Showing papers by "Tor A. Strand published in 2020"

Early Nutritional Interventions with Zinc, Selenium and Vitamin D for Raising Anti-Viral Resistance Against Progressive COVID-19.

Abstract: Objectives: The novel coronavirus infection (COVID-19) conveys a serious threat globally to health and economy because of a lack of vaccines and specific treatments. A common factor for conditions that predispose for serious progress is a low-grade inflammation, e.g., as seen in metabolic syndrome, diabetes, and heart failure, to which micronutrient deficiencies may contribute. The aim of the present article was to explore the usefulness of early micronutrient intervention, with focus on zinc, selenium, and vitamin D, to relieve escalation of COVID-19. Methods: We conducted an online search for articles published in the period 2010–2020 on zinc, selenium, and vitamin D, and corona and related virus infections. Results: There were a few studies providing direct evidence on associations between zinc, selenium, and vitamin D, and COVID-19. Adequate supply of zinc, selenium, and vitamin D is essential for resistance to other viral infections, immune function, and reduced inflammation. Hence, it is suggested that nutrition intervention securing an adequate status might protect against the novel coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome - coronavirus-2) and mitigate the course of COVID-19. Conclusion: We recommended initiation of adequate supplementation in high-risk areas and/or soon after the time of suspected infection with SARS-CoV-2. Subjects in high-risk groups should have high priority as regards this nutritive adjuvant therapy, which should be started prior to administration of specific and supportive medical measures.

Effects of vitamin B12 supplementation on neurodevelopment and growth in Nepalese Infants: A randomized controlled trial.

Abstract: Background Vitamin B12 deficiency is common and affects cell division and differentiation, erythropoiesis, and the central nervous system. Several observational studies have demonstrated associations between biomarkers of vitamin B12 status with growth, neurodevelopment, and anemia. The objective of this study was to measure the effects of daily supplementation of vitamin B12 for 1 year on neurodevelopment, growth, and hemoglobin concentration in infants at risk of deficiency. Methods and findings This is a community-based, individually randomized, double-blind placebo-controlled trial conducted in low- to middle-income neighborhoods in Bhaktapur, Nepal. We enrolled 600 marginally stunted, 6- to 11-month-old infants between April 2015 and February 2017. Children were randomized in a 1:1 ratio to 2 μg of vitamin B12, corresponding to approximately 2 to 3 recommended daily allowances (RDAs) or a placebo daily for 12 months. Both groups were also given 15 other vitamins and minerals at around 1 RDA. The primary outcomes were neurodevelopment measured by the Bayley Scales of Infant and Toddler Development 3rd ed. (Bayley-III), attained growth, and hemoglobin concentration. Secondary outcomes included the metabolic response measured by plasma total homocysteine (tHcy) and methylmalonic acid (MMA). A total of 16 children (2.7%) in the vitamin B12 group and 10 children (1.7%) in the placebo group were lost to follow-up. Of note, 94% of the scheduled daily doses of vitamin B12 or placebo were reported to have been consumed (in part or completely). In this study, we observed that there were no effects of the intervention on the Bayley-III scores, growth, or hemoglobin concentration. Children in both groups grew on an average 12.5 cm (SD: 1.8), and the mean difference was 0.20 cm (95% confidence interval (CI): −0.23 to 0.63, P = 0.354). Furthermore, at the end of the study, the mean difference in hemoglobin concentration was 0.02 g/dL (95% CI: −1.33 to 1.37, P = 0.978), and the difference in the cognitive scaled scores was 0.16 (95% CI: −0.54 to 0.87, P = 0.648). The tHcy and MMA concentrations were 23% (95% CI: 17 to 30, P < 0.001) and 30% (95% CI: 15 to 46, P < 0.001) higher in the placebo group than in the vitamin B12 group, respectively. We observed 43 adverse events in 36 children, and these events were not associated with the intervention. In addition, 20 in the vitamin B12 group and 16 in the placebo group were hospitalized during the supplementation period. Important limitations of the study are that the strict inclusion criteria could limit the external validity and that the period of vitamin B12 supplementation might not have covered a critical window for infant growth or brain development. Conclusions In this study, we observed that vitamin B12 supplementation in young children at risk of vitamin B12 deficiency resulted in an improved metabolic response but did not affect neurodevelopment, growth, or hemoglobin concentration. Our results do not support widespread vitamin B12 supplementation in marginalized infants from low-income countries. Trial registration ClinicalTrials.gov NCT02272842 Universal Trial Number: U1111-1161-5187 (September 8, 2014) Trial Protocol: Original trial protocol: PMID: 28431557 (reference [18]; study protocols and plan of analysis included as Supporting information).

Effect of prebiotic and probiotic supplementation on neurodevelopment in preterm very low birth weight infants: findings from a meta-analysis.

Abstract: Preterm very low birth weight (VLBW) infants are at risk of gut dysbiosis and neurodevelopmental deficits. Prebiotics and probiotics may modulate gut microbiota and influence brain functions. This review synthesizes literature on effect of prebiotic and/or probiotic supplementation in preterm VLBW on their neurodevelopmental outcomes. Search was done using PubMed and CENTRAL. Randomized controlled trials (RCTs) in preterm infants (<37 weeks gestation) and/or infants with birth weight <1500 g that evaluated the effect of prebiotic and/or probiotic supplementation on neurodevelopmental outcomes were included. Weighted mean difference in cognitive and motor scores; pooled relative risks for cognitive and motor impairment, cerebral palsy, hearing, and visual impairment were estimated. Quality of evidence was assessed using the GRADE criteria. Out of 275 articles identified, seven were included for review. All, except one, were done in preterms <33 weeks of gestation. Age of assessment of outcomes was ≥18–22 months of corrected age in five studies. Interventions did not decrease or increase the risk of cognitive and motor impairment, cerebral palsy, visual, and hearing impairment. Quality of evidence was “low” to “very low.” Limited evidence from RCTs does not demonstrate a difference in neurodevelopmental outcomes between prebiotic/probiotic treated and untreated control groups.

