DRUGS AND SUPPLEMENTS

Lignans

March 22, 2017

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Lignans

Natural Standard Bottom Line Monograph, Copyright © 2013 (www.naturalstandard.com). Commercial distribution prohibited. This monograph is intended for informational purposes only, and should not be interpreted as specific medical advice. You should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.

While some complementary and alternative techniques have been studied scientifically, high-quality data regarding safety, effectiveness, and mechanism of action are limited or controversial for most therapies. Whenever possible, it is recommended that practitioners be licensed by a recognized professional organization that adheres to clearly published standards. In addition, before starting a new technique or engaging a practitioner, it is recommended that patients speak with their primary healthcare provider(s). Potential benefits, risks (including financial costs), and alternatives should be carefully considered. The below monograph is designed to provide historical background and an overview of clinically-oriented research, and neither advocates for or against the use of a particular therapy.

Related Terms

  • Enterolignans, flax lignans, heterolignans, lignan precursors, mammalian lignans, phytoestrogens, tetrahydrofuran lignans, vegetal estrogens.

  • Select lignan examples: Acetoxyisolariciresinol, acetoxypinoresinol, actaealactone, agastenol, agastinol, aglacin A, aglacin B, aglacin C, aglacin D, alpha-conidendrin, ambrosidine, anolignan A, anolignan B, anolignan C, AP9-cd, arabelline, arborone, arctigenin, arctiin, arylnaphthalide lignan, aryltetralin cyclic ether lignans, beilschmin A, beilschmin B, beilschmin C, benzofuran lignans, beta-apopicropodophyllin, beta-peltatin methyl ether, bursehernin, burseranin, cinnamophilin, cleistanone, cleistanthin A, cleistanthin C, cleistanthin D, clusin, cyclolariciresinol, cyclolignans, dehydro-beta-peltatin methyl ether, dehydrodesoxypodophyllotoxin, dehydropodophyllotoxin, demethoxystegane, demethyldeoxypodophyllotixin, demethylisolariciresinol, deoxydehydropodophyllotoxin, deoxypicropodophyllin, deoxypodophyllotoxin, deoxypodorhizone, desmethoxydeoxypodophyllotoxin, dibenzocyclooctadiene, dibenzyl butyrolactol, dibenzylbutadiene, didehydroarctigenin, didymochlaenone A, didymochlaenone B, di-O-methyltetrahydrofuroguaiacin B, diphyllin, dysosmarol, egonol, elenoside, eleutheroside E, enterodiol, enterofuran, enterolactone, epiashantin, epieudesmin, episteganangin, etoposide, eudesmine, furanoid lignan, gomisin A, gosimin J, gomisin K, grandisin, guggulu, hattalin, helioxanthin, hemiariensin, hernanol, hernolactone, hinokinin, homoegonol, honokiol, hydroxyenterolactone, hydroxymatairesinol, hydroxypinoresinol, hydroxyyatein, isochaihulactone, isodeoxypodophyllotoxin, isolariciresinol, jusmicranthin, justicidin A, justicidin B, justiciresinol, kadsurarin, kusunokinol, lariciresinol, lignan glycoside, linola 989, liriodendrin, machilin A, machilin D, maculatin, majidine, matairesinol (MAT), methoxypodophyllotoxin, methoxyyatein, methyl p-hydroxyphenyllactate, monoepoxylignan, morelensin, naphthalenic lignan lactone 3a, nemerosin, neoisostegane, niranthin, nirtetralin, nordihydroguaiaretic acid (NDGA), nortrachelogenin, nortracheloside, nyasol, olivil, oxomatairesinol, patavine, phillyrin, phyllanthin, picro-beta-peltatin methyl ether, picropolygamain, pinoresinol, podophyllotoxin (CPH 86), podorhizol, praderin, S-8921, sauchinone, saururin A, schizandrin, secoisolariciresinol, sesamin, sesamol, shonanin, simplexoside, steganacin, steganangin, steganoate A, steganoate B, steganolide A, strychnoside, styraxjaponoside A, styraxjaponoside B, syringaresinol, taiwanin A, taxiresinol, teniposide, tetrahydronaphthalene lignan, tibeticoside, tortoside A, trachelogenin, trachelogenin amide, tracheloside, tsugacetal, tuberculatin, valerian, vanprukoside, veraguensin, wikstromol, yatein.

