High prevalence of severe vitamin D deficiency in combined antiretroviral therapy-naive and successfully treated Swiss HIV patients

To evaluate the prevalence of 25-hydroxyvitamin D [25(OH)D] deficiency in HIV-positive patients, a population at risk for osteoporosis.

Functional and physiological role of vitamin C transporters

Vitamin C (ascorbic acid) is required for the synthesis of collagen, carnitine, catecholamine and the neurotransmitter norepinephrine. Vitamin C also plays an important role in protection against oxidative stress. Transporters for vitamin C and its oxidized form dehydroascorbate (DHA) are crucial to keep vitamin concentrations optimal in the body. The human SLC23 family consists of the Na(+)-dependent vitamin C transporters SVCT1 (SLC23A1) and SVCT2 (SLC23A2) and the orphan transporter SVCT3 (SLC23A3). Phylogenetically, the SLC23 family belongs to the nucleobase-ascorbate transporter family although no specificity for nucleobases has yet been demonstrated for the human members of this family. In fact, the SVCT1 and SVCT2 transporters are rather specific for ascorbic acid. SVCT1 is expressed in epithelial tissues such as intestine, where it contributes to the maintenance of whole-body ascorbic acid levels, whereas the expression of SVCT2 is relatively widespread either to protect metabolically active cells and specialized tissues from oxidative stress or to deliver ascorbic acid to tissues that are in high demand of the vitamin for enzymatic reactions. DHA, the oxidized form of ascorbic acid is taken up and distributed in the body by facilitated transport via members of the SLC2/GLUT family (GLUT1, GLUT3, and GLUT4). Although, the main focus of this review is on the SLC23 family of ascorbic acid transporters, transporters of DHA and nucleobases are also briefly discussed for completeness.

Hemorrhage in vitamin K deficiency--a preventable entity

Der diaplazentare Transport von Vitamin K ist kaum messbar, die Muttermilch ist arm an Vitamin K und die intestinale Flora von Neugeborenen produziert praktisch kein Vitamin K. Deshalb weisen gesunde Neugeborene «physiologischerweise» tiefe Vitamin-K-Spiegel auf, was durch Verminderung der Vitamin-K-abhängigen Gerinnungsfaktoren zu schweren Mangelblutungen führen kann. Die klassische Form der Vitamin-K-Mangelblutung tritt mit einer Inzidenz von bis zu 1.5% bis zum 7. Lebenstag auf, die Spätform wird bis zur 12. Lebenswoche bei bis zu 10 von 100000 Neugeborenen festgestellt. Mit einer adäquaten Vitamin-K-Prophylaxe lassen sich Vitamin-K-Mangelblutungen grösstenteils verhindern. Die heute in der Schweiz empfohlene Prophylaxe von 3 oralen Dosen à 2 mg Konakion® MM in der 4. Lebensstunde, am 4. Lebenstag und in der 4. Lebenswoche ist bezüglich unerwünschter Nebenwirkung äusserst sicher, insbesondere besteht kein erhöhtes Krebsrisiko. Angesichts der dramatischen Folgen der häufig intrakraniell lokalisierten Vitamin-K-Mangelblutungen ist sowohl bei medizinischen Fachpersonen als auch bei den Eltern eine möglichst gute Compliance für diese einfache und sichere Prophylaxe wie auch eine entsprechende Aufklärung anzustreben.

Transport model of the human Na+-coupled L-ascorbic acid (vitamin C) transporter SVCT1

Vitamin C (L-ascorbic acid) is an essential micronutrient that serves as an antioxidant and as a cofactor in many enzymatic reactions. Intestinal absorption and renal reabsorption of the vitamin is mediated by the epithelial apical L-ascorbic acid cotransporter SVCT1 (SLC23A1). We explored the molecular mechanisms of SVCT1-mediated L-ascorbic acid transport using radiotracer and voltage-clamp techniques in RNA-injected Xenopus oocytes. L-ascorbic acid transport was saturable (K(0.5) approximately 70 microM), temperature dependent (Q(10) approximately 5), and energized by the Na(+) electrochemical potential gradient. We obtained a Na(+)-L-ascorbic acid coupling ratio of 2:1 from simultaneous measurement of currents and fluxes. L-ascorbic acid and Na(+) saturation kinetics as a function of cosubstrate concentrations revealed a simultaneous transport mechanism in which binding is ordered Na(+), L-ascorbic acid, Na(+). In the absence of L-ascorbic acid, SVCT1 mediated pre-steady-state currents that decayed with time constants 3-15 ms. Transients were described by single Boltzmann distributions. At 100 mM Na(+), maximal charge translocation (Q(max)) was approximately 25 nC, around a midpoint (V(0.5)) at -9 mV, and with apparent valence approximately -1. Q(max) was conserved upon progressive removal of Na(+), whereas V(0.5) shifted to more hyperpolarized potentials. Model simulation predicted that the pre-steady-state current predominantly results from an ion-well effect on binding of the first Na(+) partway within the membrane electric field. We present a transport model for SVCT1 that will provide a framework for investigating the impact of specific mutations and polymorphisms in SLC23A1 and help us better understand the contribution of SVCT1 to vitamin C metabolism in health and disease.

