetic acid (5HIAA) and homovanillic acid, increase in the
cerebrospinal fluid of humans after administration of SAMe. The interplay of folate and SAMe pathways in
influencing mood is a topic of considerable study, with recent work linking red cell folate levels to levels of
5HIAA in cerebrospinal fluid. Reductions in S-adenosyl-methionine syntlietase and phosphatidylcholine in
erythrocytes of depressed patients suggest a disruption of SAMe-dependent pathways, and form the basis for the
use of SAMe in depressed patients (see below).
SAMe has been shown invitroto enhance ATP levels in erythrocytes, enabling restoration of cell shape and
conservation of deformability. Invivo, blood viscosity was reduced following injection of SAMe.
Pharmacokinetic Properties
Limited trials in healthy volunteers have demonstrated very low bioavailability after oral administration of
SAMe, indicative of a significant first-pass effect and rapid metabolism in the liver. Peak plasma concentrations
obtained with an enteric-coated tablet formulation are dose related, with a peak plasma concentration of 0.5 to 1
mg/L achieved 3 to 5 hours after single doses in the range of 400 to 1000mg.
Single intravenous doses of SAMe (100 and 500mg) have yielded volumes of distribution of 0.41 and 0.44
L/kg, respectively. Plasma protein binding is 5% or less. The rate of distribution to all body tissues is related to
their degree of vascularity and blood flow. SAMe crosses the blood-brain barrier, with slow accumulation in the
cerebrospinal fluid. Animal data suggest that exogenously administered SAMe follows the same metabolic
pathways as the endogenous compound, namely, transmethylation, transsulphuration and decarboxylation. By
24 hours after intravenous administration of SAMe 100 or 500mg in healthy volunteers, 34% and 40% of
unchanged drug, respectively, had appeared in urine. Urinary excretion of an oral 200mg dose of SAMe has
been reported as 15.5% in 48 hours with faeces containing 23.5% at 72 hours. The remainder was probably
incorporated into stable cellular pools. The half-life of SAMe in healthy volunteers was 80 to 100 minutes and
121 ininutes in a small group of patients with chronic liver disease.
Trials in small numbers of patients with various types of chronic liver disease, including biliary or alcoholic
cirrhosis, hepatitis or drug-induced cholestasis, have confirmed the short term effect of SAMe (intravenously or
orally) relative to placebo in normalising measures of liver function (e.g. plasma levels of aspartate
aminotransferase, γ-glutamyl transpeptidase, alkaline phosphatase, cysteine, taurine and methionine). Patients
with chronic lead poisoning have shown reversal of liver enzyme abnormalities after SAMe therapy. Moreover,
severe pruritus has been ameliorated in patients with cholestasis of diverse aetiology.
Of interest is the apparent ability of SAMe, when given concomitantly, to protect against hepatic dysfunction
caused by other drugs, including steroids, certain anticon-vulsants, and tricyclic antidepressants, paracetamol
and alcohol. SAMe was effective in normalising biochemical parameters in small groups of patients with
metabolic disorders of bilirubin and porphyrin metabolism, such as Gilbert’s syndrome and infantile porphyria
cutanea tarda.
https://link.springer.com/article/10.2165%2F00003495-198938030-00004 3/32
11/30/21, 3:08 PM S-Adenosyl-L-Methionine | SpringerLink
reduced, especially in suicidal patients. Furthermore SAMe treatment was well tolerated, an asset in patients
who experience significant adverse effects from tricyclic antidepressant therapy. The relative efficacy of SAMe
administered orally should be pursued in longer term trials.
Adverse Effects
SAMe is very well tolerated. At oral doses of up to 1600mg daily no adverse effects have been noted other than
occasional mild gastrointestinal effects. In a study of 20,641 patients with osteoarthritis the tolerability was
assessed as good to very good in 87% of patients, the withdrawal rate being 5.2%, primarily early in treatment
when doses were highest. In depressed patients tolerability was also good, with only a few patients developing
anxiety. However, the transition from depression to hypomania was noted in some patients with bipolar illness.
Dosage
The recommended daily dose of SAMe for the treatment of liver disorders, such as cholestasis, is 800mg
parenterally or 1600mg orally. For parenteral administration in depressive illness 200 to 400 mg/day should be
given for 15 to 20 days. Oral therapy is in the dose range 400 to 1600 mg/day.
