Obesity, Metabolic Syndrome, and Nutrition

Introduction

The increasing number of young patients with obesity worldwide is a major challenge for health care systems in industrial and in low- and middle-income countries. Childhood obesity tracks into adolescence and adulthood and is strongly correlated with the risk of adult poor health. Obesity is associated with an increased individual risk for the development of cardiometabolic comorbidities, as well as a decrease in health-related quality of life. A sedentary lifestyle and high-calorie diet combined with a genetic predisposition have been shown to be a key factor in developing obesity. Recent data suggest that the early-life environment can have lasting effects on the physiology and metabolism of the fetus and is associated with the early metabolic programming of human health. Some studies reviewed in this chapter show that a number of in utero exposures such as maternal diet and maternal intake of nonnutritive sweeteners (NNS) during pregnancy are associated with the subsequent development of childhood obesity and metabolic risk of the offspring. A metabolic signature at birth may help elucidate the mechanisms involved in metabolic health later in life. One of the reviewed studies investigated metabolic changes in cord blood that may predict subsequent infant overweight and obesity. Early-life nutrition also has a significant impact on lifelong health. One of the studies evaluated the impact of consumption of cow’s milk fat during infancy and childhood and child adiposity. Its findings demonstrate that compared to children who consumed reduced fat, milk, children who consumed whole milk had lower odds of overweight and obesity. An-other study revealed that higher fruit juice intake in infancy was associated with greater abdominal adiposity in mid-childhood and early adolescence.
School environments that support healthy food behaviors may positively influence child-hood obesity. School free fruit and vegetable (FFV) policies are used to promote healthy dietary habits and tackle obesity; however, a recent reviewed study observed that the nationwide FFV policy did not have any notable beneficial effect on weight status.
Other studies included in this chapter evaluated the impact of the diet composition on adiposity, fat distribution, and cardiometabolic risk markers. Different nutrient intakes in childhood were differentially associated with adolescent body fat accumulation. Addition-ally, the impact of higher consumption of ultraprocessed foods (UPFs) during childhood on increased adiposity is presented. One study found that the replacement of dietary carbohydrates with fats had favorable effects on lipoprotein cholesterol concentrations in adolescents and adults when fats were consumed as monounsaturated or polyunsaturated fatty acids but not as saturated fatty acids. In adults, the benefits of a high adherence to the Mediterranean diet (MD) to prevent cardiovascular events are widely known. A cur-rent systematic review presented in the chapter assessed whether interaction effects occur between an obesity genetic risk score and the adherence to MD on adiposity and metabolic syndrome (MetS) also in the young ages.
Children with obesity are prone to develop obesity-related comorbidities. One of the main comorbidities is nonalcoholic fatty liver disease (NAFLD). Current data found that dietary sugar restriction reduces hepatic de novo lipogenesis (DNL) and fasting insulin, in addition to reductions in hepatic fat among adolescents with NAFLD.
An additional study evaluated the potential relationship between vitamin D and cardio-metabolic risk among children, and reported that vitamin D supplementation had positive effects on high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and total cholesterol (TC), with several significant changes persisting during the post supplementation period.
Finally, considering the deleterious consequences of obesity in childhood, public health interventions are urgently called to take nutritional measures with policies that encourage healthy eating among children.
In this chapter, we review a selection of 15 notable articles published between July 2021 and June 2022, focusing on the relation between nutrition, obesity, and metabolic comorbidities from infancy to childhood and young adulthood.

Maternal Diet during Pregnancy and Risk of Childhood Obesity

Cord blood metabolic signatures predictive of childhood overweight and rapid growth

Comments: Childhood obesity is a condition which, throughout the past 100 years, has trans-formed from a sign of wealth and health to a disease that according to the WHO is “one of the most serious challenges of the 21st century” [1, 2]. Considering its complex and multiorgan health consequences, understanding in utero perturbations that lead to the development of obesity and obesity-related complications and identifying early predictive markers is of utmost importance. 

