Metabolomics provides a comprehensive assessment of numerous small molecules in biological samples. As it integrates the effects of exogenous exposures, endogenous metabolism, and genetic variation, metabolomics is well-suited for studies examining metabolic profiles associated with a variety of chronic diseases. In this review, we summarize the studies that have characterized the effects of various pre-analytical factors on both targeted and untargeted metabolomic studies involving human plasma, serum, and urine and were published through 14 January 2019. A standardized protocol was used for extracting data from full-text articles identified by searching PubMed and EMBASE. For plasma and serum samples, metabolomic profiles were affected by fasting status, hemolysis, collection time, processing delays, particularly at room temperature, and repeated freeze/thaw cycles. For urine samples, collection time and fasting, centrifugation conditions, filtration and the use of additives, normalization procedures and multiple freeze/thaw cycles were found to alter metabolomic findings. Consideration of the effects of pre-analytical factors is a particularly important issue for epidemiological studies where samples are often collected in nonclinical settings and various locations and are subjected to time and temperature delays prior being to processed and frozen for storage.

Extensive evidence has demonstrated that many antioxidants such as vitamin C, vitamin E, carotenoids and polyphenols have protective effects in preventing cardiovascular disease (CVD), a chronic disease that is mediated by oxidative stress and inflammation. This review focuses on evidence from prospective cohort studies and clinical trials in regard to the associations between plasma/dietary antioxidants and cardiovascular events. Long-term, large-scale, population-based cohort studies have found that higher levels of serum albumin, bilirubin, glutathione, vitamin E, vitamin C, and carotenoids were associated with a lower risk of CVD. Evidence from the cohort studies in regard to dietary antioxidants also supported the protective effects of dietary vitamin E, vitamin C, carotenoids, and polyphenols on CVD risk. However, results from large randomized controlled trials did not support long-term use of single antioxidant supplements for CVD prevention due to their null or even adverse effects on major cardiovascular events or cancer. Diet quality indexes that consider overall diet quality rather than single nutrients have been drawing increasing attention. Cohort studies and intervention studies that focused on diet patterns such as high total antioxidant capacity have documented protective effects on CVD risk. This review provides a perspective for future studies that investigate antioxidant intake and risk of CVD.