5

Vitamin C

SUMMARY

Vitamin C functions physiologically as a water-soluble antioxidant by virtue of its high reducing power. It is a cofactor for enzymes involved in the biosynthesis of collagen, carnitine, and neurotransmitters in vitro, and it can quench a variety of reactive oxygen species and reactive nitrogen species in aqueous environments. Evidence for in vivo antioxidant functions of ascorbate include the scavenging of reactive oxidants in activated leukocytes, lung, and gastric mucosa, and diminished lipid peroxidation as measured by urinary isoprostane excretion. To provide antioxidant protection, a Recommended Dietary Allowance (RDA) of 90 mg/day for adult men and 75 mg/day for adult women is set based on the vitamin C intake to maintain near-maximal neutrophil concentration with minimal urinary excretion of ascorbate. Because smoking increases oxidative stress and metabolic turnover of vitamin C, the requirement for smokers is increased by 35 mg/day. Estimates of median dietary intakes of vitamin C for adults are 102 mg/day and 72 mg/day in the United States and Canada, respectively. The Tolerable Upper Intake Level (UL) for adults is set at 2 g/day; the adverse effects upon which the UL is based are osmotic diarrhea and gastrointestinal disturbances.

BACKGROUND INFORMATION

Vitamin C is a water-soluble vitamin that is essential for all humans and a few other mammals that lack the ability to biosynthesize the compound from glucose because they lack the enzyme gulono-



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement



Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.

OCR for page 95
DRI DIETARY REFERENCE INTAKES FOR Vitamin C, Vitamin E, Selenium, and Carotenoids 5 Vitamin C SUMMARY Vitamin C functions physiologically as a water-soluble antioxidant by virtue of its high reducing power. It is a cofactor for enzymes involved in the biosynthesis of collagen, carnitine, and neurotransmitters in vitro, and it can quench a variety of reactive oxygen species and reactive nitrogen species in aqueous environments. Evidence for in vivo antioxidant functions of ascorbate include the scavenging of reactive oxidants in activated leukocytes, lung, and gastric mucosa, and diminished lipid peroxidation as measured by urinary isoprostane excretion. To provide antioxidant protection, a Recommended Dietary Allowance (RDA) of 90 mg/day for adult men and 75 mg/day for adult women is set based on the vitamin C intake to maintain near-maximal neutrophil concentration with minimal urinary excretion of ascorbate. Because smoking increases oxidative stress and metabolic turnover of vitamin C, the requirement for smokers is increased by 35 mg/day. Estimates of median dietary intakes of vitamin C for adults are 102 mg/day and 72 mg/day in the United States and Canada, respectively. The Tolerable Upper Intake Level (UL) for adults is set at 2 g/day; the adverse effects upon which the UL is based are osmotic diarrhea and gastrointestinal disturbances. BACKGROUND INFORMATION Vitamin C is a water-soluble vitamin that is essential for all humans and a few other mammals that lack the ability to biosynthesize the compound from glucose because they lack the enzyme gulono-

OCR for page 95
DRI DIETARY REFERENCE INTAKES FOR Vitamin C, Vitamin E, Selenium, and Carotenoids lactone oxidase. The term vitamin C refers to both ascorbic acid and dehydroascorbic acid (DHA), since both exhibit anti-scorbutic activity. Ascorbic acid, the functional and primary in vivo form of the vitamin, is the enolic form of an α-ketolactone (2,3-didehydr L -threo-hexano-1,4-lactone). The two enolic hydrogen atoms give the compound its acidic character and provide electrons for its function as a reductant and antioxidant. Its one-electron oxidation product, the ascorbyl radical, readily dismutates to ascorbate and DHA, the two-electron oxidation products. Both the ascorbyl radical and DHA are readily reduced back to ascorbic acid in vivo. However, DHA can be hydrolyzed irreversibly to 2,3-diketogulonic acid. The molecular structure of ascorbic acid contains an asymmetric carbon atom that allows two enantiomeric forms, of which the L form is naturally occurring (the D -form, isoascorbic or erythorbic acid, provides antioxidant but little or no anti-scorbutic activity), as shown in Figure 5-1. Function The biological functions of ascorbic acid are based on its ability to provide reducing equivalents for a variety of biochemical reactions. Because of its reducing power, the vitamin can reduce most physiologically relevant reactive oxygen species (Buettner, 1993). As such, the vitamin functions primarily as a cofactor for reactions requiring a reduced iron or copper metalloenzyme and as a protective antioxidant that operates in the aqueous phase both intra- and extracellularly (Englard and Seifter, 1986; Halliwell and Whiteman, 1997; Tsao, 1997). Both the one- and the two-electron oxidation products of the vitamin are readily regenerated in vivo—chemically and enzymatically—by glutathione, nicotinamide adenine dinucleotide (NADH), and nicotinamide adenine dinucleotide phosphate (NAD-PH) dependent reductases (May et al., 1998; Park and Levine, 1996). Vitamin C is known to be an electron donor for eight human enzymes. Three participate in collagen hydroxylation; two in carnitine biosynthesis; and three in hormone and amino acid biosynthesis. The three enzymes that participate in hormone and amino acid biosynthesis are dopamine-β-hydroxylase, necessary for the biosynthesis of the catecholamines norepinephrine and epinephrine; peptidyl-glycine monooxygenase, necessary for amidation of peptide hormones; and 4-hydroxyphenylpyruvatedioxygenase, involved in tyrosine metabolism. Ascorbate's action with these enzymes in-

OCR for page 95
DRI DIETARY REFERENCE INTAKES FOR Vitamin C, Vitamin E, Selenium, and Carotenoids FIGURE 5-1 Chemical structure of ascorbic acid. volves either monooxygenase or dioxygenase activities (Levine et al., 1996b). As a cofactor for hydroxylase and oxygenase metalloenzymes, ascorbic acid is believed to work by reducing the active metal site, resulting in reactivation of the metal-enzyme complex, or by acting as a co-substrate involved in the reduction of molecular oxygen. The

OCR for page 95
DRI DIETARY REFERENCE INTAKES FOR Vitamin C, Vitamin E, Selenium, and Carotenoids best known of these reactions is the posttranslational hydroxylation of peptide-bound proline and lysine residues during formation of mature collagen. In these reactions, ascorbate is believed to reactivate the enzymes by reducing the metal sites of prolyl (iron) and lysyl (copper) hydroxylases (Englard and Seifter, 1986; Tsao, 1997). Evidence also suggests that ascorbate plays a role in or influences collagen gene expression, cellular procollagen secretion, and the biosynthesis of other connective tissue components besides collagen, including elastin, fibronectin, proteoglycans, bone matrix, and elastin-associated fibrillin (Ronchetti et al., 1996). The primary physical symptoms of ascorbic acid's clinical deficiency disease, scurvy, which involves deterioration of elastic tissue, illustrate the important role of ascorbate in connective tissue synthesis. Ascorbic acid is involved in the synthesis and modulation of some hormonal components of the nervous system. The vitamin is a co-factor for dopamine-β-hydroxylase, which catalyzes hydroxylation of the side chain of dopamine to form norepinephrine, and α-amidating monooxygenase enzymes, involved in the biosynthesis of neuropeptides. Other nervous system components modulated by ascorbate concentrations include neurotransmitter receptors, the function of glutamatergic and dopaminergic neurons, and synthesis of glial cells and myelin (Englard and Seifter, 1986; Katsuki, 1996). Because of its ability to donate electrons, ascorbic acid is an effective antioxidant. The vitamin readily scavenges reactive oxygen species (ROS) and reactive nitrogen species (RNS) (e.g., hydroxyl, peroxyl, superoxide, peroxynitrite, and nitroxide radicals) as well as singlet oxygen and hypochlorite (Frei et al., 1989; Halliwell and Whiteman, 1997; Sies and Stahl, 1995). The one- and two-electron oxidation products of ascorbate are relatively nontoxic and easily regenerated by the ubiquitous reductants glutathione and NADH or NAD-PH. The relatively high tissue levels of ascorbate provide substantial antioxidant protection: in the eye, against photolytically generated free-radical damage; in neutrophils, against ROS produced during phagocytosis; and in semen, against oxidative damage to sperm deoxyribonucleic acid (DNA) (Delamere, 1996; Fraga et al., 1991; Levine et al., 1994). Ascorbic acid protects against plasma and low-density lipoprotein (LDL) oxidation by scavenging ROS in the aqueous phase before they initiate lipid peroxidation (Frei et al., 1988; Jialal et al., 1990) and possibly by sparing or regenerating vitamin E (Halpner et al., 1998). Evidence suggests that ascorbate