In this perspective, new metabolomic analysis might offer relevant information on the profiling of circulating small molecules that might characterize a metabolic state able to predict infant growth and overweight and obesity. Interestingly, in this study authors attempted to characterize the cord blood metabolic signatures of rapid growth in infancy and overweight in early childhood in 4 European birth cohorts, using un-targeted liquid chromatography–mass spectrometry (LCMS)-based metabolic profiling. Authors were able to show that cholestenone and branched-chain amino acid levels in cord blood are predictive of rapid growth and overweight/obesity, respectively, among healthy deliveries from 4 European populations.

In multivariate analysis, authors also showed that the addition of metabolites substantially improved prediction of both rapid growth and overweight compared with models using traditional risk factors alone. Thus, cholestenone and branched-chain amino acids resulted to be suggestive of a role of the gut microbiome and nutrient signaling, respectively, in child growth trajectories.

Early infancy represents a window of developmental plasticity during which environ-mental exposures can modulate the risk of chronic disease. Accelerated postnatal weight gain trajectories are associated with increased risk of diabetes, obesity, and cardiovascular diseases both in humans and mammalian models. These data have implications for public health, as the postnatal period offers a window during which optimizing nutrition and/or growth rates could reap lifelong benefits. Thus, identifying early markers of rapid infancy weight gain, a potentially modifiable risk factor for obesity and type 2 diabetes, may eventually permit interventions targeting children at high risk for metabolic disease.
Metabolomic analysis allows comprehensive quantification of hundreds of nutrients, metabolic intermediates, and small molecules from biological samples and has proven a powerful tool for biomarker discovery. Thus, further studies evaluating the cord blood metabolic signatures related to obesity risk and its related complications are aimed in order to better tailor preventive strategies to contrast obesity epidemic since early childhood.

Maternal diet quality during pregnancy is associated with biomarkers of metabolic risk among male offspring

Comments: A growing body of evidence indicates that prenatal exposures, such as maternal high fat or high-sugar diets, can have obesogenic effects in the offspring [3, 4]. Therefore, there is an urgent need to identify modifiable risk factors in pregnancy that could inform public health interventions and reduce the burden of obesity. The Healthy Eating Index-2010 (HEI) measures dietary patterns that are marked by higher consumption of vegetables, fruit, fish, and unsaturated fats, in conjunction with lower intakes of red and processed meat and saturated fats. 

This study aimed to examine the association of maternal diet quality in pregnancy, as indicated by the HEI, with offspring metabolic biomarkers and body composition at age 4–7 years. On average, women had an HEI score of 55.0 throughout pregnancy, and 43.0% had a score >57, a threshold associated with lower adiposity at birth in this cohort. Women with a score >57 consumed fewer carbohydrates, less total fat, and slightly less protein compared with women with a score ≤57. A higher HEI score was associated with higher education, lower pre pregnancy body mass index (BMI), not smoking during pregnancy, and lower physical activity. 

This may indicate that women with a higher HEI score had in general better lifestyle behavior. Higher maternal diet quality during pregnancy was associated with a more favorable glucose-insulin homeostasis and lipid profile in male offspring, as indicated by lower concentrations of glucose, insulin and homeostatic model assessment of insulin resistance, and the ratio of fasting triacylglycerols: HDL cholesterol, even after accounting for potential confounders and mediators.

However, following further adjustment for the child’s HEI score and physical activity levels, the magnitudes of associations for glucose and triacylglycerols:HDL were slightly attenuated and no longer reached the threshold of statistical significance. This observation may point to the significance of healthy lifestyle also in early childhood to modify cardiometabolic risk biomarkers. Interestingly, among girls, maternal HEI score was not associated with metabolic biomarkers or body composition after accounting for maternal and perinatal characteristics. This remarkable observation of sex dimorphism of maternal diet effect on metabolic biomarkers of the offspring may be explained by studies of the epigenome and transcriptome of murine and human placentas that have shown sex-specific differences in gene expression with respect to maternal diet during pregnancy [5, 6]. 

