Dietary Intake Of Ascorbic Acid Research Articles

Ascorbic acid intake is inversely associated with prevalence of depressive symptoms in US midlife women: A cross-sectional study

BackgroundWith the endocrine changes in menopausal transition period, associations between dietary ascorbic acid intake and depressive symptoms may be different. This investigation examined cross-sectional relations between dietary ascorbic acid intake of women and prevalence of depressive symptoms. MethodsThis is a secondary analysis performed on a subsample of the Study of Women's Health Across the Nation (SWAN). Women enrolled had measures of CES-D depression scores and ascorbic acid intake. Regression models were used to study cross-sectional associations between ascorbic acid intake and depressive symptoms. ResultsA total of 3088 women aged 42–52 years at baseline were included in the present study. Dietary ascorbic acid intake was inversely associated with depressive symptoms. The adjusted OR and 95% CI of depressive symptoms was 0.699 (0.524 – 0.934) in quartile 4 (the highest) versus quartile 1 (the lowest) of the ascorbic acid intake. Restricted cubic spline analyze showed a suggestion of L-shaped associations between ascorbic acid intake and depressive symptoms. ConclusionsAscorbic acid intake is inversely associated with prevalence of depressive symptoms in midlife women. Future prospective cohort studies are needed to confirm these findings.

Pathways of Gastric Carcinogenesis, Helicobacter pylori Virulence and Interactions with Antioxidant Systems, Vitamin C and Phytochemicals.

Helicobacter pylori is a class one carcinogen which causes chronic atrophic gastritis, gastric intestinal metaplasia, dysplasia and adenocarcinoma. The mechanisms by which H. pylori interacts with other risk and protective factors, particularly vitamin C in gastric carcinogenesis are complex. Gastric carcinogenesis includes metabolic, environmental, epigenetic, genomic, infective, inflammatory and oncogenic pathways. The molecular classification of gastric cancer subtypes has revolutionized the understanding of gastric carcinogenesis. This includes the tumour microenvironment, germline mutations, and the role of Helicobacter pylori bacteria, Epstein Barr virus and epigenetics in somatic mutations. There is evidence that ascorbic acid, phytochemicals and endogenous antioxidant systems can modify the risk of gastric cancer. Gastric juice ascorbate levels depend on dietary intake of ascorbic acid but can also be decreased by H. pylori infection, H. pylori CagA secretion, tobacco smoking, achlorhydria and chronic atrophic gastritis. Ascorbic acid may be protective against gastric cancer by its antioxidant effect in gastric cytoprotection, regenerating active vitamin E and glutathione, inhibiting endogenous N-nitrosation, reducing toxic effects of ingested nitrosodimethylamines and heterocyclic amines, and preventing H. pylori infection. The effectiveness of such cytoprotection is related to H. pylori strain virulence, particularly CagA expression. The role of vitamin C in epigenetic reprogramming in gastric cancer is still evolving. Other factors in conjunction with vitamin C also play a role in gastric carcinogenesis. Eradication of H. pylori may lead to recovery of vitamin C secretion by gastric epithelium and enable regression of premalignant gastric lesions, thereby interrupting the Correa cascade of gastric carcinogenesis.

Dietary Intake of Ascorbic Acid Attenuates Lipopolysaccharide-Induced Sepsis and Septic Inflammation in ODS Rats.