Vitamin D status in early childhood is not associated with cognitive development and linear growth at 6–9 years of age in North Indian children: a cohort study

Abstract: Vitamin D is important for brain function and linear growth. Vitamin D deficiency during pregnancy has been linked with impaired neurodevelopment during early childhood. However, there is limited evidence from population-based studies on the long-term impact of vitamin D deficiency on cognitive development and linear growth. The objective of the current analysis is to examine whether vitamin D deficiency during infancy and early childhood is associated with cognitive development and linear growth measured in school age. This is a follow-up study of a placebo-controlled trial among 1000 North Indian children 6–30 months of age. We measured growth and neurodevelopment in 791 of these children when they were 6–9 years old. Neurodevelopment was measured using the Wechsler Intelligence Scale for Children, 4th edition INDIA, the Crichton Verbal Scale, NEPSY-II subtests, and the BRIEF 2. We categorized vitamin D concentrations during infancy and early childhood according to the US Institute of Medicine’s recommendations; serum 25(OH)D 20 ng/ml as sufficient. In multivariable regression models, adjusting for relevant confounders, we estimated the association between vitamin D status, growth and neurodevelopmental outcomes. Among the 791 children, baseline vitamin D status was available for 716. Of these, 45.8% were vitamin D deficient, 32.7% were inadequate, and 21.5% were sufficient. Vitamin D status was not associated with any of the cognitive outcomes or linear growth [Adjusted β coefficient for height for age z-score between deficient and sufficient children was − 0.06 (95% CI − 0.24 to 0.11)] at follow up. Our findings do not support the notion that poor vitamin D status in early childhood is an important limitation for cognitive development and linear growth. The trial was first registered at www.clinicaltrials.gov as NCT00717730 in July, 2008, and at CTRI/2010/091/001090 in August, 2010 and then as CTRI/2016/11/007494 in November 2016.

An analysis of clinical predictive values for radiographic pneumonia in children

Abstract: Introduction : Health care providers in resource-limited settings rely on the presence of tachypnea and chest indrawing to establish a diagnosis of pneumonia in children. We aimed to determine the test characteristics of commonly assessed signs and symptoms for the radiographic diagnosis of pneumonia in children 0-59 months of age. Methods : We conducted an analysis using patient-level pooled data from 41 shared datasets of pediatric pneumonia. We included hospital-based studies in which >80% of children had chest radiography performed. Primary endpoint pneumonia (presence of dense opacity occupying a portion or entire lobe of the lung or presence of pleural effusion on chest radiograph) was utilized as the reference criterion radiographic standard. We assessed the sensitivity, specificity, and likelihood ratios for clinical findings, and combinations of findings, for the diagnosis of primary endpoint pneumonia among children 0-59 months of age. Results : Ten studies met inclusion criteria comprising 15,029 children; 24.9% (n=3,743) had radiographic pneumonia. The presence of age-based tachypnea demonstrated a sensitivity of 0.92 and a specificity of 0.22 while lower chest indrawing revealed a sensitivity of 0.74 and specificity of 0.15 for the diagnosis of radiographic pneumonia. The sensitivity and specificity for oxygen saturation <90% was 0.40 and 0.67 respectively, and was 0.17 and 0.88 for oxygen saturation <85%. Specificity was improved when individual clinical factors such as tachypnea, fever, and hypoxemia were combined, however, the sensitivity was lower. Conclusions : No single sign or symptom was strongly associated with radiographic primary end point pneumonia in children. Performance characteristics were improved by combining individual signs and symptoms.

Mild to Moderate Iodine Deficiency and Inadequate Iodine Intake in Lactating Women in the Inland Area of Norway.

Abstract: Breastfed infants are dependent on an adequate supply of iodine in human milk for the production of thyroid hormones, necessary for development of the brain. Despite the importance of iodine for infant health, data on Norwegian lactating women are scarce. We measured iodine intake and evaluated iodine status and iodine knowledge among lactating women. From October to December 2018, 133 mother-infant pairs were recruited in a cross-sectional study through two public health care centers in Lillehammer and Gjovik. Each of the women provided two human milk specimens, which were pooled, and one urine sample for analysis of iodine concentration. We used 24-hour dietary recall and food frequency questionnaire (FFQ) to estimate short-term and habitual iodine intake from food and supplements. The median (P25, P75) human milk iodine concentration (HMIC) was 71 (45, 127) µg/L-of which, 66% had HMIC <100 µg/L. The median (P25, P75) urinary iodine concentration (UIC) was 80 µg/L (52, 141). The mean (± SD) 24-hour iodine intake and habitual intake was 78 ± 79 µg/day and 75 ± 73 µg/day, respectively. In conclusion, this study confirms inadequate iodine intake and insufficient iodine status among lactating women in the inland area of Norway and medium knowledge awareness about iodine.