Access options
39,95 €
Price includes VAT (India)
References
1. Adachi Y, Nanno T, Kanbe A, Inufusa H, Yamashita M, et al. The effects of S-adenosylmethionine on
intrahepatic cholestasis. Japanese Archives of Internal Medicine 33: 185–192, 1986
Google Scholar
https://link.springer.com/article/10.2165%2F00003495-198938030-00004 4/32
11/30/21, 3:08 PM S-Adenosyl-L-Methionine | SpringerLink
PubMed
CAS
Google Scholar
3. Agnoli A, Martucci N, Manna V. On the antidepressant effect of SAMe: clinical and pharmaco-EEG
study with SAMe alone and in association with a beta-2 stimulant drug, phenoterole. Clinical
Neuropharmacology 7 (Suppl. 1): 104–105, 1984
Google Scholar
Google Scholar
5. Alvarez E. SAMe and depression. In Mato (Ed.) 1st Conference on biomedical pharmacological and
clinical aspects of transmethylation, pp. 107–114, Spain, 1986
Google Scholar
6. Alvarez E, Udina C, Guillamat R. Shortening of latency period in depressed patients treated with SAM
and other antidepressant drugs. Cell Biology Reviews S1: 103–110, 1987
Google Scholar
Google Scholar
8. Arias IM. Ion transport into and out of the liver. In Keppler D, Popper H, Bianchi L, et al. (Eds)
Mechanisms of hepatocyte injury and death, pp 49–56, MTP Press, Lancaster, UK, 1983
Google Scholar
9. Arias IM. Mechanisms and consequences of ion transport in the liver. In Popper H, Schaffner F (Eds)
Progress in liver diseases, vol. III, pp. 145–159, Grune & Stratton Inc, Orlando, USA, 1986
Google Scholar
Google Scholar
PubMed
CAS
Google Scholar
12. Baldessarini RJ, Kopin IJ. S-Adenosyl-L-methionine in brain and other tissues. Journal of
Neurochemistry 13: 769–777, 1966
PubMed
CAS
Google Scholar
13. Barber JR, Morimoto BH, Brunauer LS, Clarke S. Metabolism of S-adenosyl-L-methionine in intact
human erythrocytes. Biochimica et Biophysica Acta 887: 361–372, 1986
https://link.springer.com/article/10.2165%2F00003495-198938030-00004 5/32
11/30/21, 3:08 PM S-Adenosyl-L-Methionine | SpringerLink
Google Scholar
14. Batlle AM Del C, Paredes SR, Fukuda H, Kozicki PA, Rossetti MV. S-adenosyl-L-methionine, a
mechanism for its action on lead mobilisation and disposal in lead poisoning. Biochemical Archives 2:
293–303, 1986
Google Scholar
15. Batlle AM Del C, Stella AM, De Kaminsky AR, Kaminsky C, Mariano HG. Two cases of infantile
porphyria cutanea tarda: successful treatment with oral S-adenosyl-L-methionine and low-dose oral
chloroquine. British Journal of Dermatology 116: 407–415, 1987
Google Scholar
16. Bell KM, Plon L, Bunney Jr WE, Potkin SG. S-adenosylmethionine treatment of depression: a controlled
clinical trial. American Journal of Psychiatry 145: 1110–1114, 1988
PubMed
CAS
Google Scholar
17. Berger R, Nowak H. A new medical approach to the treatment of osteoarthritis: report of an open phase
IV study with ademetionine (Gumbaral). American Journal of Medicine 83 (Suppl. 5A): 84–88, 1987
PubMed
CAS
Google Scholar
18. Boelsterli UA, Rakhit G, Balazs T. Modulation by S-adenosyl-L-methionine of hepatic Na+, K+-ATPase,
membrane fluidity, and bile flow in rats with ethinyl estradiol-induced cholestasis. Hepatology 3: 12–17,
