Lignans
Lignan/Drug Interactions:
AlcoholAlcohol: In rats, lignans altered hepatic enzymes such as acyl-CoA oxidase, aldehyde dehydrogenase, and 3-ketoacyl-CoA thiolase (112). Therefore, lignans may increase the effects of alcohol use. AndrogensAndrogens: In a human study, lignans from flaxseed decreased the free androgen index (83). Antiangiogenic drugsAntiangiogenic drugs: Based on in vitro studies, lignans found in flaxseed may have angiogenic properties (9). AntibioticsAntibiotics: Based on human and in vitro studies, antibiotic use may alter lignan metabolism by altering the intestinal flora that are necessary for metabolizing lignans (94; 95; 11). There is a report that use of antibiotics may decrease urinary enterolactone levels for longer than 40 days (113). Genetic influences may also play a role in lignan metabolism (114). Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Based on in vitro research, lignans may have antiplatelet activity (20; 23; 22; 21). Antidiabetic agentsAntidiabetic agents: In human research, a semisynthetic lignan glycoside derivative of the medicinal herb Podophyllum emodi was found to lower glucose levels (84); however, results are conflicting (115). In a retrospective cohort study, lignan intake was negatively correlated with fasting insulin and C-peptide levels (43). Antifungal agentsAntifungal agents: Based on in vitro research, lignans isolated from Taxus baccata and Phyllanthus piscatorum may have antifungal activity (10; 12). AntihypertensivesAntihypertensives: Based on a clinical study in postmenopausal women with vascular disease, lignans from flaxseed may significantly reduce blood pressure during mental stress (74). In other human studies, supplementation with a lignan complex containing secoisolariciresinol diglucoside did not change blood pressure (81; 80). Anti-inflammatory agentsAnti-inflammatory agents: Based on in vitro studies, lignans may have anti-inflammatory activity, although conflicting evidence also exists (17; 15; 14; 19; 7; 16; 18). Some lignans inhibit COX-1 enzymes in vitro (15; 14). Antilipemic agentsAntilipemic agents: In animal studies, lignans increased HDL levels and HDL:total cholesterol ratios while decreasing LDL, total cholesterol, triglycerides, and serum malondialdehyde levels (109; 36). In humans, flaxseed supplementation caused a significant decrease in total serum cholesterol (83). In other human studies, there was evidence that lignans may increase LDL and apolipoprotein B (43). Further research is necessary. It should be noted, however, that there are hundreds of different lignans and that different lignans may have different effects. AntiprotozoalsAntiprotozoals: Based on in vitro research, some lignans may have antiprotozoal activity against Leishmania promastigotes, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, and Plasmodium falciparum (12; 68). Antituberculosis agentsAntituberculosis agents: In an in vitro study, a lignan extracted from Valeriana laxiflora exhibited activity against Mycobacterium tuberculosis (75). Antiviral agentsAntiviral agents: In in vitro research, several lignans exhibited antiviral activity against human immunodeficiency virus (HIV) strains, hepatitis B, and other viruses (25; 29; 28; 55; 30). Aromatase inhibitorsAromatase inhibitors: Some theoretical precursors of mammalian lignans are weak-to-moderate inhibitors of human aromatase activity (85; 157; 86). Cardiac glycosidesCardiac glycosides: Based on in vitro studies, lignans, including enterolactone, enterodiol, and mammalian lignan derivatives, may have digoxin-like activity (32; 31). CNS depressantsCNS depressants: Based on a mouse study, the lignan elenoside may have central depressive properties (71; 72). Another lignan, hydroxypinoresinol, was able to bind to benzodiazepine receptors (70). Cytochrome P450 3A(4,5,7) substratesCytochrome P450 3A(4,5,7) substrates: In an in vitro study, enterolactone and secoisolariciresinol activated the pregnane X receptor (40). Since one of the primary targets of pregnane X receptor activation is the induction of CYP3A4, lignan use may interfere with drugs metabolized by this isoenzyme. DiureticsDiuretics: Based on a rat study, the lignan elenoside may have an antidiuretic effect and decrease sodium excretion (44). EstrogensEstrogens: In epidemiological and in vitro studies, lignans, including enterolactone and secoisolariciresinol, exhibited weak estrogenic and antiestrogenic properties, and bound to sex hormone-binding globulin (88; 89; 90; 91; 92). However, lignans extracted from Ephedra viridis did not exhibit estrogenic