SAM-e Monograph

Scientific name of SAM-e:
S-Adenosylmethionine

Action of SAM-e:
May help to support healthy neurotransmitter balance; mood enhancer

SAM-e is used for these common wellness concerns:
Mild to moderate mood changes or depressed mood caused by everyday stress, occasional nervousness, nervous tension or anxiety

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promote fast-acting relaxation when you need it most.

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promote positive mood balance all day strong.

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promote long-lasting energy and mental sharpness.

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promote a deep, restful night's sleep.

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support Emotional Wellness in kids ages 7 thru 13.

An Overview of SAM-e

SAM-e (pronounced “sammy”) is a naturally occurring chemical that performs a wide range of functions throughout the body. In clinical study, SAM-e supplementation has demonstrated a broad spectrum of action to stimulate neurotransmitter productivity and maintain healthy cell-to-cell communication.

Italian researchers discovered the benefits of SAM-e in the 1970s, when they observed it to have significant effects on individuals experiencing mood changes. SAM-e has been available over the counter in the United States since 1996, and is widely used as a dietary supplement to provide positive support for:

  • Depressed mood and mild to moderate mood changes caused by everyday stress
  • Occasional nervousness, nervous tension and anxiety

SAM-e is a vital component for the function of multiple body systems, aiding in the healthy balance of the neurotransmitters Serotonin and Dopamine, which are associated with mood balance and overall emotional wellbeing.

Science and Pharmacology of SAM-e

S-Adenosylmethionine (SAM-e) is a physiological agent formed in the liver when the essential amino acid Methionine combines with Adenosine Triphosphate (ATP) by way of a process called methylation. It is then broken down and used in over 40 critical biochemical processes throughout the body.

SAM-e has a significant first-pass absorption rate, with approximately 50 percent of the SAM-e taken being metabolized in the liver upon oral administration. In laboratory settings, SAM-e has been shown to increase S-Adenosylmethionine levels in cerebrospinal fluid, which indicates that SAM-e is able to pass through the blood-brain barrier. Further laboratory research demonstrates that SAM-e is active in the Dopaminergic system. These effects suggest that SAM-e acts as a natural reuptake inhibitor to support healthy neurotransmitter balance in the brain.

SAM-e Safety and Usage

SAM-e is an all-natural supplement available at most nutrition stores in the United States and Europe. It is available in doses varying from 50 milligrams to 1000 milligrams. Studies suggest that the optimum dosage amount is around 200 milligrams daily. However, some users taking doses as high as 1000 to 1600 milligrams also report satisfactory results.

What are the potential side effects of SAM-e?

The most commonly reported side effects of SAM-e are gastrointestinal. A very small percentage of users experience heartburn, nausea and stomachache.

Is SAM-e safe for children?

Clinical study data regarding SAM-e use in children is limited. SAM-e should not be administered without the supervision of a professional healthcare provider.

Does SAM-e adversely interact with prescription drugs?

SAM-e occurs naturally in the human body. Taking SAM-e while taking prescription medications is not known to cause adverse reactions. If you are taking a prescription medication, it is recommended that you consult with your prescribing doctor before making any changes or additions to your current treatment plan.

What precautions should I take before beginning SAM-e?

Consult with your healthcare provider before beginning a wellness plan that includes dietary supplements like SAM-e.

  • Do not take SAM-e if you are pregnant or nursing
  • Do not take SAM-e if you are currently taking a prescription MAOI
  • Do not take SAM-e if you are currently taking a protease inhibitor for HIV/AIDS
  • Do not operate vehicles or heavy machinery until you know how SAM-e affects you

SAM-e Clinical Studies

Clinical Study Meta-Analysis and Peer Reviews

1. S-adenosyl-l-methionine (SAMe) as antidepressant: meta-analysis of clinical studies.
Bressa GM.
Department of Psychiatry, University Cattolica Sacro Cuore School of Medicine, Italy.
Acta Neurol Scand Suppl. 1994;154:7-14. PMID: 7941964 [Read the Abstract]

Excerpt From This Meta-Analysis:
INTRODUCTION - S-adenosyl-l-methionine (SAMe) is a naturally-occurring substance which is a major source of methyl groups in the brain.
MATERIAL AND METHODS - We conducted a meta-analysis of the studies on SAMe to assess the efficacy of this compound in the treatment of depression compared with placebo and standard tricyclic antidepressants.
RESULTS -Our meta-analysis showed a greater response rate with SAMe when compared with placebo, with a global effect size ranging from 17% to 38% depending on the definition of response, and an antidepressant effect comparable with that of standard tricyclic antidepressants.
CONCLUSION - The efficacy of SAMe in treating depressive syndromes and disorders is superior with that of placebo and comparable to that of standard tricyclic antidepressants. Since SAMe is a naturally occurring compound with relatively few side-effects, it is a potentially important treatment for depression.

