Biochemical Indicators Of Vitamin Research Articles

Retinol and Betacarotene Status in Mother-Infant Dyads and Associations between Them

Background/Aims: Assessing the diet and biochemical indicators of vitamin A deficiency (VAD) in high-risk populations is crucial in cases where this deficiency is mainly caused by chronically inadequate intake. This study aimed to determine the retinol and betacarotene status in mother-infant dyads, and to evaluate the associations between them. Methods: Umbilical cord serum, maternal serum, and colostrum were collected from 134 healthy mothers living in a risk region for VAD. Vitamin A and betacarotene were quantified by liquid chromatography, and dietary information was collected using a food frequency questionnaire. Results: Although the overall mean intakes of vitamin A and betacarotene were considered adequate, 16% of the women had insufficient intake. Mean retinol levels were also adequate, yet low levels were diagnosed in about 8% of the mothers, based on maternal serum and colostrum, and in 16% of the cord serum samples. Retinol and betacarotene were positively associated in cord serum (p = 0.004), maternal serum (p = 0.041), and colostrum (p < 0.001) but was not associated with dietary intake. Conclusions: A diagnosis of adequacy based on mean biochemical and dietary data of this population in fact masks the marginal vitamin A status presented by mothers and children.

A novel device for assessing dark adaptation in field settings.

BackgroundAberrant dark adaptation is common to many ocular diseases and pathophysiological conditions, including vitamin A deficiency, cardiopulmonary diseases, and hypoxia. Scotopic vision and pupillary responsiveness have typically been measured using subjective, time-consuming methods. Existing techniques are particularly challenging for use in developing country settings, where vitamin A deficiency remains a major public health problem. Our aim was design a compact, low cost, and easily operated device to assess dark adaptation in the field.MethodsThe Portable Field Dark Adaptometer (PFDA) incorporates a digital camera, a retinal bleaching flash, and a Ganzfeld light source inside a pair of light-obscuring goggles. After a ~10 min period of dark adaption, the infrared camera digitally records afferent pupillary responses to graded light stimuli (−2.9 to 0.1 log cd/m2). We tested this device in a variety of field settings to assess: a) ease of use and b) whether test data could clearly and accurately depict the well-known dose-response relationship between light intensity and pupil contraction. A total of 822 videos were collected. We used an open source video analysis software to measure pupil size in pixel units. Pupillary responsiveness was expressed as the percent change in pupil size from pre- to post-light exposure. Box plots, t test, and multi-level mixed effects linear regression modeling were used to characterize the relationship between light intensity and pupillary response.ResultsThe PFDA was employed with only minor technical challenges in Bangladesh, Kenya, Zambia, and Peru. Our data show a clear linear increase in pupillary constriction with increasing log light intensity. Light intensity was a strong predictor of pupillary response, regardless of baseline pupil size.ConclusionsThe consistent physiological response demonstrated here supports the use of the PFDA as a reliable tool to measure dark adaptation. As a next step, PFDA measurements will be validated against biochemical indicators of vitamin A status and hypoxemia. Ultimately, this new technology may provide a novel approach for nutritional assessment, with potential clinical applications.Electronic supplementary materialThe online version of this article (doi:10.1186/s12886-015-0062-7) contains supplementary material, which is available to authorized users.