  • Select lignan-containing examples: AC Linora, Acanthopanax koreanum, Achillea clavennae, Aglaia cordata, Annona montana, Anthriscus sylvestris, Arctium lappa L. (Compositae), Asparagus africanus, barley bran, Beilschmiedia tsangii, black cohosh (Actaea racemosa), black sesame, Brucea javanica, Bursera graveolens, Bursera morelensis, Bursera permollis, Calyptranthes pallens, Casearia membranacea, Cephalaria ambrosioides, Cinnamomum philippinense, Cleistanthus collinus, Commiphora mukul, CPH 82 (Reumacon®), creosote bush, Croton spp., Cryptocarya crassinervia, Cunninghamia konishii, Didymochlaena truncatula, Dysosma versipellis, Ephedra viridis, Euodia daniellii, Flanders flaxseed, flaxseed, forsythia fruit (Forsythia viridissima L.), Fraxinus sieboldiana, Haplophyllum spp., Hernandia nymphaeifolia, Hernandia ovigera, Hernandia peltata, Herpetospermum caudigerum, Hyptis tomentosa, Illicium floridanum, Ipomoea cairica, Justicia spp., Kadsura matsudai, Lancea tibetica, Larrea spp., Leontopodium alpinum Cass., linseed, Linum spp., Magnolia spp., oat bran, olive oil, Phillyrea latifolia, Phlomis brunneogaleata, Phyllanthus spp., Picea glehni, Pinus densiflora, Podophyllum emodi, Proresid®, Putoria calabrica, red pine, rye, rye bran, rye seeds, Saururus chinensis, Saussurea lappa, schisandra fruit, Schizandra arisanensis, sesame, sesame oil, sesame seed, Sesamum indicum, Sinomenium acutum, Steganotaenia araliacea, Strychnos vanprukii, Styrax japonica, Taiwania cryptomerioides, Taxus baccata, Taxus wallichiana, Trachelospermum jasminoides, Valeriana laxiflora, virgin olive oil, wheat bran, wholemeal rye bread.

  • Note: Lignan should not be confused with lignin, a complex chemical compound found in wood and the cell walls of plants.

Background

  • Lignans are a group of chemical compounds found in whole grains, seeds, nuts, fruits, and vegetables, particularly in flaxseed and sesame seed. The health effects of lignans have been found to largely depend on the particular type of lignan.

  • There is limited scientific evidence that lignans may be taken to prevent or treat cardiovascular disease, cognitive performance, high cholesterol, high blood pressure, rheumatoid arthritis and several types of cancer. Although some clinical research has been conducted, additional and higher-quality studies are needed before a conclusion may be made about the use of lignans for any condition.

Scientific Evidence

Uses

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Grade*

Antioxidant

There is conflicting evidence regarding the efficacy of lignans as antioxidants. Further research is needed.

C

Breast cancer

Early research suggests that lignans may play a role in breast cancer risk reduction. Additional research is needed in this area.

C

Cognitive performance

Limited evidence suggests that increased lignan intake may be associated with better cognitive performance (mental processes). Further research is needed.

C

Colorectal cancer

Limited evidence suggests that increased dietary lignan intake is correlated with a reduced colorectal cancer risk. Further research is needed.

C

Endometrial cancer

Limited evidence suggests that increased dietary lignan intake may be correlated with a reduced endometrial cancer risk. Additional research is needed in this area.

C

Heart disease

There is conflicting evidence regarding the use of lignans for cardiovascular risk reduction. Further research is needed.

C

High blood pressure

Limited evidence suggests that increased dietary lignan intake may lower blood pressure. Further research is needed.

C

High cholesterol

Limited evidence suggests that sesamin, a lignan found in sesame, may reduce cholesterol levels, especially low-density lipoprotein (LDL) cholesterol. Additional research is needed in this area.