2. Alternative therapies: Part I. Depression, diabetes, obesity.
Morelli V, Zoorob RJ.
Louisiana State University School of Medicine in New Orleans, USA.
Am Fam Physician. 2000 Sep 1;62(5):1051-60. PMID: 10997530 [Read the Full Text]

Excerpt From This Review:
"Another potential antidepressant is SAM-e, which is a molecule found naturally in all human cells. It plays a role in the many methylation reactions of the body, including gene expression, cell membrane homeostasis, and hormone and neurotransmitter synthesis.

The rationale for the use of SAM-e in depression stems from its role in the metabolism of serotonin, dopamine and melatonin. Oral and intravenous SAM-e supplementation has been shown to significantly increase SAM-e levels in cerebrospinal fluid, indicating SAM-e's crossover through the blood-brain barrier. This has been associated with increased levels of serotonin metabolites in cerebrospinal fluid. Some depressed patients may have low serotonin levels associated with low levels of SAM-e."

3. The use of diet and dietary components in the study of factors controlling affect in humans: a review.
Young SN.
Department of Psychiatry, McGill University, Canada.
J Psychiatry Neurosci. 1993 Nov;18(5):235-44. PMID: 8297922 [Read the Abstract]

Clinical Trials and Laboratory Tests

1. Neuroendocrine effects of S-adenosyl-L-methionine, a novel putative antidepressant.
Fava M, Rosenbaum JF, MacLaughlin R, Falk WE, Pollack MH, Cohen LS, Jones L, Pill L.
Clinical Psychopharmacology Unit, Massachusetts General Hospital, Harvard Medical School
Psychiatr Res. 1990;24(2):177-84. PMID: 2120432 [Read the Abstract]

2. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders.
Bottiglieri T, Hyland K, Reynolds EH.
Metabolic Disease Center, Baylor Research Institute
Drugs. 1994 Aug;48(2):137-52. PMID: 7527320 [Read the Abstract]

3. Homocysteine, folate, methylation, and monoamine metabolism in depression.
Bottiglieri T, Laundy M, Crellin R, Toone BK, Carney MW, Reynolds EH.
Department of Neurology, King's College Hospital
J Neurol Neuro. Psychiatry. 2000 Aug;69(2):228-32. PMID: 10896698 [Read the Abstract]

4. Lowered serum n-3 polyunsaturated fatty acid (PUFA) levels predict the occurrence of postpartum depression: further evidence that lowered n-PUFAs are related to major depression.
De Vriese SR, Christophe AB, Maes M.
Department of Internal Medicine, Division of Nutrition, University of Ghent, Ghent, Belgium.
1: Life Sci. 2003 Nov 7;73(25):3181-7. PMID: 14561523 [Read the Abstract]

5. The influence of phosphatidylserine supplementation on mood and heart rate when faced with an acute stressor.
Benton D, Donohoe RT, Sillance B, Nabb S.
Department of Psychology, University of Wales Swansea,UK
Nutr Neurosci. 2001;4(3):169-78. PMID: 11842886 [Read the Abstract]

6. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders.
Bottiglieri T, Hyland K, Reynolds EH.
Metabolic Disease Center, Baylor Research Institute, Dallas, Texas.
Drugs. 1994 Aug;48(2):137-52. PMID: 7527320 [Read the Abstract]

7. Rapidity of onset of the antidepressant effect of parenteral S-adenosyl-L-methionine.
Fava M, Giannelli A, Rapisarda V, Patralia A, Guaraldi GP.
Depression Research Program, Massachusetts General Hospital,USA.
Psychiatry Res. 1995 Apr 28;56(3):295-7. PMID: 7568552 [Read the Abstract]

8. Double-blind, placebo-controlled study of S-adenosyl-L-methionine in depressed postmenopausal women.
Salmaggi P, Bressa GM, Nicchia G, Coniglio M, La Greca P, Le Grazie C.
Obstetrics and Gynecology Department, University La Sapienza School of Medicine, Rome, Italy.
Psychother Psychosom. 1993;59(1):34-40. PMID: 8441793 [Read the Abstract]

9. Efficacy of S-adenosyl-L-methionine in speeding the onset of action of imipramine.
Berlanga C, Ortega-Soto HA, Ontiveros M, Senties H.
Special Studies Clinic, Mexican Institute of Psychiatry
Psychiatry Res. 1992 Dec;44(3):257-62. PMID: 1289923 [Read the Abstract]

10. Oral S-adenosylmethionine in depression: a randomized, double-blind, placebo-controlled trial.
Kagan BL, Sultzer DL, Rosenlicht N, Gerner RH.
Am J Psychiatry. 1990 May;147(5):591-5. PMID: 2183633 [Read the Abstract]