Dietary Intake and Biomarkers of Folate and Cobalamin Status in Norwegian Preschool Children: The FINS-KIDS Study

Abstract: BACKGROUND Folate and cobalamin (vitamin B-12) are essential for growth and development. However, few population-based studies have investigated B-vitamin status in children. OBJECTIVES This study aimed to assess biomarkers of folate and vitamin B-12 status and to explore their dietary determinants in healthy Norwegian children. METHODS Using baseline data obtained from a randomized controlled trial on the effect of fish intake on neurodevelopment in children aged 4-6 y, we measured the plasma concentrations of folate, cobalamin, total plasma homocysteine (tHcy), and methylmalonic acid (MMA). Food-frequency questionnaires (FFQs) were used to assess dietary intake. We used unadjusted and multiple linear regression models to explore the determinants of biomarker concentrations. RESULTS The median (IQR) of plasma folate (n = 197) and plasma cobalamin (n = 195) concentrations were 15.2 (12.2-21.1) nmol/L and 785 (632-905) pmol/L, respectively. Plasma folate concentrations of 0.26 μmol/L) and 8 children had elevated tHcy concentrations (>6.5 μmol/L). Plasma folate concentration was inversely correlated with tHcy (ρ = -0.24, P < 0.001); we found no correlation between tHcy and cobalamin (ρ = -0.075, P = 0.30). Children who consumed vitamin supplements had 51% higher plasma folate concentrations (P < 0.0001) than those who did not. Consumption of red meat for dinner more than twice a week was associated with 23% lower plasma folate (P < 0.01). No other significant associations between dietary intake and the biomarkers were observed. CONCLUSIONS The Norwegian preschool children from this cohort had adequate vitamin B-12 status. Poor folate status was common and associated with elevated tHcy. The implications of poor folate status during childhood should be a prioritized research question. This trial was registered at ClinicalTrials.gov as NCT02331667.

Vitamin B12, Folate, and Cognition in 6- to 9-Year-Olds: A Randomized Controlled Trial

Abstract: BACKGROUND AND OBJECTIVES: Vitamin B12 and folate are important for normal brain development. Our objective for this study was to measure the effects of 6-month supplementation of vitamin B12 and/or folic acid in early childhood on cognition when the children were 6 to 9 years old. METHODS: The study is a follow-up of a factorial randomized, double-blind, placebo-controlled trial in 1000 North Indian children. Children 6 to 30 months of age were randomly assigned to receive a placebo or 1.8 µg of vitamin B12, 150 mg of folic acid, or both daily for 6 months. After 6 years, we re-enrolled 791 of these children for cognitive assessments. We compared the scores of the main outcomes (the Wechsler Intelligence Scale for Children, Fourth Edition [India], the Crichton Verbal Scale, and subtests of the NEPSY-II) between the study groups. We also measured the associations between markers of the B vitamins (plasma cobalamin, folate, and total homocysteine concentrations) in early childhood and the cognitive outcomes. RESULTS: There were no differences between the intervention groups and the placebo group on the cognitive outcomes. Plasma cobalamin, folate, and total homocysteine concentrations in early childhood were associated with the cognitive outcomes at follow-up in the unadjusted models. These associations disappeared in models adjusted for relevant confounders. CONCLUSIONS: Our findings, from both an observational and a randomized design suggest that vitamin B12 and folate in children 6 to 36 months have limited public health relevance for long-term cognition.

Vitamin B-12 Supplementation during Pregnancy and Early Lactation Does Not Affect Neurophysiologic Outcomes in Children Aged 6 Years

Abstract: Background Deficiency of vitamin B-12 is common in pregnant Indian women. Assessment of neurophysiological measures using event-related potentials (ERPs) may yield additional information on the effects of maternal B-12 supplementation on child brain function. Objectives The objective of the study was to evaluate the effects of vitamin B-12 supplementation (50 μg daily orally) during pregnancy on the childhood ERP measures of positive waveform ∼300 ms after stimulus (P300) and mismatch negativity. Methods This study was a follow-up of children born to pregnant women who received oral vitamin B-12 supplements (n = 62) compared with children of pregnant women who received placebo (n = 70) from a randomized controlled trial. The mean ± SD child age was 72 ± 1 mo. We used the Enobio system to assess the ERP measures P300 and mismatch negativity. Results There were no significant differences in the primary outcomes, amplitudes, and latencies of the P300 results and the mismatch negativity between children in the supplementation and placebo groups. We combined the intervention and placebo groups for secondary analyses. On multiple variable regression analysis after adjusting for treatment group, intrauterine growth restriction, and home environment, P300 amplitude in children was significantly higher in the lowest tertile of third-trimester maternal methylmalonic acid (MMA) concentrations (β = 3034.04; 95% CI: 923.24, 5144.83) compared with the highest MMA tertile (β = 1612.12; 95% CI: -258.86, 3483.10, P = 0.005). Conclusions While no significant effects of maternal vitamin B-12 supplementation on children's ERP measures were seen at 72 mo, elevated maternal MMA concentrations in the third trimester were negatively associated with P300 amplitude in children. It may be worthwhile to study the impact of maternal and infant vitamin B-12 supplementation on childhood brain structure and function in longer and larger trials. The parent trial was registered at clinicaltrials.gov as NCT00641862.

Prevalence of Underweight, Overweight, and Obesity in Adults in Bhaktapur, Nepal in 2015–2017

Abstract: Introduction: There is an increase in the double burden of malnutrition globally, with a particular rise documented in Asia. In Nepal, undernutrition has been prevalent for decades. Today, however, the incidence of overweight and obesity (OWOB) in the country has increased substantially. There is a need to conduct local studies reporting on the concurrent burden of both underweight and OWOB across adult populations. This study addresses this need by describing the distribution of body mass index (BMI) in a defined population of adults living in the peri-urban community of Bhaktapur, Nepal. Material and methods: For this cross-sectional analysis, we used data that were available from 600 women and 445 men whose children were enrolled in an individually randomized, double-blind, placebo-controlled trial assessing the effect of daily vitamin B12 supplementation. Upon enrolment of their 6-11-month old children, mothers and fathers were interviewed about their socio-demographic details. In addition, their weight and height were measured by trained field workers. Each parent's BMI was calculated as the ratio of body weight (in kg) and height squared (in m), expressed as kg/m2, and categorized according to the WHO recommendation. We used linear and multinomial logistic regression models to assess associations between the BMI of the mothers and fathers, and their baseline characteristics. Results: The mean BMI was 23.7 kg/m2 for both the mothers and fathers with a standard deviation (SD) of 3.6 and 3.7, respectively. The proportion categorized as underweight, overweight, and obese was also similar in the two groups with around 5% being underweight, 30% being overweight and 5% being obese. Age was positively associated with BMI in both groups. Those categorized as daily wage earner had a lower mean BMI than those in other occupational groups. Conclusion: Our results contribute to documenting the burden of both under- and overnutrition in a selected group of young adults living in a peri-urban community in Nepal. As Nepal is undergoing an improvement in its economic situation, as well as a nutrition transition, it is important to provide sufficient information to enable timely action, and evidence-based decision-making to prevent a further increase in Nepal's growing double burden of malnutrition.