OCR for page 95
DRI DIETARY REFERENCE INTAKES FOR Vitamin C, Vitamin E, Selenium, and Carotenoids also provides antioxidant protection indirectly by regenerating other biological antioxidants such as glutathione and α-tocopherol back to their active state (Jacob, 1995). Ascorbic acid functions as a reducing agent for mixed-function oxidases in the microsomal drug-metabolizing system that inactivates a wide variety of substrates, such as endogenous hormones or xenobiotics (i.e., other chemical compounds such as drugs, pesticides, or carcinogens that are foreign to humans) (Tsao, 1997). The activity of both microsomal drug-metabolizing enzymes and cytochrome P-450 electron transport is lowered by ascorbate deficiency. The vitamin is involved in the biosynthesis of corticosteroids and aldosterone and in the microsomal hydroxylation of cholesterol in the conversion of cholesterol to bile acids. In reactions similar to the hydroxylation of proline for collagen synthesis, ascorbate is required along with iron at two steps in the pathway of carnitine biosynthesis. Ascorbic acid modulates iron absorption, transport, and storage (Gosiewska et al., 1996). Limited data suggest that ascorbate modulates prostaglandin synthesis and thus exerts bronchodilatory and vasodilatory as well as anticlotting effects (Horrobin, 1996). Physiology of Absorption, Metabolism, and Excretion Absorption and Transport Intestinal absorption of ascorbic acid occurs through a sodium-dependent active transport process that is saturable and dose dependent (Rumsey and Levine, 1998; Tsao, 1997). At low gastrointestinal ascorbate concentrations, active transport predominates, while simple diffusion occurs at high concentrations. Some 70 to 90 percent of usual dietary intakes of ascorbic acid (30 to 180 mg/day) are absorbed; however, absorption falls to about 50 percent or less with increasing doses above 1 g/day (Kallner et al., 1979). The bioavailabilities of the vitamin from foods and supplements are not significantly different (Johnston and Luo, 1994; Mangels et al., 1993). Cellular transport of ascorbic acid and DHA is mediated by transporters that vary by cell type (Jacob, 1999; Tsao, 1997). DHA is the form of the vitamin that primarily crosses the membranes of blood and intestinal cells, after which it is reduced intracellularly to ascorbic acid. Accumulation of ascorbate into neutrophils and lympho-

OCR for page 95
DRI DIETARY REFERENCE INTAKES FOR Vitamin C, Vitamin E, Selenium, and Carotenoids cytes is mediated by both high- and low-affinity transporters, and the vitamin is localized mostly in the cytosol. Intracellularly and in plasma, vitamin C exists predominately in the free reduced form as ascorbate monoanion, as shown in Figure 5-1 (Levine et al., 1994). Metabolism and Excretion Since the immediate oxidized forms of vitamin C are readily reduced back to ascorbic acid, relatively small amounts of the vitamin are lost through catabolism. The primary products of oxidation beyond DHA include oxalic and threonic acids, L -xylose, and ascorbate 2-sulfate (Jacob, 1999). With large intakes of the vitamin, unabsorbed ascorbate is degraded in the intestine, a process that may account for the diarrhea and intestinal discomfort sometimes reported by persons ingesting large doses (see section on “Adverse Effects”). Besides dose-dependent absorption, a second primary mechanism for regulation of body ascorbate content is renal action to conserve or excrete unmetabolized ascorbate. Recent studies have shown that little unmetabolized ascorbate is excreted with dietary intakes up to about 80 mg/day and that renal excretion of ascorbate increases proportionately with higher intakes (Blanchard et al., 1997; Melethil et al., 1986). Body Stores Dose-dependent absorption and renal regulation of ascorbate allow conservation of the vitamin by the body during low intakes and limitation of plasma levels at high intakes. Tissue-specific cellular transport systems allow for wide variation of tissue ascorbate concentrations. High levels are maintained in the pituitary and adrenal glands, leukocytes, eye tissues and humors, and the brain, while low levels are found in plasma and saliva (Hornig, 1975). Due to homeostatic regulation, the biological half-life of ascorbate varies widely from 8 to 40 days and is inversely related to the ascorbate body pool (Kallner et al., 1979). Similarly, catabolic turnover varies widely, about 10 to 45 mg/day, over a wide range of dietary intakes due to body pool size. A total body pool of less than 300 mg is associated with scurvy symptoms (Baker et al., 1971), while maximum body pools are limited to about 2 g (Kallner et al., 1979). At very low ascorbate intakes, essentially no ascorbate is excreted unchanged and a minimal loss occurs.

OCR for page 95
DRI DIETARY REFERENCE INTAKES FOR Vitamin C, Vitamin E, Selenium, and Carotenoids Clinical Effects of Inadequate Intake Scurvy, the classic disease of severe vitamin C deficiency, is characterized by symptoms related to connective tissue defects. Scurvy usually occurs at a plasma concentration of less than 11 µmol/L (0.2 mg/dL). Clinical features of scurvy include follicular hyperkeratosis, petechiae, ecchymoses, coiled hairs, inflamed and bleeding gums, perifollicular hemorrhages, joint effusions, arthralgia, and impaired wound healing (Baker et al., 1971; Chazan and Mistilis, 1963; Levine et al., 1996b). Other symptoms include dyspnea, edema, Sjögren's syndrome (dry eyes and mouth), weakness, fatigue, and depression. In experimental subjects made vitamin C deficient but not frankly scorbutic, gingival inflammation (Leggott et al., 1986) and fatigue (Levine et al., 1996a) were among the most sensitive markers of deficiency. Vitamin C deficiency in infants may result in bone abnormalities such as impaired bone growth and disturbed ossification, hemorrhagic symptoms, and resultant anemia (Jacob, 1999). Lack of ascorbate-related hydroxyproline and hydroxylysine formation needed for collagen cross-linking may explain many of the connective tissue and hemorrhagic manifestations of scurvy, however, the specific histologic defects have not been identified. Oxidative degradation of some blood coagulation factors due to low plasma ascorbate concentrations may contribute to hemorrhagic symptoms (Parkkinen et al., 1996). Scurvy is rare in developed countries but is occasionally seen in individuals who consume few fruits and vegetables, peculiar or restricted diets, or in those who abuse alcohol or drugs. In the United States, low blood ascorbate concentrations are more prevalent in men, especially elderly men, than in women and are more prevalent in populations of lower socioeconomic status (LSRO/FASEB, 1989). Infantile scurvy is rarely seen, because human milk provides an adequate supply of vitamin C and infant formulas are fortified with the vitamin. SELECTION OF INDICATORS FOR ESTIMATING THE REQUIREMENT FOR VITAMIN C Antioxidant Functions There is much support for the role of increased oxidative stress in the pathogenesis of cardiovascular disease (Jialal and Devaraj, 1996; Witztum and Steinberg, 1991). The most plausible and biologically

