
By Joel Dahms, MS
Senior Manager, Editorial and Marketing Content
Lignans, the low molecular weight polyphenols found in plants whose name derives from the Latin for “wood,” are known to be beneficial for general health. Large trials have suggested a modest but statistically significant reduction in risk of mortality with higher lignan intake among healthy people,1-3 and some evidence suggests that higher lignan intake reduces risk of incident type 2 diabetes (T2D).4 Now, analysis of two long-running prospective cohort studies has found that lignan intake is linked to reduced risk for all-cause mortality and lower cardiovascular disease (CVD) mortality in individuals diagnosed with T2D, especially in non-white individuals.5
In the study, researchers analyzed data from nearly 8,500 participants with incident T2D in two prospective US cohort studies: the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). They looked at average daily intake of total lignans and of four specific lignans (secoisolariciresinol [SECO], matairesinol [MAT], pinoresinol [PINO], and lariciresinol [LARIC]) calculated from food frequency questionnaires updated every 2-4 years during follow-up.5
After adjusting for a wide range of potential confounding factors, the findings showed that the risk for all-cause mortality was 17% lower in participants in the highest vs the lowest quintile of total lignan intake following a T2D diagnosis (HR=0.83; CI 0.74, 0.94). For individual lignans, they found an 11% lower risk for all-cause mortality associated with higher intake of MAT (HR=0.89; CI 0.80, 0.99) and 22% lower for higher SECO consumption following T2D diagnosis (HR=0.78; CI 0.69, 0.87). Higher SECO intake was also significantly associated with lower CVD (HR=0.78; CI 0.63, 0.96) and cancer mortality (HR=0.72; CI 0.55, 0.95). Increase in lignan intake from before to after a T2D diagnosis also showed favorable associations with all-cause mortality: HR=0.83 (CI 0.75, 0.93) for total lignans, HR=0.86 (CI 0.77, 0.96) for MAT, and HR=0.82 (CI 0.72, 0.90) for SECO. While there was a trend toward reduced mortality risk when PINO and LARIC intake were examined independently, neither was significant.5
In subgroup analyses, non-white individuals showed an even more pronounced effect of lignan consumption on all-cause mortality, with a hazard ratio of the highest quintile vs the lowest of 0.32 (CI, 0.14-0.76); for white individuals it was 0.84 (CI, 0.75-0.95). Some other interesting findings included that for participants without T2D symptoms at diagnosis, the relationship between lignan intake and all-cause mortality appeared stronger, and the association tended to be more pronounced in individuals who were diagnosed with T2D after the age of 65 and in those who maintained a higher score of low-risk lifestyle behaviors. While there was a dose-response relationship between lignan and reduced risk of mortality to a point, the beneficial results plateaued when post-diagnosis total lignan intake reached around 500 ug/d; beyond that, there did not seem to be much further benefit.5
While this study has limitations, including the observational nature of the study using dietary recall, that they only looked at four major subtypes of lignans, the potential for residual confounding, and the fact that the participants were mostly white US healthcare professionals, there are some tantalizing takeaways. While it should come as no surprise that lignan consumption is associated with health, it is interesting that this factor alone may have such a significant impact not only on risk of T2D4 but outcomes for those who are subsequently diagnosed. Only in the past few years has the medical mainstream come to recognize the possibility of remission from T2D,6 something that functional medicine practitioners have long been aware of, and lignan consumption, along with other dietary and lifestyle change, may be an important aspect of that.
While it remains to be seen if some of the subgroup analyses hold up to further scrutiny, several of the findings are at least worth a mention:
- Non-white participants in the study had a much larger reduction in mortality risk from consuming lignans, which suggests a potentially important point of leverage for those with T2D in communities of color. However, since non-white participants only made up around five percent of the sample, the authors themselves mention that this finding will need further study.
- The association between lignan intake and reduced mortality risk tended to be more pronounced in individuals who were diagnosed with T2D after the age of 65. It’s not clear why this might be, but it suggests that patients diagnosed later in life may get more benefit from consuming lignans.
