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PubMed2002

Flavonoid inhibition of sodium-dependent vitamin C transporter 1 (SVCT1) and glucose transporter isoform 2 (GLUT2), intestinal transporters for vitamin C and Glucose.

Vitamin C and flavonoids, polyphenols with uncertain function, are abundant in fruits and vegetables. We postulated that flavonoids have a novel regulatory action of delaying or inhibiting absorption of vitamin C and glucose, which are structurally similar. From six structural classes of flavonoids, at least 12 compounds were chosen for studies. We investigated the effects of selected flavonoids on the intestinal vitamin C transporter SVCT1(h) by transfecting and overexpressing SVCT1(h) in Chinese hamster ovary cells. Flavonoids reversibly inhibited vitamin C transport in transfected cells with IC(50) values of 10-50 microm, concentrations expected to have physiologic consequences. The most potent inhibitor class was flavonols, of which quercetin is most abundant in foods. Because Chinese hamster ovary cells have endogenous vitamin C transport, we expressed SVCT1(h) in Xenopus laevis oocytes to study the mechanism of transport inhibition. Quercetin was a reversible and non-competitive inhibitor of ascorbate transport; K(i) 17.8 microm. Quercetin was a potent non-competitive inhibitor of GLUT2 expressed in Xenopus oocytes; K(i) 22.8 microm. When diabetic rats were administered glucose with quercetin, hyperglycemia was significantly decreased compared with administration of glucose alone. Quercetin also significantly decreased ascorbate absorption in normal rats given ascorbate plus quercetin compared with rats given ascorbate alone. Quercetin was a specific transport inhibitor, because it did not inhibit intestinal sugar transporters GLUT5 and SGLT1 that were injected and expressed in Xenopus oocytes. Quercetin inhibited but was not transported by SVCT1(h). Considered together, these data show that flavonoids modulate vitamin C and glucose transport by their respective intestinal transporters and suggest a new function for flavonoids.

Animals↗
PubMedDate not supplied

Reduction in estimated vitamin A intake induced by new food composition tables in Japan, where vitamin A is taken mostly from plant foods.

A revised edition of the standard tables of food composition was implemented in Japan in 2005; one of the major revision points is the change of retinol activity equivalents for pro-vitamin A carotenoids. This preliminary analysis was conducted to examine whether the revision affects the estimation of vitamin A intake; and if so, to what extent. Accordingly, a field survey was conducted to collect 24-h duplicates of daily foods of citizens, and 26 adult women volunteered. Application of the procedures in the new and previous standard tables of food composition gave 537 microg retinol activity equivalent and 704 microg retinol equivalence, respectively, for daily vitamin A intake. Thus, the changes in retinol activity equivalents induced substantial reduction (by 24%) in estimation of vitamin A intake among the Japanese population, for whom pro-vitamin A carotenoids in plant foods are the major sources (76%) for vitamin A, and retinol accounts for only 35% (on the retinol activity equivalent basis).

Adult↗
PubMed1995

Interaction among vitamin C, vitamin E, and beta-carotene.

The effects of vitamin C (ascorbic acid), vitamin E (alpha-tocopherol), and beta-carotene as antioxidants and their cooperative action against the oxidation of lipid in solution, membranes, and lipoproteins have been studied and reviewed. Ascorbic acid and alpha-tocopherol act as potent, and probably the most important, hydrophilic and lipophilic antioxidants, respectively. They function at their own site individually and furthermore act synergistically. beta-Carotene has lower reactivity toward radicals than does alpha-tocopherol and acts as a weak antioxidant in solution. It is more lipophilic than alpha-tocopherol and is assumed to be present at the interior of membranes or lipoproteins, which enables it to scavenge radicals within the lipophilic compartment more efficiently than does alpha-tocopherol. The cooperative interaction between vitamin C and vitamin E may be quite probable, that of vitamin C and beta-carotene is improbable, whereas that between vitamin E and beta-carotene may be possible.

Antioxidants↗
PubMed1996

Hyperhomocysteinemia in chronic alcoholism: correlation with folate, vitamin B-12, and vitamin B-6 status.

