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Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki and * Institute for Preventive Medicine, Nutrition and Cancer, Folkhälsan Research Center, Helsinki and Division of Clinical Chemistry, University of Helsinki
2To whom correspondence should be addressed. E-mail: annamari.kilkkinen{at}ktl.fi.
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ABSTRACT |
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 TOP ABSTRACT SUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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KEY WORDS: • biological marker • cross-sectional studies • diet • lignans
Lignans (a form of phytoestrogens) are naturally occurring diphenolic plant compounds. Recently, some of these compounds have been reported to possess a broad spectrum of biological properties, giving them the potential to reduce the risk of breast, prostate and colon cancers as well as cardiovascular diseases (1–3). Some epidemiologic studies also suggest that lignans may protect against these diseases (4–8).
Lignans are widely distributed in plants (9,10). Flaxseed is the richest known dietary source of lignans; other seeds, nuts, whole grains, berries, fruits and vegetables contain lesser amounts. After consumption, plant lignans are enzymatically converted by the gut microflora, resulting in the formation of mammalian lignans (11,12). The most abundant mammalian lignan is enterolactone (EL).
To understand the effect of lignans on human health, it is essential to quantify their dietary intake as well as trace their main sources in the diet. The purpose of the present study was to assess the intake of dietary lignans using the recently developed phytoestrogen database and to identify the sources of lignans in the Finnish adult population. We also evaluated whether serum EL concentration may serve as a biomarker of lignan intake.
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SUBJECTS AND METHODS |
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TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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The study population consisted of Finnish men and women (aged 25–64 y) participating in a cross-sectional dietary survey carried out in 1997. The study methods and design were described in detail previously (13–15). Briefly, an independent random sample (n = 10,000), stratified by 10-y age groups, regions and gender, was drawn from the National Population Register. For the dietary survey, a subsample of 4000 subjects (40%) was randomly allocated; of these, 2862 participated in the dietary survey. Background information was collected through a self-administered questionnaire and dietary intake was assessed using a 24-h recall. To estimate validity and repeatability of the 24-h recall, a 48-h dietary recall and a 3-d food record were collected from a randomly chosen subpopulation of the same study (n = 223 and n = 334, respectively). Lignan intake, i.e., matairesinol (MAT) and secoisolariciresinol (SECO) and their sum, was quantified according to the recently developed phytoestrogen database (16). Ten subjects with extremely high lignan intake (>17 mg/d) were excluded from the analyses.
Serum was stored at -20°C and an unthawed aliquot was used for analyses of EL concentration by time-resolved fluoroimmunoassay [n = 2753; (17,18)]. On the basis of our previous observation that use of antimicrobials during the preceding 12 mo decreased serum EL concentration (14), the association of lignan intake to serum EL concentration was analyzed separately in nonusers (n = 926 for men and n = 858 for women) and users (n = 373 for men and n = 587 for women) of antimicrobials. Data on the use of antimicrobials were derived from the nationwide prescription register of the Social Insurance Institution. The survey was approved by the Ethics Committee of the National Public Health Institute.
Statistical methods.
The mean intake of both plant lignans (MAT and SECO) and their sum with SEM (µg/d) was calculated, and lignan density of diet with SEM (µg/MJ) was estimated. Differences in lignan density of diet using the categories gender, age, BMI, education and smoking were tested by a mixed model for measurement error. In addition to the 24-h dietary data, the model used auxiliary information from a 48-h dietary recall and a 3-d food record data. The attenuated regression coefficient (variance of the 24-h recall data divided by variance of the 3-d record data) was 1.18. Because dietary lignan intakes were not normally distributed, log-transformed values were used in the models. Further, intakes of MAT and SECO from different foods were estimated.
The Spearman’s correlation coefficient between serum EL concentration and both lignan intake and consumption of lignan-containing foods was calculated. ANOVA was used to examine the association of lignan intake with serum EL concentration; the subjects were divided into quintiles according to the their lignan intake and lignan density of the diet and mean EL concentration with 95% confidence interval in each quintile was calculated. Similar analyses of users of antimicrobials were done using tertiles.
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RESULTS |
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TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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The distribution of lignan (sum of MAT and SECO) intake was very skewed to the right; 34% of the subjects had intakes < 100 µg/d, and intake exceeded 0.5 mg/d in 50 (1.8%) subjects only. In men, the mean daily lignan intake was 173 ± 3 µg (19 ± 0.4 µg/MJ), with a range of 0–1044 µg (244 µg/MJ). The corresponding values for women were 151 ± 3 µg (23 ± 0.4 µg/MJ) and 0–874 µg (155 µg/MJ). Thus, total lignan intake was higher in men than in women (P < 0.0001), whereas women had a higher lignan density in their diet than men (P < 0.0001).
