Odd notes and high points...
Natural vitamin D toxicities are limited to ingestion of four known
calcinogenic species:
Cestrum diurnum,Trisetum flavescens, Solanum
malacoxylon and
Solanum glaucophyllum.
Unfortunately, the existence of
vitamin supplements have not only eliminated rickets and other horrible
consequences of vitamin D deficiency, but have also made
artificially-induced
vitamin D toxicity possible.
Animals with access to sunlight usually do not need dietary vitamin D, because ultraviolet light converts 7-dehydrocholesterol (abundant in skin) to the vitamin D3 cholecalciferol. Vitamin D2 (ergocalciferol) is created from the plant steroid ergosterol. One International Unit of Vitamin D is 0.025 micrograms of either D2 or D3. D2 is catabolized much sooner than D3 (at least in chicks) and is not as readily converted to the 25OH form in overdose situations. Perhaps that is why D3 is more than 10 times as toxic as D2.
The most active form of vitamin D is the 1,25 diOH form. The OH is added to the 25 position in the liver and to the 1 position mostly in the kidney. Once so activated, vitamin D is a hormone that interacts with the DNA of target cells (bone, gut, kidney, etc.) to promote the transcription of specific proteins responsible for its actions.
That 1-hydroxylation is promoted by low phosphorus, low calcium (via parathyroid hormone) and calcitonin and inhibited by the 1,25 diOH D itself.
Active vitamin D increases gut absorption of calcium and phosphorus, resorption of calcium and phosphorus by the kidneys and increased bone turnover (needed for proper bone formation and mineralization, but also specifically promotes bone resorption).
Dietary overdose of vitamin D results in relatively successful shutdown of 1-hydroxylation, but 25OH D builds up to such high levels that it begins to overwhelm and turn on 1,25 OH D receptors around the body without being further hydroxylated. Ingestion of the toxic calcinogenic plants causes even more severe toxicity because the active compound is actually fully active 1,25 OH D3 form. That's right - the "animal" form. In plants. Wierd, eh?
Recommendations range from 2.5 micrograms (100IU) per day for adult Canadians to 10 micrograms per day for Canadian infants (400 IU). USRDA is 5 micrograms per day. 2000 IU daily poisons children, and especially sensitive kids have been intoxicated with less than half of that.
The principal direct toxic effects of vitamin D are excessive absorption of calcium from the intestine and resorption of calcium from bone. This results in deposition of calcium and phosphorus in soft tissues all over the body, with particular damage to the heart, blood vessels and kidneys. This a fairly reliable method for inducing high blood pressure in model animals (such as dogs). This is presumably renal hypertension caused by calcification of the renal arteries. Extreme toxicities caused by the calcinogenic plants results in calcium deposition in and damage to lungs, tendons, ligaments with attendent lameness.
There are some workers in this field that believe that fears of vitamin D toxicity are overblown and they may be be preventing certain target populations from receiving adequate vitamin D. These target populations include residents of the urban Northern United States who are not exposed to much sun in the summer because of clothing and urban habits, and are not exposed at all in the winter. Please read Vieth's article on this subject (provided in class; Am J Clin Nutr 1999;69:842-856), but read it closely and critically. What criteria of vitamin D status does he emphasize? Is this valid? What would his recommendations do to the margin of safety for vitamin D intakes?