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Hypovitaminosis C in patients treated with high-dose interleukin 2 and lymphokine-activated killer cells.

Patients (n = 15) with metastatic malignant melanoma, hypernephroma, and colon carcinoma received a three-phase adoptive immunotherapy protocol: phase 1, 10(5) units (high-dose) interleukin-2 (IL-2) iv every 8 h or 1 mg/m2 continuous intravenous infusion; phase 2, 6.5 d rest + leukapheresis; phase 3, 4 d of high-dose IL-2 plus three infusions of autologous lymphokine-activated killer cells. Toxicities of treatment included fever, chills, tachycardia, hypotension, vomiting, diarrhea, and fluid retention. Patients entering the trial were not malnourished, and mean plasma ascorbic acid concentrations before therapy were normal (36.3 +/- 14.2 mumol/L). Mean concentrations dropped by 80% after the first phase of treatment with high-dose IL-2 alone (to 7.4 +/- 4.5 mumol/L). Mean plasma ascorbic acid concentrations remained severely depleted (between 4.5 and 7.4 mumol/L) throughout the remainder of the 15-d treatment. Ascorbic acid concentrations became undetectable (less than 2.8 mumol/L) in 12/15 patients during this time. Blood pantothenate and plasma vitamin E concentrations remained within normal limits in all patients tested throughout the phases of therapy.

Adult↗

Asthma, inhaled oxidants, and dietary antioxidants.

The possible influence of dietary antioxidants, especially vitamin C, on the increasing prevalence of asthma is explored. Vitamin C intake in the general population appears to correlate with asthma, suggesting that a diet low in vitamin C is a risk factor for asthma. Epidemiological studies show associations among oxidant exposure, respiratory infections, and asthma in children of smokers. Symptoms of ongoing asthma in adults appear to be increased by exposure to environmental oxidants and decreased by vitamin C supplementation. There is evidence that oxidants produced endogenously by overactive inflammatory cells contribute to ongoing asthma. Vitamin C is the major antioxidant substance present in the airway surface liquid of the lung, where it could be important in protecting against both endogenous and exogenous oxidants. Nitrogen oxides are exemplary of oxidants that could arise from both endogenous and environmental sources, which are protected against by vitamin C, and that may be important in causation and propagation of asthma.

Administration, Oral↗

Ascorbate is depleted by smoking and repleted by moderate supplementation: a study in male smokers and nonsmokers with matched dietary antioxidant intakes.

BACKGROUND: Lack of reliable dietary data has hampered the ability to effectively distinguish between effects of smoking and diet on plasma antioxidant status. As confirmed by analyses of comprehensive food-frequency questionnaires, the total dietary intakes of fruit and vegetables and of dietary antioxidants were not significantly different between the study groups in the present study, thereby enabling isolation of the effect of smoking. OBJECTIVE: Our objective was to investigate the effect of smoking on plasma antioxidant status by measuring ascorbic acid, alpha-tocopherol, gamma-tocopherol, beta-carotene, and lycopene, and subsequently, to test the effect of a 3-mo dietary supplementation with a moderate-dose vitamin cocktail. DESIGN: In a double-blind, placebo-controlled design, the effect of a vitamin cocktail containing 272 mg vitamin C, 31 mg all-rac-alpha-tocopheryl acetate, and 400 microg folic acid on plasma antioxidants was determined in a population of smokers (n = 37) and nonsmokers (n = 38). The population was selected for a low intake of fruit and vegetables and recruited from the San Francisco Bay area. RESULTS: Only ascorbic acid was significantly depleted by smoking per se (P < 0.01). After the 3-mo supplementation period, ascorbic acid was efficiently repleted in smokers (P < 0.001). Plasma alpha-tocopherol and the ratio of alpha- to gamma-tocopherol increased significantly in both supplemented groups (P < 0.05). CONCLUSIONS: Our data suggest that previous reports of lower concentrations of plasma vitamin E and carotenoids in smokers than in nonsmokers may primarily have been caused by differences in dietary habits between study groups. Plasma ascorbic acid was depleted by smoking and repleted by moderate supplementation.

Adult↗

Vitamin C status and mortality in US adults.

