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Vitamin A serum and dietary vitamin A intake in lung cancer patients.

Clinical and experimental evidence indicates a possible role for vitamin A deficiency in the pathogenesis of bronchogenic carcinoma. We, therefore, measured serum vitamin A levels in 67 newly diagnosed non-resectable lung cancer patients. In 43 of these patients daily vitamin A intake was also determined. Serum vitamin A levels were within the normal range of the general population of 66 of the 67 patients. Eighteen of 43 patients had daily vitamin A intakes less than 5000 IU/day while 25 patients had daily intake above this level. The serum vitamin A level did not correlate with histologic subtype, extent of disease or presence or absence of hepatic metastases. While these data suggest that vitamin A deficiency was not implicated in pulmonary carcinogenesis, more definitive conclusions await prospective evaluation of high risk individuals followed serially for many years.

Adult↗

Effects on bone mineral density of calcium and vitamin D supplementation in elderly women with vitamin D deficiency.

OBJECTIVE: Calcium and vitamin D deficiency is common in older individuals, particularly those who live in nursing homes, and increases the risk of osteoporosis and fractures. METHODS: We conducted a randomized double-blind placebo-controlled study of combined supplementation with 500 mg of elemental calcium, as carbonate, and 400 IU of vitamin D bid for 12 months in women older than 65 years of age with vitamin D deficiency, defined as serum 25(OH)D concentrations </=12 ng/ml. RESULTS: Mean patient age was 75 +/- 7 years, and median daily dietary intakes of calcium and vitamin D were 697 mg and 66.8 IU in the supplemented group (n = 95) and 671 mg and 61.8 IU in the placebo group (n = 97). The median serum 25(OH)D level was 7.0 ng/ml in both groups, and the medial intact parathyroid hormone (PTHi) levels were 49 and 48 pg/ml in the supplemented and placebo groups, respectively. The median increase in serum 25(OH)D was 22.0 ng/ml in the supplemented group and 4 ng/ml in the placebo group (P < 0.0001), and the median PTHi decrease was 17 and 5 pg/ml, respectively (P < 0.0001). The median bone mineral density increase was significantly greater in the supplemented group than in the placebo group: +2.98% vs. -0.21% at L2-L4 (P = 0.0009), +1.19% and -0.83% at the femoral neck (P = 0.015), +0.86% and -0.56% at the trochanter (P = 0.015), and +0.99% and +0.11% for the whole body (P = 0.01). Similarly, the median decrease in the main bone markers was significantly greater in the treated group than in the placebo group: -1.35 microg/l vs. +0.50 microg/l for bone alkaline phosphatase (P = 0.008), -16.6 nmol/mmol creatinine vs. -2.3 nmol/mmol creatinine for urinary type I amino-terminal telopeptide (P = 0.001), and -896 pmol/l vs. -201 pmol/l for serum type I carboxy-terminal telopeptide (P = 0.003). We found no significant differences between the two groups for serum calcium, although urinary calcium excretion changed more in the supplemented group than in the placebo group. In conclusion, bone mass in older women with vitamin D deficiency increases significantly at the lumbar spine, femur, trochanter, and whole body after calcium and vitamin D supplementation for 1 year, and concomitantly bone markers improved as vitamin D levels returned to normal.

Aged↗

Intercomparison of methods for the determination of vitamins in foods. Part 2. Water-soluble vitamins.