The study strength includes the relatively large number of included mother-offspring pairs with the long-term evaluation. The main limitation of the study is that the calculation of the HEI was based on data from dietary recalls collected over the course of pregnancy, which may suffer from recall bias. Nevertheless, the onset of childhood obesity and associated metabolic traits that occur at early ages highlights the gestational period as a critical window during which prevention efforts could have long-lasting impacts.

Associations of maternal non-nutritive sweetener intake during pregnancy with offspring body mass index and body fat from birth to adolescence

Comments: Nonnutritive sweeteners (NNS) are widely consumed as “healthier” alternatives to sugar. Yet, recent evidence suggests NNS may adversely influence weight gain and metabolic health. The impact of NNS during critical periods of early development has rarely been studied. A recent study had shown, by triangulating evidence from humans, mice, and cultured adipocytes, that maternal NNS consumption during pregnancy may program obesity risk in offspring through effects on adiposity and adipocyte differentiation [7].

The purpose of the reviewed study was to examine the extent to which NNS intake during pregnancy is associated with offspring BMI z-score trajectory and body fat measured from birth to 18 years, using mother-child pairs. The findings of the study show that mothers who had the highest quartile of NNS intake versus the lowest quartile (Q4 vs. Q1) had higher pre pregnancy BMI and were more likely to be of White Ethnicity and smoke during pregnancy, which may point to less healthy lifestyle behaviors in general. In unadjusted and adjusted multivariable regression models, NIOS intake in the highest versus lowest quartiles was associated with higher BMI z-score at infancy, early childhood, mid-childhood, and early adolescence, but not birth. High Maternal NNS intake was also associated with higher sum of skinfolds in early childhood, mid-childhood, and early adolescence compared with low maternal NNS intake. In adjusted mixed-effect models, there was a positive interaction between the maternal NNS intake – offspring BMI z-score relationship and child age, which means that the strength of the association between maternal NNS intake and offspring BMIz-score increased as the children aged.

The strengths of the study are the relatively large sample size, the detailed information collected (including covariates), and the longitudinal design as the researchers examined childhood BMI z-score longitudinally, from birth to age 18 years, and the use of 2 different measurements of body fat (sum of skinfolds and fat mass index).The limitation of the study is that, since most of the participants were college educated and of White ethnicity, it limits the generalizability of the results. Also, the researchers did not include post exposure factors such as child dietary habits or physical activity, which could potentially modify relationships between maternal NNS consumption and childhood growth and adiposity. Moreover, these results are observational, and therefore conclusions about causality cannot be drawn.

Nutrition during Childhood and Risk of Childhood Obesity

Longitudinal associations of fruit juice intake in infancy with DXA-measured abdominal adiposity in mid-childhood and early adolescence

Comments: Early introduction of complementary foods, sugar-sweetened beverages, and unsweetened fruit juice has been directly associated with obesity in young children [8].The American Academy of Pediatrics recommends breast milk to be the sole source of nutrients during the infant’s first 6 months of life and that solid foods or liquids be introduced around 6 months of age [9]. The American Academy of Pediatrics also recommends avoiding fruit juice and sugar-sweetened beverages during the infant's first year [9] because they have a high sugar content, lower nutrient content, and links with obesity and particularly with abdominal obesity.

Excessive adiposity and particularly abdominal adiposity is an independent risk factor for impaired glucose metabolism and to adverse cardiometabolic health in children[10]. Understanding the early-life factors influencing these abdominal adiposity measures is therefore important with the aim to develop strategies to prevent excessive abdominal adiposity and its associated cardiometabolic disease risk.

