Vitamin E-responsive macrocytic anemia in protein-calorie malnutrition. Measurements of vitamin E, folic acid, vitamin C, vitamin B12 and iron.
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Anemia, Macrocytic↗
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Vitamin A utilization studies. IV. Relative utilization of vitamin A alcohol, vitamin A acetate and vitamin A natural esters as affected by variations in dosage level, quantity and character of diluent, and quantity of dietary fat.
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Alcohols↗
[Data on vitamin B6 deficiency, vitamin B6 requirements and supply of vitamin B6, with an estimation of the vitamin B6 content of the average Dutch meal in 1960].
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Food Analysis↗
The role of the vitamin D receptor in regulating vitamin D metabolism: a study of vitamin D-dependent rickets, type II.
In vitro studies and animal experiments suggest that the production of 1,25-dihydroxyvitamin D [1,25-(OH)(2)D] and 24,25-(OH)(2)D is reciprocally controlled by 1,25-(OH)(2)D. To investigate the role of the vitamin D receptor (VDR) in controlling vitamin D metabolism in humans, we studied 10 patients with vitamin D-dependent rickets type II due to a defective VDR. After a period of high dose calcium therapy, 7 of the patients had normal serum calcium, phosphorus, alkaline phosphatase, and plasma PTH levels (PTH-N), and 3 showed increased serum alkaline phosphatase and plasma PTH (PTH-H). Serum calcium, phosphorus, alkaline phosphatase, PTH, vitamin D metabolites, urinary calcium/creatinine, and renal phosphate threshold concentration were compared with unaffected family members that comprised the control group. Vitamin D metabolites were measured before and after an oral load of 50,000 U/m(2) cholecalciferol. Compared with the control group, 1,25-(OH)(2)D levels were significantly higher and 24,25-(OH)(2)D levels were lower in the PTH-N group and even more so in the PTH-H group. 1alpha-Hydroxylase (1-OHase) and 24-OHase activities were estimated by the product/substrate ratio. In the PTH-N group, 1-OHase activity was higher and 24-OHase activity was lower than in controls. In the PTH-H group, 1-OHase activity was even higher, probably due to an additive effect of PTH. Thus, 1,25-(OH)(2)D-liganded VDR is a major control mechanism for vitamin D metabolism, and PTH exerts an additive effect. Assessment of the influence of 1,25-(OH)(2)D shows reciprocal control of enzyme activity in man, suppressing 1-OHase and stimulating 24-OHase activity.
25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
Distribution of vitamins A and E in blood and liver of rats depleted of vitamin A or vitamin E.
Young Sprague-Dawley male rats (n = 150) were fed a semipurified diet, either without vitamin A (VA), without vitamin E (VE) or supplemented with both vitamins A and E (control). At the end of weeks 0, 1, 3, 5, 6, 7, 8 and 9, groups of rats were anesthetized with methoxyflurane, and blood was collected by cardiac puncture until the rat was exsanguinated. The liver was excised. Whole blood (WB) from each rat was fractionated into plasma (PLA), leukocytes (LEU), platelets (PLT) and erythrocytes (RBC). Each blood component was extracted with heptane and livers were extracted with CHCl3/CH3OH (2:1, v/v). The extracts were analyzed for VA and VE by high performance liquid chromatography. The relationship among blood components in the loss of VA was PLT = LEU greater than WB greater than PLA. The relationship among blood components in the loss of VE was PLA greater than RBC greater than WB greater than LEU = PLT. VA and VE levels in other blood components decreased precipitously between weeks 0 and 4 in the animals placed on deficient diets. These results and correlation analyses between vitamin contents of blood components and of livers indicate inadequacies for the use of certain blood components as monitors of lipid-soluble vitamin status in the rat.
Animals↗
Effects of sodium ascorbate (vitamin C) and 2-methyl-1,4-naphthoquinone (vitamin K3) treatment on human tumor cell growth in vitro. I. Synergism of combined vitamin C and K3 action.