Serum homocysteine concentrations have been shown to be a sensitive functional indicator of intracellular folate, vitamin B-12, and vitamin B-6 status. Chronic alcoholism is known to interfere with one-carbon metabolism, for which the above vitamins serve as coenzymes. In the present study, these vitamins were assessed in 32 chronic alcoholics and 31 healthy volunteers by measuring blood vitamin concentrations as well as serum homocysteine concentrations. In chronic alcoholics, serum pyridoxal 5'-phosphate and red blood cell folate concentrations were significantly lower than in the control subjects (P < 0.001 and P = 0.008, respectively). Mean serum homocysteine was twice as high in chronic alcoholics than in nondrinkers (P < 0.001). Beer consumers had significantly lower concentrations of homocysteine compared with drinkers of wine or spirits (P = 0.05). These results suggest that by interfering with folate or vitamin B-6 metabolism, chronic alcohol intake may impair the disposal of homocysteine through the transmethylation or transsulfuration pathways.

Adult↗
PubMed1996

Relations of vitamin B-12, vitamin B-6, folate, and homocysteine to cognitive performance in the Normative Aging Study.

We investigated the relations between plasma concentrations of homocysteine and vitamins B-12 and B-6 and folate, and scores from a battery of cognitive tests for 70 male subjects, aged 54-81 y, in the Normative Aging Study. Lower concentrations of vitamin B-12 (P=0.04) and folate (P=0.003) and higher concentrations of homocysteine (P=0.0009 ) were associated with poorer spatial copying skills. Plasma homocysteine was a stronger predictor of spatial copying performance than either vitamin B-12 or folate. The association of homocysteine with spatial copying performance was not explained by clinical diagnoses of vascular disease. Higher concentrations of vitamin B-6 were related to better performance on two measures of memory (P=0.03 and P=0.05). The results suggest that vitamins (and homocysteine) may have differential effects on cognitive abilities. Individual vitamins and homocysteine should be explored further as determinants of patterns of cognitive impairment.

Aged↗
PubMed1997

Erythrocyte vitamin E and plasma ascorbate concentrations in relation to erythrocyte peroxidation in smokers and nonsmokers: dose response to vitamin E supplementation.

Many human degenerative diseases involve free radical processes that nutritional antioxidants may ameliorate or prevent, but the optimum intake of such nutrients has yet to be established. Requirement will depend in part on the level of exposure to exogenous and endogenous reactive oxygen species. Smokers incur a sustained degree of oxidant stress from both of these sources, increasing their requirements for vitamins E and C. Male smokers (n = 50) from a Scottish population with habitually low vitamin E and vitamin C intakes consistently had lower plasma ascorbate concentrations (P < 0.02) and greater susceptibility to hydrogen peroxide-stimulated erythrocyte peroxidation in vitro (P < 0.001) than did nonsmokers (n = 50) from the same population. Erythrocyte vitamin E concentrations increased in a dose-dependent manner during 20 wk of supplementation with 70, 140, 560, and 1050 mg D-alpha-tocopherol/d. In smokers each dose was associated with a significant decrease in susceptibility of erythrocytes to peroxidation (P < 0.001). However, red cells of nonsmokers receiving the 1050-mg supplement had an increased susceptibility to peroxidation. Moreover, prolonged supplementation with D-alpha-tocopherol in nonsmokers induced a decline in plasma ascorbate concentration (P < 0.02) in association with an increasing erythrocyte vitamin E uptake (P < 0.001), and in nonsmokers receiving 1050 mg, the susceptibility to peroxidation also increased (P < 0.001). Thus, vitamin E may have prooxidant activity in nonsmokers at high and prolonged intakes.

Administration, Oral↗
PubMed2003

Plasma pyridoxal 5'-phosphate concentration is correlated with functional vitamin B-6 indices in patients with rheumatoid arthritis and marginal vitamin B-6 status.