OCR for page 95
DRI DIETARY REFERENCE INTAKES FOR Vitamin C, Vitamin E, Selenium, and Carotenoids relevant hypothesis is that the oxidative modification of low-density lipoprotein (LDL) and other lipoproteins promote atherogenesis (Berliner and Heinecke, 1996; Devaraj and Jialal, 1996; Witztum and Steinberg, 1991). Several lines of evidence suggest that oxidized LDL (oxLDL) is pro-atherogenic. Furthermore, data support the in vivo existence of oxLDL (Berliner and Heinecke, 1996; Witztum and Steinberg, 1991). In vitro studies have clearly shown that vitamin C at concentrations greater than 40 µmol/L (0.8 mg/dL) inhibits the oxidation of isolated LDL induced by transition metals, free-radical initiators, and activated human neutrophils and macrophages (Jialal and Grundy, 1991; Jialal et al., 1990; Scaccini and Jialal, 1994). This is because vitamin C effectively scavenges aqueous reactive oxygen species (ROS) and reactive nitrogen species (RNS), which prevents them from attacking LDL. Thus, in vitro vitamin C clearly functions as an antioxidant. Studies shown in Table 5-1 examined the effect of vitamin C supplementation alone on biomarkers of lipid peroxidation. Of the 13 studies, 7 showed that vitamin C supplementation resulted in a significant decrease in lipid oxidation products in plasma, LDL, or urine. The vitamin C supplements that resulted in positive effects ranged from 500 to 2,000 mg/day. The most convincing evidence that vitamin C functions as an antioxidant in vivo is the study by Reilly et al. (1996) showing that supplementation of smokers with 2.0 g vitamin C for 5 days was associated with a significant reduction in urinary isoprostanes, an indicator of oxidative stress. In the remaining six studies in which vitamin C was supplemented in amounts ranging from 500 to 6,000 mg/day, there was no significant effect of vitamin C supplementation on lipid oxidation products in plasma, urine, or plasma LDL. Carr and Frei (1999) examined the effect on LDL oxidation of supplementation with vitamin C in combination with vitamin E and β-carotene. Although these investigators have clearly shown that the supplements decrease LDL oxidation, it is difficult to assess the contribution of vitamin C alone. Vitamin C supplementation (2,000 mg/day for 4 to 12 months) in 41 patients with non-atrophic gastritis decreased gastric mucosal nitrotyrosine, a measure of RNS activity (Table 5-2) (Mannick et al., 1996). Thus, from this study and the study by Reilly et al. (1996), it can be concluded that supplementation with vitamin C results in an antioxidant effect in vivo because it significantly reduces nitrotyrosine and urinary isoprostanes. However, with respect to the effect of vitamin C on LDL oxidation, the data are inconclusive. This could be explained by the fact

OCR for page 95
DRI DIETARY REFERENCE INTAKES FOR Vitamin C, Vitamin E, Selenium, and Carotenoids that, because vitamin C is water soluble, it does not partition into the LDL particle. Also, it must be pointed out that in one of the 13 studies summarized in Table 5-1, there was an increase in plasma thiobarbituric acid reactive substances (TBARS), an indicator of oxidative stress, with a 500-mg dose of ascorbic acid (Nyyssonen et al., 1997b). Adhesion of mononuclear cells to endothelium is an early event in atherogenesis and may be triggered by oxidative stress. Smokers have low levels of vitamin C and increased oxidative stress. A recent study showed that monocytes of smokers display greater adhesion to endothelial cells than those of nonsmokers (Weber et al., 1996). When supplemented with 2,000 mg/day of vitamin C, the plasma ascorbate level of smokers increased, and adhesion of their monocytes to endothelium decreased to that seen in nonsmokers. Impaired vascular function is crucial to the clinical manifestation of atherosclerosis. As depicted in Table 5-3, numerous investigators have reported a beneficial effect of high dose vitamin C administration, either orally or intraarterially, on vasodilation. This beneficial effect of vitamin C is most likely related to its antioxidant effect. Endothelium-derived relaxing factor, nitric oxide (NO), promotes vasodilation but is rapidly inactivated by superoxide. Vitamin C improves endothelial function and vasodilation, possibly by scavenging superoxide radicals, conserving intracellular glutathione, or potentiating intracellular NO synthesis. In human endothelial cells in culture, extracellular vitamin C at physiological concentrations increased cellular NO synthesis up to threefold, and the increase in NO synthesis followed a time course similar to ascorbate uptake into the cells (Heller et al., 1999). Antioxidant Functions in Leukocytes The content of vitamin C in leukocytes is especially important because the ROS generated during phagocytosis and neutrophil activation are associated with infectious and inflammatory stresses (Jariwalla and Harakeh, 1996; Levine et al., 1994). Along with pituitary and adrenal glands and eye lens, leukocytes contain the highest vitamin C concentrations of all body tissues (Moser, 1987). Studies with guinea pigs and monkeys show that the concentration of ascorbate in the leukocytes more accurately reflects liver and body pool ascorbate than does the concentration in plasma or erythrocytes (Omaye et al., 1987). The vitamin is transported into leukocytes by an energy-dependent transport system that concentrates the vitamin some twenty-five-, forty-, and eightyfold over plasma levels in neutr-

OCR for page 95
DRI DIETARY REFERENCE INTAKES FOR Vitamin C, Vitamin E, Selenium, and Carotenoids TABLE 5-1 Effect of Vitamin C Supplementation on Biomarkers of Lipid Oxidation in Humans Reference Subjects Vitamin C Dosea (mg/d) Harats et al., 1990 17 smokers 1,000 1,500 Belcher et al., 1993 5 healthy men 1,000 Rifici and Khachadurian, 1993 4 healthy men and women 1,000 Cadenas et al., 1996 21 healthy men 1,000 Fuller et al., 1996 19 smokers (9 placebo) 1,000 Mulholland et al., 1996 16 female smokers (8 placebo) 1,000 Reilly et al., 1996 5 heavy smokers 2,000 Anderson et al., 1997 48 nonsmokers (24 females) 60 6,000 Nyyssonen et al., 1997b 59 male smokers (19 placebo) 500 (Pj) 500 (SRk) Samman et al., 1997 8 male smokers (40) 1,000 Wen et al., 1997 20 nonsmokers (9 placebo) 1,000 Harats et al., 1998 36 healthy men (50) 500 (citrus fruit supplement) Naidoo and Lux, 1998 9 healthy men, 6 healthy women 250, 500, 750 and 1,000 a Amount given in excess of variable amount consumed daily as part of the diet. b LDL = low-density lipoprotein. c TBARS = thiobarbituric acid reactive substances. d LDL oxidizability is measured by the lag time and propagation rate of in vitro lipid peroxidation. e VLDL = very low-density lipoprotein. f CD = conjugated dienes.

OCR for page 95
DRI DIETARY REFERENCE INTAKES FOR Vitamin C, Vitamin E, Selenium, and Carotenoids Duration Plasma Change Findings 2 wk 2.0-fold ↓ Plasma and LDLb TBARSc 4 wk 2.3-fold ↓ Plasma and LDL TBARS 14 d Not reported LDL oxidationd, no change 10 d Not reported ↓ VLDLe and LDL oxidation (4 hour TBARS) 30 d Not reported Urine TBARS, no change 4 wk 3.9-fold ↓ LDL Oxidizabilityd (TBARS, CDf) 14 d 3.0-fold Serum TBARS, no change 5 d Not reported 18 Urine 8-epi-PGF2a 14 d 1.2-fold Plasma MDAg /HNEh, no change ↑ TACi 14 d 1.8-fold Plasma MDA/HNE, no change ↑ TAC 2 mo 1.3-fold LDL oxidizability, no change 2 mo 1.5-fold Plasma ↑ TBARS with P Vit C No ↑ with SR Vit C (2 wk) (baseline) LDL oxidizability (CD): no change 2 wk 2.0-fold   4 wk 2.2-fold ↓ Plasma MDA (↑ erythrocyte Vit E and GSHl); no change LDL Vit E; no change in LDL oxidizability (TBARS and CD) (1 mo) (baseline) ↓ LDL oxidizability (CD) 2 mo 3.8-fold   2 wk 1.5-fold (250) 2.0-fold (500) 2.0-fold (750 and 1,000) ↓ Plasma MDA and allantoin with 500, 750 and 1,000 mg/d g MDA = malondialdehyde. h HNE = hydroxynonenal. i TAC = Total Antioxidant Capacity. j P = plain. k SR = slow release. l GSH = reduced gluthione.

