levels below 12.5 nmol/L, and lower dietary calcium intake compared with controls. In summary, these observational studies fail to provide conclusive support of a relationship between vitamin D intake and risk for either type 2 diabetes or metabolic syndrome because of the lack of consistency among studies, the paucity of high-quality large cohort studies, and the lack of strength for an association between vitamin D status and incidence of type 2 diabetes or metabolic syndrome.
The available evidence from observational studies of the associations between vitamin D and calcium and risk for type 2 diabetes or metabolic syndrome and secondary analyses from RCTs on markers of glucose tolerance proved insufficiently strong to support DRI development. The association studies linking lower serum 25OHD levels to increased risk for type 2 diabetes may be confounded by overweight and obesity, which not only predispose individuals to type 2 diabetes, but also cause lower serum 25OHD levels as a result of sequestration in fat and possibly other mechanisms. Although both retrospective and prospective studies tend to support an inverse association between serum 25OHD levels and type 2 diabetes, these studies are limited by the study design and cannot show a causal relationship. Evidence from RCTs on the effect of vitamin D supplements on incident diabetes or markers of glucose homeostasis is variable, and few RCTs showing significant results were identified. Taken together, the evidence in support of a role for vitamin D as a modulator of pancreatic endocrine function and insulin synthesis and secretion is not conclusive and therefore is not sufficient to support glucose tolerance as an indicator for DRI development.
The committee considered falls and physical performance as independent indicators. However, because of the integration of these indicators in the literature reviewed by the committee, the evidence for both indicators is examined together in this section.
The risk of falling is a major concern among the elderly, because falls can lead to fracture and long-term disability or death in this population. Vitamin D is necessary for normal development and growth of muscle fibers, and vitamin D deficiency may adversely affect muscle strength. Muscle weakness and pain (myopathy) are characteristics of rickets and osteomalacia and contribute to poor physical performance (Prineas et al., 1965; Skaria et al., 1975; Yoshikawa et al., 1979). Thus vitamin D-deficiency muscle weakness and the implications of poor muscle tone suggest a re-