Lignans: A Comprehensive Reference
1. Identity and Chemical Classification
Lignans are polyphenolic phytochemicals that have varying biological activities under several contexts. Lignans are a group of diphenol derivatives with dibenzylbutane skeleton structures and characteristics similar to those of phytoestrogens. More precisely, lignans are phytoestrogens with estrogenic or antiestrogenic activity, comprising 2-phenylpropane units.
Lignans are secondary plant metabolites, which are produced from shikimic acid via the phenylpropanoid pathway. In plants, lignans are biosynthesized along the phenylpropanoid pathway, resulting in the biosynthesis of lignin, a plant polymer of the cell wall. They develop from flavonoid precursors and are responsible for conferring resistance to plants against pathogens and predators.
Structurally, eight classes of lignans are recognized: furofuran, furan, dibenzylbutane, dibenzylbutyrolactone, aryltetralin, arylnaphthalene, dibenzocyclooctadiene, and dibenzylbutyrolactol.
Phytoestrogens are polyphenolic non-steroidal plant compounds with estrogen-like biological activity. Based on their chemical structure, phytoestrogens can be classified into four main groups: isoflavonoids, flavonoids, stilbenes, and lignans. Since phytoestrogens are structurally very similar to the estrogen 17beta-estradiol, they may exhibit selective estrogen receptor modulating activities.
1.1 Key Plant Lignans
Lignan precursors that have been identified in the human diet include pinoresinol, lariciresinol, secoisolariciresinol, matairesinol, and others. Secoisolariciresinol and matairesinol were among the first lignan precursors identified in the human diet and are therefore the most extensively studied.
The most pharmacologically prominent plant lignan is secoisolariciresinol diglucoside (SDG). The primary lignan found in flaxseed is 2,3-bis (3-methoxy-4-hydroxybenzyl) butane-1,4-diol (secoisolariciresinol), which is stored as the conjugate secoisolariciresinol diglucoside (SDG) in its native state in the plant.
1.2 Mammalian (Entero-) Lignans
The enterolignans, enterodiol and enterolactone, are formed by the action of intestinal bacteria on lignan precursors found in plants. Because enterodiol and enterolactone can mimic some of the effects of estrogens, their plant-derived precursors are classified as phytoestrogens.
The main difference between enterolignans and plant lignans is that enterolignans have a hydroxyl group at the meta (3′) position of the aromatic ring, making them chemically stable, whereas plant lignans have oxygenated substituents at the 3′ and 4′ positions.
2. Natural Sources
Lignans are present in a wide variety of plant foods, including seeds (flax, pumpkin, sunflower, poppy, sesame), whole grains (rye, oats, barley), bran (wheat, oat, rye), beans, fruit (particularly berries), vegetables, and beverages like tea, coffee, and wine.
Secoisolariciresinol, matairesinol, pinoresinol, and lariciresinol contribute substantially to total dietary lignan intakes, although this varies with dietary pattern.
Flaxseed is by far the richest dietary source of plant lignans, and lignan bioavailability can be improved by crushing or milling flaxseed. Lignans are not associated with the oil fraction of foods, so flaxseed oils do not typically provide lignans unless ground flaxseed has been added to the oil. Flaxseed contains levels of these phytoestrogens which are 75–800 times greater than any other plant food.
While most research on phytoestrogen-rich diets has focused on soy isoflavones, lignans are the principal source of dietary phytoestrogens in the typical Western diet.
A variety of factors may affect the lignan content of plants, including geographic location, climate, maturity, and storage conditions.
Sesame (Sesamum indicum) is another important lignan source, containing the distinctive furofuran-type lignans sesamin and sesamolin. Extracts of the bark of Eucommia ulmoides are used in Chinese traditional medicine (known as tu-chung) and represent a commercial source of pinoresinol diglucoside. Two lignan glycosides have also been found in the aerial portion of Lespedeza cuneata (Fabaceae), known as Chinese bushclover, a plant that has been used in traditional medicine for the treatment of diseases including diabetes, hematuria, and insomnia. Mexican Bursera plants have been used in traditional medicine for treating various pathophysiological disorders and are a rich source of lignans.