In this study, by using data from Project Viva, a longitudinal Boston area pre birth cohort, authors attempted to examine the associations of exposure to fruit juice intake in infancy with repeated measures of abdominal adiposity assessed by dual-energy X-ray absorptiometry in mid-childhood and early adolescence. Particularly, authors showed that higher fruit juice intake at age 1 year was associated with persistently greater visceral adipose tissue, subcutaneous abdominal adipose tissue, and total abdominal adipose tissue area standard deviation scores in mid-childhood and early adolescence. These associations were observed to be greater in magnitude for visceral adipose tissue than for subcutaneous abdominal adipose tissue and total abdominal adipose tissue. Thus, these results suggest that exposure to higher fruit juice intake in infancy is associated with persistently greater abdominal adiposity, particularly visceral adiposity, in mid-childhood and early adolescence.

These findings reinforce the recommendations of limiting infant intake of fruit juice, which could have later impact on visceral adiposity in childhood and adolescence. In addition, these results support the implementation of early-life behavioral interventions to counter obesogenic feeding practices during infancy, particularly in those populations at higher risk of obesity and diabetes.

Cow’s milk fat and child adiposity: a prospective cohort study

Comments: International guidelines recommend that children aged 9 months to 2 years consume whole (3.25%) fat cow’s milk, and children older than age 2 years consume reduced(0.1–2%) fat cow’s milk to prevent obesity [11–13].

Previous systematic reviews already revealed that whole milk was associated with lower risk of childhood overweight or obesity among children aged 9 months to 18 years [14]. A recent study from the USA estimated the associations of the frequency and fat content of early childhood milk intake with early adolescent adiposity and cardiometabolic risk [15]. Its finding showed that consumption of higher-fat cow’s milk in early childhood was not associated with increased adiposity or adverse cardiometabolic health over a decade later.

The current study evaluated the longitudinal relationship between cow’s milk fat(0.1–3.25%) intake and BMI z-score in childhood. On average, children who consumed whole milk had a 0.1 lower BMI z-score than children who consumed reduced fat milk. The researchers found that compared to children who consumed reduced fat (0.1–2%) milk, there was evidence that children who consumed whole milk had 16% lower odds of overweight and 18% lower odds of obesity.

Possible mechanisms underlying the observed relationship include that children who consume higher cow’s milk fat may be more satiated than those who consume reduced fat cow’s milk, leading them to consume a lower quantity of cow’s milk or other energy-dense foods contributing to higher energy intake. Hormones secreted in response to whole milk consumption such as cholecystokinin and glucagon-like peptide 1 may play a role. Cow’s milk fat contains unique fatty acids such as trans palmitoleic acid and conjugated linoleic acid, which may provide cardiometabolic benefits relative to other fatty acids. Therefore, cow’s milk fat may not contribute to energy storage and adipose tissue as significantly as other types of dietary fat. Also, a lower-fat diet in early life may program the body to favor energy storage over utilization, which may increase the risk of obesity over the life course.

The strengths of the current study are its design to overcome weaknesses of previous analyses and minimize risk of bias through a large prospective cohort study with adjustment for important potentially confounding factors. Its limitation includes that since the study participants were from healthy urban Canadian children, they may not be representative of other groups of children. Also, cow’s milk with different fat contents may have been offered to children based on parent perception of body size.

The study findings support the guideline for children aged 9 months to 2 years, but suggest that guidelines for older children may not be effective in preventing childhood overweight or obesity and adverse cardiometabolic outcomes.

A nationwide school fruit and vegetable policy and childhood and adolescent overweight: a quasi-natural experimental study

Comments: Although the global trends of rising BMI among children and adolescents have leveled off in many high-income countries, a shift toward an increased prevalence of severe forms of obesity has been documented in males and females in all age groups[16]. Therefore, a stronger and negative effect of overweight and obesity during childhood on psychosocial and cardiovascular health as well as on its related increased morbidity and mortality that urgently need to be contrasted is expected. However, to date most of the adopted strategies have failed to reach their goals in contrast to the rise of the prevalence of obesity worldwide. Thus, effective prevention strategies are needed.

Unhealthy dietary behaviors such as skipping breakfast, irregular eating patterns, and the consumption of fast food and high-sugar beverages are known to contribute to obesity and are prevalent in this group of subjects. Evidence also suggests that young people from areas of socioeconomic deprivation are less likely to consume fruit and vegetables and more likely to consume energy-dense fast foods. Understanding the social and environmental influences of eating behaviors has the potential to enhance the understanding of how to improve health outcomes for young people.

