Excessive exposure to sunlight poses no risk of vitamin D toxicity through overproduction of vitamin D precursor,
cholecalciferol, regulating vitamin D production. During
ultraviolet exposure, the concentration of vitamin D precursors produced in the skin reaches an
equilibrium, and any further vitamin D that is produced is degraded. This process is less efficient with increased melanin pigmentation in the skin. Endogenous production with full body exposure to sunlight is comparable to taking an oral dose between 250 μg and 625 μg (10,000 IU and 25,000 IU) per day. Vitamin D oral supplementation and skin synthesis have a different effect on the transport form of vitamin D, plasma
calcifediol concentrations. Endogenously synthesized vitamin D3 travels mainly with
vitamin D-binding protein (DBP), which slows hepatic delivery of vitamin D and its availability in the plasma. In contrast, orally administered vitamin D produces rapid hepatic delivery of vitamin D and increases plasma calcifediol. Still more contentious is recommending supplementation when those supposedly in need of it are labeled healthy and serious doubts exist as to the long-term effect of attaining and maintaining serum 25(OH)D of at least 80 nmol/L by supplementation. Current theories of the mechanism behind vitamin D toxicity (starting at a plasmatic concentration of ≈750 nmol/L) propose that: • Intake of vitamin D raises
calcitriol concentrations in the plasma and cell • Intake of vitamin D raises plasma
calcifediol concentrations, which exceed the binding capacity of the DBP, and free calcifediol enters the cell • Intake of vitamin D raises the concentration of vitamin D metabolites, which exceed DBP binding capacity, and free calcitriol enters the cell All of these affect gene transcription and overwhelm the vitamin D
signal transduction process, leading to vitamin D toxicity. This raises questions regarding the effects of vitamin D intake on atherosclerotic calcification and cardiovascular risk as it may be causing vascular
calcification. Calcifediol is implicated in the etiology of atherosclerosis, especially in people of color. The levels of the active form of vitamin D,
calcitriol, are inversely correlated with coronary calcification. Moreover, the active vitamin D analog,
alfacalcidol, seems to protect patients from developing vascular calcification. Serum vitamin D has been found to correlate with calcified atherosclerotic plaque in African Americans as they have higher active serum vitamin D levels compared to Euro-Americans. Higher levels of calcidiol positively correlate with aorta and carotid calcified atherosclerotic plaque in African Americans but not with coronary plaque, whereas individuals of European descent have an opposite, negative association. Among descent groups with heavy sun exposure during their evolution, taking supplemental vitamin D to attain the 25(OH)D level associated with optimal health in studies done with mainly European populations may have deleterious outcomes. Recommendations stemming from a single standard for optimal serum 25(OH)D concentrations ignore the differing genetically mediated determinants of serum 25(OH)D and may result in ethnic minorities in Western countries having the results of studies done with subjects not representative of ethnic diversity applied to them. Vitamin D levels vary for genetically mediated reasons as well as environmental ones.
Ethnic differences Possible ethnic differences in physiological pathways for ingested vitamin D, such as the
Inuit, may confound across-the-board recommendations for vitamin D levels. Inuit compensate for lower production of vitamin D by converting more of this vitamin to its most active form. Studies on the South Asian population uniformly point to low 25(OH)D levels, despite abundant sunshine. Rural men around Delhi average 44 nmol/L. Healthy Indians seem to have low 25(OH)D levels, which are not very different from healthy South Asians living in Canada. Measuring melanin content to assess skin pigmentation showed an inverse relationship with serum 25(OH)D. The uniform occurrence of very low serum 25(OH)D in Indians living in India and Chinese in China does not support the hypothesis that the low levels seen in the more pigmented are due to lack of synthesis from the sun at higher latitudes. == Comparative Toxicity: Use of Vitamin D in Rodenticides ==