Sage

Sage/Drug Interactions:

  • Alzheimer's agentsAlzheimer's agents: In human research, administration of sage has been shown to improve cognition, mood, alertness, memory retention, and attention (99; 102; 97; 1; 12; 100; 112; 98; 122). Sage may have anticholinergic activity and may improve cognition by inhibiting acetylcholinesterase (97; 1; 12; 147; 148; 114; 149; 112; 150; 99). Sage has been found to enhance cholinergic activity by inhibiting acetylcholinesterase and butyrylcholinesterase (97; 147; 148; 114; 99; 149; 112; 150). Sage essential oil and tincture may increase the anticholinergic effects of drugs used in the treatment of Alzheimer's disease (102; 99; 97).
  • Androgen deprivation therapyAndrogen deprivation therapy: In human research, sage reduced hot flashes in prostate cancer patients treated with androgen deprivation therapy (151).
  • Antianxiety agentsAntianxiety agents: In animal research, rosmarinic acid, a constituent of sage, produced anxiolytic-like effect in lower doses (152).
  • AntibioticsAntibiotics: In vitro, sage extracts had antimicrobial effects (15; 56; 9). However, in other research, sage tea or sage extract lacked an effect on colony-forming microbes in the mouth (16; 153; 18; 154; 155; 156; 9; 68; 157; 22; 158; 159; 160; 161; 162; 163; 164; 57). In vitro, a crude extract of Salvia officinalis reduced the minimum inhibitory concentrations of aminoglycosides in vancomycin-resistant enterococci (155).
  • AnticholinergicsAnticholinergics: In human and in vitro research, sage has been found to enhance cholinergic activity by inhibiting acetylcholinesterase and butyrylcholinesterase (97; 147; 148; 114; 99; 149; 112; 150).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: According to secondary sources, sage may reinforce warfarin action by heterogenous mechanisms (107).
  • Anticonvulsant agentsAnticonvulsant agents: Sage has been noted to cause seizures when the essential oil or tincture is used internally in doses of 12 drops or more (103; 104). Case studies of seizures thought to be due to exposure to sage oil have been published (105; 106). Theoretically, this may interfere with anticonvulsant drug therapy (124; 127; 125).
  • Antidiabetic agentsAntidiabetic agents: In vitro, sage had antidiabetic activity (25; 111). Also, in animal research, sage lowered plasma glucose, increased hepatocyte sensitivity to insulin, and inhibited gluconeogenesis in vitro, but lacked an effect on glucose clearance (108; 109; 110). Sage extracts are capable of selectively activating the peroxisome proliferator activator receptor-gamma, in a concentration-dependent manner, with an EC50 value of 33.7mg/L (25). Activation of peroxisome proliferator activator receptor-gamma is responsible for the antidiabetic activities of several glitazone drugs. Aqueous sage extracts inhibit alpha-glucosidase activity, at least in part due to the inhibitory effects of rosmarinic acid (111).
  • AntifungalsAntifungals: In laboratory research, essential oils from Salvia fruticosa inhibited radial growth and conidial germination of Penicillium digitatum; however, oregano, thyme, Dictamnus, and marjoram were more effective (23). Antifungal activity against Candida albicans was noted in laboratory research (157). In an aroma dispenser, sage essential oil had antifungal and antimold effects in the room (10).
  • AntihypertensivesAntihypertensives: In human research, two patients with hypertension experienced increases in blood pressure during sage essential oil therapy (99). Applied intravenously and duodenally, an aqueous-alcohol extract of sage lowered blood pressure in cats (70).
  • Anti-inflammatory agentsAnti-inflammatory agents: In in vitro and animal research, sage had anti-inflammatory activity (26; 165; 166).
  • Antilipemic agentsAntilipemic agents: Sage lowered plasma LDL cholesterol and total cholesterol and elevated HDL cholesterol in healthy humans after two weeks of treatment (48; 116).
  • Antineoplastic agentsAntineoplastic agents: Apoptosis and decreased proliferation of cancer cells have been shown in various animal and in vitro studies (167; 168; 169). In vitro, sage and its constituent monoterpenes (thujones, 1,8-cineole, and camphor) had antimutagenic effects against ultraviolet mutations (170), antimutagenic effects against mitomycin C (171), and antimutagenic effects in general (172).
  • AntiprotozoalsAntiprotozoals: In vitro, sage constituents (e.g., caffeic acid and salvianolic acids) had antileishmanial activities against intracellular amastigote stages of Leishmania parasites within macrophage-like cells in culture (71).
