S-adenosyl-L-methionine
SAMe/Drug Interactions:
AlcoholAlcohol: In human research, effects of alcohol on the kinetics of homocysteine metabolism were lacking (184). AnalgesicsAnalgesics: S-adenosyl-L-methionine (SAMe) has been shown to have anti-inflammatory and analgesic properties in animal models when given both orally and parenterally (185). AntiarrhythmicsAntiarrhythmics: Tachycardia and heart palpitations have been reported in human research (99; 125; 83; 128). Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In human research, SAMe improved prothrombin time (76; 77).Antidepressants: MAOIsAntidepressants: MAOIs: According to secondary sources, monoamine oxidase inhibitors (MAOIs) may interact with SAMe. Individuals in clinical trials experienced headache, mild dizziness, hyperinsomnia, agitation, lack of energy, drowsiness, tremors, insomnia, anxiety, and asthenia after receiving SAMe orally, intravenously, or intramuscularly (102; 84; 104; 105; 110; 52; 113; 8; 117; 118; 119; 121; 122; 103; 131; 123; 132). SAMe has been associated with hypomania and mania in patients with or without a history of bipolar disorder (11; 133; 102; 74; 8; 134; 85). Antidepressants: SSRIsAntidepressants: SSRIs: According to secondary sources, selective serotonin reuptake inhibitors (SSRIs) may interact with SAMe. Individuals in clinical trials experienced headache, mild dizziness, hyperinsomnia, agitation, lack of energy, drowsiness, tremors, insomnia, anxiety, and asthenia after receiving SAMe orally, intravenously, or intramuscularly (102; 84; 104; 105; 110; 52; 113; 8; 117; 118; 119; 121; 122; 103; 131; 123; 132). SAMe has been associated with hypomania and mania in patients with or without a history of bipolar disorder (11; 133; 102; 74; 8; 134; 85). AntihypertensivesAntihypertensives: Increased blood pressure occurred in a clinical trial (79). Anti-inflammatory agentsAnti-inflammatory agents: SAMe has been shown to have anti-inflammatory and analgesic properties in animal models when given both orally and parenterally (185). AntilipemicsAntilipemics: In a human study designed to examine the potential negative effects of SAMe on homocysteine levels, a small but statistically significant decrease in total cholesterol occurred (186). A reduction in cholesterol levels occurred in some subjects in a separate study (179). AntineoplasticsAntineoplastics: Metabolic alterations of S-adenosylmethionine have been implicated in modifying the epigenotype of cells and creating the epigenetic progenitor of cancer (187). AntipsychoticsAntipsychotics: One patient out of 15 (6.6%) was described to be hypomanic after receiving 1,600mg of oral SAMe daily (74). Anxiety, insomnia, and hostility were reported in one patient during the first five days of receiving SAMe 150mg intramuscularly (84). Four patients treated parenterally with SAMe (200mg twice daily intravenously or intramuscularly) developed psychoactivation (81). During treatment with SAMe 150mg daily intravenously, one patient (11%) displayed suicidal ideation and needed to discontinue SAMe (109). AnxiolyticsAnxiolytics: SAMe has been associated with anxiety and nervousness in some clinical trials (80; 11; 81; 18; 82; 83; 84; 52; 85). Cardiovascular agentsCardiovascular agents: Seven out of 180 patients (3.9%) receiving SAMe 800mg daily intravenously developed superficial phlebitis when SAMe was diluted in 500mL of saline or 5% dextrose and infused over two hours (110). Tachycardia and heart palpitations have been reported in human research (99; 125; 83; 128). In addition, increased blood pressure occurred in a clinical trial (79). ClomipramineClomipramine: A case report indicates possible serotonin syndrome occurring in a 71 year-old woman with depression who was receiving SAMe 100mg daily intramuscularly along with 75mg daily of clomipramine (188). The patient was previously receiving a lower dose of 25mg of clomipramine daily and at that time, adverse effects were lacking when taken concomitantly with SAMe. However, shortly after the dosage increase to 75mg, the patient became anxious, agitated, and confused. Once admitted to the hospital, the