Lower Plasma Levels Of Vitamin Research Articles

Vitamin E and Supplements Offer Eye Neuroprotection – Myth or Reality?

Background: Several studies suggested that nutrition might have an effect on eye health. Although exposure to nutrients is ubiquitous, on the other hand without it, we generally cannot survive and an exposure too high or too low causes health problems. Vitamins are a good example and the ubiquitous exposure to vitamins has led to many epidemiological studies for many diseases, including glaucoma.
 Abstract: Leading causes of vision loss include several eye conditions such as cataract and glaucoma. The role of nutritional supplementation to prevent the progression of ocular disease is of great interest to health care professionals. It is recognized that the crystalline lens and retina suffer oxidative damage and the most protective agents are anti-oxidant vitamins A, C and E. The Age-Related Eye Disease Study (AREDS), found that supplementation with vitamins C and E, reduced the risk of developing various ocular diseases. The RDA for vitamin E is 15 mg/day α-tocopherol for both women and men. Vitamin E exists naturally in nuts and seeds, in addition to dark leafy vegetables. In a recent study reported lower plasma levels of vitamin E in POAG subjects.
 Conclusion: In conclusion, exposure to nutrients although is ubiquitous, without it, in general we cannot survive. Conflicting evidence is presented for vitamins A and E in prevention of ocular disease. A number of epidemiological studies showed an increased risk of nuclear or cortical cataract in people with low blood levels of vitamin E. Furthermore, a number of studies suggested that nutrition might have an effect on the intraocular pressure (IOP) or glaucoma, arbitrated by oxidative stress.

Alteration of Blood Oxidative Stress Status in Patients with Thoracic Aortic Dissection: A Pilot Study.

Thoracic aortic dissection (TAD) is a life-threatening condition which usually occurs on an aneurysmal aortic wall. Although increasing data have shown that inflammation and oxidative stress play an important role in the patho-physiology of dissection, systemic oxidative stress status (OSS) has not been clearly determined in patients suffering from TAD. A cohort of 115 patients presenting type A or B TAD were admitted to our center from 2013 to 2017. Out of this cohort, 46 patients were included in a study on dissected aorta (LIege study on DIssected Aorta: LIDIA). In 18 out of the 46 patients, systemic OSS parameters were evaluated after TAD diagnosis by determination of eight different antioxidants, four trace elements, two markers of oxidative lipid damage and two inflammatory markers. The 18 TAD patients included 10 men and 8 women (median age: 62 years; interquartile range: 55-68) diagnosed with type A (N = 8) or B (N = 10) TAD. Low plasma levels of vitamin C, β-carotene, γ-tocopherol, thiol proteins, paraoxonase and selenium were observed in these 18 patients. By contrast, the concentration of copper and total hydroperoxides, copper/zinc ratio, as well as inflammatory markers, were higher than the reference intervals. No difference was observed in oxidative stress biomarker concentrations between type A and B TAD patients. This pilot study, limited to 18 TAD patients, revealed a heightened systemic OSS, determined at 15.5 days (median) after the initial diagnosis, in those TAD patients without complications (malperfusion syndrome and aneurysm formation). Larger studies on biological fluids are needed to better characterize the oxidative stress and interpret its consequence in TAD disease.

Prognostic role of plasma vitamin D and its association with disease characteristics in germ cell tumours.

Testicular cancer is the most common malignancy among young men. Vitamin D has pluripotent effects on cancer pathogenesis and plays a role in the metastatic cascade. The aim of this study is to analyze plasma vitamin D in association with clinico-pathological findings and prognosis in patients with germ-cell tumors (GCTs). This study included 120 newly diagnosed and/or relapsed GCT patients treated from April 2013 to July 2020, for whom plasma was available in the biobank. Blood samples were drawn the 1st chemotherapy cycle as well as before the 2nd cycle. Plasma vitamin D was measured using ELISA and correlated with disease characteristics and the outcome. For survival analysis, the cohort was dichotomized into "low" and "high" based on median vitamin D. There was no significant difference in vitamin D plasma levels between healthy donors and GCT patients (p = 0.71). Vitamin D level was not associated with disease characteristics except for brain metastases, where patients with brain metastases had a vitamin D level that was 32% lower compared to patients without brain metastases, p = 0.03. Vitamin D was also associated with response to chemotherapy, with an approximately 32% lower value in patients with an unfavorable response compared to a favorable response, p = 0.02. Moreover, low plasma levels of vitamin D were significantly associated with disease recurrence and inferior progression-free survival (PFS), but not with overall survival (OS) (HR = 3.02, 95% CI 1.36-6.71, p = 0.01 for PFS and HR = 2.06, 95% CI 0.84-5.06, p = 0.14 for OS, respectively). Our study suggests the prognostic value of pretreatment vitamin D concentrations in GCT patients. Low plasma vitamin D was associated with an unfavorable response to therapy and disease recurrence. However, it remains to be determined whether the biology of the disease confirms a causative role for low vitamin D and whether its supplementation affects the outcome.