activity in yeast (48). There is the potential for lignans to alter the effects of estrogen-containing agents. It should be noted that there are hundreds of different lignans and that different lignans may have different effects. ImmunosuppressantsImmunosuppressants: Based on in vitro research, several lignans (such as machilin A, eleutheroside E, tortoside A, and hemiariensin) may have immunosuppressive effects (57; 56; 93). LaxativesLaxatives: In one human study, the lignan enterolactone caused constipation (39). In other clinical trials, diarrhea was associated with sesamin treatment (110), CPH 82 (84), podophyllum lignan derivatives (104), and muffins containing flaxseed (64). Lignans may alter the effectiveness of laxative agents. Lignan/Herb/Supplement Interactions:
Androgenic herbs or supplementsAndrogenic herbs or supplements: In a human study, lignans from flaxseed decreased the free androgen index (83). Antiangiogenic herbsAntiangiogenic herbs: Based on in vitro studies, lignans found in flaxseed may have angiogenic properties (9). AntibacterialsAntibacterials: Based on human and in vitro studies, antibiotic use may alter lignan metabolism by altering the intestinal flora that are necessary for metabolizing lignans (94; 95; 11). There is a report that use of antibiotics may decrease urinary enterolactone levels for longer than 40 days (113). Genetic influences may also play a role (114). Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Based on in vitro research, lignans may have antiplatelet activity (20; 23; 22; 21). AntifungalsAntifungals: Based on in vitro research, lignans isolated from Taxus baccata and Phyllanthus piscatorum may have antifungal activity (10; 12). Anti-inflammatory herbs and supplementsAnti-inflammatory herbs and supplements: Based on in vitro studies, lignans may have anti-inflammatory activity, although conflicting evidence also exists (17; 15; 14; 19; 7; 16; 18). Some lignans inhibited COX-1 enzymes in vitro (15; 14). AntilipemicsAntilipemics: In animal studies, lignans increased HDL levels and HDL:total cholesterol ratios, while decreasing LDL, total cholesterol, triglycerides, and serum malondialdehyde levels (109; 36). In humans, flaxseed supplementation caused a significant decrease in total serum cholesterol (83). In other human studies, there was evidence that lignans may increase LDL and apolipoprotein B (43). Further research is necessary. It should be noted, however, that there are hundreds of different lignans and that different lignans may have different effects. AntioxidantsAntioxidants: In human, animal, and in vitro studies, some lignans exhibited antioxidant effects (158; 159; 112; 160; 48; 161; 15; 119; 162; 163; 164; 165; 17). However, one in vitro study indicated that a mammalian lignan may enhance superoxide production (166). Therefore, lignan use may alter the effect of antioxidants. Antiprotozoal herbs and supplementsAntiprotozoal herbs and supplements: Based on in vitro research, some lignans may have antiprotozoal activity against Leishmania promastigotes, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, and Plasmodium falciparum (12; 68). AntiviralsAntivirals: In in vitro research, several lignans exhibited antiviral activity against human immunodeficiency virus (HIV) strains, hepatitis B, and other viruses (25; 29; 28; 55; 30). Cardiac glycosidesCardiac glycosides: Based on in vitro studies, lignans, including enterolactone, enterodiol, and mammalian lignan derivatives, may have digoxin-like activity (32; 31). Cytochrome P450 3A(4,5,7) substratesCytochrome P450 3A(4,5,7) substrates: In an in vitro study, enterolactone and secoisolariciresinol activated the pregnane X receptor (40). Since one of the primary targets of pregnane X receptor activation is the induction of CYP3A4, lignan use may interfere with drugs metabolized by this isoenzyme. DiureticsDiuretics: Based on a rat study, the lignan elenoside may have an antidiuretic effect and decrease sodium excretion (44). HypoglycemicsHypoglycemics: In human research, a semisynthetic lignan glycoside derivative of the medicinal herb Podophyllum emodi was found to lower glucose levels (84); however, results are conflicting (115). In a retrospective cohort study, lignan intake was negatively correlated with fasting insulin and C-peptide levels (43). HypotensivesHypotensives: Based on a clinical study in postmenopausal women with vascular disease, lignans from flaxseed may significantly reduce blood pressure during mental stress (74). In other human studies, supplementation with a lignan complex containing