  • Antiviral agentsAntiviral agents: In vitro, sage extracts affected herpes simplex virus before adsorption, but lacked an effect on the intracellular virus replication (95). Extracts of sage reduced herpes simplex virus-2 plaque formation; ethanolic extracts were the most effective (173). In vitro, conjugates derived from sage constituents had inhibitory activities against HIV-1 integrase in the 3'-end processing reaction; less effect was noted against HIV-1 replication (174).
  • BenzodiazepinesBenzodiazepines: In vitro, some flavones in sage competitively inhibited benzodiazepine receptor binding (175; 176). In animal research, rosmarinic acid, a constituent of sage, produced anxiolytic-like effects in lower doses (152).
  • Cytochrome P450-modifying agentsCytochrome P450-modifying agents: Sage infusions have been found to inhibit CYP 3A4 and several isoforms (2C9, 2D6, 3A) (177; 178; 179), which may affect therapy with some drugs by decreasing their metabolism. In animal research, sage drinking increased CYP 2E1 protein and may alter drugs that are metabolized by phase I enzymes (131).
  • Dermatologic agentsDermatologic agents: Contact dermatitis may occur in some patients who are exposed to the leaves (141). Burning and pain were reported by two patients using a topical sage extract formula (96). In patients with contact dermatitis, patch tests were positive for Salvia officinalis (139; 140).
  • Drugs that may lower seizure thresholdDrugs that may lower seizure threshold: Sage has been noted to cause seizures when the essential oil or tincture is used internally in doses of 12 drops or more (103; 104). Case studies of seizures thought to be due to exposure to sage oil have been published (105; 106).
  • Drugs used for osteoporosisDrugs used for osteoporosis: In animal research, sage essential oils and monoterpene essential oil components (thujone, eucalyptol, camphor, borneol, thymol, alpha-pinene, beta-pinene, bornyl acetate, and menthol) were found to inhibit bone resorption when added to the food of rats (58).
  • EstrogensEstrogens: In in vitro research, sage essential oil showed estrogenic activity (26). In human research, extracts of the leaves of sage, alone or in combination with alfalfa, reduced hot flashes and night sweating in some menopausal women, perhaps by inducing a significant increase in prolactin and thyroid-stimulating hormone response to thyrotropin-releasing hormone (101; 117). According to secondary sources, constituents of sage have antiestrogenic effects.
  • Gastrointestinal agentsGastrointestinal agents: The adverse effects of sage have included minor dry pharynx or mild burning of the throat (with spray) (119) or nausea, vomiting, abdominal pain, cheilitis, stomatitis, dry mouth, and local irritation, according to secondary sources. In animal research, a hydroalcoholic extract of sage reduced acetic acid-induced ulcer (66). In in vitro research, sage extracts demonstrated bactericidal activities against Helicobacter pylori (68; 180).
  • HepatotoxinsHepatotoxins: In human research, sage lacked an effect on serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) (116). However, hepatoprotective effects of sage have been shown in animal and in vitro research (181; 182; 31).
  • ImmunosuppressantsImmunosuppressants: In vitro, polysaccharide fractions from sage resulted in immunomodulatory activity in the comitogenic thymocyte test (183; 184; 185).
  • Neurologic agentsNeurologic agents: In human research, administration of sage has been shown to improve cognition, mood, alertness, memory retention, and attention (99; 102; 97; 1; 12; 100; 112; 98; 122). Sage may have anticholinergic activity and may improve cognition by inhibiting acetylcholinesterase (1; 12; 97; 147; 148; 114; 149; 112; 150; 99). Sage has been found to enhance cholinergic activity by inhibiting acetylcholinesterase and butyrylcholinesterase (97; 147; 148; 114; 99; 149; 112; 150). Sage essential oil and tincture may increase the anticholinergic effects of drugs used in the treatment of Alzheimer's disease (102; 99; 97).
  • Nonsteroidal anti-inflammatory agents (NSAIDs)Nonsteroidal anti-inflammatory agents (NSAIDs): Formulations containing NSAIDs and formulations containing sage glycol plant extracts had synergistic effects and altered the release of active substances from sage extract (186; 187).
  • Respiratory agentsRespiratory agents: Sage dust may cause bronchial reactions with acute reductions of ventilatory capacity in some people, especially those employed in sage tea processing (142; 143). Chronic respiratory impairment has been documented in some sage tea processing employees (144). Sage powder should not be used for asthma, since sage powder may cause asthmatic attacks (wheezing).
