Vitamin C: should we supplement?

PURPOSE OF REVIEW: Hypovitaminosis C and vitamin C deficiency are very common in critically ill patients due to increased needs and decreased intake. Because vitamin C has pleiotropic functions, deficiency can aggravate the severity of illness and hamper recovery. RECENT FINDINGS: Vitamin C is a key circulating antioxidant with anti-inflammatory and immune-supporting effects, and a cofactor for important mono and dioxygenase enzymes. An increasing number of preclinical studies in trauma, ischemia/reperfusion, and sepsis models show that vitamin C administered at pharmacological doses attenuates oxidative stress and inflammation, and restores endothelial and organ function. Older studies showed less organ dysfunction when vitamin C was administered in repletion dose (2-3 g intravenous vitamin C/day). Recent small controlled studies using pharmacological doses (6-16 g/day) suggest that vitamin C reduces vasopressor support and organ dysfunction, and may even decrease mortality. SUMMARY: A short course of intravenous vitamin C in pharmacological dose seems a promising, well tolerated, and cheap adjuvant therapy to modulate the overwhelming oxidative stress in severe sepsis, trauma, and reperfusion after ischemia. Large randomized controlled trials are necessary to provide more evidence before wide-scale implementation can be recommended.

Is Vitamin C Supplementation in Patients with ß-Thalassemia Major Beneficial or Detrimental?

Globally, ß-thalassemia major (ß-TM) is one of the most common hereditary disorders. Multiple blood transfusions, that are a life-saving therapy in patients with ß-TM, is a major source of iron overload. Iron overload can lead to significant morbidity and mortality. Research evidence indicates that oxidative stress induced by iron overload, is one of the major precipitating causes of vitamin C deficiency in ß-TM patients. It has previously been shown that patients with ß-TM have significantly lower levels of vitamin C as compared to healthy individuals. It is believed that vitamin C can reduce both ferric (Fe(3+)) and ferrous (Fe(2+)) ions, and also facilitate the accessibility of iron to chelators through increase of iron release from the reticuloendothelial system. Despite the potential benefits of vitamin C in patients with ß-TM, several areas of concern exist that should be addressed by high quality research designs. Some recommendations have been provided through this study.

Severe vitamin C deficiency in a child newly diagnosed with T-cell ALL due to nutrient gap.

A 10-year-old boy developed a perifollicular rash during interim maintenance of T-Cell acute lymphoblastic leukaemia. Differential diagnoses included drug reaction and inflammatory process. Before diagnosis, the patient had a limited diet--low in vegetables and fruits--due to selective eating, with later anorexia and taste aversions due to chemotherapy treatment. Despite nutritional counselling and starting a multivitamin, the patient incurred severe weight loss (18.5% of his usual body weight). Serum levels of ascorbic acid were non-detectable, at <5 µmol/L, indicative of vitamin C deficiency. The patient began vitamin C supplementation containing 125 mg ascorbic acid three times a day for 7 days, then 125 mg once daily for 3 months to normalise serum vitamin C. After ascorbic acid treatment was completed, the patient started a complete multivitamin and made efforts to eat fruits and vegetables rich in vitamin C. His serum ascorbic acid concentrations normalised to 52 µmol/L 3 months after receiving supplementation.

Systematic review and meta-analysis of randomised controlled trials testing the effects of vitamin C supplementation on blood lipids.

BACKGROUND & AIMS: Randomised controlled trials (RCTs) in humans revealed contradictory results regarding the effect of vitamin C supplementation on blood lipids. We aimed to conduct a systematic review and meta-analysis of RCTs investigating the effect of vitamin C supplementation on total cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triglycerides and to determine whether the effects are modified by the participants' or intervention characteristics. METHODS: Four databases (PubMed, Embase, Scopus and Cochrane Library) were searched from inception until August 2014 for RCTs supplementing adult participants with vitamin C for ≥ 2 weeks and reporting changes in blood lipids. RESULTS: Overall, vitamin C supplementation did not change blood lipids concentration significantly. However, supplementation reduced total cholesterol in younger participants (≤52 years age) (-0.26 mmol/L, 95% CI: -0.45, -0.07) and LDL-C in healthy participants (-0.32 mmol/L, 95% CI: -0.57, -0.07). In diabetics, vitamin C supplementation reduced triglycerides significantly (-0.15 mmol/L, 95% CI: -0.30, -0.002) and increased HDL-C significantly (0.06 mmol/L, 95% CI: 0.02, 0.11). Meta-regression analyses showed the changes in total cholesterol (ß: -0.24, CI: -0.36, -0.11) and in triglycerides (ß: -0.17, CI: -0.30, -0.05) following vitamin C supplementation were greater in those with higher concentrations of these lipids at baseline. Greater increase in HDL-C was observed in participants with lower baseline plasma concentrations of vitamin C (ß: -0.002, CI: -0.003, -0.0001). CONCLUSIONS: Overall, vitamin C supplementation had no significant effect on lipid profile. However, subgroup and sensitivity analyses showed significant reductions in blood lipids following supplementation in sub-populations with dyslipidaemia or low vitamin C status at baseline. PROSPERO Database registration: CRD42014013487, http://www.crd.york.ac.uk/prospero/.