secoisolariciresinol diglucoside did not change blood pressure (81; 80). ImmunosuppressantsImmunosuppressants: Based on in vitro research, several lignans (such as machilin A, eleutheroside E, tortoside A, and hemiariensin) may have immunosuppressive effects (57; 56; 93). LaxativesLaxatives: In one human study, the lignan enterolactone caused constipation (39). In other clinical trials, diarrhea was associated with sesamin treatment (110), CPH 82 (84), podophyllum lignan derivatives (104), and muffins containing flaxseed (64). Lignans may alter the effectiveness of laxative agents. PhytoestrogensPhytoestrogens: In epidemiological and in vitro studies, lignans, including enterolactone and secoisolariciresinol, exhibited weak estrogenic and antiestrogenic properties, and bound to sex hormone-binding globulin (88; 89; 90; 91; 92). However, lignans extracted from Ephedra viridis did not exhibit estrogenic activity in yeast (48). There is the potential for lignans to alter the effects of estrogen-containing agents. It should be noted that there are hundreds of different lignans and that different lignans may have different effects. SedativesSedatives: Based on a mouse study, the lignan elenoside may have central depressive properties (71; 72). Another lignan, hydroxypinoresinol, was able to bind to benzodiazepine receptors (70). Tuberculosis herbs and supplementsTuberculosis herbs and supplements: In an in vitro study, a lignan extracted from Valeriana laxiflora exhibited activity against Mycobacterium tuberculosis (75). Lignans may increase the effectiveness of herbs and supplements taken for tuberculosis. Vitamin EVitamin E: Based on in vitro and clinical studies, ingestion of the lignan sesamin may significantly reduce the metabolism of vitamin E and decrease serum and urinary levels of its metabolites (167; 87). Lignan/Food Interactions:
Insufficient available evidence.Lignan/Lab Interactions:
AlbuminAlbumin: In humans, treatment with CPH 82 (Reumacon?), a purified semisynthetic lignan glycoside derivative of the medicinal herb Podophyllum emodi, caused a significant increase in serum albumin.ArginineArginine: In humans, supplementation with a lignan complex containing secoisolariciresinol diglucoside did not change plasma concentrations of asymmetric dimethylarginine, arginine, and symmetrical dimethylarginine (SDMA) (80). Blood pressureBlood pressure: In humans, supplementation with a lignan complex containing secoisolariciresinol diglucoside did not change blood pressure (81; 80). However, in a clinical study in postmenopausal women with vascular disease, lignans from flaxseed significantly reduced blood pressure during mental stress (74). Body weight and BMIBody weight and BMI: In humans, supplementation for six weeks with a lignan complex containing secoisolariciresinol diglucoside did not change body weight or BMI (81; 80). Coagulation panelCoagulation panel: Based on in vitro research, some lignans may have antiplatelet activity (20; 23; 22; 21). Other human research found no change in platelet count (84). Endothelin-1Endothelin-1: In humans, supplementation with a lignan complex containing secoisolariciresinol diglucoside did not change plasma concentrations of endothelin-1 (80). Free androgen indexFree androgen index: Based on a study in prostate cancer patients, lignans from flaxseed may affect prostate cancer biology and associated biomarkers, including the free androgen index (83). GlucoseGlucose: In humans, treatment with CPH 82 (Reumacon?), a purified semisynthetic lignan glycoside derivative of the medicinal herb Podophyllum emodi, resulted in a decrease in serum glucose (84). HemoglobinHemoglobin: In human research, lignans were not found to alter hemoglobin (84). HIV viral loadHIV viral load: Based on in vitro research, several lignans may have antiviral activity against strains of HIV (25; 29; 28; 55). Inflammation markersInflammation markers: In humans, supplementation with a lignan complex containing secoisolariciresinol diglucoside reduced the level of C-reactive protein (CRP) by approximately 15% (81). There were no significant differences in interleukin-6, tumor necrosis factor-alpha, soluble intracellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and monocyte chemoattractant protein-1. In humans, treatment with CPH 82 (Reumacon?), a purified semisynthetic lignan glycoside derivative of the medicinal herb Podophyllum emodi, significantly decreased of CRP, IgM, and IgA (84). In a study of rheumatoid arthritis patients, Proresid?, mainly consisting of podophyllotoxin derivatives and two glycosides thereof, significantly