Blood Ascorbic Acid Research Articles

Content of ascorbic acid in different skin phototypes in children with vitiligo

Aim. To evaluate the blood level of ascorbic acid in children with vitiligo according to skin phototype.Material and Methods. Blood ascorbic acid levels were analysed in children of different ages (6-15 years) with different types of vitiligo, depending on skin phototype. Patients were divided into two groups according to the degree and localisation of the vitiligo lesions: with non-segmental (n=116) and with segmental (n=134) vitiligo. The area of distribution of the dermatosis and its stage of development were calculated using the VIMAN and VIDA indices, respectively. Serum ascorbic acid levels were determined by liquid chromatography-mass spectrometry. Patients were classified by phototype according to T. Fitzpatrick’s classification.Results and discussion. Among the children with vitiligo studied, skin phototypes II, III and IV were identified, with a predominance of phototype III over the others. Their percentages differed in the two groups studied. In non-segmental vitiligo, there were more children with a light phototype and fewer with a dark phototype compared to the group of children with segmental vitiligo. Ascorbic acid levels were significantly reduced in children with vitiligo compared to a group of healthy children. The most pronounced decrease was observed in the group with non-segmental vitiligo in the 7-9 year age group. In both groups of patients, there was a tendency for ascorbic acid levels to decrease with age.Conclusion. The data obtained indicate that children with vitiligo have lower ascorbic acid levels than healthy children. The tendency to decrease increases with age, especially in patients with a dark phototype. This fact indicates the need to correct vitamin C levels in the body of children with vitiligo.

RELATIONSHIP OF LEAD WITH FREE RADICALS, REACTIVE OXYGEN SPECIES, OXIDATIVE STRESS AND ANTIOXIDANT ENZYMES

Heavy metals, which are high in the environment, are substances that have a high toxic effect even at low concentrations. Heavy metals taken into the organism through mouth, respiration and skin cannot be eliminated by the body's excretory pathways. In addition, since they have a durable structure, they participate in the food chain and accumulate in various body tissues. With the increase in industrial activities, heavy metal pollution has also emerged and has increased day by day. Lead is an element that is widely used in industry because it has a low melting temperature. However, it is known that lead, like other heavy metals, has an effect on problems such as environmental pollution and health problems. Occupational diseases such as lead poisoning occur as a result of direct exposure to lead. Direct exposure in this way can also cause death. Lead causes undesirable conditions such as increase of reactive oxygen species (ROS), emergence of oxidative stress and weakening of antioxidant system. Lead disrupts the prooxidant/antioxidant ratio. As a result, effects such as an increase in ROS and thus damage to the basic components of the cell such as lipid, protein and nucleic acid are observed.In particular, lead inhibits enzymes and prevents some enzymes from acting as antioxidants. As a result of exposure to lead, there is a decrease in the defense abilities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), glutathione (GSH) and ascorbic acid in blood and tissues. Lead increases lipid peroxidation and thus causes oxidative damage. Evaluation of the effect of lead at the cellular level is important in terms of developing solutions for the toxic effects of lead. In this study, the effect of lead on the cellular level in the organism and its effects on free radicals, ROS and oxidative stress were evaluated.

P1.01-071 High Dose IVAA Synergy with mEHT in Patients with Stage III-IV NSCLC: A Phase I Study

