One tablet contains:
SAM-e 200 mg. (from 400 mg. of s-adenosyl-l-methionine disulfate tosylate)
Other ingredients: magnesium stearate, cellulose, vegetable stearin, dicalcium phosphate and silica.
Contains No Added sugar, salt, dairy, yeast, wheat, corn, soy, preservatives, artificial colors or flavors.
Suggested Use: As a dietary supplement, adults take one (1) tablet, two (2) times daily between meals, or as directed by a health care professional. Store in a cool, dry place and away from direct light.
Keep out of reach of children.
QUALITY AND POTENCY GUARANTEED.
Overview:
SAM-e (S-Adenosylmethionine) plays a role in many biochemical reactions in the body including the manufacturing of neurotransmitters and phospholipids, and may be helpful in the treatment of depression, fibromyalgia, osteoarthritis, liver disorders, joint pain, and migraine headaches.
In Depth:
SAM-e strongly absorbs moisture from the environment, which can lead to a compromise in its overall quality. Consequently, our SAM-e tablets are carefully enteric-coated for the strongest protection.
SAM-e is produced in small amounts by the human body, where it is an important physiological factor in the production of many compounds. However, the body does not always produce adequate amounts of SAM-e and supplementation is sometimes required.
SAM-e has been the subject of many scientific studies in Europe. Thousands of Europeans have experienced a multitude of benefits from twenty years of its clinical use.
Depression: Sam-e may be helpful in treating mild to moderate depression faster than some prescriptions, without the side effects. (Biploar disorders should be monitored by a physician.) Antidepressants can cause liver damage, Sam-e protects the liver.
Joint and Connective Tissue: Sam-e is important in rebuilding connective tissur and cartilage. Sam-e may help those suffering from osteoarthritis. Sam-e may help to reduce pain, stiffness and inflammation associated with degenerative joint problems.
Fibromyalgia: Sam-e may reduce fatigue, pain and inflammation associated with fibromyalgia. This condition is often dificult to treat but sam-e may help those suffering by improving sleep, reducing fatigue, reducing trigger points, reducing pain and improving mood.
SAMe (S-adenosyl-methionine) is an amino acid derivative normally synthesized in the body. SAMe is used by the body in three important pathways:
1) Methylation (contributing methyl groups to activate certain molecules).
2) The synthesis of polyamines (for cell growth, gene expression, neuronal regeneration, etc.)
3) Trans-sulfuration (synthesis of cysteine, glutathione, and other sulfate chemicals).
In young, healthy people SAMe is well distributed throughout the body as a result of its synthesis from methionine by enzymes using ATP. However, in sickness and in age, system levels may become depleted. Supplementation of the co-factors folate, TMG, vitamins B6 and B12, together with SAMe appears to be an effective method to overcome this deficiency. There is evidence that SAMe may help to synthesize phosphatidylcholine, which keeps cell membranes fluid and is used in the brain to make the neurotransmitter acetylcholine.*
An agency of the U.S. Department of Health and Human Services conducted a meticulous evaluation of SAMe in year 2002. Their findings show the efficacy of SAMe in helping maintain stable mood and joint function, without any side effects. Since aging people often suffer joint discomfort and immobilization, SAMe addresses multiple problems people face as they grow older.*
SAMe (S-adenosyl-methionine) has multi-modal mechanisms of action that are used throughout the body, and especially the liver. In order to perform its detoxification role, the liver performs thousands of complex enzymatic reactions every second.
SAMe facilitates healthy methylation enzymatic processes and boosts hepatic levels of the critical antioxidant, glutathione. When liver function is compromised, glutathione is depleted, which leads to free radical damage. In addition, SAMe acts as a methyl donor in the synthesis and formation of phosphatidylcholine and L-cysteine, both necessary for maintaining liver health.*
Dosage and Use
One to four tablets daily are suggested.
Taking this product with food may avoid gastrointestinal disturbance.
Take folic acid, vitamins B12, and B6 when using SAMe.
What Makes SAMe Different?
SAMe (S-adenosyl-methionine) is an amimo acid derivative normally synthesized in the body. It is widely used in Europe as an antidepressant. There is evidence that SAMe may be the fastest acting, safest and most effective antidepressant available; may help prevent and reverse liver disease; may be effective in the treatment of fibromyalgia, chronic fatigue syndrome and osteoarthritis; and may help to synthesize phosphatidylcholine, which helps cell membranes fluid and is used in the brain to make the neurotransmitter acetylcholine.
CAUTION: Do not use SAMe with other antidepressants. At levels above 400 mg daily, SAMe may cause dry mouth, restlessness and gastrointestinal problems. Cutting back on dosage and than increasing it slowly should alleviate these symptoms.
Suggested Use: As a dietary supplement, take one tablet before meals in the morning and one in the afternoon. This may be increased by taking one tablet in the morning and two tablets in the afternoon, and for some people, an additional tablet in the evening. After two weeks, a maximum dose of two tablets in the morning, two in the afternoon, and two in the evening can be taken.
Caution: When using nutritional supplements, please inform your physician if you are undergoing treatment for a medical condition.
Facts About Depression
Medical textbooks describe depression as a mood disorder, lasting at least 2 weeks, that produces exagerated, inappropriate feelings of sadness, worthlessness, emptiness, and dejection. "Exagerated" and "inappropriate" are two important words to keep in mind. To feel upset because of a job layoff, a broken marriage, a bankruptcy, or the loss of a loved one is a perfectly normal response to an unhappy event. Generally, our upset feelings are proportional to our loss, and this "reactive depression," as doctors call is, goes away with time.
However, major depression often strikes for no apparent reason. It doesn't seem to be caused by outside events. Instead, the black mood grows and grips from within. This crippling darkness can last for weeks, months, or years, and may make it impossible for us to carry on our normal lives.
Although we're only beginning to pull back the curtains that hide the inner workings of the human brain, we do know that several neurotransmitters (chemical messangers), including norepinephrine and serotonin, help to regulate our moods and keep us happy. Depressed people tend to have lower levels of norepinephrine and serotonin. If, for any reason, the amounts of these key neurotransmitters drop below critical levels, the result may be major depression that seems to come from nowhere, linger forever, sap our energy, and ruin our lives.
