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.

Vitamin C Deficiency and the Risk of Osteoporosis in Patients with an Inflammatory Bowel Disease.

Recent research studies have shown that vitamin C (ascorbic acid) may affect bone mineral density and that a deficiency of ascorbic acid leads to the development of osteoporosis. Patients suffering from an inflammatory bowel disease are at a risk of low bone mineral density. It is vital to notice that patients with Crohn's disease and ulcerative colitis also are at risk of vitamin C deficiency which is due to factors such as reduced consumption of fresh vegetables and fruits, i.e., the main sources of ascorbic acid. Additionally, some patients follow diets which may provide an insufficient amount of vitamin C. Moreover, serum vitamin C level also is dependent on genetic factors, such as SLC23A1 and SLC23A2 genes, encoding sodium-dependent vitamin C transporters and GSTM1, GSTP1 and GSTT1 genes which encode glutathione S-transferases. Furthermore, ascorbic acid may modify the composition of gut microbiota which plays a role in the pathogenesis of an inflammatory bowel disease.

Vitamin C in Home Parenteral Nutrition: A Need for Monitoring.

To date, there are no recommendations about screening plasma vitamin C concentration and adjust its supplementation in patients on long-term home parenteral nutrition (HPN). The aim of this study was to evaluate vitamin C status and determine if a commercial multivitamin preparation (CMVP) containing 125 mg of vitamin C is sufficient in stable patients on HPN. All clinically stable patients receiving HPN or an intravenous fluid infusion at least two times per week for at least 6 months, hospitalized for nutritional assessment, were retrospectively included, for a total of 186 patients. We found that 29% of the patients had vitamin C insufficiency (i.e., <25 µmol/L). In univariate analysis, C-reactive protein (CRP) (p = 0.002) and intake of only 125 mg of vitamin C (p = 0.001) were negatively associated with vitamin C levels, and duration of follow-up in our referral center (p = 0.009) was positively associated with vitamin C levels. In multivariate analysis, only CRP (p = 0.001) and intake of 125 mg of vitamin C (p < 0.0001) were independently associated with low plasma vitamin C concentration. Patients receiving only CMVP with a low plasma vitamin C level significantly received personal compounded HPN (p = 0.008) and presented an inflammatory syndrome (p = 0.002). Vitamin C insufficiency is frequent in individuals undergoing home parenteral nutrition; therefore, there is a need to monitor plasma vitamin C levels, especially in patients on HPN with an inflammatory syndrome and only on CMVP.

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-1ß 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.

Inadequate Vitamin C Status in Prediabetes and Type 2 Diabetes Mellitus: Associations with Glycaemic Control, Obesity, and Smoking.

Vitamin C (ascorbate) is an essential micronutrient in humans, being required for a number of important biological functions via acting as an enzymatic cofactor and reducing agent. There is some evidence to suggest that people with type 2 diabetes mellitus (T2DM) have lower plasma vitamin C concentrations compared to those with normal glucose tolerance (NGT). The aim of this study was to investigate plasma vitamin C concentrations across the glycaemic spectrum and to explore correlations with indices of metabolic health. This is a cross-sectional observational pilot study in adults across the glycaemic spectrum from NGT to T2DM. Demographic and anthropometric data along with information on physical activity were collected and participants were asked to complete a four-day weighed food diary. Venous blood samples were collected and glycaemic indices, plasma vitamin C concentrations, hormone tests, lipid profiles, and high-sensitivity C-reactive protein (hs-CRP) were analysed. A total of 89 participants completed the study, including individuals with NGT (n = 35), prediabetes (n = 25), and T2DM managed by diet alone or on a regimen of Metformin only (n = 29). Plasma vitamin C concentrations were significantly lower in individuals with T2DM compared to those with NGT (41.2 µmol/L versus 57.4 µmol/L, p < 0.05) and a higher proportion of vitamin C deficiency (i.e. <11.0 µmol/L) was observed in both the prediabetes and T2DM groups. The results showed fasting glucose (p = 0.001), BMI (p = 0.001), smoking history (p = 0.003), and dietary vitamin C intake (p = 0.032) to be significant independent predictors of plasma vitamin C concentrations. In conclusion, these results suggest that adults with a history of smoking, prediabetes or T2DM, and/or obesity, have greater vitamin C requirements. Future research is required to investigate whether eating more vitamin C rich foods and/or taking vitamin C supplements may reduce the risk of progression to, and/or complications associated with, T2DM.