  • SedativesSedatives: According to secondary sources, sage may have sedative properties.
  • Thyroid hormonesThyroid hormones: In human research, sage in combination with alfalfa induced thyroid-stimulating hormone in menopausal women (101).

    • Sage/Herb/Supplement Interactions:

  • AlfalfaAlfalfa: In human research, sage increased the effects of alfalfa (Medicago sativa) in the reduction of menopausal symptoms, including hot flashes, insomnia, nocturnal sweating, dizziness, headaches, and palpitations (101).
  • Alzheimer's herbs and supplementsAlzheimer's herbs and supplements: In human research, administration of sage has been shown to improve cognition, mood, alertness, memory retention, and attention (99; 102; 97; 1; 12; 100; 112; 98; 122). Sage may have anticholinergic activity and may improve cognition by inhibiting acetylcholinesterase (1; 12; 97; 147; 148; 114; 149; 112; 150; 99). Sage has been found to enhance cholinergic activity by inhibiting acetylcholinesterase and butyrylcholinesterase (97; 147; 148; 114; 99; 149; 112; 150). Sage essential oil and tincture may increase the anticholinergic effects of drugs used in the treatment of Alzheimer's disease (102; 99; 97).
  • AntibacterialsAntibacterials: In vitro, sage extracts had antimicrobial effects (15; 56; 9). However, in other research, sage tea or sage extract lacked an effect on colony-forming microbes in the mouth (16; 153; 18; 154; 155; 156; 9; 68; 157; 22; 158; 159; 160; 161; 162; 163; 164; 57). In vitro, a crude extract of Salvia officinalis reduced the minimum inhibitory concentrations of aminoglycosides in vancomycin-resistant enterococci (155).
  • AnticholinergicsAnticholinergics: In human and in vitro research, sage has been found to enhance cholinergic activity by inhibiting acetylcholinesterase and butyrylcholinesterase (97; 147; 148; 114; 99; 149; 112; 150).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: According to secondary sources, sage may reinforce warfarin action by heterogenous mechanisms (107).
  • AnticonvulsantsAnticonvulsants: Sage has been noted to cause seizures when the essential oil or tincture is used internally in doses of 12 drops or more (103; 104). Case studies of seizures thought to be due to exposure to sage oil have been published (105; 106). Theoretically, this may interfere with anticonvulsant drug therapy (124; 127; 125).
  • AntifungalsAntifungals: In laboratory research, essential oils from Salvia fruticosa inhibited radial growth and conidial germination of Penicillium digitatum; however, oregano, thyme, Dictamnus, and marjoram were more effective (23). Antifungal activity against Candida albicans was noted in laboratory research (157). In an aroma dispenser, sage essential oil had antifungal and antimold effects in the room (10).
  • Anti-inflammatory herbs and supplementsAnti-inflammatory herbs and supplements: In in vitro and animal research, sage had anti-inflammatory activity (26; 165; 166).
  • AntilipemicsAntilipemics: Sage lowered plasma LDL cholesterol and total cholesterol and elevated HDL cholesterol in healthy humans after two weeks of treatment (48; 116).
  • AntineoplasticsAntineoplastics: Apoptosis and decreased proliferation of cancer cells have been shown in various animal and in vitro studies (167; 168; 169). In vitro, sage and its constituent monoterpenes (thujones, 1,8-cineole, and camphor) had antimutagenic effects against ultraviolet mutations (170), antimutagenic effects against mitomycin C (171), and antimutagenic effects in general (172).
  • AntioxidantsAntioxidants: According to in vitro, animal, and human research, sage may have antioxidant activity (26; 165; 33; 29; 48; 181; 131; 188; 189; 190; 22; 45; 191; 192; 38).
  • AntiparasiticsAntiparasitics: In vitro, sage constituents (e.g., caffeic acid and salvianolic acids) had antileishmanial activities against intracellular amastigote stages of Leishmania parasites within macrophage-like cells in culture (71).
  • AntiviralsAntivirals: In vitro, sage extracts affected herpes simplex virus before adsorption, but lacked an effect on the intracellular virus replication (95). Extracts of sage reduced herpes simplex virus-2 plaque formation; ethanolic extracts were the most effective (173). In vitro, conjugates derived from sage constituents had inhibitory activities against HIV-1 integrase in the 3'-end processing reaction; less effect was noted against HIV-1 replication (174).
