Circulating vitamin C and the risk of cardiovascular diseases: A Mendelian randomization study.

BACKGROUND AND AIMS: The impact of vitamin C supplementation on the risk of cardiovascular diseases (CVDs) remains uncertain with inconsistent evidence obtained from observational studies and randomized clinical trials (RCTs). We aimed to assess possible causal associations of vitamin C with major CVD events as well as their risk factors using Mendelian randomization (MR) design. METHODS AND RESULTS: Nine genetic variants associated with vitamin C at genome-wide significance (p < 5 × 10-8) were used as instrumental variables to predict plasma vitamin C levels. The primary outcomes were coronary artery disease (Ncase = 122,733 and Ncontrol = 424,528), atrial fibrillation (Ncase = 60,620 and Ncontrol = 970,216), heart failure (Ncase = 47,309 and Ncontrol = 930,014), and ischemic stroke (Ncase = 40,585 and Ncontrol = 406,111). Several CVD risk factors were also evaluated in secondary analyses. Two-sample MR analyses were performed using the inverse variance weighted method, with several sensitivity analyses. Genetically determined higher levels of plasma vitamin C were not significantly associated with any of the four examined CVD events. Likewise, there is no convincing evidence for the associations between genetically determined vitamin C and CVD risk factors, including higher blood lipids, higher blood pressure, and abnormal body composition. Sensitivity analyses using different analytical approaches yielded consistent results. Additionally, MR assumptions did not seem to be violated. CONCLUSION: This MR study does not support a causal protective role to circulate vitamin C levels on various types of CVD events. In combination with previous RCT results, our findings suggest that vitamin C supplementation to increase circulating vitamin C levels may not help in CVD prevention.

The neuropsychiatric effects of vitamin C deficiency: a systematic review.

BACKGROUND: Vitamin C deficiency may be more common than is generally assumed, and the association between vitamin C deficiency and adverse psychiatric effects has been known for centuries. This paper aims to systematically review the evidence base for the neuropsychiatric effects of vitamin C deficiency. METHODS: Relevant studies were identified via systematic literature review. RESULTS: Nine studies of vitamin C deficiency, including subjects both with and without the associated physical manifestations of scurvy, were included in this review. Vitamin C deficiency, including scurvy, has been linked to depression and cognitive impairment. No effect on affective or non-affective psychosis was identified. CONCLUSIONS: Disparate measurement techniques for vitamin C, and differing definitions of vitamin C deficiency were apparent, complicating comparisons between studies. However, there is evidence suggesting that vitamin C deficiency is related to adverse mood and cognitive effects. The vitamin C blood levels associated with depression and cognitive impairment are higher than those implicated in clinical manifestations of scurvy. While laboratory testing for ascorbic acid can be practically difficult, these findings nonetheless suggest that mental health clinicians should be alerted to the possibility of vitamin C deficiency in patients with depression or cognitive impairment. Vitamin C replacement is inexpensive and easy to deliver, although as of yet there are no outcome studies investigating the neuropsychiatric impact of vitamin C replacement in those who are deficient.

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 D and/or calcium deficient diets may differentially affect muscle fiber neuromuscular junction innervation.

INTRODUCTION: There is evidence that supports a role for Vitamin D (Vit. D) in muscle. The exact mechanism by which Vit. D deficiency impairs muscle strength and function is not clear. METHODS: Three-week-old mice were fed diets with varied combinations of Vit. D and Ca2+ deficiency. Behavioral testing, genomic and protein analysis, and muscle histology were performed with a focus on neuromuscular junction (NMJ) -related genes. RESULTS: Vit. D and Ca2+ deficient mice performed more poorly on given behavioral tasks than animals with Vit. D deficiency alone. Genomic and protein analysis of the soleus and tibialis anterior muscles revealed changes in several Vit. D metabolic, NMJ-related, and protein chaperoning and refolding genes. CONCLUSIONS: These data suggest that detrimental effects of a Vit. D deficient or a Vit. D and Ca2+ deficient diet may be a result of differential alterations in the structure and function of the NMJ and a lack of a sustained stress response in muscles. Muscle Nerve 54: 1120-1132, 2016.

