An Optimization Tool to Formulate Diets within a Supplementary Nutrition Program for Children.

Background: In large supplementary feeding programs for children, it is challenging to create and sustain contextual, acceptable, nutritionally complete, and diverse supplemental foods. For example, the Indian Supplementary Nutrition Program (SNP) supplements the dietary intake of children, pregnant and lactating women, and severely acutely malnourished (SAM) children by offering dry take home rations (THRs) or hot cooked meals (HCMs) across India, but an optimization tool is necessary to create local contextual recipes for acceptable and nutritionally adequate products. Objectives: This study aimed to create a linear programming (LP) model to optimize diverse food provisions for a SNP to meet its program guidelines, using locally available foods, within budgetary allocations. Methods: A LP algorithm with appropriate constraints was used to generate an optimal THR based on raw foods, or an optimal weekly HCM menu comprised of a lunch meal with mid-morning snacks, based on user choices of foods and recipes. The database of foods used was created by a prospective survey conducted across all states of India for this purpose, such that the recipe and food optimization was diverse and specific to the guidelines for each beneficiary group. Results: An interactive web-based app, which can optimize feeding programs at any population level, was developed for use by program implementers and is hosted at https://www.datatools.sjri.res.in/SNP/. In the Indian example analyzed here, the recommended optimized diets met the guidelines for diversified and nutritionally complete SNP provision but at a cost that was almost 25% higher than the present Indian budget allocation. Conclusions: The optimization model developed demonstrates that contextual SNP diets can be created to meet macronutrient and most essential micronutrient needs of large-scale feeding programs, but appropriate diversification entails additional costs.

Effect of calcium supplementation on reversing metformin-based inhibition of vitamin B12 bioavailability in healthy adults using a [13C] cyanocobalamin tracer - A pilot study.

BACKGROUND & AIMS: Metformin is a widely prescribed first line drug for the treatment of type 2 diabetes mellitus (DM). Studies have shown that the use of metformin is often associated with a decrease in vitamin B12 (B12) levels in patients with DM. Few studies have shown that this effect could be mitigated with calcium supplementation. In the present study, we quantified the effect of metformin, and metformin co-administered with calcium on B12 absorption using a novel stable isotope [13C] cyanocobalamin tracer. METHODS: A pilot crossover study was conducted to estimate the bioavailability of B12 in healthy subjects, using [13C] cyanocobalamin as a tracer. In the study, [13C] cyanocobalamin was administered orally to the participants followed by hourly venous sampling to measure the concentration of the tracer and estimate bioavailability. This protocol was followed for three experiment days, each separated by a one month wash out period. As part of the study, all participants received the tracer alone for the control day (C), metformin 850 mg along with the tracer for the metformin day (M) and metformin 850 mg with calcium 500 mg and the tracer for the metformin calcium day (MC). RESULTS: Seven participants completed all three experiment days. The mean B12 bioavailability (±SD, n = 7) was 42.6 ± 10.2% for the control day (C), 30.8 ± 15.3% for the metformin day (M) and 46.4 ± 8.6% for the metformin-calcium day (MC). Repeated measures ANOVA was done and the pairwise comparison showed a significant difference in the B12 bioavailability between control and metformin day (C vs M p = 0.010), and between the metformin and metformin with calcium day (M vs MC p = 0.003). CONCLUSION: B12 bioavailability reduced significantly from baseline (C) when metformin (M) was administered and this reduction was reversed when calcium was co-administered (MC) in healthy participants. In patients using metformin, calcium supplementation as a strategy to prevent B12 deficiency needs to be further studied.

Mandatory fortification of rice in the public distribution system in India: An ethics perspective.

In response to the continuing high prevalence of anaemia recorded in the National Family Health Survey-5, the Indian government launched a policy for mandatory iron fortification of the rice provided through public nutrition programmes in India. This was done even though a rigorous evidence analysis had already concluded that rice fortification was not effective in preventing anaemia or iron deficiency at the population level. Fortification also poses a potential risk of iron toxicity over time, but there is no stated time period for the policy's implementation. The risk is particularly high in segments of the population who already have a high habitual iron intake, and who could be exposed to simultaneous fortification in different staples and food commodities along with the ongoing weekly Iron and Folic Acid tablets supplementation programme. Finally, this fortification policy also requires significant additional funding and resources to implement. It is crucial to examine such mandatory health actions, and to weigh the benefits and risks of harm, using the principles of public health ethics.