  • AnxiolyticsAnxiolytics: In animal research, rosmarinic acid, a constituent of sage, produced anxiolytic-like effect in lower doses (152).
  • Cytochrome P450-modifying agentsCytochrome P450-modifying agents: Sage infusions have been found to inhibit CYP 3A4 and several isoforms (2C9, 2D6, 3A) (177; 178; 179), which may affect therapy with some drugs by decreasing their metabolism. In animal research, sage drinking increased CYP 2E1 protein and may alter drugs that are metabolized by phase I enzymes (131).
  • Dermatologic agentsDermatologic agents: Contact dermatitis may occur in some patients who are exposed to the leaves (141). Burning and pain were reported by two patients using a topical sage extract formula (96). In patients with contact dermatitis, patch tests were positive for Salvia officinalis (139; 140).
  • Gastrointestinal herbs and supplementsGastrointestinal herbs and supplements: The adverse effects of sage have included minor dry pharynx or mild burning of the throat (with spray) (119) or nausea, vomiting, abdominal pain, cheilitis, stomatitis, dry mouth, and local irritation, according to secondary sources. In animal research, a hydroalcoholic extract of sage reduced acetic acid-induced ulcer (66). In in vitro research, sage extracts demonstrated bactericidal activities against Helicobacter pylori (68; 180).
  • Hepatotoxic agentsHepatotoxic agents: In human research, sage lacked an effect on SGOT and SGPT (116). However, hepatoprotective effects of sage have been shown in animal and in vitro research (181; 182; 31).
  • HypoglycemicsHypoglycemics: In vitro, sage had antidiabetic activity (25; 111). Also, in animal research, sage lowered plasma glucose, increased hepatocyte sensitivity to insulin, and inhibited gluconeogenesis in vitro, but lacked an effect on glucose clearance (108; 109; 110). Sage extracts were capable of selectively activating the peroxisome proliferator activator receptor-gamma, in a concentration-dependent manner, with an EC50 value of 33.7mg/L (25). Activation of peroxisome proliferator activator receptor-gamma was responsible for the antidiabetic activities of several glitazone drugs. Aqueous sage extracts inhibited alpha-glucosidase activity, at least in part due to the inhibitory effects of rosmarinic acid (111).
  • HypotensivesHypotensives: In human research, two patients with hypertension experienced increases in blood pressure during sage essential oil therapy (99). Applied intravenously and duodenally, an aqueous-alcohol extract of sage lowered blood pressure in cats (70).
  • ImmunosuppressantsImmunosuppressants: In vitro, polysaccharide fractions from sage resulted in immunomodulatory activity in the comitogenic thymocyte test (183; 184; 185).
  • Neurologic herbs and supplementsNeurologic herbs and supplements: In human research, administration of sage has been shown to improve cognition, mood, alertness, memory retention, and attention (99; 102; 97; 1; 12; 100; 112; 98; 122). Sage may have anticholinergic activity and may improve cognition by inhibiting acetylcholinesterase (97; 1; 12; 147; 148; 114; 149; 112; 150; 99). Sage has been found to enhance cholinergic activity by inhibiting acetylcholinesterase and butyrylcholinesterase (97; 147; 148; 114; 99; 149; 112; 150). Sage essential oil and tincture may increase the anticholinergic effects of drugs used in the treatment of Alzheimer's disease (102; 99; 97).
  • Osteoporosis agentsOsteoporosis agents: In animal research, sage essential oils and monoterpene essential oil components (thujone, eucalyptol, camphor, borneol, thymol, alpha-pinene, beta-pinene, bornyl acetate, and menthol) were found to inhibit bone resorption when added to the food of rats (58).
  • Perillyl alcohol-containing agentsPerillyl alcohol-containing agents: The essential oil of sage has been shown to contain perillyl alcohol.
  • PhytoestrogensPhytoestrogens: In in vitro research, sage essential oil showed estrogenic activity (26). In human research, extracts of the leaves of sage, alone or in combination with alfalfa, reduced hot flashes and night sweating in some menopausal women, perhaps by inducing a significant increase in prolactin and thyroid-stimulating hormone response to thyrotropin-releasing hormone (101; 117). According to secondary sources, constituents of sage have antiestrogenic effects.
  • Respiratory agentsRespiratory agents: Sage dust may cause bronchial reactions with acute reductions of ventilatory capacity in some people, especially those employed in sage tea processing (142; 143). Chronic respiratory impairment has been documented in some sage tea processing employees (144). Sage powder should not be used for asthma, since sage powder may cause asthmatic attacks (wheezing).