In this study, authors were able to explore the effect of a nationwide program adopted in Norway. Particularly, between 2007 and 2014, schools were obligated to provide a daily piece of free fruit or vegetable to all Norwegian children in combined schools(covering grades 1–10, age 6–16 years). Interestingly, using data from 11,215 Norwegian children and early adolescents, authors have observed little evidence of any beneficial or unintended impact from exposure to the FFV policy on weight outcomes in either boys or girls at age 8.5 and 13 years. Although authors were not able to show a strong impact of the Norwegian nationwide program on prevention of obesity, these results clearly show the need of population-wide approaches and particularly combined with physical activity. These programs need to be concentrated further at school level. In fact, schools are an optimal setting for health promotion due to the potential to reach all children regardless of sociodemographics.

Meta-analyses and systematic reviews [17] of randomized controlled trials indicate that increased fruit and vegetable consumption may promote weight loss and fruit and vegetables consumed may substitute for more energy-dense foods thus preventing weight gain. Information about the possible benefits or unintended consequences of school dietary interventions is clearly important. Despite this, there are very few evaluations of school fruit and vegetable provision. Therefore, further studies are needed in order to better tailor an effective school-based strategy with the aim to contrast the alarming increase of obesity and its related complications in childhood.

Association between childhood consumption of ultraprocessed food and adiposity trajectories in the Avon Longitudinal Study of Parents and Children birth cohort

Comments: Ultraprocessed foods (UPFs) are industrial formulations of ingredients that undergo a series of physical, chemical, and biological processes. They typically lack intact healthy food components, include various additives, and tend to be more energy dense and nutritionally poorer compared with less processed alternatives. Children Are the leading consumers of UPFs. A previous systematic review showed that most studies have found positive associations between consumption of UPF and increased body fat during childhood and adolescence [18]. A more recent systematic review that included 10 studies, 5 longitudinal and 5 cross-sectional, mainly conducted in Brazil, found that in 4 longitudinal studies in children with a follow-up longer than 4 years, there was a positive association between the consumption of UPF and obesity and adiposity parameters, whereas cross-sectional studies failed to find an association [19].

The current study assessed longitudinally the associations between UPF consumption and adiposity trajectories from childhood to early adulthood in a large cohort of British children. They found that children with higher UPF consumption were more likely to have lower maternal socioeconomic profiles compared with those in lower UPF quintiles. Their findings demonstrate that among those in the highest quintile of UPF consumption compared with their lowest quintile counterpart, trajectories of BMI increased by an additional 0.06/year; fat mass index by an additional 0.03/year; weight by an additional 0.20 kg/year; and waist circumference by an additional 0.17cm/year.

The strengths of the study are the large sample size, the longitudinal long-term follow-up with a median of 10.2 years with an annual evaluation, the assessment of UPF consumption by detailed 3-day food diaries, and multiple adiposity measurements with assessment of the body fat mass by dual-energy X-ray absorptiometry measurements.

In addition, the advantage of the models they used is the inclusion of different covariates that may impact body weight such as birth weight, physical activity evaluated by accelerometer data, mean daily calorie intake, and maternal-related data (pre pregnancy BMI, marital status, educational and socioeconomic status).

The findings of this cohort study suggest that higher consumption of UPFs in childhood is associated with more rapid progression of increased BMI and fat mass into adolescence and early adulthood. Since those from the lower socioeconomic status were the main consumers of UPFs, it calls for more effective public health actions that can reduce children’s exposure and consumption of UPFs, maybe by lowering the prices of less processed alternatives and increased taxes on the food industry that promote these UPFs.