Why do brain levels of mood regulators fall in some people but not in others? We can't fully answer that question, although we know that genetics plays a major role. Depression, like other mood disorders, tends to run in families. Depression is even more likely to be shared by identical twins: if one is depressed, there's a better than 50% chance that the other will be, too.
A great deal of research has looked into possible environmental and psychological causes of depression. Some investigators believe that people who are pessimistic, often fell overwhelmed by life, or have low self-esteem are more likely to suffer from depression. It may be that some of us are lucky enough to have large reserves of "happy" neurotransmitters in our brains, but others have just enough to keep a smile on their faces.
Although biochemistry is the biggest factor in major depression, we're also affected by what happens to us in our lives. We're all hit by unpleasant events that may cause brain levels of norepinephrine and dopamine to fall temporarily. People with naturally large reserves will get through the troubling times wiht minimal difficulties, but those with low chemical levels to begin with are more likely to fall into a depression.
Excerpt from Depression and Stress Relief in The Directory of life Extension Supplements, 2000, pg 86.
SAMe is a supplement formed in the body by an enzymatic reaction between adenosine-triphosphate (ATP) and methionine. It was discovered in 1952 in Italy and has been researched and manufactured there. SAMe works closely with folic acid and vitamin B-12 and functions as a methyl donor. This nutrient comes and donates methyl molecules necessary to facilitate the manufacture of DNA and brain neurotransmitters. SAMe supports joint comfort, function and mobility in the spine, hips and knees. It is important to the joints because of its critical role in cartilage formation. Studies also show that SAMe helps support a positive outlook. It is able to cross the blood-brain barrier where it affects the synthesis and activation of various proteins, such as neurotransmitters. SAMe is known as a "methyl donor." This means that it works by giving up a piece of itself (a methyl group consisting of one carbon and three hydrogen atoms) to other molecules. Methylation plays a part in many critical cellular functions.
Warning
Individuals with bipolar (manic) depression should not take SAMe unless under professional supervision.
SAM-e is an amino acid derivative that has been clinically proven to benefit brain and joint function. Found in all living cells, SAM-e is also “activated” methionine (as essential amino acid) since it is formed by the combination of ATP with methionine.
Joint Strength: SAM-e supports the production of healthy connective tissues through transulfuration. In this process, critical components of connective tissue, including glucosamine and the condroitin sulfates, are from SAM-e metabolites.
Brain Metabolism: SAM-e methylation reactions are involved in the synthesis of neurotransmitters such as L-dopa, dopamine and related hormones, epinephrine and phosphatidylcholine (a component of lecithin).
Liver: SAM–e metabolism supports the synthesis of glutathione (GSH) and glutathione – dependent enzymes (glutathion peroxidase and glutathione – S- transference), which are substances important for liver function.
Longevity: Methylation of DNA appears to be important in the suppression of errors in DNA replication. Demethylation of DNA is considered a contributor to the aging process. Proper methylation positively influences longevity.
Dosage
Take 1 to 2 tablets per day on an empty stomach, or as directed by your qualified health consultant.
Warning
Individuals using prescribed medication such as antidepressant, including Serotonin Re- Uptake Inhibitors and MAO Inhibitors should consult a physician before using. Individuals with bi-polar disorder or manic depression should not user SAM-e. Place out of reach of children
SAM-e specifically designed to support the health of the eyes, hair, joints and bones.
SAM-e: Promotes normal joint function and may support the production of proteoglycans, the cushioning material of cartilage and joints. Promotes positive mood balance and supports the function of neurotransmitters in the brain, assists in the body's detoxification systems by promoting normal liver function and contributing to the production of the important antioxidant Glutathione.
Don't let stress rob you of a healthy lifestyle. Use cutting-edge nutrients and centuries old herbs to support the whole body at times when you need it most.
Beneficial levels of SAMe (S-Adenosyl-Methionine), an amino acid naturally produced by the body, may be reduced by aging. Many studies exist regarding the use of SAMe supplementation to enhance mood and promote a positive outlook without side effects. Clinical studies also show SAMe contributes to joint health by stimulating the production of GAGs (Glycosaminoglycans), important components of connective tissue.
Natural SAMe is a stable, bioavailable form of S-adenosyl-l-methionine. These tablets are enteric coated to prevent breakdown and inactivation of the ingredients. Dozens of clinical studies have demonstrated that SAMe supports joint comfort, function and mobility in the spine, hips and knees. It is important to the joints because of its critical role in cartilage formation. Studies also show that SAMe helps support a positive outlook. It is able to cross the blood-brain barrier where it affects the synthesis and activation of various proteins, such as neurotransmitters. SAMe is known as a "methyl donor." This means that it works by giving up a piece of itself (a methyl group consisting of one carbon and three hydrogen atoms) to other molecules. Methylation plays a part in many critical cellular functions. SAMe is present in every living cell in the body. However, levels of SAMe tend to decline with age.
Dosage
Two tablets, one to three times daily, or as recommended by your health care professional. Take tablets on an empty stomach.
Warning
If you are pregnant, breastfeeding or art taking antidepressant medication, consult your physician before using this product. Take this product under medical supervision if you have bipolar disorder. In a small percentage of people this product may cause nausea, which tends to subside with long-term use.
Although SAMe is present in all living organisms, signficant amounts of the substance are not readily available through foods. SAMe is processed from yeast, and then integrated into a stable compound. The resulting compound is then put into a specifically formulated and enteric coated tablet to further enhance stability, provide release of SAMe in the intestinal tract where it is best absorbed, and increase ease of swallowing. The end result of this is the stable and bio-available form of SAMe.
Dosage
The best time to take SAMe is on an empty stomach at least 30 minutes before a meal. To support and promote joint health, mobility and joint comfort, take 2 tablets twice a day. Clinical studies indicate that benefits may be evident in the first two weeks of supplementation and may continue for a prolonged period of time. For optimal mood and emotional well-being, take 2 tablets in the morning and 2 tablets in the afternoon .
