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.

Protein-Energy Supplementation in Early-Life Decreases the Odds of Mental Distress in Later Adulthood in Guatemala.

BACKGROUND: The prevalence of mental health concerns is growing worldwide, along with lack of access to and receipt of needed treatment. Current gaps in treatment provision have led to exploring alternative methods of prevention, with research linking nutrition and mental health, of particular relevance in low- and middle-income countries, with a high prevalence of undernutrition. OBJECTIVES: To examine whether exposure to a protein-energy nutritional supplement during the first 1000 d of life decreased odds of mental distress in adulthood among men and women in Guatemala compared with receiving a low energy-no protein supplement or supplementation outside the 1000-d window. METHODS: Data from participants (n = 1249) in a longitudinal cohort protein-energy supplementation trial (early-life, supplementation data from 1969 to 1977, ages 0-7 y; life course, outcome data from 2017-2018 follow-up, ages 40-57 y) were analyzed for associations between nutrition in the first 1000 d and mental distress in adulthood (WHO Self-Reporting Questionnaire 20 [SRQ-20]), controlling for early-life variables and current life stress; life course variables (e.g. education) were examined as potential mediators of this relation. Generalized linear mixed models and zero-inflated Poisson generalized linear mixed models were utilized. RESULTS: Both partial and full supplementation with Atole during the first 1000 d were associated with 63% (95% CI: 0.16, 0.87) and 56% (95% CI: 0.19, 1.03) lower odds, respectively, of experiencing mental distress in adulthood. Results did not differ by sex. These inverse relations remained relatively unchanged (partial OR = 0.34 [95% CI: 0.14, 0.83]; full OR = 0.38 [95% CI: 0.16, 0.92]) after controlling for early-life and life course variables, including life stress. CONCLUSIONS: Protein-energy supplementation during the first 1000 d of life in Guatemala, where undernutrition is prevalent, may reduce the prevalence of later mental distress in adulthood. This effect appears to occur directly, rather than indirectly, through pathways of life course variables such as education, wealth, and marital status.

Protein-Energy Supplementation in Early-Life Decreases the Odds of Mental Distress in Later Adulthood in Guatemala.

BACKGROUND: The prevalence of mental health concerns is growing worldwide, along with lack of access to and receipt of needed treatment. Current gaps in treatment provision have led to exploring alternative methods of prevention, with research linking nutrition and mental health, of particular relevance in low- and middle-income countries, with a high prevalence of undernutrition. OBJECTIVES: To examine whether exposure to a protein-energy nutritional supplement during the first 1000 d of life decreased odds of mental distress in adulthood among men and women in Guatemala compared with receiving a low energy-no protein supplement or supplementation outside the 1000-d window. METHODS: Data from participants (n = 1249) in a longitudinal cohort protein-energy supplementation trial (early-life, supplementation data from 1969 to 1977, ages 0-7 y; life course, outcome data from 2017-2018 follow-up, ages 40-57 y) were analyzed for associations between nutrition in the first 1000 d and mental distress in adulthood (WHO Self-Reporting Questionnaire 20 [SRQ-20]), controlling for early-life variables and current life stress; life course variables (e.g. education) were examined as potential mediators of this relation. Generalized linear mixed models and zero-inflated Poisson generalized linear mixed models were utilized. RESULTS: Both partial and full supplementation with Atole during the first 1000 d were associated with 63% (95% CI: 0.16, 0.87) and 56% (95% CI: 0.19, 1.03) lower odds, respectively, of experiencing mental distress in adulthood. Results did not differ by sex. These inverse relations remained relatively unchanged (partial OR = 0.34 [95% CI: 0.14, 0.83]; full OR = 0.38 [95% CI: 0.16, 0.92]) after controlling for early-life and life course variables, including life stress. CONCLUSIONS: Protein-energy supplementation during the first 1000 d of life in Guatemala, where undernutrition is prevalent, may reduce the prevalence of later mental distress in adulthood. This effect appears to occur directly, rather than indirectly, through pathways of life course variables such as education, wealth, and marital status.

Age at childbirth and change in BMI across the life-course: evidence from the INCAP Longitudinal Study.

