Vitamin excess/toxicity

Vitamin D toxicity has been suggested as a cause of metabolic bone disease. However, vitamin D deficiency results in bone loss, and data on vitamin D excess and metabolic bone disease remain controversial. 

Excess vitamin D can result in hypervitaminosis D with serious vitamin D toxicity characterized by hypercalcemia and nephrocalcinosis. 

The physiological role of vitamin K is in blood clotting and is essential for the synthesis of at least four of the proteins (including prothrombin) involved in this process. Vitamin K also plays a role in the synthesis of a protein (osteocalcin) in bone. Vitamin K deficiency is rare but can result from impaired absorption of fat. Vitamin K levels in the body are also reduced if the intestinal flora is killed (e.g. by antibiotics). Vitamin K toxicity is rare but can be caused by excessive intake of vitamin K supplements. Symptoms include erythrocyte haemolysis, jaundice, brain damage and reduced effectiveness of anticoagulants. 

Vitamin D is a fat-soluble vitamin, and excessive doses can accumulate in the body, leading to toxicity. Some early signs of vitamin D toxicity include headache, increased thirst, decreased appetite, metallic taste, fatigue, and gastrointestinal disturbances (nausea, vomiting, constipation, or diarrhea). Increased vitamin D toxicity is associated with hypercalcemia, high blood pressure, cardiac arrhythmias, renal failure, mood changes, and seizures. Vitamin D toxicity is a serious problem that can cause death because of cardiac and renal failure. 

Excessive intake of vitamin D Toxic effect of vitamin D, as opposed to vitamin D3... 

The fact that vitamin D3 toxicity results from primarily uncontrolled intestinal calcium absorption suggests that it is dietary calcium and not vitamin D3 that exacerbates the hypervitaminosis D3 toxicity effect [119]. This was tested by the interaction of excess vitamin D3 and calcium restriction [113]. Rats fed a calcium-deficient diet and given 25,000 IU of vitamin D3 three dmes/week for 2.5 weeks did not succumb to overt hypervitaminosis D3. Simple calcium restriction increased intestinal but not renal 24-OHase activity, presumably because of the absence of parathyroid hormone regulation in the intestine [113]. Coupled with vitamin D3, excess intestinal 24-OHase increased several fold more. However, when dietary calcium was adequate, vitamin D3 excess increased intestinal 24-OHase activity only slightly because of a suppressive mechanism regulated in part by increased blood calcitonin [120],... 

The effect of alcohol abuse, one of the most common aggravating factors in vitamin A toxicity, has been elucidated. Vitamin A toxicity was potentiated in patients who took 10 000 lU/day for sexual dysfunction, and this effect was attributed to excess alcohol consumption (95). In animals, potentiation of vitamin A toxicity by ethanol resulted in striking hepatic inflammation and necrosis accompanied by a rise in serum glutamate dehydrogenase and aspartate transaminase (96). 

Micronutrients (vitamins and minerals) are also listed on food packaging. The vitamins we require are compounds that are necessary for metahohc processes either our bodies cannot synthesize them, or they cannot synthesize them in amounts sufficient for our needs. As a result, we must obtain vitamins from dietary sources. DVs are listed for the fat-soluble vitamins—vitamins A, D, and E (Section 8.7)—but care must be taken to avoid overdoses of these vitamins. Excesses can be toxic when lai e amounts of fat-soluble vitamins accumulate in adipose tissue. Excess vitamin A is especially toxic. With water-soluble vitamins, turnover is frequent enough that the danger of excess is not normally a problem. 

The water-soluble vitamins are the eight B vitamins and vitamin G. Because excesses are excreted rather than stored, it had previously been assumed that overdosing on water-soluble vitamins has no toxic effects. With the rise in popularity of megadoses of vitamins, some toxic reactions have been observed. It does, however, take much greater quantities of water-soluble vitamins to create harmful effects than for the fat-soluble vitamins. 

Hypervitaminosis A results from the excessive intake of preformed vitamin A. Toxicity in pregnancy is related to the role of retinoic acid in regulating differentiation, resulting in birth defects. Recent reports suggest that habitual high doses of vitamin A might be associated with osteoporosis. 