The Feasibility of the Full and Modified Versions of the Alarm Distress Baby Scale (ADBB) and the Prevalence of Social Withdrawal in Infants in Nepal.

Abstract: Background Sustained social withdrawal in infancy may have organic and nonorganic causes and could hinder normal development. The Alarm Distress Baby (ADBB) scale is a widely validated screening tool of social withdrawal in children 2-24 months. The aim of the current study was to evaluate the full and modified ADBB in Nepalese infants in a community-based study. Methods We enrolled 600 infants who were video recorded during a pediatric examination. The 36 infants first enrolled were scored by an expert rater, and the subsequent 64 infants were scored by two trained staff with the full ADBB scale. Of the 600 enrolled infants, 597 videos (including the 100 infants scored with the full ADBB) were scored with the modified ADBB (m-ADBB) scale by the trained staff, with 7% double scoring. We measured the interrater agreement and psychometric properties of both scales. Results In the 64 infants scored with the full ADBB by two raters, the concordance correlation coefficients (CCCs) indicated poor interrater agreement. For the m-ADBB, the CCCs were better indicating acceptable agreement between raters. The greatest lower bound (GLB) for reliability coefficient for the full ADBB scored by an expert rater indicated good internal consistency, whereas the GLB coefficient for the m-ADBB indicated poorer internal consistency. The Spearman correlation coefficient between the total scores of the two versions was 0.82 (P < 0.001). Among the infants scored with the full ADBB, 25% had a score above cutoff (≥5). Scored with the m-ADBB in the full sample, 11.4% of the infants had a score above the suggested cutoff (≥2). In both versions, children achieved high scores on vocalization. Conclusion Our findings suggest that the m-ADBB is an acceptable approach to achieve adequate interrater agreement in a large community-based study in Nepal. Results indicate high prevalence of social withdrawal in this population. There are, however, uncertainties on the internal consistency of the scales in this setting, and the validity of the scales needs to be investigated further. More effective training strategies for administration and additional cultural-specific instructions could be important measures to explore before implementing the scale further in this setting.

Vitamin B12 concentrations in milk from Norwegian women during the six first months of lactation.

Abstract: Human milk vitamin B12 (B12) concentrations depend on maternal status and intake; only few data are available in high-income countries. We assessed human milk B12 concentrations during the first 6 months postpartum in Norwegian women and its association with maternal dietary B12 intake and maternal urinary methylmalonic acid (MMA) concentration. In this cross-sectional study, 175 mothers, exclusively (80%) or partially (20%) breastfeeding, were included. Milk B12 was measured by IMMULITE®/IMMULITE® 1000 B12 competitive protein binding assay and urinary MMA relative to creatinine (MMA/Cr) by liquid chromatography–tandem-mass spectrometry. Maternal habitual B12 intake and supplement use were estimated using a food frequency questionnaire. Mean human milk B12 concentration was 327 pmol/L (range 140–1089), with 402 pmol/L at 1 month (n = 21), 333 pmol/L at four months (n = 32), and 299 pmol/L at 6 months (n = 21). Maternal B12 intake was 5 µg/d, 89% met the Estimated Average Requirement, and supplement use did not affect milk B12 concentrations. MMA/Cr was low in all women compared with published data. In exclusively breastfeeding women, MMA/Cr (beta (95% CI) −42.5 (−82.5, −2.5) and time since birth (−4.9 (−9.6, −0.3)) were significant predictors of human milk B12 concentrations. There was no association between total B12 intake and milk B12 concentration or between total B12 intake and MMA/Cr. Maternal B12 status and human milk B12 concentrations are likely sufficient, based on adequate maternal B12 dietary intake combined with low urinary MMA concentrations. Nevertheless, milk B12 concentration fell during 6 months postpartum while maternal B12 status did not change.

Health-Related Behaviors in Adolescents Mediate the Association between Subjective Social Status and Body Mass Index.

Abstract: The aim of this study was to explore the association between adolescent subjective social status (SSS) and body mass index (BMI) at two different time points and to determine whether this association was mediated by health-related behaviors. In 2002 (n = 1596) and 2017 (n = 1534), tenth-grade students (15-16 years old) in schools in the District of Oppland, Norway, completed a survey. Four categories of perceived family economy were measured as SSS, and structural equation modeling was performed, including a latent variable for unhealthy behavior derived from cigarette smoking, snuff-use, and alcohol-drinking as well as dietary and exercise as mediators. No linear association was found between SSS and BMI in 2002 (standardized s -0.02, (95% confidence interval (CI) -0.07, 0.03)). However, an association was present in 2017 (standardized s -0.05 (95% CI -0.10, -0.001)), indicating that BMI decreased by 0.05 standard deviations (0.05 × 3.1 = 0.16 BMI unit) for every one-category increase in SSS. This association was mediated by exercise (standardized s -0.013 (95% CI -0.02, -0.004) and unhealthy behavior (standardized s -0.009 (95% CI -0.002, -0.04)). In conclusion, a direct association between SSS and BMI was found in 2017 in this repeated cross-sectional survey of 15-16-year-old Norwegian adolescents. This association was mediated through health-related behavior.