Warning
Keep out of reach of children.
Description:
SAM is formed in the body by combining the amino acid methionine with adenosyl-triphosphate (ATP).
Physiologic Functions:
Decreases serum bilirubin with Gilbert's syndrome
Essential for all sulfur-containing compounds synthesis, including glutathione and other cartilage components that contain sulfur
Functions closely with folic acid and vitamin B12 in methylation reactions
Improves binding of neurotransmitters to receptor sites
Improves fluidity of brain cell membrane
Improves membrane function of the liver
Improves the structure and function of cartilage in osteoarthritic joints
Inactivates estrogens
Increases levels of glutathionine
Increases levels of serotonin, dopamine and phosphatidylserine
May reduce the risk of liver cancer in individuals with chronic liver diseases like chronic hepatitis
Necessary for manufacture of neurotransmitters and phospholipids like phosphatidylcholine and phosphatidylserine
Promotes bile flow
Relieves inflammation and pain of osteoarthritis
Clinical Indications:
Bipolar disorder
Depression
Fertility/Infertility
Fibromyalgia
Osteoarthritis
Parkinson's disease
Cirrhosis
Drug rehabilitation
Gilbert's syndrome
Migraine
Oral contraceptive-induced liver damage
Postpartum depression
Dosages:
Depression:
200 mg. BID for 1 day; then increase to 400 mg. BID by day 3; then 400 mg. TID by day 10; then 400 mg. QID after day 20
Fibromyalgia:
200-400 mg. BID
Osteoarthritis:
Begin dosage like depression; 1200 mg daily after day 21, then reduce to maintenance of 200 mg. BID
Migraine:
200-400 mg. BID for long-term treatment
Liver disorders:
200-400 mg. BID-TID
Drug/Nutrient Interaction:
May enhance elimination of various drugs due to the effects on the liver
Contraindications:
Antidepressant activity may lead to the manic phase in bipolar individuals
Toxicity and Side Effects:
May cause nausea and gastrointestinal disturbances
Copyright 1998 - 2004 by L. Vicky Crouse, ND and James S. Reiley, ND. All rights reserved (ISSN 1527-0661).
Clinical Studies on Sam-e
SAMe for major depression: comparison with imipramine.
New publication: Chiaie et al. report the results of two multicenter studies evaluating the effects of S-adenosyl-L-methionine 1,4-butanedisulfonate (SAMe) in the treatment of 571 patients with major depression (1). The first study evaluated an oral formulation, and the second administered an intramuscular preparation. Subjects included in these investigations were diagnosed with major depressive episode with a unipolar course and no psychotic symptoms as per DSM-IV criteria. All patients had baseline Hamilton Depression Rating Scale (HAM-D) scores >18 and severity scores >4 on the Clinical Global Impression (CGI) rating scale. Only oral lorazepam (1-2.5mg daily) was allowed during the study periods for sleep induction.
The first study utilized a double-blind, randomized, double dummy design. Patients assigned to receive SAMe ingested two SAMe tablets (400mg) once daily and two "imipramine placebo" tablets three times daily. Subjects assigned to receive imipramine initially consumed two imipramine tablets (25mg) once daily and two "SAMe placebo" tablets three times daily. The duration of the trial was six weeks, with full doses of imipramine (150mg daily) being reached after 15 days. The full dose of SAMe reached a maximum of 1600mg daily.
The second study, duplicate published elsewhere (2), also utilized a double-blind, randomized, double dummy design for evaluating the efficacy of intramuscular SAMe. Those assigned to SAMe received an intramuscular injection of SAMe (400mg) and two imipramine placebo tablets three times daily. Patients assigned to imipramine received two imipramine tablets (25mg) three times daily and a placebo intramuscular injection once daily. The duration of this trial was four weeks.
The authors report that both the oral and intramuscular preparations of SAMe, as well as the oral imipramine, significantly decreased mean total HAM-D scores compared to baseline (p<0.001). However, no differences between SAMe and imipramine were observed in HAM-D or CGI scores, or in the secondary measurement of the Montgomery-Asberg Depression Rating Scale. No placebo arm was included in either trial. In both studies, significantly more patients receiving imipramine experienced drug-related adverse events compared to SAMe (p=0.001).
Analysis: This research reports similar improvements in HAM-D or CGI scores after 4-6 weeks of SAMe or imipramine. Although these results are compelling, several methodological flaws prevent the results from being considered conclusive. No placebo arm was included, and therefore the improvements in both groups cannot be distinguished from the natural history of disease in the included subjects. The short duration of the studies (albeit longer than most other studies of SAMe) may not have been adequate to observe the full effects of imipramine. Benefits of imipramine can be seen after 2 weeks, but may take up to 6-8 weeks to observe. In addition, selective serotonin reuptake inhibitors, rather than tricyclic antidepressants, have become the standard of care for major depression. Strengths of this study included the use of validated measurement scales, blinding, and randomization.
Background: SAMe is a substance naturally found in the human brain and other tissues, formed from methionine and adenosine triphosphate in a reaction catalyzed by methionine adenosyltransferase. SAMe functions as a primary methyl group donor in a variety of reactions. After donating a methyl group, SAMe is converted to S-adenosyl-homocysteine.
The mechanism by which SAMe may exert antidepressant effects has not been fully elucidated. SAMe has been found to increase levels of 5-hydroxy-indoleacetic acid, a serotonin metabolite, and homovanillic acid, a dopamine metabolite, in the cerebrospinal fluid (3;4). SAMe may also increase the responsiveness of neurotransmitter receptors.
Prior research: Several controlled trials have evaluated oral or parenteral formulations of SAMe in the management of major depression and depression associated with medical illnesses (5;6;7). Doses have ranged from 800mg to 1600mg taken daily by mouth for up to six weeks, although starting doses as low as 200mg daily have been used (8;9;10;11;12). Overall, SAMe has been reported as superior to placebo (8;9;13;14;15;16;17;18) and possibly equivalent to tricyclic antidepressants (11;12;15;19;20;21;22), although the majority of studies have had significant methodological flaws. Some research suggests that SAMe has a more rapid onset of action than tricyclic antidepressants.