Marginal Ascorbate Status (Hypovitaminosis C) Results in an Attenuated Response to Vitamin C Supplementation.

Inadequate dietary intake of vitamin C results in hypovitaminosis C, defined as a plasma ascorbate concentration ≤23 µmol/L. Our objective was to carry out a retrospective analysis of two vitamin C supplementation studies to determine whether supplementation with 50 mg/day vitamin C is sufficient to restore adequate ascorbate status (≥50 µmol/L) in individuals with hypovitaminosis C. Plasma ascorbate data from 70 young adult males, supplemented with 50 or 200 mg/day vitamin C for up to six weeks, was analyzed. Hypovitaminosis C status was identified based on plasma ascorbate being ≤23 µmol/L and the response of these individuals to vitamin C supplementation was examined. Of the participants consuming 50 mg/day vitamin C for up to six weeks, those with hypovitaminosis C at baseline achieved plasma concentrations of only ~30 µmol/L, whereas the remainder reached ~50 µmol/L. Participants who consumed 200 mg/day vitamin C typically reached saturating concentrations (>65 µmol/L) within one week, while those with hypovitaminosis C required two weeks to reach saturation. Regression modelling indicated that the participants' initial ascorbate status and body weight explained ~30% of the variability in the final ascorbate concentration. Overall, our analysis revealed that supplementation with 50 mg/day vitamin C, which resulted in a total dietary vitamin C intake of 75 mg/day, was insufficient to achieve adequate plasma ascorbate concentrations in individuals with hypovitaminosis C. Furthermore, increased body weight had a negative impact on ascorbate status.

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.

Vitamin C modulates the metabolic and cytokine profiles, alleviates hepatic endoplasmic reticulum stress, and increases the life span of Gulo-/- mice.

Suboptimal intake of dietary vitamin C (ascorbate) increases the risk of several chronic diseases but the exact metabolic pathways affected are still unknown. In this study, we examined the metabolic profile of mice lacking the enzyme gulonolactone oxidase (Gulo) required for the biosynthesis of ascorbate. Gulo-/- mice were supplemented with 0%, 0.01%, and 0.4% ascorbate (w/v) in drinking water and serum was collected for metabolite measurements by targeted mass spectrometry. We also quantified 42 serum cytokines and examined the levels of different stress markers in liver. The metabolic profiles of Gulo-/- mice treated with ascorbate were different from untreated Gulo-/- and normal wild type mice. The cytokine profiles of Gulo-/-mice, in return, overlapped the profile of wild type animals upon 0.01% or 0.4% vitamin C supplementation. The life span of Gulo-/- mice increased with the amount of ascorbate in drinking water. It also correlated significantly with the ratios of serum arginine/lysine, tyrosine/phenylalanine, and the ratio of specific species of saturated/unsaturated phosphatidylcholines. Finally, levels of hepatic phosphorylated endoplasmic reticulum associated stress markers IRE1α and eIF2α correlated inversely with serum ascorbate and life span suggesting that vitamin C modulates endoplasmic reticulum stress response and longevity in Gulo-/- mice.

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.

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.

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.

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.

Vitamin C supplementation slightly improves physical activity levels and reduces cold incidence in men with marginal vitamin C status: a randomized controlled trial.

The early indications of vitamin C deficiency are unremarkable (fatigue, malaise, depression) and may manifest as a reduced desire to be physically active; moreover, hypovitaminosis C may be associated with increased cold duration and severity. This study examined the impact of vitamin C on physical activity and respiratory tract infections during the peak of the cold season. Healthy non-smoking adult men (18-35 years; BMI < 34 kg/m2; plasma vitamin C < 45 µmol/L) received either 1000 mg of vitamin C daily (n = 15) or placebo (n = 13) in a randomized, double-blind, eight-week trial. All participants completed the Wisconsin Upper Respiratory Symptom Survey-21 daily and the Godin Leisure-Time Exercise Questionnaire weekly. In the final two weeks of the trial, the physical activity score rose modestly for the vitamin C group vs. placebo after adjusting for baseline values: +39.6% (95% CI [-4.5,83.7]; p = 0.10). The number of participants reporting cold episodes was 7 and 11 for the vitamin C and placebo groups respectively during the eight-week trial (RR = 0.55; 95% CI [0.33,0.94]; p = 0.04) and cold duration was reduced 59% in the vitamin C versus placebo groups (-3.2 days; 95% CI [-7.0,0.6]; p = 0.06). These data suggest measurable health advantages associated with vitamin C supplementation in a population with adequate-to-low vitamin C status.