100 YEARS OF VITAMIN D: Supraphysiological doses of vitamin D changes brainwave activity patterns in rats.

Low plasma levels of vitamin D causes bone mineral change that can precipitate osteopenia and osteoporosis and could aggravate autoimmune diseases, hypertension and diabetes. The demand for vitamin D supplementation becomes necessary; however, the consumption of vitamin D is not without risks, which its toxicity could have potentially serious consequences related to hypervitaminosis D, such as hypercalcemia and cerebral alterations. Thus, the present study describes the electroencephalographic changes caused by supraphysiological doses of vitamin D in the brain electrical dynamics and the electrocardiographic changes. After 4 days of treatment with vitamin D at a dose of 25,000 IU/kg, the serum calcium levels found were increased in comparison with the control group. The electrocorticogram analysis found a reduction in wave activity in the delta, theta, alpha and beta frequency bands. For ECG was observed changes with shortened QT follow-up, which could be related to serum calcium concentration. This study presented important evidence about the cerebral and cardiac alterations caused by high doses of vitamin D, indicating valuable parameters in the screening and decision-making process for diagnosing patients with symptoms suggestive of intoxication.

Clinical and Molecular Characteristics Associated with Vitamin C Deficiency in Myeloid Malignancies; Real World Data from a Prospective Cohort