2.1 Common Supplement Forms and Preparations
Dietary supplements containing lignans derived from flaxseed are available in the US without a prescription; secoisolariciresinol is the primary lignan in such supplements. These are typically available as:
- Ground flaxseed (milled whole seeds, the most common dietary form)
- SDG-standardized flaxseed extracts (capsule or tablet form, with stated SDG content)
- Flaxseed lignan complex (FLC) products such as BeneFlax®, a commercial extract standardized to 34–38% lignan content
- Sesame lignan concentrates (sesamin/episesamin)
- Hydroxymatairesinol (HMR) extracts derived from Norway spruce (Picea abies) knots
BeneFlax® received recognition from the Food and Drug Administration Agency and Health Canada as ensuring a significant source of lignan with oral consumption, and demonstrated good tolerability and safety with long-term supplementation.
3. Traditional and Historical Use
Lignans have been used for centuries in both food and traditional herbal medicine. It is important to note that lignan compounds as chemically defined entities were not isolated or described until the twentieth century; the traditional use of lignan-rich plants preceded any knowledge of the specific phytochemicals they contained.
The flax plant was first cultivated as early as 3000 BC in Mesopotamia, where it was believed to possess significant health benefits. Through the course of history, the flax plant enjoyed widespread use in ancient Greek cuisine and in ancient Roman medicine. Its historical medicinal uses include being used as a laxative as well as an expectorant responsible for soothing irritated tissue, controlling coughs, and even relieving pain.
From the Hippocratics to Dioscorides, the ancients had a good knowledge of the therapeutic action of flaxseed, which they probably obtained from experience without a proper understanding of the underlying chemistry.
In Ayurvedic medicine, flaxseed (Atasi) and sesame (Til) were used for balancing vata, nourishing reproductive tissues, improving skin health, and aiding bowel regularity. Both were considered rejuvenating and supportive of fertility and hormonal vitality. Sesame oil was used topically and internally for inflammation and joint health, indirectly delivering lignan benefits.
In Chinese traditional medicine, extracts of the bark of Eucommia ulmoides (杜仲, tu-chung) have been used as a traditional remedy for centuries. Traditional Japanese and Chinese diets are rich in foods containing phytoestrogenic compounds, whereas the Western diet is a poor source of these phytochemicals.
Two groups of compounds with diphenolic structure — the lignans and the isoflavonic phytoestrogens — were detected and identified in human urine and other biological fluids only in the latter decades of the twentieth century. These compounds are of great biological interest because they exhibit both in vitro and in vivo weak estrogenic and sometimes also antiestrogenic activities, and many plant lignans have been shown to have anticarcinogenic, antiviral, antifungal, and other biological effects. The formal chemical characterization of lignans as a class of plant metabolites is credited to work published in the early 1980s.
4. Key Constituents, Pharmacokinetics, and Mechanisms of Action
4.1 Absorption, Metabolism, and the Gut Microbiome
Secoisolariciresinol-diglucoside (SDG), a natural dietary lignan of flaxseeds now available in dietary supplements, is converted by intestinal bacteria to the mammalian lignans enterodiol and enterolactone.
Several biochemical steps are involved in plant lignan transformation into enterolignans, and the consortia of bacteria share metabolic intermediates. Bacteria utilize four sequential reactions to convert SDG to enterolactone: O-deglycosylation, O-demethylation, dehydroxylation, and dehydrogenation.
Estrogenic plant compounds from the human diet such as SDG can exert biological activity in the human body upon ingestion and bioactivation to enterodiol (END) and enterolactone (ENL). Bioavailability of lignans is influenced by the food matrix and gut microbial action, of which the latter is subject to a large interindividual variation.