Vitamin C intake, circulating vitamin C and risk of stroke: a meta-analysis of prospective studies.

BACKGROUND: Though vitamin C supplementation has shown no observed effects on stroke prevention in several clinical trials, uncertainty remains as to whether long-term, low-dose intake influences the development of stroke among general populations. Furthermore, the association between circulating vitamin C and the risk of stroke is also unclear. For further clarification of these issues, we conducted a meta-analysis of prospective studies. METHODS AND RESULTS: PubMed and EMBASE databases were searched, and the bibliographies of the retrieved articles were also reviewed to identify eligible studies. Summary relative risk (RRs) with corresponding 95% confidence intervals (CIs) were computed with a random-effects model. The summary RR for the high-versus-low categories was 0.81 (95% CI: 0.74 to 0.90) for dietary vitamin C intake (11 studies), and 0.62 (95% CI: 0.49 to 0.79) for circulating vitamin C (6 studies). The summary RR for each 100 mg/day increment in dietary vitamin C was 0.83 (95% CI: 0.75 to 0.93) (10 studies), and for each 20 µmol/L increment in circulating vitamin C was 0.81 (95% CI: 0.75 to 0.88) (5 studies). Few studies reported results for vitamin C supplements (RR for high-versus-low intake=0.83, 95% CI: 0.62 to 1.10, 3 studies). CONCLUSIONS: This meta-analysis suggests significant inverse relationships between dietary vitamin C intake, circulating vitamin C, and risk of stroke.

Efficacy of a multi micronutrient-fortified drink in improving iron and micronutrient status among schoolchildren with low iron stores in India: a randomised, double-masked placebo-controlled trial.

BACKGROUND/OBJECTIVES: A multiple micronutrient-fortified drink could be an effective strategy to combating micronutrient deficiencies in school going children. To assess the efficacy of a multiple micronutrient-fortified drink in reducing iron deficiency (ID), ID anemia (IDA), anemia and improving micronutrient status among schoolchildren with low iron stores. The study employed a school-based, randomized, double-blind, placebo-controlled design. SUBJECTS/METHODS: Schoolchildren with low serum ferritin (SF <20 µg/l) (n=246), aged 6-12 years were randomly assigned to receive either a multi-micronutrient fortified or an unfortified identical control drink. The drinks were provided 6 days/week for 8 weeks. Anthropometric and biochemical assessments were taken at baseline and endline. RESULTS: Study groups at baseline were comparable, and compliance to the intervention was similar. The overall prevalence of ID, IDA and anemia was 64%, 19% and 24%, respectively. The prevalence of ID, IDA, vitamin C and vitamin B12 deficiencies significantly reduced by 42%, 18%, 21% and 5%, respectively, in the intervention arm (P<0.01) as compared with the control arm at the end of the study. Similarly, the concentration of hemoglobin, SF, vitamin A, vitamin B12, vitamin C and body iron stores were significantly higher in the intervention arm in comparison to the control arm (P<0.001). Red cell folate levels also improved significantly in the intervention arm (P=0.04), however, serum zinc status did not change in either of the study arms. Children who had received the fortified drink had significantly lower odds of being ID (0.15; 95% confidence interval (CI): 0.09-0.27), IDA (0.14; 95% CI: 0.04-0.52), vitamin B12 deficient (0.36; 95% CI: 0.18-0.73) and vitamin C deficient (0.24; 95% CI: 0.13-0.46), after adjusting for baseline age, gender and weight. CONCLUSIONS: The multi micronutrient-fortified drink was efficacious in reducing the prevalence of ID, IDA, vitamin C and vitamin B12 deficiency and improved micronutrient status in schoolchildren.

Ascorbate status modulates reticuloendothelial iron stores and response to deferasirox iron chelation in ascorbate-deficient rats.