1983
PubMed
CAS
Google Scholar
Google Scholar
CAS
Google Scholar
21. Bottiglieri T, Chary TK, Laundy M, Carney MWP, Godfrey P, et al. Transmethylation in depression.
Alabama Journal of Medical Sciences 25: 296–301, 1988
PubMed
CAS
Google Scholar
22. Bottiglieri T, Laundy M, Martin R, Carney MWP, Nissenbaum H, et al. S-adenosyl-methionine influences
monoamine metabolism. Lancet 2: 224, 1984
PubMed
CAS
Google Scholar
PubMed
CAS
Google Scholar
24. Cabrero C, Martin Duce A, Ortiz P, Alemany S, Mato JM. Specific loss of the high-molecular-weight
form of S-adenosyl-L-methionine synthetase in human liver cirrhosis. Hepatology 88: 1530–1534, 1988
Google Scholar
25. Cacciatore L, Cozzolino G, Varriale A, Dionisio M. Treatment of pruritus in chronic liver disease with S-
adenosylmethionine. European Journal of Clinical Investigation 19 (Part II): A15, 1989
https://link.springer.com/article/10.2165%2F00003495-198938030-00004 6/32
11/30/21, 3:08 PM S-Adenosyl-L-Methionine | SpringerLink
Google Scholar
PubMed
CAS
Google Scholar
27. Carney MWP, Chary TKN, Bottiglieri T. Switch mechanism in affective illness and oral S-
adenosylmethionine (SAM). British Journal of Psychiatry 150: 724–725, 1987
PubMed
CAS
Google Scholar
28. Carney MWP, Chary TKN, Bottiglieri T, Reynolds EH. Switch and S-adenosyl-methionine. Alabama
Journal of Medical Sciences 25: 316–319, 1988
PubMed
CAS
Google Scholar
29. Carney MWP, Martin R, Bottiglieri T, Reynolds EH, Nissenbaum H, et al. Switch mechanism in affective
illness and S-adenosylmethionine. Lancet 1: 820–821, 1983
PubMed
CAS
Google Scholar
30. Carney MWP, Edeh J, Bottiglieri T, Reynolds EM, Toone BK. Affective illness and S-
adenosylmethionine: a preliminary report. Clinical Neuropharmacology 9: 379–385, 1986
PubMed
CAS
Google Scholar
31. Caruso I, Fumagalli M, Boccassini L, Sarzi Puttini P, Santandrea S, et al. Treatment of depression in
rheumatoid arthritic patients: a comparison of S-adenosylmethionine (Samyr®) and placebo in a double-
blind study. Clinical Trials Journal 24: 305–310, 1987
Google Scholar
32. Celani T, Iorio G, Vacca L, Amati A, Del Vecchio M. Electroen-cephalographic control with frequency
analysis in depressed patients treated with SAMe. Current Therapeutic Research 23: 525–527, 1978
Google Scholar
33. Chawla RK, Lewis FW, Kutner MH, Bate DM, Roy RGB et al. Plasma cysteine, cystine, and glutathione
in cirrhosis. Gastroenterology 87: 770–776, 1984
PubMed
CAS
Google Scholar
Google Scholar
35. Cimino M, Vantini G, Algeri S, Curatola G, Pezzoli C, et al. Age-related modification of dopaminergic
and β-adrenergic receptor system: restoration to normal activity by modifying membrane fluidity with S-
adenosylmethionine. Life Sciences 34: 2029–2039, 1984
PubMed
CAS
Google Scholar
36. Cohen BM, Satlin A, Zubenko GS. S-adenosyl-L-methionine in the treatment of Alzheimer’s disease.
Journal of Clinical Psychopharmacology 8: 43–47, 1988
PubMed
CAS
Google Scholar
Google Scholar
Google Scholar
PubMed
CAS
Google Scholar
PubMed
Google Scholar
41. Di Padova C, Tritapepe R, Rovagnati P, Pozzoli M, Stramentinoli G. Decreased blood levels of ethanol
and acetaldehyde by S-adenosyl-L-methionine in humans. Archives of Toxicology (Suppl. 7): 240–242,
1984b
43. Fazio C, Andreoli V, Agnoli A, Cassachia M, Cerbo R. Effetti terapeutici e meccanismo d’azione della S-
Adenosil-L-Metionina (SAM) nelle sindromi depressive. Minerva Medica 64: 1515–1529,1973
PubMed
CAS
Google Scholar
44. Fazio C, Andreoli V, Agnoli A, Casacchia M, Cerbo R, et al. Therapy of schizophrenia and depressive
disorders with S-adenosyl-L-methionine. IRCS (Research on: Clinical Pharmacology and Therapeutics;
Human Metabolism and Nutrition; Psychiatry and Clinical Psychology; Psychology) 2: 1015, 1974
Google Scholar
45. Feo F, Pascale R, Garcea R, Daino L, Pirisi L, et al. Effect of the variations of S-adenosyl-L-methionine
liver content on fat accumulation and ethanol metabolism in ethanol-intoxicated rats. Toxicology and
Applied Pharmacology 83: 331–341, 1986
PubMed
CAS
Google Scholar
46. Fiaccadori F, Frezza M, Di Padova C. Oral S-adenosylmethionine (SAMe) therapy in cholestatic patients
