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Vitamin C status and possible associations with the disease process in cystic fibrosis (CF) patients were investigated. Plasma vitamin C concentrations in patients from two different mid-European populations (Swiss, n = 62; Austrian, n = 60) taking no or low-dose vitamin C from multivitamin supplements did not differ from each other or from control subjects (n = 34). Vitamin C concentrations decreased with age (5.05 [Mu]mol .[L.sup.-1].[y.sup.-1]. When followed up for 12 mo, patients had the highest plasma vitamin C concentrations in February and the lowest in May and August (P [is less than] 0.01); the decrease in vitamin C was accompanied by increases in plasma malondialdehyde (P [is less than] 0.001) and tumor necrosis factor [Alpha] concentrations (P [is less than] 0.01). During supplementation with vitamin E for 2 mo or [Beta]-carotene for 12 mo vitamin C concentrations did not change. They correlated inversely with white blood cell count (r = -0.36, P = 0.008), bands (r = -0.36, P = 0.02), [[Alpha].sub.1]-acid glycoprotein (r = -0.45, P = 0.002), interleukin 6 (r = -0.46, P = 0.0006), and neutrophil elastase/[[Alpha].sub.1]-proteinase inhibitor complexes (r = -0.34, P = 0.02). In patients with vitamin C concentrations [is less than] 40 [Mu]mol/L, all indexes of inflammation were relatively high, whereas those with concentrations [is less than] 80 [Mu]mol/L (upper quartile of control subjects) showed clearly lower values. These results are consistent with the hypothesis that by scavenging oxygen free radicals vitamin C interacts with an inflammation-amplifying cycle of activation of alveolar macrophages and neutrophils, release of proinflammatory cytokines and oxygen free radicals, and inactivation of antiproteases.

To conduct an inpatient study on the recommended dietary allowance (RDA) for vitamin C, we developed a unique vitamin C-deficient diet using a nutrient database and selective menus. Fourteen different menus were developed offering [is greater than] 300 items with 0-2.4 mg vitamin C per serving. During the 4-6 mo volunteers were hospitalized, daily dietary vitamin C was restricted to [is less than or equal to] 5.0 mg. The mean daily dietary vitamin C intake was [is less than] 3.9 mg for the seven study subjects. With concurrent supplementation, the diet provided [is greater than or equal to] 85% of the RDA for 17 essential nutrients. Within 3 wk of admission the diet induced vitamin C deficiency as indicated by plasma concentrations, which decreased from 23 [+ or -] 6.9 to 6.9 [+ or -] 2.0 [micro] mol/L. Daily intake of vitamin C and five other nutrients was determined by nutrient database analyses. Mean energy, protein, and iron were 105-185% of the RDA and total and saturated fat were 32% and 10% of energy, respectively. Weight and nutritionally relevant indexes remained normal. Dietary adherence, calculated by the number of days with [is less than or equal to] 5.0 mg vitamin C per total study days, was 88-98% per repletion dose. Computer analyses of menu selections permitted individual preferences to be met while restricting vitamin C intake to [is less than or equal to] 5.0 mg/d. There were no complications from the diet during the depletion and repletion phases. With this diet, ascorbic acid pharmacokinetics for escalating doses could be determined in healthy volunteers.

Using a reliable, newly developed assay for ascorbic acid (reduced form) and dehydroascorbic acid (DHAA; the oxidized form) in plasma, we studied the influence of age, sex, and smoking on 219 healthy, age-stratified, and randomly selected subjects representing the Danish population. The mean ([+ or -] SD) plasma total ascorbic acid (ascorbic acid + DHAA) concentration was lower in smokers (62.8 [+ or -] 24.9 [Mu]mol/L) than in nonsmokers (74.9 [+ or -] 23.6 [Mu]mol/L) (P < 0.001) and the DHAA content was 1.8 [+ or -] 4.0% of the total ascorbic acid in smokers compared with 0.1 [+ or -] 3.1% in nonsmokers (P < 0.001). A significant inverse correlation between the DHAA fraction and the total ascorbic acid concentration was found in smokers (P < 0.002) but not in smokers; the slopes of the linear regressions were significantly different in the two groups (P < 0.002). The mean plasma concentration of total ascorbic acid was higher in females than in males (P < 0.005); this difference persisted in multivariate analysis when smoking was adjusted for. No age dependence could be identified. The data show that smoking results in severe oxidative stress, depletion of the ascorbic acid pool, and insufficient reduction capacity to maintain ascorbic acid in the reduced form in plasma. We suggest that the additional analysis of DHAA allows further differentiation in the assessment of oxidative stress and may provide an objective way of determining vitamin C requirements in smokers. Preliminary findings suggest that a vitamin C dose that results in a plasma concentration of [nearly equal] [Mu]mol/L or higher is required in smokers. Am J Clin Nutr 1997;65: 959-63.