BACKGROUND: Parity has been associated with both short- and long-term weight gain in women. However, it is not clear if timing of parity across the reproductive age has different associations with BMI. METHODS: To prospectively assess the association between age at childbirth and maternal change in BMI, we analyzed data from the ongoing INCAP Longitudinal Study, which started in 1969 in four villages in Guatemala. Cohort women (n=778) provided information on reproductive history and anthropometric measures were measured in 1988-89 (adolescence, 15 to 25y), 2002-04 (early adulthood, 26 to 36y) and 2015-17 (mid adulthood, 37 to 55y). We evaluated the associations of number of live births in the period preceding each study wave (1969-77 to 1988-89, 1988-89 to 2002-04 and 2002-04 to 2015-17) with BMI change in the same period using multivariable linear regression models. RESULTS: Number of live births between 1988 and 89 and 2002-04 was positively associated with increased BMI, while there was not an association between number of live births and BMI in the other intervals. Women who had one, two, or three or more children between 1988 and 89 and 2002-04 had 0.90 (kg/m2, 95% CI: -0.55, 2.35), 2.39 (kg/m2, 95% CI: 1.09, 3.70) and 2.54 (kg/m2, 95% CI: 1.26, 3.82) higher BMI, respectively, than women who did not give birth in the same period. CONCLUSIONS: Our findings suggest that women who had three or more children during early adulthood gained more weight compared to women who had no children in the same period. In contrast, women who had children earlier or later in their reproductive lives did not gain additional weight compared to those who did not have children during that period. Childbirth may have different associations with BMI based on the mother's age.

Two countries, similar practices: the political practices of the food industry influencing the adoption of key public health nutrition policies in Guatemala and Panama.

OBJECTIVE: To identify the corporate political activity (CPA) strategies used by food industry actors during the development of two public health nutrition policies in Central America: Law #570 (taxation of sugar-sweetened beverages) in Panama and Bill #5504 (labelling and food marketing regulations) in Guatemala. DESIGN: We triangulated data from publicly available information from 2018 to 2020, (e.g. industry and government materials; social media material) with semi-structured interviews with key stakeholders. SETTING: Guatemala and Panama. PARTICIPANTS: Government, academia and international organisations workers in health and nutrition. DESIGN: CPA strategies were categorised according to an existing internationally used taxonomy into action-based, instrumental strategies (coalition management, information management, direct involvement and influence in policy, legal action) and discursive strategies. RESULTS: Instrumental strategies included the establishment of relationships with policymakers and direct lobbying against the proposed public policies. Discursive strategies were mainly criticising on the unfounded ground that they lacked evidence of effectiveness and will imply negative impacts on the economy. The industry pointed at individuals for making their own food choices, in order to shift the focus away from the role of its products in contributing to ill health. CONCLUSION: We provide evidence of the political practices used by the food industry to interfere with the development and implementation of public health nutrition policies to improve diets in Central America. Policymakers, public health advocates and the public should be informed about those practices and develop counterstrategies and arguments to protect the public and policies from the vested interests of the food industry.

Educational inequalities in obesity: a multilevel analysis of survey data from cities in Latin America.

OBJECTIVE: Using newly harmonised individual-level data on health and socio-economic environments in Latin American cities (from the Salud Urbana en América Latina (SALURBAL) study), we assessed the association between obesity and education levels and explored potential effect modification of this association by city-level socio-economic development. DESIGN: This cross-sectional study used survey data collected between 2002 and 2017. Absolute and relative educational inequalities in obesity (BMI ≥ 30 kg/m2, derived from measured weight and height) were calculated first. Then, a two-level mixed-effects logistic regression was run to test for effect modification of the education-obesity association by city-level socio-economic development. All analyses were stratified by sex. SETTING: One hundred seventy-six Latin American cities within eight countries (Brazil, Chile, Colombia, Costa Rica, El Salvador, Guatemala, Mexico and Peru). PARTICIPANTS: 53 186 adults aged >18 years old. RESULTS: Among women, 25 % were living with obesity and obesity was negatively associated with educational level (higher education-lower obesity) and this pattern was consistent across city-level socio-economic development. Among men, 18 % were living with obesity and there was a positive association between education and obesity (higher education-higher obesity) for men living in cities with lower levels of development, whereas for those living in cities with higher levels of development, the pattern was inverted and university education was protective of obesity. CONCLUSIONS: Among women, education was protective of obesity regardless, whereas among men, it was only protective in cities with higher levels of development. These divergent results suggest the need for sex- and city-specific interventions to reduce obesity prevalence and inequalities.

