Vitamin high intakes

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). 

Fohc acid is safe, even at levels of daily oral supplementation up to 5—10 mg (97). Gastrointestinal upset and an altered sleep pattern have been reported at 15 mg/day (98). A high intake of foHc acid can mask the clinical signs of pernicious anemia which results from vitamin deficiency and recurrence of epilepsy in epileptics treated with dmgs with antifolate activity (99). The acute toxicity (LD q) is approximately 500 and 600 mg per kg body weight for rats and mice, respectively (100). 

Vitamin C is not toxic and ahypervitaminosis has not yet been described in the literature. The statement that high vitamin C intake increases the risk of kidney stones could not be maintained. 

Although most fragility fractures in women occur after age 50, certain groups of premenopausal women are at high risk for osteoporosis. The NOF recommends measuring bone mineral density in premenopausal women with risk factors in addition to sex and race, in whom treatment would be considered.1 Premenopausal women at risk for osteoporosis should follow all nonpharmacologic recommendations for exercise and adequate calcium and vitamin D intake. Currently, no good data... 

There is additional evidence of wide variation in needs in the fact that high vitamin A intakes (much higher than the supposed normal) have been found beneficial in the treatment, in certain individuals, of skin lesions, night blindness, etc., when lower doses failed. Part of the difficulty in some cases may have involved faulty absorption. Even so, a difference in need is involved, and if one individual needs to consume ten times as much as another because of difficulty in absorption, the augmented need is just as real as if the difficulty involved some other step in utilization. 

Figure 22.6 How various factors increase the risk of atherosclerosis, thrombosis and myocardial infarction. The diagram provides suggestions as to how various factors increase the risk of development of the trio of cardiovascular problems. The factors include an excessive intake of total fat, which increases activity of clotting factors, especially factor VIII an excessive intake of saturated or trans fatty acids that change the structure of the plasma membrane of cells, such as endothelial cells, which increases the risk of platelet aggregation or susceptibility of the membrane to injury excessive intake of salt - which increases blood pressure, as does smoking and low physical activity a high intake of fat or cholesterol or a low intake of antioxidants, vitamin 6 2 and folic acid, which can lead either to direct chemical damage (e.g. oxidation) to the structure of LDL or an increase in the serum level of LDL, which also increases the risk of chemical damage to LDL. A low intake of folate and vitamin B12 also decreases metabolism of homocysteine, so that the plasma concentration increases, which can damage the endothelial membrane due to formation of thiolactone.

High daily doses of retinoids can lead to hyper-vitaminosis A manifesting itself as dermal toxicity such as erythematous dermatitis, bone pains, neurological symptoms and hepatosplenomegaly. A recent study shows a correlation between low bone mineral density and too high intake of vitamin A. 

Deficiency of vitamin E is characterized by low serum tocopherol levels and a positive hydrogen peroxide hemolysis test. This deficiency is believed to occur in patients with biliary, pancreatic, or intestinal disease that is characterized by excessive steatorrhea. Premature infants with a high intake of fatty acids exhibit a deficiency syndrome characterized by edema, anemia, and low tocopherol levels. This condition is reversed by giving vitamin E. 

Severe cyanocobalamin (vitamin B12) deficiency results in pernicious anemia that is characterized by megaloblastic anemia and neuropathies. The symptoms of this deficiency can be masked by high intake of folate. Vitamin B12 is recycled by an effective enterohep-atic circulation and thus has a very long half-hfe. Absorption of vitamin B12 from the gastrointestinal tract requires the presence of gastric intrinsic factor. This factor binds to the vitamin, forming a complex that... 

Phytic acid, although restricted to a more narrow range of food products, mainly grains, complexes a broader spectrum of minerals than does oxalic acid. Decreased availability of P is probably the most widely recognized result of excessive intakes of phytic acid, yet Ca. Cu, Zn, Fe. and Mn are also complexed and rendered unavailable hy this compound. High intakes of both calcium and vitamin D help to offset ihe deleterious effects of oxalates. 

Rothman KJ, Moore LL, Singer MR, Nguyen US, Mannino S, Milunsky A. Teratogenicity of high vitamin A intake. N Engl J Med 1995 333(21) 1369-73. 

Fenech, M., Baghurst, P., Luderer, W., Turner, J., Record, S., Ceppi, M., and Bonassi, S. (2005). Low intake of calcium, folate, nicotinic acid, vitamin E, retinol, beta-carotene and high intake of pantothenic acid, biotin and riboflavin are significantly associated with increased genome instability—Results from a dietary intake and micronucleus index survey in South Australia. Carcinogenesis 26, 991-999. 

Absence of reported adverse effects does not mean that there is no potential for adverse effects from high intake. Caution should still be used when taking doses well in excess of the recommended daily amounts. Adapted from Institute of Medicine of the National Academies [www.iom.edu) Food Nutrition > Dietary Reference Intakes > DRI Tables > Vitamins. 