BACKGROUND: Low vitamin C status may increase the risk of mortality from cancer and cardiovascular disease. OBJECTIVE: The objective was to test whether an association existed between serum ascorbate concentrations and mortality and whether the association was modified by cigarette smoking status or sex. DESIGN: Serum ascorbate concentrations were measured in adults as part of the second National Health and Nutrition Examination Survey (1976-1980). Vital status was ascertained 12-16 y later. RESULTS: The relative risk (RR) of death, adjusted for potential confounders, was estimated by using Cox proportional hazards models. Men in the lowest (<28.4 micromol/L) compared with the highest (>/=73.8 micromol/L) serum ascorbate quartile had a 57% higher risk of dying from any cause (RR: 1.57; 95% CI: 1.21, 2.03) and a 62% higher risk of dying from cancer (RR: 1.62; 95% CI: 1.01, 2.59). In contrast, there was no increased risk among men in the middle 2 quartiles for these outcomes and no increased risk of cardiovascular disease mortality in any quartile. There was no association between serum ascorbate quartile and mortality among women. These findings were consistent when analyses were limited to nonsmokers or further to adults who never smoked, suggesting that the observed relations were not due to cigarette smoking. CONCLUSIONS: These data suggest that men with low serum ascorbate concentrations may have an increased risk of mortality, probably because of an increased risk of dying from cancer. In contrast, serum ascorbate concentrations were not related to mortality among women.

Adult↗

Iron deficiency anemia: higher prevalence in Mexican American than in non-Hispanic white females in the third National Health and Nutrition Examination Survey, 1988-1994.

BACKGROUND: Mexican American females have a higher prevalence of iron deficiency than do non-Hispanic white females. OBJECTIVE: The objective was to estimate the prevalence of iron deficiency anemia and examine potential reasons for this difference between Mexican American (n = 1194) and non-Hispanic white (n = 1183) females aged 12-39 y. DESIGN: We used data from the third National Health and Nutrition Examination Survey (1988-1994). Iron deficiency anemia was defined as abnormal results from >/=2 of 3 tests (erythrocyte protoporphyrin, transferrin saturation, and serum ferritin) and a low hemoglobin concentration. We used multiple logistic regression to adjust for factors that were more prevalent in Mexican American females and significantly associated with iron deficiency anemia. RESULTS: The prevalence of iron deficiency anemia was 6.2 +/- 0.8% (f1.gif" BORDER="0"> +/- SE) in Mexican American females and 2.3 +/- 0.4% in non-Hispanic white females. Mean dietary iron intake, mean serum vitamin C concentrations, and the proportion of females using oral contraceptives were similar in the 2 groups. Age <20 y and education were not associated with iron deficiency anemia. After adjustment for poverty level, parity, and iron supplement use, the prevalence of iron deficiency anemia was 2.3 times higher in Mexican American than in non-Hispanic white females (95% CI: 1.4, 3.9). In those with a poverty income ratio (based on household income) >3.0, however, the prevalence of iron deficiency anemia was 2.6 +/- 0.9% in Mexican American and 1.9 +/- 0.6% in non-Hispanic white females (NS). CONCLUSION: Although much of the ethnic disparity in iron deficiency anemia remains unexplained, factors associated with household income may be involved.

Adolescent↗

Ascorbyl palmitate enhances iron bioavailability in iron-fortified bread.

BACKGROUND: One of the strategies to control iron deficiency anemia is the fortification of food with iron. A mechanism for improving the bioavailability of iron is to add an iron absorption promoter. OBJECTIVE: The objective was to determine the effect of ascorbyl palmitate (AP) on the bioavailability of iron in fortified bread made from refined wheat flour. DESIGN: The iron bioavailability of wheat flour fortified with either ferrous sulfate alone or ferrous sulfate plus AP was studied with the use of double radio iron (55Fe and 59Fe) erythrocyte incorporation in 14 women. RESULTS: Geometric mean (+/- range of 1 SD) iron absorption from the bread fortified with ferrous sulfate was 10.5% (4.1-27.0%). The addition of AP at molar ratios of AP to Fe of 2:1 and 4:1 significantly increased iron absorption [14.6% (5.9-36.1%) and 20.2% (10.6-38.6%), respectively; P < 0.001]. CONCLUSION: AP is a strong promoter of iron absorption from fortified bread because of its thermoresistant properties.

Adult↗

Brown bowel.

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Ascorbic Acid Deficiency↗

Lack of effect of ascorbic and citric acids on calcium metabolism of chickens.