Following their formation in the gut, mammalian lignans such as enterodiol and enterolactone are absorbed in the colon and enter the hepatic portal system for conjugation in the liver. They are then excreted back into the colon through the bile duct, where they are deconjugated by the enzyme β-glucuronidase and then reabsorbed. Mammalian lignans derived from dietary phytoestrogens are present in blood, bile, faeces, urine, saliva, sperm, and milk.
Plant lignans are transformed into enterolignans, namely enterolactone (EL) and enterodiol (ED), by gut microbiota. These compounds, also named mammalian lignans, are more bioavailable compared to their precursors and are associated with beneficial effects on human health.
Inter- and intra-individual variations in enterolignan production have been observed and are attributed to individual dietary habits, food transit time, and gut microbial composition and abundance. Three different enterolignan-producing phenotypes have been defined (low, middle, and high), based on the metabolic capacity of the gut microbiota, with the differences being influenced by age, sex, and genetics.
Key factors affecting the metabolism of phytoestrogens include the gut microbiome composition and the overall diet, both of which influence bioavailability and conversion to active metabolites.
4.2 Mechanisms of Action
Lignan's enterolignan products enterodiol and enterolactone have weak estrogenic activity, but they may also exert biological effects through non-estrogenic means.
The compounds found in relatively large amounts (10–1000 times more than estrogens) in urine are modified by intestinal bacteria from plant lignans and phytoestrogens, which are present in fiber-rich food. They bind with low affinity to estrogen receptors and preliminary results suggest that they may induce production of sex hormone binding globulin (SHBG) in the liver and in this way may influence sex hormone metabolism and biological effects.
Gut bacterial metabolism is able to convert dietary lignans into therapeutically relevant polyphenols (i.e., enterolignans), such as enterolactone and enterodiol. Enterolignans are characterized by various biologic activities, including tissue-specific estrogen receptor activation, together with anti-inflammatory and apoptotic effects.
In vitro, animal, and epidemiological studies suggest that dietary lignans may be chemopreventive, potentially through anti-estrogenic, anti-angiogenic, pro-apoptotic, and anti-oxidant mechanisms.
Lignans can reduce blood pressure and improve vascular function, which is mediated through multiple mechanisms, such as enhancement of endothelial function, neutralization of reactive oxygen species (ROS), inhibition of ACE activity, modulation of the renin-angiotensin-aldosterone system (RAAS), and interaction with calcium-signaling pathways.
Lignans are considered promising for human health due to their hydrogen-donating antioxidant activity together with their ability to complex divalent transition metal cations.
Lignans have been revealed to decrease testosterone by binding it to enterohepatic circulation and inhibiting 5α-reductase, the enzyme that converts testosterone to dihydrotestosterone.
5. Scientific Evidence by Area of Use
5.1 Cardiovascular Disease
Lignans are the active compounds in flaxseed believed to mediate the cardiovascular health benefits following flaxseed consumption.
Epidemiological evidence: A prospective study examined associations between lignan intake and coronary heart disease (CHD) risk. It followed 214,108 men and women in 3 cohorts who did not have cardiovascular disease or cancer at baseline. Diet was repeatedly assessed using a validated food frequency questionnaire every 2–4 years. During 5,517,225 person-years of follow-up, 10,244 CHD cases were documented. In multivariable-adjusted analyses, comparing extreme quintiles, the pooled hazard ratios of CHD were 0.85 (95% CI: 0.79–0.92) for total lignans, 0.76 (95% CI: 0.71–0.82) for matairesinol, 0.87 (95% CI: 0.81–0.93) for secoisolariciresinol, and 0.89 (95% CI: 0.83–0.95) for both pinoresinol and lariciresinol.
In humans, higher circulating concentrations of enterolactone have been associated with lower risk of coronary heart disease in several prospective cohort studies, although the findings are not entirely consistent.