SECO made up most of the lignan intake, i.e., >70% (126 ± 3 µg/d, 14 ± 0.4 µg/MJ) in men and 
80% (121 ± 3 µg/d, 18 ± 0.4 µg/MJ) in women. MAT intake accounted for only 27% (46 ± 1 µg/d, 4.9 ± 0.1 µg/MJ) of lignan intake in men and 20% (30 ± 0.6 µg/d, 4.4 ± 0.1 µg/MJ) in women. Crude MAT and SECO intakes (P < 0.0001 and P = 0.007, respectively) as well as MAT density (P = 0.01) were higher in men than in women, whereas women had a higher SECO density in the diet (P < 0.0001).
Lignan density in the diet was higher in older than in younger subjects, among nonsmokers than smokers and among well-educated than among less educated subjects (Table 1). No consistent differences were observed between BMI categories.
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DISCUSSION |
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TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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The distribution of lignan intake was very skewed toward the higher values. The variation was limited (1 mg) and was due primarily to the range in SECO intake (0–923 µg) rather than the variation in MAT intake (0–361 µg). The mean daily intake of lignans was surprisingly low, <0.2 mg. This is far below a dose level suggested to have beneficial effects (19,20). However, to date, no appropriate daily intake of lignans has been suggested for the prevention of Western diseases, nor have the effects of low daily intakes been reported.
The traditional Finnish diet is believed to be richer in lignans than typical Western diets due to the relatively high intake of whole-grain products, particularly rye bread, and berries. However, intakes of lignans in Finland seem, in general, to be comparable to those in the United States (21–24). There were no differences in the intake of MAT (21–24). However, the mean intakes of SECO and total lignans of Finnish women were somewhat higher than intakes observed in middle-aged American women at an earlier time (22), although lower than recently published estimations (24). Correspondingly, intakes of SECO and total lignans in Finnish men were lower than the median intakes found among the male controls in a case-control study of prostate cancer in the United States (21). However, caution must be taken when comparing these reports because of differences in the way food consumption data were collected and phytoestrogen databases were developed.
Consistent with some earlier observations (22–24) of very low MAT intakes, <50 µg/d, we found notably lower MAT intake compared with SECO intake. MAT intake was higher in men than in women. This difference can be explained by men’s high consumption of cereals, especially rye, which contains substantial amounts of MAT (0.5 µg/g). Correspondingly, the higher lignan density in women compared with men is due to the fact that women consumed more lignan-containing foods in proportion to energy intake than men. The differences in lignan intake discovered between smoking and educational categories as well as age groups were very similar to those we previously found studying serum EL concentrations (15).
Sources of lignans seem to be different in Finland than in the United States (22,24). Orange juice was found to be the major source of intake of MAT in American subjects (22); in Finland, cereals, especially rye, seem to be the primary source, whereas fruit and berries (including orange juice) accounted for only 3% of MAT intake. In Finland, rye is generally eaten as whole grain and is the most consumed whole grain. Coffee was the most substantial contributor to SECO intake in the United States. By contrast, fruit and berries were the primary source of SECO in Finnish subjects, although cereals as well as vegetables also contributed substantially to the intake. Furthermore, in our population, vegetables, cereals, fruit and berries together contributed 94% to the lignan intake, whereas in American subjects, these food items accounted only for 52% of lignan intake (24).
Serum EL concentrations were greater in individuals with higher intake of lignan, compared with those with low intake. However, the variability in serum EL concentrations was quite high in each intake quintile. This may be due to the fact that the production of EL relies on colon microflora (11,12); thus, intraindividual differences in the composition and activity of microflora can affect utilization of dietary lignans and contribute to serum EL concentration. Another reason that weakens the association between lignan intake and serum EL concentration may have been the dietary method (24-h recall) we used. However, on the basis of our validation data, the correlation between serum EL and lignan intake was estimated to be attenuated only by 9%.
The strength of our study is that most of food analyses included in our database were performed in Finland using typical Finnish foods. However, our phytoestrogen database is not complete. Several new abundant EL precursors, not included in our database, have recently been discovered (25). It is unclear, however, whether their inclusion will improve association between dietary lignans and serum EL or simply increase dietary estimates similarly in all subjects. The latter possibility is supported by our finding that consumption of lignan-containing foods is similarly correlated with serum EL. Another strength of our study was the availability of data on recent use of antimicrobials. In subjects who had used antimicrobials during the preceding 12 mo, serum EL increased only slightly with increasing lignan intake compared with nonusers in whom a 50% increase was observed. Thus, in studies involving serum EL concentration, data on recent use of antimicrobials is essential.
This study shows that lignans, especially SECO, are common components of the Finnish diet. However, the mean daily lignan intake, <0.2 mg, is far below the dose level believed to have beneficial effects. The main dietary sources of lignans, i.e., whole grain, vegetables and fruits, are foods commonly associated with lower risk of cardiovascular diseases and cancer (26–28). Further, serum EL concentration is a feasible biomarker of lignan intake.
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FOOTNOTES |
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3 Abbreviations used: EL, enterolactone; MAT, matairesinol; SECO, secoisolariciresinol.
Manuscript received 29 November 2002. Initial review completed 5 January 2003. Revision accepted 10 March 2003.
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LITERATURE CITED |
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TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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coefficient for quintiles of lignan density between 24-h recall and 3-d record data was 0.12.