Ascorbic acid (AA) infusion and modulated electrohyperthermia (mEHT) are widely used by integrative cancer practitioners for many years. However, there are no sufficient data in safety, quality of life and clinical response of the above treatments in patients with stage III-IV Non-Small Cell Lung Cancer (NSCLC).We designed a Phase I trial to provide the evidence. Blood ascorbic acid in the fasting state was obtained from 35 NSCLC patients; selecting from them 15 patients with stage III-IV entered the phase I -II study. They were randomized allocated into 3 groups, and received doses 1.0, 1.2, 1.5g/kgAA infusions. Pharmacokinetic profiles were obtained when they received solely IVAA at concentrations of 1g/kg, 1.2g/kg, and 1.5g/kg, and when IVAA in combination with mEHT. The process was applied 3 times a week (every other day, weekend days off) for 8 weeks. Participants in the first group received intravenous AA (IVAA) when mEHT was finished, in the second group IVAA was administered simultaneously with mEHT and in the third group IVAA was applied first, and followed with mEHT. DLT was defined as any reversible grade ≥3 adverse events, whether hematological or non-hematological. CT enhanced scan were collected from the patients before the treatment and one month after the treatment finished. Fasting plasma AA levels were significantly correlated with stage of the disease. The overall toxicity was marginal. Thirstiness was the major symptom during all of the treatments. Peak concentration of AA was significantly higher in the simultaneous treatments than in other combinations with mEHT or in solely IV AA-managed groups. The average scores for the functioning scales continuously increased and the symptoms gradually decrease over the full cycle of the study. By using RECIST 1.1 criteria, two of four subjects diagnosed with lung squamous cell carcinoma had partial response (PR), two of four had stable disease(SD). Two of ten patients diagnosed with lung adenocarcinoma had had PR, three of ten had SD, five of ten had progressive disease. IVAA synergies with simultaneous mEHT were safe and can be well tolerated in patients. Patients diagnosed with squamous cell lung cancer were sensitive to the above two treatments. There’s a need for a phase II study with advanced NSCLC patients administering mEHT simultaneously with IVAA to assess for the efficacy and progression free survival time.

The safety and pharmacokinetics of high dose intravenous ascorbic acid synergy with modulated electrohyperthermia in Chinese patients with stage III-IV non-small cell lung cancer

Ascorbic acid (AA) infusion and modulated electrohyperthermia (mEHT) are widely used by integrative cancer practitioners for many years. However, there are no safety and pharmacokinetics data in Chinese cancer patients. We carried out a clinical trial to evaluate the safety and pharmacokinetics of those methods in patients with stage III-IV non-small cell lung cancer (NSCLC). Blood ascorbic acid in the fasting state was obtained from 35 NSCLC patients; selecting from them 15 patients with stage III-IV entered the phase I study. They were randomized allocated into 3 groups, and received doses 1.0, 1.2, 1.5g/kg AA infusions. Participants in the first group received intravenous AA (IVAA) when mEHT was finished, in the second group IVAA was administered simultaneously with mEHT and in the third group IVAA was applied first, and followed with mEHT. Pharmacokinetic profiles were obtained when they received solely IVAA and when IVAA in combination with mEHT. The process was applied 3 times a week (every other day, weekend days off) for 4weeks. We found that fasting plasma AA levels were significantly correlated with stage of the disease. Peak concentration of AA was significantly higher in the simultaneous treatments than in other combinations with mEHT or in solely IVAA-managed groups. IVAA synergy with simultaneous mEHT is safe and the concomitant application significantly increases the plasma AA level for NSCLC patients.

A phase I-II clinical trial to evaluate the safety, pharmacokinetics, and efficacy of high-dose intravenous ascorbic acid synergy with mEHT in Chinese patients with stage III-IV non-small cell lung cancer.

e20078 Background: Ascorbic acid (AA) infusion and modulated electrohyperthermia (mEHT) are widely used by integrative cancer practitioners for many years. However, there are no safety and pharmacokinetics data in Chinese cancer patients. Methods: Blood ascorbic acid in the fasting state was obtained from 35 NSCLC patients; selecting from them 15 patients with stage III-IV entered the phase I-II study. They were randomized allocated into 3 groups. Pharmacokinetic profiles were obtained when they received solely IVAA at concentrations of 1g/kg, 1.2g/kg, and 1.5g/kg, and when IVAA in combination with mEHT. The process was applied 3 times a week for 4 weeks. Participants in the first group received IVAA when mEHT was finished, in the second group IVAA was administered simultaneously with mEHT and in the third group IVAA was applied first, and followed with mEHT. All patients started the trial doses of 1 g/kg for 8 treatments. When there was no DLT observed, the test dose for patients increased to 1.2 g/kg and 1.5 g/kg. DLT was defined as any reversible grade ≥3 adverse events, whether haematological or non-haematological. Results: Fasting plasma AA levels were significantly correlated with stage of the disease. Peak concentration of AA were significantly higher in the simultaneous treatments than in other combinations with mEHT or in solely IVAAmanaged groups. The average scores for the functioning scales continuously increased and the symptoms gradually decrease over the full cycle of the study.3/7 patients with squamous cell lung cancer were CR, 4/7 were PR. 1/8 patient with adenocarcinoma cell lung cancer was PR, 5/8 were SD, and 2/8 were died. Conclusions: IVAA synergies with simultaneous mEHT is safe and the concomitant application significantly increases the plasma AA level for NSCLC patients. QOL is improved when they receive the above treatments. Patients diagnosed with squamous cell lung cancer were sensitive to the above two treatments. Clinical trial information: NCT02655913.