Bioavailability and daily requirement of vitamin B12 in adult humans: an observational study of its colonic absorption and daily excretion as measured by [13C]-cyanocobalamin kinetics.

BACKGROUND: Clinical and biochemical vitamin B12 (B12) deficiency is lower than anticipated in vegetarians. Extraileal absorption, such as from the colon, as well as reduced daily excretion, may be adaptive mechanisms to maintain B12 homeostasis with marginal intakes. OBJECTIVE: To measure the absorption of B12 from the small and large intestine, and its daily rate of excretion from the body, using a [13C]-cyanocobalamin tracer. METHODS: Oral B12 bioavailability was measured over 12 h after administration of [13C]-cyanocobalamin tracer (2.5 µg) in normal participants. The colonic B12 bioavailability was evaluated by direct instillation of [13C]-cyanocobalamin (5 µg) into the ascending colon. Bioavailability was calculated from 2-compartmental modeling of the tracer appearance in plasma. The excretion rate of B12 was measured from [13C]-cyanocobalamin elimination from the body over 4 wk after oral dosing (5 µg). RESULTS: The oral B12 bioavailability (n = 11) was 63% ± 10% measured over 12 h. A late absorption peak, accounting for 12% of the absorption, was observed after an average lag time of 8.7 h from dosing. The colonic B12 bioavailability (n = 10) was 7% ± 5% over 4 h. The daily B12 excretion rate (n = 4) was 0.7 ± 0.2 µg/d. The minimum daily requirement of B12 in these participants was derived at 1 µg /d. CONCLUSIONS: B12 is absorbed in the human colon. This observation confirms the potential contribution of the colon in daily B12 nutriture, and along with a possible lower requirement, could explain the absence of clinical deficiency in populations with marginal B12 intakes. TRIAL REGISTRATION NUMBER: This study was registered in Clinical Trials Registry of India (CTRI) with the registration number CTRI/2018/04/012957, available from https://ctri.nic.in/Clinicaltrials/showallp.php?mid1=49319&EncHid=&userName=029108.

Haemoglobin diagnostic cut-offs for anaemia in Indian women of reproductive age.

BACKGROUND: The persistent high prevalence of anaemia among Indian women of reproductive age (WRA) despite aggressive long-term iron supplementation could be related to over-diagnosis from an inappropriately high haemoglobin (Hb) diagnostic cut-off. To develop an appropriate cut-off for Indian WRA, we hypothesized that during iron-folic acid (IFA) supplementation to a mixed (anaemic/non-anaemic) WRA population, the positive slope of the Hb-plasma ferritin (PF) response in anaemic women would inflect into a plateau (zero-response) as a non-anaemic status is reached. The 2.5th percentile of the Hb distribution at this inflection point will be the diagnostic Hb cut-off for iron-responsive anaemia. METHOD: A hierarchical mixed effects model, with a polynomial mean and variance model to account for intraclass correlation due to repeated measures, was used to estimate the response curve of Hb to PF, or body iron stores, in anaemic and non-anaemic WRA (without inflammation), who were receiving a 90-day IFA supplementation. RESULTS: The Hb response curve at low PF values showed a steep increase, which inflected into a plateau at a PF of 10.1 µg/L and attained a steady state at a PF of 20.6 µg/L. The Hb distribution at the inflection was a normal probability distribution, with a mean of 12.3 g/dL. The 2.5th percentile value of this distribution, or the putative diagnostic Hb cut-off for anaemia, was 10.8 g/dL (~11 g/dL). CONCLUSION: The derived Hb cut-off is lower than the current adult values of 12 g/dL and could partly explain the persistently high prevalence of anaemia.

Prevalence of Vitamin B12 and Folate Deficiencies in Indian Children and Adolescents.