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.

A review of the literature regarding nutritional supplements and their effect on vaginal flora and preterm birth.

PURPOSE OF REVIEW: The aim of this review was to evaluate recently published review articles which examine the use of nutritional supplements to prevent preterm birth (PTB) by modifying vaginal bacteria. RECENT FINDINGS: Probiotics, vitamin D and vitamin C were all identified as nutritional supplements that have the potential to alter bacterial flora and consequently reduce PTB and treat or prevent genital infections. Evidence shows that probiotics may reduce the incidence of PTB as well as being effective at treating bacterial vaginosis, a known cause for PTB. Low vitamin D levels may be associated with bacterial vaginosis, although no evidence was identified which demonstrated that vitamin D supplementation reduced the risk of having bacterial vaginosis or PTB.There is little evidence regarding vitamin C supplementation, although it does suggest a possible benefit with regard to preterm rupture of membranes; however, this did not appear to reduce rates of PTB. SUMMARY: Although there is evidence that taking probiotics in pregnancy may reduce the incidence of PTB, it is mainly derived from small, poor quality studies. Vitamin D and vitamin C may have potential benefits, but these remain to be proven. Large randomized controlled trials are needed to more accurately evaluate the potential benefits of these low-cost interventions for reducing PTB and its consequences.

A short-term evaluation of the relationship between plasma ascorbic acid levels and periodontal disease in systemically healthy and type 2 diabetes mellitus subjects.

BACKGROUND: Deficient ascorbic acid levels (AALs) and Type 2 diabetes mellitus (T2DM) are associated with periodontal disease. This study evaluated the relationship between plasma AAL and periodontitis in systemically healthy and T2DM subjects, which to the best of our knowledge is being reported for the first time. METHODS: One hundred twenty subjects were categorized into four groups of 30 each as group 1: without periodontal disease; group 2: chronic gingivitis; group 3: chronic periodontitis, and group 4: chronic periodontitis and freshly diagnosed T2DM. Plaque index (PlI), sulcus bleeding index (SBI), and probing pocket depths (PPDs) were evaluated. Venous blood was evaluated for plasma AAL spectrophotometrically. Randomized subjects were subgrouped within groups 2-4, to receive either scaling and root planing (SRP) with dietary supplementation (450 mg) of ascorbic acid (AA) for two weeks or only SRP. After two weeks, the clinical parameters were reassessed. Tukey's multiple post hoc procedures and paired t test were used with the level of statistical significance adjusted to p ≤ .05. RESULTS: AAL plasma levels were significantly greater in group 1 than in group 2 (p = .0007) and in group 4 (p = .0003). A significant reduction in the SBI was seen in the subgroups that received dietary supplementation of vitamin C within group 2 (p = .0012) and group 4 (p = .036). CONCLUSIONS: Plasma AAL is below the normal range in systemically healthy subjects with gingivitis and diabetics with periodontitis. Dietary AA supplementation with SRP improves the SBI in subjects with gingivitis and diabetics with periodontitis.

Recent applications of engineered animal antioxidant deficiency models in human nutrition and chronic disease.

Dietary antioxidants are essential nutrients that inhibit the oxidation of biologically important molecules and suppress the toxicity of reactive oxygen or nitrogen species. When the total antioxidant capacity is insufficient to quench these reactive species, oxidative damage occurs and contributes to the onset and progression of chronic diseases, such as neurodegenerative diseases, cardiovascular diseases, and cancer. However, epidemiological studies that examine the relationship between antioxidants and disease outcome can only identify correlative associations. Additionally, many antioxidants also have prooxidant effects. Thus, clinically relevant animal models of antioxidant function are essential for improving our understanding of the role of antioxidants in the pathogenesis of complex diseases as well as evaluating the therapeutic potential and risks of their supplementation. Recent progress in gene knockout mice and virus-based gene expression has potentiated these areas of study. Here, we review the current genetically modified animal models of dietary antioxidant function and their clinical relevance in chronic diseases. This review focuses on the 3 major antioxidants in the human body: vitamin C, vitamin E, and uric acid. We examine genetic models of vitamin C synthesis (guinea pig, Osteogenic Disorder Shionogi rat, Gulo(-/-) and SMP30(-/-) mouse mutants) and transport (Slc23a1(-/-) and Slc23a2(-/-) mouse mutants), vitamin E transport (Ttpa(-/-) mouse mutant), and uric acid synthesis (Uox(-/-) mouse mutant). The application of these models to current research goals is also discussed.