Intervention evidence (cholesterol): Five intervention studies using flaxseed lignan supplements indicated beneficial associations with C-reactive protein, and a meta-analysis that included these studies also suggested lignans have a lowering effect on plasma total and low-density lipoprotein cholesterol. Three intervention studies using sesamin supplements indicated possible lipid- and blood pressure-lowering associations.
However, individual RCT results are mixed. A double-blind, randomized controlled trial in adults aged 44 to 75 years found that supplementation with 40 g/day of flaxseed led to significant reductions in LDL-cholesterol after five weeks, but the cholesterol reductions were not statistically significant following 10 weeks' supplementation. Additionally, a one-year clinical trial in postmenopausal women reported that supplementation with 40 g/day of flaxseed did not lower LDL-cholesterol compared to a placebo containing wheat germ.
In a randomized, double-blind, placebo-controlled trial in 84 patients with peripheral artery disease, 30 g/day of flaxseed for 12 months did not reduce total or LDL-cholesterol compared to placebo, although cholesterol reductions within the flaxseed-supplemented group were evident at 1 month and 6 months compared to baseline but not at 12 months.
A specific human trial using isolated SDG showed more consistent results. In a randomized double-blind placebo-controlled trial, all subjects were hypercholesterolaemic. After 8 weeks, significant reductions in total cholesterol, LDL-cholesterol, and glucose concentrations were found among those receiving 600 mg SDG per day compared with the placebo group.
Intervention evidence (blood pressure): A 2016 meta-analysis pooled the results of 15 randomized controlled trials, some in healthy participants and some in participants with chronic disease (type 2 diabetes, metabolic syndrome, peripheral arterial disease) or risk factors of cardiovascular disease. Supplementation with flaxseed was linked to a 2.9 mm Hg reduction in systolic blood pressure and a 2.4 mm Hg reduction in diastolic blood pressure; these blood pressure reductions were greater in trials of longer duration (≥12 weeks vs. <12 weeks).
Overall cardiovascular evidence quality: Eleven human observational epidemiological studies examined dietary intakes of lignans in relation to cardiovascular disease risk. Five showed decreased risk with either increasing dietary intakes of lignans or increased levels of serum enterolactone, five studies were of borderline significance, and one was null. The overall epidemiological signal is moderately consistent, while intervention evidence for isolated lignans (as opposed to whole flaxseed) is still considered preliminary and requires large-scale RCTs.
5.2 Cancer Prevention
5.2.1 Breast Cancer
Lignans can reduce the risk of postmenopausal breast cancer. In most cases, breast cancer is estrogen-dependent, meaning cancer cells express estrogen receptors. Phytoestrogens, due to their structural similarities with estrogen, are capable of binding to estrogen receptors and are therefore also referred to as selective estrogen receptor modulators. They can be either estrogen agonists or antagonists and thus influence the risk of breast cancer.
Although a number of in vitro and animal studies support a role for lignan-rich foods and purified lignans in the modulation of cancer events of the breast, prostate, and colon, epidemiological studies, sparse and often retrospective in nature, offer inconsistent findings. The most support for a role of lignans in cancer is observed for premenopausal breast cancer.
Several studies have demonstrated that regular consumption of phytoestrogens in the diet of Asian women has led to a reduction in menopausal symptoms, breast cancer, endometrial cancer, and an increase in bone mass compared to other regions.
5.2.2 Prostate Cancer
Lignans and their in vivo metabolites, especially enterolactone (ENL), have attracted substantial interest as potential chemopreventive agents for prostate cancer. Preclinical and clinical interventions performed with lignan-rich flaxseed using surrogate biomarkers as endpoints suggest that lignans may attenuate prostate carcinogenesis in individuals with increased risk or with diagnosed cancer.
No unequivocal prostate cancer risk reduction has been found for lignans in epidemiological studies, suggesting that lignan concentrations found in populations consuming a regular non-supplemented diet are not chemopreventive in prostate cancer. Presumably, the main obstacles in assessing the efficacy of food lignans is limited knowledge of the serum and tissue lignan concentrations required for the putative prevention. Further clinical studies performed with the purified compounds are required to substantiate a health claim.
