Discussion
The findings of this population-based study provide new evidence regarding the relationship between subtypes of phytoestrogens and asthma/wheeze, lung function and all-cause mortality in US adults. There was a significant association between enterolactone and a decreased risk of asthma, while enterodiol and enterolactone were both associated with a decreased risk of wheezing. In addition, our results suggested that urinary equol, enterodiol and enterolactone were associated with improved FVC and FEV1 values in all included individuals and those without asthma/wheeze. However, phytoestrogens were not associated with FVC, FEV1 or FEV1/FVC in individuals with asthma/wheeze. This study did not find an association between urinary phytoestrogens and all-cause mortality.
There were some phytoestrogen subtypes associated with asthma/wheeze in this study, which was consistent with the results of the previous abstract published.18 In addition, the present study added new evidence that urinary equol, enterodiol and enterolactone were associated with improved FVC and FEV1 values in the US population. Of note, this study found that enterligans (eg, enterodiol and enterolactone) exerted a greater protective effect on asthma/wheeze and lung function than isoflavones, although the reason remained unclear.
Since lung function (FVC, FEV1 and FEV1/FVC) was significantly lower in patients with asthma than in individuals without asthma, we explored the relationship between phytoestrogens and lung function in individuals with and without asthma. Consequently, several subtypes of phytoestrogens (equol, enterodiol and enterolactone) were observed to play a role in lung function improvement in individuals without asthma/wheeze, but not in individuals with current asthma/wheeze. A study conducted in Japan suggested the significant positive association between dietary intake of total isoflavone, genistein and daidzein and lung function in individuals with and without chronic obstructive pulmonary disease.25 However, another randomised controlled trial suggested the soy isoflavone supplement did not result in improved lung function in patients with asthma when compared with placebo.20 Although there are numerous cofactors that cannot be ignored such as sample size, ethnic difference, dosage of phytoestrogens and subclasses of phytoestrogens, the results in this study, combined with the above evidence, might indicate that some subtypes of phytoestrogens would be protective factors for lung function decline in individuals without asthma/wheeze, but not able to be a suitable treatment for lung function improvement in current asthma or wheeze.
According to stratified analyses in this study, associations between phytoestrogens and lung function differed by gender. To be specific, positive associations were observed between o-desmethylangolensin, enterolactone and FVC and FEV1 values in women, but not in men. Interestingly, the effects of phytoestrogens on lung carcinoma showed the same gender trend.26 27 It has already been established that soybean consumption increases plasma oestradiol only in women.28 However, it remains to be clarified why there is a significant association between some subtypes of phytoestrogens and lower risk of wheeze or improved lung function only in men, but not in women. Generally, the sex-specific analyses performed in this study were in agreement with the theory suggesting that phytoestrogens may be influenced by sex hormones. The study further demonstrated that sex may play an interactive role in phytoestrogen intake and human health. More research should be conducted to explore the dose-dependent effect of phytoestrogens on different genders.
The stratified analyses according to smoking showed enterolactone was also associated with higher FVC, FEV1 and FEV1/FVC values only in smokers. To our knowledge, smoking stimulates lung resident immune cells and proinflammatory mediator release, leading to enhanced neutrophil recruitment in the airways,29 which relates to lung function decline.30 Therefore, enterolactone was more effective at reducing inflammation in smokers. Interestingly, we found that the subtypes of isoflavones (eg, genistein, daidzein, equol, o-desmethylangolensin) were associated with higher risk of asthma in non-smokers. Phytoestrogen exposure in the first 6 months of life is discouraged in children with atopy or cow’s milk allergy to prevent sensitisation.31 In agreement with some evidence, soy protein products, which contain abundant phytoestrogens, may induce allergy as one of the allergens.32 It is possible that the sensitising effect may prevail over the anti-inflammatory effect in non-smokers. In order to fully understand this issue, further research is required.
We have identified the following strengths in our study. First, this study adds new evidence regarding the relationship between subtypes of phytoestrogens and lung function in individuals with and without asthma/wheeze. Second, stratified analyses evaluated the role of gender and smoking in the relationship between phytoestrogens and the outcomes. Third, the urinary phytoestrogens were standardised and precise, and the urinary content of conjugated metabolites may reflect the actual absorption of phytoestrogens.9 Fourth, the analyses had been adjusted for potential confounding factors in different models, in order to ensure that the results were reliable.
This study also has several limitations. First, the causal relationship could not be accessed due to the cross-sectional design of this study. Second, NHANES database did not contain all types of urinary phytoestrogen content, so the dietary intake of total phytoestrogens for included participants could not be calculated. Third, the diagnosis of asthma and wheeze was self-reported; therefore, the possibility of reporting bias cannot be ruled out. Fourth, there is no detailed information in NHANES database on the association between phytoestrogens and respiratory-related or asthma-related mortality.
Conclusions
In this population-based study, we add new findings regarding the correlation between phytoestrogens and asthma/wheeze, lung function and all-cause mortality among US adults. It was found that enterolactone was associated with a significant reduction in asthma risk, while enterodiol and enterolactone were both associated with a decrease in wheezing risk. We further observed that urinary equol, enterodiol and enterolactone were associated with improved FVC and FEV1 in individuals without asthma/wheeze. Furthermore, the associations between phytoestrogens and the outcome measures were inconsistent when stratified by gender and smoking. There was no association between urinary phytoestrogens and all-cause mortality in this study. Further research is required in order to confirm these results and explain the results of the subgroup analyses.