The aim of this study was to verify the protective effects of ascorbic acid (AsA) against lipopolysaccharide (LPS)-induced sepsis. The study was conducted using osteogenic disorder Shionogi (ODS) rats, which are unable to synthesize AsA. Male ODS rats (6 wk old) were fed either an AsA-free diet (AsA-deficient group), a diet supplemented with 300 mg/kg AsA (control group), or a diet supplemented with 3,000 mg/kg AsA (high-AsA group) for 8 d. On day 8, all the rats were intraperitoneally injected with LPS (15 mg/kg body weight). Forty-eight hours after the injection, the survival rates of the rats in the control (39%) and the high-AsA (61%) groups were significantly higher than that in the AsA-deficient group (5.5%). Next, we measured several inflammatory parameters during 10 h after administering LPS. At 6 h, elevated serum levels of markers for hepatic and systemic injuries were suppressed in rats fed AsA. Similarly, 10 h after LPS injection, the elevation in the serum levels of markers for renal injury were also suppressed proportionally to the amount of AsA in the diet. The elevated serum concentrations of TNFα and IL-1β by LPS in the AsA-deficient group decreased in groups fed AsA. Hematic TNFα mRNA levels at 6 h after the LPS injection were also lowered by feeding AsA. These results demonstrated that the dietary intake of AsA improved the survival rates and suppressed the inflammatory damage, in a dose-dependent manner, caused during sepsis induced by LPS in ODS rats.

Dietary fiber and colorectal cancer risk.

A meta-analysis of 13 case-control studies suggests that intakes of dietary fiber and risk of colon cancer are inversely associated. Weaker associations were observed between risk of colon cancer and dietary intake of ascorbic acid and beta-carotene.

Does vitamin C intake protect against lead toxicity?

Although several animal studies suggest a protective relationship between blood lead concentrations and ascorbic acid, there are inconclusive results regarding the beneficial effect of ascorbic acid on lead concentrations in human studies. Data from the Third National Health and Nutrition Examination Survey examined the association between ascorbic acid and blood lead concentrations in 19,578 participants ages 6-90 years without a history of lead poisoning. Elevated blood lead concentrations were found in 0.4% of adults and 0.5% of youths. Serum ascorbic acid concentrations were inversely associated with the prevalence of elevated blood lead concentrations. However, there was no significant relationship between dietary ascorbic acid intake and blood lead concentrations. This study suggests that there may be a protective relationship between ascorbic acid and lead. Questions remain regarding the unique roles of dietary vitamin C versus supplemental vitamin C in explaining this relationship.

Low dietary intake of β-carotene, α-tocopherol and ascorbic acid is associated with increased inflammatory and oxidative stress status in a Swedish cohort

Fruit and vegetable consumption has been associated with a reduced risk of several diseases including CVD. A part of these effects seen could be linked to anti-inflammatory and antioxidative effects, although this has not been thoroughly investigated. The present study was designed to investigate the effects of the dietary intake of beta-carotene, alpha-tocopherol and ascorbic acid on in vivo biomarkers of inflammation (PGF2alpha, high-sensitive C-reactive protein (hsCRP) and IL-6 formation) and oxidative stress (F2-isoprostane formation), the two important factors associated with accelerated atherosclerosis. The dietary intake of 704 participants in the Uppsala Longitudinal Study of Adult Men (ULSAM) at age 70 years was registered and inflammatory and oxidative stress biomarkers were quantified 7 years later. The registered dietary intakes of ascorbic acid and alpha-tocopherol were negatively associated linearly and in quartiles with both PGF2alpha, hsCRP, IL-6 and F2-isoprostanes, where ascorbic acid intake generally was more strongly associated. Dietary intake of beta-carotene was only significantly negatively associated with F2-isoprostanes. In conclusion, the present study is the first to suggest that the intake of food rich in antioxidants is associated with reduced cyclo-oxygenase- and cytokine-mediated inflammation and oxidative stress at 7 years of follow-up. These associations could be linked to the beneficial effects of fruit and vegetables observed on CVD.