Commentary: Postpartum vitamin A supplementation and infant mortality

Maternal vitamin A deficiency during pregnancy and lactation continues to be a concern in many regions of the world. In this issue of IJE, Gogia and Sachdev report a systematic review and meta-analysis of the effect of maternal postpartum vitamin A supplementation on infant mortality and morbidity. A total of six trials from developing countries included in the meta-analysis revealed no impact on infant mortality [relative risk (RR)1⁄4 1.05, 95% confidence interval (CI)1⁄4 0.92–1.20]. Only one trial that reported morbidity found no effect on diarrhoea or respiratory infection. Out of the six postpartum vitamin A supplementation trials included in the meta-analysis, two large ones were cluster-randomized controlled trials that also included routine pre-conceptional and/or pre-natal supplementation using small weekly doses of vitamin A, representing a supplementation regimen that was restricted neither to the postpartum period nor to the large bolus dose as per the existing WHO guidelines for postpartum supplementation with 200 000 IU of vitamin A within 6 weeks. Additionally, for one of the trials in the meta-analysis, the authors selected infants from the placebo arm of a newborn vitamin A supplementation trial, which was nested within the maternal supplementation trial. Also, three other trials included in the meta-analysis had sample sizes of 300 or less per group. Although these trials reported mortality, they did not have this as a pre-specified outcome, nor were they designed or powered to assess mortality as an outcome. The one trial with the appropriate sample size and which used the currently recommended dose of 400 000 IU vitamin A was conducted in an HIV-infected population. Thus, it is evident that the meta-analysis was based on diverse data of limited utility for discerning a mortality impact. Additionally, it mixed different forms of maternal vitamin A dosing (single with routine) over varying periods of time (from pre-conceptional through postpartum) and therefore both cumulative and timing of dosages are variable. The primary motivation for the policy related to prophylactic postpartum dosing of vitamin A did not stem from reducing infant mortality; instead, the two primary goals for this approach were to improve maternal vitamin A status and the vitamin A status of infants <6 months of age via enhancing the vitamin A content of breast milk. Several previous trials of postpartum vitamin A supplementation, not included in the meta-analysis, have demonstrated improvements in biochemical indicators of vitamin A status in mothers and their breast-fed infants, including increased breast milk concentrations of vitamin A. Based on these studies, in 1997, the WHO, UNICEF and the International Vitamin A Consultative Group (IVACG) provided guidelines for postpartum vitamin A supplementation recommending a single dose of 200 000 IU soon after delivery. This recommendation was updated in 2002 to two doses of 200 000 IU (or 400 000 IU) based on an analysis of expected change and adequacy of infant vitamin A stores suggested to be suboptimal with a single 200 000 IU dose. The revised recommendation, however, has not been widely adopted in developing countries. Only two of the six trials included in the meta-analysis tested the revised 400 000 IU of vitamin A. In a parallel meta-analysis effort, these authors have also evaluated neonatal/early infancy dosing with 50 000 IU vitamin A using data from six trials and shown no impact on infant mortality. However, combining trials which provided vitamin A within 48 h of birth vs those in which infants were dosed later during the first month of life may have yielded the null findings. Limiting the analysis to the former studies, at least in the Asian context, has shown to have a beneficial impact. In a meta-regression analysis, it was shown that newborn vitamin A supplementation likely reduces infant mortality in regions where vitamin A deficiency is common. In contrast, studies from Africa, where vitamin A deficiency was not common, have shown an overall null effect, and a potential negative effect among girls. These apparently contradictory findings have resulted in three more trials of newborn vitamin A supplementation being commissioned by the WHO, Published by Oxford University Press on behalf of the International Epidemiological Association

Folate–vitamin B-12 interaction in relation to cognitive impairment, anemia, and biochemical indicators of vitamin B-12 deficiency

Previous reports on pernicious anemia treatment suggested that high folic acid intake adversely influences the natural history of vitamin B-12 deficiency, which affects many elderly individuals. However, experimental investigation of this hypothesis is unethical, and the few existing observational data are inconclusive. With the use of data from the 1999–2002 National Health and Nutrition Examination Survey (NHANES), we evaluated the interaction between high serum folate and low vitamin B-12 status [ie, plasma vitamin B-12 < 148 pmol/L or methylmalonic acid (MMA) > 210 nmol/L] with respect to anemia and cognitive impairment. With subjects having both plasma folate ≤ 59 nmol/L and normal vitamin B-12 status as the referent category, odds ratios for the prevalence of anemia compared with normal hemoglobin concentration and impaired compared with unimpaired cognitive function were 2.1 (95% CI: 1.1, 3.7) and 1.7 (95% CI: 1.01, 2.9), respectively, for those with low vitamin B-12 status but normal serum folate and 4.9 (95% CI: 2.3, 10.6) and 5.0 (95% CI: 2.7, 9.5), respectively, for those with low vitamin B-12 status and plasma folate > 59 nmol/L. Among subjects with low vitamin B-12 status, mean circulating vitamin B-12 was 228 pmol/L for the normal-folate subgroup and 354 pmol/L for the high-folate subgroup. We subsequently showed increases in circulating homocysteine and MMA concentrations with increasing serum folate among NHANES participants with serum vitamin B-12 < 148 pmol/L, whereas the opposite trends occurred among subjects with serum vitamin B-12 ≥ 148 pmol/L. These interactions, which were not seen in NHANES III before fortification, imply that, in vitamin B-12 deficiency, high folate status is associated with impaired activity of the 2 vitamin B-12–dependent enzymes, methionine synthase and MMA–coenzyme A mutase.