patient was found to be unresponsive with tachycardia, tachypnea, diarrhea, myoclonus, generalized tremors, rigidity, hyperreflexia, shivering, profuse diaphoresis, dehydration, and fever (40.5?C). She was also found to have a white blood cell count of 13,040mm3 and elevated levels of lactic dehydrogenase and of creatinine phosphokinase. The patient was treated with dantrolene 50mg intravenously every six hours for 48 hours. The patients subsequently completely recovered. Cytochrome P450-modifying agentsCytochrome P450-modifying agents: According to secondary sources, cytochrome P450-modifying agents, including 2D6 inhibitors, may interact with SAMe.Dermatologic agentsDermatologic agents: Skin rash, pruritus, and allergic reactions have been reported in individuals receiving intravenous and oral SAMe in clinical trials (80; 51; 131; 104; 106; 73). DiureticsDiuretics: In human research, when compared with nabumetone, frequent urination was similar between groups (128). Urinary delay occurred in one subject in a clinical trial (118; 126). In a case series, urinary frequency was reported as an adverse event (85). EstrogensEstrogens: In human research, effects of estrogen on SAMe were lacking (189). Genitourinary tract agentsGenitourinary tract agents: In human research, when compared with nabumetone, frequent urination was similar between groups (128). Urinary delay occurred in one subject in a clinical trial (118; 126). In a case series, urinary frequency was reported as an adverse event (85). HepatotoxinsHepatotoxins: Elevated liver enzymes were shown in clinical studies in humans (109). Hormonal agentsHormonal agents: In human research, effects of estrogen on SAMe were lacking (189). HypoglycemicsHypoglycemics: In human research, SAMe 600mg daily given intravenously reduced blood glucose in patients with type 2 diabetes (78).Impotence agentsImpotence agents: In clinical research, men treated with SAMe saw significant improvement in arousal dysfunction compared to placebo, with improved scores after six weeks of treatment for the ability to become aroused and achieve and maintain an erection (97). LevodopaLevodopa: In patients with Parkinson's disease, levodopa increased plasma levels of SAMe (98). The authors noted that previous animal studies have suggested that in higher doses, SAMe may counteract the antiparkinsonian efficacy of levodopa, potentially contributing to the reduced efficacy of levodopa. MethotrexateMethotrexate: In a case study, SAMe in combination with other folate metabolites was useful for methotrexate-induced myelopathy (54). In one lymphoma patient receiving methotrexate, very low levels of SAMe were associated with white matter changes in the brain (190). Drug interactions are unclear. Neurologic agentsNeurologic agents: Individuals in clinical trials experienced headache, mild dizziness, hyperinsomnia, agitation, lack of energy, drowsiness, tremors, insomnia, anxiety, and asthenia after receiving SAMe orally, intravenously, or intramuscularly (102; 84; 104; 105; 110; 52; 113; 8; 117; 118; 119; 121; 122; 103; 131; 123; 132). An individual receiving oral SAMe complained of vertigo (73). SAMe has been associated with hypomania and mania in patients with or without a history of bipolar disorder (11; 133; 102; 74; 8; 134; 85). Ophthalmic agentsOphthalmic agents: Blurred vision has been reported in clinical trials (117; 118). Otic agentsOtic agents: A patient reported a hot sensation and itchiness of the ear while receiving oral SAMe 800mg twice daily for depression (8). Phosphodiesterase inhibitorsPhosphodiesterase inhibitors: In clinical research, men treated with SAMe saw significant improvement in arousal dysfunction compared to placebo, with improved scores after six weeks of treatment for the ability to become aroused and achieve and maintain an erection (97). TolcaponeTolcapone: In Parkinson's disease patients, effects of tolcapone on plasma levels of SAMe were lacking (191). Tricyclic antidepressants (TCAs)Tricyclic antidepressants (TCAs): A case report indicated possible serotonin syndrome occurring in a 71 year-old woman with depression who was