Lariciresinol

Other Names

(2S)-2alpha-(3-Methoxy-4-hydroxyphenyl)-4beta-(3-methoxy-4-hydroxybenzyl)tetrahydrofuran-3beta-methanol(2S)-Tetrahydro-2alpha-(4-hydroxy-3-methoxyphenyl)-4beta-[(4-hydroxy-3-methoxyphenyl)methyl]-3beta-furanmethanol(2S,3R,4R)-Tetrahydro-2-(4-hydroxy-3-methoxyphenyl)-4-[(4-hydroxy-3-methoxyphenyl)methyl]-3-furanmethanol2-Methoxy-4-[[(2S)-tetrahydro-2alpha-(3-methoxy-4-hydroxyphenyl)-3beta-(hydroxymethyl)furan-4beta-yl]methyl]phenol2alpha-(4-Hydroxy-3-methoxyphenyl)-3beta-(hydroxymethyl)-4beta-(4-hydroxy-3-methoxybenzyl)tetrahydrofuran3,14-dimethoxy-7,10-epoxylignan-4,15,19-triol4-((2S,3R,4R)-4-(4-hydroxy-3-methoxybenzyl)-3-(hydroxymethyl)tetrahydrofuran-2-yl)-2-methoxyphenol4-[(2S,3R,4R)-4-(4-Hydroxy-3-methoxybenzyl)-3-(hydroxymethyl)tetrahydro-2-furanyl]-2-methoxyphenol4-[(2S,3R,4R)-4-[(4-hydroxy-3-methoxyphenyl)methyl]-3-(hydroxymethyl)tetrahydrofuran-2-yl]-2-methoxyphenol4-[[(3R,4R,5S)-5-(4-hydroxy-3-methoxyphenyl)-4-(hydroxymethyl)oxolan-3-yl]methyl]-2-methoxyphenolLarch resinolLaricericinolLariciresilNSC 329247NSC329247tetrahydro-2-(4-hydroxy-3-methoxyphenyl)-4-vanillyl-3-furanmethanolTetrahydro-2-(4-hydroxy-3-methoxyphenyl)-4-[(4-hydroxy-3-methoxyphenyl)methyl]-, (2S,3R,4R)-3-furanmethanolTetrahydro-2-(4-hydroxy-3-methoxyphenyl)-4-[(4-hydroxy-3-methoxyphenyl)methyl]-, [2S-(2alpha,3beta,4beta)]-3-furanmethanol[2S-(2alpha,3beta,4beta)]-Tetrahydro-2-(4-hydroxy-3-methoxyphenyl)-4-[(4-hydroxy-3-methoxyphenyl)methyl]-3-furanmethanol

Synopsis

Lariciresinol: A Comprehensive Reference

1. Identity and Chemical Characterization

1.1 Chemical Names and Structure

Lariciresinol is a lignan, a type of phenylpropanoid. Structurally, it is a lignan consisting of a tetrahydrofuran ring substituted at positions 2, 3, and 4 by 4-hydroxy-3-methoxyphenyl, hydroxymethyl, and 4-hydroxy-3-methoxybenzyl groups, respectively (the 2S,3R,4R-diastereomer in its (+)-form). Its molecular formula is C₂₀H₂₄O₆, giving a molecular weight of approximately 364.4 g/mol, as recorded in both the PubChem and ChEBI databases.

The compound exists as two distinct enantiomers: (+)-lariciresinol (CAS 27003-73-2, PubChem CID 332427) and (−)-lariciresinol (CAS 83327-19-9, PubChem CID 23815394). The IUPAC name for (+)-lariciresinol is (2S,3R,4R)-tetrahydro-2-(4-hydroxy-3-methoxyphenyl)-4-[(4-hydroxy-3-methoxyphenyl)methyl]-3-furanmethanol, with the CAS registry number 27003-73-2. The two enantiomers differ in optical rotation but share the same connectivity; both occur in nature and have been studied for biological activity.

1.2 Classification Within the Lignan Family

Lariciresinol belongs to the subclass of tetrahydrofuran lignans (also termed furofuran-related lignans) and is classified as a phytoestrogen. Phytoestrogens include isoflavonoids, flavonoids, stilbenoids, and lignans. Lignans themselves are classified into seven main types: secoisolariciresinol (Seco), pinoresinol (Pino), matairesinol (Mat), medioresinol (Med), sesamin (Ses), syringaresinol (Syr), and lariciresinol (Lari).