OCR for page 95
DRI DIETARY REFERENCE INTAKES FOR Vitamin C, Vitamin E, Selenium, and Carotenoids Hughes C, Dutton S, Truswell AS. 1981. High intakes of ascorbic acid and urinary oxalate. J Hum Nutr 35:274–280. Hunt JR, Gallagher SK, Johnson LK. 1994. Effect of ascorbic acid on apparent iron absorption by women with low iron stores. Am J Clin Nutr 59:1381–1385. Hunter DJ, Manson JE, Colditz GA, Stampfer MJ, Rosner B, Hennekens CH, Speizer FE, Willett WC. 1993. A prospective study of the intake of vitamins C, E, and A and the risk of breast cancer. N Engl J Med 329:234–240. IOM (Institute of Medicine). 1991. Nutrition During Lactation. Washington, DC: National Academy Press. P. 179. Itoh R, Yamada K, Oka J, Echizen H, Murakami K. 1989. Sex as a factor in levels of serum ascorbic acid in a healthy elderly population. Int J Vitam Nutr Res 59:365–372. Jacob RA. 1995. The integrated antioxidant system. Nutr Res 15:755–766. Jacob RA. 1999. Vitamin C. In: Shils ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease, 9th edition. Baltimore, MD: Williams & Wilkins. Pp. 467–483. Jacob RA, Pianalto FS. 1997. Urinary carnitine excretion increases during experimental vitamin C depletion of healthy men. J Nutr Biochem 8:265–269. Jacob RA, Skala JH, Omaye ST. 1987a. Biochemical indices of human vitamin C status. Am J Clin Nutr 46:818–826. Jacob RA, Skala JH, Omaye ST, Turnlund JR. 1987b. Effect of varying ascorbic acid intakes on copper absorption and ceruloplasmin levels of young men. J Nutr 117:2109–2115. Jacob RA, Otradovec CL, Russell RM, Munro HN, Hartz SC, McGandy RB, Morrow FD, Sadowski JA. 1988. Vitamin C status and nutrient interactions in a healthy elderly population . Am J Clin Nutr 48:1436–1442. Jacob RA, Kelley DS, Pianalto FS, Swendseid ME, Henning SM, Zhang Jz, Ames BN, Fraga CG, Peters JH. 1991. Immunocompetence and oxidant defense during ascorbate depletion of healthy men. Am J Clin Nutr 54:1302S–1309S. Jacob RA, Pianalto FS, Agee RE. 1992. Cellular ascorbate depletion in healthy men. J Nutr 122:1111–1118. Jacob RA, Kutnink MA, Csallany AS, Daroszewska M, Burton GW. 1996. Vitamin C nutriture has little short-term effect on vitamin E concentrations in healthy women. J Nutr 126:2268–2277. Jacques PF, Chylack LT Jr. 1991. Epidemiologic evidence of a role for the antioxidant vitamins and carotenoids in cataract prevention. Am J Clin Nutr 53:352S–355S. Jacques PF, Taylor A, Hankinson SE, Willett WC, Mahnken B, Lee Y, Vaid K, Lahav M. 1997. Long-term vitamin C supplement use and prevalence of early age related lens opacities. Am J Clin Nutr 66:911–916. Jaffe RM, Kasten B, Young DS, MacLowry JD. 1975. False-negative stool occult blood tests caused by ingestion of ascorbic acid (vitamin C). Ann Intern Med 83:824–826. Jama JW, Launer LJ, Witteman JC, den Breeijen JH, Breteler MM, Grobbee DE, Hofman A. 1996. Dietary antioxidants and cognitive function in a population based sample of older persons. The Rotterdam Study. Am J Epidemiol 144:275–280. Jariwalla RJ, Harakeh S. 1996. Antiviral and immunomodulatory activities of asco bic acid. Subcell Biochem 25:213–231. Jarvinen R, Knekt P, Seppanen R, Teppo L. 1997. Diet and breast cancer risk in a cohort of Finnish women. Cancer Lett 114:251–253.

OCR for page 95
DRI DIETARY REFERENCE INTAKES FOR Vitamin C, Vitamin E, Selenium, and Carotenoids Jendryczko A, Tomala J. 1995. The total free radical trapping ability of blood pla ma in eclampsia . Zentralbl Gynakol 117:126–129. Jha P, Flather M, Lonn E, Farkouh M, Yusuf S. 1995. The antioxidant vitamins and cardiovascular disease. A critical review of epidemiologic and clinical trial data. Ann Intern Med 123:860–872. Jialal I, Devaraj S. 1996. The role of oxidized low density lipoprotein in atherogenesis. J Nutr 126:1053S–1057S. Jialal I, Grundy SM. 1991. Preservation of the endogenous antioxidants in low density lipoprotein by ascorbate but not probucol during oxidative modification. J Clin Invest 87:597–601. Jialal I, Vega GL, Grundy SM. 1990. Physiologic levels of ascorbate inhibit the oxidative modification of low density lipoprotein. Atherosclerosis 82:185–191. Johnston CS. 1991. Complement component Clq unaltered by ascorbate supplementation in healthy men and women. J Nutr Biochem 2:499–501. Johnston CS. 1999. Biomarkers for establishing a tolerable upper intake level for vitamin C. Nutr Rev 57:71–77. Johnston CS, Luo B. 1994. Comparison of the absorption and excretion of three commercially available sources of vitamin C. J Am Diet Assoc 94:779–781. Johnston CS, Thompson LL. 1998. Vitamin C status of an outpatient population. J Am Coll Nutr 17:366–370. Johnston CS, Martin LJ, Cai X. 1992. Antihistamine effect of supplemental ascorbic acid and neutrophil chemotaxis. J Am Coll Nutr 11:172–176. Johnston CS, Meyer CG, Srilakshmi JC. 1993. Vitamin C elevates red blood cell glutathione in healthy adults. Am J Clin Nutr 58:103–105. Johnston CS, Solomon E, Corte C. 1996. Vitamin C depletion is associated with alterations in blood histamine and plasma free carnitine in adults. J Am Coll Nutr 15:586–591. Kallner A, Hartmann D, Hornig D. 1979. Steady-state turnover and body pool of ascorbic acid in man. Am J Clin Nutr 32:530–539. Kallner AB, Hartmann D, Hornig DH. 1981. On the requirements of ascorbic acid in man: Steady-state turnover and body pool in smokers. Am J Clin Nutr 34:1347–1355. Karra MV, Udipi SA, Kirksey A, Roepke JL. 1986. Changes in specific nutrients in breast milk during extended lactation . Am J Clin Nutr 43:495–503. Katsuki H. 1996. Vitamin C and nervous tissue: In vivo and in vitro aspects. Subcell Biochem 25:293–311. Keith RE. 1994. Vitamins and physical activity. In: Wolinsky I, Hickson JF, eds. Nutrition in Exercise and Sport, 2nd edition. Boca Raton, FL: CRC Press. Pp. 159–183. Kelly FJ, Mudway I, Blomberg A, Frew A, Sandstrom T. 1999. Altered lung antioxidant status in patients with mild asthma. Lancet 354:482–483. Kennes B, Dumont I, Brohee D, Hubert C, Neve P. 1983. Effect of vitamin C supplements on cell-mediated immunity in old people. Gerontology 29:305–310. Knekt P, Jarvinen R, Seppanen R, Rissanen A, Aromaa A, Heinonen OP, Albanes D, Heinonen M, Pukkala E, Teppo L. 1991. Dietary antioxidants and the risk of lung cancer. Am J Epidemiol 134:471–479. Knekt P, Reunanen A, Jarvinen R, Seppanen R, Heliovaara M, Aromaa A. 1994. Antioxidant vitamin intake and coronary mortality in a longitudinal population study. Am J Epidemiol 139:1180–1189.

