The risk of abuse of vitamin supplements.

The article presents the results of studies on potential risks associated with the abuse of vitamin supplements which until recently had been considered not only highly effica- cious, but also completely safe. Particular consideration is given to vitamins A, E, D and C. The necessity to control the intake of vitamin supplements and even to strictly super- vise the supply to high risk patients is highlighted.

Fatal vitamin C-associated acute renal failure.

Although daily ingestion of high-dose vitamin C is generally regarded as largely innocuous, fatal nephrotoxicity can occur in some rare circumstances. We report a case where the patient, who chose to forgo any advanced conventional medical intervention (dialysis and mechanical ventilation), had failed to disclose his use of high-dose vitamin C and subsequently died. Intra-renal oxalate crystal deposition was demonstrated at autopsy. Directed enquiry with the family then revealed his high-dose vitamin C usage. Even though fully-informed discussion was limited by incomplete prospective disclosure, it remains the prerogative of any competent patient to decline any treatment, including those that may be considered life-saving.

Evaluation of subchronic chlorpyrifos poisoning on hematological and serum biochemical changes in mice and protective effect of vitamin C.

Chlorpyrifos (CPF) is one of the most widely used organophosphorous insecticides in agriculture with its attendant adverse health outcomes. This study aimed at evaluating the effect of subchronic oral CPF administration on hematological and serum biochemical indices, and the possible ameliorating effect of vitamin C on the indices in mice. Thirty mice divided into 3 groups of 10 mice each were used for this study. Mice in group I (control) were dosed with vegetable oil, while those in group II were given CPF (21.3 mg/kg~ 1/5(th) LD(50)) only. Mice in group III were pretreated with vitamin C (100 mg/kg) prior to dosing with CPF 30 min later (Vitamin C + CPF-treated group). This regime was given to each group of mice three times a week for a period of ten weeks. During the study period, mice were examined for signs of toxicity, and weight of each mouse was measured every week. At the end of the study period, blood samples were collected from the mice and analyzed for packed cell volume (PCV), total red blood cell (RBC), white blood cell (WBC) and total protein (TP). Serum obtained from the blood was analyzed for Na( +, K+ and Cl-), urea, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). The results showed that mice in the vitamin C + CPF-treated group exhibited milder signs of toxicity and significant increase in weight gain (p<0.01) compared to the CPF-treated group. No significant increase in weight in the CPF-treated group was observed compared to the control. There was a significant increase in PCV, RBC, Hb, TP and creatinine, but a significant decrease was obtained in WBC, ALT and AST in the CPF-treated group compared to the control. All the parameters with the exception of WBC, ALT and AST (which increased significantly), were significantly decreased in the vitamin C + CPF-treated group compared to CPF-treated group. ALP was significantly elevated in the CPF-treated group compared to both the control and vitamin C + CPF-treated group. No significant changes in urea and the measured electrolytes in all three groups, except a significant decrease in the concentration of Na(+) was observed in the CPF-treated group compared to the control. The study demonstrated that pretreatment of CPF-administered mice with vitamin C significantly altered some important hematological and serum biochemical parameters, revealing the protective action of the vitamin against some organ damage induced by CPF.

Middle molecules: toxicity and removal by hemodialysis and related strategies.

Renal failure results in the retention of metabolites which may arbitrarily be grouped according to their molecular weight: low (< 300 daltons molecular weight), middle (300-15,000 daltons), and high (> 15,000 daltons). Opinion in respect to the relative importance of these groups varies. Initially it was thought that small molecules were important. In the mid-1970s, investigators identified the possible pathophysiological role of middle molecules. However, since positive identification of such molecules was difficult, opinion has shifted back in favor of small molecules, and little attention, with the exception of beta 2 microglobulin, has been paid to middle molecules and their removal by hemodialysis and related therapies. In this review current knowledge regarding middle molecules identified as uremic toxins and their removal by hemodialysis and associated therapies are discussed.

[Severe Vicedrin poisoning in a 17-month-old girl]. / Tezká intoxikace Vicedrinem u 17 mesícního devcátka.

The child ingested 7 tabl. of VICEDRIN (a combination of phenacetin, ephedrin, chinin, acid. ascorbicum), the total dose of phenacetin was 140 mg/kg of b.w. Lethal doses of phenacetin vary between 100-200 mg/kg, the sensitivity to phenacetin being increased in infants. Toxicological examination in this case revealed a high concentration of phenacetin in urine. The clinical signs of intoxication were vomiting (hematemesis), methemoglobinemia and somnolence. 2 hemoperfusions were performed lasting 6 hrs and 5 hrs resp. (HEMASORB 400 A 4), the second one were combined with hemodialysis because after the first perfusion a high concentration of metabolic products of phenacetin was detected in urine. After the second perfusion the status of the child rapidly improved and we could discharge the patient of the 10th day after admission. Hemoperfusion is recommended in severe intoxication with phenacetin, the combination with, hemodialysis is possible to remove its metabolic product.