Micronutrient status and its effect on glycaemic indices in type 2 diabetics with foot ulcer in Ibadan, Nigeria.

BACKGROUND: Micronutrients are required by organisms in trace concentrations sufficient to maintain homeostasis. Deficiency of these elements could result in different medical and metabolic abnormalities. There are limited data on micronutrient status in type 2 diabetics with foot ulcer (DM+FU). Premised on this, this study investigated micronutrient levels of DM+FU and examined their effects on glycaemic indices. METHODS: One hundred and twenty participants, comprising seventy DM+FU and fifty non-diabetic participants (controls) aged 40-60 years, were recruited for the study. Ten millilitres of fasting blood samples were collected from each participant after obtaining their consent and levels of vitamin C, vitamin E, copper, selenium, zinc, FPG and HbAlc were measured. The data were analyzed using 't'- test and Pearson's correlation coefficients. Statistical significant was considered at p<0.05. RESULTS: FPG and HbAlc were significantly higher in DM+FU (12.98±0.43 mmol/l; 8.63±0.24 %) than in controls (5.09±0.08 mmol/l; 4.08±0.11 %). Vitamin C (3.7610.43 vs. 5.57±0.43 ptmol/l; p=0.003), vitamin E (19.57±1.01 vs. 25.57±0.27 pLimol/l; p=0.000) and selenium (0.48±0.01 vs. 0.81±0.04 srmol/l; p=0.000) were substantially lower in DM+FU compared with controls. However, no significant changes were observed when levels of copper and zinc were compared in all participants. Data revealed inverse associations between micronutrients and glycaemic indices (vitamin C/ FPG: (r= 0.250, p=0.037); Cu/HbA Ic: (r= 0.131, p=0.365)). CONCLUSIONS: Diabetics with foot ulcer were observed to be deficient in selenium, vitamin C and vitamin E. Therefore, type 2 diabetics with foot ulcer should be advised and encouraged to take more of leafy green vegetables and unsweetened fruits.

The lower vitamin C plasma concentrations in elderly men compared with elderly women can partly be attributed to a volumetric dilution effect due to differences in fat-free mass.

Women show higher vitamin C plasma concentrations than men, but the reasons for this observation still require elucidation. The objective of the present study was to investigate whether sex differences in vitamin C plasma concentrations are present in elderly subjects and whether these differences are due to sex-specific lifestyles, total antioxidant status (TAOS) and/or body composition. Fasting plasma concentrations of vitamin C were assessed by photometric detection in a cross-sectional study of 181 women and eighty-nine men aged 62-92 years. Body composition was determined by bioelectrical impedance analysis. Vitamin C intake was assessed with a 3 d estimated dietary record. Stepwise multiple regression analyses were performed to investigate whether sex is an independent predictor of vitamin C plasma concentrations by controlling for age, vitamin C intake, lifestyle factors, TAOS and body composition. Women showed higher vitamin C plasma concentrations than men (76 v. 62 µmol/l, P< 0·0001). In the multiple regression analysis, male sex was a negative predictor of vitamin C plasma concentrations (ß = -0·214), as long as absolute fat-free mass (FFM) was not considered as a confounder. When absolute FFM was included, sex was no longer a predictor of vitamin C plasma concentrations, whereas absolute FFM (ß = -0·216), physical activity level (ß = 0·165), intake of vitamin C supplements (ß = 0·164), age (ß = 0·147) and smoking (ß = -0·125) affected vitamin C plasma concentrations. The results indicate that a higher absolute FFM, and thus a higher distribution volume of vitamin C, contributes to lower vitamin C plasma concentrations in men than women.

Distribution of vitamin C is tissue specific with early saturation of the brain and adrenal glands following differential oral dose regimens in guinea pigs.