An Experimental Evaluation of Adaptogenic Potential of Standardized Epipremnum Aureum Leaf Extract.

Background:Stress is a normal part of everyday life but chronic stress can lead to a variety of stress-related illnesses including hypertension, anxiety, and depression. In the present investigation, standardized leaf extract of Epipremnumaureum was evaluated for its anti-stress potential.Materials and Methods:For the evaluation of anti-stress activity, groups of mice (n = 6) were subjected to forced swim stress and anoxic stress tolerance test in mice 1h after daily treatment of E.aureumextract. Diazepam (5 mg/kg) was taken as a reference standard. Urinary vanillylmandelic acid (VMA) and ascorbic acid were selected as noninvasive biomarkers to assess the anti-stress activity and plasma cortisol, blood ascorbic acid, and weight of adrenal were measured. The 24 h urinary excretion of VMA and ascorbic acid were determined by spectrophotometric methods in all groups under normal and stressed conditions. The hematological parameters (neutrophils, lymphocytes, and eosinophils) were also determined.Results:Administration of E.aureumat doses of 400 and 600 mg/kg wasfound to be effective in inhibiting the stress induced urinary biochemical changes in a dose-dependent manner. Treatment with E. aureum extract prevents the rise in blood ascorbic acid and plasma cortisol. Moreover, the extract prevented the increase in weight of adrenal gland also significantly increased the anoxia stress tolerance time. Dose-dependent significant reduction in white blood cell count was observed in anoxic stress tolerance test as compared to stressed group.Conclusion:Hence, the present study provides scientific support for the positiveadaptogenic effect of E. aureum extract.

Pseudohypoglycemia or hyperglycemia caused by interference with self-monitoring blood glucose measurements in anticancer ascorbic acid therapy.