Association of Maternal Plasma Total Cysteine and Growth among Infants in Nepal: A Cohort Study.

Abstract: Cysteine is a semi-essential amino acid that has been positively associated with growth in children. However, transgenerational effects remain unclear. The aim of this analysis was to assess whether maternal plasma total cysteine (tCys) concentration is associated with various growth indicators in infants living in peri-urban settings in Bhaktapur, Nepal. We used data from the 561 mothers enrolled in an ongoing randomized controlled trial. We built linear regression models to evaluate the associations between maternal tCys and birth weight, length-for-age Z-scores (LAZ) and weight-for-length Z-scores (WLZ) at birth and six months of age. Maternal tCys was inversely associated with birth weight among boys after adjusting for confounders (p < 0.05). In addition, there was a negative association between maternal tCys and LAZ at birth (p < 0.01). No associations between maternal tCys and the other anthropometric indicators were found significant, although there was a tendency for maternal tCys to be associated positively with WLZ at birth among girls (p < 0.10). This is a first study evaluating transgenerational relation of tCys on growth in infants. Further, larger and more comprehensive studies are needed to determine if and how maternal tCys alters child growth.

Risk Assessment of "Other Substances" – L-Histidine

Abstract: The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), assessed the risk of "other substances" in food supplements and energy drinks sold in Norway. VKM has assessed the risk of doses given by NFSA. These risk assessments will provide NFSA with the scientific basis for regulating "other substances" in food supplements. "Other substances" are described in the food supplement directive 2002/46/EC as substances other than vitamins or minerals that have a nutritional and / or physiological effect. It is added mainly to food supplements, but also to energy drinks and other foods. In this series of risk assessments of "other substances" VKM has not evaluated any claimed beneficial effects from these substances, only possible adverse effects. The present report is a risk assessment of specified doses of L-histidine in food supplements, and it is based on previous risk assessments and articles retrieved from a literature search.Histidine; food supplement According to information from NFSA, L-histidine is an ingredient in food supplements and energy drinks sold in Norway. NSFA has requested a risk assessment of 550 and 600 mg/day of L-histidine from food supplements. The recommended dietary allowance (RDA) for adults of L-histidine is 14 mg/kg body weight/day (IOM, 2005), which corresponds to 980 mg/day for a 70 kg person. Oral doses has a bioavailiability of 80% or higher. Foods rich in histidine are generally protein rich foods such as meat, dairy products, legumes, fish, nuts, seeds, eggs and whole grains. Based on NHANES III (1988-1994), the overall mean intake of Lhistidine from food and food supplements in the United States was 2.2 g/day. L-histidine is a conditionally essential amino acid which is a normal constituent of most body proteins. L-histidine is also a part of many plasma proteins. It has anti-oxidant and antiinflammatory properties. Moreover, L-histidine is also a precursor of histamine and is necessary for the regulation and metabolism of trace elements such as metal ions. The human body has a large pool of L-histidine in plasma proteins, but also as carnosine in skeletal muscles and in haemoglobin. Due to the lack of adequate scientific information, a no observed adverse effect level (NOAEL) or lowest observed adverse effect level (LOAEL) have not been identified, and a tolerable upper intake level for histidine has not been established. Effects of histidin supplementation have been studied in trials with duration of up to 3-4 months. Previous risk assessments concluded that supplementation with 4.0 to 4.5 g/day of L-histidine above the dietary content does not have adverse effects in human beings, and new data retrieved in the present literature search were in accordance with these conclusions. No particular population groups have been identified as particularly susceptible to adverse effects of consuming histidine supplements. We have not identified any studies in children or adolescents. VKM concludes that: In adults (≥18 years), the specified doses 550 and 600 mg/day L-histidine in food supplements are unlikely to cause adverse health effects. In adolescents (14 to <18 years), the specified doses 550 and 600 mg/day L-histidine in food supplements are unlikely to cause adverse health effects. In children (10 to <14 years), the specified doses 550 and 600 mg/day L-histidine in food supplements are unlikely to cause adverse health effects. Children younger than 10 years were not within the scope of the present risk assessment.

Association of Plasma Total Cysteine and Anthropometric Status in 6-30 Months Old Indian Children.

Abstract: High-quality protein has been associated with child growth; however, the role of the amino acid cysteine remains unclear. The aim was to measure the extent to which plasma total cysteine (tCys) concentration is associated with anthropometric status in children aged 6–30 months living in New Delhi, India. The study was a prospective cohort study including 2102 children. We calculated Z-scores for height-for-age (HAZ), weight-for-height (WHZ), or weight-for-age (WAZ) according to the WHO Child Growth Standards. We used multiple regression models to estimate the association between tCys and the anthropometric indices. A high proportion of the children were categorized as malnourished at enrolment; 41% were stunted (HAZ ≤ −2), 19% were wasted (WHZ ≤ −2) and 42% underweight (WAZ ≤ −2). Plasma total cysteine (tCys) was significantly associated with HAZ, WHZ and WAZ after adjusting for relevant confounders (p 25th percentile. In young Indian children from low-to-middle socioeconomic neighborhoods, a low plasma total cysteine concentration was associated with an increased risk of poor anthropometric status.