Vitamin C (VitC) deficiency is surprisingly common in humans even in developed parts of the world. The micronutrient has several established functions in the brain; however, the consequences of its deficiency are not well characterised. To elucidate the effects of VitC deficiency on the brain, increased knowledge about the distribution of VitC to the brain and within different brain regions after varying dietary concentrations is needed. In the present study, guinea pigs (like humans lacking the ability to synthesise VitC) were randomly divided into six groups (n 10) that received different concentrations of VitC ranging from 100 to 1500 mg/kg feed for 8 weeks, after which VitC concentrations in biological fluids and tissues were measured using HPLC. The distribution of VitC was found to be dynamic and dependent on dietary availability. Brain saturation was region specific, occurred at low dietary doses, and the dose-concentration relationship could be approximated with a three-parameter Hill equation. The correlation between plasma and brain concentrations of VitC was moderate compared with other organs, and during non-scorbutic VitC deficiency, the brain was able to maintain concentrations from about one-quarter to half of sufficient levels depending on the region, whereas concentrations in other tissues decreased to one-sixth or less. The adrenal glands have similar characteristics to the brain. The observed distribution kinetics with a low dietary dose needed for saturation and exceptional retention ability suggest that the brain and adrenal glands are high priority tissues with regard to the distribution of VitC.

High dietary intake of vitamin C suppresses age-related thymic atrophy and contributes to the maintenance of immune cells in vitamin C-deficient senescence marker protein-30 knockout mice.

Vitamin C (VC) is an essential nutrient for humans and certain other animals. It has antioxidant properties and has been reported to ameliorate oxidative damage to lipids, DNA and proteins. However, the effects of VC on immune function are poorly understood, especially the influence of long-term high-dose VC intake on the number and function of immune cells. In the present study, to evaluate the immune effects of VC, VC-deficient senescence marker protein-30 knockout (SMP30KO) mice were fed a diet containing the recommended level of VC (20 mg/kg per d; 0·02 % VC) or a high level of VC (200 mg/kg per d; 0·2 % VC) for 1 year. The plasma VC concentration of the 0·02 % group was the same as that of age-matched C57BL/6 mice after 1 year of feeding; however, plasma VC concentration and thymus weight were significantly higher in the 0·2 % VC group than in the 0·02 % VC group. The total counts of leucocytes, lymphocytes, granulocytes and monocytes in the peripheral blood, as well as the number of splenocytes and thymocytes, were all significantly higher in the 0·2 % VC group than in the 0·02 % VC group. In addition, the number of naive T cells in peripheral blood lymphocytes, the number of memory T-cell populations in splenocytes, and the number of cluster of differentiation (CD)4⁺CD8⁺ or CD4⁺CD8⁻ or CD4⁻CD8⁺ T cells in thymocytes were all markedly higher in the 0·2 % VC group than in the 0·02 % VC group after 1 year of dietary treatment. These results suggest that a long-term high-dose intake of VC is effective in the maintenance of immune cells, partly through the suppression of age-related thymic involution in VC-deficient SMP30KO mice.

Maternal vitamin C deficiency during pregnancy results in transient fetal and placental growth retardation in guinea pigs.

