Abstract
Although numerous in vitro studies and animal model data have suggested that flavan-3-ols, the most common subclass of flavonoids in the diet, may exert protective effects against cancer, epidemiologic studies have reported inconclusive results for the association between flavan-3-ols intake and cancer risk. Therefore, we conducted this meta-analysis of epidemiologic studies to investigate the preventive effects of flavan-3-ols on various types of cancers. A total of 43 epidemiologic studies, consisting of 25 case-control and 18 prospective cohort studies, were included. A significant inverse association was shown between flavan-3-ols intake and the risk of overall cancer (relative risk (RR) 0.935, 95%CI: 0.891-0.981). When cancer types were separately analyzed, a statistically significant protective effect of flavan-3-ols consumption was observed in rectal cancer (RR 0.838, 95%CI: 0.733-0.958), oropharyngeal and laryngeal cancer (RR 0.759, 95%CI: 0.581-0.993), breast (RR 0.885, 95%CI: 0.790-0.991) in case-control studies and stomach cancer in women (RR 0.633, 95%CI: 0.468-0.858). Our analysis indicates the potential benefits of flavan-3-ols in cancer prevention.
Highlights
Dietary flavonoids are a diverse range of polyphenols that are ubiquitously found in many commonly consumed vegetables, fruits, food grains, herbal remedies, beverages, and dietary supplements
A total of 43 studies were included in this meta-analysis, and the main reasons for excluding studies from the final review were as follows: 1 study was repeated reporting [21], 2 studies were randomized controlled trials (RCTs) [22, 23], 2 studies had an outcome of cancer mortality [24, 25], 5 studies evaluated urinary flavan-3-ols [26,27,28,29,30], and 2 studies evaluated plasma flavan-3-ols [31, 32]
When the analysis was stratified by study region, the association between flavan-3-ols intake and cancer risk was observed in Europe (RR 0.926, 95%CI: 0.880-0.974; 29 studies, P for heterogeneity = 0.329, I2= 8.894%), but not in Americas (RR 0.961, 95%CI: 0.883-1.046; 13 studies, P for heterogeneity = 0.000, I2= 72.020%) or Asia (RR 0.73, 95%CI: 0.45-1.18; 1 study)
Summary
Dietary flavonoids are a diverse range of polyphenols that are ubiquitously found in many commonly consumed vegetables, fruits, food grains, herbal remedies, beverages, and dietary supplements. An extensive literature indicates that flavan-3-ols exhibit a range of biological activities both in vitro and in vivo by acting as an antioxidant, cardio-preventive, anticarcinogenic, antimicrobial, anti-viral, and neuro-protective agent [3]. When focusing on cancer preventive effects, meta-analyses of observational studies have mainly indicated an association between cancer risk and intake of other flavonoids, such as isoflavones [6, 7]. Numerous in vitro and animal model studies have suggested that flavan-3-ols act as anticarcinogens through antioxidant [8, 9] and detoxifying effects [10], modulation of the cell cycle and apoptosis [11,12,13], stimulation of the immune system [14] and DNA repair [15], and suppression of metastasis [16, 17] and inflammation [17,18,19], data from human population studies are limited and conflicting [20]
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