Disulfate monotosylate

Other Names

5'-[[(3S)-3-Amino-3-carboxypropyl]methylsulfonio]-5'-deoxy-adenosine disulfate 4-methylbenzenesulfonateAdemethionine disulfate tosylateAdemetionineAdemetionine disulfate tosylateADENOSINE, 5'-(((3S)-3-AMINO-3-CARBOXYPROPYL)METHYLSULFONIO)-5'-DEOXY-, SULFATE, 4-METHYLBENZENESULFONATE SULFATE (1:1:1:1)AdmethionineAdoMetdisulfate-p-toluenesulfonateS-(5'-Adenosyl)-L-methionine disulfate tosylateS-Adenosyl methionineS-Adenosyl-L-methionine disulfate monotosylateS-Adenosyl-L-methionine disulfate P-toluene-sulfonateS-Adenosyl-L-methionine disulfate p-toluenesulfonateS-Adenosyl-L-methionine disulfate tosylateS-Adenosyl-L-methionine disulphate tosylateS-adenosyl-L-methionine p-toluenesulfonic acid sulfateS-adenosylmethionineS-Adenosylmethionine disulfateS-Adenosylmethionine disulfate tosylateS-Adenosylmethionine p-Toluenesulfonate SulfateSAMSAM disulfate monotosylateSAM-eSAM-TSAMeSAMe disulfate monotosylateSAMe disulfate tosylateSAMe tosylate disulfateSAMe-DTSAMe-ST

Synopsis

S-Adenosylmethionine Disulfate Monotosylate (SAMe Disulfate Monotosylate)

Identity and Chemical Character

Disulfate monotosylate is one of several stabilized pharmaceutical salt forms of S-adenosyl-L-methionine (SAMe; also written S-adenosylmethionine, SAM, or SAM-e). S-Adenosyl-L-methionine is also called S-adenosyl methionine, S-adenosylmethionine, SAMe, or SAM-e in the United States, or ademetionine in Europe, and is also often abbreviated as SAM and AdoMet; it is a chemical found naturally in the body. The disulfate monotosylate form is one of at least five salts used commercially to stabilize this inherently labile molecule. The commonly used salts include tosylate, butanedisulfonate, disulfate tosylate, disulfate ditosylate, and disulfate monotosylate. At least five salts are currently available, including SAM tosylate, SAM butanedisulfonate, SAM disulfate tosylate (Swanson/Nature Made), SAM disulfate ditosylate (Natrol), and SAM disulfate monotosylate (GNC).

S-Adenosyl-L-Methionine Disulfate Tosylate, USP is a white to off-white hygroscopic powder; it is odorless and freely soluble in water. The disulfate monotosylate salt shares these general physicochemical characteristics. S-adenosyl methionine is an important physiological molecule discovered in 1952, which is formed in the body from the combination of the essential amino acid methionine with adenosine triphosphate (ATP), in a highly energy-demanding reaction controlled by the SAMe synthetase enzyme.

The active moiety in all SAMe salt forms is the same parent molecule, S-adenosyl-L-methionine. Because of structural instability, stable salt forms of SAM are required for its use as an oral drug. The disulfate monotosylate designation indicates the specific counterion composition used to achieve that stability. Because of structural instability, stable salt forms of SAMe are useful in oral compositions; commonly used salts of SAMe include, without limitation, SAMe tosylate, SAMe butanedisulfonate, SAMe disulfate tosylate, SAMe disulfate ditosylate, and SAMe disulfate monotosylate salt.

The active compound itself — SAMe — is not derived from a botanical source. The main natural source of SAMe for human beings is through intake of foods with high protein content of its methionine precursor; it is calculated that a person on a normal-protein diet averagely ingests about 1 gram of methionine to be converted into SAMe per day. SAMe is not directly obtained from dietary sources in supplemental quantities; rather, the body synthesizes it endogenously, and the salt forms used in supplements and pharmaceuticals are produced through industrial fermentation and chemical processes.

Natural Occurrence and Endogenous Synthesis

S-Adenosylmethionine (SAMe) is found in almost every tissue and fluid in the body. It is biosynthesized intracellularly in a reaction joining methionine and ATP. SAMe is an endogenous molecule synthesized from methionine by many cells in the body; however, the enzyme SAMe synthetase is found predominantly in the liver and is the rate-limiting step for SAMe synthesis in the face of hepatic compromise. The half-life of SAMe in the liver is very short, about 5 minutes, which demonstrates the avidity of the organ for this molecule.