OCR for page 95
DRI DIETARY REFERENCE INTAKES FOR Vitamin C, Vitamin E, Selenium, and Carotenoids Kritchevsky SB, Shimakawa T, Tell G, Dennis B, Carpenter M, Eckfeldt JH, Peacher-Ryan H, Heiss G. 1995. Dietary antioxidants and carotid artery wall thickness. The ARIC Study. Circulation 92:2142–2150. Kushi LH, Fee RM, Sellers TA, Zheng W, Folsom AR. 1996a. Intake of vitamins A, C, and E and postmenopausal breast cancer. The Iowa Women's Health Study. Am J Epidemiol 144:165–174. Kushi LH, Folsom AR, Prineas RJ, Mink PJ, Wu Y, Bostick RM. 1996b. Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women. N Engl J Med 334:1156–1162. Lamden MP, Chrystowski GA. 1954. Urinary oxalate excretion by man following ascorbic acid ingestion . Proc Soc Exp Biol Med 85:190–192. Laudicina DC, Marnett LJ. 1990. Enhancement of hydroperoxide-dependent lipid peroxidation in rat liver microsomes by ascorbic acid. Arch Biochem Biophys 278:73–80. Leaf CD, Vecchio AJ, Roe DA, Hotchkiss JH. 1987. Influence of ascorbic acid dose on N-nitrosoproline formation in humans. Carcinogenesis 8:791–795. Leggott PJ, Robertson PB, Rothman DL, Murray PA, Jacob RA. 1986. The effect of controlled ascorbic acid depletion and supplementation on periodontal health. J Periodontol 57:480–485. Leggott PJ, Robertson PB, Jacob RA, Zambon JJ, Walsh M, Armitage GC. 1991. Effects of ascorbic acid depletion and supplementation on periodontal health and subgingival microflora in humans. J Dent Res 70:1531–1536. Lehr HA, Weyrich AS, Saetzler RK, Jurek A, Arfors KE, Zimmerman GA, Prescott SM, McIntyre TM. 1997. Vitamin C blocks inflammatory platelet-activating factor mimetics created by cigarette smoking. J Clin Invest 99:2358–2364. Le Marchand L, Yoshizawa CN, Kolonel LN, Hankin JH, Goodman MT. 1989. Vegetable consumption and lung cancer risk: A population-based case-control study in Hawaii. J Natl Cancer Inst 81:1158–1164. Lenton KJ, Therriault H, Fulop T, Payette H, Wagner JR. 1999. Glutathione and ascorbate are negatively correlated with oxidative DNA damage in human lymphocytes. Carcinogenesis 20:607–613. Leske MC, Chylack LT Jr, Wu SY. 1991. The Lens Opacities Case-Control Study. Risk factors for cataract. Arch Ophthalmol 109:244–251. Levine GN, Frei B, Koulouris SN, Gerhard MD, Keaney JF Jr, Vita JA. 1996. Ascorbic acid reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation 93:1107–1113. Levine M, Dhariwal KR, Wang Y, Park JB, Welch RW. 1994. Ascorbic acid in neutrophils. In: Frei B, ed. Natural Antioxidants in Health and Disease. San Diego: Academic Press. Pp. 469–488. Levine M, Conry-Cantilena C, Wang Y, Welch RW, Washko PW, Dhariwal KR, Park JB, Lazarev A, Graumlich JF, King J, Cantilena LR. 1996a. Vitamin C pharmacokinetics in healthy volunteers: Evidence for a recommended dietary allowance. Proc Natl Acad Sci USA 93:3704–3709. Levine M, Rumsey S, Wang Y, Park J, Kwon O, Xu W, Amano N. 1996b. Vitamin C.In: Ziegler EE, Filer LJ Jr, eds. Present Knowledge in Nutrition, 7th edition. Washington, DC: ILSI Press. Pp. 146–159. Levy R, Shriker O, Porath A, Riesenberg K, Schlaeffer F. 1996. Vitamin C for the treatment of recurrent furunculosis in patients with impaired neutrophil functions. J lnfect Dis 173:1502–1505.

OCR for page 95
DRI DIETARY REFERENCE INTAKES FOR Vitamin C, Vitamin E, Selenium, and Carotenoids Loft S, Vistisen K, Ewertz M, Tjonneland A, Overvad K, Poulsen HE. 1992. Oxidative DNA damage estimated by 8-hydroxydeoxyguanosine excretion in humans: Influence of smoking, gender and body mass index. Carcinogenesis 13:2241–2247. Losonczy KG, Harris TB, Havlik RJ. 1996. Vitamin E and vitamin C supplement use and risk of all-cause and coronary heart disease mortality in older persons: The Established Populations for Epidemiologic Studies of the Elderly. Am J Clin Nutr 64:190–196. Løvstad RA. 1997. A study on ascorbate inhibition of ceruloplasmin ferroxidase activity . BioMetals 10:123–126. LSRO/FASEB (Life Sciences Research Office/Federation of American Societies for Experimental Biology). 1989. Nutrition Monitoring in the United States: An Update Report on Nutrition Monitoring. Prepared for the U.S. Department of Agriculture and the U.S. Department of Health and Human Services. DHHS Publication No. (PHS) 89-1255 . Washington, DC: U.S. Government Printing Office. Ludvigsson J, Hansson LO, Tibbling G. 1977. Vitamin C as a preventive medicine against common colds in children . Scand J Infect Dis 9:91–98. Ludvigsson J, Hansson LO, Stendahl O. 1979. The effect of large doses of vitamin C on leukocyte function and some laboratory parameters. Int J Vitam Nutr Res 49:160–165. Lunec J, Blake DR. 1985. The determination of dehydroascorbic acid and ascorbic acid in the serum and synovial fluid of patients with rheumatoid arthritis. Free Radic Res Commun 1:31–39. Lykkesfeldt J, Loft S, Nielsen JB, Poulsen HE. 1997. Ascorbic acid and dehydroascorbic acid as biomarkers of oxidative stress caused by smoking. Am J Clin Nutr 65:959–963. Lykkesfeldt J, Christen S, Wallock LM, Change HH, Jacob RA, Ames BN. 2000. Ascorbate is depleted by smoking and repleted by moderate supplementation: A study in male smokers and nonsmokers with matched dietary antioxidant intakes. Am J Clin Nutr 71:530–536. Mangels AR, Block G, Frey CM, Patterson BH, Taylor PR, Norkus EP, Levander OA. 1993. The bioavailability to humans of ascorbic acid from oranges, o ange juice and cooked broccoli is similar to that of synthetic ascorbic acid. J Nutr 123:1054–1061. Mannick EE, Bravo LE, Zarama G, Realpe JL, Zhang XJ, Ruiz B, Fontham ETH, Mera R, Miller MJS, Correa P. 1996. Inducible nitric oxide synthase, nitrotyrosine, and apoptosis in Helicobacter pylori gastritis: Effect of antibiotics and antioxidants. Cancer Res 56:3238–3243. Marangon K, Herbeth B, Artur Y, Esterbauer H, Siest G. 1997. Low and very low density lipoprotein composition and resistance to copper-induced oxidation are not notably modified in smokers. Clin Chim Acta 265:1–12. Marangon K, Herbeth B, Lecomte E, Paul-Dauphin A, Grolier P, Chancerelle Y, Artur Y. 1998. Diet, antioxidant status, and smoking habits in French men. Am J Clin Nutr 67:231–239. May JM, Cobb CE, Mendiratta S, Hill KE, Burk RF. 1998. Reduction of the ascorbyl free radical to ascorbate by thioredoxin reductase. J Biol Chem 273:23039–23045. May JM, Mendiratta S, Qu ZC, Loggins E. 1999. Vitamin C recycling and function in human monocytic U-937 cells. Free Radic Biol Med 26:1513–1523.