The comprehensive database on the phenolic composition of foods, Phenol-Explorer, reports 53 lignans including both parent compounds and large intestine metabolites. The plant lignans most commonly distributed in foods are reported to be lariciresinol, matairesinol, pinoresinol, and secoisolariciresinol.

2. Natural Sources and Botanical Distribution

2.1 Primary Plant Sources

Lariciresinol is widely distributed across the plant kingdom. In food, it is found in sesame seeds and Brassica vegetables, and it is also found in the bark and wood of silver fir (Abies alba).

Lignans, including lariciresinol, 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.

Quantitative analyses reveal an important hierarchy of sources. Liquid chromatography–tandem mass spectrometry was used to quantify lariciresinol, pinoresinol, secoisolariciresinol, and matairesinol in 83 solid foods and 26 beverages commonly consumed in the Netherlands. The richest source of lignans was flaxseed (301,129 µg/100 g), which contained mainly secoisolariciresinol. Lignan concentrations in sesame seeds (29,331 µg/100 g, mainly pinoresinol and lariciresinol) were also relatively high.

For grain products, lignan concentrations ranged from 7 to 764 µg/100 g; however, many vegetables and fruits had similar concentrations due to the contribution of lariciresinol and pinoresinol. Brassica vegetables contained unexpectedly high levels of lignans (185–2,321 µg/100 g), mainly pinoresinol and lariciresinol.

Lignan levels in beverages varied from 0 (cola) to 91 µg/100 ml (red wine). Only four of the 109 foods analyzed did not contain a measurable amount of lignans, and in most cases the amount of lariciresinol and pinoresinol was larger than that of secoisolariciresinol and matairesinol.

2.2 Coniferous Tree Sources

Considerable amounts of lignans are also found in coniferous trees. The type of lignans differs among species and the amounts vary in different parts of the trees. The typical lignans in the heartwood of spruce (Picea abies) include hydroxymatairesinol, α-conidendrin, conidendrinic acid, matairesinol, isolariciresinol, secoisolariciresinol, liovile, picearesinol, lariciresinol, and pinoresinol.

Large amounts of bioactive phenolic compounds are present in the wood knots of several tree species. The amount of lignans in the knots can be up to several hundred times larger than in the adjacent stemwood. Wood knots of Populus tremula and Abies balsamea growing in Europe are particularly rich in lariciresinol.

Lariciresinol has also been isolated from Araucaria araucana (Mol.) K. Koch wood alongside secoisolariciresinol, pinoresinol, eudesmin, and lariciresinol-4-methyl ether.

2.3 Contribution to Dietary Lignan Intake

A survey of 4,660 Dutch adults (aged 19–97 years) found a median total lignan intake of 979 µg/day. Total lignan intake did not differ significantly between men and women. Lignan intake was strongly skewed toward higher values (range 43–77,584 µg/d; mean 1,241 µg/d). Lariciresinol and pinoresinol together contributed 75% to lignan intake, whereas secoisolariciresinol and matairesinol contributed only 25%.

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.

3. Biosynthesis and Plant Biochemistry

Lariciresinol is produced through the enzymatic reduction of (+)-pinoresinol, catalyzed by the bifunctional, NADPH-dependent (+)-pinoresinol/(+)-lariciresinol reductase, and is a key intermediate in the lignan biosynthetic pathway in Forsythia species.

Entry into lignan enzymology was established by the approximately 3,000-fold purification of two isoforms of (+)-pinoresinol/(+)-lariciresinol reductase, a pivotal branchpoint enzyme in lignan biosynthesis. Both isoforms have comparable (~34.9 kDa) molecular mass and kinetic properties and catalyze sequential, NADPH-dependent, stereospecific hydride transfers where the incoming hydride takes up the pro-R position.

Pinoresinol/lariciresinol reductase catalyzes the first known example of a highly unusual benzylic ether reduction in plants. The enzyme was found in Forsythia intermedia and catalyzes the presumed regulatory branch-points in the pathway leading to benzylaryltetrahydrofuran, dibenzylbutane, dibenzylbutyrolactone, and aryltetrahydronaphthalene lignans.

The amino acid sequence of the reductase reveals a strong homology to isoflavone reductase, a key branchpoint enzyme in isoflavonoid metabolism primarily found in the Fabaceae. This is of evolutionary significance since both lignans and isoflavonoids have comparable plant defense properties, as well as similar roles as phytoestrogens.

