Vitamin C Deficiency, High-Sensitivity C-Reactive Protein, and Cardiac Event-Free Survival in Patients With Heart Failure.

BACKGROUND: Vitamin C is related to lower levels of high-sensitivity C-reactive protein (hsCRP), an inflammatory biomarker that predicts cardiovascular disease. Whether vitamin C deficiency is associated with hsCRP and cardiac events in heart failure (HF) patients has not been examined. PURPOSE: The aim of this study is to determine the relationships among vitamin C intake, serum levels of hsCRP, and cardiac events. METHODS: A total of 200 HF patients completed a 3-day food diary to determine vitamin C deficiency and provided blood to measure serum levels of hsCRP. Patients were followed for 2 years to obtain data on cardiac event-free survival. Moderation analyses with hierarchical logistic and Cox regressions were used for the data analysis. RESULTS: Seventy-eight patients (39%) had vitamin C deficiency and 100 (50%) had an hsCRP level higher than 3 mg/L. Vitamin C deficiency was associated with an hsCRP level higher than 3 mg/L in the hierarchical logistic regression (odds ratio, 2.40; 95% confidence interval, [1.13-5.10]; P = .023). Vitamin C deficiency (hazard ratio, 1.68; 95% CI, 1.05-2.69, P = .029) and hsCRP level higher than 3 mg/L (hazard ratio, 1.79; 95% CI, 1.07-3.01; P = .027) predicted shorter cardiac event-free survival in hierarchical Cox regression. The interaction of hsCRP level higher than 3 mg/L and vitamin C deficiency produced a 2.3-fold higher risk for cardiac events (P = .002) in moderation analysis. Higher level of hsCRP predicted shorter cardiac event-free survival only in patients with vitamin C deficiency (P = .027), but not in those with vitamin C adequacy. CONCLUSION: Vitamin C deficiency moderated the relationship between inflammation and cardiac events in patients with HF. Future study is required to determine whether adequate intake of vitamin C could play a protective role against the impact of inflammation on cardiac events in HF patients.

Vitamin C deficiency fails to protect mice from malaria.

Nutritional deficiencies are frequent in malaria-endemic areas. It seems that micronutrient antioxidants play an important role in malaria parasite's proliferation. Thus, the effect of vitamin C deficiency on malaria infection was examined in mice. When vitamin C deficient mice, L-gulono-gamma-lactone oxidase gene knockout mice which are unable to synthesize ascorbic acid, were infected with a lethal dose of Plasmodium berghei NK65-infected red blood cells, the knockout mice showed similar parasitemia kinetics and survival rates as wild-type mice. The results indicate that deficiency of vitamin C might not affect the development of the malaria parasite in mice.

Vitamin C deficiency increases basal exploratory activity but decreases scopolamine-induced activity in APP/PSEN1 transgenic mice.

Vitamin C is a powerful antioxidant and its levels are decreased in Alzheimer's patients. Even sub-clinical vitamin C deficiency could impact disease development. To investigate this principle we crossed APP/PSEN1 transgenic mice with Gulo knockout mice unable to synthesize their own vitamin C. Experimental mice were maintained from 6 weeks of age on standard (0.33 g/L) or reduced (0.099 g/L) levels of vitamin C and then assessed for changes in behavior and neuropathology. APP/PSEN1 mice showed impaired spatial learning in the Barnes maze and water maze that was not further impacted by vitamin C level. However, long-term decreased vitamin C levels led to hyperactivity in transgenic mice, with altered locomotor habituation and increased omission errors in the Barnes maze. Decreased vitamin C also led to increased oxidative stress. Transgenic mice were more susceptible to the activity-enhancing effects of scopolamine and low vitamin C attenuated these effects in both genotypes. These data indicate an interaction between the cholinergic system and vitamin C that could be important given the cholinergic degeneration associated with Alzheimer's disease.

Vitamin C deficiency in cancer patients.

PURPOSE: To assess the prevalence of vitamin C deficiency within a group of hospice patients. To assess the relationship between plasma vitamin C, dietary intake and subsequent survival. METHODS: Patients with advanced cancer were recruited from a large hospice. Data were collected on demographic details, physical functioning and smoking history. An estimate was obtained of the number of weekly dietary portions consumed equivalent to 40 mg of vitamin C, the recommended daily intake. Plasma vitamin C was measured by a single blood sample. The study had local ethical approval. RESULTS: Fifty patients were recruited (mean age 65.2 years, 28 female). Plasma vitamin C deficiency was found in 15 (30%). Dietary intake of vitamin C was correlated to plasma vitamin C (r=0.518, P<0.0001). Low dietary intake, low albumin, high platelet count, high CRP level and shorter survival were all significantly associated with low plasma vitamin C concentrations (<11 micromol/L). There was no correlation between plasma vitamin C, smoking history or physical functioning. CONCLUSION: Vitamin C deficiency is common in patients with advanced cancer and the most important factors determining plasma levels are dietary intake and markers of the inflammatory response. Patients with low plasma concentrations of vitamin C have a shorter survival.

