Safety of one 52-mumol (50,000 IU) oral dose of vitamin A administered to neonates.

A placebo-controlled trial was carried out among 2067 Indonesian neonates to assess the safety of administering one oral 52-mumol (50,000 IU) dose of vitamin A. Infants were assessed for potential acute side-effects before and throughout 48 hours after the dose. The first 965 infants were examined by cranial ultrasound before and at 24 hours after dosing to rule out intracranial haemorrhage and determine the resistive index (RI) of the anterior cerebral artery using duplex Doppler. Groups were comparable at the baseline. A bulging fontanelle occurred in the control and vitamin A groups, respectively, among 2.7% and 4.6% of the infants at 24 hours, and 2.4% and 4.5% of the infants at 48 hours. The groups did not differ in any other sign or symptom assessed. No infant developed intracranial haemorrhage. Mean RI values were normal and not different between groups at baseline or at 24 hours. Mean RI fell during the 24 hours, as normally occurs; the mean decrease was nearly identical in the two groups. A bulging fontanelle was not associated with increased rates of any sign or symptom or with an increase in RI. The 52-mumol dose of oral vitamin A may cause a small increase in intracranial volume in a small proportion of infants, but no increase in intracranial pressure. Acute side-effects following this intervention were rare and mild.     

Epidemiology of retinitis pigmentosa in the valencian community (Spain)

The purposes of this study are to determine the frequencies of the different genetic forms of retinitis pigmentosa and to perform segregation analysis in the different genetic subtypes. Retinitis pigmentosa was diagnosed in 263 persons from 132 families. The frequency of the autosomal recessive type was the highest (31.8%) while the X-linked type was very rare (1.5%). The frequency of autosomal dominant type was 14.4% and the simplex cases constituted half of the total cases of RP registered in our community. In conclusion, in our population the high proportion of simplex cases and the low number of X-linked families are noticeable. The result of segregation analysis showed good agreement with expectation in autosomal dominant and autosomal recessive families but no more than 60% of all simplex cases were autosomal recessive. The proportion of sporadic cases was estimated statistically to be 39.9% of the total simplex cases. © Wiley-Liss, Inc.     

Safety of vitamin D3 in adults with multiple sclerosis

BACKGROUND: Vitamin D3 may have therapeutic potential in several diseases, including multiple sclerosis. High doses of vitamin D(3) may be required for therapeutic efficacy, and yet tolerability--in the present context, defined as the serum concentration of 25-hydroxyvitamin D [25(OH)D] that does not cause hypercalcemia--remains poorly characterized. OBJECTIVE: The objective of the study was to characterize the calcemic response to specific serum 25(OH)D concentrations. DESIGN: In a 28-wk protocol, 12 patients in an active phase of multiple sclerosis were given 1200 mg elemental Ca/d along with progressively increasing doses of vitamin D3: from 700 to 7000 microg/wk (from 28 000 to 280 000 IU/wk). RESULTS: Mean (+/- SD) serum concentrations of 25(OH)D initially were 78 +/- 35 nmol/L and rose to 386 +/- 157 nmol/L (P < 0.001). Serum calcium concentrations and the urinary ratio of calcium to creatinine neither increased in mean values nor exceeded reference values for any participant (2.1-2.6 mmol/L and <1.0, respectively). Liver enzymes, serum creatinine, electrolytes, serum protein, and parathyroid hormone did not change according to Bonferroni repeated-measures statistics, although parathyroid hormone did decline significantly according to the paired t test. Disease progression and activity were not affected, but the number of gadolinium-enhancing lesions per patient (assessed with a nuclear magnetic brain scan) decreased from the initial mean of 1.75 to the end-of-study mean of 0.83 (P = 0.03). CONCLUSIONS: Patients' serum 25(OH)D concentrations reached twice the top of the physiologic range without eliciting hypercalcemia or hypercalciuria. The data support the feasibility of pharmacologic doses of vitamin D3 for clinical research, and they provide objective evidence that vitamin D intake beyond the current upper limit is safe by a large margin.     