The majority of trials comparing SAMe to tricyclic antidepressants (most commonly to imipramine), have been conducted over a brief period (<3 weeks), possibly too limited to accurately assess effects of tricyclics. One previous study was conducted over 6 weeks (11). At the completion of this trial, percent improvements in the imipramine group surpassed those in the SAMe group compared to baseline. However, no between-group statistical comparison was performed.
SAMe has been studied for other conditions as well, and is reported to decrease osteoarthritis pain by a small amount, with possible equivalence to NSAIDs. The evidence regarding the use of SAMe for intrahepatic cholestasis of pregnancy, fibromyalgia, or Alzheimer's disease remains inconclusive.
Safety overview: SAMe is typically well tolerated in the majority of available clinical trials. Side effects such as restlessness, anxiety, insomnia, and mania occasionally occur, and may be more common in people with bipolar disorder. Stomach upset and nausea may be experienced, particularly at higher doses. Skin rashes have been reported. There is one case report of serotonin syndrome in a woman taking SAMe 100mg daily intramuscularly with 75mg daily of clomipramine (23).
Conclusion: Several human trials report SAMe to be superior to placebo and possibly equivalent to tricyclic antidepressants (TCAs) in the management of major depression. However, most studies have been methodologically flawed and brief in duration (<6 weeks). Reliable comparisons to selective serotonin reuptake inhibitors (SSRIs) are not available. Individuals with depression who are unwilling or unable to take prescription antidepressants (such as TCAs or SSRIs) may be candidates for therapy with SAMe. Caution is warranted in patients with bipolar disorder due to reports of mania or anxiety.
1. Chiaie R, Pancheri P, Scapicchio P. Efficacy and tolerability of oral and intramuscular S-adenosyl-L-methionine 1,4-butanedisulfonate (SAMe) in the treatment of major depression: comparison with imipramine in 2 multicenter studies. Am J Clin Nutr 2002;76(suppl):1172S-1176S.
2. Pancheri P, Scapicchio P, Chiaie RD. A double-blind, randomized parallel-group, efficacy and safety study of intramuscular S-adenosyl-L-methionine 1,4-butanedisulphonate (SAMe) versus imipramine in patients with major depressive disorder. Int J Neuropsychopharmacol 2002;5(4):287-294. View Abstract
3. Ancarani E, Biondi B, Bolletta A, et al. Major depression complicating hemodialysis in patients with chronic renal failure: a multicenter, double-blind, controlled clinical trial of S-adenosyl-L-methionine versus placebo. Curr Ther Res 1993;54(6):680-686.
4. Agricola R, Dalla Verde G, Urani R, et al. S-adenosyl-L-methionine in the treatment of major depression complicating chronic alcoholism. Curr Ther Res 1994;55(1):83-92.
5. Mischoulon D, Fava M. Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence. Am J Clin Nutr 2002;76(5 Suppl):1158S-1161S. View Abstract
6. Bressa GM. S-adenosyl-l-methionine (SAMe) as antidepressant: meta-analysis of clinical studies. Acta Neurol Scand Suppl 1994;154:7-14. View Abstract
7. Delle Chiaie R, Pancheri P. [Combined analysis of two controlled multicentric, double blind studies to assess efficacy and safety of Sulfo-Adenosyl-Methionine (SAMe) vs. placebo (MC1) and SAMe vs. clomipramine (MC2) in the treatment of major depression]. J Ital Psicopatol 1999;5(1):1-16.
8. Kagan BL, Sultzer DL, Rosenlicht N, et al. Oral S-adenosylmethionine in depression: a randomized, double-blind, placebo-controlled trial. Am J Psychiatry 1990;147(5):591-595. View Abstract
9. Salmaggi P, Bressa GM, Nicchia G, et al. Double-blind, placebo-controlled study of S-adenosyl-L-methionine in depressed postmenopausal women. Psychother Psychosom 1993;59(1):34-40. View Abstract
10. Carrieri PB, Indaco A, Gentile S, et al. S-adenosylmethionine treatment of depression in patients with Parkinson's disease: a double-blind, crossover study versus placebo. Curr Ther Res 1990;48(1):154-160.
11. De Vanna M, Rigamonti R. Oral S-adenosyl-L-methionine in depression. Curr Ther Res 1992;52(3):478-485.
12. Bell KM, Potkin SG, Carreon D, et al. S-adenosylmethionine blood levels in major depression: changes with drug treatment. Acta Neurol Scand Suppl 1994;154:15-18. View Abstract
13. Barberi A, Pusateri C. Sugli effetti clinici della S-adenosil-L-metionina (SAMe) nelle sindromi depressive. Minerva Psichiatrica 1978;19:235-243.
14. Muscettola G, Galzenati M, Balbi A. SAMe versus placebo: a double blind comparison in major depressive disorders. Advances in Biochemical Psychopharmacology 1982;32:151-156. View Abstract
15. Janicak PG, Lipinski J, Davis JM, et al. S-adenosylmethionine in depression. A literature review and preliminary report. Ala J Med Sci 1988;25(3):306-313. View Abstract
16. Fava M, Giannelli A, Rapisarda V, et al. Rapidity of onset of the antidepressant effect of parenteral S-adenosyl- L-methionine. Psychiatry Res 1995;56(3):295-297. View Abstract
17. Caruso I, Fumagalli M, Boccassini L, et al. Treatment of depression in rheumatoid arthritic patients. A comparison of S-adenosylmethionine (Samyr*) and placebo in a double-blind study. Clin Trials J 1987;24(4):305-310.