PURPOSE: Recently, we reported that preferential maternal-fetal vitamin C (vitC) transport across the placenta is likely to be impaired by prolonged maternal vitC deficiency. Maintenance of a basal maternal vitC supply at the expense of the fetus may impair fetal development; however, the knowledge of vitC's impact on intrauterine development is sparse. The aim of this study was to explore the effect of maternal vitC status on fetal and placental development in guinea pigs. METHODS: Twenty pregnant Dunkin Hartley guinea pigs were randomized into four groups to receive diets either sufficient (918 mg/kg CTRL) or deficient (100 mg/kg DEF) in vitC. Cesarean sections at gestational day (GD) 45 or 56 allowed for fetal and placental measurements. RESULTS: At GD45, body, brain and placental weights were significantly reduced in DEF pups compared with CTRL (p < 0.05, p < 0.001 and p < 0.05, respectively). DEF plasma vitC levels were ~6% of those of CTRL (p < 0.0001), and the fetal/maternal plasma vitC ratio was significantly reduced at GD56 in the DEF animals compared with controls (p = 0.035). Placental vitC levels were reduced in DEF animals (p < 0.0001) and the ascorbate oxidation ratio and glutathione elevated compared with controls (p < 0.0001). CONCLUSIONS: Although no clinical differences between CTRL and DEF pups were observed at GD56, the present data suggest that vitC plays a role in early fetal development. Although no clinical differences between CTRL and DEF pups were observed at GD56, the present data suggest that vitC plays a role in early fetal development. Low maternal vitC intake during pregnancy may compromise maternal weight gain, placental function and intrauterine development.

Vegetable and fruit consumption, education and plasma vitamin C concentration in Russian and Finnish Karelia, 1992-2002.

OBJECTIVE: To examine (i) whether the consumption of fresh vegetables, fruit and berries is associated with plasma vitamin C concentration and (ii) educational differences in plasma vitamin C concentration in two neighbouring areas in Russia and Finland. DESIGN: Cross-sectional risk factor surveys in 1992, 1997 and 2002. Logistic regression analysis was applied to examine the associations of consumption of selected foods and education with plasma vitamin C concentration. SETTING: District of Pitkäranta in the Republic of Karelia, Russia and North Karelia, Finland. SUBJECTS: Adults aged 25-64 years: 579 men and 612 women in Pitkäranta; 974 men and 642 women in North Karelia. RESULTS: The plasma vitamin C concentration was strikingly low in Pitkäranta, Russia across the study years. During the 10 years of monitoring, the mean plasma vitamin C concentration among men ranged from 2·5 to 8·0 µmol/l in Pitkäranta, Russia and from 27·1 to 53·9 µmol/l in North Karelia, Finland. In both areas, daily consumption of fruit was most strongly associated with plasma vitamin C, while the association of fresh vegetable consumption with plasma vitamin C was less consistent. Consumption of berries was less important in explaining plasma vitamin C. In Pitkäranta, the plasma vitamin C concentration was lower among respondents in the lowest education group. CONCLUSIONS: Differences in the consumption of fresh vegetables and fruit resulted in notable differences in vitamin C status between Pitkäranta and North Karelia in spring. In comparative settings, knowledge of local food culture and validation pilots are important before conducting large population surveys.

Influence of daily diet on ascorbic acid supply to students.

BACKGROUND: Researchers suspect that the accepted adequate ascorbic acid plasma concentration is not being met even after dietary intake of the recommended amount of vitamin C. Current dietary intake recommendation in Poland is 60 mg per day for women and 75 mg per day for man (EAR), while in Western Europe and North America is higher and amounts to 75-90 mg per day. OBJECTIVE: The paper aimed at studying a correlation between composition of nutrients in daily diet and plasma vitamin C levels in university students. Materials and methods. This study examined diet composition and the nutritional status of ascorbic acid in plasma of 120 university students in Szczecin, Poland. Ascorbic acid was determined in blood plasma using HPLC method. The information concerning diet composition was collected using the method of "7-days food record" prior to blood collection. RESULTS: Plasma ascorbic acid deficiency (<40 µmol/L) was observed in 23% of women and 28% of men. The average plasma ascorbic acid concentration was 48.65 µmol/L in women and 45.61 µmol/L in men. The average intake of vitamin C in women with observed deficiency was average 46.55 mg/day, whereas in men it was 48.56 mg/day. CONCLUSIONS: The recommendation of dietary intake of vitamin C in Poland is low in comparison to other countries. Population- based studies are necessary to determine the actual demand for vitamin C in various population groups in Poland. Key words: nutrition, vitamins, dietary intake, diet, ascorbic acid, plasma.

Prolonged maternal vitamin C deficiency overrides preferential fetal ascorbate transport but does not influence perinatal survival in guinea pigs.