Associations between Helicobacter pylori with nonalcoholic fatty liver disease and other metabolic conditions in Guatemala.

BACKGROUND: Previous studies have suggested an association between Helicobacter pylori (H pylori) and nonalcoholic fatty liver disease (NAFLD). The aim of the current study was to examine the association in Guatemala, a region with elevated prevalences of both H pylori and NAFLD. Associations between H pylori and other metabolic conditions were also examined, as were associations between H hepaticus and H bilis and the metabolic conditions. MATERIALS & METHODS: The analysis included 424 participants from a cross-sectional study in Guatemala. H pylori seropositivity was defined as positivity for ≥ 4 antigens. Seropositivities for H bilis and H hepaticus were defined as positivity for ≥ 2 antigens. NAFLD was estimated using the Fatty Liver Index and the Hepatic Steatosis Index. Other conditions examined were obesity, central obesity, hypercholesterolemia, low HDL, diabetes and metabolic syndrome (MetSyn). Prevalence odds ratios (POR) and 95% confidence intervals (CIs) were estimated. RESULTS: No overall associations between H pylori,H hepaticus, or H bilis and NAFLD or related metabolic conditions were found. Seropositivity for H pylori antigens CagA and VacA and H hepaticus antigen HH0713 was each significantly associated with NAFLD, however. In addition, associations were observed between the H pylori antigens HyuA, HP1564, and UreA and specified metabolic conditions. CONCLUSIONS: While no overall associations between H pylori or Helicobacter species with NAFLD or related conditions were observed, some selected Helicobacter spp. antigens were associated with NAFLD. Further research is warranted to examine whether H. species are associated with any metabolic condition.

Lack of nutrient declarations and low nutritional quality of pre-packaged foods sold in Guatemalan supermarkets.

OBJECTIVE: To assess the presence of nutrition declarations and nutritional quality in pre-packaged food products sold in Guatemala. DESIGN: We photographed nutrition labels of pre-packaged foods. We extracted information about declaration of energy, total/saturated/trans-fats, total/added sugars and Na content (critical nutrients). We classified all products according to their degree of processing (NOVA classification) and nutritional quality (PAHO and WHO-Europe nutrient profile models). SETTING: Pre-packaged foods for sale in seven supermarkets in Guatemala City. PARTICIPANTS: This study did not involve human subjects. RESULTS: We assessed 3459 pre-packaged foods, including 80 % ultra-processed, 7 % processed and 13 % unprocessed/minimally processed foods or culinary ingredients. Nutritional information was available in 3021 products (87·3 %). Energy content was declared in 87·0 %; total fats in 86·1 %; saturated fats in 81·5 %; trans-fats in 48·9 %; total sugars in 70·3 %; added sugars in 0·5 % and Na/salt in 85·5 % of products. Insufficient nutrient information made impossible to assess nutritional quality in 36·6 and 17·1 % of products with the PAHO and WHO-Europe models, respectively. Using PAHO and WHO nutrient profiles, we found that 66·2 and 50 % of food products did not meet the model's nutritional criteria. CONCLUSIONS: A high proportion of pre-packaged foods with nutritional information available in Guatemalan supermarkets do not meet the nutritional criteria recommended by WHO and PAHO. Furthermore, a high proportion of products did not declare critical nutrients and many did not even provide any nutritional information. National regulations should consider making critical nutrient declarations (including trans-fats and sugars) mandatory for all products.

Socio-economic and ethnic disparities of malnutrition in all its forms in Guatemala.