Self‐monitoring blood glucose (SMBG) meters are now commonly used in diabetes management1. Many drugs, including ascorbic acid, are known to interfere with glucose measurements using these meters2. However, so far, misdiagnosis caused by interference has rarely occurred at the conventional doses. Recently, intravenous high‐dose ascorbic acid treatment has been widely used in 11,233 patients in 2006 and 8,876 patients in 2008 in the USA as one of the complementary and alternative medicines for infection and fatigue, as well as various cancers3. A 71‐year‐old woman with advanced esophageal cancer and diabetes presented to the Department of Metabolic Medicine, Osaka University Hospital, Suita, Japan, for glycemic control in November 2012. At the first visit, her glycosylated hemoglobin level was 8.8%. SMBG was carried out using the Medisafe® meter (TERUMO Corp., Tokyo, Japan) to determine the dosage of regular insulin before every meal. One day, she was given a high ascorbic acid dose (50 g) in another hospital. Her blood ascorbic acid concentration just after administration was 342 μg/mL (normal range 4.7–17.8 μg/mL), and her blood glucose level determined with the Medisafe® meter was below 1.1 mmol/L, which was ‘low’. Simultaneously, glucose levels were measured using the Glucocard® meter (ARKRAY Inc., Kyoto, Japan). According to the Glucocard® meter, her blood glucose level was above 33.3 mmol/L, which was “high.” She had neither hypoglycemic nor hyperglycemic symptoms. The fasting blood glucose level (9.3 mmol/L) determined with the Medisafe® meter 2 days after administration was close to the level (9.2 mmol/L) determined using the intra‐hospital laboratory test based on the hexokinase method (Quickauto‐Neo GLU‐HK; SHINO‐TEST Corp., Tokyo, Japan) and using an automated analyzer (JCA‐BM6050; JEOL Ltd., Tokyo, Japan). Then, the treatment with intravenous high‐dose ascorbic acid was discontinued with her consent. We prepared blood samples that contained 4.4 and 11.1 mmol/L glucose, and 0–500 μg/mL ascorbic acid. The glucose levels increased in accordance with the increased ascorbic acid concentrations using the Glucocard® meter, whereas they decreased using the Medisafe® meter. However, the glucose levels measured using the intrahospital laboratory test did not change in response to any ascorbic acid concentration (Figure 1). Figure 1 Glucose measurement interference after administration of various concentrations of ascorbic acid. Glucose concentrations were measured using Medisafe® (diamond symbols) and Glucocard® (triangular symbols) blood glucose meters, and an intra‐hospital ... The Medisafe® meter is based on the colorimetric method, which is applied to several types of Accu‐Chek® meters (Roche Diagnostics, Mannheim, Germany), whereas the Glucocard® meter is based on the electrochemical method, which is applied to many glucose meters, including the One Touch Ultra® (LifeScan Inc., Milpitas, CA, USA), FreeStyle® (Abbott Diabetes Care, Alamdea, CA, USA) and Contour® (Bayer Healthcare, Tarrytown, NY, USA) meters. As hydrogen peroxide is consumed by ascorbic acid, less hydrogen peroxide is available to react with the dye on the test strips, leading to falsely lower glucose readings by the Medisafe® meter. In contrast, ascorbic acid is oxidized at the electrode surface, and more electrons and more current are produced, leading to falsely higher glucose readings by the Glucocard® meter2. The critical glucose measurement interferences by high‐dose ascorbic acid could cause inappropriate insulin therapy or glucose administration, resulting in serious hypoglycemia or hyperglycemia. We need to understand that this type of interference occurs at the bedside; therefore, blood glucose levels just after intravenous administration of high‐dose ascorbic acid should be measured using the hexokinase method, not with these SMBG meters.

Maternal alcohol consumption may influence cord blood ascorbic acid concentration: findings from a study of Brazilian mothers and their newborns

Studies that have investigated ascorbic acid (AA) concentrations in cord blood have pointed to significant associations with maternal blood AA concentrations, smoking, age, diet, type of delivery, duration of gestation, fetal distress and birth weight. The aim of the present study was to determine the relationship between cord blood AA concentrations in newborns and maternal characteristics. A total of 117 Brazilian healthy parturients were included in this cross-sectional study. The concentrations of AA in blood were determined by the HPLC method. Data concerning socio-economic, demographic, obstetric, nutritional and health characteristics of the parturients, including alcohol consumption and smoking habit, were assessed by a standardised questionnaire. A FFQ was used to investigate the intake of foods rich in vitamin C. Cord blood AA concentration was significantly correlated with per capita income (r 0.26; P = 0.005), maternal blood AA concentration (r 0.48; P < 0.001) and maternal vitamin C-rich food intake score (r 0.36; P < 0.001). The linear regression model including maternal AA concentration, alcohol consumption, smoking, parity, vitamin C-rich food intake score and per capita income explained 31.13 % of the variation in cord blood AA concentrations in newborns. We recommend further experimental studies to assess the effects of ethanol on placental AA uptake, and epidemiological cohort studies to evaluate in detail the influence of maternal alcohol consumption on cord blood AA concentrations.

2-O-(beta-D-Glucopyranosyl)ascorbic acid, a novel ascorbic acid analogue isolated from Lycium fruit.

A novel stable precursor of ascorbic acid (vitamin C), 2-O-(beta-D-glucopyranosyl)ascorbic acid, was isolated from both the ripe fresh fruit and dried fruit of Lycium barbarum L., a plant of the Solanaceae family. The chemical structure was inferred by instrumental analyses and confirmed by chemical synthesis. The dried fruit of Lycium barbarum L. contained ca. 0.5% of it, which is comparable to the ascorbic acid content of fresh lemons. It increased the blood ascorbic acid by oral administration to rats, and it was also detected in blood from the portal vein.

Ascorbic-acid transporter Slc23a1 is essential for vitamin C transport into the brain and for perinatal survival.

