Capsaicin and cancer: Guilty as charged or innocent until proven guilty?

With an estimated 2 billion chili pepper connoisseurs worldwide, the human exposure to capsaicin is enormous. Therefore, the question whether nutritional capsaicin is a cancer causing or cancer preventive agent is of utmost importance. The gamut of human epidemiology studies suggests that capsaicin in modest, "restaurant-like" doses is not only safe to eat, but it may even provide health benefits, such as lower cancer-related death rate. Very "hot" food is, however, probably better avoided. Importantly, no increased cancer risk was reported in patients following topical (skin or intravesical) capsaicin therapy. Aberrant capsaicin receptor TRPV1 expression was noted in various cancers with potential implications for cancer therapy, diagnosis and prognostication. Indeed, capsaicin can kill cancer cells by a combination of on- and off-target mechanisms, though it remains unclear if this can be exploited for therapeutic purposes. The literature on capsaicin and cancer is vast and controversial. This review aims to find answers to questions that are relevant for our daily life and medical practice.