Hypervitaminosis chronic

With the exception of the possible development of a hypervitaminosis associated with high-dose administration of vitamin D2 or D3, the compounds discussed in this chapter are relatively safe. Allergic reactions to the injection of calcitonin and PTH have occurred and chronic use of some bisphosphonates has been associated with the development of osteomalacia. The principal side effects of intravenous bisphosphonates are mild and include low-grade fever and transient increases in serum creatinine and phosphate levels. Oral bisphosphonates are poorly absorbed and can cause esophageal and gastric ulceration. They should be taken on an empty stomach the individual must remain upright for 30 minutes after ingestion. 

Acitretin (Soriatane), a metabolite of the aromatic retinoid etretinate, is quite effective in the treatment of psoriasis, especially pustular forms. It is given orally at a dosage of 25-50 mg/d. Adverse effects attributable to acitretin therapy are similar to those seen with isotretinoin and resemble hypervitaminosis A. Elevations in cholesterol and triglycerides may be noted with acitretin, and hepatotoxicity with liver enzyme elevations has been reported. Acitretin is more teratogenic than isotretinoin in the animal species studied to date, which is of special concern in view of the drug s prolonged elimination time (more than 3 months) after chronic administration. In cases where etretinate is formed by concomitant administration of acitretin and ethanol, etretinate may be found in plasma and subcutaneous fat for many years. 

High doses of vitamin A can produce the toxic side effects of the acute or chronic hypervitaminosis A syndrome, which in humans is characterized by the following ... 

Acute hypervitaminosis A in humans requires doses of at least 600 mg in adults and 100 mg in children chronic hypervitaminosis A requires 20 to 50 mg daily for several years (Dawson, 2000). 

Chronic intoxication with vitamin A has been reported to cause variously hypercalcemia, hyperglycae-mia, increased alkaline phosphatase, hypoproteinemia, hypoprothrombinemia, increased sulfobromphthalein retention, raised serum transaminases, low serum ascorbic acid, reduced protein content of the cerebrospinal fluid, raised urinary hydroxyproline, and hypercalciuria (SED-8, 800) (14). It is not always clear, however, whether these deviations are a cause or an effect of hypervitaminosis A. 

Hypervitaminosis A can be a frequently overlooked cause of chronic headache (23). The precise cause of this, and of increased intracranial pressure in hypervitaminosis A, is controversial and unclear (24). 

For the diagnosis of hypervitaminosis A, plasma concentrations and retinol-binding protein may be misleading. Cases have been reported of hepatic fibrosis, secondary to chronic ingestion of massive doses of vitamin A, where plasma concentrations of vitamin A and retinol-binding protein at the time of diagnosis were within the reference range (43). 

Patients with renal dysfunction are known to have raised circulating vitamin A concentrations. In chronic dialysis patients, the concentration can rise steadily. The significantly increased osmotic fragility of erythrocytes observed in hemodialysed patients also seems to be related to high vitamin A concentrations. However, the similarity between uremic symptoms and those of vitamin A excess may explain why hypervitaminosis A in uremic patients is rarely reported as being associated with clinical toxicity (SEDA-12, 327). 

Bartolozzi G, Bernini G. Chronic hypervitaminosis A. Helv Paediatr Acta 1979 25 301. 

Ruby LK, Mital MA. Skeletal deformities following chronic hypervitaminosis A a case report. J Bone Joint Surg Am 1974 56(6) 1283-7. 

Table 1 Clinical effects of chronic hypervitaminosis A, in order of decreasing frequency (3,4)...

Hypervitaminosis A and D have also been associated with bone abnormalities. Vitamin D can cause resorption of calcium from bone. Chronic vitamin D intoxication may result in increased mineralization on bone and metastatic calcifications including joints, periarticular, and the kidney. Excessive vitamin D intake can cause demineralization of bone resulting in multiple fractures from very slight trauma. 

HypervitamininosisA. In high doses, retinol can be toxic. Acute poisoning is rare and dependent on the dosage form. Nausea and vomiting are the most common symptoms. Most rapidly absorbed are the "clear" emulsions (usually formulated with a Tween or other surfactant). Next in order are the standard emulsions, usually produced from fish liver oils. The most slowly absorbed are the dry tablet formulations or an oil solution in a capsule. Chronic hypervitaminosis is... 

Hypervitaminosis E. This is a relatively safe vitamin. Toxicities have been reported involving chronic administration of 300-1200 mg per day. The symptoms can be very serious and include thrombophlebitis, pulmonary embolism, hypertension, breast development in men and children, severe fatigue, and nonmalignant breast tumors. Nevertheless, the UL to RDA ratio is about 66 to 1 for adults, making it a very safe vitamin. 

HYPERVITAMINOSIS D The acute or chronic administration of excessive amounts of vitamin D can cause hypervitaminosis D and hypercalcemia. The amount of vitamin D necessary to induce this condition varies widely. As an approximation, prolonged daily ingestion of 50,000 U or more can cause poisoning. The signs and symptoms are those associated with hypercalcemia. 

Toxicology Vitamin A hypervitaminosis can lead to clinical symptoms such as headache, nausea, in chronic cases disturbances of sleep, loss of appetite, loss of hair, bone swellings in the limbs however, all symptoms disappear when the consumption of vitamin A is reduced. Acute poisonings have been observed in, e.g., polar explorers after consumption of the extremely vitamin A,-rich polar bear liver. The metabolite of R., vitamin A acid (retinoic acid, tretinoin, C20H28O3, Mr 316.44, mp. 180-182 °C) can cause malformations and thus pregnant women should not consume more than 3.3 mg of vitamin A] per day Synthesis R. was obtained in the past from fish oils, which have contents of up to 17%, while it is now mostly produced synthetically . ... 

There is growing concern in developed countries that the prevalence of chronic hypervitaminosis A may increase in future years. Vitamin A is available commercially without prescription in concentrations of 25,000-50,000 lU (Herbert,... 

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 hypervitaminosis A, recognized as a clinical entity in the mid-twentieth century, is more commonly observed and is a more subtle disease than the acute form. Many more cases of chronic hypervitaminosis A have been documented in children than in adults. 

The first human case of chronic hypervitaminosis A was described by Josephs (1944). A 3-year-old boy who had been given halibut liver oil (72 mg retinol equivalents/day for 3 months) presented with an enlarged liver and spleen and abnormal skeletal development. 

The most prominent signs of chronic hypervitaminosis A are cutaneous, including dryness of the mucous membranes. Laboratory abnormalities include radiologically detected bone changes in children, increased serum alkaline phosphatase, increased serum calcium, increased cerebrospinal fluid pressure, and disturbed blood clotting. Adverse effects associated with chronic hypervitaminosis A, in decreasing order of occurrence, are presented in Table V. 

Clinical Findings in Patients with Chronic Hypervitaminosis A in Decreasing Order of Occurrence"... 

Babb and Kieraldo (1978) reported a case of cirrhosis and portal hypertension attributable to hypervitaminosis A in a 72-year-old male who had been taking 12 mg/day of retinol for 6-7 years. Meunter et al. (1971) reviewed 17 cases of chronic vitamin A toxicity in patients receiving 12.3-180 mg retinol equiv-alents/day for several months up to 9 years. Two patients showed marked liver function impairment at 2i and 12 years, respectively, after discontinuing retinol. Marked elevations of plasma lipid levels were also noted. Deuel (1957) reported that hypervitaminosis A is accompanied by hyperlipidemia involving most of the plasma lipid fractions. 

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