Effectiveness of weekly vitamin A (10,000 IU) and iron (60 mg) supplementation for adolescent boys and girls through schools in rural and urban East Java, Indonesia

OBJECTIVE: High prevalences of vitamin A deficiency and anaemia among adolescents warrant interventions. This study evaluated the effectiveness of school-based supplementation to reduce anaemia and improve vitamin A status. DESIGN: School-based, grade-randomized, intervention. SUBJECTS AND SETTING: In all, 1757 girls and 1859 boys, aged 12-15 y, in 24 Junior High Schools. INTERVENTIONS: Weekly supplementation for 14 weeks with 60 mg iron and 250 microg folate (Fe group; n=978), 10 000 IU vitamin A (VA group; n=970) or both (VAFe group; n=1042) to subjects in 15 schools, compared to subjects in nine other schools not receiving supplements (control; n=626). RESULTS: The baseline anaemia prevalence (Hb <120 g/l) in girls was 20% (prepubertal) and 26% (pubertal), and in boys 24% (pre-pubertal) and 11% (pubertal). Serum retinol concentrations were low (<1.05 micromol/l) in 41% of boys and 45% of girls. The interventions did not increase haemoglobin concentrations. Serum retinol concentration of boys, but not girls, in the VA group increased (0.33 vs 0.07 micromol/l in controls; P<0.01). The risk factors for low serum retinol concentration were lower baseline serum retinol concentration (OR 0.02-0.03) with, for girls, nightblindness at baseline (OR 5.88), and for boys, not receiving vitamin A (OR control: 1.00; VA: 0.37; Fe: 0.77; VAFe: 0.34) and maternal illiteracy (OR mother never attended school 1.00, mother received any formal education 0.17-0.33). CONCLUSIONS: Supplementation with vitamin A increased serum retinol concentration of boys. Iron supplementation did not change Hb. This appeared to be due to poor compliance, and partly related to side effects.     

A contextual study of daily living strategies in neurocognitively impaired adults with schizophrenia

Schizophrenia is a severe mental illness often recognized as a degenerative neurocognitive condition. For some with the disorder, the impairment is fairly mild, but for others, neurocognitive abilities can be severely compromised. In this study, 5 individuals with schizophrenia had been assessed through a laboratory-based neurocognitive battery as having severe impairment. Their neurocognitive status was unknown to the author, and she was able to observe daily tasks and ask questions about strategies they employed while completing tasks, and analyze the data without preconceptions about their status. This study was guided by notions of ecological validity, which is the comparison between lab tests and real-world functioning. Despite their cognitive deficits, these individuals had remarkable strengths, which included drawing supportive people into their worlds to fulfill their daily tasks. These data contribute to the rehabilitation literature and propose remedies for struggles of daily living when one has schizophrenia.     

Vitamin D<Subscript>3</Subscript> supplementation does not modify cardiovascular risk profile of adults with inadequate vitamin D status

Purpose

The Nutrition Societies in Germany, Austria, and Switzerland recommend a daily intake of 20 µg vitamin D₃ for adults when endogenous synthesis is absent. The current study aimed to elucidate whether this vitamin D₃ dose impacts cardiovascular risk markers of adults during the winter months.

Methods

The study was conducted in Halle (Saale), Germany (51^o northern latitude) as a placebo-controlled, double-blinded, randomised trial (from January to April). A total of 105 apparently healthy subjects (male and female, 20–71 years old) were included. Subjects were randomly allocated to two groups. One group received a daily 20-µg vitamin D₃ dose (n = 54), and the other group received a placebo (n = 51) for 12 weeks. Outcome measures included blood pressure, heart rate, concentrations of renin, aldosterone, serum lipids and vascular calcification markers, and haematologic variables such as pro-inflammatory monocytes.

Results

Blood pressure and systemic cardiovascular risk markers remained unchanged by vitamin D₃ supplementation, although serum 25-hydroxyvitamin D₃ increased from 38 ± 14 to 73 ± 16 nmol/L at week 12. The placebo and vitamin D groups did not differ in their final cardiovascular risk profile.