The only proven requirement for ascorbic acid (vitamin C) is in preventing scurvy, presumably because it is a cofactor for hydroxylases required for post-translational modifications that stabilize collagen. We have created mice deficient in the mouse ortholog (solute carrier family 23 member 1 or Slc23a1) of a rat ascorbic-acid transporter, Svct2 (ref. 4). Cultured embryonic fibroblasts from homozygous Slc23a1(-/-) mice had less than 5% of normal ascorbic-acid uptake. Ascorbic-acid levels were undetectable or markedly reduced in the blood and tissues of Slc23a1(-/-) mice. Prenatal supplementation of pregnant females did not elevate blood ascorbic acid in Slc23a1(-/-) fetuses, suggesting Slc23a1 is important in placental ascorbic-acid transport. Slc23a1(-/-) mice died within a few minutes of birth with respiratory failure and intraparenchymal brain hemorrhage. Lungs showed no postnatal expansion but had normal surfactant protein B levels. Brain hemorrhage was unlikely to be simply a form of scurvy since Slc23a1(-/-) mice showed no hemorrhage in any other tissues and their skin had normal skin 4-hydroxyproline levels despite low ascorbic-acid content. We conclude that Slc23a1 is required for transport of ascorbic acid into many tissues and across the placenta. Deficiency of the transporter is lethal in newborn mice, thereby revealing a previously unrecognized requirement for ascorbic acid in the perinatal period.

The Effect of Coenzyme Q10 on Blood Ascorbic Acid, Vitamin E, and Lipid Peroxide in Chronic Cadmium Intoxication

The aim of our study was to investigate the possible protective role of coenzyme Q10 (CoQ10) administration on ascorbic acid (AsA), vitamin E (vit E), and lipid peroxide (LP) concentrations in the blood of rats chronically treated with cadmium. Results were compared to those obtained in control animals, as well as to those obtained in animals treated with olive oil. Compared to that of the control animals, the AsA concentration was significantly increased in rats treated with CoQ10 and olive oil, whereas vit E concentration was significantly increased in animals treated with cadmium, CoQ10, or cadmium + CoQ10. A significant decrease in LP concentration was noted in animals treated with cadmium or with cadmium + CoQ10o, whereas a significant increase was seen in animals treated with olive oil. Compared to that of the animals treated with olive oil, the ascorbic acid concentration was significantly decreased in rats treated with cadmium or with cadmium + CoQ10, whereas vit E concentration was significantly increased in animals treated with cadmium, CoQ10, or cadmium + CoQ10. LP concentration was significantly decreased in rats treated with cadmium, CoQ10, or cadmium + CoQ10. Our study showed that CoQ10 administration in rats chronically exposed to exogenous cadmium exerts beneficial effects on the nonenzymatic components of the antioxidant defense system, such as AsA and vit E, resulting in a decreased concentration of LP in the blood.

17β-estradiol inhibition of ascorbic acid accumulation in human intestinal Caco-2 cells

We investigated the effect of estrogen on the accumulation of ascorbic acid by human intestinal Caco-2 cells. 17β-estradiol, synthetic estrogen diethylstilbestrol, and partial agonist tamoxifen were found to inhibit ascorbic acid accumulation in a dose-dependent fashion. The inhibitory effect of estrogens can be observed at as short as 5 min of incubation. An additive effect was observed when they were used in combination. Similar to dietary flavonoids, inhibition was also observed in two other intestinal cell lines, HT-29 and IEC-6. These chemicals affected both Na +-dependent and Na +-independent(K + substituting Na +) accumulation of ascorbic acid and did not affect the efflux of accumulated ascorbic acid. Kinetic analysis of diethylstilbestrol showed a non-competitive inhibition with an apparent K i of 23 μM. The hormone-ascorbic acid interaction in the intestinal cell could help to explain the known reduction in blood ascorbic acid level among oral contraceptive users and female guinea pigs given contraceptive hormones.

Estimation of vitamin needs--riboflavin, vitamin B6 and ascorbic acid-according to blood parameters and functional-cognitive and emotional indices in a selected well-established group of elderly in a home for the aged in Israel.