OBJECTIVE: To analyse disparities of malnutrition in all its forms by socio-economic indicators in children aged <5 years, adolescent girls and women of reproductive age (WRA). DESIGN: We defined wasting/underweight, stunting/short stature, overweight and obesity following the WHO criteria for children aged <5 years, adolescents and WRA. We evaluated the prevalence of malnutrition by wealth status, education level and ethnicity (indigenous/non-indigenous). SETTING: Guatemalan 2014-2015 National Maternal and Child Health Survey. PARTICIPANTS: Children aged <5 years (n 11 962), adolescent girls aged 15-19 years (n 1086) and WRA aged 20-49 years (n 11 354). RESULTS: Stunting/short stature prevalence among children, adolescents and WRA was 2·8, 2·1 and 2·0 times higher in the poorest compared with the richest; 2·9, 2·9 and 2·1 times higher in the lower educational level than in the highest; and 1·7, 1·7 and 1·6 times higher in the indigenous than in the non-indigenous population. In contrast, overweight/obesity prevalence among children, adolescents and WRA was 1·6, 2·1 and 1·8 times higher in the richest compared with the poorest; 1·6, 1·3 and 1·3 times higher in the higher educational level than in the lowest; and 1·3, 1·7 and 1·3 times higher in the non-indigenous than in the indigenous population. CONCLUSIONS: Stunting/short stature is more prevalent among low-income, low-education and indigenous populations in all age groups. In contrast, overweight/obesity is more prevalent in high-income, high-education and non-indigenous populations in all age groups. These outcomes demonstrate socio-economic and ethnic disparities for malnutrition in all its forms.

Overabundance of unhealthy food advertising targeted to children on Guatemalan television.

To assess, for the first time, the extent (by hour channel) and nature (e.g. persuasive marketing techniques (PMT) and health-related claims) of unhealthy food advertisements (ads) targeted at children (3-11 years) on the six most-watched television (TV) channels in Guatemala. We recorded 864 h of video on the six most popular channels featuring children's programmes. We classified food and beverage ads as permitted or non-permitted for marketing to children, according to the 2015 World Health Organisation (WHO) nutrient profile. Furthermore, we also analysed PMT (i.e. premium offers, promotional characters, brand benefit claims) and health-related claims. Most food ads (85%) were non-permitted to be marketed to children. Non-permitted food ads were six times more likely, either on weekdays or weekends, for all programme and channel categories compared with permitted food ads. There was no difference in the frequency of non-permitted food ads between peak and non-peak hours, weekend and weekdays or children and non-children programmes. PMT and health-related claims were present in all food ads (5.3 ± 1.9 techniques/claims per ad). There is a need to regulate food ads on TV channels featuring children's programmes in Guatemala as a result of a high frequency of non-permitted food ads and extensive use of PMT together with health-related claims.

Television food and beverage marketing to children in Costa Rica: current state and policy implications.

OBJECTIVE: To examine the frequency of television (TV) food and beverage advertisements (F&B ads) to which children (4-11 years) are likely exposed and the nutrient profile of products advertised. DESIGN: TV broadcasting between September and November 2016 was recorded (288 h of children's programming; 288 h of family programming) resulting in 8980 advertisements, of which 1862 were F&B ads. Of those, 1473 could be classified into one of the seventeen food groups, and into permitted/non-permitted according to the WHO-EU nutrient profile model. Persuasive marketing techniques used were also identified. SETTING: TV programming was recorded for four weekdays and four weekend days, between 06.00 and 00.00 hours (576 total hours), for four channels (two national and two cable), in Costa Rica. RESULTS: Mean (sd) number of F&B ads/h was greater in cable than national channels (3·7 (0·4) v. 2·8 (0·4), P < 0·05) and during children's peak viewing hours (4·4 (0·4) v. 2·9 (0·3)). Of F&B ads classified with WHO-EU nutrient profile model (n 1473, 71·1 %), 91·1 % were non-permitted to be marketed to children. Categories most frequently advertised were ready-made/convenience foods (16 %), chocolates/confectionery/desserts (15 %), breakfast cereals (14 %), beverages (15 %), edible ices (9 %) and salty snacks (8 %). Non-permitted F&B ads were more likely to use promotional characters, brand benefit claims, and nutrition and health claims than permitted F&B ads. CONCLUSIONS: Children watching popular TV channels in Costa Rica are exposed to a high number of unhealthy F&B ads daily. Our findings help justify the need for regulatory actions by national authorities.

The food environment in Latin America: a systematic review with a focus on environments relevant to obesity and related chronic diseases.