receiving SAMe 100mg daily intramuscularly along with 75mg daily of clomipramine (188). The patient was previously receiving a lower dose of 25mg of clomipramine daily and at that time, adverse effects were lacking when taken concomitantly with SAMe. However, shortly after the dosage increase to 75mg, the patient became anxious, agitated, and confused. Once admitted to the hospital, the patient was found to be unresponsive with tachycardia, tachypnea, diarrhea, myoclonus, generalized tremors, rigidity, hyperreflexia, shivering, profuse diaphoresis, dehydration, and fever (40.5?C). She was also found to have a white blood cell count of 13,040mm3 and elevated levels of lactic dehydrogenase and of creatinine phosphokinase. The patient was treated with dantrolene 50mg intravenously every six hours for 48 hours. The patients subsequently completely recovered. VasodilatorsVasodilators: According to a population-based study, high blood levels of SAMe were significantly associated with high flow-mediated vasodilation (24). SAMe/Herb/Supplement Interactions:
AnalgesicsAnalgesics: SAMe has been shown to have anti-inflammatory and analgesic properties in animal models when given both orally and parenterally (185). AntiarrhythmicsAntiarrhythmics: Tachycardia and heart palpitations have been reported in human research (99; 125; 83; 128). Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In human research, SAMe improved prothrombin time (76; 77).Antidepressants: MAOIsAntidepressants: MAOIs: According to secondary sources, monoamine oxidase inhibitors (MAOIs) may interact with SAMe. Individuals in clinical trials experienced headache, mild dizziness, hyperinsomnia, agitation, lack of energy, drowsiness, tremors, insomnia, anxiety, and asthenia after receiving SAMe orally, intravenously, or intramuscularly (102; 84; 104; 105; 110; 52; 113; 8; 117; 118; 119; 121; 122; 103; 131; 123; 132). SAMe has been associated with hypomania and mania in patients with or without a history of bipolar disorder (11; 133; 102; 74; 8; 134; 85). Antidepressants: SSRIsAntidepressants: SSRIs: According to secondary sources, selective serotonin reuptake inhibitors (SSRIs) may interact with SAMe. Individuals in clinical trials experienced headache, mild dizziness, hyperinsomnia, agitation, lack of energy, drowsiness, tremors, insomnia, anxiety, and asthenia after receiving SAMe orally, intravenously, or intramuscularly (102; 84; 104; 105; 110; 52; 113; 8; 117; 118; 119; 121; 122; 103; 131; 123; 132). SAMe has been associated with hypomania and mania in patients with or without a history of bipolar disorder (11; 133; 102; 74; 8; 134; 85). Anti-inflammatory agentsAnti-inflammatory agents: SAMe has been shown to have anti-inflammatory and analgesic properties in animal models when given both orally and parenterally (185). AntilipemicsAntilipemics: In a human study designed to examine the potential negative effects of SAMe on homocysteine levels, a small but statistically significant decrease in total cholesterol occurred (186). A reduction in cholesterol levels occurred in some subjects in a separate study (179). AntineoplasticsAntineoplastics: Metabolic alterations of S-adenosylmethionine has been implicated in modifying the epigenotype of cells and creating the epigenetic progenitor of cancer (187). AntioxidantsAntioxidants: In human research, SAMe improved levels of plasma and reduced glutathione, and malondialdehyde (further details are lacking) (77).AntipsychoticsAntipsychotics: One patient out of 15 (6.6%) was described to be hypomanic after receiving 1,600mg of oral SAMe daily (74). Anxiety, insomnia, and hostility were reported in one patient during the first five days of receiving SAMe 150mg intramuscularly (84). Four patients treated parenterally with SAMe (200mg twice daily intravenously or intramuscularly) developed psychoactivation (81). During treatment with SAMe 150mg daily intravenously, one patient (11%) displayed suicidal ideation and needed to discontinue SAMe (109). AnxiolyticsAnxiolytics: SAMe has been associated with anxiety and nervousness in some clinical trials (80; 11; 81; 18; 82; 83; 84; 52; 