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.

[The use of alimentary antioxidants in diet therapy of geriatric patients during the period of the surgical treatment]. / Ispol'zovanie alimentarnykh antioksidantov v dietoterapii geriatricheskikh bol'nykh v period khirurgicheskogo lecheniia.

Analysis of actual feeding of 277 geriatric patients suffering from urology disease. The patients had a combined deficient of vitamin A, vitamin C, vitamin of the B group, beta-capotene and mineral substances. Diets 1a, 1, 5, 7, 9, 15 could not provide daily needs for antioxidant nutrients. Antioxidant and antiinflammatory effects of the dietary supplement containing natural antioxidants in 122 oncourology patients after operation was indicated. So there was reason to fortify diets of patients with antioxidant dietary supplement during the period of surgical treatment.

[The influence of vegetable biologically active food additives on men's health]. / Vliianie rastitel'noi biologicheski aktivnoi dobavki k pishche na zdorov'e cheloveka.

The young people of draft age often have breach of a the dietary, that guite often is accompanied by decrease resistance and adaptation of opportunities. Application vegetative BAS to food (the beet with selderej) separately or especially together with liquid biphidiumbacterin gives good therapeutic effect.

Plasma vitamin C and food choice in the third Glasgow MONICA population survey.

STUDY OBJECTIVE: To determine the contribution of different foods to the estimated intakes of vitamin C among those differing in plasma vitamin C levels, and thereby inform dietary strategies for correcting possible deficiency. DESIGN: Cross sectional random population survey. SETTING: North Glasgow, Scotland, 1992. PARTICIPANTS: 632 men and 635 women, aged 25 to 74 years, not taking vitamin supplements, who participated in the third MONICA study (population survey monitoring trends and determinants of cardiovascular disease). MEASUREMENTS AND MAIN RESULTS: Dietary and sociodemographic information was collected using a food frequency and lifestyle questionnaire. Plasma vitamin C was measured in non-fasted venous blood samples and subjects categorised by cut points of 11.4 and 22.7 micromol/l as being of low, marginal or optimal vitamin C status. Food sources of dietary vitamin C were identified for subjects in these categories. Plasma vitamin C concentrations were compared among groups classified according to intake of key foods. More men (26%) than women (14%) were in the low category for vitamin C status; as were a higher percentage of smokers and of those in the older age groups. Intake of vitamin C from potatoes and chips (fried potatoes) was uniform across categories; while the determinants of optimal versus low status were the intakes of citrus fruit, non-citrus fruit and fruit juice. Optimal status was achieved by a combined frequency of fruit, vegetables and/or fruit juice of three times a day or more except in older male smokers where a frequency greater than this was required even to reach a marginal plasma vitamin C level. CONCLUSION: Fruit, vegetables and/or fruit juice three or more times a day increases plasma vitamin C concentrations above the threshold for risk of deficiency.

Diet and dermatology. The role of dietary manipulation in the prevention and treatment of cutaneous disorders.

The role of dietary manipulation and vitamins in the prevention and treatment of certain skin diseases is reviewed. Manipulation of nutrition by either diet restriction or supplementation can effect cutaneous disorders such as skin cancer, wound healing, atopic dermatitis, psoriasis, and dermatitis herpetiformis.

Vitamin C requirements in postoperative patients.

The postoperative ascorbic acid requirements of 63 surgical patients were assessed by measurement of buffy layer leucocyte ascorbic acid and the ascorbic acid content of white blood cells. There was a significant reduction in ascorbic acid levels following surgery. The postoperative changes were unrelated to the extent of surgical trauma or the volume of blood transfused during surgery but there was a significant correlation between postoperative ascorbic acid measurements and white blood cell counts. It appears that postoperative leucocytosis and release by the bone marrow of white blood cells with a low ascorbic acid content may partly account for the postoperative changes in buffy layer and white blood cell ascorbic acid measurements. However, surgical operations were followed by an authentic increase in ascorbic acid requirements, and there was a 42 per cent reduction in circulating white blood cell ascorbic acid levels on the third postoperative day. The findings of this study create an argument for the use of ascorbic acid supplements in surgical patients although it is unlikely that postoperative changes in leucocyte ascorbic acid have pathologic significance in wound repair.