OBJECTIVE: Food environments may be contributing to the rapid increase in obesity occurring in most Latin American (LA) countries. The present study reviews literature from LA that (i) describes the food environment and policies targeting the food environment (FEP); and (ii) analytic studies that investigate associations between the FEP and dietary behaviours, overweight/obesity and obesity related chronic diseases. We focus on six dimensions of the FEP: food retail, provision, labelling, marketing, price and composition. DESIGN: Systematic literature review. Three databases (Web of Science, SciELO, LILACS) were searched, from 1 January 1999 up to July 2017. Two authors independently selected the studies. A narrative synthesis was used to summarize, integrate and interpret findings. SETTING: Studies conducted in LA countries. PARTICIPANTS: The search yielded 2695 articles of which eighty-four met inclusion criteria. RESULTS: Most studies were descriptive and came from Brazil (61 %), followed by Mexico (18 %) and Guatemala (6 %). Studies were focused primarily on retail/provision (n 27), marketing (n 16) and labelling (n 15). Consistent associations between availability of fruit and vegetable markets and higher consumption of fruits and vegetables were found in cross-sectional studies. Health claims in food packaging were prevalent and mostly misleading. There was widespread use of marketing strategies for unhealthy foods aimed at children. Food prices were lower for processed relative to fresh foods. Some studies documented high sodium in industrially processed foods. CONCLUSIONS: Gaps in knowledge remain regarding policy evaluations, longitudinal food retail studies, impacts of food price on diet and effects of digital marketing on diet/health.

Assessing cohesion and diversity in the collaboration network of the SALURBAL project.

The SALURBAL (Urban Health in Latin America) Project is an interdisciplinary multinational network aimed at generating and disseminating actionable evidence on the drivers of health in cities of Latin America. We conducted a temporal multilayer network analysis where we measured cohesion over time using network structural properties and assessed diversity within and between different project activities according to participant attributes. Between 2017 and 2020 the SALURBAL network comprised 395 participants across 26 countries, 23 disciplines, and 181 institutions. While the cohesion of the SALURBAL network fluctuated over time, overall, an increase was observed from the first to the last time point of our analysis (clustering coefficient increased [0.83-0.91] and shortest path decreased [1.70-1.68]). SALURBAL also exhibited balanced overall diversity within project activities (0.5-0.6) by designing activities for different purposes such as capacity building, team-building, research, and dissemination. The network's growth was facilitated by the creation of new diverse collaborations across a range of activities over time, while maintaining the diversity of existing collaborations (0.69-0.75 between activity diversity depending on the attribute). The SALURBAL experience can serve as an example for multinational research projects aiming to build cohesive networks while leveraging heterogeneity in countries, disciplines, career stage, and across sectors.

Growth patterns in childhood and adolescence and adult body composition: a pooled analysis of birth cohort studies from five low and middle-income countries (COHORTS collaboration).

OBJECTIVE: We examined associations among serial measures of linear growth and relative weight with adult body composition. DESIGN: Secondary data analysis of prospective birth cohort studies. SETTINGS: Six birth cohorts from Brazil, Guatemala, India, the Philippines and South Africa. PARTICIPANTS: 4173 individuals followed from birth to ages 22-46 years with complete and valid weight and height at birth, infancy, childhood and adolescence, and body composition in adult life. EXPOSURES: Birth weight and conditional size (standardised residuals of height representing linear growth and of relative weight representing weight increments independent of linear size) in infancy, childhood and adolescence. PRIMARY OUTCOME MEASURES: Body mass index, fat mass index (FMI), fat-free mass index (FFMI), fat mass/fat-free mass ratio (FM/FFM), and waist circumference in young and mid-adulthood. RESULTS: In pooled analyses, a higher birth weight and relative weight gains in infancy, childhood and adolescence were positively associated with all adult outcomes. Relative weight gains in childhood and adolescence were the strongest predictors of adult body composition (ß (95% CI) among men: FMI (childhood: 0.41 (0.26 to 0.55); adolescence: 0.39 (0.27 to 0.50)), FFMI (childhood: 0.50 (0.34 to 0.66); adolescence: 0.43 (0.32 to 0.55)), FM/FFM (childhood: 0.31 (0.16 to 0.47); adolescence: 0.31 (0.19 to 0.43))). Among women, similar patterns were observed, but, effect sizes in adolescence were slightly stronger than in childhood. Conditional height in infancy was positively associated with FMI (men: 0.08 (0.03 to 0.14); women: 0.11 (0.07 to 0.16)). Conditional height in childhood was positively but weakly associated with women's adiposity. Site-specific and sex-stratified analyses showed consistency in the direction of estimates, although there were differences in their magnitude. CONCLUSIONS: Prenatal and postnatal relative weight gains were positive predictors of larger body size and increased adiposity in adulthood. A faster linear growth in infancy was a significant but weak predictor of higher adult adiposity.

