S-adenosyl-L-methionine (SAMe) is found in all living cells.
SAMe is a naturally occurring molecule that is formed in the body from methionine, an essential amino acid. Up to half of the daily intake of methionine is metabolized into SAMe in the liver.
Vitamin B6, B12, and folic acid are required for proper formation and metabolism of SAMe.
SAMe is present only in minute amounts in the diet, and its principal source in the body is through methionine metabolism. Supplements are the only significant dietary source of SAMe.
An average adult produces 7-8 g of SAMe each day.
SAMe plays an important role as a methyl donor in more than 100 methyltransferase reactions. Methylation is a key step in the biosynthesis of DNA, RNA, phospholipids, proteins, epinephrine, melatonin, and neurotransmitters.
SAMe was first marketed as a prescription drug in 1976 in Italy and became available as a dietary supplement in the U.S. in 1999. Since S-adenosyl-L-methionine is not a stable molecule, commercial products are the tosylate, disulfate tosylate, disulfate ditosylate, or disulfate monotosylate and butanedisulfonate salts. The butanedisulfonate form of SAMe is primarily delivered via injections and is not used as a dietary supplement.
SAMe is available in certain countries outside the U.S. as a prescription drug for depression, osteoarthritis, and liver disease.
SAMe is essential for three key metabolic pathways: transmethylation, transsulfuration, and polyamine synthesis.
In transmethylation reactions, SAMe donates a methyl group to a wide variety of substrates including DNA, proteins, neurotransmitters, and phospholipids.
In transsulfuration reactions, SAMe is converted to cysteine in a series of enzymatic steps. Cysteine is a precursor of glutathione, a major cellular antioxidant. SAMe also stimulates the synthesis of the proteoglycans used for cartilage regeneration.
Polyamines are involved in regulation of cell growth. SAMe is involved in synthesis of the polyamines spermidine and spermine through the aminopropylation pathway. Spermidine and spermine have anti-inflammatory and analgesic effects.
Four hundred to 1600 mg of SAMe has been used in treating depression and osteoarthritis and has been well-tolerated without severe side effects. Some people experience stomachache.
SAMe has been administered as a prescription drug in Italy since 1976. During that time, about 17 million people have been exposed to SAMe without any reports of serious adverse events.
So far there are no reported adverse interactions with SAMe and other drugs, dietary supplements, or foods.
There is little clinical data on doses greater than 1600 mg/day, so this dose should be considered the upper limit.
Patients with bipolar (manic) depression should not take SAMe without physician supervision. A study of parenteral SAMe found that manic phase was accentuated in one of fifteen of these patients.
SAMe is not recommended for use by children.
Lactating and pregnant women should consult their medical supervisors. In some clinical trials, doses of 3200 mg/day were administered intravenously to pregnant women without any harm to mother or offspring.
Combining SAMe with monoamine oxidase inhibitors (MAOIs), such as isocarboxazid (Marplan), or selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac), or tricyclic antidepressants (TCAs), such as amitriptyline (Elavil), may increase a risk of serotonin syndrome. This syndrome occurs when high concentrations of serotonin build up in the body. High levels of serotonin cause anxiety, restlessness, muscle twitching, and tremor. Consulting with a physician or pharmacist before taking these medications with concomitant use of SAMe is required.
Tramadol (Ultram) is an analgesic used for the treatment of moderate pain. This medication can increase a risk of serotonin syndrome. It is advisable for people taking tramadol to avoid SAMe supplements.
Information on the relationship between substances and disease is provided for general information, in order to convey a balanced review of the scientific literature. In many cases the relationship between a substance and a disease is tentative and additional research is needed to confirm such a relationship.
S-adenosyl-L-methionine (SAMe) as an adjunct for resistant major depressive disorder: an open trial following partial or nonresponse to selective serotonin reuptake inhibitors or venlafaxine.
Thirty people taking antidepressants (SSRIs) but still suffering from depressive symptoms added 800 mg of SAMe for 2 weeks, then 1600 mg for the remaining 4 weeks or the clinical trial. Significant improvement in depressive symptoms was demonstrated by results of the Hamilton Depression Rating Scale. This trial showed a response rate to SAMe of 50% and a complete remission rate of 43%. The authors concluded that these results warrant a placebo-controlled trial in resistant depression. 13
S-Adenosyl-L-methionine for treatment of depression, osteoarthritis, and liver disease.