The effects of sodium ascorbate (vitamin C) and 2-methyl-1,4-naphthoquinone (vitamin K3) administered separately or in combination on the in vitro cultured human neoplastic cell lines MCF-7 (breast carcinoma), KB (oral epidermoid carcinoma), and AN3-CA (endometrial adenocarcinoma) have been examined. When given separately, vitamin C or K3 had a growth inhibiting action only at high concentrations (5.10(3) mumol/1 and 10(5) nmol/l, respectively). Combined administration of both vitamins demonstrated a synergistic inhibition of cell growth at 10 to 50 times lower concentrations. At this level separately given vitamins are not toxic. The sensitivity to this treatment was somewhat different in the three cell lines, being slightly higher for KB line. This tumor cell growth inhibitory effect was completely suppressed by the addition of catalase to the culture medium containing vitamins C and K3, suggesting an excessive production of hydrogen peroxide as being implied in mechanisms responsible for the above-mentioned effects.
Adenocarcinoma↗
Binding properties of plasma vitamin D-binding protein and intestinal 1,25-dihydroxyvitamin D3 receptor in piglets with pseudo-vitamin D-deficiency rickets, type I: treatment effects with pharmacological doses of vitamin D3.
The effective treatment of the rachitic symptoms of pseudo-vitamin D-deficiency rickets, type I (PVDRI) by massive doses of vitamin D3 was examined. For this purpose, the affinities and the maximum binding capacities (Bmax) of the plasma vitamin D-binding protein (DBP) and of the intestinal 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) receptor for vitamin D3, 25-hydroxyvitamin D3 (25-OHD3) and 1,25-(OH)2D3, were investigated in normal piglets and in rachitic piglets that suffered from PVDRI. The piglets were 5 to 10 weeks old and of both sexes. The Bmax of plasma DBP for 25-OHD3 was 6.77 +/- 0.45 microM for PVDRI piglets and 7.30 +/- 0.41 microM for control piglets and showed no differences between the two groups. Equilibrium association constants (Ka) of DBP for 25-OHD3 were 4.3 x 10(8) M-1 for PVDRI piglets and 4.0 x 10(8) M-1 for controls and showed also no differences between the two groups. Similarly the Ka of DBP for 1,25-(OH)2D3 was also the same for rachitic and control piglets (1.45 x 10(7) and 1.54 x 10(7) M-1, respectively). Due to the lower circulating concentration of 1,25-(OH)2D3 in the plasma of rachitic piglets compared to that of controls its free metabolite index was significantly lower in rachitic (0.42 +/- 0.05 x 10(-5)) than in control piglets (3.63 +/- 0.30 x 10(-5)). The Kd and Bmax of the intestinal nuclear receptor for 1,25-(OH)2D3 of rachitic and control piglets were 0.31 +/- 0.05 and 0.33 +/- 0.05 nM and 674 +/- 103 and 719 +/- 123 fmol/mg protein, respectively, and were also not different between the two groups of piglets. It was concluded from these observations that the rachitic symptoms of PVDRI piglets resulted solely from the lower free 1,25-(OH)2D3 concentration in plasma compared to that of normal piglets. The relative affinities of the intestinal 1,25-(OH)2D3 receptor for vitamin D3 and 25-OHD3 were also measured. It was found that 50% displacement of 1,25-(OH)2D3 from the intestinal receptor of PVDRI and control piglets required a 220,000- and 245,000-fold excess of the free concentration of vitamin D3, respectively, and a 20- to 42- and 23- to 71-fold excess of the free concentration of 25-OHD3, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Comparison of a vitamin E-rich diet and supplemental vitamin E on measures of vitamin E status and lipoprotein profile.