In vitro and in vivo reports in the literature indicate that lignans have the capacity to affect the pathogenesis of prostate cancer. However, their precise mechanism of action in prostate carcinogenesis remains unclear.
Evidence quality for cancer: The body of evidence for lignans in cancer prevention is currently characterized by substantial preclinical (in vitro and animal) data, mixed and inconsistent epidemiological findings, and few adequately powered human clinical trials using isolated lignan compounds. This area must be considered preliminary.
5.3 Type 2 Diabetes and Metabolic Syndrome
Lignans have shown potential in mitigating conditions such as cardiovascular disease, diabetes, and metabolic syndrome.
Animal and human study evidence supports the hypothesis that flaxseed lignan complex (FLC) at a dose of 600 mg secoisolariciresinol diglucoside (SDG) per day for three months would combat hyperglycaemia, dyslipidemia, blood pressure, central obesity, prothrombotic state, inflammation, and LDL oxidation. Sixteen type 2 diabetic patients completed the corresponding double-blind, randomised crossover placebo-controlled study. Prior to correction for multiple comparisons, FLC caused decreased fasting plasma glucose, A1c, inflammation (CRP and IL-6), and increased bleeding time. After correction for multiple comparisons, FLC induced a statistically significant increase in bleeding time and smaller waist circumference gain.
Human lignan intake has been associated with reducing the homeostatic model assessment for insulin resistance (HOMA-IR) values related to preventing obesity and diabetes.
Evidence quality: The human evidence for lignan effects on glycemic parameters is suggestive but limited. Existing trials are small, of short duration, and often use whole flaxseed rather than isolated lignans, making it difficult to attribute effects specifically to the lignan fraction.
5.4 Menopausal Symptoms
Lignans may have therapeutic potential for postmenopausal symptoms, including cardiovascular disease, osteoporosis, and psychological disorders.
Mammalian metabolites (enterolactone and enterodiol) exhibit structural similarity to estradiol, enabling lignans to modulate hormonal balance and exert estrogen-like effects. Estrogen deficiency due to ovarian aging blocks the negative feedback system, leading to various menopausal symptoms, including face flushing, skin dryness, anxiety and more severe conditions such as cardiovascular disorders, osteoporosis, and depression.
Specific trial data for isolated lignans on hot flushes remain limited. The daily consumption of a low-fat muffin enriched with SDG (500 mg/day) for 6 weeks had no effect on endothelial functioning in healthy postmenopausal women.
Evidence quality: The plausibility of lignan effects on menopausal symptoms is supported by mechanistic data, and observational data from Asian populations consuming high-phytoestrogen diets is suggestive; however, specifically designed, well-powered RCTs on lignan isolates for menopausal symptom endpoints are lacking. This area should be characterized as preliminary.
5.5 Bone Health
Lignans may promote bone health through their interaction with estrogen receptor β and help prevent hormone-dependent cancers such as breast and endometrial cancer by modulating estrogen signaling pathways.
Osteoporosis results from an imbalance between the activities of osteoblasts and osteoclasts and is characterized by reduced bone mineral density and degradation of trabecular tissues, resulting in fragility fractures. Lignans help to alleviate menopausal symptoms in postmenopausal women, such as osteoporosis and decreased bone production, by decreasing the production of androgen and increasing the synthesis of estrogen.
Evidence quality: Mechanistic pathways are well described in preclinical models; however, dedicated clinical trial evidence for lignans specifically on bone mineral density outcomes is limited and requires further investigation.
5.6 Blood Pressure and Anti-Obesity Effects
Scientific evidence from animal and clinical trials reviewed suggested that lignans also provide important beneficial effects in lowering blood pressure and in reducing body weight, BMI, and central adiposity.
