Flaxseed Modulates Estrogen Metabolism in Postmenopausal Women—Comparison with Soy
By Donald Brown, ND
Founder and Director,
Natural Product Research Consultants, Inc.
Advisory Board, American Botanical Council
President’s Advisory Board, Bastyr University, Seattle
Advisor to the Office of Dietary Supplements at the
National Institutes of Health
Dr. Brown is a consultant for Nature’s Way, Inc..
Source: Brooks JD, et al. Supplementation with flaxseed alters estrogen metabolism in postmenopausal women to a greater extent than does supplementation with an equal amount of soy. Am J Clin Nutr 2004;79:318-325.
Abstract: In a randomized, double-blind, placebo-controlled, parallel trial, 46 postmenopausal women were recruited for a study to compare the effects of flaxseed and soy on estrogen metabolism. Volunteers had not taken estrogen replacement therapy in the previous three months or used phytoestrogen supplements in the past one month and were required to have normal thyroid function. Volunteers were assigned randomly to receive flaxseed, soy, or placebo muffins. The flaxseed group consumed muffins containing 25 g ground flaxseed, which provided 50 mg/d of the lignan precursor secoisolariciresinol diglycoside (26.4 mg/d of secoisolariciresinol). The soy group ate 25 g/d soy flour in the form of soy muffins, which provided 41.9 mg/d isoflavones (15.5 mg/d daidzein, 25.7 mg/d genistein, and 0.7 mg/d glycitein). Muffins eaten by volunteers in both treatment groups also contained 20.7 g white flour. The placebo group received muffins made with whole-wheat flour. All muffins were formulated to be isocaloric and spices were used to make them all taste similar. Participants were allowed to continue their regular diet. The study duration was 16 weeks.
Urinary phytoestrogen, 2-hydroxyestrone (2OHE1), and 16a-hydroxyestrone (16aOHE1) concentrations were analyzed. Serum estradiol, estrone, and estrone sulfate were measured as was bone-specific alkaline phosphatase (AP), an indicator of bone turnover. Urinary deoxypyridinoline (DPD), an indicator of bone resorption, also was measured. These outcome measures were determined at baseline and week 16.
Urinary phytoestrogen excretion was significantly increased at 16 weeks compared to baseline in the soy and flaxseed groups (21.84 ± 4.37 and 41.05 ± 8.49 µmol/d, respectively;
P < 0.001), but not in the placebo group. At week 16, although total urinary phytoestrogen excretion in the soy compared to the flaxseed group was not significantly different, the type of phytoestrogens in the urine did differ. Volunteers in the soy group excreted primarily daidzein, genistein, and equol, while those in the flaxseed group excreted primarily enterodiol and
enterolactone.
Urinary 2OHE1 and 16aOHE1 concentrations and the 2OHE1:16aOHE1 ratio did not differ between the placebo group and treatment groups at baseline. After 16 weeks of treatment, the urinary 2OHE1 concentration was significantly increased in the flaxseed group (5.60 ± 0.93 vs. 7.25 ± 1.48 µg/24 hours, respectively; P = 0.05), but not in the soy or placebo groups. No significant differences were seen in the 16aOHE1 concentration in any of the groups at the end of the trial. A significant increase in the 2OHE1:16aOHE1 ratio was observed in the flaxseed group after treatment (P = 0.005); however, absolute values were not reported.
Intra- and inter-group changes in the serum AP and urinary DPD concentrations were not significant at week 16 compared to baseline. A significant inverse correlation was noted between serumAP and total urinary lignan excretion in the flaxseed group (significance level not reported). Serum hormone concentrations did not change significantly in any group from baseline to week 16.
Comments
Flaxseed and soy are rich sources of lignans and isoflavones, respectively. Both are considered phytoestrogens and bear diphenolic ring structures similar to those found in endogenous estrogens.1 Like soy, some studies have found that flaxseed consumption influences endogenous hormone concentrations in postmenopausal women,2,3 while a study in premenopausal women found no change in serum hormones following flaxseed consumption.4 Modulation of estrogen metabolism has the potential to influence tissue estrogen exposure and therefore risk of breast cancer and osteoporosis.