Effects of mild vitamin a deficiency on lung maturation in newborn rats: a morphometric and morphologic study

OBJECTIVE To evaluate the effects of a 60% vitamin A deficiency (VAD) on the two postnatal stages of lung development: alveolarization and microvascular maturation. Lungs from deficient rats were compared to age-matched controls. STUDY DESIGN Starting at 3 weeks before mating, female rats were maintained under a diet lacking vitamin A. Due to the slow depletion of the vitamin A liver stores the pregnant rats carried to term and delivered pups under mild VAD conditions. Mothers and offspring were then kept under the same diet what resulted in a mean reduction of vitamin A plasma concentration of about 60% vs. controls during the whole experimental period. Pups were sacrificed on days 4, 10 and 21 and their lungs fixed and analyzed by means of a combined morphologic and morphometric investigation at light and electron microscopic levels. RESULTS During the whole experiment, body weights of VAD animals were lower than controls with a significant decrease on day 10. On days 4, 10 and 21 the pulmonary structure was in a comparable gross morphologic state in both groups. Despite this morphologic normality, quantitative alterations in some functional parameters could be detected. On day 4, lung volume and the volume and surface area of air spaces were decreased, while the arithmetic mean barrier thickness and type 2 pneumocyte volume were increased in the VAD group. On day 21, some changes were again manifest mainly consisting in an augmentation of the vascularization and a decrease in interstitial volume in deficient animals. CONCLUSIONS Mild VAD causes no gross disturbances in the postnatal phases of lung development in rats. However, a body weight-related transient retardation of lung maturation was detectable in the first postnatal week. At 3 weeks, the VAD lungs showed a more mature vascular system substantiated by an increase in volume of both capillary volume and the large non-parenchymal vessels. In view of these quantitative alterations, we suspect that mild VAD deregulates the normal phases of body and lung growth, but does not induce serious functional impairments.

Expression, purification and low-resolution structure of human vitamin C transporter SVCT1 (SLC23A1)

Expression and purification of human membrane proteins for structural studies represent a great challenge. This is because micro- to milligram amounts of pure isolated protein are required. To this aim, we successfully expressed the human vitamin C transporter-1 (hSVCT1; SLC23A1) in Xenopus laevis oocytes and isolated highly pure protein in microgram amounts. Recombinant hSVCT1 was functional when expressed in oocytes and glycosylated. Structural analysis of purified hSVCT1 by transmission electron microscopy and single particle analysis unveiled its shape, dimensions and low-resolution structure as well as the existence of a major monomeric and minor dimeric population. Chemical crosslinking of isolated oocyte membranes containing expressed hSVCT1 indicated similar oligomeric states of hSVCT1 in lipid bilayers. This work reports the first purification and structural analysis of a human SVCT protein and opens the way for future functional and structural studies using purified hSVCT1.

2D and 3D crystallization of a bacterial homologue of human vitamin C membrane transport proteins

Most organisms are able to synthesize vitamin C whereas humans are not. In order to contribute to the elucidation of the molecular working mechanism of vitamin C transport through biological membranes, we cloned, overexpressed, purified, functionally characterized, and 2D- and 3D-crystallized a bacterial protein (UraDp) with 29% of amino acid sequence identity to the human sodium-dependent vitamin C transporter 1 (SVCT1). Ligand-binding experiments by scintillation proximity assay revealed that uracil is a substrate preferably bound to UraDp. For structural analysis, we report on the production of tubular 2D crystals and present a first projection structure of UraDp from negatively stained tubes. On the other hand the successful growth of UraDp 3D crystals and their crystallographic analysis is described. These 3D crystals, which diffract X-rays to 4.2Å resolution, pave the way towards the high-resolution crystal structure of a bacterial homologue with high amino acid sequence identity to human SVCT1.