Many patients with rheumatoid arthritis (RA) have low plasma pyridoxal-phosphate (PLP) but a normal erythrocyte aspartate aminotransferase activity coefficient (alpha EAST), a measure of vitamin B-6 status in the erythrocytes, compared with healthy subjects. The goal of the present study was to examine the correlations of PLP levels in these two compartments (plasma and erythrocytes) with other established indices of vitamin B-6 status, and to determine which indicator better reflects functional status of vitamin B-6 in patients with RA. Multiple indices of vitamin B-6 status were measured in 33 patients with RA. Plasma PLP, urinary 4-pyridoxic acid (4-PA), net increase in plasma total homocysteine after a methionine load (DeltatHcy) and net increase in urinary xanthurenic acid after a tryptophan load (DeltaXA) were log-transformed to reach normality for statistical analyses. We found that log-plasma PLP levels were inversely correlated with both log-DeltatHcy (r = -0.368, P = 0.035) and log-DeltaXA (r = -0.333, P = 0.05). Plasma PLP was not correlated with alpha EAST or urinary 4-PA excretion. In contrast, erythrocyte PLP was inversely correlated with alpha EAST (r = -0.431, P = 0.012) and positively correlated with log-4-PA (r = 0.475, P = 0.005), but erythrocyte PLP was not correlated with the outcomes of a methionine or tryptophan load test. Erythrocyte PLP and log-4-PA, but not plasma PLP, were correlated with dietary intake of vitamin B-6 after adjusting for protein intake (r = 0.420, P = 0.015 and r = 0.333, P = 0.05, respectively). We suggest that in patients with RA, plasma PLP levels are a better diagnostic indicator of functional vitamin B-6 status than erythrocyte PLP levels.

Adult↗
PubMed2004

Reasonable estimates of serum vitamin E, vitamin C, and beta-cryptoxanthin are obtained with a food frequency questionnaire in older black and white adults.

Few studies provide correlations between different indicators of the dietary intakes of older (>or= 65 y) black and white adults. This study compared the usual intakes of vitamin E, vitamin C, and selected carotenoids estimated by a modified Harvard food frequency questionnaire (FFQ) to those estimated by multiple 24-h recalls, and to blood concentrations of components in a randomly selected sample of participants in the Chicago Health and Aging Project (CHAP). Subjects (n = 59) were interviewed to complete multiple 24-h recalls over a year's time, then completed an FFQ and subsequently provided a fasting blood specimen within 2 mo. Dietary estimates were energy-adjusted separately for men and women. Significant (P < 0.05) correlations between total (diet and supplement) FFQ estimates and serum measures of vitamin E and vitamin C were as follows: 0.49 and 0.39 for blacks, and 0.42 and 0.29 for whites, respectively. The highest correlations between serum and FFQ indicators were for dietary beta-cryptoxanthin (0.46), total alpha-tocopherol (0.46) and total beta-carotene (0.44) among whites; among blacks, the highest correlations were for dietary alpha-carotene (0.81), total alpha-tocopherol (0.53) and total beta-cryptoxanthin (0.50); all were significant (P < 0.05). Further adjustment for age, gender, BMI, and educational level minimally altered these coefficients. These findings indicate that the modified Harvard FFQ provides reasonable estimates of serum levels of vitamin E, vitamin C and beta-cryptoxanthin among CHAP participants.

Aged↗
PubMed2002

Use and indication of vitamin D and vitamin D analogues in patients with renal bone disease.

Vitamin D plays a pivotal role in the pathogenesis and treatment of renal bone disease. Vitamin D levels decline in the early phase of renal failure, however, through a compensatory mechanism parathyroid hormone (PTH) stimulates the production of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3), calcitriol) to return it to normal circulating concentrations. Nevertheless, resistance to calcitriol is observed and may be related to the decreased presence of the heterodimeric, DNA-binding partner for the vitamin D receptor protein. In end-stage kidney disease (ESKD) the circulating levels of calcitriol are invariably low. The indications of vitamin D therapy are the replacement of the missing hormone vs suppression of hyperparathyroidism (HPT) requiring daily low-dose oral vs intermittent 'pulse' or oral administration. However, this therapy must be accompanied by careful patient monitoring to avoid hypercalcaemia and low bone turnover. Low bone turnover is not merely a histologic entity, but a clinical condition associated with a high risk of extraosseous calcifications, in particular in the cardiovascular system, leading to increased morbidity. Thus, determination of bone turnover in patients with ESKD is essential. Bone biopsy is the gold standard to assess bone turnover, however, it is not always available and nephrologists rely on PTH levels. The intact PTH assay measures PTH(1-84) and large C-PTH fragments, which may antagonize the PTH(1-84) effects on bone. An assay that measures exclusively PTH(1-84) has recently become available and a calculated PTH(1-84)/C-PTH fragment ratio has been shown to be the best predictor of bone turnover in patients with ESKD not treated with vitamin D or with other medications known to affect bone metabolism. 1,25-dihydroxy-22-oxavitamin D(3) (22-oxacalcitriol, OCT) is a vitamin D analogue that could control serum PTH concentrations without deleterious effects on bone.

