Increased Urinary Lignan Excretion Associated with Decreased Risk of Uterine Fibroids
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: Atkinson C, et al. Lignan and isoflavone excretion in relation to uterine fibroids: A case-control study of young to middle-aged women in the United States. Am J Clin Nutr 2006;84:587-593.
Abstract: In a population-based case-control study, women were evaluated to determine if there was a relationship between uterine fibroid risk and phytoestrogen exposure. Female participants were drawn from a larger case-control study of risk factors for uterine fibroids.1 Final analysis was based on 173 uterine fibroid cases (mean age 45.8 ± 6.3 years) and 173 controls (mean age 44.4 ± 6.7 years). Cases were slightly older, were more likely to be African American and to have a family history of uterine fibroids, had a higher BMI, and were less likely to consume soy foods than controls. The cases and controls did not differ significantly by current smoker status, levels of education and income, number of live births, and prior use of oral contraceptives. In addition to a larger structured questionnaire used as part of the main case-control study, women were asked to complete two dietary questionnaires. These corresponded to the days of their overnight urine collections described below.
Two overnight urine collections (48 hours apart) were analyzed for isoflavonoids (daidzein, genistein, equol, and O-desmethyl-angolensin) and lignans (enterodiol and enterolactone). Urinary creatinine (Cr) concentrations were measured as well. Urinary phytoestrogen data were expressed per mg Cr, which is a commonly used method of adjusting phytoestrogen concentration for variability of urinary output. Logistic regression was used to determine associations between the mean excretion of the two collections and the risk of uterine fibroids. In the evening on which each overnight urine collection began, participants were asked to complete a self-administered, structured questionnaire regarding their diet earlier in the day of the collection.
The mean adjusted excretion of isoflavones (sum of daidzein, genistein, equol, and O-desmethylangolensin) did not differ significantly between cases and controls: 2.33 ± 5.82 (range: 0.11-50.80) compared with 2.60 ± 5.90 (0.16-43.53) nmol/mg Cr, respectively (P = 0.68). Cases had significantly less (P < 0.01) mean lignan excretion (sum of enterodiol and enterolactone) than did controls: 2.86 ± 3.45 (0.03-20.54) compared with 4.57 ± 6.67 (0.06-60.29) nmol/mg Cr, respectively. In logistic regression analyses of continuous data, total urinary isoflavone excretion was not associated with risk of uterine fibroids. Total urinary lignan excretion and excretion of the individual metabolites were associated with a significantly lower risk of uterine fibroids. The trend for a reduced risk of uterine fibroids with increasing quartiles of lignan excretion was significant (P < 0.01), but in adjusted analyses (adjusted for age, BMI, race, family history of uterine fibroids) this trend was still evident but no longer significant. Such trends were noted for enterolactone but not enterodiol.
Comments
Completed at the Fred Hutchinson Cancer Research Center and University of Washington in Seattle, this interesting study adds another potential health benefit for dietary lignans: prevention of uterine fibroids. Although larger and more focused trials will be needed to confirm these results, there appears to be a growing shift away from primary focus on isoflavones in the diet to lignans. This has especially been the case with regard to prevention of breast cancer (particularly premenopausal) with particular focus on the mammalian lignan enterolactone.2 It should be noted that soy intake was low in the study population; future trials may determine a possible protective link with soy isoflavones and uterine fibroid risk.
Although focus has been on flax and ground flaxseed as a primary source of dietary lignans, it's important to note the primary lignan in flax, secoisolariciresinol, is first converted to enterodiol by gut microflora and then converted to enterolactone. We are learning that there are dietary and supplemental lignans that direct precursors of enterolactone. One study found that sesame seeds rival flax as a precursor to mammalian lignans and more efficiently raise levels of enterolactone.3 The primary dietary lignan in sesame seed is matairesinol. A new Finnish study that has been submitted for publication has found that the dominant lignan in wheat triticale, barley, corn, amaranth, and quinoa bran is 7-hydroxymatairesinol (7-HMR).4 Both matairesinol and HMR are direct precursors of enterolactone. So, while manufacturers of flax and flax extracts have pushed women to increase flax in their diet or supplement with flax extracts, health care practitioners should be aware that population studies showing potential health benefits of enterolactone are probably linked to dietary sources such as the grains mentioned above and sesame seeds as opposed to flax.
Conclusion: Interest in the health benefits of lignans for women continues to grow. Previous studies have found reduced risk of breast cancer (particularly premenopausal) as well as preliminary data suggesting cardiovascular health benefits and some effects on menopausal symptoms such as hot flashes. Although preliminary in nature, this new trial suggests that dietary lignan sources that effectively raise enterolactone levels may be associated with decreased risk of uterine fibroids.
References
1. Atkinson C, et al. Overnight urinary isoflavone excretion in a population of women living in the United States, and its relationship to isoflavone intake. Cancer Epidemiol Biomarker Prev 2002;11:253-260.
2. Piller R, et al. Plasma enterolactone and genistein and the risk of premenopausal breast cancer. Eur J Cancer Prev 2006;15:225-232.
3. Coulman KD, et al. Whole sesame seed is as rich a source of mammalian lignan precursors as whole flaxseed. Nutr Cancer 2005;52:156-165.
4. Smeds AI, et al. Identification of 7-hydroxymatairesinol and several other previously unidentified lignans in cereals, oilseeds, and nuts—the role of extraction method. Process Chemistry Centre, Laboratory of Organic Chemistry, Åbo Akademi University, Biskopsgatan 8, FI-20500, Åbo/Turku, Finland. Unpublished manuscript, submitted for publication September, 2006.
Brown D. Increased urinary lignan excretion association with decreased risk of uterine fibroids. Altern Ther Women's Health 2007;9(1):7-8.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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