No benefits of prolonged vitamin D3 supplementation for adaptations to resistance training in old adults

Abstract: Background: Lifestyle therapy with resistance training is a potent measure to counteract age-related loss in muscle strength and mass. Unfortunately, many individuals fail to respond in the expected manner. This phenomenon is particularly common among older adults and those chronically diseased (e.g. chronic obstructive pulmonary disease, COPD), and may involve endocrine variables such as vitamin D. At present, the effects of vitamin D supplementation on responses to resistance training remain largely unexplored. Methods: Ninety-five male and female participants (healthy, n=71; COPD, n=24; age 68 {+/-} 5 years) were randomly assigned to receive either vitamin D3 or placebo supplementation for 28 weeks in a double-blinded manner (latitude 61{degrees}N, September-May). Seventy-eight participants completed the RCT, which was initiated by 12 weeks of supplementation-only (in average, 3333 IU.day-1), followed by 13 weeks of combined supplementation (2000 IU.day-1) and supervised whole-body resistance training (twice weekly), interspersed with testing and measurements. Outcome measures included multiple assessments of muscle strength (n=7), endurance performance (n=6), and muscle mass (n=3, legs, primary), as well as muscle quality (legs), muscle biology (m. vastus lateralis; muscle fibre characteristics, transcriptome), and health-related variables (e.g. visceral fat mass and blood lipid profile). For main outcome domains such as muscle strength and muscle mass, weighted combined factors were calculated from the range of singular assessments. Results: Overall, 13 weeks of resistance training increased muscle strength (13% {+/-} 8%), muscle mass (9% {+/-} 8%) and endurance performance (one-legged, 23% {+/-} 15%; whole-body, 8% {+/-} 7%), assessed as weighted combined factors, and were associated with changes in health variables (e.g. visceral fat, -6% {+/-} 21%; [LDL]serum, -4% {+/-} 14%) and muscle tissue characteristics such as fibre type proportions (e.g. IIX, -3%-points), myonuclei.fibre-1 (30% {+/-} 65%), total RNA/rRNA abundances (15%/6-19%), and transcriptome profiles (e.g. ~336 differentially expressed genes). Vitamin D3 supplementation led to robust increases in [25(OH)D]serum ({Delta}49% vs placebo), but did not affect training-associated changes for any of the main outcome domains, with no interaction being evident with disease status or pre-RCT [25(OH)D]serum. In secondary analyses, vitamin D3 affected expression of gene sets involved in vascular functions in muscle tissue, strength gains in participants with high fat mass, and [cortisol]serum ({Delta}20%), all of which advocate further study. Conclusions: Vitamin D3 supplementation did not affect muscular responses to resistance training in old adults with or without COPD.

Vitamin D Status and Its Determinants in A Paediatric Population in Norway

Abstract: Recommendations for sufficient vitamin D intake in children were recently revised in Norway. However, optimal levels of vitamin D are still debated and knowledge on supplementation and vitamin D levels in healthy children in Norway is scarce. Therefore, we measured the plasma-concentration of 25-hydroxyvitamin D (25(OH)D) in children and adolescents attending the outpatient paediatric clinics in Innlandet Hospital Trust, Norway during two consecutive years (2015-2017). We recruited 301 children and adolescents aged 5 months to 18 years (mean 7.8, SD 4.4 years) for the study and obtained sample material for 25(OH)D measurements from 295 (98%). Information on diet, vitamin D supplementation, sun exposure, ethnicity, parental education and general health was collected by questionnaire. 25(OH)D levels were analysed and determinants for 25(OH)D were estimated by linear regression. 1.0% of the children had deficient levels (25(OH)D < 25 nmol/L) and 21.0% had insufficient levels (25-50 nmol/L). 25(OH)D levels ranging from 50 to 75 nmol/L were found among 38.3%, while 39.7% had levels above 75 nmol/L. The mean 25(OH)D level was 70.0 nmol/L (SD 23.4, range 17-142 nmol/L) with a significant seasonal variation with lowest levels in mid-winter and highest in late summer. In addition to seasonal variation independent determinants for 25(OH)D-levels were age of the child, parental ethnicity, vitamin D supplementation and soda consumption. Along with parental ethnicity other than Nordic, age was the strongest determinant of 25(OH)D, with adolescents having the lowest levels.

The Reliability of Iodine Concentration in Diaper-Retrieved Infant Urine Using Urine Collection Pads, and in Their Mothers’ Breastmilk

Abstract: Mild to moderate iodine deficiency is common among women of childbearing age. Data on iodine status in infants are sparse, partly due to the challenges in collecting urine. Urinary iodine concentration (UIC) is considered a good marker for recent dietary iodine intake and status in populations. The aim of this study was to investigate the reliability of iodine concentration measured in two spot-samples from the same day of diaper-retrieved infant urine and in their mothers' breastmilk. We collected urine and breastmilk from a sample of 27 infants and 25 mothers participating in a cross-sectional study at two public healthcare clinics in Norway. The reliability of iodine concentration was assessed by calculating the intraclass correlation coefficients (ICC) and the coefficient of variation (CV). The ICC for infants' urine was 0.64 (95% confidence interval (CI) 0.36-0.82), while the ICC for breastmilk was 0.83 (95% CI 0.65-0.92) Similarly, the intraindividual CV for UIC was 0.25 and 0.14 for breastmilk iodine concentration (BIC). Compared to standard methods of collecting urine for measuring iodine concentration, the diaper-pad collection method does not substantially affect the reliability of the measurements.

