Evidence for a recommended dietary allowance for vitamin C from pharmacokinetics: a comment and analysis

The current recommended dietary allowance (RDA) for vitamin C, as proposed by the Food and Nutrition Board/National Research Council in 1980 and reconfirmed in 1989, is 60 mg daily for nonsmoking adult males. Levine et al. [Levine, M., Conry-Cantilena, C., Wang, Y., Welch, R. W., Washko, P. W., et al. (1996) Proc. Natl. Acad. Sci. USA 93, 3704-3709], based on a study of vitamin C pharmacokinetics in seven healthy men, have now proposed that the RDA should be increased to 200 mg daily. I have examined, in brief, the experimental and conceptual bases for this new recommendation and its implications for public health and nutrition policy and programs. Using, for illustrative purposes only, data extracted from each of two recent dietary surveys of noninstitutionalized adult males living in households in the Netherlands and the United States, it is predicted that the prevalence of intakes inadequate to meet the individual's own requirement would be about 96% or 84%, respectively, if the criteria of adequacy used for derivation of the 200 mg RDA are accepted. Depending upon the particular average requirement value for ascorbic acid that might be derived from their data, the proposal by Levine et al. would mean a desirable increase in mean intakes in these two populations by as much about 2-to 3-fold. Hence, before an action of this kind is to be recommended, an answer must be sought to the question whether current experimental data including the criteria selected (saturation kinetics) are adequate to establish a new set of requirements for vitamin C, which then carry such profound policy implications. This will require critical assessment of all of the available evidence emerging from laboratory, clinical, and epidemiological studies to determine whether it provides a sufficient rationale for accepting criteria of vitamin C adequacy such as those proposed by Levine et al. and the requirement estimates so derived.     

Persistent acute renal failure with renal artery stenosis: cure following reconstructive arterial operation

A case of acute renal failure is reported in which renal function returned after surgical correction of renal artery stenosis to the sole functioning kidney. Acute renal failure associated with renal vascular lesions is reviewed. Although often clinically apparent vascular obstruction may be asymptomatic and should be considered in cases of prolonged acute renal failure.     

A case-control study of menopausal estrogen therapy and breast cancer

The association between estrogen replacement therapy and female breast cancer was studied in two Los Angeles area retirement communities. The 138 study cases of breast cancer occurring in residents younger than 75 years were compared with age- and race-matched community control subjects. The risk ratio for a total cumulative dose in excess of 1,500 mg was estimated to be 2.5 in women with intact ovaries. This increase was present using various independent sources of drug usage information but was inconsistent at low dose and undetectable in oophorectomized women. No important sources of confounding could be identified, and no risk modifiers could be identified except for a history of surgically confirmed benign breast disease. In such women with intact ovaries, the risk ratio for a high cumulative dose rose to 5.7 relative to nonusers with normal breasts.     

Terminal (1)(q43) long-arm deletion of chromosome no. 1 in a three-year-old female

A 3-year-old Latin female is reported with a terminal deletion of the No. 1 chromosome, karyotype formula 46, XX, del(1) (q43). Principle clinical features include: Anatomic - microcephaly; bilateral, convergent strabismus; epicanthus; brachycephaly; bulbar nose; sparse hair; partial soft tissue syndactylism between 2nd and 3rd fingers which are slightly tapered; whorls on all 10 fingers; mild prognathism; solitary kidney; vaginal stenosis; vesicoureteral reflux; asymmetric feet; and subluxation of peroneal tendons around the fibula with severe pronation and heal valgus deformity. Neurologic - moderate motor and mental retardation; high-pitched, shrill cry; absent pincer grasp at 3 years; and grand mal seizures documented from 9 months of age.     

The effect of respiratory immunization on cell-mediated immune effector cells of the lung

In order to understand the mechanisms of cellular immune injury in hypersensitivity pneumonitis, the effect of type of antigen on cell-mediated immunity in guinea-pigs receiving respiratory immunization was studied. Lymphocytes obtained by pulmonary lavage were compared with those from peritoneal exudate following immunization with either a soluble protein, human serum albumin, or a particulate suspension of Thermoactinomyces vulgaris. Assays were obtained without mixing cells from these two sources. Statistically significant increases (13-22%) in the number of alveolar rosette-forming cells (RFC) were found in the animals immunized with either antigen, but only the particulate T. vulgaris was also capable of inducing a systemic increase of such cells. That this increase in RFC could be due to specifically reactive lymphocytes was demonstrated by the production of antigen-stimulated macrophage migration inhibition. Some evidence was obtained that indicated that T. vulgaris could act both as a non-specific B-cell stimulant and a specific T-cell activator. The concept of a hypothetical pulmonary 'barrier' is discussed which must be overcome to induce systemic immune responses following respiratory immunization. T. vulgaris must be added to the list of known agents or means for overcoming this 'barrier'.     

Outcome of unsuspected pneumococcemia in children not initially admitted to the hospital

The records were reviewed of 97 episodes of unsuspected pneumococcemia in children not initially admitted to the hospital. Antimicrobial agents were prescribed at the first visit for 46 children; at the second visit 37 of them were improved and nine were not. No antimicrobial agents were prescribed at the first visit for 51; at the second visit 16 of these patients were improved and 35 were not. Pneumococcemia persisted in two treated children and in 13 untreated children. Meningitis was identified later in four children (two treated and two untreated). Although pneumococcemia in children may be a transient event, it may also persist or result in meningitis or other localized infections.