Chronic Kidney Disease-Mineral and Bone Disorder↗
PubMed1997

Treatment of cholestatic children with water-soluble vitamin E (alpha-tocopheryl polyethylene glycol succinate): effects on serum vitamin E, lipid peroxides, and polyunsaturated fatty acids.

BACKGROUND: Treatment of vitamin E-deficient cholestatic children with water-soluble alpha-tocopherol polyethylene glycol succinate (TPGS) was previously shown to normalize vitamin E status and to improve neurological outcome. METHODS: Because vitamin E plays an important role as a free-radical scavenger, we studied the effects of long-term TPGS supplementation on lipid peroxidation and polyunsaturated fatty acid status in 15 children ages 9 months-3.4 years (median, 1.3 years) with chronic cholestasis with low serum vitamin E concentrations [1.95 (0.8-3.7) mg/L; median (1st-3rd quartile)]. The previous supplementation of alpha-tocopherol was replaced by a 20% solution of TPGS in one daily dose of 20 IU/kg. Serum alpha-tocopherol, plasma lipid peroxides expressed as thiobarbiturate reactive substance concentration (TBARS) and plasma phospholipid fatty acid profile were estimated at baseline and again after 1 month in all 15 patients, and after 1 year of TPGS therapy in 11 patients. RESULTS: alpha-Tocopherol was significantly increased after 1 month [6.9 (4.4-8.4) mg/L; p = 0.008] and rose further after 1 year [9.7 (7.2-14.9) mg/L]; similar results were obtained for the ratio vitamin E/total lipids. TBARS concentrations were significantly higher in cholestatic children at baseline [2.9 (1.5-3.32) nmol/ml] than in a control group [1.2 (1.1-1.3) nmol/ml; p = 0.0006], but were not changed significantly during TPGS therapy [after 1 year 2.34 (1.9-3.0) nmol/ml]. Compared with controls, the contributions of polyunsaturated fatty acids to total phospholipid fatty acids were markedly decreased in cholestatic patients at baseline [27.7 (22.4-31.5)% versus 36.9 (34.5-39.0)%; p = 0.001] and did not show major changes after 1 year of TPGS supplementation. CONCLUSIONS: We conclude that oral TPGS supplementation of cholestatic children can quickly normalize serum vitamin E levels but does not improve the increased lipid peroxidation and poor polyunsaturated fatty acid status.

Child, Preschool↗
PubMed1982

Oral vitamin D and ultraviolet radiation for the prevention of vitamin D deficiency in the elderly.

Different methods for the prevention and treatment of vitamin D deficiency were studied in 42 institutionalized elderly people. One group received ultraviolet radiation (UVR) on a large area of the body surface once a week for three months. The results were compared with those in groups receiving either 450 IU vitamin D2 together with 420 mg calcium daily, 420 mg calcium alone, or no treatment. A significant increase in serum 25-hydroxyvitamin D was obtained with UVR. A similar increase was obtained with oral vitamin D2. A small but significant decrease in serum alkaline phosphatase was observed in subjects receiving vitamin D and calcium or calcium alone. No effects on serum phosphate, urinary cyclic adenosine monophosphate and urinary calcium were seen. Though brief UVR at one-week intervals is an efficient and safe method for prevention of vitamin D deficiency in the elderly, it is in our experience time-consuming for the ward staff and thus less convenient than oral vitamin D supplementation.

Administration, Oral↗
PubMed1988

Effect of high doses of dietary vitamin E on the concentrations of vitamin E in several brain regions, plasma, liver, and adipose tissue of rats.