Risk Assessment of "Other Substances" – L-Glutamine and L-glutamic Acid

Abstract: The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), assessed the risk of "other substances" in food supplements and energy drinks sold in Norway. VKM has assessed the risk of doses given by the NFSA. These risk assessments will provide the NFSA with the scientific basis for regulating the addition of “other substances” to food supplements and other foods. "Other substances" are described in the food supplement directive 2002/46/EC as substances other than vitamins or minerals that have a nutritional or physiological effect. They are added mainly to food supplements, but also to energy drinks and other foods. VKM has not in this series of risk assessments of "other substances" evaluated any claimed beneficial effects from these substances, only possible adverse effects. Grey Literature Løvik et al.; EJNFS, 12(8): 54-57, 2020; Article no.EJNFS.58915 55 The present report is limited to the use of L-glutamine and L-glutamic acid in food supplements. Risks related to glutamine and glutamic acid added to food and drinks, protein hydrolysates or high dietary protein intake are outside the scope of the opinion. The report is based on previous risk assessments of glutamine and glutamic acid and scientific papers retrieved from a comprehensive literature search. L-glutamine is considered a non-essential amino acid in humans. In addition to its role in protein synthesis and the handling by the body of ammonia (via urea cycle), L-glutamine participates in other complex metabolic pathways e.g. in the central nervous system, immune system, and insulin secretion. L-glutamine is deaminated by glutaminase to form glutamic acid. L-glutamine is available from all protein-containing foods. High-protein foods contain the most (e.g. meat, fish, eggs and dairy products). L-glutamic acid is a non-essential amino acid. At physiological conditions its side chain is fully ionised, i.e. it exists in the form of glutamate. In addition to its role as substrate in protein synthesis, glutamic acid has important metabolic roles as a source of α-ketoglutarate in the citric acid cycle and in the handling by the body of ammonia (via urea cycle). Glutamic acid is also a major neurotransmitter. In the unbound form only, glutamic acid is responsible for umami, one of the five basic tastes sensed by humans. Glutamic acid is used as a flavour enhancer in the form of its salt monosodium glutamate. All meats, poultry, fish, eggs, and dairy products are excellent sources of glutamic acid. Some protein-rich plant foods also serve as sources, e.g. wheat protein contains 30% to 35% glutamic acid. According to information from the NFSA, L-glutamine and glutamic acid are ingredients in food supplements sold in Norway. The NFSA has requested a risk assessment of the following doses of L-glutamine in food supplements: 3500 mg/day, 5000 mg/day, 8000 mg/day, 10000 mg/day, 12000 mg/day, 15000 mg/day, and 16500 mg/day, and the following doses of glutamic acid: 1000 mg/day, 2000 mg/day, 3000 mg/day, 4000 mg/day, 5000 mg/day, and 5500 mg/day. Dietary intake in Norway is not known, but data from the third National Health and Nutrition Examination Survey (NHANES III) 1988-1994 in the USA suggest a mean dietary intake of about 15 g glutamic acid per day. In phase 1 of the present evaluation of "other substances", previous reports that assessed the safety of L-glutamine or L-glutamic acid supplementation in humans were identified. For the present report, a systematic literature search was performed to retrieve human studies published in the period 2011-2015, and in addition separate literature searches were performed for animal studies and studies in children and adolescents. The main search retrieved no publications reporting results from trials with L-glutamine or L-glutamic acid in healthy humans, nor did the search for studies in children and adolescents identify any relevant publications. Three human studies on glutamates were included as part of the risk assessment of glutamic acid. The search for animal studies retrieved four relevant reports. No major specific issues related to safety of L-glutamine and L-glutamic acid used as food supplements were identified in previous reports. However, a lack of studies in healthy adult individuals as well as in children was pointed out, and in particular the absence of long-term studies in healthy individuals. According to previous reports, short-term intake of doses of L-glutamine up to 0.5 g/kg bw per day has not been found to cause significant adverse effects. Up to 1.5 g per day of Lglutamic acid has been reported not to be associated with adverse effects. Conclusions in previous reports have indicated maximum supplemental levels of 3.5 and 5 g per day of Lglutamine and 1 g per day of Lglutamic acid. For the risk characterisation of L-glutamine, in the absence of long-term human studies in healthy individuals, VKM will base the value of comparison on the highest dose tested (no observed adverse effect level; NOAEL) in two 90-day studies in rodents, 3832 mg/kg bw per day. Employing an uncertainty factor of 10 for the extrapolation between species, the value of comparison is set to 383 mg/kg bw per day, corresponding to 26.8 g per day in a 70 kg adult. Data from studies in Løvik et al.; EJNFS, 12(8): 54-57, 2020; Article no.EJNFS.58915 56 various patient groups support the data from the two animal studies indicating the absence of significant adverse effects with this dose. In the risk characterisation of L-glutamic acid, in the absence of any unequivocally demonstrated reproducible adverse effect in short-term human studies and an absence of long-term studies in healthy individuals, VKM will base the value of comparison on the highest dose tested (NOAEL) in a 28-day study in rodents, 953 mg/kg bw per day. Employing an uncertainty factor of 10 for the extrapolation between species, the value of comparison is set to 95 mg/kg bw, corresponding to 6.7 g per day in a 70 kg adult. Data from early long-term studies in humans (doses up to 45 g per day) and in animals as well as short-term studies on glutamates support the data from the animal study indicating the absence of significant adverse effects with this dose. Based on these data, the Norwegian Scientific Committee for Food Safety (VKM) concludes that:

Agreement Between Mothers and Fieldworkers While Assessing Child Development Using Ages and Stages Questionnaires, Third Edition in Nepal

Abstract: Background: The Ages and Stages Questionnaires, Third Edition (ASQ-3) is becoming a widely used developmental assessment tool. The ASQ-3 can be completed by the caregivers (referred to as "mail out"), or by trained personnel under direct observation of the children (referred to as "home procedure"). Aim: The study was carried out to compare results obtained by the ASQ mail out with those of the ASQ home procedure in a community setting of Bhaktapur, Nepal. Methods: Trained fieldworkers (FWs) performed developmental assessment of 134 children aged 9 months in their homes using the ASQ home procedure. A few days before these assessments, mothers were asked to fill in the same ASQ-3 questionnaire. The concordance correlation coefficient (CCC) was calculated to measure their agreement. Result: The agreement between the ASQ mail out and home procedure was fair for the total score (CCC = 0.54). For the sub-scales, the agreement was good for the gross motor (CCC = 0.65), for the remaining subscales agreement was poor (CCC < 0.4). Conclusion: In resource limited setting like Nepal, the ASQ mail out represents an easy method to assess child development by caretakers at home; however, with the poor agreement between different methods of assessments, we cannot conclude that a single method is superior or most optimal and this question should be investigated further. When either of the method home procedure or mail out is opted, the results should be interpreted with cautions.

