Importance: Lignans are phytoestrogens abundant in Western diets and may be associated with
type 2 diabetes (T2D) risk. Objective: To prospectively investigate associations between lignan
intake and T2D incidence. Design, Setting, and Participants: Population-based cohort study of
US men and women enrolled in the Nurses’ Health Study (NHS, 1984-2018), NHSII (1991-
2019), and Health Professionals Follow-Up Study (HPFS, 1986-2020), as well as 496
participants from the Men’s Lifestyle Validation Study (MLVS). Participants were free of T2D,
cardiovascular disease, and cancer at baseline. Data were analyzed from November 2022 to
July 2023. Exposures: Total and individual lignans were assessed using a validated food
frequency questionnaire, which was updated every 2 to 4 years. In the MLVS, lignan intake was
measured using 2 sets of 7-day diet records (7DDRs). Main Outcomes and Measures: Incident
T2D cases were confirmed using American Diabetes Association diagnostic criteria. Cox
proportional hazards models were used to assess multivariable-adjusted associations. Results:
The current study included 201 111 participants (mean [SD] age, 44.7 [10.1] years; 161 169
female participants [80.2%]; 2614 African American participants [1.3%], 1609 Asian participants
[0.8%], 2414 Hispanic and other race or ethnicity participants [1.2%], and 194 474 White
participants [96.7%]) from the HPFS, NHS, and NHSII studies. The median (IQR) total lignan
intake of the highest quintile ranged from 355.1 (330.2-396.9) μg/d in NHS to 459.9 (422.2-
519.5) μg/d in HPFS at the median follow-up time. Over 5 068 689 person-years, 20 291 incident
cases of T2D were identified. Higher lignan intake was inversely associated with T2D incidence,
except for lariciresinol. The multivariable-adjusted pooled hazard ratios (HRs) for the highest vs
lowest quintiles were 0.87 (95% CI, 0.83-0.91) for total lignans, 0.72 (95% CI, 0.69-0.76) for
secoisolariciresinol, 0.92 (95% CI, 0.87-0.96) for pinoresinol, 0.93 (95% CI, 0.89-0.98) for
matairesinol, and 0.99 (95% CI, 0.94-1.04) for lariciresinol. Secoisolariciresinol intake exhibited
a significant inverse association with T2D risk among individuals with obesity (HR, 0.75 for body
mass index [BMI] ≥30; 95% CI, 0.71-0.79 vs HR, 0.82 for BMI <25; 95% CI, 0.81-0.83; P < .001
for interaction) and premenopausal women (HR, 0.67 for premenopausal women; 95% CI, 0.65-
0.69 vs HR, 0.82 for the past use of hormones; 95% CI, 0.76-0.88; P = .003 for interaction).
Dietary lignan assessed with 7DDRs was associated with lower HbA 1c levels (percentage
change range from −0.92% to 1.50%), as well as lower C-reactive protein levels and better lipid
profiles. Conclusions and Relevance: This cohort study found that long-term lignan consumption
was associated with a lower T2D risk, particularly among individuals with obesity and
premenopausal women.
JAMA Netw Open., 2024, 2024 Aug 1;7(8):e2426367. doi:10.1001/jamanetworkopen.2024.26367