One International Unit (IU) of vitamin D3 is equivalent to 25 ng or 65 pmoles. In the United States, the principal form of vitamin D supplementation for food was vitamin D2 in the interval 1930–1965; since 1965 the predominant form of vitamin D supplementation has been vitamin D3. A joint US/Canadian committee of the Institute of Medicine (IOM) recommended in 2010 that the Recommended daily Dietary Allowance (RDA) of vitamin D (either D2 or D3) for a person age 9–70 is 600 IU/day and for persons over 70 years is 800 IU/day.
Figure 1 illustrates the multiple contributions of vitamin D to good health. Besides the classical contributions of vitamin D, via 1α,25(OH)2D3, and its endocrine system responsible for maintaining calcium homeostasis, because of the wide tissue distribution of the VDR, the scope of the vitamin D endocrine system is now known to be much more comprehensive. Thus the vitamin D endocrine system also includes the immune system (both innate and adaptive), the pancreas β-cell secretion of insulin, the heart and cardio vascular system, and muscle.
Fig1. A summary of the contributions of the vitamin D endocrine system to good health. 1α,25(OH)2D3, enzymatically produced by either the kidney or paracrine 25(OH)D3-1α-hydroxylase, is carried throughout the blood compartment by the vitamin D binding protein (DBP). The 1α,25(OH)2D3 enters any of the some 30 cell types that are known to contain the vitamin D receptor (VDR) and stimulates a variety of genomic and rapid responses that can contribute to good health. These responder cell types are organized, in the left-hand column (light green color), into five primary vitamin D-dependent physiological systems. The 1α,25(OH)2D3 brain system is at the present time only studied in rodent systems. The center column tabulates for each of the five major vitamin physiological systems the nature of their biological responses. The right hand column lists known examples of vitamin D deficiency related diseases that are “associated” with each physiological system. In general, only for the calcium homeostasis physiological system have randomized clinical trials (with humans) been carried out showing that correction of the vitamin D deficiency by increased vitamin D3 intake can minimize the disease studied. The blood levels of 25(OH)D have been shown to be correlated with varying extents of vitamin D deficiency. The inset table (bottom left) summarizes, for humans, the changes in the circulating levels of 25(OH)D that are linked to varying degrees of vitamin D deficiency (from severe to insufficient to sufficient, etc.). From a clinical perspective this information can be utilized to determine the recommended daily intake of vitamin D3 to maintain good vitamin D health.
As emphasized by the IOM committee, an assessment of a person’s vitamin D status can be carried out by determining their serum level of 25(OH)D. The inset table in Figure 1 shows for humans the correlation of the serum level of 25(OH)D with the severity of vitamin D deficiency.
The classic deficiency state resulting from a dietary absence of vitamin D or lack of ultraviolet (sunlight) exposure is the bone disease called rickets in children or osteomalacia in adults. Historically, the identification of rickets as a disease state allowed G. Mellanby in 1920 to induce rickets in puppies experimentally by nutritionally withholding fat extracts. This work resulted in the discovery of vitamin D3 and appreciation that in the absence of sunlight, that vitamin D3 was an essential trace dietary constituent (e.g., a vita min) that was important for bone mineralization.
The clinical features of rickets and osteomalacia depend upon the age of onset. The classical skeletal dis orders of rickets in very young children include deformity of the bones, especially in the knees, wrists, and ankles as well as associated changes in the costochondrial joint junctions, which have been termed by some as the rachitic rosary. If rickets devel ops in the first 6 months of life, infants may suffer from convulsions or develop tetany due to a low blood calcium level (usually <7 mg/100 mL), but may have only minor skeletal changes. After 6 months bone pain as well as tetany is likely to be present. Since osteomalacia occurs after growth and development of the skeleton are complete (i.e., the adult stage of life), its main symptoms are muscular weakness and bone pain, with little bone deformity.