18. Carney MW, Edeh J, Bottiglieri T, et al. Affective illness and S-adenosyl methionine: a preliminary report. Clin Neuropharmacol 1986;9(4):379-385. View Abstract
19. Miccoli L, Porro V, Bertolino A. Comparison between the antidepressant activity and of S- adenosylmethionine (SAMe) and that of some tricyclic drugs. Acta Neurol (Napoli) 1978;33 (3):243-255. View Abstract
20. Scarzella R, Appiotti A. Confronto clinico in doppio cieco della SAMe versus clorimipramina nelle sindromi depressive. Rivista Sperimentale di Freniatria 1978;102:359-365.
21. Monaco P, Quattrocchi F. [Study of the antidepressive effects of a biological transmethylating agent (S-adenosyl-methione or SAM)]. Rivista di Neurologia 1979;49(6):417-439. View Abstract
22. Bell KM, Plon L, Bunney WE, Jr., et al. S-adenosylmethionine treatment of depression: a controlled clinical trial. Am J Psychiatry 1988;145(9):1110-1114. View Abstract
23. Iruela LM, Minguez L, Merino J, et al. Toxic interaction of S-adenosylmethionine and clomipramine. Am J Psychiatry 1993;150(3):522. View Abstract
PHYSIOLOGY:
SAMe is produced in the liver from the amino acid methionine. In the body, SAMe functions as a methylation agent, transferring methyl groups between molecules. SAMe is the most effective of all methyl donors. It participates in 35-40 essential biochemical processes including detoxification reactions and manufacture of brain chemicals, antioxidants and joint tissue structures. Folic acid and vitamin B-12 are necessary for the synthesis of SAMe, and deficiencies of these vitamins result in low concentrations of SAMe in the central nervous system (CNS). Low blood or CNS levels have been detected in people with cirrhosis of the liver, coronary heart disease, Alzheimer's disease and depression. SAMe has been effectively used as an anti-depressant; it is beneficial for disorders of the joints and connective tissues, such as osteoarthritis and fibromyalgia; it promotes the health of the liver; and it may lower homocysteine levels, an amino acid acid associated with cardiovascular disease.
INDICATIONS:
Depression, Fibromyalgia, Osteoarthritis, Migraine Headaches, Liver Disorders, Male Infertility.
Dosage:
Depression Use: 400 mg. - 1600 mg. daily in divided doses. Liver Problem Use: Up to 1600 mg. daily in divided doses. Osteoarthritis: 200 mg. - 1200 mg. daily in divided doses. Migraine Headache and Fibromyalgia Use: 400 mg. daily. SAMe should be taken on an empty stomach, i.e. one hour before or two hours after meals.
WARNING:
Individuals being treated for neurological conditions and those with bipolar disorder (manic-depressive illness) should take this product only under professional supervision. Do not take if using MAO inhibitors.
SAM-e is "shorthand" for a chemical found in the body called S-adenosylmethionine. SAM-e is not a vitamin but a special chemical that is obtained from food sources and manufactured in the body from food. Its role is to provide a specific building block (called a "methyl group") for the manufacture of a variety of the body's vital substances including the hereditary material, DNA.
SAM-e's current popularity as a dietary supplement stems from its use in the treatment of mental disorders, particularly depression. A variety of studies have shown SAM-e to be effective as a treatment for mild to moderate depression. For several years, SAM-e has been a prescription medication for the treatment of depression in several European countries. In the U.S., SAM-e is available without a prescription as a dietary supplement.
Because depression is a serious illness, depressed individuals should consult a mental health professional rather than use SAM-e to self-treat their depression. SAM-e should not be taken with other psychiatric medications as it may augment or interfere with their actions.
Besides depression, SAM-e may be helpful in relieving symptoms of anxiety, osteoarthritis, multiple sclerosis, fibromyalgia, Parkinson's disease, and Alzheimer's disease. It also may be helpful in reducing the risk of heart disease.
Unlike prescription drugs, SAM-e is not tested for purity, efficacy or safety by the Food and Drug Administration because it is classified as a dietary supplement. In doses generally taken (200 mg - 800 mg per day), SAM-e appears to be non-toxic and causes hardly any side effects.
Written by Eric Golanty, Ph.D, thehealthchannel.com Editorial Team
S-Adenosylmethionine (SAMe) - A Very Important Natural Product
by Dr. Michael Murray
S-Adenosylmethionine (SAMe) is a key physiological agent formed in the body by combining the essential amino acid methionine to adenosyl-tri-phosphate (ATP). SAMe was discovered in Italy in 1952. Not surprisingly, most of the research on SAMe has been conducted in the country of its discovery.
Because SAMe is manufactured from methionine, one would think that dietary sources of methionine would provide the same benefits as SAMe. However, high doses of methionine have not been shown to increase levels of SAMe, nor does it provide the same pharmacological activity as SAMe, and high dosages of methionine are associated with some degree of toxicity.
Normally the body manufactures all the SAMe it needs from the amino acid methionine. However, a deficiency of methionine, vitamin B12, or folic acid can result in decreased SAMe synthesis. In addition, tissue levels of SAMe are typically low the elderly and in patients suffering from osteoarthritis, depression, and various liver disorders.
Pharmacology
SAMe is involved in over 40 biochemical reactions in the body. It functions closely with folic acid and vitamin B12 in "methylation" reactions. Methylation is the process of adding a single carbon unit (a methyl group) to another molecule. SAMe is many times more effective in transferring methyl groups than other methyl donors. Methylation reactions are critical in the manufacture of many body components especially brain chemicals as well as in detoxification reactions.
SAMe is also required in the manufacture of all sulfur-containing compounds in the human body including glutathione (discussed below) and various sulfur-containing cartilage components.
The beneficial effects of SAMe supplementation are far-reaching due to its central role in so many metabolic processes.
Clinical Indications
There are five principle uses of SAMe: depression, osteoarthritis, fibromyalgia, liver disorders, and migraine headaches.
Depression
SAMe is necessary in the manufacture of important brain compounds such as neurotransmitters and phospholipids like phosphatidylcholine and phosphatidylserine. Supplementing the diet with SAMe in depressed patients results in increased levels of serotonin, dopamine, and phosphatidylserine, and improved binding of neurotransmitters to receptor sites, resulting in increased serotonin and dopamine activity and improved brain cell membrane fluidity resulting in significant clinical improvement.