Human and guinea pig fetuses are completely dependent on an adequate maternal vitamin C (vitC) intake. Shortage of micronutrients can have negative implications for fetal health and pregnancy outcome; however, knowledge of maternal vitC deficiency's impact on fetal development is sparse and reports of pregnancy outcome have been divergent. The present study investigated whether maternal vitC deficiency affects pregnancy outcome and plasma vitC distribution between the mother and the offspring in a guinea pig model. A total of eighty pregnant Dunkin Hartley guinea pigs were randomised into two weight-stratified groups receiving either a deficient (100 mg/kg DEF) or a control (923 mg/kg CTRL) diet. VitC levels were measured in plasma during pregnancy and postpartum, and in the plasma and brain of newborns. Pregnancy outcome was recorded with respect to birth weight and perinatal survival and were similar between groups. Plasma vitC in dams declined throughout gestation in both groups (P< 0·01). Compared with maternal plasma vitC, plasma vitC of newborn pups was found to be significantly lower in the DEF group (P< 0·001) and higher in the CTRL group (P< 0·001), respectively. Brain vitC levels were significantly reduced in DEF newborn pups (P< 0·001). The present results indicate that preferential transport of vitC from the mother to the fetus is overridden during sustained maternal vitC deficiency, maintaining maternal vitC concentration at the expense of the offspring. This contradicts the notion that a fetus is protected from vitC deficiency by the placental Na-dependent vitC co-transporter, SVCT2, thus fetal development may be susceptible to the negative effects of maternal vitC deficiency.

Is vitamin C intake too low in dialysis patients?

Vitamin C has several well-established roles in physiology including synthesis of collagen, carnitine and epinephrine, absorption of dietary iron, and mobilization of storage iron for erythropoeisis. Loss of several of these functions explains the pathology of scurvy, where defective collagen synthesis and anemia are major symptoms. Vitamin C deficiency is very common in dialysis patients and may arise from dialytic vitamin C clearance, restricted intake of vitamin C-rich foods, and increased vitamin C catabolism in vivo from inflammation. In the dialysis population, greater vitamin C intake may be needed for optimal health. Relationships between intake, body distribution, inflammation, and dialytic losses are complex and need further study. Concern about vitamin C metabolism leading to accumulation of tissue oxalate has led to the recommendation that vitamin C intake equals, but not exceeds, the intake recommended for the general population. Vitamin C deficiency in dialysis patients may have clinical consequences; a study in Renal Research Institute clinics found an association with periodontal disease. Data also support a role for vitamin C in prevention of dialysis-related anemia. New research questions are proposed in this editorial, with a discussion of strategies to determine the optimal provision of vitamin C for CKD patients.

Vitamin C in sepsis.

Bacterial bloodstream infection causes septic syndromes that range from systemic inflammatory response syndrome (SIRS) and encephalopathy to severe sepsis and septic shock. Microvascular dysfunction, comprising impaired capillary blood flow and arteriolar responsiveness, precedes multiple organ failure. Vitamin C (ascorbate) levels are low in critically ill patients. The impact of ascorbate administered orally is moderate because of its limited bioavailability. However, intravenous injection of ascorbate raises plasma and tissue concentrations of the vitamin and may decrease morbidity. In animal models of polymicrobial sepsis, intravenous ascorbate injection restores microvascular function and increases survival. The protection of capillary blood flow and arteriolar responsiveness by ascorbate may be mediated by inhibition of oxidative stress, modulation of intracellular signaling pathways, and maintenance of homeostatic levels of nitric oxide. Ascorbate scavenges reactive oxygen species (ROS) and also inhibits the NADPH oxidase that synthesizes superoxide in microvascular endothelial cells. The resulting changes in redox-sensitive signaling pathways may diminish endothelial expression of inducible nitric oxide synthase (iNOS), tissue factor and adhesion molecules. Ascorbate also regulates nitric oxide concentration by releasing nitric oxide from adducts and by acting through tetrahydrobiopterin (BH4) to stimulate endothelial nitric oxide synthase (eNOS). Therefore, it may be possible to improve microvascular function in sepsis by using intravenous vitamin C as an adjunct therapy.