Background: Low-fat soluble-antioxidant status is associated with an increased risk of heart disease. Objective: The aim of this study was to examine whether low plasma concentrations of vitamin C confer an independent risk of acute myocardial infarction (AMI). Design: Male patients (n = 180) aged [is less than]65 y with a first AMI and without an existing diagnosis of angina ([is greater than]6 mo) who were admitted within 12 h after onset of symptoms were compared with apparently healthy volunteers (n = 177). Plasma concentrations and dietary intakes of vitamin C were determined during hospitalization and 3 mo later. Results: Compared with the control subjects, the patients had higher total cholesterol and lower HDL-cholesterol concentrations and more of them smoked. The relative risk of AMI for the lowest compared with the highest quintile of plasma vitamin C during hospitalization (14.5 and [is greater than]60.5 [Mu]mol/L, respectively) was 8.37 (95% CI: 3.28, 21.4) after adjustment for classic risk factors. At 3 mo, mean ([+ or -] SEM) plasma vitamin C concentrations in patients had increased significantly, from 19.6 [+ or -] 1.2 to 35.1 [+ or -] 1.9 [Mu]mol/L (P [is less than] 0.001) and no longer conferred a risk of AMI [relative risk: 1.02 (95% CI: 0.51, 2.03)]. Habitual dietary vitamin C intake of patients (before AMI) did not differ significantly from that of control subjects. The increase in plasma vitamin C after recovery from the infarction could not be explained by a similarly large increase in dietary vitamin C. Conclusions: A low plasma concentration of vitamin C was not associated with an increased risk of AMI, irrespective of smoking status. The apparent risk of AMI due to a low plasma vitamin C concentration was distorted by the acute phase response. Am J Clin Nutr 2000;71:1181-6. KEY WORDS Vitamin C, ascorbic acid, acute myocardial infarction, smoking, acute phase response, risk, diet, men, Scotland

Background: Endogenous reactive oxygen species appear to contribute to aging and cancer and dietary antioxidants, present in fruit and vegetables, counteract these effects. Objective: The objective was to examine the association between intracellular glutathione, ascorbate (vitamin C), and [Alpha]-tocopherol (vitamin E) in human lymphocytes. Design: The study group consisted of 240 healthy nonsmoking volunteers with an approximately equal number of male and female subjects subdivided into 3 age groups: 18-39, 40-59, and [is greater than or equal to] 60 y). Glutathione, glutathione disulfide, ascorbate, and [Alpha]-tocopherol were measured in lymphocytes by HPLC. Results: The average concentration of antioxidants in lymphocytes was 27 [+ or -] 8 nmol/mg protein for glutathione, 21 [+ or -] 8 nmol/mg protein for ascorbate, and 0.4 [+ or -] 0.2 nmol/mg protein for [Alpha]-tocopherol. There was a strong positive correlation between glutathione and ascorbate (r = 0.62, P [is less than] 0.001). No correlation was observed for glutathione and ascorbate with [Alpha]-tocopherol. The concentration of glutathione in lymphocytes was inversely correlated with age (r = - 0.19, P [is less than] 0.01), as was that of ascorbate (r = - 0.22, P [is less than] 0.01), with 10-20% lower values in elderly than in young and elderly subjects. The concentrations of glutathione in lymphocytes were as much as 25% higher and those of ascorbate were as much as 38% higher during the summer than during the winter. The seasonal variation of ascorbate in lymphocytes was described by a linear function for age and a periodic sine function for season. Conclusion: Glutathione and ascorbate are directly correlated in human lymphocytes. Am J Clin Nutr 2000;71:1194-200. KEY WORDS Vitamin C, vitamin E, glutathione, lymphocytes, ascorbic acid, antioxidants, micronutrients, aging, elderly, cancer, reactive oxygen species, season