The synthesis of SAMe includes the methylation of homocysteine to methionine by methyltransferase enzyme and cobalamin. Abnormal levels of SAMe in the body have been reported in liver diseases and depression. Because SAMe is not readily available from dietary sources in the quantities used therapeutically, its supplementation relies entirely on stabilized salt preparations manufactured for oral or parenteral use.

Historical Discovery and Traditional Use

SAMe has no history of use in folk or traditional herbal medicine. It is a molecule whose existence and biological role were discovered entirely through modern biochemical science. SAMe, an endogenous compound that is not readily available from dietary sources, was discovered in 1952 by the late Italian scientist Giulio Cantoni, marketed since 1999 as a dietary supplement and then as an antidepressant. The chemical structure of SAMe was described as early as 1952 in a publication by Cantoni GL, "The nature of the active methyl donor formed enzymatically from L-methionine and adenosinetriphosphate," J Am Chem Soc 1952; 74:2942–2943.

The idea of administering exogenous SAMe to patients was pursued since the discovery of the molecule in the 1950s, but it was only after the second half of the 1970s that it was put into practice with the introduction into the pharmaceutical market of the first preparations — administered parenterally (both intravenous and intramuscular) or orally (gastro-protected or gastro-resistant tablets) — of salts of SAMe (such as tosylate, butanedisulfonate, or phytate), stable at room temperature.

In Europe, SAM has been classified and sold as a drug (as ademetionine) for treatment of depression, liver disorders, osteoarthritis, and fibromyalgia since 1979 in Italy, since 1985 in Spain, and since 1989 in Germany. It has been in use for decades in Europe and is a prescription medication in countries such as Italy, Spain, Germany, and Russia. SAMe is also marketed under the brand names GUMBARAL®, SAMYR®, ADOMET®, HEPTRAL®, and ADMETHIONINE® as a prescription drug approved in Russia, Italy, and Germany.

SAMe has been marketed in some European countries since the mid-1980s for the treatment of depression and for other medical conditions such as osteoarthritis, fibromyalgia, and liver disease and migraine headaches; however, it is not formally approved in the UK for the treatment of depression, and in the USA, it is classified only as a dietary supplement. In the United States, SAMe has been available as a dietary supplement since 1999, while in Europe, various pharmaceutical formulations have been available for decades.

The first clinical study of SAMe's use for depression appears to have been conducted in the 1970s (Agnoli A, Andreoli V, Casacchia M, Cerbo R, 1976, Effect of S-adenosyl-L-methionine (SAMe) upon depressive symptoms, J Psychiatr Res 1976; 13:43–54), and since then it has been repeatedly studied.

Chemistry, Stability, and Salt Forms

The instability of the parent SAMe molecule poses a unique challenge for formulation. Non-salified SAMe is very unstable at temperatures above 0°C; alongside thermolability, the second important factor of degradation of the molecule is represented by its hygroscopicity, which can be bypassed by preserving the thermostable salts of SAMe in special protection casings or by freeze-drying the salt under vacuum and putting it into a vial.

Although more-stable salt forms have been developed, SAMe is still liable to degradation, leading to distributors that may advertise a dose higher than what is actually being ingested. Stability data specific to the disulfate monotosylate salt are notable: one study using SAM disulfate monotosylate (GNC) suggests a loss of potency to 49% at day 595 while kept under refrigeration. The comparative stability and bioavailability of these various salt forms is unknown at this time, although one review is available.

The tosylate-based salts, including the disulfate monotosylate, differ in bioavailability from the butanedisulfonate form: according to one study, the oral bioavailability of the tosylate salt is 1%, and the oral bioavailability of the butanedisulfonate salt is 5%. The butanedisulfonate form appears more stable. More broadly, SAMe possesses low bioavailability (0.5–1.0%); however, enteric-coated SAMe formulations may have 2–3% bioavailability.

Regarding isomer composition, supplement labels may specify the ratio of the biologically active (S,S) isomer to the less active (R,S) isomer. One clinical study used 600 mg of SAMe disulfate monotosylate salt standardized to 45% SS and 55% RS isomer twice per day for eight weeks in patients with knee osteoarthritis. The (S,S) stereoisomer is the naturally occurring, biologically active form.

Key Constituents and Mechanisms of Action

All SAMe salt preparations, including the disulfate monotosylate form, deliver the same biologically active compound: S-adenosyl-L-methionine. Supplementation with exogenous SAMe follows the same metabolic pathway as the natural molecule derived from nutritional methionine. The pharmacological effects are therefore attributed to the parent SAMe molecule.