An intercomparison of methods involving 18 European laboratories was organized to assess the state-of-the-art of vitamin determination in foods. Each laboratory received identical samples of dry food reference material (homogeneous powders, milk powder, pork muscle and haricot vert beans), which have recently been certified for major dietary components and elements. Each laboratory was requested to perform the analyses by its own routine methods. The results for water-soluble vitamins are reported. The reproducibility for the determination of vitamin B1 in milk powder, pork muscle and haricot vert beans with high-performance liquid chromatography (HPLC), fluorimetric and microbiological methods was good, with the relative standard deviation of reproducibility (RSDReprod) ranging from 11 to 18%. Differences between laboratories for the determination of the vitamin B2 content of milk powder, pork muscle and haricot vert beans determined using HPLC and microbiological methods were very high, with RSDReprod ranging from 28 to 74%. The extraction and hydrolysis procedures were probably the most important sources of variation. For vitamin B6 various HPLC and microbiological methods were used. The variation in the results for vitamin B6 was high, except in milk powder. The RSDReprod ranged from 18 to 51%. A major part of this variability was due to differences in the extraction and hydrolysis procedures and problems with the identification of the vitamin B6 vitamers by HPLC. Variation in the results for niacin obtained with the microbiological methods in milk powder, pork muscle and haricot vert beans, was small; RSDReprod = 9-15%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Trace nutrients. 3 Magnesium, copper, zinc, vitamin B6, vitamin B12 and folic acid in the British household food supply.

1. Intakes of magnesium, copper, zinc, vitamin B6, vitamin B12 and folic acid in Britain were calculated by applying the values selected for the 4th edition of McCance and Widdowson's The Composition of Foods (Paul & Southgate, 1978) to the amounts of food recorded in the National Food Survey made during 1976 (Ministry of Agriculture, Fisheries and Food, 1977). 2. National average intakes were (/person per d): Mg 249 mg, Cu 1.51 mg, Zn 9.1 mg, vitamin B6 1.36 mg, vitamin B12 6.6 micrograms free folic acid 105 microgram and total folic acid 190 micrograms. Corresponding intakes (/person) in families with four or more children were 10-20% lower. 3. A comparison of intakes with those recommended in Canada (Department of National Health and Welfare, 1976) and the USA (National Research Council, 1974) or by WHO (1973) indicated that for folic acid average values were particularly low, and only for vitamin B12 were the recommendations significantly exceeded. 4. Contributions from alcoholic drinks and confectionery were also calculated and found, on average, to be significant for cu, vitamin B12 and folic acid. 5. The losses of B-vitamins which might occur on cooking are discussed.

Alcoholic Beverages↗

Effect of intramuscular vitamin A injection on plasma levels of vitamin A and retinol-binding protein in malnourished children.

1. Serum levels of retinol-binding protein (RBP), total vitamin A and retinyl ester were measured in twenty-four malnourished children with corneal lesions and nine normal children. 2. Initially, the RBP and vitamin A levels were significantly lower in malnourished children than in normal children. 3. After intramuscular injection of 30000 microgram of aqueous vitamin A, serum levels of total vitamin A were increased significantly at 24 h and tended to fall within 5 d of treatment in both groups. 4. Before treatment, retinyl ester accounted for less than 10% of the vitamin in circulation. After vitamin A injection, it increased to 30%, a level much lower than that reported in patients with hypervitaminosis A. 5. There was no significant difference between the two groups of children and none of them showed clinical signs of toxicity. These observations indicate that administration of massive doses of vitamin A over a short period will not produce toxic effects even in malnourished children.

Child, Preschool↗

[Vitamin A requirement of fattening turkeys. 1. Vitamin A requirement of fattening turkeys under conditions of intensive rearing on the ground].

In two experiments with a total of 2,250 fattening turkeys at VEB KIM Turkey and Goose Production Gühlen-Glienicke graded doses of vitamin A (0...20,000 I.U./kg feed) in a ration type poor in vitamin A and carotene were tested in dependence on sex. After a 20-day depletion period the vitamin A supplement of 0, 125 and 250 I.U.vitamin A/kg feed resulted in vitamin A deficiency symptoms after feeding this ration for 1 week. A supplement of between 500 and 1,000 I.U. vitamin A/kg feed diminished consumption in some cases significantly. On the basis of parameters of the fattening performance and of the vitamin A content of the liver it could be proved that the optimal growth of the male and female animals requires approximately 2,000 I.U. and the adequate storage of vitamin A in the liver approximately 5,000 I.U./kg feed. The requirements are fulfilled by the current supplements of the mixed feed for fattening turkeys kept intensively on the ground.