and reversibly reduced C-reactive protein, IgG, and IgM (104). Insulin levelsInsulin levels: In a retrospective cohort study, lignan consumption was negatively correlated with fasting insulin levels (43). Lipid panelLipid panel: In humans, sesamin treatment significantly reduced total cholesterol, LDL cholesterol, and apoprotein B (110; 83). In humans, supplementation with a lignan complex containing secoisolariciresinol diglucoside had no effect on plasma concentrations of total cholesterol, LDL cholesterol, HDL cholesterol, or triglycerol (82). In human studies, there is evidence that a diet containing lignans may increase LDL cholesterol and apo B (43). Based on animal studies, lignans may increase HDL cholesterol levels and the ratio of HDL cholesterol to total cholesterol, while decreasing LDL and total cholesterol levels (109; 36). One clinical trial found that there was an inverse association between high dietary lignan intake and plasma triglyceride levels (168). It should be noted, however, that there are hundreds of different lignans and that different lignans may have different effects. Liver function testsLiver function tests: In rats, oral administration of sesamin significantly increased trifunctional enzyme, acyl-CoA oxidase, bifunctional enzyme, aldehyde dehydrogenase, and 3-ketoacyl-CoA thiolase, but decreased the transcription of the genes encoding the enzymes for fatty acid synthesis (112). In mice, the lignan nordihydroguaiaretic acid (NDGA) increased serum alanine aminotransferase levels (108). Human study found no change in liver enzymes (84). MammographyMammography: Based on two population studies, there may be an association between dietary lignan intake and mammographic density (169; 88). However, one study reported an inverse association and the other reported a positive association. It should be noted, however, that there are hundreds of different lignans and that different lignans may have different effects. Nitrite, nitrateNitrite, nitrate: In humans, supplementation with a lignan complex containing secoisolariciresinol diglucoside did not change plasma concentrations of nitrite and nitrate (80). Prostate-specific antigen (PSA)Prostate-specific antigen (PSA): Based on a study performed on prostate cancer patients, lignans found in flaxseed may alter levels of PSA (83). In this study, PSA levels increased in one study population yet decreased in another. Renal function testsRenal function tests: In a mouse lupus model, lignan metabolites delayed the onset of proteinuria, with preservation of glomerular filtration rate and renal size (59). In human research, no change was noted in creatinine with lignan use (84). Rheumatoid factor (RF)Rheumatoid factor (RF): In a study of rheumatoid arthritis patients, Proresid?, mainly consisting of podophyllotoxin derivatives and two glycosides thereof, significantly reduced the synovitis index, ESR, orosomucoid, and RF-titer (104). These levels reverted towards baseline when treatment was stopped. Sex hormone levelsSex hormone levels: In a study performed on prostate cancer patients, lignans found in flaxseed decreased total testosterone levels (83). In epidemiological and in vitro studies, lignans, including enterolactone and secoisolariciresinol, exhibited weak estrogenic and antiestrogenic properties, and bound to sex hormone-binding globulin (88; 89; 90; 91; 92). However, lignans extracted from Ephedra viridis did not exhibit estrogenic activity in yeast (48). Based on an in vitro study, the crude lignans from rye (Secale cereale) may inhibit the production of progesterone in trophoblast tumor cells (118). Sodium levelsSodium levels: Based on a rat study, the lignan elenoside may have an antidiuretic effect and decrease sodium excretion (44). Tuberculosis testsTuberculosis tests: In an in vitro study, a lignan extracted from Valeriana laxiflora inhibited Mycobacterium tuberculosis (75). UrinalysisUrinalysis: Based on a rat study, the lignan elenoside may have an antidiuretic effect and decrease sodium excretion (44). In a cohort study, women with uterine fibroids excreted in their urine had lower levels of lignans (76). Vitamin ElevelsVitamin Elevels: Based on in vitro and clinical studies, ingestion of the lignan sesamin may significantly reduce the metabolism of vitamin E and decrease serum and urinary levels of its metabolites (167; 87). White blood cell differentialWhite blood cell differential: Based on in vitro studies, several lignans may have immunosuppressive effects (57; 56; 93). Other human research found no change in white blood cell count (84).