Plasma ascorbic acid concentrations and fat distribution in 19 068 British men and women in the European Prospective Investigation into Cancer and Nutrition Norfolk cohort study

Antioxidants, such as ascorbic acid, play a role in scavenging free radicals to protect against oxidative endothelial damage. Excess fat may promote fatty acid oxidation and increase free radical concentrations, which could result in increased antioxidant use. Whether plasma ascorbic acid concentrations are associated with fat distribution remains unclear. Our aim was to examine the association between abdominal obesity, as measured by the waist-to-hip ratio, and plasma ascorbic acid concentrations in the general population. We examined the cross-sectional relation between anthropometric measurements of fat distribution and plasma ascorbic acid concentrations in 19 068 men and women aged 45-79 y without known chronic illness. Dietary ascorbic acid intake was estimated for a subgroup of 8178 men and women who kept 7-d food diaries coded for nutrient intake. The waist-to-hip ratio was inversely related to plasma ascorbic acid concentrations in both men and women. This association was independent of body mass index, age, vitamin supplement use, cigarette smoking, and socioeconomic group. Waist and hip circumferences showed separate and opposite associations with plasma ascorbic acid concentrations, independent of body mass index and other covariates. Dietary ascorbic acid intake only partly explained the observed associations. Plasma ascorbic acid was associated with fat distribution independent of body mass index. Differences in dietary intake and lifestyle habits, underlying systemic oxidative stress, or both may explain the inverse relation between fat distribution and plasma ascorbic acid concentrations. Additional studies are needed to determine the underlying explanation of these observations.

Selenium and antioxidant vitamin status of elderly German women

Low antioxidant intake and status have been shown to be associated with an elevated risk for various diseases. Data on the status of antioxidant vitamins, selenium and coenzyme Q10 of younger female seniors are scarce. The aim of this study was to assess the status of these antioxidants, as well as influencing factors such as dietary intake, anthropometric data and educational level in female seniors (60-70 years) in Germany. Dietary intake of alpha-tocopherol, beta-carotene and ascorbic acid was determined by a 3-day diet record. Serum concentrations of alpha-tocopherol, beta-carotene, ascorbic acid, selenium and coenzyme Q10 were measured. Anthropometric measures, socioeconomic and educational status were assessed. In total, 178 elderly women without severe diseases in the region of Hannover, Germany, were included in the study. The mean (+/- s.d.) age and BMI of the women was 63.2 (2.73) years and 25.6 (3.77) kg/m2, respectively. The study participants were generally better educated than the overall German female population. Dietary intake of the ascorbic acid and alpha-tocopherol was below RDA in six and 75% of the women, respectively. In comparison to estimated desirable serum concentrations of alpha-tocopherol, ascorbic acid, beta-carotene and selenium, lower concentrations were found in 23, 1, 6, and 39% of the women, respectively. Ascorbic acid (r = 0.205, P = 0.009) and beta-carotene (r = 0.173, P = 0.025) intake were significantly associated with serum concentrations. Beta-carotene concentrations were influenced by the type of diet, BMI, and school education (R2 = 0.128, P < 0.001). Serum selenium was positively associated with alcohol intake (r = 0.229, P = 0.003). Neither employment nor vocational training was predictive for the serum concentrations of antioxidant vitamins, selenium or coenzyme Q10. Poor status of selenium and alpha-tocopherol is highly prevalent even among younger, well-educated female seniors, whereas ascorbic acid and beta-carotene status seems sufficient in most women.