In animal models, dietary supplementation with SDG-enriched flaxseed powder (0.02%) significantly reduced blood pressure in rats fed a high-fat, high-fructose diet. SDG reduced blood pressure in Dawley male rats by inhibiting angiotensin-converting enzyme (ACE).
The anti-obesity effects of lignans are mediated through multiple interconnected mechanisms, such as modulation of appetite-regulation hormones. Among emerging dietary interventions, lignans have shown promising potential in ameliorating obesity and its associated metabolic disturbances. Most of this evidence, however, derives from cell and animal studies, with clinical data still sparse.
5.7 Antioxidant and Anti-Inflammatory Effects
Lignans have been suggested to promote health beneficial effects such as antioxidant, antitumor, estrogenic and antiestrogenic activities and protection against coronary heart diseases.
A growing body of evidence highlights their broad spectrum of health-promoting properties, including antioxidant, anti-inflammatory, and hormone-regulating effects. Lignans are believed to have direct antioxidant properties and can inhibit lipid peroxidation in tissues such as the brain.
5.8 Antimicrobial Activity
Lignans' antimicrobial activity against bacteria, fungi, and viruses is being increasingly recognized. Many plant lignans have been shown to have anticarcinogenic, antiviral, antifungal, and other interesting biological effects in vitro; however, clinical evidence in humans for antimicrobial applications is currently lacking.
6. Body Systems Associated with Lignans
The majority of studies demonstrate that SDG interferes with the development of different types of diseases like cardiovascular, diabetic, lupus nephritis, bone, kidney, menopause, reproduction, mental stress, immunity, atherosclerosis, hemopoietic, liver necrosis, and urinary disorders due to its various biological properties including anti-inflammatory, antioxidant, antimutagenic, antimicrobial, antiobesity, antihypolipidemic, and neuroprotective effects.
Lignans have demonstrated beneficial effects for cardiovascular disease, as well as in maintaining blood glucose levels, supporting cardiac health, promoting anti-obesity effects, decreasing the risk of renal diseases, enhancing brain function, improving skin and gut health, among others.
- Endocrine/hormonal system: Phytoestrogenic modulation of estrogen receptors α and β; induction of SHBG; modulation of androgen metabolism
- Cardiovascular system: Effects on blood lipids, blood pressure, endothelial function, and inflammatory biomarkers such as CRP
- Oncology: Investigated for chemopreventive potential in hormone-dependent cancers (breast, prostate, endometrial, colorectal)
- Metabolic system: Glycemic control and insulin sensitivity, central adiposity
- Skeletal system: Bone density through estrogen receptor β interaction
- Gastrointestinal system: Prebiotic-like interaction with gut microbiota affecting enterolignan production
- Neurological system: Neuroprotective potential in emerging preclinical research
7. Dosage Forms and Dosages Reported in Studies
The following dosages are drawn directly from peer-reviewed studies; they represent research doses, not universal recommendations.
- Flaxseed (ground/whole): 40 g/day in a double-blind, randomized controlled trial in adults aged 44–75 years, examined for LDL-cholesterol effects over five and ten weeks. 30 g/day for 12 months in a placebo-controlled trial in 84 patients with peripheral artery disease.
- SDG (secoisolariciresinol diglucoside) — isolated extract: 300 mg SDG per day and 600 mg SDG per day were compared against placebo in hypercholesterolaemic subjects over 8 weeks; significant reductions in total cholesterol, LDL-cholesterol, and glucose were found in the 600 mg group.
- Flaxseed lignan complex (FLC) — SDG-equivalent: 600 mg SDG per day for three months was used in a double-blind, randomised crossover placebo-controlled study in type 2 diabetic patients.
- SDG extract (flaxseed, standardized) — capsule form: Lignan capsules containing 300 mg flaxseed (SDG) extract were used in a randomized double-blind controlled trial examining cardiovascular outcomes in healthy volunteers (the CardioFlax Study).
- SDG-enriched muffin: 500 mg SDG per day delivered in a low-fat muffin for 6 weeks in postmenopausal women, finding no effect on endothelial functioning.