Adipose Tissue↗

Effects of a progestogen and a sequential type oral contraceptive on plasma vitamin A, vitamin E, cholesterol and triglycerides.

Fasting blood samples were taken from 13 college students who had never been on oral contraceptives in two menstrual cycles. During the first cycle, the control cycle, each girl donated three blood samples; the first sample was given between days 1 and 5, the second sample between days 13 and 17, and the third sample between days 22 and 26 of the menstrual cycle. In the second menstrual cycle, the experimental cycle, nine girls were given Micronor, a progestogen type oral contraceptive and four girls were given Ortho-Novum SQ, a sequential type oral contraceptive. Four blood samples were obtained from each of the subjects: the first three samples were obtained in the three periods corresponding to those in the control cycle, and the fourth was taken 2 days after the subjects had stopped taking the oral contraceptive. Results showed that estrogen significantly raised plasma vitamin A and triglycerides. The progestogen, at low concentration, had little or no effect on these two lipid materials. At a higher concentration the progestogen enhanced the effect of the estrogen on plasma vitamin A and triglycerides. These effects were extended to at least 2 days after subjects had ceased taking the oral contraceptive. Plasma vitamin E levels in the subjects given Ortho-Novum SQ, were consistently but not statistically higher in the experimental cycle than in the control cycle. The correlation coefficient between vitamin E and triglycerides was statistically significant while those between the vitamin A and vitamin E and between vitamin A and triglycerides were not. Cholesterol was not affected by either Micronor or Ortho-Novum SQ.

Adult↗

Vitamin E supplementation in very-low-birth-weight infants: long-term follow-up at two different levels of vitamin E supplementation.

This study evaluates the need of vitamin E supplementation in very-low-birth-weight infants by long-term follow-up of plasma vitamin E status during the first 15 mo of life, with two different levels of supplementation. The subjects were 51 newborn infants with birth weights less than or equal to 1520 g. During hospitalization the infants were fed human milk. On the third day of life oral vitamin E supplementation of less than or equal to 10 mg/d was started in all infants. In addition, 23 infants selected at random were given intramuscular vitamin E (20 mg/kg/d) during the first 3 d. The data indicate that the 10 mg/d supplement resulted in an adequate plasma concentration of vitamin E. After cessation of supplementation at age 3 mo, the risk of low plasma vitamin E levels increased. Although intramuscular administration resulted in long-lasting increments in mean plasma vitamin E values, some later levels in these infants were marginal.

Follow-Up Studies↗

Vitamin A turnover in rats as influenced by vitamin A status.

Vitamin A turnover was studied in rats fed vitamin A-sufficient (+A) or vitamin A-deficient (--A) diets for 24--25 days. Hepatic vitamin A stores of the +A group (543 microgram) were significantly larger than those of the --A group (11 microgram) and similarly, the plasma vitamin A concentration of the +A group (56 microgram/dl) was significantly higher than that of the --A group (26 microgram/dl). Rats were injected intravenously with plasma containing tritium-labeled retinol (3H-ROH) obtained from vitamin A-deficient donor rats previously fed 3H-ROH. Plasma samples from injected recipients were collected over a 48-hour period. Kinetic analysis of plasma tracer concentration versus time curves indicated that the data fit a three-pool model. The plasma vitamin A turnover rate of the +A group was significantly more rapid than that of the --A group (5.19 versus 1.98 microgram/hour). Plasma fractional turnover rates for the +A group (1.31 hour--1) were not significantly different from those of the --A group (0.90 hour--1). The data suggest that for both dietary groups, the metabolism of retinol associated with the prealbumin and retinol-binding protein complex involved extensive recycling among the liver, plasma, interstitial fluid and peripheral tissues.