Enhancers of Iron Absorption: Ascorbic Acid and other Organic Acids

Ascorbic acid (AA), with its reducing and chelating properties, is the most efficient enhancer of non-heme iron absorption when its stability in the food vehicle is ensured. The number of studies investigating the effect of AA on ferrous sulfate absorption far outweighs that of other iron fortificants. The promotion of iron absorption in the presence of AA is more pronounced in meals containing inhibitors of iron absorption. Meals containing low to medium levels of inhibitors require the addition of AA at a molar ratio of 2:1 (e.g., 20 mg AA: 3 mg iron). To promote absorption in the presence of high levels of inhibitors, AA needs to be added at a molar ratio in excess of 4:1, which may be impractical. The effectiveness of AA in promoting absorption from less soluble compounds, such as ferrous fumarate and elemental iron, requires further investigation. The instability of AA during food processing, storage, and cooking, and the possibility of unwanted sensory changes limits the number of suitable food vehicles for AA, whether used as vitamin fortificant or as an iron enhancer. Suitable vehicles include dry-blended foods, such as complementary, precooked cereal-based infant foods, powdered milk, and other dry beverage products made for reconstitution that are packaged, stored, and prepared in a way that maximizes retention of this vitamin. The consumption of natural sources of Vitamin C (fruits and vegetables) with iron-fortified dry blended foods is also recommended. Encapsulation can mitigate some of the AA losses during processing and storage, but these interventions will also add cost. In addition, the bioavailability of encapsulated iron in the presence/absence of AA will need careful assessment in human clinical trials. The long-term effect of high AA intake on iron status may be less than predicted from single meal studies. The hypothesis that an overall increase of dietary AA intake, or fortification of some foods commonly consumed with the main meal with AA alone, may be as effective as the fortification of the same food vehicle with AA and iron, merits further investigation. This must involve the consideration of practicalities of implementation. To date, programs based on iron and AA fortification of infant formulas and cow's milk provide the strongest evidence for the efficacy of AA fortification. Present results suggest that the effect of organic acids, as measured by in vitro and in vivo methods, is dependent on the source of iron, the type and concentration of organic acid, pH, processing methods, and the food matrix. The iron absorption-enhancing effect of AA is more potent than that of other organic acids due to its ability to reduce ferric to ferrous iron. Based on the limited data available, other organic acids may only be effective at ratios of acid to iron in excess of 100 molar. This would translate into the minimum presence/addition of 1 g citric acid to a meal containing 3 mg iron. Further characterization of the effectiveness of various organic acids in promoting iron absorption is required, in particular with respect to the optimal molar ratio of organic acid to iron, and associated feasibility for food application purposes. The suggested amount of any organic acid required to produce a nutritional benefit will result in unwanted organoleptic changes in most foods, thus limiting its application to a small number of food vehicles (e.g., condiments, beverages). However, fermented foods that already contain high levels of organic acid may be suitable iron fortification vehicles.

Relation of ascorbic acid to bone mineral density and self-reported fractures among US adults.

Ascorbic acid is an essential nutrient involved in collagen formation, and its deficiency is associated with abnormal bone development. To examine the relation of ascorbic acid to bone mineral density and the prevalence of self-reported fractures, the authors analyzed data collected from 13,080 adults enrolled in the Third National Health and Nutrition Examination Survey (NHANES III) during 1988-1994. Because they identified three-way interactions among smoking, history of estrogen use, and dietary and serum ascorbic acid in postmenopausal women, they analyzed these relations stratified by smoking and estrogen use. Dietary ascorbic acid intake was independently associated with bone mineral density among premenopausal women (p = 0.002). Among men, serum ascorbic acid was associated in a nonlinear fashion with bone mineral density (p < 0.05), and dietary ascorbic acid intake was associated in a nonlinear fashion with self-reported fracture (p = 0.05). Among postmenopausal women without a history of smoking or estrogen use, serum ascorbic acid was unexpectedly associated with lower bone mineral density (p = 0.01). However, among postmenopausal women with a history of smoking and estrogen use, a standard deviation increase in serum ascorbic acid was associated with a 49% decrease in fracture prevalence (p = 0.001). Dietary and serum ascorbic acid measures were associated inconsistently with bone mineral density and self-reported fracture among adult participants in NHANES III.

