Dietary supplements, dietary patterns, and prostate cancer prevention

Abstract

Dietary supplements are widely used among men in the US. The effect of vitamin and mineral supplements on the risk of non-communicable diseases in ‘generally healthy’ populations is controversial. Current guidelines conclude present evidence is insufficient to use supplements to prevent chronic diseases. Multivitamins are the most widely used dietary supplements among older men in the US. While large RCT and several observational studies suggest null associations between multivitamin use and overall prostate cancer risk, some evidence suggest regular or long-term multivitamin use was associated with increased risk of advanced prostate cancer, characterized by disease progression and poorer survival. Supplemental zinc use is also common among US adults. Normal prostate tissue contains one of the highest concentrations of zinc in the body, and mechanistic evidence indicates it is important for prostate health. While typical doses of individual zinc supplements were around the recommend dietary allowance of zinc, some supplements have even higher doses, exceeding the recommend amount ten-fold and far exceeds the upper intake limits. It has been hypothesized that zinc might only be beneficial for prostate health within a certain range. In populations insufficient zinc intake, low zinc might increase prostate cancer risk or mortality, while in populations with sufficient zinc intake from food, additional excessive supplemental zinc may do harm. Prostate cancer is also highly heritable. A combined genetic risk score of common variants have gain significant interest in recent years. Among men at high genetic risk, evidence has suggested that maintain a healthy weight, being physically active and not smoking was associated with significant lower risk of aggressive prostate cancer. How dietary patterns may influence prostate cancer risk among these men is currently unknown. Therefore, utilizing data from a large prospective cohort, the Health Professionals Follow-up Study (HPFS), we conducted the following three studies. In Chapter 1, we investigated the association between multivitamin use frequency and duration in relation to subtype specific prostate cancer. We found no evidence to suggest regular or long-duration multivitamin use was associated with risk of overall or aggressive prostate cancer in a well-nourished adult male population. In Chapter 2, we examined the association between zinc supplement use in relation to clinically relevant prostate cancer in terms of dosage and duration. We found that excessively high-dose and long-duration supplemental zinc intake was associated with increased risk of lethal and aggressive prostate cancer. Given the strong association between excessive supplemental zinc use and increased risk of clinically important prostate cancer, caution is warranted regarding usage of excessive zinc supplement among adult males. In Chapter 3, we evaluated whether men at a high genetic risk for prostate cancer, defined by a high polygenic risk score, can lower their risk of either overall or lethal prostate cancer by adhering to a healthy diet. Our analysis demonstrates that high genetic risk of prostate cancer might be attenuated by adopting a healthy diet. Among men with high genetic risk, adhering to a diabetes-risk reducing diet or a low hyperinsulinemia diet was associated with significant lower risk of metastatic disease and prostate cancer death. Together with maintaining a healthy weight and being physically active, encouraging lifestyle modifications to reduce the risk of developing insulin resistance and hyperinsulinemia may be a potential primary prevention strategy of aggressive prostate cancer among men with high genetic predisposition for prostate cancer.