Animals↗

Changes in hepatic parenchymal and nonparenchymal cell vitamin A content during vitamin A depletion in the rat.

Levels of total, unesterified and esterified retinol were determined in liver, liver parenchymal cells (PC) and liver nonparenchymal cells (NPC) during vitamin A depletion in rats. Liver vitamin A levels decreased from 113 to 4 micrograms over a 97-d experimental period; plasma retinol concentrations did not change significantly during this time. Initially, greater than 90% of hepatic vitamin A was in the esterified form and most (93%) was localized in NPC. During vitamin A depletion, there were significant declines in retinyl ester content of both PC and NPC, but unesterified retinol levels were not significantly affected. Plasma retinol concentrations were significantly correlated with unesterified retinol mass in PC and NPC, but not with retinyl ester mass. Although 94% of the liver's negative vitamin A balance was due to changes in NPC retinyl ester levels, the fractional rate of retinyl ester loss from PC and NPC was almost identical. Since unesterified retinol levels in plasma, PC and NPC appeared to be conserved even when liver retinyl ester stores were virtually depleted, and since the retinol utilization rate was apparently not decreasing during this stage of vitamin A depletion, these data support the hypotheses that homeostatic mechanisms controlling the three pools of unesterified retinol are linked, and that vitamin A utilization rate is maintained as long as unesterified retinol levels in plasma, PC and NPC are normal.

Animals↗

Absorption and conversion of 11,12-(3)H-beta-carotene to vitamin A in Sprague-Dawley rats of different vitamin A status.

The aim of this study was to determine the bioavailability and bioconversion to vitamin A of a single oral dose in oil or an aqueous dispersion of labeled beta-carotene in rats of different vitamin A status. Weanling Sprague-Dawley rats were fed a vitamin A-deficient diet and supplemented for 4 wk with 0, 7, 21 and 63 micro g/(rat. d) of retinyl acetate. The rats, of different vitamin A status, were then given a single oral dose of 11,12-(3)H-beta-carotene (0.15 micro mol) dissolved in corn oil or dispersed in aqueous Tween 80. The rats were killed 4 or 24 h after the dose, and serum, liver, the entire digestive tract, other tissues, urine and feces were analyzed for carotenoids, retinoids and associated radioactivity. At 4 h after the dose, 85 +/- 9% of the administered radioactivity was recovered. Almost 50% of the dose was present as intact beta-carotene in the large intestine where further absorption and conversion was ruled out. The absorption of beta-carotene was very low, and < 5% of the radioactive dose was converted to retinoids. The absorption and conversion to vitamin A did not differ among rats of different vitamin A status. The results suggest that a single oral dose of beta-carotene might not be an effective way of raising vitamin A stores in the body.

Administration, Oral↗

Vitamin K deficiency and osteopenia in disuse-affected limbs of vitamin D-deficient elderly stroke patients.

Bone mineral density is reduced in stroke patients on the hemiplegic and contralateral sides, reflecting a degree of paralysis and vitamin D deficiency. Because the deficiency of vitamin K, a factor essential for site-specific carboxylation of bone Gla protein, is also associated with reduced bone mineral density, an additional contribution of vitamin K to bone changes was assessed in 168 elderly patients with long-standing post-stroke hemiplegia and hypovitaminosis D. Sera were analyzed to relate vitamin K1 concentrations to bone-related biochemical indexes and bone mineral density measured by radiodensitometry of the second metacarpal. Bone mineral density was lower on both sides in patients than in the 56 controls (P < 0.02). Serum vitamin K1 concentrations, which correlated positively with bone Gla protein concentrations (P < 0.0001), were lower in patients (0.48 +/- 0.47 nmol/L) than controls (1.33 +/- 0.49; P < 0.0001). Serum bone Gla protein and 25-hydroxyvitamin D concentrations were lower in patients than controls (P < 0.0001), whereas ionized Ca concentrations were higher in patients (1.277 +/- 0.041 mmol/L) than controls (1.210 +/- 0.049; P < 0.0001), correlating with the Barthel index. Multivariate linear regression identified vitamin K1, bone Gla protein, 25-hydroxyvitamin D, ionized calcium, and the Barthel index as independent bone mineral density determinants on the hemiplegic side and 25-hydroxyvitamin D, calcium, and the Barthel index on the intact side. Immobilization and vitamin K deficiency had stronger osteopenic effects on the hemiplegic side than contralaterally.