- Sesame lignans (sesamin/episesamin): 50 mg/day of sesame lignans (1:1 mixture of sesamin and episesamin) for 28 days was used in one small, placebo-controlled study.
8. Safety Considerations and Notable Interactions
8.1 General Safety Profile
Lignan precursors in food are not known to have any serious adverse effects.
Flaxseeds, which are rich in lignan precursors as well as dietary fiber, may increase stool frequency or cause diarrhea in doses of 45 to 50 g/day in adults.
One small, placebo-controlled study found that 50 mg/day of sesame lignans (1:1 mixture of sesamin and episesamin) for 28 days did not result in any serious adverse effects, although abdominal flatulence was associated with the sesame lignan supplementation.
8.2 Anticoagulant and Platelet Effects
Melatonin, flaxseed, and grape seed extract affect platelet aggregation activity and/or blood coagulation activity in humans in RCTs. RCTs have additionally shown that flaxseed oil decreases platelet aggregation. This finding is notable in the context of concurrent anticoagulant therapy, as additive effects on bleeding risk cannot be excluded. The flaxseed lignan complex was itself observed to increase bleeding time in a small diabetic cohort study (see section 7 above).
8.3 Estrogenic Activity and Hormone-Sensitive Conditions
Lignans are plant-derived biphenolic compounds with multiple hydroxyl groups, which, upon ingestion, are metabolized by gut microbiota into enterolignans — enterolactone and enterodiol. These mammalian metabolites exhibit structural similarity to estradiol, enabling lignans to modulate hormonal balance and exert estrogen-like effects. This weak estrogenic/anti-estrogenic activity is relevant for individuals with hormone-sensitive conditions.
In an analysis of breast cancer survivor supplement use, 31% of reported dietary supplement ingredients caused estrogenic activity that could further potentiate estrogenic exposure. This may reduce the effectiveness of hormone therapy and therefore worsen patients' prognoses.
SDG supplementation produces a dose-related cessation or lengthening (by 18–39%) of estrous cycles, reduces immature ovarian relative weight, and delays puberty in experimental animals. The clinical significance of this finding in humans at dietary or supplemental doses has not been established.
8.4 Interactions with Hormonal Cancer Therapies
Lignans' phytoestrogenic activity raises theoretical concerns about interactions with selective estrogen receptor modulators (SERMs) such as tamoxifen. Several dietary supplements have potential pharmacokinetic and pharmacodynamic interactions that may change their clinical efficacy or potentiate adverse effects of the adjuvant endocrine therapy prescribed for breast cancer treatment. Specific, well-powered studies on lignan-tamoxifen interactions in humans are absent from the published literature.
8.5 Variability Due to Gut Microbiome
Key factors affecting the metabolism of phytoestrogens include the gut microbiome composition and the overall diet, both of which influence bioavailability and conversion to active metabolites. Because the health effects of lignans are substantially mediated by gut microbial conversion to enterolactone and enterodiol, individuals with dysbiosis, those taking antibiotics, or those with reduced gut microbial diversity may experience substantially different biological effects from the same dietary or supplemental lignan dose.
8.6 Pregnancy and Reproductive Considerations
SDG supplementation produces a dose-related cessation or lengthening of estrous cycles and delays puberty in experimental animals. Extrapolation of these findings to humans requires caution, and the reproductive safety of high-dose isolated lignan supplementation in pregnancy has not been adequately studied in controlled human trials.
8.7 Flaxseed Oil versus Ground Flaxseed
Flaxseed is by far the richest dietary source of plant lignans, and lignan bioavailability can be improved by crushing or milling flaxseed. Lignans are not associated with the oil fraction of foods, so flaxseed oils do not typically provide lignans unless ground flaxseed has been added to the oil. Individuals who use flaxseed oil assuming it delivers lignans may not receive the expected phytoestrogenic effects.
References
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