A pooled analysis of nine prospective studies on 293,172 subjects for a follow-up of 10 years that included information on vitamin E, C, and carotenoids (52) was conducted the results suggest that high supplemental vitamin C intakes (>700 mg/day) reduced the incidence of major coronary heart disease. The risk reduction induced by vitamin E or carotenoids was very small. 

Vitamin C results from long-term trials are also conflicting. However, high intake was never found to increase mortality, and moderate intake between 100 and 200 mg/day essentially shows some benefit either taken as a supplement or with a diet plus supplements, particularly in elderly. However, there is no benefit in using dosages higher than 400 mg/day. 

A pooled analysis (52) of nine studies (NHS was divided into two studies) reached the following conclusion The results suggest a reduced incidence of major events at high supplemental vitamin C intakes. The risk reduction at high vitamin E or carotenoid intakes appear small. ... 

Rotterdam 6 yr 5395 M-F High intakes of vitamin E and C are associated with a lower risk of Alzheimer disease activity is more evident in smokers high intakes of /3-carotene may protect against cardiovascular disease (201,202)... 

Figure 29-4. Stellate cell lipid droplets present in a biopsy obtained from the liver of a patient experiencing vitamin A toxicity. Image obtained from electron microscopy of a biopsied human liver showing the characteristic lipid droplets (LD) found in hepatic stellate cells (SC).These lipid droplets are highly enriched in vitamin A, and the size and number of lipid droplets is influenced by dietary vitamin A intake and nutritional status. In this image of a human stellate cell, the nucleus (N) is compressed by the surrounding lipid droplets, and very little cell cytoplasm within the stellate cell can be seen in this view.Adjoining the stellate cell are two hepatocytes (H).

Possibly beneficial effects of intakes more than adequate to meet requirements the promotion of optimumhealth and life expectancy. There is evidence that relatively high intakes of vitamin E and possibly other antioxidant nutrients (Section 4.6.2) may reduce the risk of developing cardiovascular disease and some forms of cancer. High intake of folate during early pregnancy reduces the risk of neural tube defects in the fetus (Section 10.9.4). 

A small proportion of dietary retinol is oxidized to retuioic acid, which is absorbed into the portal circulation and bound to serum albumin. Some retinyl esters are also transferred into the portal circulation. Patients with abeta-lipoproteinemia, who are unable to synthesize chylomicrons, can nevertheless maintain adequate vitamin A status if they are provided with relatively high intakes of retinol. 

Bones joint pains, thickening of the long bones, hypercalcemia, and calcification of soft tissues, but with reduced bone mineral density. High intakes of vitamin A are associated with an increased rate of loss of bone mineral density with age, and some studies have shown that intakes above 1,500 /xg per day are associated with increased incidence of osteoporosis and hip fracture, although other studies have not shown any relationship between vitamin A intake and osteoporosis (Institute of Medicine, 2001). At high levels of intake, vitamin A both stimulates bone... 

Very high intakes may antagonize vitamin K and hence potentiate anticoagulant therapy. This is probably the result of inhibition of the vitamin K quinone reductase, but a-tocopheryl quinone may compete with vitamin K hydroquinone and hence inhibit carboxylation of glutamate in target proteins (Section 5.3.1). 

Vitamin E and Cataracts There is good evidence that cataracts are the result of oxidative damage to a-crystaUin in the lens of the eyes, and therefore high intakes of antioxidants might be expected to be beneficial. Of 10 controlled trials, 5 showed a protective effect of vitamin E supplements, and 5 showed no effect (Institute of Medicine, 2000). 

Although pyridoxine is taken up and phosphorylated by muscle (and other tissues), the resultant pyridoxine phosphate is not oxidized to pyridoxal phosphate. It has been suggested that the neurotoxicity of high intakes of pyridoxine (Section 9.9.6.4) may be caused by the uptake and trapping of pyridoxine, and hence competition with pyridoxal, resulting in depletion of tissue pyridoxal phosphate and a deficiency of the metabolically active form of the vitamin. 

A small number of patients show one or the other of the biochemical signs associated with vitamin Be deficiency despite apparendy adequate status, and require high intakes of the vitamin to normalize the abnormal metabolic marker. These are genetic diseases and have been termed vitamin Be dependency syndromes. 

Early studies suggested that folate supplements exacerbate or hasten the development of the neurological damage in vitamin B12 deficiency. There is little evidence that this is so, but high intakes of folate will prevent the development of megaloblastic anemia in vitamin B12 deficiency. In up to one-third of... 

The only pharmacological use of vitamin B12, other than for the treatment of deficiency or for rare children with vitamin dependency diseases affecting the binding of the coenzyme to methylmalonyl CoA mutase (Section 10.8.2), is as an antidote for cyanide poisoning. Supplements of vitamin B12 are available for strict vegetarians who might be at risk of deficiency. There is no evidence of any adverse effects of high intakes of vitamin B12. 

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