Safety Of Vitamin Research Articles

Vitamin C-induced erythrocyte damage in premature infants

This study was undertaken after the observation in a premature infant of a hemolytic anemia with Heinz bodies that appeared to result from administration of a multivitamin preparation. In vitro incubation of erythrocytes of premature infants with sodium ascorbate (0.1 mg/ml) for 3 hours significantly raised the number of Heinz body-containing cells from 17.6 +/- 5.7% to 27.2 +/- 8.2% (mean +/- SE). Erythrocytes of term infants and those of adults developed Heinz bodies after exposure to higher sodium ascorbate concentrations (1.0 mg/ml). Erythrocytes of adult and newborn guinea pigs were similarly affected by sodium ascorbate. Daily intraperitoneal injections of 500 mg of sodium ascorbate, given for 7 days to four adult guinea pigs, caused significant Heinz body formation. These studies indicate that the erythrocytes of premature infants are uniquely sensitive to the development of Heinz bodies after exposure to sodium ascorbate. The levels required to produce Heinz bodies in vitro are in the range of those found in vivo after routine administration of vitamin C to premature infants. The significance of these observations in the development of hyperbilirubinemia in premature infants and in the safety of vitamin C remains to be determined.

Tocopherol Efficacy and Safety for Preventing Retinopathy of Prematurity: A Randomized, Controlled, Double-Masked Trial

To test the efficacy and safety of vitamin E in preventing retinopathy of prematurity, 287 infants with birth weights of less than 1.5 kg or gestational ages of less than 33 weeks were enrolled within 24 hours of birth in a randomized, double-masked trial of IV, followed by oral, placebo v tocopherol (adjusted to plasma levels of 3 to 3.5 mg/dL). In the 196 infants completing ophthalmic follow-up, tocopherol did not prevent retinopathy of prematurity of any stage (28% placebo treated v 26% tocopherol treated) or moderately severe retinopathy of prematurity (8% placebo treated v 11% tocopherol treated). Cicatricial sequelae were not significantly different (1/97 placebo treated v 3/99 tocopherol treated), with one placebo-treated infant and one tocopherol-treated infant having retinal detachments. Among all 232 infants examined, those treated with tocopherol had more retinal hemorrhage than placebo-treated infants (8/121 placebo treated v 16/111 tocopherol treated), and retinal hemorrhage correlated positively (P less than .01) with plasma levels of tocopherol after the first 2 weeks of age. Prospective monitoring of morbidity including late-onset sepsis, necrotizing enterocolitis, etc revealed no differences between groups except that grades 3 and 4 intraventricular hemorrhage occurred more frequently in infants weighing less than 1 kg at birth who had received tocopherol (14/42, 33%) v those who had received placebo (4/43, 9%) (P less than .02). Our data do not support the use of tocopherol for prophylaxis against retinopathy of prematurity in premature infants and suggest that IV tocopherol treatment starting on day 1 may increase the incidence of hemorrhagic complications of prematurity, particularly in infants with birth weights of less than 1 kg.

COMMITTEE ON NUTRITION

FOR MORE than 40 years it has been known that vitamin D is essential for maintenance of normal calcium metabolism in man. Efforts over this period have been directed toward establishing an adequate intake of vitamin D throughout the population. National advisory committees in many countries have formulated recommended allowances for the various age groups, public health education programs have stressed the need for the vitamin and the value of sunshine, and the vitamin has been made available to the population at large through provision of inexpensive vitamin supplements and, more recently, the enrichment of milk and a number of commonly used foodstuffs. In consequence, vitamin D deficiency rickets, once a common pediatric problem, is now relatively rare in the United States and other parts of the world. On the other hand, it has also long been known that vitamin D is potentially dangerous in very high dosage. It had been thought originally that the margin of safety between the requirement of vitamin D and its toxic dosage was very great. However, reports from Great Britain and Switzerland in 1952 drew attention to a group of infants with unexplained hypercalcemia. Additional cases of infantile hypercalcemia began to appear throughout the British Isles, and patients with mild or severe manifestations have been reported in the United States, Canada, and elsewhere. On the basis of circumstantial evidence, vitamin D was implicated in the pathogenesis of the disease, and, as a result, there has been a growing question about the safety of vitamin D intakes which appreciably exceeded the 400 I.U. daily allowance currently recommended for prevention of vitamin D deficiency during growth, pregnancy, and lactation.