85). Cardiovascular agentsCardiovascular agents: Seven out of 180 patients (3.9%) receiving SAMe 800mg daily intravenously developed superficial phlebitis when SAMe was diluted in 500mL of saline or 5% dextrose and infused over two hours (110). Tachycardia and heart palpitations have been reported in human research (99; 125; 83; 128). In addition, increased blood pressure occurred in a clinical trial (79). CholineCholine: S-adenosylmethionine is produced in a pathway that uses choline as a methyl group donor (192). In human research, choline supplementation reduced SAMe levels in folate-compromised men (193). Choline was significantly and positively related to the ratio of plasma SAMe to S-adenosylhomocysteine in children with cystic fibrosis (194). Cytochrome P450-modifying agentsCytochrome P450-modifying agents: According to secondary sources, cytochrome P450-modifying agents, including 2D6 inhibitors, may interact with SAMe.Dermatologic agentsDermatologic agents: Skin rash, pruritus, and allergic reactions have been reported in individuals receiving intravenous and oral SAMe in clinical trials (80; 51; 131; 104; 106; 73). DiureticsDiuretics: In human research, when compared with nabumetone, frequent urination was similar between groups (128). Urinary delay occurred in one subject in a clinical trial (118; 126). In a case series, urinary frequency was reported as an adverse event (85). Docosahexaenoic acid (DHA)Docosahexaenoic acid (DHA): In human research, the ratio of DHA in phosphatidylcholine to phosphatidylcholine in plasma was directly correlated with the ratio of SAMe to S-adenosylhomocysteine (195). Folic acidFolic acid: In human research, folic acid increased SAMe levels in patients with intermediate hyperhomocysteinemia (196). In human research, 5-methyltetrahydrofolate uses folate in converting homocysteine to methionine, which is then used to form S-adenosylmethionine (197). Differences in the ratio of SAMe to S-adenosylhomocysteine were lacking in patients supplemented with folate or folate plus methylcobalamin (198). Genitourinary tract agentsGenitourinary tract agents: In human research, when compared with nabumetone, frequent urination was similar between groups (128). Urinary delay occurred in one subject in a clinical trial (118; 126). In a case series, urinary frequency was reported as an adverse event (85). HepatotoxinsHepatotoxins: Elevated liver enzymes were shown in clinical studies in humans (109). Hormonal agentsHormonal agents: In human research, effects of estrogen on SAMe were lacking (189). HypoglycemicsHypoglycemics: In human research, SAMe 600mg daily given intravenously reduced blood glucose in patients with type 2 diabetes (78).HypotensivesHypotensives: Increased blood pressure occurred in a clinical trial (79). Impotence agentsImpotence agents: In clinical research, men treated with SAMe saw significant improvement in arousal dysfunction compared to placebo, with improved scores after six weeks of treatment for the ability to become aroused and achieve and maintain an erection (97). MethionineMethionine: In human research, the plasma SAMe:S-adenosylhomocysteine ratio increased after methionine supplementation (199). MineralsMinerals: In human research, a vitamin-mineral supplement resulted in improvements in SAMe levels in patients with autism (200). In elderly individuals, effects of B vitamins on SAMe levels were lacking (201). Neurologic agentsNeurologic agents: Individuals in clinical trials experienced headache, mild dizziness, hyperinsomnia, agitation, lack of energy, drowsiness, tremors, insomnia, anxiety, and asthenia after receiving SAMe orally, intravenously, or intramuscularly (102; 84; 104; 105; 110; 52; 113; 8; 117; 118; 119; 121; 122; 103; 131; 123; 132). An individual receiving oral SAMe complained of vertigo (73). SAMe has been associated with hypomania and mania in patients with or without a history of bipolar disorder (11; 133; 102; 74; 8; 134; 85). Ophthalmic agentsOphthalmic agents: Blurred vision has been reported in clinical trials (117; 118). Otic agentsOtic agents: A patient reported a hot sensation and itchiness