The discrepancy has several possible ACET explanations, including differences in study design and type of vitamin intake, differences in vitamin dosage used, differences in the assessment of vitamins intake and potential biases in each study. The lack of a statistically significant outcome in the clinical trials may have been caused by any of several methodological limitations of trials, such as short follow-up period and high levels of vitamins used. Several meta-analyses of RCTs have also analyzed the effect of vitamins on the prevention of gastrointestinal cancer. Wu revealed that vitamin A intake was inversely associated with GC risk by a meta-analysis, while other researchers came to a opposite conclusion. They found that antioxidant vitamins supplements cannot prevent GC, and may even increase overall mortality. However, there were many limitations in these meta-analyses. Firstly, the RCTs included in previous meta-analyses had higher doses than those usually found in individuals who ate a balanced diet, and some trials used dosages well above the recommended UL. The doses used in this study are more reasonable. Secondly, in prior articles, many retrospective case-control studies on this topic were excluded, despite which showed strongly that vitamins intake can prevent GC. In fact, most RCTs included in previous meta-analyses were not designed primarily to investigate the relationship between vitamins consumption and GC. This led to a lack of adjustment for the main confounders of GC. Moreover, most of these RCTs were performed in high-risk individuals, such as longtime smokers, and subjects with a history of premalignant 2,3-DCPE hydrochloride lesions, which may not reflect the vitamin intake of normal risk population. Thus, the total number of subjects of previous meta-analyses was not very substantial and their conclusions should be treated with caution. This paper includes discussion of many well designed observational studies. These were conducted in normal risk populations, and are closely related to the topic. Indeed, it should not be assumed that RCTs always provide high-quality evidence for therapy. High-quality observational studies are also important sources of powerful evidence in meta-analyses.. Some studies have reported other non-antioxidant vitamins�� that affect GC prevention, others have focused on antioxidant vitamins. However, in daily diet, it is difficult to draw distinctions between non-antioxidant vitamins and antioxidant ones.