To evaluate the vitamin status and the effects of micronutrient supplementation as determined by biochemical assays and functional, cognitive and emotional tests in a selected well-established group of elderly people, average age above 80 years. Dietary consumption was evaluated by in-person interview using a food frequency questionnaire. Medical, biochemical, nutritional, functional, cognitive and behavioral parameters were assessed in elderly subjects (n = 12) living in a home for the aged, at baseline and after 42 days of micronutrient supplementation. The same parameters were assessed in additional subjects (n = 9), at baseline only. In all subjects, most of the micronutrients were not supplied at an adequate level. Supplementation of micronutrients at a level of 100% RDA improved parameters related to vitamin status, the activation coefficients (AC) of GR (glutathione reductase) and AST, blood ascorbic acid concentrations, functional-cognitive evaluation values, blood pressure, pulse rate, and serum cholesterol and triglycerides levels. At baseline, the following parameters significantly correlated with vitamin intake and were used for the estimation of vitamin needs: AC of GR, Tinetti Balance Evaluation, FIM and recorded morbidity. On the basis of limited available data, calculation of vitamin needs based on regression lines resulted in estimates (mg/day) of: > 150 for ascorbic acid, > 3 for riboflavin, > 3 for vitamin B6. Expanding the current practice of supplementing micronutrients at a level of 100% RDA (in tablet form) that already exists in some elderly societies should be considered after a comprehensive study in a large group of elderly people.

Biochemical validation of a self-administered semi-quantitative food-frequency questionnaire

The present study is a biochemical validation of a food-frequency questionnaire (FFQ) with optical reading, i.e. containing food portion photographs to help to assess quantities. Forty-four healthy subjects, non-smokers and not taking vitamin supplements, were recruited for the study. After completion of the questionnaire, subjects were asked to keep a 7 d weighed dietary record (7DR). Three 24 h urine samples were collected on 3 different days over the week of food recording for the analysis of urea-N, P and K. On the 4th day of food recording, blood was collected for determination of alpha-tocopherol, beta-carotene and ascorbic acid. N, P and K determined in urines and from 7DR were significantly correlated (Spearman rank correlation test), r values being 0.77, 0.57 and 0.42 respectively. The correlations with the FFQ were significant only for N (r 0.45) and P (r 0.39). Blood ascorbic acid and beta-carotene concentrations correlated with dietary intake when determined from 7DR (both r 0.44), but not when determined from FFQ. No correlation was found for alpha-tocopherol. The data obtained seem to prove the validity of the FFQ in defining eating patterns in terms of some nutrients, but not vitamins, at least as far as non-supplemented subjects are concerned. The way in which foods were grouped in the questionnaire could account for these results.

Ascorbic acid during cerebral ischemia in newborn piglets.

We measured ascorbic acid (reduced and oxidized) in brain, CSF and blood, before, during and after cerebral ischemia in newborn piglets. Bilateral carotid ligation induced a 54% decrease in cerebral blood flow (p < 0.01) and a 43% decrease in the cerebral metabolic rate of oxygen (p < 0.01). After ischemia and reperfusion, we obtained a 60% decrease (p < 0.01) in total brain ascorbic acid content. CSF ascorbic acid increased during reperfusion: +60% at 30 min (p < 0.001) and +160% at 120 min (p < 0.05). Blood ascorbic acid content did not change. These changes and the absence of massive oxidation of ascorbic acid in brain tissue suggest release of ascorbic acid by the brain during ischemia.

Effect of vitamin C on copper and iron status in men and guinea pigs.

Healthy individual were given 2 g of vitamin C per day for 2 months. Whole blood iron, ascorbic acid, hemoglobin, and serum ceruloplasmin were determined at the beginning, and 1 or 2 months after the start of the experiment. The concentration of ascorbic acid was observed to increase significantly in the blood, while blood iron, hemoglobin, and serum ceruloplasmin levels significantly increased at the end of the 1st month, but decreased to control levels at the end of the 2nd month. Male albino guinea pigs were administered 8, 180, and 360 mg of vitamin C per day for 2 months. Liver ferritin iron, liver copper, serum copper, and serum ceruloplasmin levels significantly decreased, but there was no significant change in hemosiderin iron while blood ascorbic acid significantly increased at the end of the 2 month period. There was no significant change in serum iron and hematocrit levels. These results suggest that vitamin C has an antagonistic effect on copper metabolism in guinea pigs but not in humans either on copper or iron metabolisms.