Transmethylation

SAMe is an essential factor in three major biochemical pathways (most important in the liver): transmethylation, transsulfuration, and aminopropylation. SAMe is the primary "methyl" donor for a variety of methyl-transfer reactions in DNA, RNA, proteins, lipids, and small molecules in the body. The basic transmethylation process involves the enzymatic transfer of a methyl group from SAMe to a target molecule, with the result being methylation of the target and generation of S-adenosylhomocysteine; the S-adenosylhomocysteine is then hydrolyzed into adenosine and homocysteine.

Most cells contain numerous SAMe-dependent methyltransferases that can transfer the methyl group (–CH3) to all varieties of key substrates, including nucleic acid, protein, phospholipids, and monoamine neurotransmitters. SAMe, as a major methyl donor, exerts its influence on central nervous system function through cellular transmethylation pathways, including the methylation of DNA, histones, protein phosphatase 2A, and several catecholamine moieties.

Transsulfuration

The transsulfuration pathway begins with S-adenosylhomocysteine (SAH), the residual structure of SAMe upon donating the methyl group; hydrolysis of SAH yields homocysteine, which in turn converts to cystathionine, then cysteine, and eventually to glutathione, the hepatocellular antioxidant and detoxification agent. This pathway underpins much of SAMe's described hepatoprotective activity, because S-adenosylmethionine is defined as a precursor of glutathione and polyamine synthesis, acting as a methyl donor in cellular transmethylation reactions, particularly in the liver.

Aminopropylation (Polyamine Synthesis)

The aminopropylation pathway is initiated with SAMe through decarboxylation; the decarboxylated SAMe then couples with putrescine to generate spermidine and spermine, which are critical to cell growth, differentiation, and the stability of DNA and RNA. Furthermore, methylthioadenosine (MTA), the by-product of polyamine synthesis, is a powerful analgesic and anti-inflammatory agent; this may be, at least partially, responsible for the clinical benefits observed in the treatment of osteoarthritis, rheumatoid arthritis, and fibromyalgia with SAMe.

Neurotransmitter Modulation

Another major role of SAMe is in polyamine biosynthesis; in particular, it is involved in the biosynthesis of several hormones and neurotransmitters that affect mood, such as dopamine and serotonin. In rodents, SAMe dose-dependently decreases immobility time in the forced swimming test and increases concentrations of CNS monoamine neurotransmitters serotonin and norepinephrine. Researchers are not fully certain how SAMe works to relieve depression, but they speculate it might increase the amount of serotonin in the brain, as some antidepressants do.

Hepatic and Epigenetic Effects

SAMe is anti-apoptotic in normal hepatocytes and normal colon epithelial cells, but pro-apoptotic in liver human hepatocellular carcinoma (HCC), HepG2 cells, and colon cancer cells. At the epigenetic level, exogenous administration of AdoMet (SAMe) increases the intracellular ratio of AdoMet to AdoHcy, thereby stimulating DNA methyltransferase (DNMT) activity resulting in increased DNA methylation. In addition to its role as a cofactor of transmethylation reactions, AdoMet can also act as a regulator of DNA methylation metabolism by inhibiting demethylase activity.

Scientific Evidence by Area of Use

Depression

Overall, the evidence that oral SAMe may be helpful for depression is not conclusive. At least 40 studies in people have evaluated SAMe for depression, and many of them showed evidence of beneficial effects; however, most of these trials lasted only a few weeks, included a small number of participants, and were not of the highest scientific quality. Also, some studies used injected SAMe rather than an oral form.

SAMe has been compared to placebo for depressive symptoms in 19 randomized controlled trials (RCTs); six of nine controlled studies conducted between 1976 and 1988 reported that intravenous (200–400 mg/d) or intramuscular (45–200 mg/d) SAMe was more effective than placebo for depression. Starting in the 1990s, adequate oral doses (800–1,600 mg) of enteric-coated, stabilized SAMe could be utilized in clinical studies. Overall, 12 of the 19 randomized, placebo-controlled trials showed the antidepressant effect of SAMe to be significantly greater than placebo for depressive syndromes (P < .05), although many of these studies used samples in which diagnostic criteria for major depressive disorder (MDD) were not required or MDD was not a primary diagnosis.