Based on results from a number of clinical studies it appears that SAMe is perhaps the most effective natural antidepressant (although a strong argument could be made for the extract of St. John's wort standardized to contain 0.3% hypericin).
Several studies have compared SAMe to antidepressant drugs. These studies have shown that SAMe is better tolerated and has a quicker onset. In one study comparing SAMe to desipramine, at the end of the 4-week trial 62% of the patients treated with SAMe and 50% of the patients treated with desipramine had significantly improved. Regardless of the type of treatment, patients with a 50% decrease in their Hamilton Depression Scale (HAM-D) score showed a significant increase in plasma SAMe concentration. These results suggest that one of the ways that tricyclic drugs exert antidepressive effects is by raising SAMe levels.
Detailed clinical evaluations utilizing electroencephalograms (EEGs), event-related potentials (ERPs) and low-resolution brain electromagnetic tomography (LORETA) have clearly indicated a central nervous system antidepressant action of SAMe.
Osteoarthritis
SAMe has also demonstrated impressive results in the treatment of osteoarthritis. A deficiency of SAMe in the joint tissue, just like a deficiency of glucosamine, leads to loss of the gel-like nature and shock absorbing qualities of cartilage. As a result, osteoarthritis can develop.
In vitro studies have shown that SAMe exerts a number of effects that appear to be highly relevant in the treatment of osteoarthritis. First of all, SAMe has been shown to be very important in the manufacture of cartilage components. This effect has been demonstrated very well in humans. In one double-blind study conducted in Germany, the 14 patients with osteoarthritis of the hands that were given SAMe demonstrated increased cartilage formation as determined by magnetic resonance imaging (MRI). These results indicate SAMe is capable of producing improvements in the structure and function of cartilage in joints affected by osteoarthritis. In addition to this effect, SAMe has also demonstrated some mild pain-relieving and anti-inflammatory effects in animal studies. All of these effects combine to produce exceptional clinical benefits.
In double-blind trials, SAMe has demonstrated similar reductions in pain scores and clinical symptoms to NSAIDS like ibuprofen, indomethacin, naproxen, and piroxicam. What all of these studies indicate is that SAMe appears to offer significant advantages over NSAIDs. While these drugs are associated with significant risk of toxicity, side effects, and actual promotion of the disease process in osteoarthritis, SAMe offers similar benefits without risk or side effect.
Fibromyalgia
SAMe has been shown in four double-blind clinical studies to produce excellent benefits in patients suffering from fibromyalgia. In one of the studies, SAMe was compared to transcutaneous electrical nerve stimulation (TENS) - a popular treatment for fibromyalgia - in 30 patients with fibromyalgia. Patients receiving SAMe (200 mg by injection and 400 mg orally daily) demonstrated significantly greater clinical benefit as noted by a decreased number of tender points, subjective feelings of pain and fatigue, and improved mood. TENS offered little benefit on most symptoms while SAMe was deemed "effective in relieving the signs and symptoms of primary fibromyalgia."
Liver Disorders
SAMe has been shown to be quite beneficial in several liver disorders including cirrhosis, Gilbert's syndrome, and oral contraceptive-induced liver damage. Its benefits are related to its function as the major methyl donor in the liver and it's lipotropic activity. One of the leading contributors to impaired liver function is diminished bile flow or cholestasis. SAMe is beneficial for a variety of liver disorders because of its ability to promote bile flow and relieve cholestasis.
One of the greatest risks of chronic liver diseases such as chronic hepatitis is liver cancer. Supplementation with SAMe appears to be very much indicated in these patients in the attempt to reduce the risk for liver cancer. Animal studies have shown a significant protective effect for supplemental SAMe against liver cancer in animals exposed to liver carcinogens.
Migraine
SAMe has also been shown to be of benefit in the treatment of migraine headaches. The benefit arises gradually and long-term treatment is required for therapeutic effectiveness.
Dosage
In general, the longer that SAMe is used the more beneficial the results. It is perfectly suited for long-term use because of its excellent safety profile. The typical dosage range is 100 to 200 mg twice daily.
No significant side effects have been reported with oral SAMe other than the occasional nausea and gastrointestinal disturbances. However, individuals with bipolar (manic) depression should not take SAMe unless under strict medical supervision because SAMe's antidepressant activity may lead to the manic phase in these individuals. This effect is exclusive to some individuals with bipolar depression.
Interactions and Contraindications
SAMe functions very closely with vitamin B12, folic acid, vitamin B6 and choline in methylation reactions. Because of SAMe's effects on the liver, it may enhance the elimination of various drugs from the body. The clinical significance of this effect has not been fully determined.
It has been cautioned that SAMe be avoided in patients Parkinson's disease. Animal studies indicate that excessive methylation is associated with Parkinson's disease and SAMe excess has caused Parkinson's disease-like effects in animal studies. In addition, both animal and human studies indicate that increased methylation can cause the depletion of dopamine and block the effects of L-dopa. This line of research is contradicted, however, by preliminary evidence that SAMe may improve the emotional depression and the impaired mental function that is often associated with Parkinson's disease. Nonetheless, it is recommended that patients with Parkinson's disease avoid supplementing with SAMe until more is known.
Key References:
1. Stramentinoli G. Pharmacologic aspects of S-adenosylmethionine. Pharmacokinetics and pharmacodynamics. Am J Med 1987;83(5A):35-42.
2. Bressa GM. S-adenosyl-l-methionine (SAMee) as antidepressant: Meta-analysis of clinical studies. Acta Neurol Scand 1994;154(suppl):7-14.
3. Saletu B, Anderer P, Di Padova C, Assandri A, Saletu-Zyhlarz GM. Electrophysiological neuroimaging of the central effects of S-adenosyl-L-methionine by mapping of electroencephalograms and event-related potentials and low-resolution brain electromagnetic tomography. Am J Clin Nutr 2002;76(5):1162S-71S.