Multilocational hepatocyte transplantation for treatment of congenital ascorbic acid deficiency rats.

We attempted multilocational hepatocyte transplantation (HCTx) including hepatocyte-bearing polyurethane foam (PUF) to treat congenitally ascorbic acid (AsA) biosynthetic enzyme-deficient (ODS-od/od) rats. Hepatocytes isolated from the liver of congeneic rats were transplanted into the portal vein (Pv), spleen (Sp), omentum (Om), and mesentery (Ms). Hepatocyte-bearing PUF was transplanted into the Om and Ms. Experimental groups were divided into four groups (group I; Pv + Sp, group II; Pv + Sp + Om + Ms, group III; Pv + Sp + hepatocyte-bearing PUF, group IV; control). The average serum AsA level of the surviving rats in group II and III was significantly higher than that in group I 3 mo after HCTx. Histological examination showed small foci of surviving hepatocytes in the Om and Ms tissues and in the connective tissue in the PUF. ODS-od/od rats survived for a long time by multilocational HCTx.

Macrophage functions in aging: effects of vitamin C deficiency.

Groups of young adult and senescent guinea pigs were fed normal and vitamin C deficient diets for 4 weeks and tested for their peritoneal macrophage functions. Serum levels of vitamin C in deficient animals indicated a progressive state of ascorbic acid deficiency and correlated well with the clinical signs and symptoms of scurvy. Fewer macrophages were obtained from the peritoneal cavities of deficient animals and morphologically they were smaller in size. Adverse effects of vitamin C deficiency were enhanced in aged animals. Significantly greater number of aged animals died by 4 weeks of deficiency. Deficient senescent animals had greater decline in macrophage random migration and bactericidal capacity. Following phagocytic stimuli, superoxide anion generation also significantly decreased. Data suggest that vitamin C deficiency might affect macrophage functions in the aged more profoundly and could compromise parameters of host defenses effective against microbial infections.

Ascorbic acid synthesis in certain guinea pigs.

Three guinea pigs fed a vitamin C-free diet manifested no symptoms of scurvy even after 4-8 months, normally increased in body weight and excreted quantities of ascorbic acid in urine far exceeding the total body pool of ascorbic acid. The course of healing subsequent to experimental trauma in one of these animals proved to be entirely normal and vitamin C concentration in its liver after 8 months of a scorbutogenic regimen was found to be more than twice that in guinea pigs with a daily intake of 10 mg ascorbic acid. It is evident that certain guinea pigs are capable to synthesize ascorbic acid that fully covers the needs of the organism. However, the freqency of occurence of such guinea pigs appears to be extremely small.

Changes in ascorbic acid metabolism of the offspring following high maternal intake of this vitamin in the pregnant guinea pig.

Guinea pigs were fed a control (0.05%) or a high (0.5%) ascorbic acid diet during the last half of pregnancy. When the pups were tested at 5 and 10 days of life the ones from the high-ascorbic-acid group demonstrated a marked increase in 14CO2 excretion, compared with the control pups, following an intraperitoneal injection of 14C-labeled ascorbic acid. When the animals were weaned to an ascorbic-acid-deficient diet signs of scurvy appeared earlier in the pups from the high vitamin C group and their survival was shorter. When excretion of labeled CO2 in both groups was correlated with the day of onset of scurvy signs, a linear correlation was found between these two parameters, suggesting that the earlier appearance of signs of scurvy in the experimental pups is secondary to an increased rate of ascorbic acid catabolism.

Suppression of adrenocorticotrophic activity in the ascorbic acid deficient guinea-pig.

1. Adrenocortical hyperactivity caused by a marked increase in circulating corticotrophin occurred in guinea-pigs on a diet deficient in ascorbic acid.2. Betamethasone prevented the rise in the blood ACTH concentration in scorbutic animals and also the increased steroid production per gramme adrenal tissue in vitro. It diminished the adrenal hypertrophy and partially suppressed the rise in plasma cortisol.3. Ninety minutes after the injection of ascorbic acid corticotrophin could no longer be detected in the plasma of scorbutic animals.4. Neither the survival time nor the weight loss was affected by betamethasone treatment.