The object of this study was to assess the influence of high levels of dietary vitamin E on vitamin E concentrations in specific areas of the brain. Four-week-old male rats were fed vitamin E-deficient, control, and high-vitamin E (1,000 IU/kg) diets for 4 months. Concentrations of alpha-tocopherol in serum, adipose tissue, liver, cerebrum, cerebellum, and striatum were determined by liquid chromatography with fluorescence detection. In the high-vitamin E group, alpha-tocopherol concentrations in cerebrum, cerebellum, and striatum increased uniformly to 1.4-fold of values in controls; serum, adipose tissue, and liver attained even higher concentrations: 2.2-, 2.2-, and 4.6-fold, respectively, of control values. As observed before, brain levels of alpha-tocopherol were somewhat resistant to vitamin E deficiency, in contrast to the peripheral tissues.

Adipose Tissue↗
PubMed1985

Vitamin D deficiency rickets and vitamin B12 deficiency in vegetarian children.

During the years 1978-83 four vegetarian children have been admitted to the pediatric departments of Ullevaal and Aker Hospitals in Oslo and Haukeland Hospital, Bergen, with the diagnosis of vitamin D deficiency rickets. One had vitamin B12 deficiency as well. All had been fed a vegetarian diet with some cows' milk, but without vitamin supplementation. All had marked hypocalcemia, and three had tetany or convulsions. All responded well to conventional doses of vitamin D therapy. Two of the mothers had vitamin D deficiency, and one of them also had vitamin B12 deficiency. This report describes the case histories of these children, and also discusses predisposing factors of vegetarian diets for the development of nutritional rickets.

Child Nutritional Physiological Phenomena↗
PubMed1999

Selective interaction of vitamin D receptor with transcriptional coactivators by a vitamin D analog.

The nuclear vitamin D receptor (VDR) is a member of a nuclear receptor superfamily and acts as a ligand-dependent transcription factor. A family of cotranscriptional activators (SRC-1, TIF2, and AIB-1) interacts with and activates the transactivation function of nuclear receptors in a ligand-dependent way. We examined interaction of VDR with these coactivators that was induced by several vitamin D analogs, since they exert differential subsets of the biological action of vitamin D through unknown mechanisms. Unlike other vitamin D analogs tested, OCT (22-oxa-1alpha,25-dihydroxyvitamin D3) induced interaction of VDR with TIF2 but not with SRC-1 or AIB-1. Consistent with these interactions, only TIF2 was able to potentiate the transactivation function of VDR bound to OCT. Thus, the present findings suggest that the structure of VDR is altered in a vitamin D analog-specific way, resulting in selective interactions of VDR with coactivators. Such selective interaction of coactivators with VDR may specify the array of biological actions of a vitamin D analog like OCT, possibly through activating a particular set of target gene promoters.

Animals↗
PubMed1967

Vitamin B12 absorption studies: effect of parenteral non-radioactive B12 on serum level of 57CO vitamin B12.

The intestinal absorption of (57)Co vitamin B(12) has been measured by counting the radioactivity in the serum, and the effect of the parenteral administration of 1 mg. non-radioactive vitamin B(12) two hours after the oral dose has been studied. When parenteral vitamin B(12) was not given, the mean radioactivity in the serum was lower in both patients with pernicious anaemia and in control subjects, and the results in the patients with pernicious anaemia were more definitive. There was no significant difference between the results obtained with an Ekco scaler and those with an I.D.L. scaler. This is the simplest and most convenient method of measuring vitamin B(12) absorption. It is suggested that the test be standardized by giving 0.5 mug. (57)Co vitamin B(12) with a maximal histamine stimulation of intrinsic factor secretion, but without a parenteral dose of non-radioactive vitamin B(12). The results are expressed most usefully as a percentage of the administered dose per litre of serum or plasma.

Anemia, Pernicious↗
PubMed1984

[Caloric value of food and coverage of the recommended nutritional intake of vitamins in the adult human. Principle foods containing vitamins].