Deficiencies of vitamin B12 (B12) and folate (FA) are of particular interest due to their pleiotropic role in 1-carbon metabolism. In addition to adverse birth outcomes, deficiencies of B12 and FA, or an imbalance in FA/B12 status, are linked to metabolic disorders. Indian diets that are predominantly plant food-based could be deficient in these vitamins, but there are no national estimates of the prevalence of B12 and FA deficiency in Indian children and adolescents, nor their associations with age, sex and growth indicators. The recent Comprehensive National Nutrition Survey (CNNS-2016-18) provided estimates of the prevalence of B12 and FA deficiency at the national and state levels among preschool (1-4 years: 9976 and 11,004 children, respectively), school-age children (5-9 years: 12,156 and 14,125) and adolescents (10-19 years: 11,748 and 13,621). Serum B12 and erythrocyte FA were measured by the direct chemiluminescence method and their deficiency was defined using WHO cut-offs. The prevalence of B12 and FA deficiency was high among adolescents (31.0%, CI: 28.7-33.5 and 35.6%, CI: 33.1-8.2) compared to school-age (17.3%, CI: 15.4-19.3 and 27.6%, CI: 25.5-29.9) and preschool children (13.8%, CI: 11.7-16.2 and 22.8%, CI: 20.5-25.2, respectively). The prevalence of both B12 and FA deficiency was significantly higher by 8% and 5%, respectively, in adolescent boys compared to girls. There was no association between anthropometric undernutrition and B12 and FA deficiency. There was wide regional variation in the prevalence of B12 and FA deficiency, but no rural-urban differences were observed across all age groups. The national prevalence of B12 deficiency among preschool or school-age children was <20% (the cut-off that indicates a public health problem). However, FA deficiency in these age groups and both FA and B12 deficiencies in adolescents were >20%, warranting further investigation.

Growth in Infancy and Childhood and Age at Menarche in Five Low- or Middle-Income Countries: Consortium of Health Orientated Research in Transitional Societies (COHORTS).

BACKGROUND: Earlier age at menarche is associated with behavioral and noncommunicable disease risks. The influence of birth weight (BW) (intrauterine) and postnatal growth on age at menarche is not well studied in low- and middle-income countries (LMICs). OBJECTIVE: Therefore, we investigated these associations in 5 LMIC birth cohorts. METHODS: We analyzed data from Brazil, Guatemala, India, the Philippines, and South Africa (n = 3983). We derived stunting (< -2 SD scores) at 24 mo using the WHO child growth standards. We generated interaction terms with categorized BW and conditional weight (lighter < 0 or heavier ≥ 0), and height (shorter < 0 or taller ≥ 0) z-scores. We categorized early-, modal-, and late-onset menarche and used multilevel ordinal regression. We used multilevel linear regression on continuous age at menarche. RESULTS: Mean age at menarche was 12.8 y (95% CI: 12.7 12.9). BW was not associated with age at menarche. Conditional height at 24 mo and mid-childhood (OR: 1.35; 95% CI: 1.27, 1.44 and 1.32; 1.25, 1.41, respectively) and conditional weight at 24 mo and mid-childhood (OR: 1.15; 1.08, 1.22 and 1.18; 1.11, 1.25, respectively) were associated with increased likelihood of early-onset menarche. Being heavier at birth and taller at 24 mo was associated with a 4-mo (95% CI: 0.8, 7.6) earlier age at menarche than being lighter at birth and shorter at 24 mo. Being heavier at birth but lighter in mid-childhood was associated with a 3-mo (95% CI: 0.8, 4.8) later age at menarche than being lighter at birth and mid-childhood. Age at menarche was 7 mo later in stunted than nonstunted girls. CONCLUSION: Age at menarche is inversely related to relative weight gain but also to rapid linear growth among those born shorter but remained stunted, and those born taller and grew excessively. These findings do not deter the global health goal to reduce growth faltering but emphasize the potential adverse effects of an obesogenic environment on adolescent development.

The Need for Food Fortification With Zinc in India: Is There Evidence for This?

There has been recent advocacy for food fortification with zinc in India. However, there are three important conditions that should be established before fortifying food with any micronutrient, which requires that there should be i) Established high prevalence of biochemical or sub-clinical deficiency (≥20%), ii) Low dietary intakes that increase the risk of deficiency, and iii) Evidence of efficacy of supplementation from clinical trials. For zinc, all three conditions are not satisfied. The prevalence of low serum zinc concentrations in Indian children is well below 20% (~6%), signifying that zinc deficiency is not a public health problem. There is no risk of dietary zinc inadequacy in Indian populations where intake has been measured. Finally, there is no robust evidence that zinc-fortified foods improve functional outcomes, even if the serum zinc concentration is increased. Thus, contemporary evidence does not justify the need for food fortification with zinc in India.

A proposed method for defining the required fortification level of micronutrients in foods: An example using iron.

