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Nutritional Epidemiology

Intake of the Plant Lignans Secoisolariciresinol, Matairesinol, Lariciresinol, and Pinoresinol in Dutch Men and Women¹

Ivon E. J. Milder^*,, Edith J. M. Feskens^*,2, Ilja C. W. Arts, H. Bas Bueno de Mesquita^*, Peter C. H. Hollman and Daan Kromhout^*

^* Centre for Nutrition and Health, National Institute for Public Health and the Environment, 3720 BA Bilthoven, The Netherlands, and RIKILT-Institute of Food Safety, Wageningen University and Research Centre, 6700 AE Wageningen, The Netherlands

²To whom correspondence should be addressed. E-mail: EJM.Feskens{at}rivm.nl.

	ABSTRACT

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
Enterolignans (enterolactone and enterodiol) are phytoestrogens that are formed by the colonic microflora from plant lignans. They may reduce the risk of certain types of cancer and cardiovascular diseases. Initially, only secoisolariciresinol and matairesinol were considered to be enterolignan precursors, but recently, new precursors such as lariciresinol and pinoresinol were identified. We recently developed a lignan database including 4 major enterolignan precursors. We used this database to estimate lignan intake in a representative sample of Dutch men and women participating in the Dutch Food Consumption Survey, carried out in 1997–1998. Median total lignan intake among 4660 adults (19–97 y old) was 979 µg/d. Total lignan intake did not differ between men and women; thus, the lignan density of the diet was significantly higher (P < 0.001) in women than in men. Lignan intake was strongly skewed toward higher values (range 43–77584 µg/d, mean 1241 µg/d). Lariciresinol and pinoresinol contributed 75% to lignan intake, whereas secoisolariciresinol and matairesinol contributed only 25%. The major food sources of lignans were beverages (37%), vegetables (24%), nuts and seeds (14%), bread (9%), and fruits (7%). Lignan intake was significantly (P < 0.001) correlated with intake of dietary fiber (r = 0.46), folate (r = 0.39), and vitamin C (r = 0.44). Older persons, nonsmokers, vegetarians, and persons with a low BMI or a high socioeconomic status had higher lignan intakes than their counterparts. In brief, this study shows that the amount of enterolignan precursors in the diet has previously been largely underestimated.

KEY WORDS: • lignans • diet • phytoestrogens • intake

Lignans are biphenolic compounds present in plant foods. Some plant lignans can be converted by intestinal bacteria into the "enterolignans," enterolactone and enterodiol (1,2). Enterolignans are present in human plasma and urine and were reported to possess biological activities, such as (anti-) estrogenic and antioxidant action; therefore, they may reduce the risk of certain types of cancer as well as cardiovascular diseases (3–6).

It has long been assumed that only secoisolariciresinol and matairesinol were converted into enterolignans. Secoisolariciresinol and matairesinol are present in seeds, grains, vegetables and fruits, tea, coffee, and wine (7). Flaxseed contains by far the highest lignan concentration (of secoisolariciresinol) of any food for which data have been published. More recently, other enterolignan precursors, i.e., lariciresinol, pinoresinol, arctigenin, 7-hydroxymatairesinol, syringaresinol, and medioresinol were discovered (8). In an in vitro experiment, lariciresinol and pinoresinol had a conversion degree of 100 and 55%, respectively, which is similar to, or even higher than the conversion degree of secoisolariciresinol and matairesinol. The conversion degree of the other new precursors was much lower (15%).

Observational studies [reviewed in (6)] used plasma or urinary enterolignans or lignan intake to estimate exposure, and both methods gave conflicting results. In case-control studies (9–11), inverse associations between plasma or urinary lignans and breast cancer risk were observed, but in prospective studies, this was not confirmed (12–14). For cardiovascular diseases, inverse associations with serum lignans were reported in 2 Finnish studies (15,16). Studies regarding lignan intake and disease have considered only secoisolariciresinol and matairesinol. Protective associations were reported for breast (17,18), ovarian (19), endometrial (20), and thyroid cancers (21). In one study, a protective effect for breast cancer was found only for high intakes of matairesinol, but not for secoisolariciresinol or the sum of secoisolariciresinol and matairesinol (22). In a case-control study in a multiethnic population in the United States, no association was found between intakes of secoisolariciresinol and matairesinol and breast cancer risk (23), whereas in one cohort study, a high intake of secoisolariciresinol was associated with increased breast cancer risk (24). However, this association was no longer statistically significant after adjustment for alcohol intake (24).