OBJECTIVE: To determine whether dietary modification rather than use of supplements can raise indices of vitamin E status to potentially cardioprotective levels. DESIGN: Eight week randomised controlled trial with parallel treatments to compare increased use of vitamin E-rich foods, supplementation with 200 IU of vitamin E, and a placebo. SETTING: Dunedin, New Zealand. SUBJECTS: Ninety subjects were recruited, of whom 82 non-smoking, free-living individuals aged 22-72 y with plasma cholesterol <7.5 mmol/l completed the trial. MAIN OUTCOME MEASURES: Dietary intakes, plasma alpha tocopherol, plasma alpha tocopherol/cholesterol ratio and lipoprotein cholesterol. RESULTS: Consumption of an additional 12 mg of vitamin E (alpha tocopherol equivalents) from dietary sources was primarily achieved through the replacement of saturated fat-rich foods with unsaturated fats rich in vitamin E, nuts and vegetables. This resulted in a 3.4 micromol/l increase in plasma alpha tocopherol at week 6 (95% CI 1.6-5.3), and 0.9 micromol/mmol in plasma alpha tocopherol/cholesterol at weeks 4 and 6 (95% CI 0.3-1.4 and 0.4-1.4, respectively) when compared with the placebo group. In the supplement group, plasma alpha tocopherol and plasma alpha tocopherol/cholesterol were significantly increased within 2 weeks and remained so throughout the 8 week intervention. CONCLUSION: Increasing dietary vitamin E intake can increase plasma alpha tocopherol levels, although factors other than dietary intake are also important determinants. The extent of dietary modification required to achieve potentially cardioprotective levels of plasma alpha tocopherol is difficult in practice. SPONSORSHIP: The study was supported through the Otago Medical Research Foundation Laurenson Award.
Adult↗
A negative vitamin D response DNA element in the human parathyroid hormone-related peptide gene binds to vitamin D receptor along with Ku antigen to mediate negative gene regulation by vitamin D.
We found that the human parathyroid hormone-related peptide (hPTHrP) gene contained a DNA element (nVDREhPTHrP) homologous to a negative vitamin D response element in the human parathyroid hormone gene. It bound to vitamin D receptor (VDR) but not retinoic acid Xalpha receptor (RXRalpha) in the human T cell line MT2 cells. VDR binding to this element was confirmed by the Southwestern assay combined with immunodepletion using anti-VDR monoclonal antibody, and this binding activity was repressed by 1,25-dihydroxyvitamin D3. Such a repression was reversed by acid phosphatase treatment, suggesting that 1,25-dihydroxyvitamin D3 phosphorylates VDR to weaken its binding activity to nVDREhPTHrP. In electrophoretic mobility shift assay, we found anti-Ku antigen antibody specifically supershifted the MT2 nuclear proteinnVDREhPTHrP complex. The nVDREhPTHrP-bearing reporter plasmid produced vitamin D-dependent inhibition of the reporter activity in MT2 cells, which was markedly masked by the introduction of the Ku antigen expression vector in the antisense orientation. On the other hand, such a procedure did not perturb the vitamin D response element-mediated gene stimulation by vitamin D. These results indicate that nVDREhPTHrP interacts with Ku antigen in addition to VDR to mediate gene suppression by vitamin D.
Antigens, Nuclear↗
Vitamin B12 in human colostrum and milk. Quantitation of the vitamin and its binder and the uptake of bound vitamin B12 by intestinal bacteria.
The concentration of vitamin B12 was measured by microbiological assay in 229 samples of normal human colostrum and milk taken at various stages of lactation. Colostrum obtained within 48 hours of delivery contains high concentrations of vitamin B12 (mean 2 431 pg/ml), but within a few days the levels fall to a range similar to the levels in normal serum. The vitamin B12 binding capacity of 111 samples of colostrum and milk was estimated by gel filtration or charcoal binding. Colostrum samples have a mean binding capacity of 72 ng/ml, while the binding capacity in milk is only one third of this value. The ability of a range of intestinal bacteria to take up colostrum-bound vitamin B12, was assessed. All the organisms took up free vitamin B12, but when the vitamin was bound in colostrum, there was little or no uptake even after 24 hours incubation.