From a plant-ecology perspective, lignans are a large, structurally diverse class of vascular plant metabolites having a wide range of physiological functions and pharmacologically important properties. Because of their pronounced antibiotic, antioxidant, and antifeedant properties, a major role of lignans in vascular plants is to help confer resistance against various opportunistic biological pathogens and predators.

4. Traditional and Historical Use

Lariciresinol as an isolated compound is a modern scientific discovery; it was not known or used in isolation in historical medical traditions. However, the plant materials richest in lariciresinol — including sesame seeds, flaxseed, and various conifers — have extensive traditional use across multiple cultures, and the broader class of plant lignans is now understood to have constituted a significant and biologically active component of these traditional preparations.

Secoisolariciresinol and matairesinol were among the first lignan precursors identified in the human diet and are therefore the most extensively studied. Lariciresinol, along with pinoresinol, was only recognized as an important enterolignan precursor more recently. Until recently, only secoisolariciresinol and matairesinol were considered enterolignan precursors, but several new precursors have been identified, of which lariciresinol and pinoresinol have a high degree of conversion. Quantitative data on the contents in foods of these new enterolignan precursors were not previously available.

Sesame (Sesamum indicum), one of the richest food sources of lariciresinol and related lignans, has been used for millennia across Asia, Africa, and the Middle East as a food oil, condiment, and medicinal agent. Flaxseed, similarly a major lignan source, has been used since antiquity in Mediterranean and Near Eastern cultures as food and medicine. These are historical uses of the whole plant material; lariciresinol specifically was not identified in these traditional contexts.

5. Key Constituents, Metabolites, and Mechanisms of Action

5.1 Gut Microbial Conversion to Enterolignans

The biological activity of lariciresinol in mammals is significantly mediated through its transformation by intestinal bacteria. The bioactivity of dietary lignans depends on their transformation by gut bacteria in the colon. Several authors have described the transformation by bacterial communities of plant lignans into enterodiol and enterolactone.

Matairesinol, secoisolariciresinol, lariciresinol, and pinoresinol are converted to mammalian lignans (enterodiol and enterolactone) by gut microbial action. A metabolic scheme describing the conversion of the most abundant new mammalian lignan precursors, pinoresinol and lariciresinol, has been described.

Matairesinol and hydroxymatairesinol (HMR) are directly converted to enterolactone, while pinoresinol, lariciresinol, and secoisolariciresinol are first converted to enterodiol, which then partially converts to enterolactone.

Lariciresinol has been described to increase significantly in subjects analyzed, formed from syringaresinol and pinoresinol following the production of pinoresinol from pinoresinol diglucoside. Demethylation is followed by dehydroxylation to produce enterodiol.

When first discovered, the mammalian lignan metabolites enterodiol and enterolactone were thought to originate from the ovaries, but further study in antibiotic-treated and germ-free rats indicated that intestinal bacteria are required for the production of both enterodiol and enterolactone. This was later confirmed in humans. The mechanism by which gut microbiota enzymes metabolize lignans is now well-established.

5.2 Phytoestrogenic Activity

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.

Intestinal microbiota metabolize plant-derived lignan precursors into enterolignans, enterodiol, and enterolactone. The latter two are classified as phytoestrogens because of their ability to mimic some of the effects of estrogens. Therefore, research on lignans in cancer prevention has primarily focused on hormone-associated cancers, such as breast, endometrial, ovarian, and prostate cancers.

Lignans are known to exert antioxidant and anti-inflammatory activities, together with activity in estrogen receptor-dependent pathways.

5.3 Antioxidant Mechanisms

Lariciresinol itself, independent of its gut-metabolized products, demonstrates direct antioxidant activity. The compound inhibits lipid peroxidation and is additionally a good scavenger of superoxide radicals. Lignans — among them lariciresinol — inhibit lipid peroxidation. The trapping capacity of lariciresinol in one test series was shown to be 7.3 mmol/g, compared to 6.8 mmol/g for the well-known antioxidant Trolox® in the same test series.

At the molecular level, in vitro studies with the (+)-enantiomer have elucidated specific pathways. (+)-Lariciresinol isolated from Rubia philippinensis was examined for antioxidative activity and for its inhibitory effect on the generation of reactive oxygen species (ROS) in murine macrophage (RAW 264.7) cells. It possessed strong radical scavenging activity and reducing power, and inhibited ROS generation in a dose-dependent manner without cytotoxicity. The transcriptional and translational levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were markedly higher in the treated group. Lariciresinol treatment also increased the transcriptional and translational activities of Nrf2 with a corresponding increase in heme oxygenase-1 (HO-1) expression.