Background:Vitamin C is an essential water-soluble vitamin required for many redox reactions in our body and its deficiency causes scurvy, a well characterized disease with multiple hematological manifestations. Studies dating back to 1950's demonstrated that patients with myeloid neoplasms tend to have lower plasma levels of vitamin C than healthy controls. Recent studies have shown that as much as 80% of patients with hematological malignancies in a cohort from Denmark had low vitamin C levels. Myeloid neoplasms tend to harbor mutations in epigenetic regulators which play a role in DNA methylation. One such mutation commonly seen in myeloid neoplasms and clonal hematopoiesis of indeterminate potential (CHIP) is TET2 for which vitamin C serves as a cofactor. There is a scarcity of clinical data on patients with low vitamin C level in myeloid neoplasms. Our study investigated the rates of vitamin C deficiency and the disease clinical and genomic characteristics associated with it at our center.Methods:We retrospectively collected data from a prospectively maintained list of patients treated for myeloid neoplasms at a large tertiary cancer center on whom vitamin C levels where serially collected during the study period. We obtained multiple baseline characteristics at the time of diagnosis including cytogenetic and molecular mutational data. Baseline characteristics were defined using descriptive statistics. Categorical variables were compared using a Fisher's exact test and continuous variables were analyzed using Mann Whitney U test for statistical significance. Institutional review board approval was obtained for the study. Statistical analysis was done using R Studio version 1.4.1717.Results:A total of 50 patients with myeloid neoplasms were identified with vitamin C levels available at least once during the study period. Nine (18%) patients had a low vitamin C level (LOW) defined as less than 0.4 mg/dl as per the Mayo lab testing with a reference range between 0.4 to 2.0 mg/dl. Baseline characteristics of patients with low vitamin C level and patients with normal vitamin C level (NORMAL) are shown in Table 1. The median vitamin C level in the LOW group was 0.2 mg/dl and NORMAL group was 1 mg/dl (p <0.001). The median age at diagnosis for patients in the LOW cohort was 64 years compared to 72 years for patients with normal vitamin C level (p = 0.015). Twenty-two (53.6%) of patients were female in the NORMAL cohort while six patients (66.7%) were females in the LOW cohort (p=NS). In the vitamin C LOW group only 55% of the patients were white compared to 83% in the NORMAL group (p = 0.093). The majority of patients in the Vit C LOW group had acute myeloid leukemia (AML) 44.5%, compared to 9.8% in the group with normal vitamin C levels (p = 0.03). Median white blood cell count, platelet counts, peripheral blast count and bone marrow blast count were not statistically significant amongst the 2 groups. Majority of patients in both groups 56.1% (NORMAL) vs 77.8% (LOW) had normal cytogenetics at the time of diagnosis (p = 0.284). There was a higher tendency to harbor ASXL1 and IDH2 mutation in the cohort with LOW levels 44.5% (p = 0.09) and 22.2% (p value = 0.143) compared to 17% and 4.8% respectively in the NORMAL cohort.Conclusions:Our analysis of the baseline characteristics of patients with myeloid neoplasms with vitamin C levels reveals interesting findings including a lower age at diagnosis for patients with low vitamin C levels and higher proportion of patients with acute myeloid leukemia compared to the cohort with normal levels. We also noted a higher tendency for occurrence of certain molecular mutations including ASXL1 and IDH2 among the patients with low vitamin C level. With recent papers implicating the role of ASXL1 in leukaemogenesis these findings suggest the hypothesis that vitamin C deficiency could accelerate clonal evolution with a higher tendency to transform into acute leukemia at a lower age. Further multi-institutional studies are needed to understand the relevance of low vitamin C level in myeloid neoplasms and the role of therapeutic vitamin C supplementation to retard leukaemogenesis. [Display omitted] DisclosuresPatel: Celgene-BMS: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; PVI: Honoraria. Awan: Cardinal Health: Consultancy; Abbvie: Consultancy; Merck: Consultancy; Beigene: Consultancy; Johnson and Johnson: Consultancy; Astrazeneca: Consultancy; BMS: Consultancy; Janssen: Consultancy; Genentech: Consultancy; Dava Oncology: Consultancy; Verastem: Consultancy; ADCT therapeutics: Consultancy; Incyte: Consultancy; MEI Pharma: Consultancy; Karyopharm: Consultancy; Kite pharma: Consultancy; Celgene: Consultancy; Gilead sciences: Consultancy; Pharmacyclics: Consultancy. Anderson: Celgene, BMS, Janssen, GSK, Karyopharm, Oncopeptides, Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Madanat: Blue Print Pharmaceutical: Honoraria; Stem line pharmaceutical: Honoraria; Onc Live: Honoraria; Geron Pharmaceutical: Consultancy.

Histone deacetylase inhibitors regulate vitamin C transporter functional expression in intestinal epithelial cells

Intestinal absorption of vitamin C in humans is mediated via the sodium-dependent vitamin C transporters (hSVCT1 and hSVCT2). hSVCT1 and hSVCT2 are localized at the apical and basolateral membranes, respectively, of polarized intestinal epithelia. Studies have identified low plasma levels of vitamin C and decreased expression of hSVCT1 in patients with several inflammatory conditions including inflammatory bowel disease (IBD). Investigating the underlying mechanisms responsible for regulating hSVCT1 expression are critical for understanding vitamin C homeostasis, particularly in conditions where suboptimal vitamin C levels detrimentally affect human health. Previous research has shown that hSVCT1 expression is regulated at the transcriptional level, however, little is known about epigenetic regulatory pathways that modulate hSVCT1 expression in the intestine. In this study, we found that hSVCT1 expression and function were significantly decreased in intestinal epithelial cells by the histone deacetylase inhibitors (HDACi), valproic acid (VPA), and sodium butyrate (NaB). Further, expression of transcription factor HNF1α, which is critical for SLC23A1 promoter activity, was significantly down regulated in VPA-treated cells. Chromatin immunoprecipitation (ChIP) assays showed significantly increased enrichment of tetra-acetylated histone H3 and H4 within the SLC23A1 promoter following VPA treatment. In addition, knockdown of HDAC isoforms two, and three significantly decreased hSVCT1 functional expression. Following VPA administration to mice, functional expression of SVCT1 in the jejunum was significantly decreased. Collectively, these in vitro and in vivo studies demonstrate epigenetic regulation of SVCT1 expression in intestinal epithelia partly mediated through HDAC isoforms two and three.