Two daily food consumption models were defined. One of them (I) is representative of the French eating habits, the other (E) of a diet with a theoretically balanced content of macronutrients for a caloric intake of 2,500 kcal. For each of these two models, four menus were calculated to obtain four caloric levels (1,500, 2,000, 2,500 and 3,000 kcal). The vitamin content of these menus was established on the basis of the literature (food composition tables). Nutritional losses resulting from usual cooking methods were taken into account. The results show that the dietary intake of some vitamins, such as folic acid, pantothenic acid, vitamin A, beta-carotene, vitamin C and B1, was likely to be inadequate and are in agreement with those of epidemiologic surveys carried out in developed countries. The threshold of 80% of the recommended allowances is not reached with a caloric level of 2,500 kcal (balanced diet) or 2,700 kcal (unbalanced diet). For an allowance of 1,500 kcal, most of the vitamins do not reach or just reach 50% of the recommended level. This result shows that the former eating habits of the French population, whose caloric intake was high (more than 3,000 kcal), were correct as they covered the recommended intakes of micronutrients. This work corroborates the great importance of some food groups in covering the recommended vitamin intakes and underlines the necessity of diversifying food.

Adult↗
PubMed1995

Protection from oxidized LDL-induced leukocyte adhesion to microvascular and macrovascular endothelium in vivo by vitamin C but not by vitamin E.

BACKGROUND: The ability of oxidized LDL (oxLDL) to stimulate leukocyte-endothelium interaction is considered to be an important aspect of its proatherogenic action. Using intravital fluorescence microscopy in the dorsal skinfold chamber model in hamsters, we have previously shown that systemic administration of oxLDL stimulates leukocyte adhesion to microvascular endothelium through a mechanism that involves the generation and action of reactive oxygen species (ROS). METHODS AND RESULTS: Through the combined use of scanning electron microscopy and intravital microscopy in the same animal model, we demonstrate that oxLDL-induced leukocyte adhesion is not confined to the microcirculation but can also be observed on aortic endothelium. OxLDL-induced leukocyte adhesion to both microvascular and macrovascular endothelium was almost entirely prevented by pretreatment of the hamsters with dietary or intravenous vitamin C, which has the capacity to scavenge and neutralize ROS (arterioles: 20.5 +/- 16.4 cells/mm2 [diet] and 16.3 +/- 23.8 cells/mm2 [IV] versus 74.2 +/- 47.5 cells/mm2 [control, P < .01]; aorta: 1.0 +/- 0.4 cells/mm2 [diet] and 1.1 +/- 0.5 cells/mm2 [IV] versus 14.7 +/- 6.0 cells/mm2 [control, P < .01], 15 minutes after oxLDL, n = 7 animals per group). Vitamin C pretreatment also completely prevented oxLDL-induced leukocyte-platelet aggregate formation in the blood-stream but did not affect leukocyte rolling along the microvascular endothelium. No inhibitory effect on any of the studied parameters was observed as a result of pretreatment of the animals with the lipid-soluble antioxidants vitamin E and probucol. CONCLUSIONS: The protective effects of vitamin C on oxLDL-induced leukocyte adhesion and aggregate formation were seen at vitamin C plasma levels that can easily be reached in humans by diet or supplementation, suggesting that this could be one of the mechanisms by which vitamin C contributes to the well-documented protraction of atherogenesis as observed in large epidemiological surveys.

Animals↗
PubMed1981

Pathology of experimental vitamin D deficiency in chickens and effects of treatment with vitamin D metabolites.

Structural changes in bone, parathyroid, and ultimobranchial body were examined in three groups of chicks fed a vitamin D-deficient diet; one group was treated with vitamin D3 and another with 1,25(OH)2D3. Diets were fed from day of hatching until 5 weeks old, when deficient chicks were near death due to hypocalcemic tetany, loss of fat and muscle, and marked bone deformities. In deficient chicks, parathyroid mass increased linearly to 7.5 times normal at 5 weeks. Parathyroid cells were irregular and vacuolated, with few granules. 1,25(OH)2D3 had normal parathyroids until the fifth week, when parathyroid mass increased greatly. There were few differences in length of growth cartilage, but marked changes in length of metaphyses. Deficient chicks had metaphyses nearly five times longer than vitamin D3-treated chicks. Metaphyses in chicks given 1,25(OH)2D3 were twice as long as those of vitamin D-treated chicks at 5 weeks. Both osteoblasts and osteoclasts were more numerous in deficient chicks. These studies suggest that vitamin D3 is more effective than 1,25(OH)2D3 in preventing parathyroid and bone lesions of vitamin D deficiency.

Animals↗