Aged↗

Megaloblastic anaemia due to vitamin B12 deficiency caused by small intestinal bacterial overgrowth: possible role of vitamin B12 analogues.

Megaloblastic anaemia due to bacterial overgrowth of the small intestine is due to vitamin B12 malabsorption. This report describes a patient with bacterial overgrowth of the small intestine who had megaloblastic anaemia and malabsorption of vitamin B12, but persistently normal levels of serum vitamin B12 and normal serum and red cell folate levels. However, there was evidence of vitamin B12 deficiency as shown by an abnormal deoxyuridine suppression test and by the response to treatment with physiological doses of vitamin B12. A relative increase in biologically inactive vitamin B12 analogues may be the explanation for the normal vitamin B12 level in this patient.

Aged↗

Neonatal plasma vitamin K1 levels following oral and intramuscular administration of vitamin K1.

Vitamin K1 levels were measured by high performance liquid chromatography in cord blood (n = 33) and at the age of 97-120 h after administration of 2 mg of vitamin K1 orally (n = 88) or 1 mg of vitamin K1 by im injection (n = 88). Vitamin K1 levels were less than 0.05 micrograms/l in cord blood. The mean (range), SEM, mode and median values (micrograms/l) for the infants given oral vitamin K1 were 17.99 (1-56), 1.25, 8 and 15.5 and those for the infants given im vitamin K1 15.83 (2-57), 1.01, 11 and 14, respectively. The t-test showed no significant difference in the mean values (p = 0.09) in the infants given oral or im vitamin K.

Administration, Oral↗

Relationship between vitamin K dependent coagulation factors and anticoagulants (protein C and protein S) in neonatal vitamin K deficiency.

To determine the relationship between vitamin K dependent coagulation factors and natural anticoagulants, namely protein C and protein S, in various degrees of vitamin K deficiency, plasma values for clotting activity, protein induced by vitamin K absence (PIVKA-II), protein C antigen, gamma-carboxy protein C antigen, and protein S antigen including total and free fractions and activity of protein C were measured in 66 full term and healthy breast fed neonates who did not receive vitamin K supplement at birth. The 66 neonates were divided into a control group (17 cases) and a low group (49 cases) according to their values for clotting activity--that is, > or = 20% or < 20% during the first six days of life--and vitamin K was immediately given when the neonates showed values < 20%. In the low group clotting activity gamma-carboxy protein C, free protein S, and protein C activity was significantly decreased to a minimum on day 2 or 3, and increased in parallel after vitamin K administration. Furthermore, they were positively correlated with one another and inversely cor-correlated with the PIVKA-II concentrations. These findings suggest that simultaneous gamma-carboxylation of coagulation factors and proteins C and S acts to maintain both coagulation and anticoagulation activities in parallel at various concentrations of vitamin K. The breast milk intake in the group with low values of clotting activity was significantly lower than that in the control group during the first three days of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗

Experiences with dual protein bound aqueous vitamin B12 absorption test in subjects with low serum vitamin B12 concentrations.