The results of this study suggest that flaxseed modifies estrogen metabolism in postmenopausal women more significantly than soy. Regarding the estrogen metabolites measured in this trial, it should be noted that 2OHE1 has shown little biological activity with some antiestrogenic activity in vitro.5 Conversely, 16aOHE1 has shown estrogen agonist activity and has been shown in vitro to increase cell proliferation of human breast cancer cell lines.6 Therefore, an increase in the 2OHE1: 16aOHE1 ratio theoretically may reduce risk of breast cancer (a finding noted in women consuming Brassica vegetables).7 However, because 16aOHE1 may increase bone mineral density in postmenopausal women, concern theoretically may extend to the implications of significant reductions of this metabolite.
This trial suggests that flaxseed is capable of increasing 2OHE1 without significantly reducing 16aOHE1. This potentially could lead to a reduction in breast cancer risk without a negative effect on bone cell metabolism. While dietary supplement research in postmenopausal women over the past few years has largely featured soy/soy isoflavones and red clover isoflavone supplements, this trial suggests that flaxseed and its lignans may be an equally, if not more interesting, area of focus. Regarding dosage of flaxseed, an earlier trial using 10 g/d for seven weeks found a 34% increase in 2OHE1, as well as a 21% increase in the 2OHE1:16aOHE1 ratio.3 The trial reviewed above found a 103% increase in 2OHE1 and a 98% increase in the 2OHE1:16aOHE1 ratio using 25 g/d.
Finally, it should be noted that flaxseed is a rich source of a-linolenic acid (ALA). Flaxseed oil has been shown to reduce breast tumor growth8 and ALA has been shown to decrease the growth of breast cancer cell lines in vitro.9 Although the focus of this review has been on the flax lignans, ALA also should be considered as a contributor to the overall health effects noted in postmenopausal women consuming flaxseed.
Conclusion
The results of this study point to a need for greater focus on the potential for flaxseed as a supplement to prevent breast cancer in postmenopausal women. Use of 25 g/d led to a greater shift in estrogen metabolism in favor of less biologically active estrogens without negatively impacting bone cell metabolism. These actions, paired with the ability of flaxseed to decrease both total cholesterol and low-density lipoprotein cholesterol in postmenopausal women,10 make it an ideal candidate for future research with this population. Long-term studies with larger numbers of postmenopausal women are needed to confirm the effects of flaxseed on estrogen metabolism and its potential use as an alternative to hormone replacement therapy.
References
1. Kurzer Ms, XU X. Dietary phytoestrogens. Ann Rev Nutr 1997;17:353-381.
2. Hutchins AM, et al. Flaxseed consumption influences endogenous hormone concentrations in postmenopausal women. Nutr Cancer 2001;39:58-65.
3. Haggans C, et al. Effect of flaxseed consumption on urinary estrogen metabolites in postmenopausal women. Nutr Cancer 1999;33:188-195.
4. Frische EJ, et al. Effect of flaxseed and wheat bran on serum hormones and lignan excretion in premenopausal women. J Amer College Nutr 2003;22:550-554.
5. Bradlow HL, et al. 2-Hydroxyestrone: the "good " estrogen. J Endrocrinol 1996;150(suppl):S259-S265.
6. Gupta M, et al. Estrogenic and antiestrogenic activities of 16a- and 2-hydroxy metabolites of 17b-estradiol in MCF-7 and T47D human breast cancer cells. J Steroid Biochem Mol Biol 1998;67:413-419.
7. Fowke J, et al. Brassica vegetable consumption shifts estrogen metabolism in healthy postmenopausal women. Cancer Epidemiol Biomarkers Prev 2000;9:773-779.
8. Thompson L, et al. Flaxseed and its lignan and oil components reduce mammary tumor growth at a late stage of carcinogenesis. Carcinogenesis 1996;17:1373-1376.
9. Chajes V, et al. Influence of the n-3 fatty acids on the growth of human breast cancer cells in vitro: Relationship to peroxides and vitamin E. Breast Cancer Res Treat 1995;34:199-212.
10. Arjmandi BH, et al. Whole flaxseed consumption lowers
Founder and Director, Natural Product Research Consultants, Inc. Advisory Board, American Botanical Council Presidents Advisory Board, Bastyr University, Seattle Advisor to the Office of Dietary Supplements at the National Institutes of Health Dr. Brown is a consultant for Natures Way, Inc.. Source: Brooks JD, et al. Supplementation with flaxseed alters estrogen metabolism in postmenopausal women to a greater extent than does supplementation with an equal amount of soy. Am J Clin Nutr 2004;79:318-325.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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