Plasma ascorbic acid in patients undergoing chronic haemodialysis

Patients with renal disease receiving dialysis therapy are susceptible to a deficit in ascorbic acid (AA) caused by loss during dialysis and a restricted dietary AA intake. In previous studies, in such patients, the methods generally used for AA determination are non-specific and insensitive, and control of the easily deteriorating AA in the samples is often disregarded. The purpose of this work was to study the AA plasma levels and dialyser clearances as well as the kinetics of administered AA in a group of dialysis patients, using selective and sensitive methodology and a procedure preserving the AA sample content. Using an analytical method based on high-performance liquid chromatography and electrochemical detection, we have examined the dialyser clearance of AA as well as the pre- and post dialysis plasma levels of AA in patients on chronic dialysis therapy. The plasma AA levels were further measured after single and multiple dose supplementation of 200 mg p.o. per day. The majority of the patients (16 of 19) had pre-dialysis plasma levels below the normal range. The dialyser clearance of AA was 212 ml/min (median value). Following dialysis, the plasma AA concentrations were reduced by a median of 33%. AA supplementation significantly increased these levels; however, they dropped soon after supplementation was stopped. AA in uraemic whole blood and plasma was, on average, less stable than in samples from healthy subjects. This study, using selective analytical method with adequate stability control, confirms that AA is readily removed by conventional haemodialysis membranes. Patients on chronic haemodialysis have remarkably low plasma AA levels unless given AA supplementation.

Effect of high dietary intake of vitamin C on non-specific immune response of gilthead seabream (Sparus aurata L.)

To determine the effect of a high level of dietary intake of ascorbic acid (vitamin C) on the non-specific immune response of gilthead seabream (Sparus aurata L.), specimens were fed diets containing 500mg kg−1(control) and 3,000mg kg−1ascorbic acid for 2, 4, 6, 8 or 10 weeks. Growth, serum level of vitamin C, natural haemolytic complement activity and head-kidney leucocyte migratory, respiratory burst and phagocytic activities were studied at each one of the assayed times. A positive relationship between vitamin C intake and serum ascorbic acid was observed, the enhancement being evident after 2 weeks of administration and maintained until 10 weeks. Specimens fed a vitamin C supplemented diet showed a slightly higher (but no statistically significant) specific growth rate than fish fed the control diet. The non-specific immune response parameters assayed were enhanced by the dietary intake of vitamin C although, each one peaked at a different time: phagocytic activity after 2 weeks of administration, natural haemolytic complement activity after 6 weeks, respiratory burst after 8 weeks. However, leucocyte migration was not affected. The results indicated that the serum ascorbate concentration of specimens fed a high level of vitamin C reach a plateau. The non-specific immune response parameters assayed increased as a consequence of a high vitamin C supply, although the increase was not maintained but returned to the initial levels. This suggests that the immune response accomodates to the new high vitamin C plasma availability after a transient enhancement.

Reactive oxygen species activity and lipid peroxidation inHelicobacter pylori associated gastritis: relation to gastric mucosal ascorbic acid concentrations and effect of H pylori eradication

Background—Helicobacter pylori is an independent risk factor for gastric cancer, and this association may be due to the bacterium causing reactive oxygen species mediated damage to DNA in the gastric...

Ascorbic acid may protect against human gastric cancer by scavenging mucosal oxygen radicals.

High dietary ascorbic acid intake appears to protect against gastric cancer. This may be due to its action as a scavenger of reactive radical species formed in the gastric mucosa, resulting in a reduced level of radical-mediated DNA damage. We have studied 82 patients, of whom 37 had Helicobacter pylori-associated gastritis, a condition which predisposes to gastric cancer. Using electron paramagnetic resonance (EPR) spectroscopy we have demonstrated, for the first time, that ascorbyl radicals are generated in human gastric mucosa, presumably as a result of scavenging of free radicals by ascorbic acid. Quantification of ascorbyl radicals demonstrates that there is a higher concentration in those patients with H.pylori gastritis compared with subjects with normal histology (P < 0.01). We also found gastric mucosal luminol-enhanced chemiluminescence and malondialdehyde concentrations (which are believed to be markers of radical generation and tissue damage) to be higher in patients with H.pylori gastritis compared with those with normal histology (P < 0.001 and P < 0.01 respectively). The observed concentrations of the ascorbyl radical correlate with the level of luminol-enhanced chemiluminescence (r = 0.41, P < 0.001), but not with malondialdehyde concentrations (r = 0.08, P = 0.47). Mucosal ascorbic acid and total vitamin C concentrations did not vary between histological groups, nor did they correlate with mucosal levels of the ascorbyl radical, chemiluminescence or malondialdehyde. These data suggest that ascorbic acid is acting as a scavenger of free radicals generated in human gastric mucosa. The experiments therefore provide direct supportive evidence for the hypothesis that ascorbic acid protects against gastric cancer by scavenging reactive radical species which would otherwise react with DNA, with resultant genetic damage.