[Massive hemoptysis ten days after bronchial extraction of an accidentally inhaled tablet of ferrous sulfate]. / Hémoptysie massive dix jours après extraction bronchique d'un comprimé de sulfate ferreux inhalé accidentellement.

Fatale haemoptysis occurred as a result of circumferential caustic erosion to the right intermediate bronchus caused by a tablet of ferrous sulphate which remained in contact for 4 days. The necrotic process continued, after removal of the foreign body, in the bronchial wall and its vessels. We suggest local bronchial lavage with 1% bicarbonate saline during extraction of the tablet and subsequent follow-up fibroscopies. The discovery of a necrotic ulceration of the bronchus requires strict medico-surgical surveillance in order to rapidly intervene under cover of selective intubation when necessary.

Acute oxalate nephropathy after massive ascorbic acid administration.

A single 45-g dose of intravenous ascorbic acid, a metabolic precursor of oxalate, was administered to a patient as adjuvant therapy for primary amyloidosis and the nephrotic syndrome. Acute oliguric renal failure occurred. Postmortem histopathologic examination of renal tissue revealed extensive intratubular deposition of crystalline material, which was confirmed as calcium oxalate by a microincineration technique. There were no extrarenal deposits of calcium oxalate. Plasma oxalate and ascorbic acid concentrations were increased. We conclude that therapy with high-dose ascorbic acid is a potential cause of oxalate nephropathy.

Vitamin C intoxication and hyperoxalemia in chronic hemodialysis patients.

We studied vitamin C levels in 25 stable patients on chronic hemodialysis who were taking 0.5-1 g vitamin C orally daily and/or dialyzed against dialysate containing 33.3 micrograms/ml of vitamin C. We also studied the relationship between serum vitamin C and oxalate levels in 7 patients on chronic hemodialysis. All patients had markedly elevated pre- and postdialysis levels of vitamin C. The predialysis levels of vitamin C showed extremely good correlation to the serum oxalate levels. Overingestion of vitamin C in food or as supplementation may lead to excessive serum levels of vitamin C, resulting in hyperoxalemia that may contribute to vascular disease in patients on chronic hemodialysis.

Tolerance and effects of high doses of ascorbic acid. Dosis facit venenum.

The few literature references suggesting adverse effects of high doses of ascorbic acid are outnumbered by a large number of clinical studies in which no adverse effects have been observed. Up to 5 g ascorbic acid daily may be administered safely even over a long term. Favourable effects of even higher doses in man may justify therapeutic trials in the range of 15 g daily which in our trials have proven safe during treatment of up to 2 years. Nevertheless, trials in the high dosage range mentioned should always be closely supervised by a physician, being aware that exceptional behaviour can occur at any time, as exception proves the rule.

Influence of chronic ascorbic acid deficiency and excessive ascorbic acid intake on bile acid metabolism and bile composition in the guinea pig.

The influence of chronic ascorbic acid (AA) deficiency and excessive ascorbate consumption on bile acid metabolism, liver and plasma cholesterol levels, hepatic microsomal cytochromes and biliary lipid composition was investigated. Male weanling guinea pigs were fed a cereal-based scorbutigenic diet supplemented with four levels of AA for 7 weeks: deficient, 15 and 30 mg/kg; control, 500 mg/kg; and excess, 20,000 mg/kg. Bile acid kinetic parameters were determined following the intraperitoneal administration of [24-14C] chenodeoxycholic acid. Dietary extremes of AA caused similar alterations in the parameters studied. Relative to the control group, the deficient and excess groups exhibited reduced cytochrome P-450 concentration, lower cholesterol 7 alpha-hydroxylase activity, lower bile acid turnover rate, prolonged bile acid half-life and increased plasma and liver cholesterol concentrations. Deficient and excess groups also exhibited lower biliary cholesterol saturation (i.e., increased bile acid-neutral sterol ratios) than controls. Urinary bile acid excretion was 2- to 3-fold higher in excess guinea pigs than in the other three groups. The data demonstrate the exceptional susceptibility of cholesterol 7 alpha-hydroxylase activity to alteration by dietary extremes of AA, resulting in marked inhibition of bile acid synthesis and elevation of cholesterol levels by both inadequate and excessive AA intake.