Excessive intake of vitamin A, excluding carotene, leads to a toxic condition known as hypervitaminosis A. Symptoms of chronic hypervitaminosis A include dry and itchy skin, enlarged and potentially cirrhotic liver, and increased intracranial pressure resembling the symptoms of a brain tumor. Pregnant women should avoid consuming excessive amounts of vitamin A due to its potential to cause birth defects. The recommended upper limit for preformed vitamin A intake is 3,000 µg per day. Isotretinoin, an isomer of retinoic acid, is contraindicated in women with childbearing potential unless they have severe cystic acne that does not respond to standard treatments. Before starting treatment with isotretinoin, pregnancy must be ruled out and birth control must be used. Prolonged use of isotretinoin can elevate levels of TAG and cholesterol, which may pose a risk for cardiovascular disease.

Vitamin D, a group of sterols with hormone-like function, includes the active molecule 1,25-dihydroxycholecalciferol (calcitriol). Calcitriol binds to intracellular receptor proteins and interacts with response elements in the nuclear DNA of target cells. Similar to vitamin A, it selectively stimulates or represses gene transcription. The main role of calcitriol is to regulate the levels of calcium and phosphorus in the blood.

Endogenous vitamin precursor, 7-dehydrocholesterol, found in the dermis and epidermis of humans exposed to sunlight, is converted to cholecalciferol and transported to the liver bound to vitamin D-binding protein. Dietary sources of preformed vitamin D activity include ergocalciferol (vitamin D2) found in plants and cholecalciferol (vitamin D3) found in animal tissues. The only chemical difference between vitamin D2 and vitamin D3 is the presence of an additional double-bond and methyl group in the plant sterol. Dietary vitamin D is packaged into chylomicrons. Individuals with limited sun exposure have a dietary requirement for preformed vitamin D.
I. Retinoid toxicity 1.
Vitamin A: Excessive intake of vitamin A (but not carotene) produces a toxic syndrome called hypervitaminosis A. Amounts exceeding 7.5 mg/day of retinol should be avoided. Early signs of chronic hypervitaminosis A are reflected in the skin, which becomes dry and pruritic (because of decreased keratin synthesis); in the liver, which becomes enlarged and can become cirrhotic; and in the CNS, where a rise in intracranial pressure may mimic the symptoms of a brain tumor. Pregnant women, in particular, should not ingest excessive quantities of vitamin A because of its potential for teratogenesis (causing congenital malformations in the developing fetus). UL is 3,000 µg preformed vitamin A/day. [Note: Vitamin A promotes bone growth. In excess, however, it is associated with decreased bone mineral density and increased risk of fractures.] 2.
Isotretinoin: The drug, an isomer of retinoic acid, is teratogenic and absolutely contraindicated in women with childbearing potential unless they have severe, disfiguring cystic acne that is unresponsive to standard therapies. Pregnancy must be excluded before treatment begins, and birth control must be used. Prolonged treatment with isotretinoin can result in an increase in TAG and cholesterol, providing some concern for an increased risk of CVD.
XII. VITAMIN D
The D vitamins are a group of sterols that have a hormone-like function. The active molecule, 1,25-dihydroxycholecalciferol ([1,25-diOH-D3], or calcitriol), binds to intracellular receptor proteins. The 1,25-diOH-D3–receptor complex interacts with response elements in the nuclear DNA of target cells in a manner similar to that of vitamin A (see Fig. 28.20) and either selectively stimulates or represses gene transcription. The most prominent actions of calcitriol are to regulate the serum levels of calcium and phosphorus.
A. Distribution 1.
Endogenous vitamin precursor: 7-Dehydrocholesterol, an intermediate in cholesterol synthesis, is converted to cholecalciferol in the dermis and epidermis of humans exposed to sunlight and transported to liver bound to vitamin D–binding protein.
2.
Diet: Ergocalciferol (vitamin D2), found in plants, and cholecalciferol (vitamin D3), found in animal tissues, are sources of preformed vitamin D activity (Fig. 28.22). Vitamin D2 and vitamin D3 differ chemically only in the presence of an additional double-bond and methyl group in the plant sterol. Dietary vitamin D is packaged into chylomicrons. [Note: Preformed vitamin D is a dietary requirement only in individuals with limited exposure to sunlight.]