11. The antidepressant potential of oral S-adenosyl-l-methionine.
Rosenbaum JF, Fava M, Falk WE, Pollack MH, Cohen LS, Cohen BM, Zubenko GS.
Clinical Psychopharmacology Unit, Massachusetts General Hospital, Boston 02114.
Acta Psychiatr Scand. 1990 May;81(5):432-6. PMID: 2113347 [Read the Abstract]

12. S-adenosylmethionine treatment of depression: a controlled clinical trial.
Bell KM, Plon L, Bunney WE Jr, Potkin SG.
University of California, Irvine Medical Center, Orange 92668.
Am J Psychiatry. 1988 Sep;145(9):1110-4. PMID: 3046382 [Read the Abstract]

13. The influence of S-adenosylmethionine (SAM) on prolactin in depressed patients.
Thomas CS, Bottiglieri T, Edeh J, Carney MW, Reynolds EH, Toone BK.
Int Clin Psychopharmacol. 1987 Apr;2(2):97-102. PMID: 3298421 [Read the Abstract]

14. Effects of S-adenosyl-methionine on plasma norepinephrine, blood pressure, and heart rate in healthy volunteers.
Sherer MA, Cantoni GL, Golden RN, Rudorfer MV, Potter WZ.
Psychiatry Res. 1986 Feb;17(2):111-8. PMID: 3961029 [Read the Abstract]

15. Study of the antidepressive effects of a biological transmethylating agent (S-adenosyl-methione or SAM)
Monaco P, Quattrocchi F.
Riv Neurol. 1979 Nov-Dec;49(6):417-39. PMID: 549212 [Read the Abstract]

16. Influence of SAMe on the modifications of brain polyamine levels in an animal model of depression.
Genedani S, Saltini S, Benelli A, Filaferro M, Bertolini A.
Department of Biomedical Sciences, Section of Pharmacology, University of Modena and Reggio Emilia,Italy.
Neuroreport. 2001 Dec 21;12(18):3939-42. PMID: 11742215 [Read the Abstract]

17. The use of diet and dietary components in the study of factors controlling affect in humans: a review.
Young SN.
Department of Psychiatry, McGill University, Canada.
J Psychiatry Neurosci. 1993 Nov;18(5):235-44. PMID: 8297922 [Read the Abstract]

18. Neuroendocrine effects of S-adenosyl-L-methionine, a novel putative antidepressant.
Fava M, Rosenbaum JF, MacLaughlin R, Falk WE, Pollack MH, Cohen LS, Jones L, Pill L.
Clinical Psychopharmacology Unit, Massachusetts General Hospital, Harvard Medical School
Psychiatr Res. 1990;24(2):177-84. PMID: 2120432 [Read the Abstract]

19. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders.
Bottiglieri T, Hyland K, Reynolds EH.
Metabolic Disease Center, Baylor Research Institute
Drugs. 1994 Aug;48(2):137-52. PMID: 7527320 [Read the Abstract]

20. Homocysteine, folate, methylation, and monoamine metabolism in depression.
Bottiglieri T, Laundy M, Crellin R, Toone BK, Carney MW, Reynolds EH.
Department of Neurology, King's College Hospital
J Neurol Neurosurg Psychiatry. 2000 Aug;69(2):228-32. PMID: 10896698 [Read the Abstract]

21. Role of the dopaminergic system in depression.
Kapur S, Mann JJ.
Department of Psychiatry, University of Pittsburgh School of Medicine, PA.
Biol Psychiatry. 1992 Jul 1;32(1):1-17. PMID: 1391289 [Read the Abstract]

22. S-adenosyl-L-methionine prevents 5-HT(1A) receptors up-regulation induced by acute imipramine in the frontal cortex of the rat.
Bellido I, Gomez-Luque A, Plaza A, Rius F, Ortiz P, Sanchez de la Cuesta F.
Department of Pharmacology and Clinical Therapeutics, School of Medicine, University of Malaga, Spain
Neurosci Lett. 2002 Mar 15;321(1-2):110-4. PMID: 11872268 [Read the Abstract]

23. S-adenosyl-L-methionine prevents 5-HT(1A) receptors up-regulation induced by acute imipramine in the frontal cortex of the rat.
Bellido I, Gomez-Luque A, Plaza A, Rius F, Ortiz P, Sanchez de la Cuesta F.
Department of Pharmacology and Clinical Therapeutics, School of Medicine, University of Malaga, Spain
Neurosci Lett. 2002 Mar 15;321(1-2):110-4. PMID: 11872268 [Read the Abstract]

24. Influence of SAMe on the modifications of brain polyamine levels in an animal model of depression.
Genedani S, Saltini S, Benelli A, Filaferro M, Bertolini A.
Department of Biomedical Sciences, Section of Pharmacology, University of Modena and Reggio Emilia,Italy.
Neuroreport. 2001 Dec 21;12(18):3939-42. PMID: 11742215 [Read the Abstract]

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Last Updated: February 2012 [PHMF-02-0]