with chronic liver disease. Interim analysis of a placebo (P) controlled clinical trial. Journal of
Hepatology 7 (Suppl. 1): 31, 1988
Google Scholar
47. Finkelstein JD, Kyle WE, Martin JJ, Pick A-M. Activation of cystathionine synthase by
adenosylmethionine and adenosy-lethionine. Biochemical and Research Communications 66: 81–87,
1975
CAS
Google Scholar
48. Frezza M, Centini G, Cammareri G, Le Grazie C, Di Padova C. S-adenosylmethionine for the treatment
of intrahepatic cholestasis of pregnancy. Results of a controlled clinical trial. Hepato-gastroenterology, in
press, 1989
49. Frezza M, Di Padova C. Italian Study Group for SAMe in Liver Disease. Multicenter placebo controlled
clinical trial of intravenous and oral S-adenosylmethionine (SAMe) in cholestatic patients with liver
https://link.springer.com/article/10.2165%2F00003495-198938030-00004 8/32
11/30/21, 3:08 PM S-Adenosyl-L-Methionine | SpringerLink
Google Scholar
PubMed
CAS
Google Scholar
51. Frezza M, Pozzato G, Pison G, Zalateo C, Chiesa L, et al. S-adenosylmethionine counteracts oral
contraceptive hepatotoxicity in women. American Journal of Medical Sciences 293: 234–238, 1987b
Google Scholar
PubMed
CAS
Google Scholar
53. Fricker G, Landmann L, Meier PJ. Ethinylestradiol (EE) induced structural and functional alterations of
rat liver plasma membranes and their reversal by S-adenosylmethionine (SAMe) in vitro. Abstract no. 24.
Hepatology 8: 1224, 1988
Google Scholar
54. Gatto G, Caleri D, Michelacci S, Sicuteri F. Analgesizing effect of a methyl donor (S-adenosyl
methionine) in migraine: an open clinical trial. International Journal of Clinical Pharmacology Research
6: 15–17, 1986
PubMed
CAS
Google Scholar
55. Gentile S, Persico M, Orlando C, Le Grazie C, Di Padova C, et al. Effect of different doses of S-adenosyl-
L-methionine (SAMe) on nicotinic acid-induced hyperbilirubinaemia in Gilbert’s syndrome.
Scandinavian Journal of Clinical and Laboratory Investigation 48: 525–529, 1988
PubMed
CAS
Google Scholar
56. Gentile S, Persico M, Russo FS, Le Grazie C, Di Padova C, et al. Effect of S-adenosylmethionine
(SAMe) on antipyrine and rifamycin-SV half-life and serum total bibirubin in cirrhotic patients. Journal
of Hepatology, in press, 1989
57. Giannuoli G, Tine F, Malizia G, Saracco G, Verme G, et al. S-adenosylmethionine for treatment of
pruritus in compensated chronic liver disease. A pilot study. Abstract no. 24. Hepatology 6: 1110, 1986
Google Scholar
PubMed
CAS
Google Scholar
PubMed
CAS
Google Scholar
60. Hirata F, Axelrod J. Phospholipid methylation and biological signal transmission. Science 209: 1082–
1090, 1980
PubMed
CAS
Google Scholar
https://link.springer.com/article/10.2165%2F00003495-198938030-00004 9/32
11/30/21, 3:08 PM S-Adenosyl-L-Methionine | SpringerLink
61. Hirata F, Viveros OH, Diliberto EJ, Axelrod J. Identification and properties of two methyltransferases in
conversion of phosphatidylethanolamine to phosphatidylcholine. Proceedings of the National Academy of
Sciences 78: 1718–1721, 1978
Google Scholar
62. Horowitz JH, Rypins EB, Henderson JM, Heymsfield SB, Moffitt SD, et al. Evidence for impairment of
transsulfuration pathway in cirrhosis. Gastroenterology 81: 668–675, 1981
PubMed
CAS
Google Scholar
PubMed
CAS
Google Scholar
64. Janicak PG, Lipinski J, Davis JM, Comaty JE, Waternaux C, et al. S-adenosylmethionine in depression: a
literature review and preliminary report. Alabama Journal of Medical Sciences 25: 306–313,1988
PubMed
CAS
Google Scholar
65. Kagan BL, Sultzer DL, Rosenlicht N, Gemer RH. Oral S-adenosyl-methionine in depression: a double-
blind, placebo controlled trial. Submitted to American Journal of Psychiatry for publication Küfferle B,
Grünberger J. Early clinical double-blind study with S-adenosyl-L-methionine: a new potential
antidepressant. In Costa & Racagni (Eds) Typical and atypical antidepressants: Clinical Practice, pp. 175–
180, Raven Press, New York, 1982
Google Scholar
66. Lafuenti G, Plotti G, Nicolanti G, Caruso A, Tibollo FG, et al. Valutazione delie modificazioni di
parametri clinici e biochimici in gravide con colestasi in terapia con S-adenosyl-L-methionine per os.