Iron chelation is essential to patients on chronic blood transfusions to prevent toxicity from iron overload and remove excess iron. Deferasirox (DFX) is the most commonly used iron chelator in the United States; however, some patients are relatively refractory to DFX therapy. We postulated that vitamin C supplementation would improve the availability of transfusional iron to DFX treatment by promoting iron's redox cycling, increasing its soluble ferrous form and promoting its release from reticuloendothelial cells. Osteogenic dystrophy rats (n = 54) were given iron dextran injections for 10 weeks. Cardiac and liver iron levels were measured after iron loading (n = 18), 12 weeks of sham chelation (n = 18), and 12 weeks of DFX chelation (n = 18) at 75 mg/kg/day. Ascorbate supplementation of 150 ppm, 900 ppm, and 2250 ppm was used in the chow to mimic a broad range of ascorbate status; plasma ascorbate levels were 5.4 ± 1.9, 8.2 ± 1.4, 23.6 ± 9.8 µM, respectively (p < 0.0001). The most severe ascorbate deficiency produced reticuloenthelial retention, lowering total hepatic iron by 29% at the end of iron loading (p < 0.05) and limiting iron redistribution from cardiac and hepatic macrophages during 12 weeks of sham chelation. Most importantly, ascorbate supplementation at 2250 ppm improved DFX efficiency, allowing DFX to remove 21% more hepatic iron than ascorbate supplementation with 900 ppm or 150 ppm (p < 0.05). We conclude that vitamin C status modulates the release of iron from the reticuloendothelial system and correlates positively with DFX chelation efficiency. Our findings suggest that ascorbate status should be probed in patients with unsatisfactory response to DFX.

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.

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.

Nocturnal haemoglobin oxygen saturation variability is associated with vitamin C deficiency in Tanzanian children with sickle cell anaemia.

AIM: To compare pulse oximetry in children with sickle cell anaemia (SCA) and controls and test the hypothesis that vitamin C deficiency (VCD; <11.4 µmol/L) is associated with nocturnal haemoglobin oxygen desaturation in SCA. METHODS: We undertook nocturnal and daytime pulse oximetry in 23 children with SCA (median age 8 years) with known steady-state plasma vitamin C concentrations and 18 siblings (median 7 years). RESULTS: Median nocturnal delta 12 s index (delta12 s), a measure of haemoglobin oxygen saturation (SpO(2)) variability, was 0.38 (interquartile range 0.28-0.51) in SCA and 0.35 (0.23-0.48) in controls, with 9/23 and 6/18, respectively, having a delta12 s >0.4, compatible with obstructive sleep apnoea (OSA). Eleven of twenty-three with SCA had VCD; logged vitamin C concentrations showed a 66% decrease per 0.1 unit increase in delta12 s ([95% CI -86%, -15%]; p=0.023) and delta12 s >0.4 was associated with VCD (odds ratio 8.75 [1.24-61.7], p=0.029). Daytime and mean nocturnal SpO(2) were lower in SCA but there was no association with vitamin C. CONCLUSION: Obstructive sleep apnoea (OSA), detected from nocturnal haemoglobin oxygen saturation variability, is common in Tanzanian children and associated with vitamin C Deficiency in SCA. The direction of causality could be determined by comparing OSA treatment with vitamin C supplementation.

Vitamin C requirement in surgical patients.

PURPOSE OF REVIEW: To summarize recent findings on vitamin C status and assess the requirement and optimal dose of supplementation in surgical patients. RECENT FINDINGS: Blood vitamin C concentration falls after uncomplicated surgery and further decreases in surgical intensive care unit patients. The decline may be owing to increased demand caused by increased oxidative stress. To normalize plasma vitamin C concentration, much higher doses than the recommended daily allowance or doses recommended in parenteral nutrition guidelines are needed in these patients. In uncomplicated surgical patients, more than 500 mg/day of vitamin C may be required, with much higher doses in surgical intensive care unit patients. In uncomplicated gastrointestinal surgery, continuous parenteral administration of 500 mg/day of vitamin C reduced postoperative oxidative stress as manifested by reduced urinary excretion of isoprostane. In some studies, postoperative atrial fibrillation was prevented after cardiac surgery by perioperative vitamin C supplementation. In critically ill patients, some prospective randomized controlled trials support parenteral supplementation of high doses of vitamin C, E and trace elements. SUMMARY: Vitamin C requirement is increased in surgical patients, and the potential advantage of supplementation is to increase the plasma and tissue levels of vitamin C and thereby reduce oxidative stress. Although some clinical benefits of high-dose vitamin C supplementation have been shown in the critically ill, the optimal dose for supplementation and the clinical benefits remain to be investigated in surgical patients.