Lessons learned from cancer prevention studies with nutrients and non‐nutritive dietary constituents

Abstract

Epidemiological studies have observed the association between dietary patterns and the risk of certain types of cancer. Extensive studies have been conducted on the cancer preventive activities of constituents from food and beverages. While laboratory research has shown impressive and promising results, such promising cancer preventive activities have not been demonstrated in many human intervention trials. This article analyzes the major differences between these different types of studies and the limitations of these studies. Animal and cell line studies usually use optimal conditions in order to demonstrate the hypothesized effects, sometimes without considering the human relevance. On the other hand, some clinical trials were designed without a good understanding of the biochemical and pharmacological properties of the agents used. Lessons learned from these studies will be illustrated using vitamin E, β-carotene and selenium as examples for nutrients, and green tea polyphenols as an example for non-nutritive dietary constituents. From the lessons learned, we believe that more interdisciplinary collaboration and integration of laboratory and human studies would effectively advance the field of cancer prevention.

Gut/Oral Bacteria Variability May Explain the High Efficacy of Green Tea in Rodent Tumor Inhibition and Its Absence in Humans

“…Published reviews detail the many rodent studies documenting the ability of GT extract or GT polyphenol consumption to prevent digestive tract tumors [ 6 , 7 ]. Studies of the oral cavity and the esophagus include usage of hamster, rat, and mouse models to show that GT extract or purified polyphenols in drinking water can inhibit the induction of tumors by various carcinogens at both sites [ 8 , 9 , 10 , 11 , 12 , 13 ]. Additional studies show efficacy of GT in preventing cancer of the colon and liver, and non-digestive tract sites such as prostate and lung, and that this inhibition can occur whether the GT or GT polyphenols are present during or after carcinogen exposure [ 2 , 14 , 15 ].…”

“…Plasma and cellular levels of intact catechins are often quite low due to poor uptake by gut epithelium, compared to concentrations used in in vitro studies, as commented on by Yang and Wang [ 4 ]. The major tea catechins including EGCG, as predicted by Lipinski’s rule of five, due to large size, presence of hydrated shells, and their polarity, are poorly absorbed by cells [ 4 , 13 , 35 , 36 , 37 ]. In the case of oral epithelium, which is exposed to undiluted GT in tea drinkers, concentrations of catechins are high, hundreds of micrograms per mL, but exposure is transient, so absorption of the unaltered molecules into cells is suboptimal.…”

Green Tea and Its Extracts in Cancer Prevention and Treatment

“…For all of the above groups, examples are known for both carcinogenic and preventive effects, like carcinogenic (e.g., red meat, [29]) or anticarcinogenic food (tea extracts, [30]); carcinogenic (e.g., vitamin A and ß carotene, [31]) or preventive food supplements (e.g., herbal preparations, [32]), or chemopreventive chemicals (e.g., NSAIDS and colon cancer, [33]); the number of proven or putative carcinogens among chemicals is very high.…”

Alpha-Tocopherol prevents esophageal squamous cell carcinoma by modulating PPARγ-Akt signaling pathway at the early stage of carcinogenesis

“…Furthermore, some recent studies suggested that vitamin E and analog promoted lung cancer progression [ 14 ] and melanoma metastasis in mice [ 15 ]. The interpretation of these results may vary and the cancer preventive activities of tocopherols are still unclear [ 5 , 16 ].…”