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Effect of Flaxseed and Wheat Bran on Serum Hormones and Lignan Excretion in Premenopausal Women

Department of Food Science and Nutrition, University of Minnesota, St. Paul (E.J.F., A.M.H., M.C.M., J.L.S.), Minnesota
Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis (W.T.), Minnesota

Address correspondence to: Joanne L. Slavin, Ph.D., Department of Food Science and Nutrition, 1334 Eckles Av., University of Minnesota, St. Paul, MN 55108. E-mail: jslavin{at}umn.edu

	ABSTRACT

TOP FOOTNOTES ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS CONCLUSIONS ACKNOWLEDGMENTS REFERENCES

 
Objective: To examine the effects of flaxseed consumption (a lignan-rich plant food) alone and in combination with wheat bran on serum hormones and urinary lignan excretion in premenopausal women.

Methods: Sixteen subjects were studied for four feeding treatments lasting two menstrual cycles each in a randomized, crossover design. During each treatment, subjects consumed their habitual diets supplemented with baked goods containing no flaxseed or wheat bran, 10 g of flaxseed, 28 g of wheat bran, or 10 g of flaxseed plus 28 g of wheat bran/day. Serum samples collected during the mid-luteal phase of the second menstrual cycle of each diet treatment were analyzed for serum hormones and sex hormone binding globulin. Urine samples collected during the same time period were analyzed for urinary lignan excretion.

Results: There were no changes in serum hormone concentrations or sex hormone binding globulin on any of the treatments. Urinary lignan excretion significantly increased on diet treatments that included flaxseed, but inclusion of wheat bran did not significantly alter lignan excretion.

Conclusions: Urinary lignan excretion increased with flaxseed consumption, but serum hormones did not change in this group of premenopausal women. Consumption of wheat bran with flaxseed did not alter urinary lignan excretion associated with flaxseed consumption.

Key words: flaxseed, wheat bran, lignans, hormones, human

	INTRODUCTION

TOP FOOTNOTES ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS CONCLUSIONS ACKNOWLEDGMENTS REFERENCES

 
Breast cancer risk is linked to hormonal factors and diet. Lignans are diphenolic compounds that are similar in structure to endogenous sex steroid hormones and are hypothesized to act in vivo to alter hormone metabolism and subsequent cancer risk [1]. Flaxseed is the richest known dietary source of lignans. The primary plant lignans, secoisolariciresinol and matairesinol, are metabolized by the human intestinal microflora into the biologically active mammalian lignans enterodiol and enterolactone, respectively [2]. Enterodiol can also be oxidized by the intestinal microflora to form enterolactone [3]. Dietary factors, such as dietary fiber, may change intestinal microflora and thus impact on lignan metabolism. Additionally, since phytoestrogens have been proposed as dietary biomarkers, food components that alter their levels are of interest [4].

Consumption of dietary fiber has been proposed to be chemoprotective because of its influence on endogenous sex hormone concentrations [5]. In premenopausal women, dietary fiber reduces serum estrone and 17ß-estradiol concentrations [6] and is negatively correlated with urinary estrogen excretion [7]. These effects may result from partial interruption of the enterohepatic circulation of estrogen. Wheat bran, a concentrated source of insoluble dietary fiber, reduced serum estrone and 17ß-estradiol concentrations in premenopausal women [8]. Wheat bran can also influence the bioavailability of isoflavones, phytoestrogens found in soybeans [9].

The purpose of this study was to investigate the effects of flaxseed consumption alone and in combination with wheat bran on serum sex hormone and binding protein concentrations and urinary lignan excretion in premenopausal women. We have previously reported that this dietary intervention altered urinary estrogen excretion in pattern protective against breast cancer [10].

	MATERIALS AND METHODS

TOP FOOTNOTES ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS CONCLUSIONS ACKNOWLEDGMENTS REFERENCES

 
Subjects
Extensive details about this study have been previously published [10]. Sixteen women, ages 20 to 38 years of age (mean 26 ± 5 years) participated in the study. The study design, approved by the Institutional Review Board: Human Subjects Committee at the University of Minnesota, was a randomized, cross-over trial consisting of four feeding treatments, each treatment beginning on day one (menses) of the menstrual cycle and lasting two menstrual cycles each. There were no washout cycles between the treatments and subjects were free-living throughout the duration of the study. Subjects consumed their habitual diets plus a supplement of two baked goods (cookies or muffins), which provided the following per day: Control, no flaxseed or wheat bran; flaxseed, 10 g flaxseed and no wheat bran; wheat bran, 28 g wheat bran and no flaxseed; and wheat bran/flaxseed, 10 g flaxseed plus 28 g wheat bran.

Fourteen of the sixteen subjects completed all four dietary treatments. One subject completed only the control, flaxseed and wheat bran/flaxseed diets and another completed only the flaxseed, wheat bran, and wheat bran/flaxseed diets due to personal schedule conflicts. Data for the feeding treatments these two subjects completed are included in the statistical analyses. Diet analyses were performed with the Minnesota Nutrition Data System (NDS) software, developed by the Nutrition Coordinating Center, University of Minnesota (Minneapolis, MN; Food Database Version 6A, Nutrient Database 21, 1992).

Sample Collection and Analysis
During the eight-month study period, subjects recorded basal body temperature daily and performed LH surge testing to detect ovulation using a commercial kit (OvuQuick One-Step, Quidel Corp., San Diego, CA). Ovulation was defined as one day after a LH surge and was verified by luteal serum progesterone concentrations.

Biological sample collection was performed during the second menstrual cycle of each diet treatment. During the mid-luteal phase (days 6, 7, and 8 after estimated ovulation), subjects completed three consecutive 24-hour urine collections and two consecutive days of fasted blood draws. Subjects also recorded all food and drink consumed during the collection periods using three-day self-reported food records.

