Fruit and Vegetable Consumption and Risk of Endometriosis

H. R. Harris; A. C. Eke; J. E. Chavarro; S. A. Missmer

Disclosures

Hum Reprod. 2018;33(4):715-727. 

In This Article

Abstract and Introduction

Abstract

Study Question Is there an association between intake of fruits and vegetables and risk of laparoscopically confirmed endometriosis?

Summary Answer Higher intake of fruits, particularly citrus fruits, is associated with a lower risk of endometriosis.

What is Known Already Two case–control studies have examined the associations between fruit and vegetable intake and endometriosis risk with contrasting results. Diets rich in fruits and vegetables include higher levels of pro-vitamin A nutrients (alpha-carotene, beta-carotene, beta-cryptoxanthin) and women with endometriosis have been reported to have lower intake of vitamin A than women without endometriosis.

Study Design Size, Duration A prospective cohort study using data collected from 70 835 premenopausal women from 1991 to 2013 as part of the Nurses' Health Study II cohort.

Participants/Materials, Setting, Methods Diet was assessed with a validated food frequency questionnaire (FFQ) every 4 years. Cases were restricted to laparoscopically confirmed endometriosis. Cox proportional hazards models were used to calculate rate ratios (RR) and 95% CI.

Main Results and the Role of Chance During 840 012 person-years of follow-up, 2609 incident cases of laparoscopically confirmed endometriosis were reported (incidence rate = 311 per 100 000 person-years). We observed a non-linear inverse association between higher fruit consumption and risk of laparoscopically confirmed endometriosis (P significance of the curve = 0.005). This inverse association was particularly evident for citrus fruits. Women consuming ≥1 servings of citrus fruits/day had a 22% lower endometriosis risk (95% CI = 0.69–0.89; P trend = 0.004) compared to those consuming <1 serving/week. No association was observed between total vegetable intake and endometriosis risk. However, women consuming ≥1 servings/day cruciferous vegetables had a 13% higher risk of endometriosis (95% CI = 0.95–1.34; P trend = 0.03) compared to those consuming <1 serving/week. Of the nutrients examined, only beta-cryptoxanthin intake was significantly associated with lower endometriosis risk (RR fifth quintile = 0.88; 95% CI = 0.78–1.00; P trend = 0.02).

Limitations Reasons for Caution Some error in the self-reporting of dietary intake is expected, however, use of a validated FFQ and examining diet prospectively across multiple time points, make it unlikely that this non-differential misclassification strongly influenced the results.

Wider Implications of the Findings Our findings suggest that a higher intake of fruits, particularly citrus fruits, is associated with a lower risk of endometriosis, and beta-cryptoxanthin in these foods may partially explain this association. In contrast to what we hypothesized, consumption of some vegetables increased endometriosis risk which may indicate a role of gastrointestinal symptoms in both the presentation and exacerbation of endometriosis-related pain; however, it is not clear what components of these foods might underlie the observed associations. Future studies examining dietary patterns that consider different combinations of food intake may help clarify these associations.

Study Funding/Competing Interest(s) This work was supported by research grants HD4854, HD52473 and HD57210 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and grant P30 DK046200 from the National Institute of Diabetes and Digestive and Kidney Diseases. The Nurses' Health Study II is supported by the Public Health Service grant UM1 CA176726 from the National Cancer Institute, National Institutes of Health. HRH is supported by the National Cancer Institute, National Institutes of Health (K22 CA193860). No competing interests.

Introduction

Endometriosis is a hormone-dependent disorder characterized by the presence of endometrial-like tissue in extra-uterine sites, often resulting in a chronic, inflammatory reaction. It affects ~10% of reproductive age women (Missmer and Cramer, 2003) and current evidence indicates that genetic, environmental, immunological and inflammatory factors all play roles in its pathogenesis (Treloar et al., 1999; Lebovic et al., 2001; Nothnick, 2001; Missmer et al., 2004; Eisenberg et al., 2012; Rahmioglu et al., 2014). Dietary factors may have a role in the etiology of endometriosis through, e.g. influences on steroid hormones, inflammation or food contaminants.

To our knowledge, only two studies have examined the associations between fruit and vegetable intake and endometriosis risk with contrasting results. An Italian hospital-based case–control study reported that those with laparoscopically confirmed endometriosis had a significantly lower intake of both fresh fruit and green vegetables (Parazzini et al., 2004), while a population-based case–control study in Washington state, USA found no association with vegetable consumption but greater fruit intake among women with endometriosis (Trabert et al., 2010). Diets rich in fruits and vegetables include higher levels of pro-vitamin A nutrients (alpha-carotene, beta-carotene, beta-cryptoxanthin) and women with endometriosis have been reported to have a lower intake of vitamin A than women without endometriosis (Mier-Cabrera et al., 2009). In-vitro studies also suggest that vitamin A may influence endometriosis (Casey et al., 1994; Sawatsri et al., 2000; Tee et al., 2006). For example, in human endometrial cells retinoic acid has been shown to suppress interleukin-6 (IL-6) mRNA expression levels (Sawatsri et al., 2000) and elevated levels of IL-6 have been observed in the peritoneal fluid of women with endometriosis (Harada et al., 1997; Punnonen et al., 1996)

In this study, we used data from the US prospective Nurses' Health Study II to investigate whether intake of fruits, vegetables, nutrients concentrated in these foods (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, zeaxanthin and lycopene), or retinol activity equivalents were associated with incident laparoscopically confirmed endometriosis over a 22-year follow-up period. We also examined whether the associations between these factors and endometriosis varied according to the fertility status of the participants and whether the associations were modified by cigarette smoking.

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