Effect of Ascorbic Acid Supplementation on Phagocytic Function in Rats during Ageing.

Ageing is associated with greater susceptibility to nutritional deficiencies and to progressive senescence of the immune system. Ascorbic acid has been reported to have a corrective influence on the alteration of immunological functions that occurs during ageing. We examined the effect of a daily oral dose of ascorbic acid (20mg/100g body weight for 15, 30, and 60 days) on immune responses in young and old rats. A significant increase was observed in the total leucocyte count in both young and old rats after 60 days of ascorbic acid supplementation. When rats were fed the normal diet, the values of phagocytosis, nitroblue tetrazolium reduction test, and soluble immune complex were lower in the older animals than in the younger. On supplementation with ascorbic acid, an increase in all these immunological functions was observed, the increment being highly significant in old rats after 60 days of ascorbic acid supplementation. Hence, our results suggest that dietary intake of ascorbic acid influences the cell-mediated immunity during the ageing process.

The relationship between dietary ascorbic acid intake and serum lipid concentration in the aged

The aim of this study was to investigate the relationship between dietary ascorbic acid intake and serum lipid concentration in the aged. The amount of dairy food intake for three consecutive days were measured and the serum levels of total-cholesterol (TC), triglyceride (TG), HDL-cholesterol (HDLC) were determined 279 subjects (135 males and 135 females), 65 years and over living in one community. The LDL-cholesterol (LDLC) was calculated by (TC-HDLC)-TG x 0.2. Dietary ascorbic acid intake showed no significantly difference between males and females, but had a significantly positive correlation with HDLC, the intake of carbohydrates and protein and total fat. However it had a significantly negative correlation with LDLC and LDLC/HDLC. Multiple regression analysis showed that dietary ascorbic acid intake had a statistically significant relationship with HDLC, LDLC and LDLC/HDLC. Since HDLC, which is known to be an anti-atherogenic, was related to increase in the dietary ascorbic acid intake, and LDLC, which is known to be an atherogenic, was related to its decrease, it was suggested that dietary ascorbic acid intake might have an important effect on the genesis and prevention of atherogenic diseases.

Effect of ascorbic acid and its synthetic lipophilic derivative ascorbyl palmitate on phorbol ester-induced skin-tumor promotion in mice

The effect of topical application of ascorbic acid (AA) and ascorbyl palmitate (AP) on 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced tumor promotion in mouse skin was investigated. A single application of TPA decreased epidermal AA by 45%. Repetitive application of 6 and 28 mumol AA with 2 nmol TPA inhibited tumor multiplicity by 39% and 76%. Repetitive application of 0.16, 0.8, and 4.0 mumol AA with 5 nmol TPA inhibited tumor multiplicity by 16%, 46%, and 91%. Because AA may be poorly absorbed cutaneously, we evaluated the effect of dietary AA. Supplementation of drinking water with AA increased epidermal ascorbic acid levels by 50%. Dietary intake of AA did not inhibit TPA-induced tumor promotion. Preliminary data suggest that the mice not receiving AA developed increased epidermal AA levels in response to the tumor promoting regimen. Recently we have found that dietary AP inhibited TPA-induced biochemical parameters associated with tumor promotion.