C

Prostate cancer

Limited evidence suggests that increased dietary lignan intake may be correlated with a reduced prostate cancer risk. Additional research is needed in this area.

C

Rheumatoid arthritis

Limited evidence suggests that lignans may be useful in reducing inflammation in rheumatoid arthritis. Further research is needed.

C

Thyroid conditions (cancer)

Limited evidence suggests that secoisolariciresinol, a type of lignan, may be associated with a lower thyroid cancer risk. Further research is needed in this area.

C

Cervical cancer

Limited research suggests that high levels of lignans in the diet and the blood may be associated with a higher risk of cervical lesions. Additional research is needed in this area.

D

*Key to grades:A: Strong scientific evidence for this use; B: Good scientific evidence for this use; C: Unclear scientific evidence for this use; D: Fair scientific evidence against this use (it may not work); F: Strong scientific evidence against this use (it likely does not work).

Tradition/Theory

The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious and should be evaluated by a qualified health care professional.

  • Abnormal heart rhythms, allergies, angiogenesis (new blood vessel growth), anthelmintic (antihelminthic, expels parasitic worms), antibacterial, antifungal, anti-inflammatory, antiplatelet, antiviral, asthma, atherosclerosis (hardening of the arteries), cathartic (promotes bowel movement), chemopreventive (disease-preventing agent), constipation, detoxification, diabetes, diuresis (increasing urine flow), estrogen-like activity, fever, fibromyalgia, fibrosarcoma, heart attack, hepatitis, herpes simplex virus, HIV, human papilloma virus, immune suppression, insecticide, ischemia-reperfusion injury prevention, kidney protection, leukemia, liver cancer, low back pain, lung cancer, lupus, malaria, menopausal symptoms, non-small cell lung cancer, obesity, osteoporosis (bone loss), ovarian cancer, pain, parasitic infection, pleurisy (inflammation of the membranes surrounding the lungs), prostate disorders, sedative, sun protection, snakebites, stomach cancer, stress, stroke, tuberculosis, ulcers, uterine fibroids, wound healing.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older)

  • As an antioxidant, 500 milligrams of secoisolariciresinol diglucoside baked into a low-fat muffin has been taken by mouth daily for six weeks.

  • For cardiovascular disease, 500 milligrams of secoisolariciresinol diglucoside baked into a low-fat muffin has been used daily for six weeks.

  • For rheumatoid arthritis, six capsules containing 300 milligrams of CPH 82 (Reumacon®, 50 milligrams of lignans per capsule) have been taken by mouth daily for 12 weeks. Six 50-milligram capsules of Proresid®, the main component being podophyllotoxin-B-D-benzylidene-glycoside, have been taken by mouth daily for three months, and then reduced to four capsules daily for seven months.

Children (under 18 years old)

  • There is no proven safe or effective dose for lignans in children.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

  • Avoid with known allergy or hypersensitivity to lignans, flaxseed, sesame seeds, or any plants that produce them.

Side Effects and Warnings

  • Lignans may cause abdominal pain, constipation, diarrhea, gastrointestinal discomfort, headaches, heart problems, renal colic, and skin itching.

  • Use cautiously in patients with prostate abnormalities, as increased lignan intake may alter prostate cancer biomarkers, such as prostate-specific antigen (PSA).

  • Some lignans may increase the risk of bleeding. Caution is advised in patients with bleeding disorders or those taking drugs, herbs, or supplements that may increase the risk of bleeding. Dosing adjustments may be necessary.

  • Some lignans may lower insulin and blood sugar levels. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Blood glucose levels may need to be monitored by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.

  • Some lignans may lower blood pressure. Caution is advised in patients taking drugs, herbs, or supplements that lower blood pressure.

  • Use cautiously in patients using central nervous system (CNS) depressants, as some lignans exhibit central depressive properties. Theoretically, concurrent use may increase the risk of sedation.

