Critique of the U-shaped serum 25-hydroxyvitamin D level-disease response relation

Previous work has suggested an optimal serum 25-hydroxyvitamin D [25(OH)D] level near 20-30 ng/mL, above which disease risk may increase. Although based primarily on a prostate cancer study in Nordic countries, examples include esophageal, and pancreatic cancer, cardiovascular disease, and all-cause mortality rate. However, these studies apparently are not representative of the findings in the literature for these diseases or disease outcome in general. The prostate cancer study was from Nordic countries and used serum 25(OH)D levels from more than 15 years prior to cancer diagnosis for about half of the cases. Most studies of prediagnostic serum 25(OH)D find no significant correlation with risk of prostate cancer. Many risk-modifying factors for prostate cancer exist that observational studies generally do not include. The esophageal cancer data were from a region of China with high incidence of esophageal cancer. The pancreatic study was conducted on smokers in Finland. Both the esophageal and pancreatic studies are at odds with many ecological and observational studies in various countries. When several studies for cardiovascular disease, and all-cause mortality rate are combined in preliminary meta-analyses, the best fits to the data show a monotonic decrease of hazard ratio with increasing logarithm of serum 25(OH)D. Thus, little support exists for the U-shaped serum 25(OH)D level-disease response relation, and the few studies that do should not be used in forming public health policies regarding vitamin D and ultraviolet-B irradiance.