Biochemical indicators of vitamin B 12 and folate insufficiency and cognitive decline

In some prospective studies, associations of serum vitamin B(12) and homocysteine concentrations with cognitive decline have been reported but few have examined the role of methylmalonic acid, a more specific marker of vitamin B(12) deficiency than homocysteine. The aim of the study was to determine whether serum concentrations of vitamin B(12) or selected metabolites are related to cognitive decline. A total of 516 subjects were selected in a stratified random sampling design from among Chicago Health and Aging Project participants for clinical evaluation. We used linear mixed models to examine the association of blood markers of vitamin B(12) status to change in cognitive scores over 6 years. Cognitive function was assessed every 3 years and measured as the sum of standardized scores on four tests. Probable vitamin B(12) deficiency was observed in 14.2% of the sample. Elevated serum concentrations of homocysteine were present in 19.2% of subjects, and of methylmalonic acid, in 36.4%. Higher serum methylmalonic acid concentrations were predictive of faster rates of cognitive decline (beta = -0.00016, SE = 0.0001, p = 0.004) and higher serum vitamin B(12) concentrations were associated with slower rates of cognitive decline (beta = +0.00013, SE < 0.0001, p = 0.005) in multivariable adjusted mixed models. Serum concentrations of homocysteine had no relationship to cognitive decline. Serum methylmalonic acid and vitamin B(12) concentrations may be the more important risk factors for cognitive decline when compared to serum homocysteine concentrations, particularly in older populations exposed to food fortification and possible supplements containing folic acid.

Vitamin K status is associated with childhood bone mineral content

In adult bone, vitamin K contributes to bone health, probably through its role as co-factor in the carboxylation of osteocalcin. In children, the significance of vitamin K in bone-mass acquisition is less well known. The objective of this longitudinal study was to determine whether biochemical indicators of vitamin K status are related to (gains in) bone mineral content (BMC) and markers of bone metabolism in peripubertal children. In 307 healthy children (mean age 11.2 years), BMC of the total body, lumbar spine and femoral neck was determined at baseline and 2 years later. Vitamin K status (ratio of undercarboxylated (ucOC) to carboxylated (cOC) fractions of osteocalcin; UCR) was also measured at both time points. Markers of bone metabolism, sex steroids, vitamin D status and growth hormones were measured at baseline only. Large variations in the levels of the UCR were found at both time-points, indicating a substantial interindividual difference in vitamin K status. Improvement of vitamin K status over 2 years (n 281 children) was associated with a marked increase in total body BMC (r -49.1, P<0.001). The UCR was associated with pubertal stage, markers of bone metabolism, sex hormones and vitamin D status. A better vitamin K status was associated with more pronounced increase in bone mass in healthy peripubertal children. In order to determine the significance of these findings for childhood bone health, additional paediatric studies are needed.

Effect of consumption of the nutrient-dense, freshwater small fishAmblypharyngodon molaon biochemical indicators of vitamin A status in Bangladeshi children: a randomised, controlled study of efficacy

In Bangladesh, some commonly consumed, indigenous, freshwater small fish species (eaten whole with bone, head and eyes) such as mola (Amblypharyngodon mola) are nutrient-dense, containing preformed vitamin A as retinol and especially 3,4-dehydroretinol. The objective of the present randomised, controlled efficacy study was to evaluate the effects of mola on biochemical indicators of vitamin A status. Children (n 196), aged 3-7 years, with serum retinol 0.36-0.75 micromol/l, were randomly allocated to one of three treatment groups to receive a daily test meal (6 d/week for 9 weeks) of rice and vegetable curry (no vitamin A) ad libitum and 50 g fish curry consisting of: (1) mola, 600 retinol activity equivalents (RAE) (using 40 % biological activity of 3,4-dehydroretinol isomers) (experimental group, n 66); (2) rui (Labeo rohita), a large fish (no vitamin A), with added retinyl palmitate, 600 RAE (positive control group, n 65); or (3) rui, 0 RAE (negative control group, n 65). The nutrient compositions of the dishes were analysed. After 9 weeks, no significant treatment effects were observed for serum retinol (P = 0.52) and retinol-binding protein (P = 0.81) in the experimental group compared with the negative control, whereas the positive control improved significantly (P < 0.001). The present results do not suggest conversion of the large amount of 3,4-dehydroretinol in mola curry to retinol. Further research on the functional effect of mola in humans is needed. Mola is a nutrient-dense animal-source food, rich in haem Fe, Zn and especially Ca, thus consumption of mola in Bangladesh should continue to be encouraged.