OCR for page 95
DRI DIETARY REFERENCE INTAKES FOR Vitamin C, Vitamin E, Selenium, and Carotenoids McKeown-Eyssen G, Holloway C, Jazmaji V, Bright-See E, Dion P, Bruce WR. 1988. A randomized trial of vitamins C and E in the prevention of recurrence of colorectal polyps. Cancer Res 48:4701–4705. McLaran CJ, Bett JHN, Nye JA, Halliday JW. 1982. Congestive cardiomyopathy and haemochromatosis—Rapid progression possibly accelerated by excessive ingestion of ascorbic acid. Aust NZ J Med 12:187–188. Melethil S, Mason WD, Chang C-J. 1986. Dose-dependent absorption and excretion of vitamin C in humans. Int J Pharmaceut 31:83–89. Mentzer WC, Collier E. 1975. Hydrops fetalis associated with erythrocyte G-6-PD deficiency and maternal ingestion of fava beans and ascorbic acid. J Pediatr 86:565–567. Metz J, Hundertmark U, Pevny I. 1980. Vitamin C allergy of the delayed type. Contact Dermatitis 6:172–174. Millar J. 1995. The nitric oxide/ascorbate cycle: How neurones may control their own oxygen supply. Med Hypoth 45:21–26. Miller JZ, Nance WE, Norton JA, Wolen RL, Griffith RS, Rose RJ. 1977. Therapeutic effect of vitamin C. A co-twin control study. J Am Med Assoc 237:248–251. Mirvish SS. 1994. Experimental evidence for inhibition of N-nitroso compound formation as a factor in the negative correlation between vitamin C consumption and the incidence of certain cancers . Cancer Res 54:1948S–1951S. Mitch WE, Johnson MW, Kirshenbaum JM, Lopez RE. 1981. Effect of large oral doses of ascorbic acid on uric acid excretion by normal subjects. Clin Pharmcol Ther 29:318–321. Montalto MB, Benson JD, Martinez GA. 1985. Nutrient intakes of formula-fed infants and infants fed cow's milk. Pediatrics 75:343–351. Morrow JD, Frei B, Longmire AW, Gaziano JM, Lynch SM, Shyr Y, Strauss WE, Oates JA, Roberts LJ II. 1995. Increase in circulating products of lipid peroxidation (F2-isoprostanes) in smokers. N Engl J Med 332:1198–1203. Morse EH, Clark RP, Keyser DE, Merrow SB, Bee DE. 1975. Comparison of the nutritional status of pregnant adolescents with adult pregnant women. I. Biochemical findings. Am J Clin Nutr 28:1000–1013. Moser U. 1987. Uptake of ascorbic acid by leukocytes. Ann NY Acad Sci 498:200–215. Moss AJ, Levy AS, Kim I, Park YK. 1989. Use of Vitamin and Mineral Supplements in the United States: Current Users, Types of Products, and Nutrients. Advance Data, Vital and Health Statistics of the National Center for Health Statistics. Number 174. Hyattsville, MD: National Center for Health Statistics. Pp. 1–19. Motoyama T, Kawano H, Kugiyama K, Hirashima O, Ohgushi M, Yoshimura M, Ogawa H, Yasue H. 1997. Endothelium-dependent vasodilation in the brachial artery is impaired in smokers: Effect of vitamin C. Am J Physiol 273:H1644–H1650. Mudway IS, Krishna MT, Frew AJ, MacLeod D, Sandstrom T, Holgate ST, Kelly FJ. 1999. Compromised concentrations of ascorbate in fluid lining the respiratory tract in human subjects after exposure to ozone. Occup Environ Med 56:473–481. Mulholland CW, Strain JJ, Trinick TR. 1996. Serum antioxidant potential, and lipoprotein oxidation in female smokers following vitamin C supplementation. Int J Food Sci Nutr 47:227–231. Naidoo D, Lux O. 1998. The effect of vitamin C and E supplementation on lipid and urate oxidation products in plasma. Nutr Res 18:953–961.

OCR for page 95
DRI DIETARY REFERENCE INTAKES FOR Vitamin C, Vitamin E, Selenium, and Carotenoids Ness AR, Khaw KT, Bingham S, Day NE. 1996. Vitamin C status and respiratory function. Eur J Clin Nutr 50:573–579. Newmark HL, Scheiner MS, Marcus M, Prabhudesai M. 1976. Stability of vitamin B12 in the presence of ascorbic acid. Am J Clin Nutr 29:645–649. Newton HM, Schorah CJ, Habibzadeh N, Morgan DB, Hullin RP. 1985. The cause and correction of low blood vitamin C concentrations in the elderly. Am J Clin Nutr 42:656–659. NRC (National Research Council). 1989. Recommended Dietary Allowances, 10th edition. Washington, DC: National Academy Press. Nyyssonen K, Parviainen MT, Salonen R, Tuomilehto J, Salonen JT. 1997a. Vitamin C deficiency and risk of myocardial infarction: Prospective population study of men from eastern Finland. Br Med J 314:634–638. Nyyssonen K, Poulsen HE, Hayn M, Agerbo P, Porkkala-Sarataho E, Kaikkonen J, Salonen R, Salonen JT. 1997b. Effect of supplementation of smoking men with plain or slow release ascorbic acid on lipoprotein oxidation. Eur J Clin Nutr 51:154–163. Ocke MC, Bueno-de-Mesquita HB, Feskens EJ, van Staveren WA, Kromhout D. 1997. Repeated measurements of vegetables, fruits, beta-carotene, and vit mins C and E in relation to lung cancer. Am J Epidemiol 145:358–365. Omaye ST, Skala JH, Jacob RA. 1986. Plasma ascorbic acid in adult males: Effects of depletion and supplementation . Am J Clin Nutr 44:257–264. Omaye ST, Schaus EE, Kutnink MA, Hawkes WC. 1987. Measurement of vitamin C in blood components by high-performance liquid chromatography. Implication in assessing vitamin C status . Ann NY Acad Sci 498:389–401. Ono K. 1986. Secondary hyperoxalemia caused by vitamin C supplementation in regular hemodialysis patients. Clin Nephrol 26:239–243. Oreopoulos DG, Lindeman RD, VanderJagt DJ, Tzamaloukas AH, Bhagavan HN, Garry PJ. 1993. Renal excretion of ascorbic acid: Effect of age and sex. J Am Coll Nutr 12:537–542. Ortega RM, Lopez-Sobaler AM, Quintas ME, Martinez RM, Andres P. 1998. The influence of smoking on vitamin C status during the third trimester of pregnancy and on vitamin C levels in maternal milk. J Am Coll Nutr 17:379–384. O'Toole P, Lombard M. 1996. Vitamin C and gastric cancer: Supplements for some or fruit for all? Gut 39:345–347. Panayiotidis M, Collins AR. 1997. Ex vivo assessment of lymphocyte antioxidant status using the comet assay. Free Rad Res 27:533–537. Pandey DK, Shekelle R, Selwyn BJ, Tangney C, Stamler J. 1995. Dietary vitamin C and beta-carotene and risk of death in middle-aged men. The Western Electric Study. Am J Epidemiol 142:1269–1278. Panush RS, Delafuente JC, Katz P, Johnson J. 1982. Modulation of certain immunologic responses by vitamin C. III. Potentiation of in vitro and in vivo ly phocyte responses. Int J Vitam Nutr Res Suppl 23:35–47. Park JB, Levine M. 1996. Purification, cloning and expression of dehydroascorbic acid-reducing activity from human neutrophils: Identification as glutaredoxin. Biochem J 315:931–938. Parkkinen J, Vaaranen O, Vahtera E. 1996. Plasma ascorbate protects coagulation factors against photooxidation . Thromb Haemost 75:292–297. Pelletier O. 1977. Vitamin C and tobacco. Int J Vitam Nutr Res Suppl 16:147–170. Perrig WJ, Perrig P, Stahelin HB. 1997. The relation between antioxidants and memory performance in the old and very old. J Am Geriatr Soc 45:718–724.