Investigating the Risk of Equine Motor Neuron Disease in a Brazilian Stable and Successful Intervention

We carried out an investigation to identify the factors that predispose to the risk of equine motor neuron disease (EMND) and evaluated the long-term impact of an intervention. Data on several biomarkers, including antioxidants (α-tocopherols, β-carotenes, glutathione peroxidase (GSHPx)), and superoxide dismutase (SOD1), neurofilaments, and other putative risk factors hypothesized to associate with the likelihood of EMND were collected. The data were analyzed for their significance of association with the condition. The EMND outbreak started in 1991 and continued until 1998. A total of 69 EMND cases and 64 control horses met the inclusion criteria and were enrolled in the study. Most cases (74%) occurred in 1996 and 1997. Horses afflicted with EMND had significantly lower plasma levels of vitamin E than control horses (0.381 vs. 1.148 μg/mL). There were no significant differences in the levels of vitamin A, β-carotenes, GSHPx, or the activities of SOD1 between EMND cases and control horses. Horses afflicted with EMND had significantly higher serum levels of phosphorylated neurofilament heavy than controls (2.85 vs. 0.27 ng/mL). The probability of EMND diagnosis increased above 50% when the serum levels of phosphorylated neurofilament heavy increased beyond 2.54 ng/mL. Mixed and Brazilian breeds had a significantly higher risk of EMND in comparison to Standardbred horse among the study population. In 1997, there was a change in the diet where better quality green hay was used. The incidence of EMND dropped to 0 in 1 year after intervention and remained at that level for the past 20 years.

Vitamin D Supplementation is a Promising Therapy for Pancreatic Ductal Adenocarcinoma in Conjunction with Current Chemoradiation Therapy.

The cancer-associated fibroblasts (CAFs) in pancreatic ductal adenocarcinoma (PDAC) are well known to play a dominant role in distant metastasis. Nevertheless, the effect on CAFs with current chemoradiation therapies remains uncertain. This study aimed to reveal the role of CAFs under current chemoradiation therapy (CRT) and investigate the factors regulating CAFs. α-SMA-positive cells in 86 resected PDAC specimens with/without preoperative CRT were evaluated by immunohistochemistry. Various factors, including the plasma levels of vitamin D, were investigated for association with the number of CAFs or distant metastasis-free survival (DMFS). Human pancreatic satellite cells (hPSCs) extracted from clinical specimens were used to validate the factors. All PDAC samples contained CAFs but the number varied widely. Multivariate analysis for DMFS indicated a larger number of CAFs was a significant risk factor. Univariate analysis for the number of CAFs identified two clinical factors: preoperative CRT and lower plasma levels of vitamin D. In subgroup analysis, the higher plasma level of vitamin D was a dominant factor for longer DMFS in PDAC patients after preoperative CRT. These results were validated by using extracted hPSCs. Irradiation activated stromal cells into CAFs facilitating malignant characteristics of PDAC and the change was inhibited by vitamin D supplementation in vitro. In conjunction with established current therapies, vitamin D supplementation may be an effective treatment for PDAC patients by inactivating CAFs.

Vitamin C supplementation in the critically ill: A systematic review and meta-analysis.

Background:Low plasma levels of vitamin C are associated with adverse outcomes, including increased mortality, in critically ill patients. Several trials have suggested that the administration of intravenous vitamin C in this setting may have beneficial effects, such as reducing the incidence of organ failure and improving survival. However, these studies have generally involved combination therapies consisting of vitamin C along with other antioxidants, confounding the effects of vitamin C alone. The primary objective of this meta-analysis is to investigate the effects of isolated intravenous supplementation of vitamin C in adults with critical illness.Methods:A database search was conducted for studies on the use of intravenous vitamin C in adult patients with critical illness. The primary outcome assessed was mortality at the longest follow-up time available. Secondary outcomes were the duration of mechanical ventilation, duration of vasopressor support, fluid requirements, and urine output in the first 24 h of intensive care unit admission.Results:Five studies (four randomized controlled trials and one retrospective review) enrolling a total of 142 patients were included in this meta-analysis. Compared with controls, the administration of intravenous vitamin C was associated with a decreased need for vasopressor support (standardized mean difference −0.71; 95% confidence interval (−1.16 to −0.26); p = 0.002) and decreased duration of mechanical ventilation (standardized mean difference −0.5; 95% confidence interval (−0.93 to −0.06); p = 0.03), but no difference was found in mortality (odds ratio 0.76; 95% confidence interval (0.27 to 2.16); p = 0.6). Trends were also noted toward decreased fluid requirements and increased urine output. No adverse effects were reported.Conclusion:The administration of intravenous vitamin C may lead to vasopressor sparing effects and a reduced need for mechanical ventilation in the critically ill, without affecting overall mortality. However, these results should be interpreted in light of the limitations of the primary literature and should serve as a preview of upcoming trials in this area.