Vitamin K, bone turnover, and bone mass in girls

Vitamin K has been suggested to have a role in bone metabolism, and low vitamin K intake has been related to low bone density and increased risk of osteoporotic fracture. The objective of this study was to determine whether phylloquinone (vitamin K(1)) intake and biochemical indicators of vitamin K status are related to bone mineral content (BMC) and markers of bone formation and bone resorption in girls. Vitamin K status [plasma phylloquinone concentration and percentage of undercarboxylated osteocalcin (%ucOC)] was measured at baseline in a study of 245 healthy girls aged 3-16 y. Cross-linked N-telopeptide of type 1 collagen (NTx) breakdown, osteocalcin, and bone-specific alkaline phosphatase were measured to reflect bone resorption and formation. BMC of the total body, lumbar spine, and hip and dietary phylloquinone intake were measured annually for 4 y. Phylloquinone intake (median: 45 microg/d) was not consistently associated with bone turnover markers or BMC. Better vitamin K status (high plasma phylloquinone and low %ucOC) was associated with lower bone resorption and formation. Plasma phylloquinone was inversely associated with NTx and osteocalcin concentrations (P < 0.05), and %ucOC was positively associated with NTx and bone-specific alkaline phosphatase concentrations (P < 0.05). Indicators of vitamin K status were not consistently associated with current BMC or gain in BMC over the 4-y study period. Better vitamin K status was associated with decreased bone turnover in healthy girls consuming a typical US diet. Randomized phylloquinone supplementation trials are needed to further understand the potential benefits of phylloquinone on bone acquisition in growing children.

Relationships between vitamin A, iron status and helminthiasis in Bangladeshi school children.

To explore the relationships between biochemical indicators of vitamin A and iron status and the intestinal helminths Ascaris lumbricoides and hookworm in primary school children. Two rural governmental schools in northwestern Bangladesh. Cross-sectional study. The sample consisted of 164 children in grades 3-5. Serum retinol and beta-carotene (by high-performance liquid chromatography, HPLC), haemoglobin (HemoCue), ferritin (enzyme-linked immunoadsorbent assay, ELIZA) and height and weight were measured. Dietary intake of vitamin A was assessed using a food frequency questionnaire and faecal analyses were done using Stoll's egg-count technique. The mean serum retinol was 26.8 microg dl(-1) and 20% had a level of < 20 microg dl(-1), the cut-off value for low vitamin A status. There was a strong positive association between serum beta-carotene and serum retinol (r = 0.44, P < 0.001), suggesting those with higher retinol levels had a higher carotene intake. Thirty-one per cent were anaemic (Hb < 11.5 g dl(-1)), 30% had iron deficiency (serum ferritin < 12.0 microg l(-1)) and 14% were suffering from iron deficiency anaemia. Children with a serum retinol level of 20 microg dl(-1) had significantly lower ferritin (14.0 compared to 26.0 microg l(-1), P = 0.005) and Hb levels (11.7 compared to 12.4 g dl(-1), P = 0.005) than those with higher levels. The proportion of iron deficiency anaemia was significantly greater among children with hookworm. Our data suggest that hookworm exerts its impact on iron status independently of the vitamin A status of the host. Programmes to improve iron status should consider including both vitamin A prevention programmes and deworming.

“THE SU.VI.MAX STUDY”: A Primary Prevention Trial using Nutritional Doses of Antioxidant Vitamins and Minerals in Cardiovascular Diseases and Cancers

The “ SUpplementation en VItamines et Minéraux Antio Xydants” (SU.VI.MAX) Study is a randomized double-blind, placebo-controlled, primary-prevention trial which started in 1994 in France. This epidemiologic study is designed to test the efficacy of a daily supplementation with antioxidant vitamins (vitamin C, 120 mg, vitamin E, 30 mg, and β-carotene, 6 mg) and minerals (selenium, 100 μg, and zinc, 20 mg) at nutritional doses, in reducing the main causes of premature death (cancers and cardiovascular diseases); 12,735 eligible subjects (women aged 35 to 60 years, and men aged 45 to 60 years) were included in 1994 and and will be followed up for 8 years. Participants undergo a yearly visit consisting, every other year, of either biological sampling or clinical examination. They also regularly provide information on health events and dietary intake by filling out computerized questionnaires using the Minitel Telematic Network. After 2 years of supplementation, biochemical indicators of vitamin and trace element status reach reasonable level without reaching concentrations as high as those observed in intervention studies, which tested relatively high doses of antioxidants, and ended up with higher risk of pathology.