Eating contexts and their associations with sociodemographic factors in Brazilian adolescents (EVA-JF Study)

Comments: The rising incidence of metabolic diseases, namely, obesity, MetS, or type 2 diabetes mellitus, is one of the main social challenges ahead now and in the coming years. These diseases are closely related to dietary habits which need to be evaluated in the clinical setting of all outpatient pediatric obesity clinic. Diet surveys have been continuously demonstrating negative changes in the eating habits of adolescents, with reduced consumption of fruits and vegetables, increased consumption of soft drinks and other sugary drinks, and replacement of traditional culinary preparations, based on unprocessed or minimally processed foods, by UPFs. However, eating habits also include some peculiar aspects such as eating contexts (e.g., skipping breakfast, eating out, eating in front of screens, watching TV, playing video games, or using smartphone/tablet/computer) or while studying and having meals without company which have been shown to be associated with a lower diet quality, lower daily ingestion of vitamins and minerals, and a greater BMI.

Therefore, the aim of this exploratory study was to estimate associations of eating contexts with food consumption according to the degree of industrial processing and overweight indicators in a relatively large sample of Brazilian adolescents. Particularly, authors were able to show that inappropriate eating contexts at breakfast and dinner were associated with a lower consumption of unprocessed or minimally processed foods and culinary ingredients, a higher consumption of UPFs, greater BMI-forage, and greater percentage of body fat in Brazilian adolescents. Therefore, results of this study are relevant in order to provide information to design actions and nutrition programs applicable to the school environment, to improve food practices, prevent overweight, and promote an improvement in the health of the young population, since many lifestyle behaviors and risk factors tend to continue into adulthood.

Vegetarian diet, growth, and nutrition in early childhood: a longitudinal cohort study

Comments: Vegetarian and vegan diets have become more popular also among children in recent years. However, these diets may have the risk of nutrient insufficiency without appropriate clinical follow-up and supplement use. On the other side, interventional trials have consistently demonstrated that consumption of plant-based diets reduces body fat in overweight and obese subjects, even when controlling for energy intake. The Major dietary mechanisms that may lead to reduced body fat include reduced caloric density, improved gut microbiota symbiosis, increased insulin sensitivity, reduced trimethylamine-N-oxide, activation of peroxisome proliferator-activated receptors, and overexpression of mitochondrial uncoupling proteins. Collectively, these factors improve satiety and increase energy expenditure leading to reduced body weight [20].The aim of the current study was to examine the relationships between vegetarian diet and growth, micronutrient stores, and serum lipids among healthy children. A higher percentage of children with vegetarian diet were more likely to have Asian Ethnicity (33.8 vs. 19.0%), and a higher percentage of them got iron supplementation and vitamin D supplementation compared to nonvegetarian (10.6 vs. 5.6% and 49.6vs. 41.9%, respectively), which may affect the results of the association between vegetarian diet and micronutrients.

The researchers did not find evidence of differences in mean BMI z-score or BMI z score growth rates between children with vegetarian diet and nonvegetarian diet. They found that vegetarian diet was associated with higher odds of underweight, but there was no evidence of an association with overweight or obesity. They found a weak association between vegetarian diet and lower mean height z-score. No associations were found between vegetarian diet and serum ferritin, vitamin D, or serum lipids. Children with a vegetarian diet who consumed little to no cow’s milk had lower serum lipids than children with a nonvegetarian diet. It may be assumed that children with vegetarian diet who do not consume cow’s milk may drink a larger volume of plant-based milks, which have been identified to have a lipid-lowering effect in adults. However, children with and without vegetarian diet who consumed the recommended 2 cups of cow’s milk per day had similar serum lipids.

The strengths of the study are the large sample size, the longitudinal design of the study, availability of anthropometric measures that were obtained by trained research assistants during each visit, and the inclusion in the analysis of potential confounders that were collected at each health care visit, along with exposure and outcome measures. The limitations of the study include the absence of detailed measures of dietary intake and physical activity and information on parental dietary intake which may impact body weight; also, the relatively short time follow-up duration of an average 2.8 years. Therefore, larger longitudinal cohort studies are required to allow the evaluation of the different types of vegetarian diet on longer-term outcomes.