Konsum und Kontrolle : wie Vitamin C zu einem Allheilmittel werden konnte

Künstliches Vitamin C ist heute ein Massenprodukt. Dass sich Ascorbinsäure seit ihrer Erfindung 1933 zu einem alltäglichen Konsumgut mausern konnte, ist weniger durch ihr medizinisches Potential zu erklären, sondern verdankt sich vielmehr einem dynamischen Zusammenspiel von Produktion, Vermarktung und Gesundheitspolitik. Der Beitrag fokussiert insbesondere auf die komplexen Interaktionen zwischen Gesundheitskonzepten, diagnostischen Instrumenten und ärztlichem Blick. Dabei scheinen nicht nur die Differenzen zwischen „rein naturwissenschaftlichen“ und „ärztlich-biologischen“ Standpunkten auf, sondern es zeigt sich auch, dass Nahrungsbestandteile immer auch gesundheitspolitisch und ethisch aufgeladen sind.

Vitamin D Deficiency and Depressive Symptomatology in Psychiatric Patients Hospitalized with a Current Depressive Episode: A Factor Analytic Study.

BACKGROUND Low vitamin D levels have been associated with depressive symptoms in population-based studies and non-clinical samples as well as with clinical depression. This study aimed to examine the association of vitamin D levels with the severity and dimensions of depressive symptoms in hospitalized patients with a current episode of depression taking into account confounding variables. METHODS We investigated 380 patients (mean age 47 ± 12 years, 70% women) who were consecutively hospitalized with a main diagnosis of an ICD-10 depressive episode. All patients self-rated depressive symptom severity with the Hospital Anxiety and Depression Scale (HADS-D), the Beck Depression Inventory-II (BDI-II), and the Brief Symptom Inventory. A principal component analysis was performed with all 34 items of these questionnaires and serum levels of 25-hydroxyvitamin D3 (25-OH D) were measured. RESULTS Vitamin D deficiency (< 50 nmol/l), insufficiency (50-75 nmol/l), and sufficiency (> 75 nmol/l) were present in 55.5%, 31.8% and 12.6%, respectively, of patients. Patients with vitamin D deficiency scored higher on the HADS-D scale and on an anhedonia symptom factor than those with insufficient (p-values ≤ 0.023) or sufficient (p-values ≤ 0.008) vitamin D. Vitamin D deficient patients also scored higher on the BDI-II scale than those with sufficient vitamin D (p = 0.007); BDI-II cognitive/affective symptoms, but not somatic/affective symptoms, were higher in patients with vitamin D deficiency (p = 0.005) and insufficiency (p = 0.041) relative to those with sufficient vitamin D. Effect sizes suggested clinically relevant findings. CONCLUSIONS Low vitamin D levels are frequent in hospitalized patients with a current episode of depression. Especially 25-OH D levels < 50 nmol/l were associated with cognitive/affective depressive symptoms, and anhedonia symptoms in particular.

Re-emerging Vitamin D deficiency epidemic and its implications on the public health in the US

Vitamin D is essential in maintaining the bone health and Calcium homeostasis in the body. These actions are mediated through the Vitamin D receptors (VDR) present in cells through which the activated vitamin D acts [1]. In the past, it was known that these receptors existed in the intestine and bone cell. However, recent discovery of VDR in other tissues as well, has broadened the action of Vitamin D and increased its adequate intake [1].^ In the past, Vitamin D deficiency was most common among institutionalized, elderly patients and children and thought to be extinct in the healthy population. However, recent evidence has shown that, prevalence of vitamin D deficiency is increasing into an epidemic status in the overall population of the United States, including the healthy individuals [2-3]. The increased daily-recommended requirement and other multiple factors are responsible for the re-emergence of this epidemic [4-5]. Some of these factors could be used to control the epidemic. Studies have also shown the association between vitamin D deficiency and increased risk for developing chronic diseases such as diabetes, hypertension, multiple sclerosis, arthritis, and some fatal cancers like prostate, colon and breast cancers [1, 4, 6-14]. This issue results in increased disease burden, morbidity and mortality in the community [15-20].^ Methods: The literature search was conducted using the University of Texas Health Science Center at Houston (UTHSC) and University of Texas Southwestern Medical Center (UTSW) online library. The key search terms used are “vitamin D deficiency And prevalence Or epidemiology”, “vitamin D deficiency And implication And public health” using PubMed and Mesh database and “vitamin D deficiency” using systematic reviews. The search is limited to Humans and the English language. The articles considered for the review are limited to Healthy US population to avoid health conditions that predispose the population to vitamin D deficiency. Only US population is considered to narrow down the study.^ Results: There is an increased prevalence of low levels of Vitamin D levels below the normal range in the US population regardless of age and health status. Vitamin D deficiency is also associated with increased risk of chronic illnesses and fatal cancers.^ Conclusion: This increased prevalence and the association of the deficiency with increased all-cause mortality has increased the economic burden and compromised the quality of life among the population. This necessitates the health care providers to routinely screen their patients for the Vitamin D status and counsel them to avoid the harmful effects of the Vitamin D deficiency. ^