In 2006, the WHO published a framework for calculating the desired level of fortification of any micronutrient in any staple food vehicle, to reduce micronutrient malnutrition. This framework set the target median nutrient intake, of the population consuming the fortified food, at the 97.5th percentile of their nutrient requirement distribution; the Probability of Inadequacy (PIA) of the nutrient would then be 2.5%. We argue here that the targeted median nutrient intake should be at Estimated Average Requirement (50th percentile), since the intake distribution will then overlap the requirement distribution in a population that is in homeostasis, resulting in a PIA of 50%. It is also important to recognize that setting the target PIA at 2.5% may put a sizable proportion at risk of adverse consequences associated with exceeding the tolerable upper limit (TUL) of intake. This is a critical departure from the WHO framework. For a population with different age- and sex-groups, the pragmatic way to fix the fortification level for a staple food vehicle is by achieving a target PIA of 50% in the most deprived age- or sex-group of that population, subject to the condition that only a very small proportion of intakes exceed the TUL. The methods described here will aid precision in public health nutrition, to pragmatically determine the precise fortification level of a nutrient in a food vehicle, while balancing risks of inadequacy and excess intake.

A risk-based approach to measuring population micronutrient status from blood biomarker concentrations.

Background: Nutrient biomarkers and their definitive cut-offs are used to classify individuals as nutrient-deficient or sufficient. This determinism does not consider any uncertainty, and a probability approach, using biomarker distributions, is then preferable to define the risk of nutrition deficiency when in populations. Method: Healthy 1-19-year-old children and adolescents were selected from the Comprehensive National Nutrition Survey (CNNS), to obtain probability distributions of their retinol, zinc and vitamin B12, along with erythrocyte folate. Model-based estimates of location, scale and shape parameters of these distributions were obtained across ages. Subsequently, in the entire sample of 1-19 year old children of CNNS, the population risk of deficiency (PRD) which is average risk of deficiency in individuals in the population was computed, which is "of concern" when >50%. When individual risk of deficiency is >97.5% it is called "severe risk of deficiency" (SRD). Results: In the entire CNNS sample, the PRD of concern was low for serum retinol (3.6-8.2%), zinc (0-5.5%), and SRD of vitamin B12 and erythrocyte folate were 2.3-7.2% and 4.2-9.7%, respectively, across age and sex groups. Conclusion: This proposed method assesses the adequacy of nutrient exposures without relying on pre-defined deterministic biomarker cut-offs to define micronutrient deficiency and avoids errors in exposure assessment.

Prevalence of and Factors Associated With High Blood Pressure Among Adolescents in India.

Importance: High blood pressure (BP) in children and adolescents is becoming one of the most common health conditions worldwide and is much more widely prevalent than previously thought. Objective: To estimate the prevalence of high BP in adolescents in India and identify associated factors. Design, Setting, and Participants: This cross-sectional study is a secondary analysis of data from the Comprehensive National Nutrition Survey (CNNS, 2016-2018), which used a multistage, stratified, probability proportion to size cluster sampling design to enroll a nationally representative sample of households and individuals aged 10 to 19 years across all states and union territories of India. Adolescents with acute or chronic illness, physical deformity, mental illness, or cognitive disability were excluded from the survey. Because BP was measured only in children between 10 and 19 years of age, only data from children within this age group were included for secondary analyses. Data analysis was performed from March 2021 to April 2022. Exposures: Anthropometry. Main Outcomes and Measures: On the basis of the 2017 American Academy of Pediatrics guidelines, high BP was defined as stage 1 and 2 hypertension, with BP above the 95th percentile in children younger than 13 years and greater than 130/80 mm Hg in children 13 years or older. The association of age, sex, region, socioeconomic status, body mass index, fasting blood glucose, hemoglobin A1c, and lipid profile with high BP were examined using log binomial regression. Results: Among 16 182 eligible children aged 10 to 19 years (mean [SD] age, 14.2 [2.8] years; 7849 [48.5%] female and 8333 [51.5%] male), 11 718 had valid BP data with 3 repeated readings. the prevalence of high BP was 35.1% (95% CI, 31.5%-38.9%) in children aged 10 to 12 years and 25.1% (95% CI, 22.5%-28.0%) in children 13 years or older. Overweight and obesity were associated with a higher risk of high BP in both younger (prevalence ratio, 1.17; 95% CI, 1.04-1.34) and older children (prevalence ratio, 1.33; 95% CI, 1.18-1.49). The prevalence of high BP in younger children with stunting was high at 40.1% (95% CI, 31.9%-48.9%) and was 21.9% (95% CI, 18.2%-26.1%) among older children with stunting. In both age groups, high BP coexisted with other cardiovascular disease risk factors, such that adolescents with high fasting blood glucose, high hemoglobin A1c, high triglyceride, and high low-density lipoprotein cholesterol levels had a higher risk of high BP. Conclusions and Relevance: In this cross-sectional study, the prevalence of high BP, along with cardiovascular risk factors, was substantial in Indian adolescents. There is a need to screen and identify adolescents who have high BP and initiate interventions to control the burden of hypertension and its consequences in India.