The beneficial results plateaued when post-diagnosis total lignan intake reached around 500 ug/d. If true, this suggests that it would be quite easy for patients (with or without T2D) to consume this amount. Lignans are found in many grains, seeds, legumes, and vegetables, but particularly rich sources include flax and sesame seeds (both especially good sources), as well as cashews, peanuts, broccoli, and Brussels sprouts, and consuming small amounts of any of these daily may provide the full benefit.
There are many potential mechanisms by which lignans may improve health in the body. Lignans are the principal source of dietary phytoestrogens in the Western diet and in the body are turned into the enterolignans enterodiol and enterolactone by gut bacteria, which have weak estrogenic activity but have many other effects. While some studies have found contradictory results, many studies have suggested that lignans improve glucose metabolism,7 potentially by promoting glucose uptake through the GLUT4 transporter8 or by reducing insulin resistance in the liver.9
Of course, any functional medicine prevention or treatment plan is a multimodal approach that encompasses many modalities and does not focus on a single nutrient as an intervention. However, as part of a dietary plan to incorporate beneficial nutrients, increasing intake of lignans may be a consideration, especially for those at risk of or diagnosed with T2D. Indeed, lignan intake is highlighted in IFM’s Phytonutrient Spectrum tool, which encourages eating foods of a variety of colors to improve phytonutrient intake and overall health, as well as in IFM’s Cardio Food Plan, which is designed for those with or at risk for metabolic syndrome/T2D.
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REFERENCES
- Chen Z, Qian F, Hu Y, et al. Dietary phytoestrogens and total and cause-specific mortality: results from 2 prospective cohort studies. Am J Clin Nutr. 2023(1);117:130-140. doi:10.1016/j.ajcnut.2022.10.019
- Tresserra-Rimbau A, Rimm EB, Medina-Remón A, et al. Polyphenol intake and mortality risk: a re-analysis of the PREDIMED trial. BMC Med. 2014;12:77. doi:10.1186/1741-7015-12-77
- Zamora-Ros R, Jiménez C, Cleries R, et al. Dietary flavonoid and lignan intake and mortality in a Spanish cohort. Epidemiology. 2013;24(5):726-733. doi:10.1097/ede.0b013e31829d5902
- Wang S, Hu Y, Liu B, Li Y, Wang M, Sun Q. Lignan intake and type 2 diabetes incidence among US men and women. JAMA Netw Open. 2024;7(8):e2426367. doi:10.1001/jamanetworkopen.2024.26367
- Liu B, Hu Y, Wang S, Wang M, Rimm EB, Sun Q. Lignan intake and mortality among adults with incident type 2 diabetes—prospective cohort studies. Am J Clin Nutr. Published online January 10, 2025. doi:10.1016/j.ajcnut.2025.01.008
- Riddle MC, Cefalu WT, Evans PH, et al. Consensus report: definition and interpretation of remission in type 2 diabetes. Diabetes Care. 2021;44(10):2438-2444. doi:10.2337/dci21-0034
- Laveriano-Santos EP, Luque-Corredera C, Trius-Soler M, et al. Enterolignans: from natural origins to cardiometabolic significance, including chemistry, dietary sources, bioavailability, and activity. Crit Rev Food Sci Nutr. Published online July 1, 2024. doi:10.1080/10408398.2024.2371939
- Zhou F, Furuhashi K, Son MJ, et al. Antidiabetic effect of enterolactone in cultured muscle cells and in type 2 diabetic model db/db mice. Cytotechnology. 2017;69(3):493-502. doi:10.1007/s10616-016-9965-2
- Charytoniuk T, Iłowska N, Berk K, Drygalski K, Chabowski A, Konstantynowicz-Nowicka K. The effect of enterolactone on sphingolipid pathway and hepatic insulin resistance development in HepG2 cells. Life Sci. 2019;217:1-7. doi:10.1016/J.LFS.2018.11.044