Glutathione Blood Levels and Other Oxidant Defense Indices in Men Fed Diets Low in Vitamin C

Because ascorbic acid is an important contributor to the oxidant defense system in body tissues, we studied the effects of a low dietary intake of ascorbic acid on various indicators of oxidant defense and oxidant damage. During a 13-wk study eight healthy men (25-43 y), residing in a live-in metabolic unit, were fed controlled diets containing different amounts of ascorbic acid for four consecutive periods: period 1 = 250 mg/d for 4 d; period 2 = 5 mg/d for 32 d; period 3 = 10 or 20 mg/d for 28 d and period 4 = 60 or 250 mg/d for 28 d. Measurements were made at several time intervals of the activities of glutathione peroxidase and superoxide dismutase in RBC, DNA strand breaks in mononuclear leucocytes, glutathione concentrations in plasma and RBC and NAD and NADP in RBC. After 60 d of low ascorbic acid intakes and associated with plasma ascorbic acid levels less than 6 mumol/L, the total glutathione concentration and the reduced glutathione:oxidized glutathione ratio were decreased in plasma. At the same time NAD and NADP levels in RBC were elevated. It seems that chronic marginal vitamin C deficiency states may be associated with selected biochemical changes in oxidant defense indices.

Role of dietary ascorbic acid in vitellogenesis in rainbow trout ( Salmo gairdneri)

Adult rainbow trout which were fed a diet devoid of ascorbic acid for 21 months, including the stages of gonadal development, showed no macroscopic signs of avitaminosis C and no increased mortality compared to a control group of fish with dietary supplementation of this vitamin. Fish without dietary supplementation of ascorbic acid contained more lipid in the liver and less in the ovaries than the reference fish. The lipid metabolism of the maturing fish is thus affected when the dietary intake of ascorbic acid is very low or absent. Fish without dietary ascorbic acid became anaemic (reduced levels of haemoglobin and haematocrit) towards the end of the feeding period. The serum levels of oestradiol-17β and vitellogenin were also lower in these fish. Possible modes of action of ascorbic acid in maturing rainbow trout are discussed on the basis of the presented analytical data on ascorbic acid, gross composition, blood serum levels of oestradiol-17β, vitellogenin, total protein, albumin, cholesterol, calcium, phosphorus and haematological parameters.

A case-control study of plasma ascorbate and acute necrotizing ulcerative gingivitis.

Data from animal studies and from studies of patients with acute necrotizing ulcerative gingivitis (ANUG) have provided suggestive evidence for an association between ascorbate deficiency and disease risk. Further, there is biological plausibility for such an association, due to the role of ascorbate in collagen synthesis and leukocyte function. A case-control study of plasma ascorbate and ANUG was performed on 60 patients with a history of ANUG infection and 60 age-race-sex-matched controls. No cases had had active lesions for at least two months prior to their vitamin assay to avoid any potential reduction of dietary intake of ascorbic acid due to the presence of painful mouth lesions. According to results obtained by use of a modification of the 2,4-dinitrophenylhydrazine method for determination of total plasma ascorbate, the mean and standard error of the mean of plasma ascorbate for all ANUG cases was 0.07 +/- 0.006 mmol/L; the mean for all controls was 0.10 +/- 0.006 mmol/L. Paired differences in plasma ascorbic acid concentrations between cases and controls were significantly different from zero (p less than 0.001). The unadjusted relative risk (RR) of ANUG as obtained by conditional logistic regression for subjects whose plasma ascorbic acid concentration was at or below the median value for controls, relative to subjects with higher values, was 7.3 (90% confidence interval, 3.0 - 17.4; one-sided p value less than 0.001). Patients with a history of ANUG ingested a daily average of 1.2 +/- 0.2 servings of dietary ascorbic acid, as compared with a daily average of 1.9 +/- 0.2 servings for healthy controls.(ABSTRACT TRUNCATED AT 250 WORDS)