4. Soeken KL, Lee WL, Bausell RB, Agelli M, Berman BM. Safety and efficacy of S-adenosylmethionine (SAMe) for osteoarthritis. J Fam Pract 2002;51(5):425-30.
5. Jacobsen S, Danneskiold-Samsoe B, Andersen RB. Oral S-adenosylmethionine in primary fibromyalgia: double-blind clinical evaluation. Scand J Rheumatol 1991;20:294-302.
6. Di Benedetto P, Iona LG and Zidarich V: Clinical evaluation of S-adenosyl-L-methionine versus transcutaneous nerve stimulation in primary fibromyalgia. Curr Ther Res 53:222-9, 1993.
7. Avila MA, Garcia-Trevijano ER, Martinez-Chantar ML, et al. S-Adenosylmethionine revisited: its essential role in the regulation of liver function. Alcohol 2002;27(3):163-7.
8. Cheng H, Gomes-Trolin C, Aquilonius SM, et al. Levels of L-methionine S-adenosyltransferase activity in erythrocytes and concentrations of S-adenosylmethionine and S-adenosylhomocysteine in whole blood of patients with Parkinson's disease. Exp Neurol 1997;145:580-5.
9. Charlton CG, Crowell B Jr. Parkinson's disease-like effects of S-adenosyl-L-methionine: effects of L-dopa. Pharmacol Biochem Behav 1992;43:423-31.
10. Di Rocco A, Rogers JD, Brown R, Werner P, Bottiglieri T. S-Adenosyl-Methionine improves depression in patients with Parkinson's disease in an open-label clinical trial. Mov Disord 2000;15(6):1225-9.
SAMe to the Rescue
by Allen S. Josephs, M.D.
Since I became interested in the field of nutrition approximately ten years ago, early on my attention turned to a nutrient known as SAMe (S-adenosyl methionine). SAMe is a powerful antioxidant and is critical in the methylation cycle. This cycle provides the body the ability to repair cells and detoxify.
In the mid 1980s, a prestigious medical journal known as the American Journal of Medicine did an entire symposium on SAMe documenting benefits for various disease conditions. In the last several years, SAMe has become an extremely popular supplement.
A government report recently concluded that the dietary supplement, SAMe, appears equally effective as prescription drugs for both depression and osteoarthritis. This was released in an evidence report summary on the supplement that was sponsored by the U.S. Department of Health and Human Resources. A group of researchers examined 102 clinical trials regarding SAMe. This team of researchers worked for more than three years to conduct a literature review on these 102 clinical trials. The team's key findings on SAMe included that it was thought to be as effective as prescription anti-depressants; that it worked as effectively for osteoarthritic pain as non-steroidal, anti-inflammatory drugs and that it may even help some liver conditions. Although SAMe appeared to be as efficacious as standard anti-depressant medication, it did not have any of the side-effects of prescription anti-depressants such as headaches, weight gain and most significantly, sexual dysfunction.
This is exciting news. It provides individuals with a healthy alternative for health benefits with osteoarthritis and depression. SAMe has also been shown in several clinical trials to be effective for fibromyalgia, a disabling condition effecting millions of individuals in this country. SAMe also may lower homocysteine levels. High levels of homocysteine have been proven to cause strokes and heart attacks. It is critical that SAMe be consumed at levels that are effective; most studies used 800 mg–1,600 mg per day. It is also important to understand that SAMe must be taken in a stabilized and standardized tablet form (this is one of the rare examples of a nutrient that is superior in a tablet form). SAMe is 50% elemental, so a product must provide 800 mg gross to equal 400 mg elemental.
SAMe is an important biological agent in the human body, participating in over 40 essential biochemical reactions. SAMe participates in detoxification reactions and in the manufacture of brain chemicals, antioxidants, joint tissue structures, and many other important components.
Government Report Concludes: Dietary Supplement SAM-e Equally Effective as Prescription Drugs for Depression, Osteoarthritis
The popular, over-the-counter dietary supplement SAM-e, shows promise as an equivalent treatment to prescription drugs for depression and osteoarthritis and may help some chronic liver conditions. This information comes from a just-released Evidence Report Summary on the supplement sponsored by the U.S. Department of Health and Human Services' (HHS) Agency for Healthcare Research and Quality (AHRQ).
"The Department of Health and Human Services hired an impeccable group of researchers to examine 102 clinical studies to determine whether or not SAM-e works ... their results are quite compelling," said Hyla Cass, M.D., a Los Angeles-based clinical psychiatrist and UCLA assistant professor.
The Evidence Report on SAM-e was prepared for the HHS by Rand Corporation, a Southern Calif.-based think tank. A 16-person team of medical professionals worked for more than three years to conduct a literature review and synthesis of evidence on 102 different human clinical studies of SAM-e to determine its efficacy for treatment of depression, osteoarthritis and cholestasis of pregnancy and intrahepatic cholestasis associated with liver disease.
According to the Evidence Report's summary, the team's key findings include evidence that SAM-e:
*Is as effective as prescription antidepressants
*Fights osteoarthritis pain as well as non-steroidal anti-inflammatory drugs (NSAIDS)
*Helps some liver conditions
Also according to the summary, the objective of the Evidence Report "was to conduct a search of the published literature on the use of S-adenosyl-L-methionine (SAM-e) for the treatment of osteoarthritis, depression and liver disease." The summary refers to the high annual costs -- $43.7 to $52.9 billion -- associated with treatment and lost wages for depression. It also states that an estimated 15 percent of Americans suffer from arthritis and the annual cost to society is estimated at $95 billion. Osteoarthritis is the most common form of arthritis.
SAM-e and Depression
Among the findings culled from 47 studies on the treatment of depression, the summary concludes that "compared to the use of conventional antidepressant pharmacology, treatment with SAM-e was not associated with a statistically significant difference in outcomes."
"These new findings suggest that SAM-e works as effectively as prescription drugs and it does it without the side effects," added Dr. Cass.