Nutrition and Risk of Obesity-Related Comorbidities

Association between diet quality index and cardiometabolic risk factors in adolescents: Study of Cardiovascular Risks in Adolescents (ERICA)

Comments: Diet-related cardiometabolic diseases, such as obesity, diabetes, and cardiovascular disease, inflict considerable implications on our health and economy, also in childhood. Using dietary patterns to assess the association between diet and health outcomes has been suggested to be a potential tool to be integrated to the traditional single-nutrient approach [21, 22]. The main advantages of these indices are the possibility to assess the complexity of the human diet and summarize it into a score, taking into account dietary patterns, guidelines for a healthy diet, and food preparation methods. A dietary pattern summary score can be used to evaluate a subject’s overall diet and categorize their intake based on the degree of adherence to the eating recommendations used to construct the score. This multidimensional approach allows us to detect the collective impact of multiple nutrients and delivering practical, holistic dietary messages, consistent with public health recommendations. However, most dietary indices were developed based on nutritional recommendations for adult populations and, consequently, are improper to accurately assess diet quality in adolescents.

Current evidence about the associations between each of these diet quality scores and cardiometabolic risk in pediatric populations is inconsistent, underscoring the need for prospective cohort studies that investigate the relationship between diet quality and cardiometabolic risk factor. In this study, by using the Diet Quality Index for Adolescents, which was designed and validated in a sample of adolescents enrolled in the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA), authors were able to explore the relationship between diet quality and cardiometabolic markers in a nationally representative sample Brazilian adolescents. Particularly, they showed that in normal-weight girls, higher scores were associated with better cardiometabolic profiles; however, no association was observed in those with overweight/obesity. In boys, a better quality of diet was associated with lower concentrations of LDL cholesterol, independent of the weight status, and with TC only in those with overweight/obesity. Thus, the evaluated score might be a helpful tool characterizing the association between diet quality and cardiometabolic markers in adolescents with the aim to modify some cardiometabolic risk factors present in childhood and adolescence that are known to persist into adulthood, increasing the risk for premature development of cardiovascular disease and type 2 diabetes.

Further studies evaluating ethnic and regional differences in these and other available scores might offer more validation tools in childhood adoptable in the clinical setting.

Dietary macronutrient composition in relation to circulating HDL and non-HDL cholesterol: a federated individual-level analysis of cross-sectional data from adolescents and adults in 8 European studies

Comments: Cardiovascular diseases represent the most common cause of death worldwide with clear evidences of the development of precocious alterations already since childhood. Although different factors including obesity, chronic inflammation, cytokine, and chronic disease might negatively affect cardiovascular risk, alterations in the lipoprotein metabolism such as high concentrations of TC and LDL cholesterol and low concentrations of HDL cholesterol certainly represent the key risk factors accounting for ∼50% of cardiovascular diseases.

LDL cholesterol, intermediate-density lipoproteins, very low-density lipoproteins, and remnant lipoproteins represent the non-HDL cholesterol components of atherogenic particles. Interestingly, dietetic approaches aimed to affect the composition of the macronutrient have shown to modify these atherogenic particles, thus affecting the cardiovascular risk. Recent data have shown that non-HDL cholesterol correlated more closely with cardiovascular risk than LDL cholesterol, and non-HDL cholesterol has therefore recently emerged as a new target for the prevention of cardiovascular events [23]. Therefore, comprehensive studies evaluating the effects of diet on atherogenic molecules are needed in order to characterize the cardiovascular risk related to HDL and non-HDL cholesterol.

Thus, in this study authors investigated the association of the isocaloric replacement of carbohydrates with total fat or different types of fat with blood lipoproteins HDL cholesterol, non-HDL cholesterol, and the ratio of HDL cholesterol to TC (HDL cholesterol/TC) by sex and age in 8 European observational studies participating in the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI)project. Interestingly, authors were able to show that the isocaloric replacement of carbohydrates with total fats or monounsaturated fatty acids was positively associated with HDL cholesterol, whereas the replacement of carbohydrates with saturated fatty acids was positively associated with non-HDL cholesterol concentrations. The replacement of carbohydrates with polyunsaturated fatty acids was inversely associated with non-HDL cholesterol concentrations.