Conclusion

Daily supplementation of 20 µg vitamin D₃ during winter is unlikely to change cardiovascular risk profile.

     

Localization of retinol (vitamin A) in rat testes

The purpose of the study was to determine the intracellular location of exogenously injected labeled vitamin A (retinol) in rat testes by light and electron microscopic autoradiography. Tritium-labeled vitamin A mixed in vitamin A-free rat serum was injected intracapsularly in one testis in adult rats. At intervals of 30 minutes, 2 hours, and 4 hours following injection the treated testes were removed the processed for autoradiography. The results show that in the testes vitamin A is localized at three sites: within the macrophages of the interstitial tissue, in the lipid droplets of the Sertoli cells, and in the spermatids in association with Golgi saccules. To confirm the autoradiographic localization of vitamin A, the cellular retinol-binding protein (CRBP) assay demonstrates the presence of CRBP in the interstitial tissue and seminiferous tubules. The results of the study suggest a possible role of vitamin A in spermiogenesis in rat testes.     

The proposal of the activities of daily living (ADL) index for institutionalized older adults

The purpose of this study was to propose the ADL index constructed with a unidimensional scale based on item difficulty for institutionalized older adults. Six hundreds and three subjects (159 males and 444 females) were divided into the following four groups based on assisting devices for movement: G1 did not use assisting devices for movement; G2 used a stick or a walker; G3 used a wheelchair; G4 could not move. As the results of examinations from the points of the approximation of proportions, non-answer rates and agreement rates of each item according to 74 ADL items representing 9 ADL domains, the 27 ADL items were selected as utility items. The reliability and unidimensionality of the ADL index consisting of 27 items were considered to be high. As the results of examining the difficulty of items and ADL ability characteristics of each group, the ADL concerning movement and other lower limb activity in G1 and G2, and concerning changes of posture and manual activity in G3 and G4 were considered to reflect the individual differences of ADL ability, respectively. The numbers of ADL items which should first be assessed in each group were as follows: 20 items in G1; 21 items in G2; 21 items in G3; 11 items in G4.     

Evaluation of vitamin A absorption by using oil-soluble and water-miscible vitamin A preparations in normal adults and in patients with gastrointestinal disease.

We evaluated vitamin A absorption in 50 healthy adults and 26 gastrointestinal-disease patients by measuring the postabsorptive response in plasma retinyl esters after oral doses of the vitamin. On 3 consecutive days, two physiologic-dose tests of 2000-2400 retinol equivalents (RE) and one pharmacologic-dose test (84,000 RE) were administered. The physiologic doses were given as an oil-soluble or a water-miscible preparation. In gastrointestinal-disease patients the physiologic-dose test was highly correlated with the pharmacologic-dose test for the oil-soluble preparation as determined by peak rise (r = 0.50, P less than 0.05) and area under the curve (r = 0.56, P less than 0.01), suggesting that the physiologic dose is valid for investigating vitamin A absorption. Intestinal-disease or resection patients absorbed preparations poorly. Pancreatic-disease patients absorbed the oil-soluble preparation poorly. Physiologic rather than pharmacologic doses of vitamin A can be used to study vitamin A absorption.     

Extra-hepatic vitamin A concentrations in captive Rhesus (Macaca mulatta) and Marmoset (Callithrix jacchus) monkeys fed excess vitamin A