To further evaluate the potentially protective effects of plant lignan intake, it is essential to include the newly discovered lignan precursors, lariciresinol and pinoresinol. Thus, we recently developed a method to determine secoisolariciresinol, matairesinol, lariciresinol, and pinoresinol in foods (25), and a food composition database with data on these major enterolignan precursors (26). We used this database to estimate the intake of these lignans in a large, representative population sample in the Netherlands. In addition, we identified the main food sources of lignans, and dietary and lifestyle factors associated with lignan intake.

	SUBJECTS AND METHODS

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
    Food Consumption Survey. As previously described in detail (27), the National Food Consumption Survey 1997–1998 was carried out among a sample of households representative of the Dutch population (28). A household was defined as one or more persons living together in one house, eating together a home-prepared hot meal on at least 4 d/wk. Institutionalized persons, persons who did not speak Dutch sufficiently well to complete the interview, and children < 1 y old were excluded. A total of 6250 persons (2885 men and 3365 women) aged 1–97 y, from 2564 different households participated in the study. The response rate was 68.5%. In the present study, we used only data of adults (19 y, n = 4661). Food consumption data were collected by trained dietitians using a 2-d dietary record. The record days were equally distributed over the 7 d of the week and over the year (holidays excluded). Intakes of nutrients were calculated using the 1996 release of the Dutch Food Composition Database (29). Intake of folate was calculated using the 2001 release (30) because data on folate had increased since the earlier release. Other variables included age, height, weight, socioeconomic status (based on occupation and attained educational level), and lifestyle variables such as smoking and consumption of a vegetarian diet.

    Lignan contents. The lignan database used comprises lignan contents of a comprehensive set of Dutch plant foods containing data on 83 solid foods, such as oilseeds, nuts, grain products, fruits, vegetables, and legumes, and 26 alcoholic and nonalcoholic beverages (26). Plant foods were selected for inclusion in the database using data from the Food Consumption Survey. In general, plant foods with a mean consumption of >3 g/(person · d) were selected. For fruits, a limit of 1 g/(person · d) was used, and for beverages this was 10 g/(person · d). Lariciresinol, pinoresinol, secoisolariciresinol, and matairesinol were quantified using a LC-tandem MS method (25). Lignans were measured in composite samples that consisted of products purchased at 3 locations: an outlet of a nation-wide supermarket chain, a local grocery, and an open-air street market (fresh products), or of 3 brands (prepackaged products).

    Lignan intake calculations. For each person, lignan intake was calculated by multiplying the consumption of each food by its lignan content. Food data were coded into 1167 entries of the Dutch Food Composition Table (29). For 13% of the foods, lignan contents were derived from chemical analyses of the food concerned or calculated on the basis of the dry-weight content, 18% was calculated from recipes, and 16% was derived from a similar food (e.g., for port wine, lignan contents of red wine were assigned). For the recipe calculations, we used standard recipes (29,31). When standard recipes were not available, they were derived from food labels. For 35% of the foods, we assumed that there were no lignans present (mainly animal products). For the remaining 18% of the foods, a lignan content of 0 was assigned. These were mainly products used by <1% of the population because all plant foods with a relatively high consumption level were selected for analysis (26).

    Statistical analysis. Statistical analyses were performed using the SAS statistical package (SAS, release 8.02, SAS Institute). Differences were considered significant at P < 0.05. Children (<19 y, n = 1539) and pregnant women (n = 50) were excluded from the analyses. One person was excluded from the analyses because he received enteral feeding only. Thus, the study population consisted of 4660 persons: 2116 men and 2544 women.

