Vitamin toxic dosage

The toxic dosage determined by Kretzschmar and Leuschner in animal experiments was confirmed in our clinical investigations with patients. Oral doses of 50 to 120 mg vitamin A acid daily cause side-effects, such as severe headaches, dryness of the lips, etc. (Table 22.1). However, a dose of 10 to 20 mg is well tolerated by most patients. The clinically visible side-effects encountered with oral vitamin A acid at doses of 100 mg correspond to those observed with high doses of vitamin A palmitate. 

As the above mentioned studies with high supplementation dosages exemplarily show, there is no known toxicity for phylloquinone (vitamin Kl), although allergic reactions are possible. This is NOT true for menadione (vitamin K3) that can interfere with glutathione, a natural antioxidant, resulting in oxidative stress and cell membrane damage. Injections of menadione in infants led to jaundice and hemolytic anemia and therefore should not be used for the treatment of vitamin K deficiency. 

Toxic effects have been observed when large dosages of some vitamins are ingested. Generally the water-soluble vitamins are less toxic, since excess quantities are usually excreted in the urine. Excessive amounts of fat-soluble vitamins, however, are stored in the body, which makes toxic levels of these vitamins easier to obtain. 

Prolonged administration of large dosages of vitamin E may result in muscle weakness, fatigue, headache, and nausea. This toxicity can be reversed by discontinuing the large-dose supplementation. 

Toxicity of vitamin K has not been well defined. Jaundice may occur in a newborn if large dosages of vitamin K are given to the mother before birth. Although kemicterus may result, this can be prevented by using vitamin K. 

The effects of most vitamin B overdoses have not been documented, although large dosages of pyridoxine have been reported to cause peripheral neuropathies. Ataxia and numbness of the hands and feet and impairment of the senses of pain, touch, and temperature may result. Excessive niacin intake may result in flushing, pruritus, and gastrointestinal disturbances. These symptoms are due to niacin s ability to cause the release of histamine. Large dosages of niacin can result in hepatic toxicity. 

Another possible dietary factor concerns the essential fatty acid content of human and artificial milk. It has been postulated by Sinclair that many modern dietaries are deficient in the essential polyethenoid fatty acids (EFA) and that in consequence there is a rise in unesterified (and more active) vitamin D and in unesterified cholesterol. He has suggested that a part of the etiology of infantile idiopathic hypercalcemia may be attributed to EFA deficiency (S5). He has pointed to the lower content of certain unsaturated fatty acids in cow s milk as compared with human milk as a factor in the development of idiopathic hypercalcemia in artificially fed infants. He considers that dried milk has an even lower content of essential fatty acids than liquid cow s milk and that the longer it is stored the lower does the essential fatty acid content become. On the basis of some observations on rats, he suggests that a dietary deficiency of the essential fatty acids increases susceptibility to the possible toxic effects of vitamin D. The age of the rats, the duration of the essential fatty acid deficient diet, or the dosage of vitamin D is not mentioned, and there would appear to be no other experimental data to support these views. 

Solubility is important in other ways as well. For example, because the pesticide DDT is fat-soluble, it is retained and concentrated in animal tissues, where it causes detrimental effects. This is why DDT, even though it is effective for killing mosquitos, has been banned in the United States. Also, the solubilities of various vitamins are important in determining correct dosages. The insolubility of barium sulfate means it can be safely used to improve X-ray images of the gastrointestinal tract, even though Ba2+ ions are quite toxic. 

Osteomalacia—the adult form of rickets—is another calcium deficiency disease. Instead of making bones more brittle and porous as osteoporosis does, osteomalacia makes bones more flexible, resulting in deformities and pain. The cause is usually vitamin D deficiency, and the most effective reversal is short-term use of high dosages of vitamin D, gradually reducing dosages to 400 lU (International Units) daily. This should always be done under the supervision of a doctor since vitamin D is a very potent hormone and can become toxic if improperly used. 

Nieman and Obbink (1954) have provided an extensive review of the subchronic toxicity of vitamin A preparations and of retinol that appeared in the literature up to the early 1950s. The studies described were carried out in a variety of animal species but primarily in the rat dosages ranged from 3 to 180 mg retinol equivalents/day and the duration of treatment varied from a few days to several weeks. 

Human beings seem to become adapted to low intakes of thiamine, under favorable conditions. Requirements are increased in conditions that involve increased metabolism such as exercise, fever, and hyperthyroidism. The health and motility of the intestinal tract is also a factor. Needs are increased only up to a plateau, since urinary excretion tends to keep pace with consumption, even from low levels. It is thus not clear how the ingestion daily of thiamine in excess of apparent needs is literally a margin of safety against a future stress. Very high dosages for short times have produced no toxic symptoms, but protracted use of thiamine without other B vitamins may produce undesirable effects. 

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