  • Lignans may interfere with the way the body processes certain drugs, herbs, or supplements using the liver's cytochrome P450 enzyme system. As a result, the levels of these agents may change in the blood and may cause increased or decreased effects or potentially serious adverse reactions. Patients taking any medications should check the package insert and speak with a qualified healthcare professional, including a pharmacist, about possible interactions.

  • Use cautiously in patients taking diuretics (agents that increase urine flow), as lignans may have antidiuretic properties.

  • Use cautiously in patients taking estrogens. Because lignans contains estrogen-like chemicals, the effects of other agents believed to have estrogen-like properties may be altered. Some lignans have also exhibited antiestrogenic properties.

  • Use cautiously in patients with compromised immune systems or those taking immunomodulators, as several lignans may have immunosuppressive effects.

  • Use cautiously in patients taking antibiotics, because antibiotics may significantly lower serum lignan levels.

  • Use cautiously in pregnant or breastfeeding women, due to a lack of available scientific data.

  • Avoid in patients with known allergy or hypersensitivity to lignans, flaxseed, sesame seeds, or any plants that produce them.

Pregnancy and Breastfeeding

  • Lignans are not recommended in pregnant or breastfeeding women, due to a lack of available scientific data.

Interactions

Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.

Interactions with Drugs

  • Some lignans may increase the risk of bleeding when taken with drugs that increase the risk of bleeding. Some examples include aspirin, anticoagulants (blood thinners) such as warfarin (Coumadin®) or heparin, antiplatelet drugs such as clopidogrel (Plavix®), and nonsteroidal anti-inflammatory drugs such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®).

  • Some lignans may lower insulin and blood sugar levels. Caution is advised when using medications that may affect blood sugar. Patients taking insulin or drugs for diabetes by mouth should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.

  • Lignans may cause low blood pressure. Caution is advised in patients taking drugs that lower blood pressure.

  • Lignans may increase the amount of drowsiness caused by some drugs. Examples include central nervous system (CNS) depressants, benzodiazepines such as lorazepam (Ativan®) or diazepam (Valium®), barbiturates such as phenobarbital, narcotics such as codeine, some antidepressants, and alcohol. Caution is advised while driving or operating machinery.

  • Lignans may interfere with the way the body processes certain drugs using the liver's cytochrome P450 enzyme system. As a result, the levels of these drugs may change in the blood and may cause increased or decreased effects or potentially serious adverse reactions. Patients taking any medication should check the package insert and speak with a qualified healthcare professional, including a pharmacist, about possible interactions.

  • Because some lignans have estrogen-like or antiestrogenic properties, the effects of other agents believed to have estrogen-like properties may be altered.

  • Lignans may also interact with agents that affect the immune system, alcohol, androgens, antiangiogenic drugs, antibiotics, anticancer agents, antifungal agents, anti-inflammatory agents, antiprotozoals, antituberculosis agents, antiviral agents, aromatase inhibitors, cardiac glycosides, diuretics, laxatives, and lipid-lowering agents.

Interactions with Herbs and Dietary Supplements

  • Some lignans may increase the risk of bleeding when taken with herbs and supplements that are believed to increase the risk of bleeding. Multiple cases of bleeding have been reported with the use of Ginkgo biloba, and fewer cases with garlic and saw palmetto. Numerous other agents may theoretically increase the risk of bleeding, although this has not been proven in most cases.

  • Some lignans may lower insulin and blood sugar levels. Caution is advised when using herbs or supplements that may affect blood sugar. Blood glucose levels may require monitoring, and doses may need adjustment.

  • Lignans may cause low blood pressure. Caution is advised in patients taking herbs or supplements that lower blood pressure.

  • Lignans may increase the amount of drowsiness caused by some herbs or supplements.

  • Lignans may interfere with the way the body processes certain herbs or supplements using the liver's cytochrome P450 enzyme system. As a result, the levels of these drugs may be altered in the blood.

  • Because some lignans have estrogen-like or antiestrogenic properties, the effects of other agents believed to have estrogen-like properties may be altered.