Association between vitamin C deficiency and dialysis modalities.

AIM: We designed a cross-sectional study to investigate plasma vitamin C level in patients who underwent maintenance haemodialysis (MHD) and continuous ambulatory peritoneal dialysis (CAPD) to explore whether there is a difference in vitamin C deficiency between MHD patients and CAPD patients. METHODS: This investigation included 382 dialysis patients without vitamin C supplement before the study. Demographic characteristics, laboratory tests, ascorbic acid and total plasma vitamin C level were measured. A linear regression model was built to explore the association between vitamin C deficiency and dialysis modalities after adjusting for age, dialysis vintage, gender, Charlson index, modality of dialysis and hsCRP. RESULTS: The range of plasma vitamin C level was from 0.48 µg/mL to 31.16 µg/mL. 35.9% (n = 137) patients had severe vitamin C deficiency (<2 µg/mL). Plasma vitamin C level was inversely associated with age and dialysis vintage. After age and dialysis vintage were adjusted, vitamin C deficiency was associated with MHD. R square for model fitting was relatively low, which implied that there were other vitamin C influencing factors not included in the model. CONCLUSIONS: Vitamin C deficiency is common in dialysis patients, especially in patients treated with MHD.

Inverse association of vitamin C with cataract in older people in India.

OBJECTIVE: To examine the association between vitamin C and cataract in the Indian setting. DESIGN: Population-based cross-sectional analytic study. PARTICIPANTS: A total of 5638 people aged ≥60 years. METHODS: Enumeration of randomly sampled villages in 2 areas of north and south India to identify people aged ≥60 years. Participants were interviewed for socioeconomic and lifestyle factors (tobacco, alcohol, household cooking fuel, work, and diet); attended a clinical examination, including lens photography; and provided a blood sample for antioxidant analysis. Plasma vitamin C was measured using an enzyme-based assay in plasma stabilized with metaphosphoric acid, and other antioxidants were measured by reverse-phase high-pressure liquid chromatography. MAIN OUTCOME MEASURES: Cataract and type of cataract were graded from digital lens images using the Lens Opacity Classification System III (LOCS III), and cataract was classified from the grade in the worse eye of ≥4 for nuclear cataract, ≥3 for cortical cataract, and ≥2 for posterior subcapsular cataract (PSC). Any cataract was defined as any unoperated or operated cataract. RESULTS: Of 7518 enumerated people, 5638 (75%) provided data on vitamin C, antioxidants, and potential confounders. Vitamin C was inversely associated with cataract (adjusted odds ratio [OR] for highest to lowest quartile = 0.61; 95% confidence interval (CI), 0.51-0.74; P=1.1×10(-6)). Inclusion of other antioxidants in the model (lutein, zeaxanthin, retinol, ß-carotene, and α-tocopherol) made only a small attenuation to the result (OR 0.68; 95% CI, 0.57-0.82; P < 0.0001). Similar results were seen with vitamin C by type of cataract: nuclear cataract (adjusted OR 0.66; CI, 0.54-0.80; P < 0.0001), cortical cataract (adjusted OR 0.70; CI, 0.54-0.90; P < 0.002), and PSC (adjusted OR 0.58; CI, 0.45-0.74; P < 0.00003). Lutein, zeaxanthin, and retinol were significantly inversely associated with cataract, but the associations were weaker and not consistently observed by type of cataract. Inverse associations were also observed for dietary vitamin C and cataract. CONCLUSIONS: We found a strong association with vitamin C and cataract in a vitamin C-depleted population. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

High dietary fat and cholesterol exacerbates chronic vitamin C deficiency in guinea pigs.