Dietary patterns, plasma vitamins and Trans fatty acids are associated with peripheral artery disease

BackgroundTo investigate the association between dietary patterns (DP), plasma vitamins and trans fatty acids (TFAs) with the likelihood of peripheral artery disease (PAD).MethodsNational Health and Nutrition Examination Survey (NHANES) data for the years 1999–2002 were used. PAD was diagnosed by ankle brachial index assessment. Plasma concentrations of vitamins were measured using high performance liquid chromatography. Vitamin D levels were measured by radioimmunoassay. Analysis of covariance, principal components analysis (PCA) and adjusted logistic regression were applied, accounting for the survey design and sample weights.ResultsOf the 4864 eligible participants, 2482 (51.0%) were men and 269 (5.5%) had prevalent PAD. PCA uncovered three DPs which accounted for 56.8% of the variance in dietary nutrients consumption including DP1 (fatty acids and cholesterol), DP2 (minerals, vitamins and fiber), and DP3 (polyunsaturated fatty acids [PUFA]). PAD patients had a significantly higher serum concentrations of trans 9-octadecenoic acid and trans 9, trans 12-octadienoic acid as well as lower plasma levels of vitamin D, retinol, retinyl stearate and retinyl palmitate (p < 0.001 for all comparisons). In models adjusted for age, race, diabetes, cholesterol, hypertension, smoking and energy intake, individuals in the highest quartile of the DP1 had higher odds for PAD compared with those in the lowest quartile [(odds ratio (OR): 6.43, 95% confidence interval (CI): 2.00–20.63 p < 0.001], while those in the highest quartile of DP2 and DP3 had lower odds of PAD relative to those in the lowest quartile (OR:0.28, OR:0.44, respectively; p < 0.001 for both comparisons).ConclusionWe found that quality of diet, plasma vitamins and TFAs are associated with the likelihood of PAD. If confirmed in prospective studies, the possibility that dietary factors, plasma vitamins and TFAs might be valuable for preventing or delaying the clinical progression of PAD, should be investigated in intervention trials.

Abstract P520: Low Plasma Levels of Vitamin D are Not Associated With Carotid Artery Stiffness in Hypertension

Objectives: Recent studies suggest an association between vitamin D deficiency and prevalence of cardiovascular disease in the general population. However, the evidence of a relationship between vitamin D status and vascular functional changes in hypertension is currently controversial. We aimed to investigate if the presence of low serum vitamin D levels is associated with an increased arterial stiffness in essential hypertension. Design and Method: In 151 essential hypertensive patients (53±13 y, 71 males) we measured serum 25(OH)-vitamin D levels and performed a carotid ultrasound examination to determine variables of carotid stiffness, such as distensibility, compliance, Young elastic modulus and beta-stiffness. Furthermore, in a subgroup of 86 subjects we evaluated the augmentation index and the pulse wave velocity. The patients were subdivided into two groups according to the 25(OH)-vitamin D levels, lower or higher than 30 nmol/L. Results: A plasma vitamin D level lower than 30 nmol/L was found in 83 (55%) of 151 patients. Patients with low vitamin D levels were significantly older than those with a normal value of serum vitamin D. No significant differences in carotid artery distensibility, compliance, Young elastic modulus, and beta-stiffness were observed between patients with plasma vitamin D below or above 30 nmol/L. Also, the augmentation index and the pulse wave velocity were comparable in hypertensive patients with lower or higher plasma vitamin D levels. Conclusions: This study does not support the hypothesis of an association between vitamin D deficiency and functional vascular changes in hypertensive patients.

The Molecular Mechanisms of Vitamin A Deficiency in Multiple Sclerosis.