"This is big news for patients who suffer side effects from prescription antidepressants such as headaches, weight gain and the most significant -- sexual dysfunction."
SAM-e and Joint Health
The team also examined 14 studies of osteoarthritis, which causes pain in the joints. The Evidence Report summary concludes that SAM-e appears to work as effectively as non-steroidal anti-inflammatory drugs (NSAIDS) in treating osteoarthritis.
SAM-e and Liver Disease
More than 40 studies of liver disease were analyzed for the Evidence Report. The summary states promise that SAM-e may have an effect on intrahepatic cholestasis of pregnancy. This condition, caused by elevated levels of bilirubin in the liver, occurs in 1 in 500 to 1,000 pregnancies.
The report's summary recommends more studies on SAM-e in the area of liver disease as well as depression and osteoarthritis to understand "the risk benefit ratio of SAM-e compared to conventional therapy, especially for depression and osteoarthritis."
Consumers interested in learning more may view the SAM-e Evidence Report Summary by logging onto the Department of Health and Human Services' Agency for Healthcare Research Quality web site at http://www.ahrq.gov/clinic/epcsums/samesum.htm.
The entire SAM-e Evidence Report is expected to be available to the public at the same web address in late 2002.
About SAM-e
SAM-e is an acronym for S-adenosyl-L-methionine, a natural compound found in every human cell and involved in over 35 biochemical processes in the body. Low levels of SAM-e in the body have been correlated with depression. In addition, clinical research findings as demonstrated in this Report Executive Summary support SAM-e's ability to promote joint and liver health.
SAM-e has been touted for its fast acting mood elevating benefits and lack of side effects (such as weight gain and sexual problems) commonly found in prescription anti-depressants. It was officially introduced into the U.S. as a dietary supplement in 1998.
SAM-e: Improving Joint Function, Mood & Much More
By Allen S. Josephs, M.D.
The Vioxx saga continues. For those of you who have not been following the news, Vioxx, the blockbuster arthritis drug from Merck, was voluntarily recalled by the pharmaceutical company on September 30, 2004, after a clinical study showed that users were at an increased risk of suffering heart attack or stroke. It has been estimated that Vioxx may have led to more than 27,000 heart attacks and cardiac deaths before it was removed from the market. Merck has estimated that it expects lawsuits from upwards of 16,000 customers, although the number could be much higher. The tort attorneys are licking their chops. Merck, which has been around since the early 1900s, faces the real possibility that this "mega"-lawsuit could actually bankrupt the company. These comments were mentioned in a recent article in New York Magazine. Although Bextra and Celebrex, the two other COX-2 inhibitors, are for the time being considered "safe," I would not be surprised if, at some point down the road, these drugs possibly suffered a similar fate as Vioxx.
For the tens of millions of arthritis sufferers in this country, the treatment options have now become much more limited. There is clearly uncertainty about the remaining two COX-2 inhibitors, Bextra and Celebrex. The other drug options are the typical non-steroidal, anti-inflammatory drugs, such as ibuprofen and naproxen. Unfortunately, these drugs are fraught with tremendous side effects, including significantly increased risk of gastrointestinal bleeding, kidney and liver failure, and even congestive heart failure. There is, however, a tremendous alternative that I would like to share with you.
There was a study published earlier this year in the journal BMC Musculoskeletal Disorders. Sixty-one adults over the age of forty with a history of osteoarthritis of the knee were enrolled in a study to compare the difference between Celebrex and a nutrient known as S-adenosyl-l-methionine, commonly known as SAM-e. The study was randomized and double-blinded, with half of the group receiving SAM-e 1,200 mg daily and the other half group receiving full-strength Celebrex 200 mg a day for a total of sixteen weeks. The results were quite amazing. In the first month of the study, the Celebrex group showed a reduction in pain that was statistically significant. However, by the second month, those patients taking SAM-e had a similar reduction in the level of pain compared to the group being treated with Celebrex. It was concluded that SAM-e had a slower onset of action, but it was as effective as Celebrex in the management of symptoms of knee osteoarthritis.
SAM-e is an interesting nutrient. It was first discovered in Italy over fifty years ago. Soon thereafter, it became extremely popular throughout Europe, and only in the last few years has it been available in the United States. The exact mechanism as to how SAM-e diminishes pain in osteoarthritis is not clearly known. There is some evidence that suggests that it may reduce inflammation, as well as stimulating production of certain proteins to improve joint function. SAM-e, however, has also been shown in other clinical trials to have benefits for depression, headaches, and even fibromyalgia. SAM-e was even the subject of discussion in an entire symposium from the prestigious American Journal of Medicine in the 1980s. SAMe also has benefits for:
Brain Metabolism. SAM-e methylation reactions are involved in the synthesis of neurotransmitters, such as L-dopa and dopamine, and their related hormones, epinephrine and phosphatidylcholine (a component of lecithin).
Longevity. Methylation of DNA appears to be important in the suppression of errors in DNA replication. Demethylation of DNA is considered a contributor to the aging process. Proper methylation, through substances such as SAM-e, positively influences longevity.
Liver. SAM-e metabolism supports the synthesis of glutathione (GSH) and glutathione-dependent enzymes (glutathione peroxidase and glutathione-S-transferase), which are powerful antioxidants that are also important for liver function.
SAM-e is manufactured under low temperature and low humidity, and are enteric-coated to ensure a biologically active product. SAM-e is a chiral molecule and therefore consists of two forms: (S,S) SAM-e and (R,S) SAM-e. The biologically active form is the (S,S) structure, while the (R,S) structure is biologically inactive. Our SAM-e is made naturally by microbiological fermentation and then specially processed without solvents to preserve 68-80% (S,S) SAM-e, the highest active level available.
Just remember that when using this product for arthritis or any other conditions listed above, the response is not immediate. It can take weeks or a few months to see benefits. Also, SAM-e is very synergistic and safe to use with Joint Support and glucosamine/chondroitin/MSM joint health products. In addition, I would refer you back to a recent newsletter that I wrote about other natural options for healthy joints. |