OCR for page 95
DRI DIETARY REFERENCE INTAKES FOR Vitamin C, Vitamin E, Selenium, and Carotenoids Peters EM, Goetzsche JM, Grobbelaar B, Noakes TD. 1993. Vitamin C suppleme tation reduces the incidence of postrace symptoms of upper-respiratory-tract infection in ultramarathon runners. Am J Clin Nutr 57:170–174. Pfeffer F, Valdes-Ramos R, Avila-Rosas H, Meza C, Casanueva E. 1996. Iron, zinc and vitamin C nutritional status is not related to weight gain in pregnant women. Nutr Res 16:555–564. Phull PS, Price AB, White KL, Schorah CJ, Jacyna MR. 1999. Gastroduodenal mucosal vitamin-C levels in Helicobacter pylori infection. Scand J Gastroenterol 34:361–366. Pirkle JL, Flegal KM, Bernert JT, Brody DJ, Etzel RA, Maurer KR. 1996. Exposure of the US population to environmental tobacco smoke: The Third National Health and Nutrition Examination Survey, 1988 to 1991 . J Am Med Assoc 275:1233–1240. Podmore ID, Griffiths HR, Herbert KE, Mistry N, Mistry P, Lunec J. 1998. Vitamin C exhibits pro-oxidant properties. Nature 392:559. Pohl H, Reidy JA. 1989. Vitamin C intake influences the bleomycin-induced chr mosome damage assay: Implications for detection of cancer susceptibility and chromosome breakage syndromes. Mutat Res 224:247–252. Powers HJ, Loban A, Silvers K, Gibson AT. 1995. Vitamin C at concentrations observed in premature babies inhibits the ferroxidase activity of caeruloplasmin. Free Radic Res 22:57–65. Prieme H, Loft S, Nyyssonen K, Salonen JT, Poulsen HE. 1997. No effect of supplementation with vitamin E, ascorbic acid, or coenzyme Q10 on oxidative DNA damage estimated by 8-hydroxy-7,8-dihydro-2'-deoxyguanosine excretion in smokers. Am J Clin Nutr 65:503–507. Pryor WA. 1992. Biological effects of cigarette smoke, wood smoke, and the smoke from plastics: The use of electron spin resonance. Free Radic Biol Med 13:659–676. Pryor WA. 1997. Cigarette smoke radicals and the role of free radicals in chemical carcinogenicity. Environ Hlth Perspect 105:875–882. Pryor WA, Prier DG, Church DF. 1983. Electron-spin resonance study of mai stream and sidestream cigarette smoke: Nature of the free radicals in gasphase smoke and in cigarette tar. Environ Hlth Perspect 47:345–355. Rajalakshmi R, Deodhar AD, Ramarkrishnan CV. 1965. Vitamin C secretion during lactation. Acta Paediatr Scand 54:375–382. Rebouche CJ. 1995. Renal handling of carnitine in experimental vitamin C def ciency. Metabolism 44:1639–1643. Rees DC, Kelsey H, Richards JDM. 1993. Acute haemolysis induced by high dose ascorbic acid in glucose-6-phosphate dehydrogenase deficiency. Br Med J 306:841–842. Rehman A, Collis CS, Yang M, Kelly M, Diplock AT, Halliwell B, Rice-Evans C. 1998. The effects of iron and vitamin C co-supplementation on oxidative da age to DNA in healthy volunteers. Biochem Biophys Res Commun 246:293–298. Reilly M, Delanty N, Lawson JA, Fitzgerald GA. 1996. Modulation of oxidant stress in vivo in chronic cigarette smokers . Circulation 94:19–25. Rhead WJ, Schrauzer GN. 1971. Risks of long-term ascorbic acid overdosage. Nutr Rev 29:262–263. Rifici VA, Khachadurian AK. 1993. Dietary supplementation with vitamins C and E inhibits in vitro oxidation of lipoproteins. J Am Coll Nutr 12:631–637.

OCR for page 95
DRI DIETARY REFERENCE INTAKES FOR Vitamin C, Vitamin E, Selenium, and Carotenoids Rimm EB, Stampfer MJ, Ascherio A, Giovannucci E, Colditz GA, Willett WC. 1993. Vitamin E consumption and the risk of coronary heart disease in men . N Engl J Med 328:1450–1456. Rivers, JM. 1987. Safety of high-level vitamin C ingestion. Ann NY Acad Sci 498:445–454. Robertson JM, Donner AP, Trevithick JR. 1989. Vitamin E intake and risk of cataracts in humans. Ann NY Acad Sci 570:372–382. Rokitzki L, Hinkel S, Klemp C, Cufi D, Keul J. 1994. Dietary, serum and urine ascorbic acid status in male athletes. Int J Sports Med 15:435–440. Rokkas T, Papatheodorou G, Karameris A, Mavrogeorgis A, Kalogeropoulos N, Giannikos N. 1995. Helicobacter pylori infection and gastric juice vitamin C levels. Impact of eradication . Dig Dis Sci 40:615–621. Romney SL, Duttagupta C, Basu J, Palan PR, Karp S, Slagle NS, Dwyer A, Wassertheil-Smoller S, Wylie-Rosett J. 1985. Plasma vitamin C and uterine cervical dysplasia. Am J Obstet Gynecol 151:976–980. Ronchetti IP, Quaglino D Jr, Bergamini G. 1996. Ascorbic acid and connective tissue. Subcell Biochem 25:249–264. Rose RC, Richer SP, Bode AM. 1998. Ocular oxidants and antioxidant protection. Proc Soc Exp Biol Med 217:397–407. Rumsey SC, Levine M. 1998. Absorption, transport, and disposition of ascorbic acid in humans . J Nutr Biochem 9:116–130. Russell AL. 1967. Epidemiology of periodontal disease. Int Dent J 17:282–296. Sahyoun NR, Jacques PF, Russell RM. 1996. Carotenoids, vitamins C and E, and mortality in an elderly population . Am J Epidemiol 144:501–511. Salmenpera L. 1984. Vitamin C nutrition during prolonged lactation: Optimal in infants while marginal in some mothers. Am J Clin Nutr 40:1050–1056. Salonen JT, Salonen R, Nyyssonen K, Korpela H. 1992. Iron sufficiency is associated with hypertension and excess risk of myocardial infarction: The Kuopio Ischemic Heart Disease Risk Factor Study (KIHD). Circulation 85:864–876. Samman S, Brown AJ, Beltran C, Singh S. 1997. The effect of ascorbic acid on plasma lipids and oxidisability of LDL in male smokers. Eur J Clin Nutr 51:472–477. Sasaki A, Kondo K, Sakamoto Y, Kurata H, Itakura H, Ikeda Y. 1997. Smoking cessation increases the resistance of low-density lipoprotein to oxidation. Atherosclerosis 130:109–111. Satarug S, Haswell-Elkins MR, Tsuda M, Mairiang P, Sithithaworn P, Mairiang E, Esumi H, Sukprasert S, Yongvanit P, Elkins DB. 1996. Thiocyanate-independent nitrosation in humans with carcinogenic parasite infection. Carcinogenesis 17:1075–1081. Sauberlich HE. 1994. Pharmacology of vitamin C. Annu Rev Nutr 14371–391. Scaccini C, Jialal I. 1994. LDL Modification by activated polymorphonuclear leukocytes: A cellular model of mild oxidative stress. Free Radic Biol Med 16:49–55. Schectman G, Byrd JC, Hoffmann R. 1991. Ascorbic acid requirements for smokers: Analysis of a population survey. Am J Clin Nutr 53:1466–1470. Schmidt KH, Hagmaier V, Hornig DH, Vuilleumier JP, Rutishauser G. 1981. Urinary oxalate excretion after large intakes of ascorbic acid in man. Am J Clin Nutr 34:305–311. Schrauzer GN, Rhead WJ. 1973. Ascorbic acid abuse: Effects on long-term ingestion of excessive amounts on blood levels and urinary excretion. Int J Vitam Nutr Res 43:201–211.

OCR for page 95
DRI DIETARY REFERENCE INTAKES FOR Vitamin C, Vitamin E, Selenium, and Carotenoids Schrauzer GN, Ishmael D, Kiefer GW. 1975. Some aspects of current vitamin C usage: Diminished high-altitude resistance following overdosage. Ann NY Acad Sci 258:377–381. Schwartz J, Weiss ST. 1994. Relationship between dietary vitamin C intake and pulmonary function in the First National Health and Nutrition Examination Survey (NHANES I). Am J Clin Nutr 59:110–114. Schwarz KB, Cox J, Sharma S, Witter F, Clement L, Sehnert SS, Risby TH. 1995. Cigarette smoking is pro-oxidant in pregnant women regardless of antioxidant nutrient intake. J Nutr Environ Med 5:225–234. Sharpe PC, MacAuley D, McCrum EE, Stott G, Evans AE, Mulholland C, Boreham CA, Duly E, Trinick TR. 1994. Ascorbate and exercise in the Northern Ireland population. Int J Vitam Nutr Res 64:277–282. Shekelle RB, Lepper M, Liu S, Maliza C, Raynor WJ, Rossof AH. 1981. Dietary vitamin A and risk of cancer in the Western Electric Study . Lancet 2:1185–1190. Shilotri PG, Bhat KS. 1977. Effect of mega doses of vitamin C on bactericidal activity of leukocytes . Am J Clin Nutr 30:1077–1081. Siegel C, Barker B, Kunstadter M. 1982. Conditioned oral scurvy due to megavitamin C withdrawal. J Periodontol 53:453–455. Sies H, Stahl W. 1995. Vitamins E and C, beta-carotene, and other carotenoids as antioxidants . Am J Clin Nutr 62:1315S–1321S. Simon JA. 1992. Vitamin C and cardiovascular disease: A review. J Am Coll Nutr 11:107–125. Simon JA, Hudes ES, Browner WS. 1998. Serum ascorbic acid and cardiovascular disease prevalence in US adults . Epidemiology 9:316–321. Singh RB, Ghosh S, Niaz MA, Singh R, Beegum R, Chibo H, Shoumin Z, Postiglione A. 1995. Dietary intake, plasma levels of antioxidant vitamins, and oxidative stress in relation to coronary artery disease in elderly subjects . Am J Cardiol 76:1233–1238. Sinha R, Block G, Taylor PR. 1993. Problems with estimating vitamin C intakes. Am J Clin Nutr 57:547–550. Skaper SD, Fabris M, Ferrari V, Carbonare MD, Leon A. 1997. Quercetin protects cutaneous tissue-associated cell types including sensory neurons from oxidative stress induced by glutathione depletion: Cooperative effects of ascorbic acid. Free Radic Biol Med 22:669–678. Sneed SM, Zane C, Thomas MR. 1981. The effects of ascorbic acid, vitamin B6, vitamin B12, and folic acid supplementation on the breast milk and maternal nutritional status of low socioeconomic lactating women. Am J Clin Nutr 34:1338–1346. Solzbach U, Hornig B, Jeserich M, Just H. 1997. Vitamin C improves endothelial dysfunction of epicardial coronary arteries in hypertensive patients. Circulation 96:1513–1519. Specker BL, Beck A, Kalkwarf H., Ho M. 1997. Randomized trial of varying mineral intake on total body bone mineral accretion during the first year of life. Pediatrics 99:e12. Stein HB, Hasan A, Fox IH. 1976. Ascorbic acid-induced uricosuria. Ann Intern Med 84:385–388. Taddei S, Virdis A, Ghiadoni L, Magagna A, Salvetti A. 1998. Vitamin C improves endothelium-dependent vasodilation by restoring nitric oxide activity in essential hypertension. Circulation 97:2222–2229.