Vitamin D is a pro-hormone that comes in two forms, cholecalciferol (vitamin D3) and ergocalciferol (vitamin Dj) (Haddad and Hahn 1973). Most of vitamin D is obtained as vitamin D3, through synthesis in the skin after exposure to UVB radiation (typically from sunlight) of wavelengths 290-315 nm (Holick 1995). The synthesis converts 7-dehydrocholesterol (DHC-7) to pre-vitamin D3, which is then quickly converted by heat induction to vitamin D3. Overexposure to UVB radiation does not cause vitamin D toxicity as excess pre-vitamin D3 and vitamin D3 is inactivated by radiation (Holick et al. 1981, Webb et al. 1989). Vitamin D3 can also be obtained from animal-based food products, with oily fish (e.g., salmon, sardines, and mackerel) being the best natural source, and egg yolk and meat containing smaller quantities. Vitamin D2 is the plant form of vitamin D and can occur naturally in some types of mushrooms (Lamberg-Allardt 2006). 

An extensive study was carried out in rats given excessive vitamin A in doses sufficient to cause both growth disturbances and fatty livers (Mallia et al., 1975). The hypervitaminotic rats showed large increases in serum vitamin A levels, which were mainly due to elevations in the circulating levels of retinyl esters, and decreased levels of serum RBP. In these toxic rats, most of the serum vitamin A and virtually all of the retinyl esters were found in association with the serum lipoproteins of hydrated density < 1.21. It was concluded that the serum lipoproteins play an important role in the transport of the vitamin A that accumulates in the serum in hypervitaminosis A. It was also suggested that serum lipoproteins may nonspecifically deliver vitamin A to biological membranes and, hence, lead to vitamin A toxicity. 

Data consistent with this interpretation have been obtained in studies on vitamin A transport in human vitamin A toxicity (Smith and Goodman, 1976). In three patients with chronic hypervitaminosis A, the toxic state in each was associated with increased plasma levels of total vitamin A and particularly of retinyl esters. In contrast, plasma RBP levels were normal, and there was a molar excess of total vitamin A in relation to RBP. The data suggest that vitamin A toxicity appears to occur in vivo only when the level of vitamin A in the body is such that retinol begins to circulate in plasma and is presented to membranes in a... 

Chronic toxic symptoms (hypervitaminosis A) may occur in adults who receive doses of vitamin A in excess of 50,000 lU daily over a prolonged period. Lesser doses will produce symptoms in children infants who receive 18,500 lU daily may show signs of toxicity within 12 weeks. Acute toxicity occurs in adults who are given massive doses of 2 to 5 million lU daily, and in infants from doses as low as 75,000 to 300,000 lU daily. Vitamin C can help prevent the harmful effects of vitamin A toxicity. When excess intake of vitamin A is discontinued, recovery is usually rapid and complete in some cases, the toxicity symptoms disappear within 72 hours. 

Production and oxidation both serve to maintain normal tissue retinoid levels. Nonetheless, these physiological processes can be overwhelmed by an excess of dietary vitamin A, resulting in excessive vitamin A in tissues and plasma, or by the use of synthetic retinoids that lead to substantial elevations in tissue bioactive retinoids (see the article section Hypervi-taminosis A and Vitamin A Toxicity ). 

Of the water-soluble vitamins, intakes of nicotinic acid [59-67-6] on the order of 10 to 30 times the recommended daily allowance (RE)A) have been shown to cause flushing, headache, nausea, and moderate lowering of semm cholesterol with concurrent increases in semm glucose. Toxic levels of foHc acid [59-30-3] are ca 20 mg/d in infants, and probably approach 400 mg/d in adults. The body seems able to tolerate very large intakes of ascorbic acid [50-81-7] (vitamin C) without iH effect, but levels in excess of 9 g/d have been reported to cause increases in urinary oxaHc acid excretion. Urinary and blood uric acid also rise as a result of high intakes of ascorbic acid, and these factors may increase the tendency for formation of kidney or bladder stones. AH other water-soluble vitamins possess an even wider margin of safety and present no practical problem (82). 

There is only a limited capacity to metabolize vitamin A, and excessive intakes lead to accumulation beyond the capacity of binding proteins, so that unbound vitamin A causes tissue damage. Symptoms of toxicity affect the central nervous system (headache, nausea. 

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