Effect of exogenous ascorbic acid intake on biosynthesis of ascorbic acid in mice

The effect of exogenous ascorbic acid intake on biosynthesis of ascorbic acid in mice has been studied. After the mice were on diets containing added ascorbic acid for two months, the activities of ascorbic acid synthesizing enzymes in the mouse liver homogenates were measured using L-gulono-γ-lactone as a substrate. Exogenous ascorbic acid intake (0.5, 1 or 5% in the diet) was able to increase the concentration of ascorbic acid in the blood and to decrease the activities of ascorbic acid synthesizing enzymes in mouse liver. The results suggest that ascorbic acid synthesis was controlled by local regulatory mechanism or by the concentration of ascorbic acid in the hepatic portal blood. Ingestion of dietary erythorbic acid, a stereoisomer of ascorbic acid, had no effect on the activities of ascorbic acid synthesizing enzymes.

Congenital Ascorbic Acid Deficiency in Pigs

In a swine production herd, spontaneous scurvy was observed among piglets 2–3 weeks after weaning. All affected pigs had the same boar as both maternal and paternal grandfather. The affected pigs had only traces of ascorbic acid in blood and tissues as compared to litter mates and other normal pigs. The ratio between the total numbers of normal and affected pigs in the 4 litters concerned was in agreement with a 3:1 segregation, which is characteristic of simple autosomal recessive inheritance in matings between non-affected carriers. Two affected pigs were restored to normal when given ascorbic acid in the diet. Without vitamin C supplement affected pigs died or had to be euthanized. Liver microsomes from an affected pig were unable to synthesize ascorbic acid in vitro with 1-gulonolactone as a substrate, unlike microsomes from normal control pigs.

The effect of subclinical ascorbate deficiency on periodontal health in nonhuman primates.

The aim of this study was to evaluate the effects of chronic subclinical ascorbic acid deficiency on periodontal health in a nonhuman primate model. Young adult Macaca fascicularis monkeys were fed an ascorbic acid free diet for nine weeks followed by a diet with a suboptimal level of ascorbic acid for an additional sixteen weeks. During the 25‐week period, a pair fed control group was fed a nutritionally adequate diet in amounts equivalent to that consumed by the experimental group. From the second week onward, whole blood ascorbic acid levels in the experimental animals but not in pair fed controls were significantly reduced. Experimental animals did not develop clinical signs of ascorbate deficiency, and there was little evidence of spontaneous gingivitis or periodontitis in either group between weeks 0 and 23. At week 23, plaque‐associated periodontitis was experimentally induced to evaluate the response of the periodontal tissues to the underlying subclinical ascorbate deficiency. Gingival index scores and pocket depth measurements were significantly greater in the ascorbate deficient animals than in controls. Preliminary studies of leukocyte function suggested that this susceptibility to periodontitis might be related to impaired polymorphonuclear leukocyte chemotaxis and phagocytosis. This study indicates that the periodontium is vulnerable to chronic inflammation as a consequence of subclinical ascorbic acid deficiency.

Endosulfan intoxication: Blood glucose, electrolytes, Ca levels, ascorbic acid and glutathione in rats

Endosulfan-induced changes in blood glucose, plasma electrolytes, and blood and brain ascorbic acid, hexokinase and glutathione have been investigated following acute and subacute administration in 12 h fasted male rats. After a single oral dose of endosulfan (40 mg/kg) a significant increase in blood glucose, blood ascorbic acid, and blood and brain glutathione was observed. The maximum increase in blood glucose was observed at 2 h (36%). Increase in blood and brain glutathione was highly significant at 4 h (50 and 43%, respectively). The blood ascorbic acid slowly increased by 19% over controls during the treatment period. No significant change in brain hexokinase was observed. Repeated oral administration of endosulfan (0.625 to 20 mg/kg) for 7 weeks had no effect on plasma sodium and potassium. At the highest dose (20 mg/kg), blood glucose was slightly increased (16%). Plasma Ca was significantly decreased, the maximum fall (35%) being observed at 4 h.