Bacteria↗
[Provision of residents of the city of Kiev with vitamins C and B1. Effectiveness of a complex vitamin-mineral preparation in preventing spring vitamin deficiencies].
The investigation was conducted on provision with vitamins C and B1 of Kyiv inhabitants limited contingent at spring period and efficiency of complex vitamin-mineral preparations in normalisation of the vitamins level in blood of human-subjects. The deficit of vitamin C in 54% and vitamin B1 in 18.5% of the investigated people was revealed. Supradin gave the best results among rest preparations ("Centrum", "Vitrum", "Duovit", "Multi-Tabs") in the normalization of the level of vitamin C and biologically-active form of thiamine (thiamindiphosphate) in the blood of investigated people.
Ascorbic Acid↗
Identification of 7-dehydrocholesterol, vitamin D3, 25(OH)-vitamin D3 and 1,25(OH)2-vitamin D3 in Solanum glaucophyllum cultures grown in absence of light.
Solanum glaucophyllum contains the calciotropic hormone 1, 25-dihydroxy-vitamin D3 (1,25(OH)2D3). The metabolic pathway leading to the formation of 1,25(OH)2D3 in the plant is largely unknown. Specifically, there is controversy about the participation of a photolytic reaction in the generation of vitamin D3 and its metabolites. To investigate the requirement for light, S. glaucophyllum tissue (callus) and cell suspension cultures grown under strict conditions of darkness were extracted with chloroform/methanol (1:2, v/v) followed by purification of the lipidic fraction by Sephadex LH-20 and high-performance liquid chromatography. HPLC peaks with elution times similar to those of authentic samples of 7-dehydrocholesterol, vitamin D3, 25(OH)D3 and 1,25(OH)2D3 were detected. The presence of 1,25(OH)2D3 was also evidenced by [3H]1,25(OH)2D3 competitive binding analysis using the chick hormone intestinal receptor. Furthermore, 7-dehydrocholesterol, vitamin D3, 25(OH)D3 and 1,25(OH)2D3 were unequivocally identified by mass spectrometry. Incubation of control samples of 7-dehydrocholesterol under the same conditions as S. glaucophyllum cultures did not result in vitamin D3 formation, excluding the influence of light in these experiments. The results suggest that a synthetic route of vitamin D3 compounds independent of light operates in Solanum glaucophyllum cultured in vitro.
Argentina↗
The B vitamins and vitamin C in human nutrition. II. 'Conditional' B vitamins and vitamin C.
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Ascorbic Acid↗
Antioxidant and co-antioxidant activity of vitamin C. The effect of vitamin C, either alone or in the presence of vitamin E or a water-soluble vitamin E analogue, upon the peroxidation of aqueous multilamellar phospholipid liposomes.
Thermally labile azo-initiators, dissolved in either the aqueous or lipid phase, have been used to generate peroxyl radicals at a known, steady rate in an aqueous dispersion of dilinoleoylphosphatidylcholine multilamellar liposomes at 37 degrees C in order to study the antioxidant behaviour of ascorbate itself and ascorbate in combination with either alpha-tocopherol or a water-soluble alpha-tocopherol analogue (TROLOX(-]. It is found that ascorbate is an effective inhibitor of peroxidations initiated in the aqueous phase, with each ascorbate terminating 0.6 radical chains (i.e., n = 0.6), but it is a very poor inhibitor of peroxidations initiated in the lipid phase. Peroxidations initiated in the lipid-phase in the presence of either alpha-tocopherol or TROLOX(-) indicate that ascorbate is an excellent synergist with both phenolic antioxidants (n = 0.4). In peroxidations initiated in the aqueous phase ascorbate acts as a co-antioxidant with TROLOX(-) (n = 0.7), but the interpretation of the approximately additive effect obtained in the presence of alpha-tocopherol is complicated by the fact that under the experimental conditions employed alpha-tocopherol alone does not give a distinct, measurable inhibition period. The latter problem is shown to be due to a non-uniform distribution of the water-soluble initiator within the liposome. Other examples of the complicating effects of non-uniform distributions of reactants in kinetic studies of the autoxidation of organic substrates dispersed in water are described.
