Hypervitaminosis D - Long Term Effects of Supplementary Oral Intake

Long Term Effects of Supplementary Oral Intake

Excessive exposure to sunlight poses no risk in 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 reach 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, which slows hepatic delivery of vitamin D and the availability in the plasma.

Orally administered vitamin D produces rapid hepatic delivery of vitamin D and increases plasma calcifediol. One of the richest food sources of vitamin D — wild salmon — would require 35 ounces (1 kg) to provide 10,000 IU. It has been argued that ingestion of vitamin D in large amounts was achieved in the process of grooming by furry human ancestors and that from UV-exposed human skin secretions early humans ingested vitamin D by licking the skin, however this putative ingestion of vitamin D by early humans is not quantified. A study found 34% of its sample of healthy western Canadians to be under 40nmol/L at some point and 97% to be under 80nmol/L at least once.

It has been questioned whether to ascribe a state of sub-optimal vitamin D status when the annual variation in ultraviolet will naturally produce a period of falling levels, and such a seasonal decline has been a part of Europeans' adaptive environment for 1000 generations. 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 80nmol/L by supplementation.

Current theories of the mechanism behind vitamin D toxicity 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 in which affect gene transcription and overwhelm the vitamin D signal transduction process, leading to vitamin D toxicity.