Ultraprocessed Products as Food Fortification Alternatives: A Critical Appraisal from Latin America.

Ultraprocessed products (UPPs), associated with obesity and non-communicable diseases (NCDs), are becoming predominant on the global market and a target for market-driven fortification initiatives. The aim of this article is to describe the implications of adding micronutrients to UPPs with excessive amounts of critical nutrients associated with NCDs and provide recommendations for legislation and policies. UPPs with added micronutrients such as breakfast cereals, sugar-sweetened beverages, powder beverages, fruit juices, sauces, and bouillon cubes, among others, are commonly available and heavily promoted in Latin American countries. Misleading advertising of UPPs with added micronutrients and with excessive content of sugar, fat, and salt might increase the consumption of such products, giving them a "health halo effect" that leads consumers to overestimate their nutritional quality and healthfulness. Although international collections of standards such as the Codex Alimentarius provide some guidelines on this matter, countries need to implement national legislations, through a food systems approach, to regulate the marketing and labeling of UPPs. Lastly, there is still the need to foster research to close knowledge gaps and help countries to guide the process of food fortification strategies from a regulatory standpoint.

Subjective social status is associated with happiness but not weight status or psychological distress: An analysis of three prospective birth cohorts from low- and middle-income countries.

Background: Subjective social status (SSS, perception of social position relative to a frame of reference) has been associated with physical, mental and socio-emotional wellbeing. However, these associations may be susceptible to unmeasured confounding by life course objective socio-economic position (SEP; such as wealth, education and employment) and life satisfaction. Purpose: To estimate the association of position on ladders of perceived community respect and perceived economic status with weight, distress and wellbeing, independent of objective SEP in cohorts from three low and middle-income countries. Methods: We used data from birth cohorts in Guatemala (n = 1258), Philippines (n = 1323) and South Africa (n = 1393). We estimated the association of perceived community respect and perceived economic status with body mass index (kg/m2), the World Health Organization's Self-Reported Questionnaire-20 (SRQ-20) for psychological distress, and Lyubomirsky's Subjective Happiness Scale. We estimated these associations using robust linear regression models adjusting for indicators of life course objective SEP, early life characteristics, adult covariates, and life satisfaction. Results: Participants in South Africa (age 27-28y) rated themselves higher on average for both the respect (7 vs 5 in Guatemala and 6 in Philippines) and economic (5 vs 3 in Guatemala and 4 in Philippines) ladder measures. Position on neither community respect nor economic ladders were associated with BMI or psychological distress. Higher position on community respect (Guatemala: 0.03, 95%CI: 0.01, 0.04; Philippines: 0.03, 95% CI: 0.02, 0.05; South Africa: 0.07, 95%CI: 0.04, 0.09) and economic (Guatemala: 0.02, 95%CI: 0, 0.04; Philippines: 0.04, 95%CI: 0.02, 0.07; South Africa: 0.07, 95%CI: 0.04, 0.10) ladders were associated with greater happiness. Conclusions: Subjective social status showed small but consistent associations with happiness in birth cohorts independent of life-course SEP.

Circulating bile acid concentrations and non-alcoholic fatty liver disease in Guatemala.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a major liver disease worldwide. Bile acid dysregulation may be a key feature in its pathogenesis and progression. AIMS: To characterise the relationship between bile acid levels and NAFLD at the population level METHODS: We conducted a cross-sectional study in Guatemala in 2016 to examine the prevalence of NAFLD. Participants (n = 415) completed questionnaires, donated blood samples and had a brief medical exam. NAFLD was determined by calculation of the fatty liver index. The levels of 15 circulating bile acids were determined by LC-MS/MS. Adjusted prevalence odds ratios (PORadj ) and 95% CI were calculated to examine the relationships between bile acid levels (in tertiles) and NAFLD. RESULTS: Persons with NAFLD had significantly higher levels of the conjugated primary bile acids glycocholic acid (GCA) (PORadj T3 vs T1  = 1.85), taurocholic acid (TCA) (PORadj T3 vs T1  = 2.45) and taurochenodeoxycholic acid (TCDCA) (PORadj T3 vs T1  = 2.10), as well as significantly higher levels the unconjugated secondary bile acid, deoxycholic acid (DCA) (PORadj T3 vs T1  = 1.78) and its conjugated form, taurodeoxycholic acid (TDCA) (PORadj T3 vs T1  = 1.81). CONCLUSIONS: The bile acid levels of persons with and without NAFLD differed significantly. Among persons with NAFLD, higher levels of the conjugated forms of CA (i.e. GCA, TCA) and the secondary bile acids that derive from CA (i.e. DCA, TDCA) may indicate there is hepatic overproduction of CA, which may affect the liver via aberrant signalling mediated by the bile acids.