Giornale Italiano di Ostetricia e Ginecologia 5: 357–361, 1988
Google Scholar
67. Lieber CS, DeCarli IM, Kim C, Lowe N, Sasaki R, et al. S-adenosyl-L-methionine (SAMe) attenuates
alcohol-induced mitochondrial injury in the baboon. Abstract no. 773. Hepatology 8: 1412, 1988
Google Scholar
68. Lipinski JF, Cohen BM, Frankenburg F, Tohen M, Waternaux C, et al. Open trial of S-
adenosylmethionine for treatment of depression. American Journal of Psychiatry 141: 448–450, 1984
PubMed
CAS
Google Scholar
69. Loguercio C, Nardi G. Abnormal concentration of red blood cell cysteine in cirrhotics and its correction
by S-adenosylmethionine. Abstract no. 311. Journal of Hepatology 5 (Suppl. 1): 161, 1987
Google Scholar
70. Maeda N, Kon K, Sekiya M, Shiga T. Increase of ATP level in human erythrocytes induced by S-
adenosyl-L-methionine. Biochemical Pharmacology 35: 625–629, 1986
PubMed
CAS
Google Scholar
71. Manzillo G, Fiaccadori F, Frezza M, Di Padova C. Results of a placebo (P) controlled clinical trial with
oral S-adenosylmethionine (SAMe) in cholestatic patients with chronic liver disease. Abstract no; 187.
Hepatology 8: 1265, 1988
Google Scholar
https://link.springer.com/article/10.2165%2F00003495-198938030-00004 10/32
11/30/21, 3:08 PM S-Adenosyl-L-Methionine | SpringerLink
72. Marchesini G, Almasio P, Luca A, Maggioni Moratti E, Pisi E, et al. Sulfur amino acid (SAA) pattern in
compensated chronic liver diseases. European Journal of Clinical Investigation 19 (Part II): A94, 1989
Google Scholar
73. Marchesini G, Bianchi GP, Lolli R, Zoli M, Pisi E. Effect of S-adenosylmethionine (SAMe) on plasma
levels of sulfur-containing amino acids (SCAA) in patients with liver cirrhosis. Journal of Hepatology 7
(Suppl. 1): 148, 1988
Google Scholar
74. Martin Duce A, Ortiz P, Cabrero C, Mato JM. S-Adenosyl-L-methionine synthetase and phospholipid
methyltransferase are inhibited in human cirrhosis. Hepatology 8: 65–68, 1988
CAS
Google Scholar
75. Matsui Y, Kubo Y, Iwata N. S-Adenosyl-L-methionine prevents ischemic neuronal death. European
Journal of Pharmacology 144: 211–216, 1987
PubMed
CAS
Google Scholar
76. Mazzanti R, Arcangeli A, Salvadori G, Smorlesi C, Di Perri T, et al. On the anti-steatosic effects of S-
adenosyl-L-methionine in various chronic liver diseases (multicentre study). Current Therapeutic
Research 25: 25–34, 1979
Google Scholar
77. Mudd SM, Poole JR. Labile methyl balances for normal humans on various dietary regimes. Metabolism
24: 721–735, 1975
PubMed
CAS
Google Scholar
78. Muscettola G, Galzenati M, Balbi A. SAMe versus placebo: a double blind comparison in major
depressive disorders. In Costa & Racagni (Eds) Typical and atypical antidepressants: clinical practice, pp.
151–156, Raven Press, New York, 1982
Google Scholar
Google Scholar
80. Ortiz P, Martin Duce A, Cabrero C. Phospholipid methylation and S-adenosylmethionine synthesis in
human liver cirrhosis. Cell Biology Reviews SI: 59–66, 1987
Google Scholar
81. Owen JS, Bruckdorfer KR, Day RC, Mclntyre N. Decreased erythrocyte membrane fluidity and altered
lipid composition in human liver disease. Journal of Lipid Research 23: 124–132, 1982
PubMed
CAS
Google Scholar
82. Paredes SR, Juknat de Geralnik AA, Batlle AM Del C, Conti HA. Beneficial effect of S-adenosyl-L-
methionine in lead intoxication. Another approach to clinical therapy. International Journal of