Commercially available radioimmunoassay kits were used to determine serum concentrations of 17ß-estradiol (E2), dehydroepiandrosterone sulfate (DHEAS) (Pantex, Santa Monica, CA), estrone (E1), progesterone (P) (ICN Biomedicals, Inc., Irvine, CA) and serum sex hormone-binding globulin (SHBG) (Diagnostic Systems Labs, Inc., Webster, TX). Intra- and interassay coefficients of variation were 7.5% and 11.1% for E2, 6.1% and 6.8% for DHEAS, 5.6% and 6.0% for E1, 4.01% and 2.67% for P, and 2.7% and 1.5% for SHBG, respectively. Three controls were run for each assay, with an overall mean (± SEM) coefficient of variation of 7.4 ± 0.5%. The results given are based on duplicate assays.

Urine samples were analyzed for lignan (enterodiol, enterolactone and matairesinol) content by isotope dilution gas chromatography-mass spectrometry according to the method developed by Adlercreutz et al. [11].

Statistical Analysis
Statistical analyses were performed using the Statistical Analysis System (SAS Proprietary Software Release 8.0, SAS Institute Inc., Cary, NC). Results were analyzed using a repeated measure analysis of variance (ANOVA) within subject. Analyses were conducted to determine differences between diet treatments as well as the main effects from flaxseed and wheat bran, the two factors in the two-by-two factorial design. Effects of diet (flaxseed vs. wheat bran vs. wheat bran/flaxseed) and order of diets on serum hormone concentrations and urinary lignan excretion were evaluated. Six subjects did not ovulate every cycle throughout the study. Analyses were conducted both excluding and including anovulatory cycles. Since the inclusion of the anovulatory cycles did not change the results, the data is presented with these cycles included.

	RESULTS

TOP FOOTNOTES ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS CONCLUSIONS ACKNOWLEDGMENTS REFERENCES

 
Serum hormone concentrations on each of the four diet treatments are presented in Table 1. There were no statistically significant changes in serum hormone concentrations during any of the diet treatments.

	DISCUSSION

Our results support the hypothesis that consumption of flaxseed increases urinary lignan excretion, but wheat bran feeding at 28 gm per day does not alter lignan excretion in premenopausal women. Consequently, the results of this study suggest that any chemoprotective affects associated with flaxseed and/or wheat bran are not the result of a change in serum hormone concentrations in premenopausal women but are the result of some other biological mechanism.

Previous studies using premenopausal women have examined the urinary and fecal lignan excretion after consumption of 10 g of flaxseed powder [15, 16]. In 19 premenopausal women, flaxseed feeding at 10 g/day for three menstrual cycles significantly increased urinary [15] and fecal [16] lignan excretion. The lignan excretion varied greatly among subjects (3- to 285-fold increase), and excretion was not altered by phase of the menstrual cycle or by duration of flaxseed consumption. Another report using the same subjects stated that 10 g flaxseed per day increased the length of the luteal phase of the menstrual cycle [17], suggesting that lignans or another component of flaxseed have hormonal effects in premenopausal women.

It is currently not clear how lignans and dietary fiber may influence breast cancer risk. Tew et al. [9] reported that a wheat fiber-supplemented diet containing 40 g dietary fiber reduced dietary absorption of the phytoestrogen genistein from tofu and textured vegetable protein in premenopausal women. Other investigators have shown that water insoluble dietary fiber binds steroid hormones in vitro [18]. Based on these findings, we anticipated that wheat bran might interfere with lignan absorption from flaxseed, which in turn would decrease any lignan-induced physiological effect. However, our results do not support this hypothesis. Lampe et al. [19] also found no effect of wheat bran consumption on urinary excretion of the isoflavan equol in premenopausal women.

	CONCLUSIONS

TOP FOOTNOTES ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS CONCLUSIONS ACKNOWLEDGMENTS REFERENCES

 
Both phytoestrogens and dietary fiber have been shown to have cancer protective effects, but dietary fiber may change phytoestrogen metabolism in the large intestine, potentially changing their biological effects. Since diets high in phytoestrogens tend to be high in dietary fiber, it is difficult to distinguish between these components when investigating effects of these substances on cancer risk. Therefore, we attempted to analyze the effects of these components separately by feeding flaxseed as a source of lignans, alone and in combination with wheat bran as a source of dietary fiber. Our findings that flaxseed significantly increases urinary excretion of lignans without changing the serum hormone concentrations in this group of premenopausal women suggests that the chemoprotective effects reported for flaxseed may result from a mechanism other than a hormonal effect. In addition, our finding that wheat bran had no effect on either urinary lignan excretion or serum hormone concentrations suggests that wheat bran does not interfere with the metabolism of the lignans. Further research is needed to evaluate the interactions of flaxseed components with other dietary variables and to understand the biological mechanisms causing the chemoprotective effects of flaxseed.

	ACKNOWLEDGMENTS

TOP FOOTNOTES ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS CONCLUSIONS ACKNOWLEDGMENTS REFERENCES

 
This study was supported by Grant 96-35200-3208 from the United States Department of Agriculture and Grant M01-RR00400 from the National Center for Research Resources, National Institutes of Health.

	FOOTNOTES

TOP FOOTNOTES ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS CONCLUSIONS ACKNOWLEDGMENTS REFERENCES

 
Dr. Hutchins is now at the Department of Nutrition, Arizona State University East, Mesa, Arizona 85212.

Dr. Martini is now with Kraft Foods, Glenview, Illinois 60025.

Received October 10, 2002. Accepted May 22, 2003.

	REFERENCES

TOP FOOTNOTES ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS CONCLUSIONS ACKNOWLEDGMENTS REFERENCES

 

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