Vitamin A, considered to be an essential nutrient, has important actions in immunological responses and the central nervous system (CNS). Neuroimmunological functions of vitamin A are mediated through its active metabolite, retinoic acid (RA). In the CNS, RA contributes to regeneration and plasticity, while also playing a key role in enhancing tolerance and reducing inflammatory responses by regulating T cell, B cell and dendritic cell populations. However, evidence has indicated lower plasma levels of vitamin A in patients with multiple sclerosis (MS). Vitamin A deficiency leads to dysregulation of immune tolerance and pathogenic immune cell production in this disease. Vitamin A may ameliorate MS pathogenesis through numerous mechanisms including a reduction in inflammatory processes by re-establishing the balance between pathogenic (Th1, Th17, Th9) and immunoprotective cells (Th2, Tregs), modulating B cell and dendritic cell function as well as increasing tolerance of autoimmunity and regeneration in the CNS. Thus, the results from the current review suggest that vitamin A can be considered as a potential treatment in MS disease management.

Lower Plasma Levels of Antioxidant Vitamins in Patients with Metabolic Syndrome: A Case Control Study.

Metabolic syndrome (MS) is a coexistence of metabolic risk factors affecting the development of cardiovascular diseases. Reactive oxygen species, which are excessively produced in MS, participate in its pathogenesis. Vitamins A, C and E are an important part of the non-enzymatic antioxidative barrier in humans. The aim of the study was to estimate plasma vitamin A, C and E levels and the intake of these vitamins from the diet in patients with MS. The study included 182 patients with MS, 94 men and 88 women, aged 30-65 years (mean 57.31 ± 8.28 years). The control group was comprised of 91 subjects, 56 men and 35 women, aged 41-65 years (mean 57.75 ± 5.84 years). The MS diagnosis was based on IDF criteria. The determination of the serum level of vitamin A, C and E was performed using the spectrophotometric method. The food intake was assessed by 24-h dietary recall. The mean plasma vitamin A, C and E levels were significantly lower in MS patients than in the controls (p = 0.05). No correlation was found between vitamin A, C and E intake from the diet and their plasma concentrations in MS patients. Plasma vitamin A, C and E deficiency was observed significantly more often in MS patients than in the control group (15.38% vs. 2.19%, 79.12% vs. 8.79% and 60.45% vs. 5.49%, p < 0.0001, respectively). BMI was the one factor significantly affecting the mean value of vitamin A, C and E levels in MS patients. MS patients demonstrated significantly lower plasma levels of vitamin A, C and E compared to the healthy subjects. Lower plasma levels of antioxidant vitamins with their high intake from the diet indicate antioxidant barrier impairment in MS patients.

New Reference Values for Vitamin C Intake

The German, Austrian, and Swiss nutrition societies are the editors of the ‘reference values for nutrient intake'. They have revised the reference values for the intake of vitamin C and published them in February 2015. The average vitamin C requirement in healthy adults is considered to be the vitamin C amount that compensates for the metabolic losses of vitamin C, and ensures a fasting ascorbate plasma level of 50 µmol/l. Based on the present data from studies with non-smoking men, metabolic losses of 50 mg/day are assumed, as well as an absorption rate of 80% and an urinary excretion of 25% of the vitamin C intake. Taking this into account, the calculated average requirement in men is 91 mg/day. Considering a coefficient of variation of 10%, a reference value (recommended intake) of 110 mg/day for men is derived. The vitamin C requirement in women as well as in children and adolescents is extrapolated from the requirement in men and in relation to their body weight. This results in a recommended intake of about 95 mg/day for adult women. Because the requirement in pregnant and lactating women is increased, higher recommended intakes are derived for them, 105 mg/day for pregnant women from the fourth month on and 125 mg/day for lactating women, respectively. For boys and girls at the age of 1 to under 15 years, there are increasing recommended intake values from 20 to 85 mg/day. For male and female adolescents, at the age of 15 to under 19 years, the recommended intake is 105 and 90 mg, respectively. As smokers have higher metabolic losses and lower plasma levels of vitamin C than non-smokers (turnover is 40% higher), the reference value for vitamin C intake is set to 135 mg/day for female smokers and 155 mg/day for male smokers. For infants in their first year of life, the reference value (estimated value) is set to 20 mg vitamin C/ day, based upon the lowest observed vitamin C intake for infants in the United Kingdom and the United States, that obviously meets the requirement in infants and that is 3 times higher than the amount necessary to prevent scurvy (7 mg/day).