Prevalence of metabolic syndrome among adolescents in India: a population-based study.

BACKGROUND: In India, the prevalence of overweight among adolescents is on the rise, setting the stage for an increase in metabolic syndrome (MS). This paper presents the national prevalence of MS in adolescents in India. METHODS: A nationally representative data of adolescents (10-19 years) from the Comprehensive National Nutrition Survey was used. MS was defined based on the NCEP-ATP III criteria for adolescents. Bivariate analysis was used to report socio-demographic differentials in prevalence and to assess interstate variability. Multivariate logistic regression model was constructed to measure the association between socio-demographic characteristics and prevalence of MS. Census data from 2011 was projected to 2017 to calculate burden. RESULTS: The prevalence of MS was 5.2% among adolescents. 11.9%, 15.4%, 26.0%, 31.9% and 3.7% had central obesity, high blood pressure, hypertriglyceridemia, low HDL-cholesterol and high fasting glucose, respectively. The prevalence was higher among males (5.7% vs. 4.7%, adjusted odds ratio (AOR): 1.3, 95% confidence interval [CI]: 1.0, 1.6), those residing in urban areas (7.9% vs 4.2%, AOR: 1.4, 95% CI: 1.1, 1.8), and from wealthier households as compared to their counterparts (8.3% vs. 2.4%, AOR: 3.4, 95% CI: 2.1, 5.5). There was wide interstate variability in the prevalence of MS (0.5% - 16.5%). In 2017, 14.2 million adolescents had MS in India. CONCLUSIONS: The prevalence of MS among adolescents in India is low and clustered in urban areas and richer households. Early prevention interventions promoting a healthy lifestyle, especially in high prevalence areas, are needed to keep MS from becoming a public health issue.

Effects of early-life poverty on health and human capital in children and adolescents: analyses of national surveys and birth cohort studies in LMICs.

The survival and nutrition of children and, to a lesser extent, adolescents have improved substantially in the past two decades. Improvements have been linked to the delivery of effective biomedical, behavioural, and environmental interventions; however, large disparities exist between and within countries. Using data from 95 national surveys in low-income and middle-income countries (LMICs), we analyse how strongly the health, nutrition, and cognitive development of children and adolescents are related to early-life poverty. Additionally, using data from six large, long-running birth cohorts in LMICs, we show how early-life poverty can have a lasting effect on health and human capital throughout the life course. We emphasise the importance of implementing multisectoral anti-poverty policies and programmes to complement specific health and nutrition interventions delivered at an individual level, particularly at a time when COVID-19 continues to disrupt economic, health, and educational gains achieved in the recent past.

Reference cut-offs to define low serum zinc concentrations in healthy 1-19 year old Indian children and adolescents.

BACKGROUND/OBJECTIVES: Population zinc (Zn) status assessment is based on serum zinc concentration (SZC) cut-offs defined by the International Zinc Nutrition Consultative Group (IZiNCG). The objective of this study is to derive reference SZC cut-offs in apparently healthy 1-19 year Indian children and adolescents using comprehensive national nutrition survey (CNNS) data, and to measure the prevalence of Zn deficiency. SUBJECTS/METHODS: Apparently healthy children (n = 12,473) were selected from the CNNS, by including the highest 2 wealth quintiles, and excluding stunted, thin and obese children, and those with CRP > 5 mg/L, anaemia, hypo-albuminemia, diabetes, recent diarrhoea and history of smoking. The 2.5th centile of age-based distributions defined the SZC cut-offs, used to measure the prevalence of Zn deficiency in India, as against the IZiNCG cut-offs. RESULTS: The present study SZC cut-offs were significantly lower, by 10-18 µg/dL, than the IZiNCG cut-offs; more in adolescents. Prevalence of Zn deficiency in the entire CNNS, with these cut-offs, was 2.7 (<10 years) to 5.5 (10-19 years) times lower than with the IZiNCG cut-offs. No geographical state, nor any age group, had Zn deficiency as a serious public health problem (≥20%). In contrast, with IZiNCG cut-offs, 9-27 states (depending on age group) had a public health problem. CONCLUSIONS: The present study reference SZC cut-offs for Zn deficiency are lower than the IZiNCG cut-offs, and their rigorous selection from a national sample makes them more appropriate for use in India. A re-examination of the global applicability of IZiNCG recommended cut-offs in other LMICs appears appropriate.