of the ear while receiving oral SAMe 800mg twice daily for depression (8). PhytoestrogensPhytoestrogens: In human research, effects of estrogen on SAMe were lacking (189). VasodilatorsVasodilators: According to a population-based study, high blood levels of SAMe were significantly associated with high flow-mediated vasodilation (24). VitaminB6VitaminB6: In human research, effects of moderate vitamin B6 restriction on the postprandial methionine (SAMe precursor) cycle rates were lacking (202). Vitamin B12Vitamin B12: In human research, a combination of SAMe and vitamin B12 resulted in increased prothrombin time, clearance of BSF, and total proteinemia, and decreased AST, ALT, gamma-glutamyl transpeptidase (GGT), total bilirubin levels, alkaline phosphatase, and levels of immunoglobulins A, M, and G (203). VitaminsVitamins: In human research, a vitamin-mineral supplement resulted in improvements in SAMe levels in patients with autism (200). In elderly individuals, effects of B vitamins on SAMe levels were lacking (201). SAMe/Food Interactions:
Insufficient available evidence.SAMe/Lab Interactions:
5-Hydroxyindoleacetic acid (5-HIAA)5-Hydroxyindoleacetic acid (5-HIAA): In human research, SAMe increased levels of cerebrospinal 5-hydroxyindoleacetic acid (5-HIAA) (11). Amino acidsAmino acids: In human research, SAMe increased fasting taurine and cystine levels (152). Plasma cystine, taurine, and methionine were investigated in separate human research; however, details are lacking (204; 205).Blood pressureBlood pressure: Increased blood pressure occurred in a clinical trial (79). CholesterolCholesterol: In a human study designed to examine the potential negative effects of SAMe on homocysteine levels, a small but statistically significant decrease in total cholesterol occurred (186). A reduction in cholesterol levels occurred in some subjects in a separate study (179). DopamineDopamine: In human research, SAMe increased dopamine levels (132). Heart rateHeart rate: Tachycardia and heart palpitations have been reported in human research (99; 125; 83; 128). Homovanillic acidHomovanillic acid: In human research, SAMe increased levels of cerebrospinal homovanillic acid (11). FormaldehydeFormaldehyde: In human research, SAMe increased serum formaldehyde in three subjects (96). GlucoseGlucose: SAMe 600mg daily given intravenously reduced blood glucose in patients with type 2 diabetes (78).GlutathioneGlutathione: In human research, SAMe improved levels of plasma and reduced glutathione (further details are lacking) (77).HomocysteineHomocysteine: In human research, effects of SAMe on homocysteine were lacking (96; 186; 146). In other research, SAMe decreased homocysteine levels (206). Liver function testsLiver function tests: In human research, improvements in levels of aspartate transaminase, alanine transaminase, alkaline phosphatase, gamma-glutamyl transpeptidase, albumin, LDH, and sulfobromophthalein have occurred (177; 151; 181; 157; 76; 180; 77; 179; 39). Decreases were noted in BSP, SGOT, SGPT and gamma-GT in SAMe-treated patients (150). In human research, SAMe decreased total and direct bilirubin (139; 157; 180). In a human study designed to examine the potential negative effects of SAMe on homocysteine levels, a small but statistically significant increase in ALT occurred (186). MalondialdehydeMalondialdehyde: In human research, SAMe improved levels of malondialdehyde (further details are lacking) (77).Mean corpuscular volumeMean corpuscular volume: In human research, SAMe reduced levels of mean corpuscular volume (77).NoradrenalineNoradrenaline: In human research, SAMe increased noradrenaline levels (132). ProlactinProlactin: In human research, SAMe decreased prolactin levels (171). Prothrombin timeProthrombin time: In human research, SAMe improved prothrombin time (76; 77).SAMeSAMe: In human research, SAMe increased SAMe in blood, urine, and cerebrospinal fluid (157; 142; 11; 132; 146). Total proteinTotal protein: In human research, SAMe improved total protein levels (76).White blood cellsWhite blood cells: In human research, SAMe reduced levels of eosinophils and leukocytes (77).