  • Lignans may also interact with androgenic herbs and supplements, antiangiogenic herbs and supplements, antibacterials, anticancer herbs and supplements, antifungals, anti-inflammatory herbs and supplements, antioxidants, antiprotozoal herbs and supplements, antivirals, cardiac glycosides, diuretics, herbs and supplements that affect the immune system, laxatives, lipid-lowering herbs and supplements, tuberculosis herbs and supplements, and vitamin E.

Author Information

  • This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

References

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

  1. Cotterchio M, Boucher BA, Manno M, et al. Dietary phytoestrogen intake is associated with reduced colorectal cancer risk. J Nutr 2006;136(12):3046-3053. View Abstract

  2. Hallund J, Ravn-Haren G, Bugel S, et al. A lignan complex isolated from flaxseed does not affect plasma lipid concentrations or antioxidant capacity in healthy postmenopausal women. J Nutr 2006;136(1):112-116. View Abstract

  3. Hallund J, Tetens I, Bugel S, et al. Daily consumption for six weeks of a lignan complex isolated from flaxseed does not affect endothelial function in healthy postmenopausal women. J Nutr 2006;136(9):2314-2318. View Abstract

  4. Hallund J, Tetens I, Bugel S, et al. The effect of a lignan complex isolated from flaxseed on inflammation markers in healthy postmenopausal women. Nutr Metab Cardiovasc Dis 2008;18(7):497-502. View Abstract

  5. Horn-Ross PL, Hoggatt KJ, Lee MM. Phytoestrogens and thyroid cancer risk: the San Francisco Bay Area thyroid cancer study. Cancer Epidemiol Biomarkers Prev 2002;11(1):43-49. View Abstract

  6. Kilkkinen A, Erlund I, Virtanen MJ, et al. Serum enterolactone concentration and the risk of coronary heart disease in a case-cohort study of Finnish male smokers. Am J Epidemiol 2006;163(8):687-693. View Abstract

  7. Kreijkamp-Kaspers S, Kok L, Bots ML, et al. Dietary phytoestrogens and vascular function in postmenopausal women: a cross-sectional study. J Hypertens 2004;22(7):1381-1388. View Abstract

  8. Low YL, Taylor JI, Grace PB, et al. Polymorphisms in the CYP19 gene may affect the positive correlations between serum and urine phytoestrogen metabolites and plasma androgen concentrations in men. J Nutr 2005;135(11):2680-2686. View Abstract

  9. McCann SE, Ambrosone CB, Moysich KB, et al. Intakes of selected nutrients, foods, and phytochemicals and prostate cancer risk in western New York. Nutr Cancer 2005;53(1):33-41. View Abstract

  10. Penumathsa SV, Koneru S, Thirunavukkarasu M, et al. Secoisolariciresinol diglucoside: relevance to angiogenesis and cardioprotection against ischemia-reperfusion injury. J Pharmacol Exp Ther 2007;320(2):951-959. View Abstract

  11. Stuedal A, Gram IT, Bremnes Y, et al. Plasma levels of enterolactone and percentage mammographic density among postmenopausal women. Cancer Epidemiol Biomarkers Prev 2005;14(9):2154-2159. View Abstract

  12. van der Schouw YT, Kreijkamp-Kaspers S, Peeters PH, et al. Prospective study on usual dietary phytoestrogen intake and cardiovascular disease risk in Western women. Circulation 2005;111(4):465-471. View Abstract

  13. Vanharanta M, Voutilainen S, Rissanen TH, et al. Risk of cardiovascular disease-related and all-cause death according to serum concentrations of enterolactone: Kuopio Ischaemic Heart Disease Risk Factor Study. Arch Intern Med 2003;163(9):1099-1104. View Abstract

  14. Wu WH, Kang YP, Wang NH, et al. Sesame ingestion affects sex hormones, antioxidant status, and blood lipids in postmenopausal women. J Nutr 2006;136(5):1270-1275. View Abstract

  15. Zeleniuch-Jacquotte A, Lundin E, Micheli A, et al. Circulating enterolactone and risk of endometrial cancer. Int J Cancer 2006;119(10):2376-2381. View Abstract

Copyright © 2013 Natural Standard (www.naturalstandard.com)

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

Updated:  

March 22, 2017