The Agency for Healthcare Research and Quality (AHRQ) included 28 studies evaluating the efficacy of SAMe to decrease symptoms of depression. Compared to placebo, SAMe was associated both statistically and clinically with significant improvements in the score of the Hamilton Rating Scale for Depression. When compared to conventional antidepressants, treatment with SAMe was not associated with a statistically significant difference in outcomes suggesting SAMe was as effective as certain prescription antidepressant drugs. 10
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.
Two multi-center, double-blind clinical trials were conducted with patients to confirm the efficacy and safety of SAMe in the treatment of major depression. Each study compared SAMe to imipramine for depression. In one study, subjects received 1600 mg/day of SAMe orally or 150 mg imipramine. In the second study subjects received 400 mg/day SAMe intramuscularly or 150 mg imipramine. The anti-depressive effectiveness of both oral and intramuscular SAMe was comparable to imipramine. In addition, SAMe had fewer adverse events and was better tolerated than imipramine. 12
Double-blind, placebo-controlled pharmacodynamic studies with a nutraceutical and a pharmaceutical dose of ademetionine (SAMe) in elderly subjects, utilizing EEG mapping and psychometry.
Twelve normal, older subjects participated in this double-blind, placebo-controlled crossover study. Six men and six women were randomly assigned to receive 1600 mg SAMe, 400 mg SAMe, or a placebo for 15 weeks. With this crossover design, each subject received each treatment, separated by a two week washout period. Brain function was assessed by EEG recordings and psychometric tests at 0, 1, 3, and 6 hours after SAMe or placebo on days 1 and 15 of each period. SAMe at both doses was associated with improvement in brain function. Dose-efficacy calculations determined that 1600 mg was more effective than 400 mg but both SAMe doses were more effective than placebo. 6
Arthritis:
S-Adenosyl-L-methionine for treatment of depression, osteoarthritis, and liver disease.
Ten studies were included in the ARHQ review of the efficacy of SAMe to decrease pain of osteoarthritis. One large randomized clinical trial showed an effect size in favor of SAMe of 0.20 (95 percent CI) compared to placebo, thus demonstrating a decrease in the pain of osteoarthritis. Compared to treatment with non-steroidal anti-inflammatory medication, treatment with SAMe was not associated with a statistically significant difference in outcomes. 10
S-adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: a double-blind cross-over trial.
Fifty-six adults with osteoarthritis of the knee enrolled in a randomized double-blind study of SAMe versus celecoxib. Subjects were randomly assigned to receive 1200 mg SAMe or 200 mg celecoxib daily for 16 weeks. During month one, the celecoxib group demonstrated significantly greater pain reduction than the SAMe group (p=0.024). However, during month two and later there was no difference between the SAMe and celecoxib groups (p<0.01). Both groups demonstrated a notable improvement from baseline. Joint function continued to improve in both groups for the duration of the study. The results of this study indicate that SAMe and celecoxib are both effective for osteoarthritis. Larger studies of longer duration are indicated. 8
Liver Disease:
S-Adenosyl-L-methionine for treatment of depression, osteoarthritis, and liver disease.
The AHRQ included 6 studies in a meta-analysis of the efficacy of SAMe to relieve pruritus and decrease elevated bilirubin levels associated with intrahepatic cholestasis caused by a variety of liver diseases. Patients treated with SAMe were twice as likely as placebo-treated patients to have a reduction in pruritus. 10
S-Adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial.
In this multicenter trial, 123 people with alcoholic cirrhosis were randomly assigned to receive either 1200 mg of SAMe or a placebo daily for two years. The mortality or liver transplantation rates were 30% for the placebo group versus 16% for the SAMe supplemented group. This was not a statistically significant difference (p=0.077). If people with advanced liver disease at the beginning of the trial were excluded from the analysis, a statistically significant difference was evident (29% vs. 12%, p=0.025). The results of this randomized, double-blind, placebo-controlled trial indicate that SAMe may help to reduce mortality and progression to liver transplant for people with alcoholic cirrhosis, particularly for those with less advanced disease. 7
The dietary supplement information contained on this site has been compiled from published sources thought to be reliable, but it cannot be guaranteed. Efforts have been made to assure this information is accurate and current. However, some of this information may be purported or outdated due to ongoing research or discoveries. The authors, editors and publishers cannot accept responsibility for errors or omissions or for any consequences from applications of the information in this site and make no warranty, expressed or implied, with respect to the contents herein.
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