Vitamin C deficiency - or hypovitaminosis C defined as a plasma concentration below 23 µm - is estimated to affect hundreds of millions of people in the Western world, in particular subpopulations of low socio-economic status that tend to eat diets of poor nutritional value. Recent studies by us have shown that vitamin C deficiency may result in impaired brain development. Thus, the aim of the present study was to investigate if a poor diet high in fat and cholesterol affects the vitamin C status of guinea pigs kept on either sufficient or deficient levels of dietary ascorbate (Asc) for up to 6 months with particular emphasis on the brain. The present results show that a high-fat and cholesterol diet significantly decreased the vitamin C concentrations in the brain, irrespective of the vitamin C status of the animal (P < 0·001). The brain Asc oxidation ratio only depended on vitamin C status (P < 0·0001) and not on the dietary lipid content. In plasma, the levels of Asc significantly decreased when vitamin C in the diet was low or when the fat/cholesterol content was high (P < 0·0001 for both). The Asc oxidation ratio increased both with low vitamin C and with high fat and cholesterol content (P < 0·0001 for both). We show here for the first time that vitamin C homoeostasis of brain is affected by a diet rich in fat and cholesterol. The present findings suggest that this type of diet increases the turnover of Asc; hence, individuals consuming high-lipid diets may be at increased risk of vitamin C deficiency.

Low levels of vitamin C in dialysis patients is associated with decreased prealbumin and increased C-reactive protein.

BACKGROUND: Subclinical inflammation is a common phenomenon in patients on either continuous ambulatory peritoneal dialysis (CAPD) or maintenance hemodialysis (MHD). We hypothesized that vitamin C had anti-inflammation effect because of its electron offering ability. The current study was designed to test the relationship of plasma vitamin C level and some inflammatory markers. METHODS: In this cross-sectional study, 284 dialysis patients were recruited, including 117 MHD and 167 CAPD patients. The demographics were recorded. Plasma vitamin C was measured by high-performance liquid chromatography. And we also measured body mass index (BMI, calculated as weight/height(2)), Kt/V, serum albumin, serum prealbumin, high-sensitivity C-reactive protein (hsCRP), ferritin, hemoglobin. The relationships between vitamin C and albumin, pre-albumin and hsCRP levels were tested by Spearman correlation analysis and multiple regression analysis. Patients were classified into three subgroups by vitamin C level according to previous recommendation 12 in MHD and CAPD patients respectively: group A: < 2 ug/ml (< 11.4 umol/l, deficiency), group B: 2-4 ug/ml (11.4-22.8 umol/l, insufficiency) and group C: > 4 ug/ml (> 22.8 umol/l, normal and above). RESULTS: Patients showed a widely distribution of plasma vitamin C levels in the total 284 dialysis patients. Vitamin C deficiency (< 2 ug/ml) was present in 95(33.45%) and insufficiency (2-4 ug/ml) in 88(30.99%). 73(25.70%) patients had plasma vitamin C levels within normal range (4-14 ug/ml) and 28(9.86%) at higher than normal levels (> 14 ug/ml). The similar proportion of different vitamin C levels was found in both MHD and CAPD groups. Plasma vitamin C level was inversely associated with hsCRP concentration (Spearman r = -0.201, P = 0.001) and positively associated with prealbumin (Spearman r = 0.268, P < 0.001), albumin levels (Spearman r = 0.161, P = 0.007). In multiple linear regression analysis, plasma vitamin C level was inversely associated with log(10)hsCRP (P = 0.048) and positively with prealbumin levels (P = 0.002) adjusted for gender, age, diabetes, modality of dialysis and some other confounding effects. CONCLUSIONS: The investigation indicates that vitamin C deficiency is common in both MHD patients and CAPD patients. Plasma vitamin C level is positively associated with serum prealbumin level and negatively associated with hsCRP level in both groups. Vitamin C deficiency may play an important role in the increased inflammatory status in dialysis patients. Further studies are needed to determine whether inflammatory status in dialysis patients can be improved by using vitamin C supplements.