Five experiments were carried out in which various levels of calcium and ascorbic acid or citric acid were fed to adult male chickens, young chickens, or young coturnix. Observations were made on body weight, feed efficiency, plasma calcium and tibia mineral content. One percent dietary ascorbic acid had no adverse effect on body weight, tibia ash or tibia calcium content of adult male chickens over a 224-day period, even at calcium levels as low as 0.026% of the diet. In growing chicks, body weight and plasma calcium and tibia mineral content varied with the calcium level of the diet, but were not influenced by ascorbic acid even at 0.65% of the diet. Citric acid at the same molar level was also ineffective in altering calcium metabolism in growing chickens. Growing coturnix showed differences in growth and tibia ash content with 0.4% and 0.85% calcium, but there were no pronounced effects caused by dietary ascorbic acid. There is no evidence in this work that these relatively high levels of ascorbic acid or citric acid have any adverse effect on calcium metabolism because of their chelating properties.

Animals↗

Effect of ascorbic acid nutriture on protein-bound hydroxyproline in guinea pig plasma.

This paper provides indirect evidence that ascorbate nutriture affects plasma concentrations of complement component C1q in the guinea pig. C1q is a protein with a hydroxyproline-rich region similar in structure to collagen. It is essential for complement-mediated lysis of pathogens and may also facilitate phagocytic activity of macrophages and neutrophils. Since C1q is the only hydroxyproline-containing protein in the euglobulin fraction of plasma, it can be quantified indirectly by precipitating this fraction, hydrolyzing it and estimating hydroxyproline colorimetrically. We investigated the effect of ascorbate nutriture on protein-bound hydroxyproline (PBH) in the euglobulin fraction of plasma of young male guinea pigs. The animals had been depleted of ascorbate for 3 wk to produce scurvy and then repleted (6 wk) as follows: 0.5, 2.0 and 10.0 mg ascorbate/100 g body weight per d or 10 g ascorbate per liter of drinking water. PBH values were significantly correlated (P less than 0.001) with dietary ascorbate (+ 0.74) and with liver ascorbate (+ 0.75). Plasma PBH was significantly higher (P less than 0.01, Scheffé's test) in guinea pigs fed ample ascorbate (10.0 mg/100 g body weight per day) or tissue-saturating levels (10 g/L of drinking water) than in those fed adequate (2.0 mg/100 g body weight) or suboptimal (0.5 mg/100 g body weight) levels. These data are consistent with the known biochemical role of ascorbic acid in hydroxyproline biosynthesis and suggest a possible link between ascorbate and the immune response via C1q.

Animals↗

Effect of ascorbic acid on guinea pig adrenal adenylate cyclase activity and plasma cortisol.

Intra-adrenal ascorbic acid (AsA) concentrations exert a braking or modulating effect upon steroid release. Because changes in steroidogenesis are mediated through alterations in adenylate cyclase activity (ACL), the effect of varied AsA plasma concentrations on guinea pig adrenal ACL activity and plasma cortisol was studied. Forty-two male guinea pigs were randomly allocated to the following seven groups: controls, scorbutic, and groups given 0.1, 5, 10, 20 or 100 mg ascorbic acid/100 g body weight, respectively. Scorbutic animals had very low levels of AsA in comparison to control animals. Plasma AsA levels increased as AsA dose increased. The levels of AsA in the group given 0.1 mg AsA were higher than in controls. Basal adenylate cyclase activity did not vary significantly among animal groups. In contrast, values for NaF-stimulated ACL activity showed a progressive decrease with increasing AsA doses. A highly significant correlation was found between decreasing ACL activity and increasing plasma AsA concentrations. On the other hand, NaF-responsive ACL activity was higher in scorbutic animals than in any other group. Higher mean cortisol values were found in the scorbutic group than in the controls, correlating with high levels of NAF-stimulated ACL activity. Higher mean cortisol values were also found in the group given 0.1 mg AsA although ACL activity in this group was not affected. This finding, coupled with reduced ACL activity in these groups, is consistent with the inhibitory effect of a megadose of AsA on production of cortisol from the adrenal. The above data may suggest that differing plasma concentrations of AsA regulate in vivo steroidogenesis by altering the activity of the membrane-bound enzyme adenylate cyclase.

Adenylyl Cyclases↗