Genetic evidence for the role of GDP-mannose in plant ascorbic acid (vitamin C) biosynthesis

Vitamin C (l-ascorbic acid; AsA) acts as a potent antioxidant and cellular reductant in plants and animals. AsA has long been known to have many critical physiological roles in plants, yet its biosynthesis is only currently being defined. A pathway for AsA biosynthesis that features GDP-mannose and l-galactose has recently been proposed for plants. We have isolated a collection of AsA-deficient mutants of Arabidopsis thaliana that are valuable tools for testing of an AsA biosynthetic pathway. The best-characterized of these mutants (vtc1) contains ≈25% of wild-type AsA and is defective in AsA biosynthesis. By using a combination of biochemical, molecular, and genetic techniques, we have demonstrated that the VTC1 locus encodes a GDP-mannose pyrophosphorylase (mannose-1-P guanyltransferase). This enzyme provides GDP-mannose, which is used for cell wall carbohydrate biosynthesis and protein glycosylation as well as for AsA biosynthesis. In addition to genetically defining the first locus involved in AsA biosynthesis, this work highlights the power of using traditional mutagenesis techniques coupled with the Arabidopsis Genome Initiative to rapidly clone physiologically important genes.

Evidence for a recommended dietary allowance for vitamin C from pharmacokinetics: A comment and analysis

The current recommended dietary allowance (RDA) for vitamin C, as proposed by the Food and Nutrition Board/National Research Council in 1980 and reconfirmed in 1989, is 60 mg daily for nonsmoking adult males. Levine et al. [Levine, M., Conry-Cantilena, C., Wang, Y., Welch, R. W., Washko, P. W., et al. (1996) Proc. Natl. Acad. Sci. USA 93, 3704–3709], based on a study of vitamin C pharmacokinetics in seven healthy men, have now proposed that the RDA should be increased to 200 mg daily. I have examined, in brief, the experimental and conceptual bases for this new recommendation and its implications for public health and nutrition policy and programs. Using, for illustrative purposes only, data extracted from each of two recent dietary surveys of noninstitutionalized adult males living in households in the Netherlands and the United States, it is predicted that the prevalence of intakes inadequate to meet the individual’s own requirement would be about 96% or 84%, respectively, if the criteria of adequacy used for derivation of the 200 mg RDA are accepted. Depending upon the particular average requirement value for ascorbic acid that might be derived from their data, the proposal by Levine et al. would mean a desirable increase in mean intakes in these two populations by as much about 2- to 3-fold. Hence, before an action of this kind is to be recommended, an answer must be sought to the question whether current experimental data including the criteria selected (saturation kinetics) are adequate to establish a new set of requirements for vitamin C, which then carry such profound policy implications. This will require critical assessment of all of the available evidence emerging from laboratory, clinical, and epidemiological studies to determine whether it provides a sufficient rationale for accepting criteria of vitamin C adequacy such as those proposed by Levine et al. and the requirement estimates so derived.

Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance.

Determinants of the recommended dietary allowance (RDA) for vitamin C include the relationship between vitamin C dose and steady-state plasma concentration, bioavailability, urinary excretion, cell concentration, and potential adverse effects. Because current data are inadequate, an in-hospital depletion-repletion study was conducted. Seven healthy volunteers were hospitalized for 4-6 months and consumed a diet containing <5 mg of vitamin C daily. Steady-state plasma and tissue concentrations were determined at seven daily doses of vitamin C from 30 to 2500 mg. Vitamin C steady-state plasma concentrations as a function of dose displayed sigmoid kinetics. The steep portion of the curve occurred between the 30- and 100-mg daily dose, the current RDA of 60 mg daily was on the lower third of the curve, the first dose beyond the sigmoid portion of the curve was 200 mg daily, and complete plasma saturation occurred at 1000 mg daily. Neutrophils, monocytes, and lymphocytes saturated at 100 mg daily and contained concentrations at least 14-fold higher than plasma. Bioavailability was complete for 200 mg of vitamin C as a single dose. No vitamin C was excreted in urine of six of seven volunteers until the 100-mg dose. At single doses of 500 mg and higher, bioavailability declined and the absorbed amount was excreted. Oxalate and urate excretion were elevated at 1000 mg of vitamin C daily compared to lower doses. Based on these data and Institute of Medicine criteria, the current RDA of 60 mg daily should be increased to 200 mg daily, which can be obtained from fruits and vegetables. Safe doses of vitamin C are less than 1000 mg daily, and vitamin C daily doses above 400 mg have no evident value.

Ascorbic acid; vitamin C in wound healing; Annotated bibliography.

Mode of access: Internet.