Recent work examining vitamin A (VA) status of rhesus monkeys (Macaca mulatta) used as models for human biomedical research has revealed subtoxic hepatic VA concentrations. Livers of marmoset monkeys (Callithrix jacchus), another experimental animal, were also high in VA as was serum retinyl ester concentration. Both species consumed common research diets that provided up to four times the amount of VA (retinyl acetate) as currently recommended by the National Research Council. To further define the effects of chronically high dietary VA as found in many human subpopulations, we analyzed lung and kidney tissues from subtoxic rhesus and marmoset monkeys (n = 10 each) for retinol and retinyl esters. Marmoset kidneys contained 0.88 +/- 0.66 micromol VA/g and was nearly the same as hepatic VA at 1.40 +/- 0.44 micromol/g (p = 0.143). In contrast, rhesus kidney VA concentrations were 0.0100 +/- 0.0032 micromol/g, even though liver reserves were 18.8 +/- 6.4 micromol VA/g (p < 0.0001). Lung tissue VA concentrations, 0.0022 +/- 0.0012 and 0.0061 +/- 0.0025 micromol/g for marmosets and rhesus, respectively, were lower as compared with kidney (p < 0.011). Kidney and lung VA in monkeys with adequate, but not excessive, VA stores have not been determined; hence, interpretation of these findings is limited to tissue retinol and retinyl ester profiles and extrapolation from other species rather than direct comparison to "normal" values.     

Safety and tolerability of a liquid bovine rotavirus pentavalent vaccine (LBRV-PV) in adults

BackgroundRotavirus Gastroenteritis (RVGE) is an important global public health problem. Recently a Lyophilized Pentavalent Human Bovine Reassortant Rotavirus vaccine (BRV-PV, Rotasiil) was licensed in India. A Liquid formulation of the same vaccine (LBRV-PV) was tested in a Phase I clinical trial.MethodsTotal 20 healthy adults were given a single oral dose of LBRV-PV and were followed for one month for safety outcomes: immediate reactions, solicited reactions, unsolicited adverse events and serious adverse events.ResultsAll 20 adults completed the study without any major protocol deviations. No immediate reaction, solicited reactions and unsolicited adverse events were reported during the study. No clinically significant changes were seen in the vital parameters and safety laboratory test results.ConclusionsLBRV-PV developed in India was safe and well tolerated in adults. Further clinical development of this vaccine in infants should be undertaken.Trial Registration – CTRI/2015/11/006,384.     

Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status

BACKGROUND: Cases of enhanced anticoagulant effect in response to high-dose vitamin E supplementation have been reported among patients taking oral anticoagulants. Although a vitamin E-vitamin K interaction was proposed to underlie this effect, it has not been systematically investigated in adults with normal baseline coagulation status. OBJECTIVE: The objective was to study the effect of 12 wk of supplementation with 1000 IU RRR-alpha-tocopherol/d on biochemical measures of vitamin K status in men and women not taking oral anticoagulants. DESIGN: Vitamin K status, which was assessed with the use of plasma phylloquinone concentrations, the degree of under-gamma-carboxylation of prothrombin (proteins induced by vitamin K absence-factor II, PIVKA-II), and the percentage of undercarboxylated osteocalcin (ucOC), was determined in 38 men and women with rheumatoid arthritis (study A) and in 32 healthy men (study B) participating in 2 independent, 12-wk randomized clinical trials of vitamin E supplementation (1000 IU/d). RESULTS: Mean (+/- SD) PIVKA-II increased from 1.7 +/- 1.7 to 11.9 +/- 16.1 ng/mL (P < 0.001) in study A and from 1.8 +/- 0.6 to 5.3 +/- 3.9 ng/mL (P < 0.001) in study B in response to 12 wk of vitamin E supplementation. An increase in PIVKA-II is indicative of poor vitamin K status. In contrast, the other measures of vitamin K status (ie, plasma phylloquinone concentration and percentage of ucOC) did not change significantly in response to the supplementation. CONCLUSIONS: High-dose vitamin E supplementation increased PIVKA-II in adults not receiving oral anticoagulant therapy. The clinical significance of these changes warrants further investigation, but high doses of vitamin E may antagonize vitamin K. Whether such an interaction is potentially beneficial or harmful remains to be determined.     

Rapid determination of vitamin A (retinol) and vitamin E (alpha-tocopherol) in human serum by isocratic adsorption HPLC

The simultaneous determination of alpha-tocopherol and retinol in human serum is reported. The separation is carried out by means of isocratic HPLC on adsorption columns. UV-Detection is possible by using either one wavelength for both compounds (300 nm), or after a lambda change mode with typical wavelengths for alpha-tocopherol (292 nm) and retinol (325 nm). According to short retention times (10 min) and rapid extraction the method is useful for clinical research and allows about 50 analyses per day and operator. Blood from 176 human volunteers was collected and alpha-tocopherol and retinol levels in serum determined with this method. Statistical evaluation of different selected groups shows typical significant differences of alpha-tocopherol and retinol concentrations in smokers and oral contraceptive users.     