Associations between aflatoxin B1-albumin adduct levels with metabolic conditions in Guatemala: A cross-sectional study.

BACKGROUND AND AIMS: Metabolic conditions such as obesity, type 2 diabetes, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD) are highly prevalent in Guatemala and increase the risk for a number of disorders, including hepatocellular carcinoma (HCC). Aflatoxin B1 (AFB1) levels are also notably elevated in the population and are known to be associated with HCC risk. Whether AFB1 also contributes to the high prevalence of the metabolic disorders has not been previously examined. Therefore, the purpose of this study was to assess the association between AFB1 and the metabolic conditions. METHODS: Four-hundred twenty-three individuals were included in the study, in which AFB1-albumin adduct levels were measured in sera. Metabolic conditions included diabetes, obesity, central obesity, metabolic syndrome, and NAFLD. Crude and adjusted prevalence odds ratios (PORs) and 95% confidence intervals (95% CI) were estimated for the associations between the metabolic conditions and AFB1-albumin adduct levels categorized into quartiles. RESULTS: The study found a significant association between AFB1-albumin adduct levels and diabetes (Q4 vs Q1 POR = 3.74, 95%CI: 1.71-8.19; P-trend .003). No associations were observed between AFB1-albumin adduct levels and the other conditions. CONCLUSIONS: As diabetes is the metabolic condition most consistently linked to HCC, the possible association between AFB1 exposure and diabetes may be of public health importance. Further studies are warranted to replicate the findings and examine potential mechanisms.

Assessing the Validity of Normalizing Aflatoxin B1-Lysine Albumin Adduct Biomarker Measurements to Total Serum Albumin Concentration across Multiple Human Population Studies.

The assessment of aflatoxin B1 (AFB1) exposure using isotope-dilution liquid chromatography-mass spectrometry (LCMS) of AFB1-lysine adducts in human serum albumin (HSA) has proven to be a highly productive strategy for the biomonitoring of AFB1 exposure. To compare samples across different individuals and settings, the conventional practice has involved the normalization of raw AFB1-lysine adduct concentrations (e.g., pg/mL serum or plasma) to the total circulating HSA concentration (e.g., pg/mg HSA). It is hypothesized that this practice corrects for technical error, between-person variance in HSA synthesis or AFB1 metabolism, and other factors. However, the validity of this hypothesis has been largely unexamined by empirical analysis. The objective of this work was to test the concept that HSA normalization of AFB1-lysine adduct concentrations effectively adjusts for biological and technical variance and improves AFB1 internal dose estimates. Using data from AFB1-lysine and HSA measurements in 763 subjects, in combination with regression and Monte Carlo simulation techniques, we found that HSA accounts for essentially none of the between-person variance in HSA-normalized (R2 = 0.04) or raw AFB1-lysine measurements (R2 = 0.0001), and that HSA normalization of AFB1-lysine levels with empirical HSA values does not reduce measurement error any better than does the use of simulated data (n = 20,000). These findings were robust across diverse populations (Guatemala, China, Chile), AFB1 exposures (105 range), HSA assays (dye-binding and immunoassay), and disease states (healthy, gallstones, and gallbladder cancer). HSA normalization results in arithmetic transformation with the addition of technical error from the measurement of HSA. Combined with the added analysis time, cost, and sample consumption, these results suggest that it may be prudent to abandon the practice of normalizing adducts to HSA concentration when measuring any HSA adducts-not only AFB1-lys adducts-when using LCMS in serum/plasma.