OCR for page 95
DRI DIETARY REFERENCE INTAKES FOR Vitamin C, Vitamin E, Selenium, and Carotenoids Thomas MR, Kawamoto J, Sneed SM, Eakin R. 1979. The effects of vitamin C, vitamin B6, and vitamin B12 supplementation on the breast milk and maternal status of well-nourished women. Am J Clin Nutr 32:1679–1685. Thomas MR, Sneed SM, Wei C, Nail PA, Wilson M, Sprinkle EE. 1980. The effects of vitamin C, vitamin B6, vitamin B12, folic acid, riboflavin, and thiamin on the breast milk and maternal status of well-nourished women at 6 months postpartum. Am J Clin Nutr 33:2151–2156. Timimi FK, Ting HH, Haley EA, Roddy MA, Ganz P, Creager MA. 1998. Vitamin C improves endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. J Am Coll Cardiol 31:552–557. Ting HH, Timimi FK, Boles KS, Creager SJ, Ganz P, Creager MA. 1996. Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus. J Clin Invest 97:22–28. Ting HH, Timimi FK, Haley EA, Roddy MA, Ganz P, Creager MA. 1997. Vitamin C improves endothelium-dependent vasodilation in forearm resistance vessels of humans with hypercholesterolemia. Circulation 95:2617–2622. Tiselius HG, Almgard LE. 1977. The diurnal urinary excretion of oxalate and the effect of pyridoxine and ascorbate on oxalate excretion. Eur Urol 3:41–46. Tlaskal P, Novakova V. 1990. Vitamins C and E in neonates and their mothers. Cesk Pediatr 45:339–343. Tribble DL, Giuliano LJ, Fortmann SP. 1993. Reduced plasma ascorbic acid concentrations in nonsmokers regularly exposed to environmental tobacco smoke. Am J Clin Nutr 58:886–890. Tsao CS. 1997. An overview of ascorbic acid chemistry and biochemistry. In: Packer L, Fuchs J, eds. Vitamin C in Health and Disease. New York: Marcel Dekker. Pp. 25–58. Tsao CS, Leung PY. 1988. Urinary ascorbic acid levels following the withdrawal of large doses of ascorbic acid in guinea pigs. J Nutr 118:895–900. Tsao CS, Salimi SL. 1984. Effect of large intake of ascorbic acid on urinary and plasma oxalic acid levels. Int J Vitam Nutr Res 54:245–249. Udipi SA, Kirksey A, West K, Giacoia G. 1985. Vitamin B6, vitamin C and folacin levels in milk from mothers of term and preterm infants during the neonatal period. Am J Clin Nutr 42:522–530. Urivetzky M, Kessaris D, Smith AD. 1992. Ascorbic acid overdosing: A risk factor for calcium oxalate nephrolithiasis . J Urol 147:1215–1218. Valkonen M, Kuusi T. 1998. Passive smoking induces atherogenic changes in low-density lipoprotein . Circulation 97:2012–2016. VanderJagt DJ, Garry PJ, Bhagavan HN. 1987. Ascorbic acid intake and plasma levels in healthy elderly people. Am J Clin Nutr 46:290–294. Van Eekelen M. 1953. Occurrence of vitamin C in foods. Proc Nutr Soc 12:228–232. Vitale S, West S, Hallfrisch J, Alston C, Wang F, Moorman C, Muller D, Singh V, Taylor HR. 1993. Plasma antioxidants and risk of cortical and nuclear cataract. Epidemiology 4:195–203. Vogel RI, Lamster IB, Wechsler SA, Macedo B, Hartley LJ, Macedo JA. 1986. The effects of megadoses of ascorbic acid on PMN chemotaxis and experimental gingivitis. J Periodontol 57:472–479. Wandzilak TR, D'Andre SD, Davis PA, Williams HE. 1994. Effect of high dose vitamin C on urinary oxalate levels. J Urol 151:834–837. Wang Y, Russo TA, Kwon O, Chanock S, Rumsey SC, Levine M. 1997. Ascorbate recycling in human neutrophils: Induction by bacteria. Proc Natl Acad Sci USA 94:13816–13819.

OCR for page 95
DRI DIETARY REFERENCE INTAKES FOR Vitamin C, Vitamin E, Selenium, and Carotenoids Waring AJ, Drake IM, Schorah CJ, White KL, Lynch DA, Axon AT, Dixon MF. 1996. Ascorbic acid and total vitamin C concentrations in plasma, gastric juice, and gastrointestinal mucosa: Effects of gastritis and oral supplementation. Gut 38:171–176. Wassertheil-Smoller S, Romney SL, Wylie-Rosett J, Slagle S, Miller G, Lucido D, Duttagupta C, Palan PR. 1981. Dietary vitamin C and uterine cervical dysplasia. Am J Epidemiol 114:714–724. Weber C, Wolfgang E, Weber K, Weber PC. 1996. Increased adhesiveness of isolated monocytes to endothelium is prevented by vitamin C intake in smokers. Circulation 93:1488–1492. Wen Y, Cooke T Feely, J. 1997. The effect of pharmacological supplementation with vitamin C on low-density lipoprotein oxidation. Br J Clin Pharmacol 44:94–97. Witt EH, Reznick AZ, Viguie CA, Starke-Reed P, Packer L. 1992. Exercise, oxidative damage and effects of antioxidant manipulation . J Nutr 122:766–773. Witztum JL, Steinberg D. 1991. Role of oxidized low density lipoprotein in atherogenesis. J Clin Invest 88:1785–1792. Woolfe SN, Kenney EB, Hume WR, Carranza FA Jr. 1984. Relationship of ascorbic acid levels of blood and gingival tissue with response to periodontal therapy. J Clin Periodontol 11:159–165. Yong LC, Brown CC, Schatzkin A, Dresser CM, Slesinski MJ, Cox CS, Taylor PR. 1997. Intake of vitamins E, C, and A and risk of lung cancer. The NHANES I Epidemiologic Followup Study. Am J Epidemiol 146:231–243. Young JC, Kenyon EM, Calabrese EJ. 1990. Inhibition of beta-glucuronidase in human urine by ascorbic acid. Hum Exp Toxicol 9:165–170. Zatonski W, Przewozniak K, Howe GR, Maisonneuve P, Walker AM, Boyle P. 1991. Nutritional factors and pancreatic cancer: A case-control study from south west Poland. Int J Cancer 48:390–394.