Biochemistry 17: 625–629, 1985a
PubMed
CAS
Google Scholar
83. Paredes SR, Kozicki PA, Batlle AM Del C. S-adenosyl-L-methionine a counter to lead intoxication?
Comparative Biochem-istry and Physiology 82B: 751–757, 1985b
https://link.springer.com/article/10.2165%2F00003495-198938030-00004 11/32
11/30/21, 3:08 PM S-Adenosyl-L-Methionine | SpringerLink
CAS
Google Scholar
84. Pascale R, Daino L, Garcea R, Frassetto S, Ruggiu ME, et al. Inhibition by ethanol of rat liver
plasmamembrane (Na+, K+) ATP ase. Protective effect of S-adenosyl-L-methionine, L-methionine and
N-acetylcysteine. Toxicology and Applied Pharmacology 97: 216–229, 1989
PubMed
CAS
Google Scholar
85. Pezzoli C, Fiorini RM, Curatola G, Stramentinoli G. S-adenosylmethionine protects against erythrocyte
membrane alterations induced in rabbits by cholesterol-rich diet. Pharmacological Research
Communications 15: 785–795, 1983
PubMed
CAS
Google Scholar
87. Piccinino F, Sagnelli E, Pasquale G, Giusti G. S-adenosyl-methionine in patients with chronic active
hepatitis treated with steroids. Italian Journal of Gastroenterology 14: 186–188, 1982
Google Scholar
Google Scholar
CAS
Google Scholar
90. Reynolds EH, Carney MWP, Toone BK. Methylation and mood. Lancet 2: 196–198, 1984
PubMed
CAS
Google Scholar
91. Reynolds EH, Carney MWP, Toone BK, Thomas CS, Edeh J, et al. Transmethylation and
neuropsychiatry. Cell Biology Reviews S1: 93–102, 1987
Google Scholar
92. Reynolds EH, Stramentinoli G. Folic acid, S-adenosylmethionine and affective disorder. Psychological
Medicine 13: 705–710, 1983
PubMed
CAS
Google Scholar
93. Rosenbaum JF, Fava M, Falk WE, Pollack MH, Cohen LS. Oral S-adenosylmethionine in major
depression. Abstract no. IOC. Presented at the 141st Annual Meeting of the American Psychiatric
Association, Montreal, 7–12 May, 1988a
94. Rosenbaum JF, Fava M, Falk WE, Pollack MH, Cohen LS, et al. An open-label pilot study of oral S-
adenosyl-L-methionine in major depression: interim results. Psychopharmacology Bulletin 24: 189–194,
1988b
PubMed
CAS
Google Scholar
95. Salerno MT, Vendemiale G, Amendola A, Trione T, Palasciano G, et al. Effect of orally administered S-
adenosyl-L-methionine (SAMe) in patients with alcoholic liver disease. Abstract no. 756. Digestive
Diseases and Sciences 31 (Suppl): 192S, 1986
https://link.springer.com/article/10.2165%2F00003495-198938030-00004 12/32
11/30/21, 3:08 PM S-Adenosyl-L-Methionine | SpringerLink
Google Scholar
Google Scholar
97. Sato H, Hariyama H, Moriguchi K. S-adenosyl-L-methionine protects the hippocampal CA1 neurons
from the ischemic neuronal death in rat. Biochemical and Biophysical Research Communications 150:
491–496, 1988
PubMed
CAS
Google Scholar
98. Schreiber AJ, Simon FR. Estrogen-induced cholestasis: clues to pathogenesis and treatment. Hepatology
3: 607–613, 1983
PubMed
CAS
Google Scholar
99. Schreiber AJ, Warren G, Sutherland E, Simon FR. S-adenosylmethionine (SAMe)-induced cytoprotection
against bile acid-induced cholestasis. Abstract. Gastroenterology 84: 1395, 1983
Google Scholar
100. Stramentinoli G. Adomet as a drug: pharmacokinetic and pharmacological aspects. In Borchardt et al.
(Eds) Biological methylation and drug design, pp. 315–326, The Humana Press, Clifton, New Jersey,
1986a
Google Scholar
Google Scholar
Google Scholar
PubMed
CAS
Google Scholar
PubMed
CAS
Google Scholar
PubMed
CAS
Google Scholar
PubMed
CAS
Google Scholar
https://link.springer.com/article/10.2165%2F00003495-198938030-00004 13/32
11/30/21, 3:08 PM S-Adenosyl-L-Methionine | SpringerLink
PubMed
CAS
Google Scholar
PubMed
CAS
Google Scholar
PubMed
CAS
Google Scholar
110. Tolbert LC. MAT kinetics in affective disorders; and schizophrenia: an account. Alabama Journal of
Medical Sciences 25: 291–296, 1988
PubMed
CAS
Google Scholar
Google Scholar
112. Trovarelli G, De Medio GE, Porcellati S, Stramentinoli G, Porcellati G. The effect of S-adenosyl-L-
methionine on ischemia-induced disturbances of brain phospholipid in the gerbil. Neurochemical
Research 8: 1597–1609, 1983
PubMed
CAS
Google Scholar
114. Vendemiale G, Altomare E, Trizio T, Le Grazie C, Di Padova C, et al. Effects of oral S-adenosyl-L-
methionine on hepatic glutathione in patients with liver disease. Scandinavian Journal of
Gastroenterology, in press, 1989a
115. Vendemiale G, Altomare E, Trizio T, Salerno MT, Stufano N, et al. Effect of S-adenosyl-L-methionine on
hepatic glutathione in patients with liver injury. Abstract 358. Digestive Diseases and Sciences 31
(Suppl.): 92, 1986
Google Scholar
116. Vore M. Estrogen cholestasis. Membranes, metabolites, or receptors? Gastroenterology 93: 643–647,
1987
PubMed
CAS
Google Scholar
117. Yousef IM, Barnwell SG, Tuchweber B, Weber A, Roy CC. Effect of complete sulfation of bile acids on
bile formation in rats. Hepatology 7: 535–542, 1987
PubMed
CAS
Google Scholar
118. Zeisel SM, Poole JR. Dietary intake of methionine: influence on brain S-adenosylmethionine. In Usdin E,
Boechardt RT, Greveling CR (Eds) Transmethylation, pp 59–68, Elsevier/North-Holland, The
Netherlands, 1979
https://link.springer.com/article/10.2165%2F00003495-198938030-00004 14/32
11/30/21, 3:08 PM S-Adenosyl-L-Methionine | SpringerLink
Google Scholar
Download references
Author information
Affiliations
Authors
1. Heather A. Friedel
View author publications
2. Karen L. Goa
View author publications
3. Paul Benfield
View author publications
Corresponding author
Correspondence to
Heather A. Friedel.
Additional information
Various sections of the manuscript reviewed by: E. Alvarez, Department of Psychiatry, School of Medicine,
Sant Pau Hospital, Barcelona, Spain; I. Caruso, Department of Rheumatology, L. Sacco Hospital, Milan, Italy;
P.K. Chiang, Division of Biochemistry, Walter Reed Army Institute of Research, Washington DC, USA: M.
Frezza, Institute of Medical Pathology; University of Trieste, Trieste, Italy; D.E. Furst, Department of
Medicine, University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey, USA: M.H.
Lader, Institute of Psychiatry; University of London, London, England; J.M. Mato, Departamento de
Metabolismo, Nutrition y Hormonas, Fundación Jiménez Diaz, Madrid, Spain; S. Montgomery, Academic
Department of Psychiatry, St Mary’s Hospital Medical School, London, England; E.H. Reynolds, King’s
College Hospital, London, England; M. Tanaka, Department of Pharmacology, Kurume University School of
Medicine, Kurume, Japan; G.C. Weir, Joslin Diabetes Center, Boston, Massachusetts, USA: R.L. Williams, The
Drug Studies Unit, University of California, San Francisco, California, USA.