The Janus-faced manifestations of homozygous familial hypobetalipoproteinemia due to apolipoprotein B truncations

Familial hypobetalipoproteinemia is a codominant disorder characterized by low plasma levels of low-density lipoprotein cholesterol and apolipoprotein B (apoB), which in ∼50% of the cases is due to mutations in APOB gene. In most cases, these mutations cause the formation of truncated apoBs of various sizes, which have a reduced capacity to bind lipids and form lipoprotein particles. Here, we describe 2 children with severe hypobetalipoproteinemia found to be homozygous for novel APOB gene mutations. The first case (HBL-201) was an asymptomatic 13-year-old boy incidentally found to have slightly elevated serum transaminases associated with hepatic steatosis. He was homozygous for a truncated apoB (2211 amino acids, apoB-48.74) whose size is similar to that of wild-type apoB-48 (2152 amino acids) produced by the intestine. ApoB-48.74 is expected to be incorporated into chylomicrons in the intestine but might have a reduced capacity to form secretion-competent very low–density lipoprotein in the liver. The second patient (HBL-96) was a 6-month-old girl suspected to have abetalipoproteinemia, for the presence of chronic diarrhea, failure to thrive, extremely severe hypobetalipoproteinemia, and low plasma levels of vitamin E and vitamin A. She was homozygous for a nonsense mutation (Gln513*) resulting in a short truncated apoB (apoB-11.30), which is not secreted into the plasma. In this patient, the impaired chylomicron formation is responsible for the severe clinical manifestations and growth retardation. In homozygous familial hypobetalipoproteinemia, the capacity of truncated apoBs to form chylomicrons is the major factor, which affects the severity of the clinical manifestations.

Association of increased carotid intima-media thickness and lower plasma levels of vitamin C and vitamin E in old age subjects: implications for Alzheimer's disease.

In light of the recent advances regarding the role of vascularity in Alzheimer's disease (AD) pathophysiology, the relationship between plasma levels and activities of the major antioxidant molecules and the carotid intima-media thickness (C-IMT) of older persons with no or very mild cognitive impairment was evaluated. The underlying hypothesis is that the IMT may be an indirect index of vascular damage in persons with low levels of plasma antioxidants. Plasma levels of vitamins A, C, E, of uric acid as well as activities of the plasma antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured. Plasma levels of vitamins C and E significantly decreased among participants from the first to the fourth IMT quartile, with a linear slope only for vitamin C. Compared to participants in the lowest vitamin C quartile, the probability to have IMT >1.2 mm significantly decreased among persons from the second to the fourth quartile independent of confounders. In conclusion, only vitamin C plasma levels appear to be selectively associated with the risk of increasing C-IMT. An adequate vitamin C status might be particularly important for protection against AD and other clinical manifestations of vascular and cognitive ageing.

Oxidative Stress in Children on Peritoneal Dialysis

Enhanced oxidative stress has been observed in dialysis and predialysis adult patients with chronic kidney disease (CKD), which resulted in increased mortality and morbidity within this population. Not much attention in the literature has been paid to nonenzymatic antioxidant defense in children with CKD on peritoneal dialysis (PD). The aim of the present study was to describe the plasma, erythrocyte, and dialysate concentrations of oxidized (GSSG) and reduced glutathione (GSH) and vitamins A, E, and C in a pediatric PD population. 10 children on PD and 27 age-matched healthy subjects were enrolled in the study. Erythrocyte and plasma GSH concentrations were lower in PD patients, erythrocyte concentration of GSSG remained unchanged, and plasma GSSG was significantly higher in children on PD. Children on PD exhibited decreased plasma concentrations of antioxidant vitamins compared to healthy subjects. Moreover, we documented loss of vitamins A, E, and C into ultrafiltrate. Such low plasma levels of vitamins A, E, and C and simultaneously decreased activity of erythrocyte GSH may be responsible for the increased oxidative stress occurring in children with CKD on PD.