A dual isotope vitamin B12 absorption test in which vitamin B12 is given both in aqueous solution and bound to protein (chicken serum), was evaluated in 26 controls and 68 patients with subnormal serum vitamin B12 concentrations (19 with pernicious anaemia, 13 with iron deficiency, seven after partial gastrectomy, seven with malabsorptive states, five with folate deficiency, four with chronic alcoholism and 13 in whom no cause was apparent). In control patients protein bound absorption decreased with age; isotope excretion was 1.0% or over in those aged under 60 and 0.5% or over in those aged 60 and above. Malabsorption of protein bound vitamin B12 with normal aqueous absorption occurred in five patients with iron deficiency, three with alcoholism, two after partial gastrectomy, two with folate deficiency and in one with a malabsorptive state. In alcoholics abstinence produced an improvement in protein bound absorption. All patients in the group for whom no cause could be found for the subnormal serum vitamin B12 concentration had normal aqueous absorption but four had malabsorption of protein bound vitamin. Although the dual isotope test gave reproducible results and was consistent with the standard Schilling test some anomalies were detected; nine patients had reduced aqueous absorption with normal protein bound absorption. Despite this the dual test may prove useful in determining the importance of a subnormal vitamin B12 concentration where the cause is not clinically apparent. Further development is needed before it can be considered for routine use.

Absorption↗

Vitamin K metabolism in a patient resistant to vitamin K antagonists.

We investigated various pharmacokinetic and pharmacodynamic parameters in a 63-year-old man, resistant to warfarin, fluindione, acenocoumarol and phenprocoumon. Daily doses of up to 30 mg of the long-acting phenprocoumon yielded a drug concentration of 85 mg/l (usual range 1-5 mg/l) but the international normalized ratio remained around 1. The plasma half-life of phenprocoumon was approximately 350 h (normal 120-150 h). Thus, the resistance was not due to malabsorption or to an accelerated metabolism of the drug. The level of vitamin K1 (1,202 ng/l) was insufficient to induce resistance. Decarboxyprothrombin concentrations were low, demonstrating that the gamma-carboxylation of the precursors of the vitamin K-dependent coagulation factors was not effectively reduced. The concentration of vitamin K epoxide, normally increased under oral anticoagulation, correlated to the vitamin K concentration (r2 = 0.77) but the quotient epoxide/vitamin K remained 4-fold lower than that of 22 warfarin-sensitive patients, suggesting an absence of blockade of the vitamin K reductase by phenprocoumon. This resistance to all the molecular forms of the vitamin K antagonists is most likely due to a reduced affinity of the drugs to a mutant vitamin K reductase.

Drug Resistance↗

Relationship of folate, vitamin B-6, vitamin B-12, and methionine intake to incidence of colorectal cancers.

It is hypothesized that diets deficient in folate, methionine, and vitamins B-6 and B-12 cause DNA hypomethylation and, as a result, increase risk of colorectal cancers. Furthermore, it is proposed that alcohol, a methyl group antagonist, increases risk of colorectal cancers among those with low intake of folate. Data from the Iowa Women's Health Study, a population-based cohort of incident cancer, were used to examine the relationship of folate, methionine, and vitamins B-6 and B-12 to occurrence of cancers of the colon (n = 598) and rectum (n = 123) over 13 yr of follow-up. There were no independent associations of folate, methionine, or vitamins B-6 and B-12 derived from a food frequency questionnaire with incidence of colon cancer. Adjusted relative risks (RRs) of rectal cancer were similar across categories of folate, vitamin B-12, and methionine intake, but RRs increased progressively with increasing intake of vitamin B-6 [P (for trend) = 0.03]. RRs suggested that incidence of cancer of the proximal colon was lower among those with 1) high folate and high vitamin B-12 intake [RR = 0.59, 95% confidence interval (CI) = 0.39-0.89] and 2) high folate and high vitamin B-6 intake (RR = 0.65, 95% CI = 0.50-0.84) than among those with the lowest intake of these nutrients. Incidence of cancer of the proximal colon was also somewhat lower among those with high folate and low alcohol intake (RR = 0.44, 95% CI = 0.22-0.89). Findings provide limited support for an association between dietary factors involved in DNA methylation and risk of cancers of the colon and rectum.

Aged↗