https://link.springer.com/article/10.2165%2F00003495-198938030-00004 15/32
11/30/21, 3:08 PM S-Adenosyl-L-Methionine | SpringerLink
Download citation
DOI: https://doi.org/10.2165/00003495-198938030-00004
Keywords
Taurine
Chronic Liver Disease
Cholestasis
Clomipramine
Lead Poisoning
Access options
39,95 €
Price includes VAT (India)
Sections
References
Summary
References
Author information
Additional information
Rights and permissions
About this article
Advertisement
https://link.springer.com/article/10.2165%2F00003495-198938030-00004 16/32
11/30/21, 3:08 PM S-Adenosyl-L-Methionine | SpringerLink
Google Scholar
PubMed CAS
Google Scholar
Google Scholar
Google Scholar
Google Scholar
Google Scholar
https://link.springer.com/article/10.2165%2F00003495-198938030-00004 17/32
11/30/21, 3:08 PM S-Adenosyl-L-Methionine | SpringerLink
Google Scholar
Google Scholar
Google Scholar
Google Scholar
PubMed CAS
Google Scholar
PubMed CAS
Google Scholar
Google Scholar
Google Scholar
Google Scholar
PubMed CAS
Google Scholar
PubMed CAS
Google Scholar
PubMed CAS
Google Scholar
Google Scholar
CAS
Google Scholar
PubMed CAS
Google Scholar
PubMed CAS
Google Scholar
PubMed CAS
Google Scholar
https://link.springer.com/article/10.2165%2F00003495-198938030-00004 19/32
11/30/21, 3:08 PM S-Adenosyl-L-Methionine | SpringerLink
Google Scholar
Google Scholar
PubMed CAS
Google Scholar
PubMed CAS
Google Scholar
PubMed CAS
Google Scholar
PubMed CAS
Google Scholar
PubMed CAS
Google Scholar
Google Scholar
Google Scholar
33. Chawla RK, Lewis FW, Kutner MH, Bate DM, Roy
RGB et al. Plasma cysteine, cystine, and glutathione
in cirrhosis. Gastroenterology 87: 770–776, 1984
PubMed CAS
Google Scholar
Google Scholar
PubMed CAS
Google Scholar
PubMed CAS
Google Scholar
Google Scholar
Google Scholar
PubMed CAS
Google Scholar
PubMed
Google Scholar
PubMed CAS
Google Scholar
Google Scholar
PubMed CAS
Google Scholar
Google Scholar
CAS
Google Scholar
Google Scholar
PubMed CAS
Google Scholar
Google Scholar
PubMed CAS
Google Scholar
Google Scholar
PubMed CAS
Google Scholar
PubMed CAS
Google Scholar
https://link.springer.com/article/10.2165%2F00003495-198938030-00004 23/32
11/30/21, 3:08 PM S-Adenosyl-L-Methionine | SpringerLink
Google Scholar
PubMed CAS
Google Scholar
PubMed CAS
Google Scholar
PubMed CAS
Google Scholar
Google Scholar
PubMed CAS
Google Scholar
PubMed CAS
Google Scholar
PubMed CAS
Google Scholar
https://link.springer.com/article/10.2165%2F00003495-198938030-00004 24/32
11/30/21, 3:08 PM S-Adenosyl-L-Methionine | SpringerLink
Google Scholar
Google Scholar
Google Scholar
PubMed CAS
Google Scholar
Google Scholar
PubMed CAS
Google Scholar
Google Scholar
https://link.springer.com/article/10.2165%2F00003495-198938030-00004 25/32
11/30/21, 3:08 PM S-Adenosyl-L-Methionine | SpringerLink
Google Scholar
Google Scholar
CAS
Google Scholar
PubMed CAS
Google Scholar
Google Scholar
PubMed CAS
Google Scholar
Google Scholar
Google Scholar
Google Scholar
PubMed CAS
Google Scholar
PubMed CAS
Google Scholar
CAS
Google Scholar
PubMed CAS
Google Scholar
PubMed CAS
Google Scholar
Google Scholar
Google Scholar
https://link.springer.com/article/10.2165%2F00003495-198938030-00004 27/32
11/30/21, 3:08 PM S-Adenosyl-L-Methionine | SpringerLink
CAS
Google Scholar
PubMed CAS
Google Scholar
Google Scholar
PubMed CAS
Google Scholar
PubMed CAS
Google Scholar
Google Scholar
Google Scholar
PubMed CAS
Google Scholar
https://link.springer.com/article/10.2165%2F00003495-198938030-00004 28/32
11/30/21, 3:08 PM S-Adenosyl-L-Methionine | SpringerLink
PubMed CAS
Google Scholar
Google Scholar
Google Scholar
Google Scholar
Google Scholar
PubMed CAS
Google Scholar
PubMed CAS
Google Scholar
PubMed CAS
Google Scholar
PubMed CAS
Google Scholar
PubMed CAS
Google Scholar
PubMed CAS
Google Scholar
PubMed CAS
Google Scholar
PubMed CAS
Google Scholar
Google Scholar
PubMed CAS
Google Scholar
Google Scholar
PubMed CAS
Google Scholar
PubMed CAS
Google Scholar
Google Scholar
Switch Edition
Academic Edition
Corporate Edition
Home
Impressum
Legal information
Privacy statement
California Privacy Statement
How we use cookies
Manage cookies/Do not sell my data
Accessibility
Contact us
Affiliate program
Not logged in
- 49.34.168.28
Not affiliated
Springer Nature
https://link.springer.com/article/10.2165%2F00003495-198938030-00004 31/32
11/30/21, 3:08 PM S-Adenosyl-L-Methionine | SpringerLink
https://link.springer.com/article/10.2165%2F00003495-198938030-00004 32/32