Mean and median lignan intake (µg/d), lignan density [µg/(MJ · d)], and the contribution of each individual lignan to the mean total lignan intake were calculated. Because previous studies considered only intake of secoisolariciresinol and matairesinol, we evaluated the agreement between quartiles of intake of the 4 lignans and quartiles of intake of secoisolariciresinol plus matairesinol using the percentage agreement (%) and weighted statistic (32). The contribution of individual foods and food groups to the mean lignan intake was calculated, and the percentage of users of each food or food group was determined. Mean lignan intakes for men and women, adjusted for age, and intakes in age categories adjusted for gender, were compared using analysis of covariance after log transformation of the individual lignan intakes. Similarly, mean lignan intakes stratified by other selected lifestyle characteristics were adjusted for age and gender. Spearman’s partial rank-order correlation coefficients were calculated between total lignan intake, intake of selected nutrients, and intake of each of the individual lignans, after adjusting for total energy intake.

	RESULTS

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
Lignan intake ranged from 43 to 77584 µg/d, and was strongly skewed toward higher values (Fig. 1). The median lignan intake in this population was 979 µg/d (mean 1241 µg/d, SD 2052 µg/d), on the 2 d surveyed (Table 1). In each person, all 4 lignans contributed to lignan intake, except for matairesinol, for which intake was 0 in 27 persons (0.6% of the population). On a population level, lariciresinol contributed 43% to the lignan intake, pinoresinol 32%, secoisolariciresinol 24%, and matairesinol only 1%. Intake of each of the individual lignans was correlated (P < 0.001) with total lignan intake. After adjustment for total energy intake, Spearman correlation coefficients were 0.52 for secoisolariciresinol, 0.64 for matairesinol, 0.95 for lariciresinol, and 0.90 for pinoresinol. When we compared classification of subjects in quartiles based on the intake of the 4 lignans, and quartiles based on intake of secoisolariciresinol and matairesinol, 42.3% of the subjects were classified into the same quartile, for 40.1% the classification differed by 1 quartile, and for 17.6% of the subjects classification differed by 2 or 3 quartiles. The weighted was 0.38.

View larger version (17K): [in this window] [in a new window]   FIGURE 1 Distribution of total lignan intake among 4660 adults in the Dutch Food Consumption Survey 1997–1998.

	DISCUSSION

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

Although several studies reported intakes of secoisolariciresinol and matairesinol, it is difficult to compare these results across populations. In addition to actual differences in the lignan content of the diet, differences may also result from differences in reporting of intake data, composition of the population, and especially from the lignan food composition data used. Our estimate of the mean daily intake of secoisolariciresinol plus matairesinol (303 µg/d) is higher than that previously reported by Horn-Ross and co-workers for women in the United States (175 µg/d) (33) and (108 µg/d) (24), but lower than that reported by De Kleijn and co-workers (645 µg/d) (34) for another population of women in the United States. Our result is similar to the reported intake for men and women in Finland (434 µg/d) (35). Keinan-Boker et al. (36) reported considerably higher (1110 µg/d) intakes of secoisolariciresinol plus matairesinol for Dutch middle-aged and elderly women than those found in this study. This may be explained in part by the difference in study population because we found that intake increased with age. However, the difference in lignan composition data is probably more important. For the calculation of lignan intake, Keinan-Boker and co-workers used the same method as De Kleijn (34), in which 7 category scores, instead of exact lignan contents, were used for the calculation of lignan intake. These scores were based on the highest reported value found in the literature. For some products, the content of secoisolariciresinol and matairesinol was derived from the amount of enterolignans produced after in vitro fermentation. This leads to an overestimation of the amount of secoisolariciresinol and matairesinol if the product also contains other enterolignan precursors. For the present study, all foods were analyzed in one laboratory. We collected data on all important lignan sources in the Netherlands, and values for all foods were obtained with the same validated method (25).