Nutrition assessment in children with short bowel syndrome weaned off parenteral nutrition: a long-term follow-up study

Purpose The purpose of the study was to assess long-term growth and nutrition status of children with neonatal short bowel syndrome (SBS) after weaning off parenteral nutrition (PN). Methods Eight children with neonatal SBS weaned from PN therapy for more than 2 years were studied. Medical records were reviewed; anthropometric measurements and blood test (hemoglobin, albumin and prealbumin, immunoglobulin, electrolytes, trace elements, and fat-soluble vitamins) were assayed during follow-up. Results Anthropometric measurements, weight for age, and height for age were normal in all children; one child was found to be overweight according to weight for height z score. No children were found to have anemia, although one presented with macrocytosis and another had microcytosis. Low serum concentrations of zinc in 3 cases and iron in 1 case were detected. Immunoglobulin levels of all children were within the reference value. Low plasma levels of vitamin A in 2 cases, vitamin E in 4 cases, and β-carotene in 2 cases were found; one of them had obviously low levels of the 3 fat-soluble vitamins. Conclusion Children with SBS are still at risk for different nutrient malabsorption even after weaning off PN for a long time. Therefore, they need long-term, regular monitoring and intensive nutritional care to prevent various nutrient deficiencies.

Low vitamin K status is associated with osteoarthritis in the hand and knee

Poor intake of vitamin K is common. Insufficient vitamin K can result in abnormal cartilage and bone mineralization. Furthermore, osteophyte growth, seen in osteoarthritis (OA), may be a vitamin K-dependent process. We undertook this study to determine whether vitamin K deficiency is associated with radiographic features of OA. We conducted an analysis among 672 participants (mean age 65.6 years, 358 women) in the Framingham Offspring Study, a population-based prospective observational cohort. Levels of plasma phylloquinone (the primary form of vitamin K) had previously been measured in these participants, for whom we also had bilateral hand and knee radiographs. The main outcomes were 1) prevalence ratios (PRs) of OA, osteophytes, and joint space narrowing (JSN) per quartile of plasma phylloquinone level for each joint, adjusting for correlated joints using generalized estimating equations, and 2) adjusted mean number of joints with each feature per quartile of plasma phylloquinone level. Analyses were conducted in hands and knees separately and adjusted for age, sex, body mass index, total energy intake, plasma vitamin D, and femoral neck bone mineral density. The PRs for OA, osteophytes, and JSN and adjusted mean number of joints with all 3 features in the hand decreased significantly with increasing plasma phylloquinone levels (P<or=0.03 for all). For example, as plasma phylloquinone levels rose, the PR for hand OA decreased from 1.0 to 0.7 (P=0.005). For the knee, only the PR for osteophytes and the adjusted mean number of knee joints with osteophytes decreased significantly with increasing plasma phylloquinone levels (PR decreased from 1.0 to 0.6, P=0.01). These observational data support the hypothesis of an association between low plasma levels of vitamin K and increased prevalence of OA manifestations in the hand and knee.

Lower Plasma Vitamin E Levels Are Associated With the Frailty Syndrome: The InCHIANTI Study

The primary biologic mechanism that causes frailty in older persons has never been adequately explained. According to recent views, oxidative stress may be the driving force of this condition. We tested the hypothesis that, independent of confounders, low plasma levels of vitamin E (alpha-tocopherol), the main fat-soluble human antioxidant, are associated with the frailty syndrome in older persons free from dementia and disability. The study sample included 827 older (> or =65 years) persons (women, 54%) who participated in a population-based epidemiological study. Frail participants were identified based on the presence of at least three of five of the following features: self-reported weight loss, low energy, slow gait speed, low grip strength, and low physical activity. Participants with none of these features were considered nonfrail, while participants with one or two were considered intermediate frail. Plasma vitamin E levels were determined using reverse-phase high-performance liquid chromatography. Measured confounders included lower extremity muscle strength, cognitive function, diseases, and factors related to vitamin E metabolism. Age- and gender-adjusted levels of vitamin E decreased gradually from the nonfrail to the frail group (p for trend =.015). In the logistic model adjusted for multiple potential confounders, participants in the highest vitamin E tertile were less likely to be frail than were participants in the lowest vitamin E tertile (odds ratio, 0.30; 95% confidence interval, 0.10-0.91). Our findings show an association between low circulating levels of one of the most important components of the human antioxidant system and the presence of frailty.