  • RhubarbRhubarb: In clinical research, a topical preparation of rhubarb and sage extracts was more effective than a sage extract alone for herpes (96).
  • SedativesSedatives: According to secondary sources, sage may have sedative properties.
  • Seizure threshold-lowering agentsSeizure threshold-lowering agents: Sage has been noted to cause seizures when the essential oil or tincture is used internally in doses of 12 drops or more (103; 104). Case studies of seizures thought to be due to exposure to sage oil have been published (105; 106).
  • SumacSumac: The combination of sage and sumac extracts was the most effective antioxidant blend in peanut oil (46).
  • Thyroid agentsThyroid agents: In human research, sage in combination with alfalfa induced thyroid-stimulating hormone in menopausal women (101).

    • Sage/Food Interactions:

  • GeneralGeneral: Sage has been used as a spice in food for centuries and may be considered safe for this use in nonallergic people. Sage was found to contain antioxidant phenols that may be useful in preventing food spoilage (30; 193; 27).
  • AlfalfaAlfalfa: In human research, sage increased the effects of alfalfa (Medicago sativa) in the reduction of menopausal symptoms, including hot flashes, insomnia, nocturnal sweating, dizziness, headaches, and palpitations (101).
  • RhubarbRhubarb: In clinical research, a topical preparation of rhubarb and sage extracts was more effective than a sage extract alone for herpes (96).

    • Sage/Lab Interactions:

  • Blood pressureBlood pressure: In human research, two patients with hypertension experienced increases in blood pressure during sage essential oil therapy (99). Applied intravenously and duodenally, an aqueous-alcohol extract of sage lowered blood pressure in cats (70).
  • Bone mineral densityBone mineral density: In animal research, sage essential oils and monoterpene essential oil components (thujone, eucalyptol, camphor, borneol, thymol, alpha-pinene, beta-pinene, bornyl acetate, and menthol) were found to inhibit bone resorption when added to the food of rats (58).
  • Coagulation panelCoagulation panel: According to secondary sources, sage may reinforce warfarin action by heterogenous mechanisms (107).
  • Complement pathwayComplement pathway: Rosmarinic acid inhibited complement-dependent inflammatory processes (165).
  • CytokinesCytokines: Borneol, an active component of Salvia officinalis essential oil, decreased cytokine (IL-1beta and IL-6) mRNA expression in colonic inflammation (194).
  • EicosanoidsEicosanoids: Eicosanoid inhibition in rat leucocytes was found in the alcohol extract (50mcg/mL) of sage and was shown by the monoterpenoids alpha-pinene and geraniol (0.2mM), but not 1,8-cineole, thujone, or camphor (26). In laboratory research, constituents of sage, carnosic acid and carnosol, potently inhibited human 5-lipoxygenase and suppressed proinflammatory responses of stimulated human polymorphonuclear leukocytes (195).
  • Lipid profileLipid profile: Sage lowered plasma LDL cholesterol and total cholesterol and elevated HDL cholesterol in healthy humans after two weeks of treatment (48; 116).
  • Liver enzymesLiver enzymes: In human research, sage lacked an effect on SGOT and SGPT (116). However, hepatoprotective effects of sage have been shown in animal and in vitro research (181; 182; 31).
  • Serum glucose levelsSerum glucose levels: In vitro, sage had antidiabetic activity (25; 111). Also, in animal research, sage lowered plasma glucose, increased hepatocyte sensitivity to insulin, and inhibited gluconeogenesis in vitro, but lacked an effect on glucose clearance (108; 109; 110).
  • Serum levels of cytochrome P450-metabolized drugs or herbsSerum levels of cytochrome P450-metabolized drugs or herbs: Sage leaf infusions have been found to inhibit CYP 3A4 and several isoforms (177) that may inhibit drug and herb metabolism.
  • Serum prolactin levelsSerum prolactin levels: In menopausal women, sage in combination with alfalfa induced a significant increase in prolactin (101).
  • Thyroid panelThyroid panel: In menopausal women, sage in combination with alfalfa induced a significant increase in thyroid-stimulating hormone (101).
  • White blood cellsWhite blood cells: In animal research, a sage tincture reduced the total leukocyte and monocytes percentages and the activation of circulating phagocytes and decreased nitric oxide synthesis (196).