From 1973 to 1988, 14 double-blind European studies showed that intravenous and intramuscular preparations of SAMe were more effective than placebo and comparable to imipramine, amitriptyline, and clomipramine for treatment of major depression. A 2024 systematic review and meta-analysis published in the European Psychiatry journal further assessed this body of evidence: the study was conducted by Limveeraprajak and colleagues at Mahidol University; it noted that SAMe, a naturally occurring body chemical available as a dietary supplement discovered in the 1950s, is associated with depression when deficient. Larger, double-blind randomized controlled studies are warranted to confirm the antidepressant effectiveness of SAMe.

One landmark human trial examined SAMe as an augmentation agent: adverse events for patients who received adjunctive placebo versus SAMe were similar; there were no statistically significant differences in laboratory results and vital signs at endpoint between the two treatment groups, with the exception of a slightly higher mean supine systolic blood pressure reading for patients treated with adjunctive SAMe relative to placebo (mean difference: 3.1 mm Hg). There were no serious adverse events reported during the study, and there were no reports of serotonin syndrome when combining SAMe with serotonin reuptake inhibitors in that trial.

Only one study has specifically evaluated SAMe as the disulfate monotosylate salt: one study used the disulfate monotosylate salt. The majority of clinical evidence on SAMe for depression used parenteral formulations or other salt forms (primarily tosylate and butanedisulfonate). Evidence strength: preliminary to moderate; the signal is positive but methodological limitations mean conclusions cannot be drawn with confidence, particularly for oral administration of the disulfate monotosylate form specifically.

Osteoarthritis

The results of research on SAMe for osteoarthritis are mixed. The most rigorous synthesis of this evidence is a 2009 Cochrane systematic review (Cochrane Database of Systematic Reviews, CD007321): S-Adenosylmethionine may be a viable treatment option but the evidence about its effectiveness and safety is equivocal. The AHRQ Evidence Report (2002) reviewed 14 studies focused on osteoarthritis as part of its broader evidence summary: researchers identified 102 relevant studies in three selected areas — 47 studies for depression, 14 studies for osteoarthritis, and 41 studies for liver disease — and the majority of the studies enrolled small numbers of patients, and the quality of the studies varied greatly.

A clinically important human trial used the disulfate monotosylate salt form directly: 600 mg (as SAMe disulfate monotosylate salt standardized to 45% SS and 55% RS isomer) twice per day for eight weeks in patients with knee osteoarthritis reduced the VAS pain score by 25% after four weeks and by 48% after eight weeks, while various subscores on functional health measures (COOP, SF-36, Biodex, and WOMAC) also improved; notably, SAMe had a slower onset of action compared with 200 mg of celecoxib, but equivalent efficacy after eight weeks.

Other osteoarthritis studies using related salt forms showed: up to 400 mg intravenously per day for five days, followed by 200 mg orally three times per day for the remainder of one month, reduced total osteoarthritis scores by 55% with similar efficacy to 1,200 mg of ibuprofen per day but with fewer side effects (5 vs. 16), or 150 mg of indomethacin but with fewer reported adverse events than indomethacin (11% vs. 29%).

Some of the participants in depression studies who also had osteoarthritis said their joint symptoms improved when they took SAMe. Evidence strength: mixed; some active comparator trials show non-inferiority to NSAIDs, but the Cochrane review's conclusion remains equivocal, and the evidence base is characterized by small, methodologically variable studies.

Liver Diseases

SAMe has also been studied for other liver diseases, including alcoholic liver cirrhosis, hepatitis C, various types of cholestasis, and nonalcoholic steatohepatitis, as well as for the prevention of liver cancer, but research is inconclusive. A particularly relevant set of findings concerns intrahepatic cholestasis: oral administration of SAMe to patients suffering from intrahepatic cholestasis had improvements in both pruritus and biochemical markers of cholestasis.

Studies using related salt forms document liver-specific outcomes: 400 mg (SAMe p-toluene-sulfonate) three times per day for 6–24 months in patients with alcoholic liver disease or non-alcoholic liver disease reduced the rate of mortality/liver transplantation from 29% to 12%, improving survival or delaying need for liver transplant in patients with less severe disease, and increased total hepatic glutathione by 71% and reduced glutathione by 69% in patients with alcoholic liver disease, and by 79% and 76%, respectively, in patients with non-alcoholic liver disease.