An important consideration in interpreting the results from our study is that the dietary survey was not designed to investigate lignan consumption. As a result, consumption of seeds was not queried in detail. For example, no distinction was made between whole-grain wheat bread and multigrain bread. However, retail data (37) show that in 1998, 8% of purchased breads were multigrain. Multigrain bread differs in composition between different manufacturers or brands, and almost all multigrain breads contain flaxseed and various other seeds. Thus, in general, the lignan content of multigrain bread is much higher than that of whole-grain wheat bread. To evaluate the potential underestimation of lignan intake caused by the lack of data on multigrain bread, we assumed that 8% of the bread reported as whole-grain wheat bread was actually multigrain bread. The lignan content of multigrain bread was previously determined in a composite sample of 6 commonly consumed multigrain breads (26). Using these assumptions, median total lignan intake increased from 979 to 1132 µg/d, 16% higher than in our previous estimation (Table 1). However, because the composition of multigrain breads is highly variable, we chose not to include the lignan intake from multigrain bread in our estimation (Table 1). Because the share of multigrain bread has been increasing since 1998 (up to 12% in 2001, the last year for which data were available) (37), an important recommendation for future research is to evaluate the intake of seeds from bread in more detail.

Another limitation of the present study is that effects of food processing were only partially taken into account. In general, the lignan contents of foods as they were usually consumed were available from chemical analysis. For example, fresh fruits were analyzed because they were usually consumed. Values for dried or canned foods were derived from values of fresh fruits, allowing for differences in dry weight. Most vegetables were analyzed only in the raw form, although in 1998, the mean consumption of boiled vegetables was higher than that of raw vegetables. This choice was made because many vegetables are also consumed raw, and other preparation methods such as stir-frying and simmering are also common. Because we previously found that the lignan content of some boiled vegetables was decreased (25% on average) (26), this may have caused overestimation of the lignan intake from vegetables.

In this study, beverages, vegetables, seeds, bread, and fruits were the major sources of dietary lignans. These lignan sources were similar to those found in previous studies in the Netherlands, Finland, Germany, and the United States (22,33,34,36,38), even though previous studies examined intake only of secoisolariciresinol and matairesinol. However, the relative importance of sources varied among the populations studied. The contribution of vegetables, especially Brassica vegetables to lignan intake in our study, was higher than that in previous studies. This can be explained by the relatively high amount of lariciresinol and pinoresinol in these vegetables. Previously reported contributions of coffee and tea to lignan intake varied greatly from 0.2% (34) to 44% (33), both for postmenopausal women in the United States. Such large variations between similar populations probably do not reflect real differences in consumption, but are a result of differences in lignan data used in these studies. In previous studies, lignan data for brewed coffee and tea were not available; thus lignan contents were extrapolated from coffee powder and tea leaves, using different assumptions. In our study, we used the lignan content of brewed coffee and tea, prepared according to Dutch habits, which greatly improved the reliability of the intake calculations.

As reported earlier (14), intake of lignans was correlated with intake of dietary fiber (Spearman r = 0.46). Strong correlations were also reported for intake of dietary fiber with enterolignan concentrations in blood or urine (14,39,40). Dietary fiber was proposed as a proxy for lignan intake (14). Although we also found a strong correlation between lignan intake and dietary fiber, the fact that fiber-poor beverages were the most important sources of lignans does not support the use of dietary fiber as a proxy for lignan intake.

In conclusion, this study showed that including lariciresinol and pinoresinol greatly improves the estimation of the intake of dietary enterolignan precursors. In this population, intake of lariciresinol plus pinoresinol was 2-fold higher than that of secoisolariciresinol plus matairesinol. In addition, intake of lariciresinol and pinoresinol had a higher correlation with total lignan intake than secoisolariciresinol and matairesinol. Thus, including pinoresinol and lariciresinol will reduce exposure misclassification to enterolignans in epidemiologic studies, and may give more insight into the association between lignan intake and chronic diseases. Lignan intake was positively correlated with the intake of dietary fiber, folate, and vitamin C, and with determinants of healthy lifestyle, such as nonsmoking, use of vegetarian diet, high socioeconomic class, and low BMI; thus, these factors must be considered in epidemiologic studies assessing the health effects of lignan intake.

	FOOTNOTES

 
¹ Supported by the Netherlands Organisation for Health Research and Development (Program Nutrition: Health, Safety and Sustainability, grant 014-12-014).

Manuscript received 15 December 2004. Initial review completed 29 January 2005. Revision accepted 22 February 2005.

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TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 

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