5.4 Anti-inflammatory and Anti-menopausal Effects

Lignans are known to exert antioxidant and anti-inflammatory activities, together with activity in estrogen receptor-dependent pathways. They may have therapeutic potential for postmenopausal symptoms, including cardiovascular disease, osteoporosis, and psychological disorders. Moreover, the antitumor efficacy of lignans has been demonstrated in various cancer cell lines, including hormone-dependent breast cancer and prostate cancer, as well as colorectal cancer.

6. Scientific Evidence by Area of Use

6.1 Breast Cancer

Epidemiological Evidence

Several, but not all, epidemiological studies have reported reduced risks of breast cancer associated with either increased intake of dietary lignans and/or higher blood levels of enterolactone. Reductions in risk of breast cancer and invasive cancer were linked primarily to higher intakes of lariciresinol and pinoresinol in premenopausal women, and of lariciresinol and matairesinol in postmenopausal women.

For premenopausal women, there was a borderline significant 50% reduction in odds of having either stage I or II breast cancer, but no association with higher stages. The association was strongest for the lignans lariciresinol and pinoresinol. In postmenopausal women, there was a significant 50% reduction only in stage I cancers, and that was associated with increased intake of matairesinol. Higher total lignan and matairesinol intakes were associated with lower risk of grade 3 tumors, primarily among premenopausal women.

Studies have reported conflicting results. Several prospective cohort studies found no association between lignan intake and breast or other cancers. In contrast, a 2009 meta-analysis limited to postmenopausal women showed a 15% reduction in risk of breast cancer with high lignan intake.

Evidence strength: Epidemiological associations are mixed. Case-control studies show inverse associations for lariciresinol, particularly in premenopausal women, but prospective cohort data are inconsistent. No randomized controlled trials specifically isolating lariciresinol have been conducted in humans. Recent epidemiological studies suggest that high dietary intake of lignans and lariciresinol is associated with reduced breast cancer risk. However, no causal relationship between lariciresinol intake and breast cancer development has been established.

Preclinical (Animal and Cell) Evidence

One study investigated for the first time the effects and possible mechanisms of action of lariciresinol on hormone-responsive mammary cancer in vivo: in dimethylbenz[a]anthracene (DMBA)-induced mammary cancer in rats, lariciresinol (3 or 15 mg/kg of body weight) or vehicle was administered orally daily for 9 weeks. In estradiol-maintained ovariectomized athymic mice bearing orthotopic MCF-7 tumors, a control diet or lariciresinol-containing diet (supplemented with 20 or 100 mg lariciresinol/kg of diet) was administered for 5 weeks. In both models, lariciresinol administration inhibited tumor growth and tumor angiogenesis.

In MCF-7 cells, enterolactone significantly inhibited E2-stimulated VEGF secretion. In MCF-7 xenografts, lariciresinol administration enhanced tumor cell apoptosis and increased estrogen receptor beta expression.

Lariciresinol and its further metabolites secoisolariciresinol, enterodiol, and enterolactone were found in serum of both rats and athymic mice, confirming a similar lignan metabolism pattern as in humans.

A separate in vitro study examined lariciresinol alongside pinoresinol. The study evaluated the effect of podophyllotoxin, pinoresinol, and lariciresinol on cellular toxicity and apoptosis induction in fibroblasts, HEK-293, and SkBr3 (HER2-positive breast cancer) cell lines. Cell lines were treated for 24 and 48 hours with different concentrations of lignans. Cell viability and apoptosis were examined using MTT assay and flow cytometry; expression levels of cell cycle and apoptosis regulator genes were determined using quantitative real-time PCR. Podophyllotoxin significantly increased apoptosis in fibroblast cells compared to pinoresinol and lariciresinol (P<0.001).

Evidence strength for breast cancer: The preclinical evidence — both in rodent tumor models and cell lines — demonstrates biological plausibility for anti-proliferative, pro-apoptotic, and anti-angiogenic activity. However, this evidence is preliminary and cannot be extrapolated to humans without clinical trial data. The epidemiological human data are suggestive but inconsistent and confounded by multiple dietary variables.