However, in one study of alcohol-related liver disease, participants took SAMe for 2 years, and in that study no serious side effects were reported. Oral SAMe administration to patients with and without liver disease has resulted in increases in liver glutathione levels. Evidence strength: preliminary to moderate for cholestasis and alcoholic liver disease; findings across related salt forms are encouraging but not yet conclusive, and well-controlled RCTs remain limited.

Fibromyalgia

Oral SAMe administration to patients suffering from primary fibromyalgia resulted in significant improvement after a short-term trial (Tavoni et al., 1987). SAMe has also been studied for fibromyalgia, migraine, schizophrenia, Alzheimer's disease, and attention-deficit hyperactivity disorder, but there isn't enough evidence to reach conclusions about its effects in these conditions. Evidence strength: very preliminary; data are limited to small, early studies.

Neurological and Neurodegenerative Conditions

An emerging line of evidence suggests that abnormally low levels of endogenous SAMe may play an important role in the development of Alzheimer's disease (AD) and that SAMe may therefore have therapeutic potential in the treatment of AD. SAMe brain levels in patients with Alzheimer's disease are severely decreased; patients with Parkinson's disease have also been shown to have significantly decreased blood levels of SAMe. SAMe, as a major methyl donor, exerts its influence on central nervous system function through cellular transmethylation pathways; available evidence links deficiency or disturbance of SAMe production or transmethylation to a lifelong range of severe neuropsychiatric and neurodegenerative diseases. Evidence strength: largely preclinical and observational; large-scale human intervention trials are lacking.

Smoking Cessation

A trial of SAMe as a quit-smoking aid showed that it did not increase the quit rate or reduce withdrawal symptoms. Evidence strength: negative; this specific use is not supported by available evidence.

Body Systems and Health Areas Associated with SAMe Disulfate Monotosylate

Central Nervous System / Mood: SAMe has been found to regulate key functions in living cells; abnormal levels of SAMe in the body have been reported in liver diseases and depression.
Musculoskeletal System: SAMe is an essential substance for the maintenance of cartilage and the biosynthesis of brain chemicals.
Hepatic System: The enzyme SAMe synthetase is found in the liver and is the rate-limiting step for SAMe synthesis in the face of hepatic compromise.
Epigenetics / DNA Methylation: Proper DNA methylation is essential for normal embryonic development.
Antioxidant Defense: SAMe can methylate other metabolites such as free amino acids or neurotransmitters, and it is a precursor to the antioxidative metabolite glutathione.
Cell Growth and Differentiation: Decarboxylated SAMe couples with putrescine to generate spermidine and spermine, which are critical to cell growth, differentiation, and the stability of DNA and RNA.

Dosage Forms and Doses Reported in Studies

SAMe disulfate monotosylate and related salt forms are administered in several ways. In the United States, only oral forms are commercially available as dietary supplements. In the U.S., SAMe is available in oral form only and can be purchased as an over-the-counter tablet in pharmacies and health food stores.

Recommended daily doses of SAMe range from 200 mg to 1,600 mg taken in divided doses, depending upon the condition for which it is being taken and its severity, and upon the route of administration. Specific dosages reported in clinical studies include:

Depression (oral): Oral doses of 800–1,600 mg of enteric-coated, stabilized SAMe have been used in clinical studies since the 1990s. Doses of 200 to 1,600 mg/day have been reported for depression.
Depression (parenteral): Intravenous doses of 200–400 mg/d and intramuscular doses of 45–200 mg/d were used in earlier clinical studies conducted between 1976 and 1988.
Osteoarthritis (disulfate monotosylate, oral): 600 mg as SAMe disulfate monotosylate salt standardized to 45% SS and 55% RS isomer, twice per day for eight weeks.
Osteoarthritis (combined IV then oral): Up to 400 mg intravenously per day for five days, followed by 200 mg orally three times per day for the remainder of one month.
Osteoarthritis (maintenance): 1,200 mg/day initially; then maintenance 400 mg/day in some studies.
Liver disease (oral): 800 to 1,000 mg/day for liver disease. 400 mg (SAMe p-toluene-sulfonate) three times per day for 6–24 months has been studied in patients with alcoholic or non-alcoholic liver disease.
Fibromyalgia: Approximately 800 mg (as SAMe disulfate-p-toluenesulfonate containing 400 mg elemental SAMe) twice per day for six weeks has been studied in patients with fibromyalgia.

Regarding pharmacokinetics of oral dosing: oral SAMe achieves peak plasma concentrations 3 to 5 hours after ingestion of an enteric-coated tablet (400–1,000 mg); the half-life is about 100 minutes; and it may require up to one month to reach full effectiveness. Because SAMe is best absorbed on an empty stomach, it should be administered 30 to 60 minutes before meals or two hours after meals.