Antioxidants↗
[Determination of vitamin D in the presence of vitamin A. Utilization of the reaction of vitamin A dyshydratation for the chromatographic separation of the 2 vitamins].
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Chemistry, Pharmaceutical↗
Vitamin D-dependent recruitment of DNA-PK to the chromatinized negative vitamin D response element in the PTHrP gene is required for gene repression by vitamin D.
The mechanism of transcriptional repression by nuclear hormone receptors, especially in the presence of the ligands, is largely unknown. We previously reported that 1,25-dihydroxyvitamin D(3) (1,25 vitamin D3) inhibited expression of the parathyroid hormone-related polypeptide (PTHrP) gene through the interaction between the liganded monomeric vitamin D receptor (VDR) and the negative DNA element in the PTHrP gene (nVDRE(RP)). In this study, we employed chromatin immunoprecipitation (ChIP) assay and confirmed that 1,25 vitamin D3 recruited DNA-dependent protein kinase (DNA-PKcs) to the chromatinized nVDRE(RP). Conversely, the regulatory subunits of DNA-PK were associated with the nVDRE(RP) sequences only when 1,25 vitamin D3 was absent. VDR was constitutively associated with these chromatinized nVDRE(RP) sequences. Furthermore, DNA-PKcs could phosphorylate VDR in vitro. We raise a possibility that a conformational change of VDR through its phosphorylation mediated by DNA-PKcs underlies the mechanism of gene repression by 1,25 vitamin D3-bound VDR.
Androstadienes↗
Analysis of fat-soluble vitamins. XXIV. High performance liquid chromatographic determination of vitamin D in vitamin D resin containing powders: collaborative study.
Further study of vitamin D methodology solved the discrepancy between the AOAC chemical method, 43.068-43.078, and the HPLC assay for vitamin D3 in resin containing dry powders. The discrepancy is caused by the difference in solubility of the vitamin D3 resin in benzene and in pentane. The method has been modified accordingly, and has been adopted official first action for vitamin D3 resins and vitamin D3 resin containing powders and aqueous dispersions.
Chromatography, High Pressure Liquid↗
Folate, vitamin B6, vitamin B12, and vitamin B2 intake, genetic polymorphisms of related enzymes, and risk of colorectal cancer in a hospital-based case-control study in Japan.
We conducted a case-control study to investigate the association of nutrient intake involved in the one-carbon pathway of folate for DNA methylation and DNA synthesis and the related enzyme genetic polymorphisms with colorectal cancer. Cases were 107 patients newly diagnosed with colorectal cancer. Controls were 224 subjects matched with cases by sex, age, and residential area. Nutrient intake was assessed by a self-administered, semiquantitative food-frequency questionnaire. Four genetic polymorphisms-MTHFR C677T and A1298C, MTRR A66G, and ALDH2 Glu487Lys-were determined using blood samples. Odds ratios were calculated using conditional logistic regression analysis adjusted for smoking, alcohol consumption, body mass index, and dietary fiber intake. Although folate intake was inversely associated with colorectal cancer, this association was attenuated after further controlling for dietary fiber intake. Neither vitamin B6, vitamin B12, nor vitamin B2, nor any genetic polymorphism was significantly associated with colorectal cancer. MTRR polymorphism interacted with the association of folate (P for interaction = 0.04) or vitamin (P for interaction = 0.02) with colorectal cancer, although the other polymorphisms did not interact with any nutrient intake. In conclusion, the study did not support the existing hypothesis of gene-nutrient interaction in colorectal carcinogenesis.
Adult↗