6.2 Cardiovascular Disease and Mortality

The Zutphen Elderly Study investigated whether the intakes of four plant lignans — lariciresinol, pinoresinol, secoisolariciresinol, and matairesinol — were inversely associated with coronary heart disease (CHD), cardiovascular disease (CVD), cancer, and all-cause mortality. The study is a prospective cohort study in which 570 men aged 64–84 years were followed for 15 years. Lignan intake was related to mortality using Cox proportional hazards analysis.

The median total lignan intake in 1985 was 977 µg/day. Tea, vegetables, bread, coffee, fruit, and wine were the major sources of lignan. The total lignan intake was not related to mortality. However, the intake of matairesinol was inversely associated with CHD, CVD, and all-cause mortality (P ≤ 0.05 for all) and cancer (P = 0.06). Lariciresinol did not demonstrate a significant independent association in this cohort.

A much larger analysis extended this inquiry. A prospective study followed 214,108 men and women in three 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, including 6,283 non-fatal MI and 3,961 fatal CHD cases.

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 for matairesinol, 0.87 for secoisolariciresinol, 0.89 for pinoresinol, and 0.89 (95% CI: 0.83–0.95) for lariciresinol, with all P values for trend ≤ 0.003.

Comparing participants in the extreme quintiles of consumption, 11% to 24% lower risks of CHD were observed for total and individual lignans. The inverse associations appeared to plateau at intake levels around approximately 300 µg/day for total lignans. Lariciresinol showed a more linear association.

A study examining lignan intake and mortality after a diagnosis of type 2 diabetes found more nuanced results for lariciresinol. Among 8,465 incident type 2 diabetes cases contributing 116,026 person-years of follow-up, 4,372 deaths were documented. The pooled multivariable-adjusted hazard ratios for all-cause mortality were 0.83 for total lignans, 0.89 for matairesinol, 0.78 for secoisolariciresinol, 0.91 for pinoresinol, and 0.92 (95% CI: 0.82–1.03) for lariciresinol. Higher postdiagnosis secoisolariciresinol intake was also significantly associated with lower CVD and cancer mortality. Lariciresinol's hazard ratio crossed the null for all-cause mortality in this diabetic cohort, suggesting its independent contribution may be weaker than that of secoisolariciresinol or matairesinol.

Evidence strength for cardiovascular disease: Large prospective cohort data suggest a significant inverse association between lariciresinol intake and CHD risk, but this evidence is observational. The magnitude of the association for lariciresinol is comparable to that of other individual lignans. Residual confounding from overall diet quality and fiber intake cannot be excluded. No clinical intervention trials specifically testing lariciresinol for cardiovascular endpoints have been identified.

6.3 Antioxidant Activity

The direct antioxidant capacity of lariciresinol has been studied in vitro. Lariciresinol inhibits lipid peroxidation. Its trapping capacity in one test series was 7.3 mmol/g, compared to 6.8 mmol/g for the reference antioxidant Trolox®. Lariciresinol also reveals capacity to scavenge superoxide radicals. These findings indicate comparable or superior in vitro radical-scavenging capability relative to well-established reference antioxidants under these conditions; however, in vitro antioxidant data do not automatically predict human physiological effects.

6.4 Postmenopausal Health

Lignans including lariciresinol are known to exert antioxidant and anti-inflammatory activities, together with activity in estrogen receptor-dependent pathways. They may have therapeutic potential for postmenopausal symptoms, including cardiovascular disease, osteoporosis, and psychological disorders. Dietary intakes of plant lignans have been hypothesized to be inversely associated with the risk of developing cardiovascular disease and cancer. Most of the human evidence for postmenopausal health benefits comes from studies examining total lignan intake or total enterolactone levels, rather than lariciresinol specifically. Evidence directly attributable to lariciresinol alone for postmenopausal symptoms remains limited and indirect.

6.5 Antimicrobial Activity

The antimicrobial activities of lariciresinol and co-isolated lignans have been determined in studies on Araucaria araucana wood; lariciresinol was among five lignans identified in the heartwood of this Chilean species. This evidence comes from bioactivity-guided phytochemical studies and represents preliminary, in vitro data only.