Dosage labeling of SAMe supplement products is a known source of consumer confusion because the weight of the stabilizing salt counterion is included in some label declarations and excluded in others. The systemic bioavailability of the molecule is drastically lowered by the metabolic avidity of the liver for SAMe; whereas this high presystemic metabolism is not prejudicial in subjects suffering from hepatic diseases, it strongly compromises subjects who take SAMe orally to obtain clinical benefit related to depression or osteoarthritis, in which extrahepatic SAMe action is required.

Safety Considerations and Drug Interactions

General Tolerability

Side effects of SAMe are uncommon, and when they do occur they are usually minor problems such as nausea or digestive upsets. The most common side effect of SAMe is nausea, and diarrhea, abdominal discomfort, or vomiting occurs less frequently. Occasionally, agitation, anxiety, or insomnia can occur in patients sensitive to activating effects of SAMe. Higher doses of SAMe (1,600 mg per day) have been reported to cause drowsiness in some people.

Overall, SAMe has a favorable side-effect profile in that it does not cause sexual dysfunction or weight gain. Information on the long-term safety of SAMe is limited because the participants in most studies took it only for short periods of time. Data on the long-term safety of SAMe and its safety for use during pregnancy are too limited to draw any conclusions.

Bipolar Disorder

As with other antidepressants, SAMe can trigger hypomanic or manic symptoms in patients with bipolar disorder. SAMe is reported to induce mania in some cases; in one open study, nine of eleven people with bipolar disorder experienced a switch to an "elevated mood state" (hypomania or mania). In patients with depression, SAMe has been linked to an increased risk of switching between hypomanic or manic states, but this is mainly observed in bipolar disorder or when using intravenous or intramuscular administration rather than oral formulations.

Serotonin Syndrome Risk

One case of serotonin syndrome in a 71-year-old woman treated with escalating doses of clomipramine while taking SAMe was reported; her symptoms developed 48–72 hours after the dose of clomipramine was increased threefold (25 mg/d to 75 mg/d), while the dose of SAMe was kept constant. No other cases of serotonin syndrome attributable to SAMe have been reported, including in trials where SAMe was used to augment SSRIs and TCAs. Nevertheless, it is also possible that SAMe might interact with drugs and dietary supplements that increase levels of serotonin, such as antidepressants, L-tryptophan, and St. John's wort.

Interaction with Levodopa

SAMe may decrease levodopa levels (deficient in people who have Parkinson's disease) and thus decrease the effectiveness of medications that aim to treat Parkinson's disease by increasing levodopa levels. SAMe may relieve levodopa side effects but might reduce its effectiveness over time.

Immunocompromised Patients

There is a theoretical concern about the use of SAMe by people who are immunocompromised (such as those who are HIV-positive); immunocompromised people are at risk for Pneumocystis carinii infection, and SAMe enhances the growth of this microorganism. This concern is theoretical and has not been confirmed in clinical reports but is acknowledged by NCCIH.

Monoamine Oxidase Inhibitors (MAOIs)

SAMe should not be used if a person has used an MAO inhibitor in the past 14 days; a dangerous drug interaction could occur. MAO inhibitors include isocarboxazid, linezolid, methylene blue injection, phenelzine, rasagiline, selegiline, tranylcypromine, and others.

Homocysteine Levels

The theoretical possibility that SAMe could induce hyperhomocysteinemia has never been substantiated, nor has any confirmed case been reported. There was no significant elevation in total homocysteine when SAMe was provided to patients with depression (800–1,600 mg) over six weeks or to healthy subjects using 800 mg per day for four weeks.

Regulatory Status

Therapeutic use of SAMe has increased as dietary supplements have gained in popularity, especially after the Dietary Supplement Health and Education Act was passed in 1994; this law allowed the distribution of SAMe as a dietary supplement, and therefore allowed it to bypass the regulatory requirements for drugs of the Food and Drug Administration (FDA). Dietary Supplement Grade refers to a nutritional supplement manufactured by an FDA-registered dietary supplement manufacturer; qualified manufacturers follow applicable standards of practice, which are less stringent than those for FDA-registered drug manufacturers.

References

Health Conditions

Health conditions that Disulfate monotosylate may help support.

No conditions available.

Body Systems

Body systems that Disulfate monotosylate may help support.

No body systems available.