No adverse events after simultaneous administration of 50 000 IU vitamin A and Bacille Calmette-Guerin vaccination to normal-birth-weight newborns in Guinea-Bissau

OBJECTIVE: To determine whether the combined intervention of 50 000 IU vitamin A administered together with Bacille Calmette-Guerin (BCG) vaccination at birth was associated with adverse events, in particular bulging fontanels and adverse reactions to BCG. SUBJECTS/METHODS: From an ongoing trial, 2145 infants randomized to 50 000 IU vitamin A or placebo with BCG vaccination were recruited. Adverse events were monitored in two different ways: (A) daily clinical examinations by a medical doctor during the first 3 days post supplementation; (B) weekly interviews by a trained assistant during the first month post supplementation. RESULTS: In part A, 1271 infants were enrolled, in part B 2078. Vitamin A supplementation (VAS) was associated with a relative risk (RR) of bulging fontanels of 1.16 (95% confidence interval (CI)=0.82-1.65). The rate of health care contacts and various symptoms during the first month were comparable between the groups. VAS was associated with larger peak local reactions to BCG vaccination in boys, but not in girls (P-value for test of interaction between VAS and sex=0.02). CONCLUSION: 50 000 IU vitamin A with BCG was not associated with adverse events. The observed sex-differential effect of VAS on local reaction to BCG is in line with other observations of sex-differential effects of VAS.     

Recommended dietary intakes (RDI) of vitamin A in humans

Mean and median dietary intakes of vitamin A in the US are approximately 1000 and 624 retinol equivalents, respectively. In this paper a satisfactory vitamin A status is defined as a total-body pool that provides adequate vitamin A to meet all known physiological needs and a reserve for 4 mo on low intakes or during stress. Mean dietary intakes required to maintain an adequate body pool (ie, 20 micrograms vitamin A/g liver [0.07 mumol/g]) in reference 76-kg men and 62-kg women are 506 and 413 micrograms retinol, respectively. Recommended dietary intakes (RDI) for nearly all reference men and women are 700 micrograms and 600 micrograms, respectively. Vitamin A needs in infants, children, the elderly, and pregnant and lactating women are quantified. The toxicity of vitamin A in early pregnancy, for which a safe intake level is not known, is stressed. On many grounds these suggested lower RDI values are preferable to the 1980 RDA values.     

A lowering effect of a pharmacological dose of vitamin E on serum vitamin a in normal adults

We have studied the effects of oral vitamin E (vE) on serum vitamin A (vA) levels and vA transport proteins, retinol binding protein (RBP) and prealbumin (PA), in normal subjects taking and not taking pharmacological doses of vA and/or vE acetate. Nineteen subjects were given 9009 ug of oral vA acetate daily for one week. Ten of these continued on 9009 ug of vA daily for two weeks (group I), while nine received 147 mg of vE acetate in addition to vA (group II). A third group (group III) consisted of 10 subjects who received only 147 mg of vE daily for 3 weeks. Group IV represented control subjects not given either vA or vE pills over the 3 week study period. Groups I and II showed significant increases in serum vA levels after 1 week of vA treatment. Group I to week 3 (p<0.01) while group II serum vA levels significantly fell from week 1 to week 3 (p<0.01). No significant differences were demonstrated in RBP or PA in groups I and II. Group III showed a significant fall in serum vA and RBP levels from initial to week 3 (p<0.005) with no significant change in PA. Control subjects (group IV) showed no significant variation of any parameter over the three week test period. The fall in serum vA and RBP seen among our subjects taking vE alone is consistent with either enhanced hepatic vA uptake or increased vA transport to and utilization by peripheral tissues.