7. Body Systems and Health Areas of Association

Endocrine / Hormonal System: The enterolignans derived from lariciresinol — enterodiol and enterolactone — can mimic some of the effects of estrogens; their plant-derived precursors are accordingly classified as phytoestrogens. This positions lariciresinol within research on hormone-dependent conditions including breast, endometrial, and prostate diseases.
Gastrointestinal / Gut Microbiome: The bioactivity of lariciresinol depends substantially on its transformation by gut bacteria in the colon. Its metabolism thus reflects and influences gut microbiome composition and activity.
Cardiovascular System: Lariciresinol intake was associated with a hazard ratio of 0.89 (95% CI: 0.83–0.95) for CHD in a large pooled prospective cohort analysis.
Oncology (Hormone-Dependent Cancers): The enterolignans are classified as phytoestrogens; research on lignans in cancer prevention has primarily focused on hormone-associated cancers, such as breast, endometrial, ovarian, and prostate cancers.
Oxidative Stress and Inflammation: Lariciresinol possesses strong radical scavenging activity and upregulates cytoprotective enzymes including SOD, GPx, CAT, and HO-1 via Nrf2 activation in cell-based studies.

8. Dosage Forms and Dosages Reported in Studies

Lariciresinol is not currently the subject of standardized dosage recommendations by any regulatory body (e.g., NIH Office of Dietary Supplements, EMA, EFSA) as an isolated supplement. It is ingested as a component of whole foods. The following dosages appear in peer-reviewed research contexts only:

Animal studies (rats, oral): Lariciresinol was administered at 3 or 15 mg/kg of body weight orally daily for 9 weeks in DMBA-induced mammary tumor-bearing rats.
Animal studies (mice, dietary): In E2-maintained ovariectomized athymic mice bearing orthotopic MCF-7 tumors, diets were supplemented with 20 or 100 mg of lariciresinol per kg of diet, administered for 5 weeks.
Human dietary intake (observational): Median total lignan intake in a Dutch adult population sample was 979 µg/day. Lariciresinol and pinoresinol together contributed 75% to this total intake. This dietary exposure is far lower than the pharmacological doses tested in animals.
In vitro cell studies: Varied concentrations were used across cell-line studies (e.g., 24–48 hour treatment in MTT and flow cytometry assays) but specific molar concentrations reported in publications vary widely and are not directly translatable to human dosing.

No human clinical intervention trials using isolated lariciresinol as a defined dosage have been identified in the peer-reviewed literature.

9. Safety Considerations and Interactions

9.1 Reported Adverse Effects

Almost all studies on lignans highlight possible beneficial health effects and no adverse effects of lignans have been reported so far in human studies. However, it must be kept in mind that lignans can interact with highly sensitive hormonal systems.

9.2 Special Populations

Lignans can interact with highly sensitive hormonal systems. Lignan-containing nutritional supplements should be used with great caution, especially in infants and children or during pregnancy and lactation.

9.3 Phytoestrogenic Activity and Hormonal Interactions

Once ingested, lignans including lariciresinol undergo biotransformation by the intestinal microbiota into enterolignans — primarily enterolactone and enterodiol — which closely resemble endogenous estrogens in both structure and biological activity. Due to this similarity, lignans are classified as phytoestrogens and have been the subject of increasing scientific interest. The theoretical implication is that, at sufficient doses, lariciresinol-derived metabolites could interact with estrogen-sensitive tissues and medications that modulate the estrogen axis (e.g., selective estrogen receptor modulators, aromatase inhibitors, hormone replacement therapy). No direct human clinical interaction studies on lariciresinol specifically have been identified.

9.4 Gut Microbiome Dependence

Because the bioactivity of lariciresinol depends on its transformation by gut bacteria in the colon, the use of broad-spectrum antibiotics or conditions that substantially alter gut microbiome composition can be expected to reduce the conversion of lariciresinol to its active enterolignan metabolites. The degree of conversion is known to vary considerably between individuals.

9.5 Enantiomeric Considerations

Lariciresinol exists as two enantiomers ((+) and (−)) that may differ in biological potency. The antioxidant activity of the (+)-lariciresinol enantiomer extracted from Rubia philippinensis increased Nrf2-induced HO-1 expression in RAW264.7 murine macrophage cells. Whether enantiomeric ratio is clinically meaningful in humans has not been established.

9.6 Evidence Gaps

Formal toxicological profiling (including LD50, chronic toxicity, reproductive toxicity, and genotoxicity data) for isolated lariciresinol in humans is absent from the published literature. The absence of reported adverse events in epidemiological studies of lignan-rich diets is encouraging but does not constitute safety data for isolated, concentrated lariciresinol supplementation.

References

Health Conditions

Health conditions that Lariciresinol may help support.

No conditions available.

Body Systems

Body systems that Lariciresinol may help support.

No body systems available.