Risk Assessment of "Other Substances" – L- tryptophan

Abstract: The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), assessed the risk of "other substances" in food supplements and energy drinks sold in Norway. VKM has assessed the risk of doses given by NFSA. These risk assessments will provide NFSA with the scientific basis for regulating the addition of "other substances" to food supplements. "Other substances" are described in the food supplement directive 2002/46/EC as substances other than vitamins or minerals that have a nutritional or physiological effect. "Other substances" are added mainly to food supplements, but also to energy drinks and other foods. VKM has not in this series of risk assessments of "other substances" evaluated any claimed beneficial effects from these substances, only possible adverse effects. The present report is a risk assessment of L-tryptophan and is based on previous risk assessments of L-tryptophan and scientific papers retrieved from systematic literature searches. Grey Literature Holvik et al.; EJNFS, 12(8): 75-77, 2020; Article no.EJNFS.58922 76 L-tryptophan is an indispensable amino acid in humans, which in addition to its role in protein synthesis, also participates in complex metabolic pathways where it acts as a precursor to the potent neurotransmitter serotonin, the hormone melatonin, and the vitamin niacin (vitamin B3). L-tryptophan is available from a wide variety of protein-rich foods in the normal diet, including meat, fish, milk and dairy products, egg, beans, lentils and also bread and grains, pasta, rice, fruit and vegetables. According to information from NFSA, L-tryptophan is an ingredient in food supplements sold in Norway. NFSA has requested a risk assessment of the following doses of L-tryptophan in food supplements: 250 mg/day, 300 mg/day, and 450 mg/day for adults, adolescents and children 10 years and above. Usual dietary intake of L-tryptophan in Norway is not known, but data from the USA and the UK suggest an average dietary intake of about 900 mg/day of which the main part is bound in food protein. In phase 1 we have identified seven previous reports that have aimed to assess the safety of Ltryptophan supplementation in humans; the most recent was published by VKM in 2013. To complement the existing reports, a literature search was performed in MEDLINE and EMBASE to retrieve studies published in the period 2012-2015. This search retrieved two recent randomised trials with L-tryptophan. In addition, we performed a literature search concerning safety of Ltryptophan in children and adolescents with no time restriction. This search retrieved no relevant results that met the inclusion criteria. Four aspects related to safety of L-tryptophan were identified in previous reports: 1) adverse effects reported at high doses, including appetite suppression, nausea and vomiting, faintness, dizziness, drowsiness, tremor, fatigue, and headache; 2) a suggested, but not established, increased risk of cataract; 3) the eosinophilia-myalgia syndrome (EMS), which is thought to be caused by contaminants produced in the manufacturing of L-tryptophan supplements, however this is still unresolved; 4) the risk of adverse drug reactions caused by excessive serotonergic action by concomitant use of antidepressants, including monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants and other drugs, known as the serotonin syndrome. According to previous reports, doses of 3 to 6 g/day of L-tryptophan have been associated with adverse effects. Using an uncertainty factor of 10, conclusions in previous reports have suggested a maximum level of 220 mg/day for adults. An upper tolerable intake level (UL) of 220 mg/day was first proposed in a report by the UK Committee on the Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) in 2004, and was derived from the average dose of Ltryptophan consumed as a prescription drug against depression in the UK at the time (2228 mg/day). This level has been maintained in later reports by other committees, most recently VKM in 2013 as a tentative guidance level. Additional information from the publications retrieved in the literature search did not provide evidence of sufficient weight to change the previous conclusions concerning UL. There is a lack of well-designed supplementation studies with L-tryptophan in humans designed to address adverse effects and dose-response relationship as primary outcome. There is also a lack of data about potential adverse health effects of L-tryptophan supplementation in children and adolescents. Patients using antidepressant drugs constitute a specific vulnerable subgroup of the population with regard to possible adverse effects of L-tryptophan supplements, due to the potentially lifethreatening drug interaction effects that occur from excessive serotonergic action. The Norwegian Scientific Committee for Food Safety (VKM) concludes that:  In adults (≥18 years), the specified doses 250, 300, and 450 mg/day L-tryptophan in food supplements may represent a risk of adverse health effects.  In adolescents (14 to <18 years), the specified doses 250, 300, and 450 mg/day L-tryptophan in food supplements may represent a risk of adverse health effects. Holvik et al.; EJNFS, 12(8): 75-77, 2020; Article no.EJNFS.58922 77  In children (10 to <14 years), the specified doses 250, 300, and 450 mg/day L-tryptophan in food supplements may represent a risk of adverse health effects.  Children below 10 years were not included in this assessment.

Insights Image for “Effect of prebiotic and probiotic supplementation on neurodevelopment in preterm very low birth weight infants: findings from a meta-analysis”

Abstract: Received: 13 August 2019 Revised: 13 August 2019 Accepted: 13 August 2019 Centre for Health Research and Development, Society for Applied Studies, New Delhi, India; Centre for Intervention Science in Maternal and Child Health, Centre for International Health, University of Bergen, Bergen, Norway and Department of Research, Innlandet Hospital Trust, Brumunddal, Norway Correspondence: Ravi Prakash Upadhyay (ravi.upadhyay@sas.org.in) www.nature.com/pr