Effects of Supplementation with a Combination of Antioxidant Vitamins and Trace Elements, at Nutritional Doses, on Biochemical Indicators and Markers of the Antioxidant System in Adult Subjects

Objective: To test the impact of supplementation with nutritional doses of antioxidant nutrients on biochemical indicators of vitamin and trace element levels.Design: A randomized double-blind trial was performed comparing two groups receiving daily either a combination of vitamins (beta-carotene, 6 mg; vitamin C, 120 mg; and vitamin E, 30 mg) and trace elements (zinc, 20 mg; and selenium, 100 μg); or a placebo.Subjects: 401 subjects (166 males aged 45 to 60 years and 235 females aged 35 to 60 years).Measure of outcome: Biological markers of vitamin and trace element status and free radical parameters were measured initially, 3 months, and 6 months after supplemention.Results: Mean serum concentrations of alpha-tocopherol, vitamin C, beta-carotene, zinc and selenium increased significantly after 3 months of supplementation in the group receiving multivitamins associated with minerals. At baseline, 18.2% of the men and 5.1% of the women had low concentrations of serum vitamin C (<20 μmol/l); 2.4% of the men and 17% of the women presented low concentrations of serum retinol (<1.4 μmol/l); 18.7% of men and 10% of women had serum beta-carotene <0.30 μmol/l. None of the study subjects had serum alpha-tocopherol concentrations below the limit cut-off point (<9.3 μmol/l). Low serum zinc concentrations (<10.7 μmol/l) were found in 15.1% of men and 23.8% of women. Low serum selenium concentrations (<0.75 μmol/l) were found in 6% of men and 6.4% of women. A significant increase in plasma and red cell GPx activity was observed in groups receiving supplementation. No modifications were observed after 6 months of supplementation for malondyaldehyde.Conclusion: This study demonstrates the efficacy of an intake of antioxidant vitamins and trace elements, given at nutritional doses, on biochemical indicators of vitamin and trace elements status.

Fermentable Dietary Fibers Elevate Urinary Methylmalonate and Decrease Propionate Oxidation in Rats Deprived of Vitamin B-12

This study examines the effect of dietary fiber supplements of different degrees of bacterial fermentability on biochemical indicators of vitamin B-12 deficiency in rats. Groups of rats were fed a fiber-free diet deficient in vitamin B-12 or the fiber-free diet diluted with 5% of a poorly fermentable dietary fiber (cellulose, lignin or alginic acid) or a highly fermentable fiber (pectin, guar gum or xylan). Poorly fermentable fibers had no significant effect on apparent B-12 status, whereas the highly fermentable fibers significantly increased urinary methylmalonic acid and depressed oxidation of [14C]propionate to 14CO2. Pectin consistently induced significantly greater effects than did xylan or guar gum. The data are consistent with the hypothesis that fermentable fibers stimulate bacterial propionate production and exaggerate certain biochemical indicators of B-12 deficiency. Since pectin had a more pronounced effect than did other fermentable fibers, the possibility that pectin may also interfere with B-12 absorption requires further study.

Biochemical indicators of vitamin A depletion in children with cholestasis

Biochemical indicators of vitamin A status were measured in 24 children (1 month to 6 years old) with severe cholestasis starting early in life and in 21 children (3 months to 13 years old) with liver disease but without cholestasis. Liver vitamin A concentrations, expressed as micrograms of retinol per gram of liver (mean +/- S.D.), were 6.3 +/- 7.1 (range: 0.14 to 28) and 143 +/- 108 (range: 18 to 424), respectively, in cholestatic and non-cholestatic children. In infants less than 6 months of age, liver vitamin A values less than 10 micrograms per gm were found in 14 of 17 cholestatic children but in none of 3 non-cholestatic subjects. Plasma vitamin A values, expressed as micrograms of retinol per deciliter (mean +/- S.D.), were 23 +/- 18 (range: 3 to 62) and 46 +/- 33 (range: 14 to 125), respectively, for the two groups. Plasma retinol values less than 10 micrograms per dl were always associated with liver concentrations less than 10 micrograms per gm. Plasma retinol-binding protein was only reduced to 71% of control values in cholestatic children. The fatty acid composition of liver retinyl esters was unaffected by any condition studied. Infants with chronic cholestasis are in a precarious nutritional status very early in life relative to liver reserves of vitamin A. Plasma vitamin A values, unless less than 10 micrograms retinol per dl, are poor indicators of inadequate vitamin A status.