Does cruciferous vegetables contribute to endometriosis?

Relation

Harris HR, Eke AC, Chavarro JE, Missmer SA. Fruit and vegetable consumption and risk of endometriosis.Sum playback. 2018;33(4):715-727.

Objective

To identify associations between fruit and vegetable consumption and risk of laparoscopically confirmed endometriosis

Draft

Prospective cohort study with data from women who participated in the Nurses' Health Study II from 1991 to 2013

Participant

This study analyzed data from 70,835 premenopausal women aged 25 to 42. All women included in the study had an intact uterus. Exclusion criteria were: total energy intake 4,200 kcal per day; more than 70 foods empty in the questionnaire; diagnosis of endometriosis; history of infertility; History of cancer (other than non-melanoma skin cancer).

Study parameters assessed

Diet was assessed in 1991, 1995, 1999, 2003, 2007 and 2011 using a Food Frequency Questionnaire (FFQ) that listed over 130 foods.

Primary outcome measures

Laparoscopically confirmed endometriosis

Key insights

Analyzed separately from vegetable consumption, total fruit consumption was associated with a lower risk of endometriosis, up to 3 servings per day, after which there was no association with reduced risk (P=0.005). There was no association between total vegetable consumption and endometriosis risk, regardless of the number of servings per day.

When looking at specific fruit groups, citrus fruits have been linked to a lower risk of endometriosis. Consuming 1 serving or more of citrus fruits per day was associated with a 22% risk reduction compared to consuming less than 1 serving per week (P[trend]=0.004). This risk reduction was only observed in women who had laparoscopically confirmed endometriosis but had never reported infertility, and was greatest in ever-smokers. When this association was further narrowed by specific citrus fruits, oranges had the strongest associated risk reduction.

Looking at specific vegetables, 1 or more servings of cruciferous vegetables per day had a 13% higher risk of endometriosis (P[trend]=0.03). More specifically, Brussels sprouts (P=0.02), cauliflower (P=0.03) and raw cabbage (P=0.02) were associated with a higher risk of endometriosis. Lima beans/peas and corn were also associated with a higher risk of endometriosis, and romaine/leaf lettuce was associated with a lower risk.

What is somewhat surprising is the 13% increase in endometriosis with daily consumption of cruciferous vegetables.

Of the individual nutrients evaluated, only the highest quintile of consumption of the carotenoid β-cryptoxanthin was associated with a lower risk of endometriosis (P=0.02).

Adjusting for trans fat and omega-3 fatty acid intake did not affect the results.

Practice implications

A 22-year prospective cohort study of caregiver diet examined dietary associations with endometriosis and revealed some surprising trends. The Nurses' Health Study II (NHSII) was the first prospective cohort study to examine many associations between diet and women's health, including endometriosis.¹Endometriosis affects approximately 10% of women of childbearing age, often in the third and fourth decades of life. A major theory for the spread of endometrial tissue is retrograde menstruation through the fallopian tubes. This theory is challenged by data suggesting that retrograde menstruation is fairly common in menstruating women,²occurs in 76% to 90% and is therefore considered a “universal phenomenon”.³It is very likely that endometriosis is a multifactorial disease involving oxidative stress⁴and inflammation⁵as key players, and diet has a significant influence.

Dietary antioxidants such as vitamins E and C have been shown to reduce endometriosis pain,⁶and other antioxidant nutrients may have similar effects on pain⁷and even the pathogenesis.⁸When Harris and her team evaluated dietary patterns in NHSII, they looked for associations with antioxidants, particularly carotenoids (retinol activity equivalents such as alpha-carotene, beta-carotene, β-cryptoxanthin, lutein/zeaxanthin, and lycopene) and to determine whether these associations were altered by smoking.

Higher total fruit and vegetable consumption was associated with a reduced risk of endometriosis up to about 5 total servings per day, after which there was no risk reduction but rather a reversal in risk reduction. Daily intake of citrus fruits (oranges, grapefruit, orange juice, grapefruit juice) was associated with a 22% lower risk of endometriosis. For women who had smoked in the past, the associated risk reduction was even greater. Citrus fruits contain significant carotenoids, particularly β-cryptoxanthin, which is considered the most abundant carotenoid in human blood. It has been suggested that β-cryptoxanthin is better absorbed from its major dietary sources than other common carotenoids.⁹In preclinical data, β-cryptoxanthin reduced oxidative stress markers¹⁰and reduced inflammatory markers (liver necrosis factor [NF]-κB and tumor necrosis factor [TNF]-α expression).¹¹Such mechanisms could explain how this particular carotenoid was associated with a reduced incidence of endometriosis in the study reviewed here.

What is somewhat surprising is the 13% increase in endometriosis with daily consumption of cruciferous vegetables. While cruciferous vegetables are known for their ability to promote estrogen metabolism due to components such as indole-3-carbinol,¹²This study found that their consumption was correlated with an increased diagnosis of endometriosis. Corn and pea/lima bean intake was also associated with a higher diagnosis rate. All of these foods contain fermentable food components, which have been linked to inflammation in the gastrointestinal (GI) tract. In particular fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs),¹³which can cause gas, bloating and/or gastrointestinal distress, are found in cruciferous vegetables as well as corn and lima beans. Inflammation in the gut correlates with an increased risk of endometriosis, a connection that has been observed for years.¹⁴Irritable bowel syndrome (IBS) and endometriosis are both characterized by chronic, low-grade inflammation and mast cell involvement.¹¹Supplementing with the probiotic strainLactobacillus gasseriIt has been found to increase production of the cytokine interleukin (IL)-12 and significantly reduce menstrual pain and dysmenorrhea in women with endometriosis.³supporting the hypothesis that inflammation originating in the intestine contributes to the pathogenesis of endometriosis.

Another possibility, as suggested by the study authors, is that the nonspecific symptoms of gastrointestinal distress, such as bloating and bloating, associated with FODMAP foods may lead to more gynecologic referrals. The increase in testing may lead to higher rates of endometriosis diagnoses.

Finally, the participants in this study were exclusively nurses, who may have started eating more cruciferous vegetables after their endometriosis diagnosis. The timing of diagnosis in relation to ingestion has not been reported, so it is not possible to know the truth of this hypothesis.

Previous reports have suggested that the time between onset of symptoms and diagnosis of endometriosis may be up to 12 years.^fifteenAlthough recent reports suggest that the time lag has shortened to about 4 to 5 years, adolescents still have a longer time to diagnosis.¹⁶One recommendation suggests that women suspected of having irritable bowel syndrome who have a family history of endometriosis should be screened for the condition.¹⁷We hope to gain more clarity on dietary associations through studies similar to the one discussed here, but the cruciferous vegetable connection is something to keep in mind.

Although cohort studies are considered intermediate in the evidence pyramid,¹⁸they demonstrate associations and can make for intriguing intervention study designs. In the future, an intervention study to determine whether certain foods correlate with repeat endometriosis diagnoses appears to be one way to tease out this counterintuitive trend of cruciferous vegetables with endometriosis diagnoses.