Taken together these data confirm that the consumption of fats in place of carbohydrates have beneficial effects when fats are consumed in the form of monounsaturated fatty acids or polyunsaturated fatty acids but not saturated fatty acids. Thus, tailored dietetic approaches might strongly affect cardiovascular risk by modifying particularly those cholesterol-related atherogenic molecules. In addition, further studies confirming these data and particularly evaluating in a longitudinal setting early atherosclerotic marker [24] might fully elucidate the cause-effect relationship of such approaches aimed to reduce the cardiovascular risk already since childhood.

Dietary sugar restriction reduces hepatic de novo lipogenesis in adolescent boys with fatty liver disease

Comments: NAFLD represents the most common chronic liver disease in childhood. In addition, it is considered the hepatic manifestation of MetS, thus representing a key alteration of a relevant condition which is well known to be strongly related to an increased risk of cardiovascular disease [25, 26].
Treatment and prevention of NAFLD are based on lifestyle intervention, thus representing diet the key point for its improvement. However, some nutrients could play a role in its pathophysiology. Particularly, experimental studies in adults have shown that shifting to high-sugar diets, especially diets containing fructose, increases both hepatic DNL and hepatic fat, even in the absence of weight gain [27]. While adult data are more robust, reports in children are limited.

In this study, authors were able to test the effect of 8 weeks of dietary sugar restriction on hepatic DNL in adolescent boys with NAFLD (11–16 years old) who participated in a randomized, controlled treatment study comparing a diet low in free sugars versus their usual diet. Hepatic DNL was measured as a percentage contribution to plasma triglyceride palmitate using a 7-day metabolic labeling protocol with heavy water. Hepatic fat was measured by magnetic resonance imaging–proton density fat fraction. Interestingly, authors showed that treatment in adolescent boys with NAFLD decreased DNL by nearly one third (from 34.6 to 24.1%). Interestingly, these effects were shown to be independent of weight loss. In fact, this finding was similar, but slightly attenuated after adjusting for weight change during the intervention. In addition, authors showed that change in DNL was directly correlated with changes in free-sugar intake, fasting insulin, and alanine transaminase during the intervention. Overall, these findings are consistent with the hypothesis that dietary free-sugar restriction is a strategy for reducing hepatic DNL, which in turn is beneficial for other metabolic outcomes in pediatric NAFLD. Therefore, this study clearly confirmed the tight correlation between intake of sugar in the diet and NAFLD and particularly its ability to affect NAFLD by modulating DNL in children. Thus, due to the role of some nutrients in the pathophysiology of NAFLD, the complete knowledge of other major components is needed in order to better activate effective preventive and treatment strategies in children and adolescents at risk for or with NAFLD.

Childhood nutrient intakes are differentially associated with hepatic and abdominal fats in adolescence: the EPOCH study

Comments: Studies have shown that greater abdominal fat deposition, especially visceral fat, and hepatic fat deposition are strong risk factors for insulin resistance and other cardiometabolic risk factors in youth, independent of total adiposity [28, 29].

It is known that obesity, nutrition, lifestyle variables, genetic and epigenetic factors may be causally involved in the development of NAFLD in children. Diet composition and in particular simple carbohydrate intake (especially high fructose intake) was reported as factors that may promote the development of NAFLD, whereas nondigestible carbohydrates (dietary fiber), by affecting gut microbiota, may favor the integrity of gut wall and reduce inflammation, opposing this process [30].

This study aimed to examine whether nutrient intakes in childhood are associated with abdominal and hepatic fat depots later in adolescence. Using data from a longitudinal cohort, they showed that nutrient intakes in childhood (∼10 years of age)were differentially associated with different types of abdominal and ectopic fat deposition later in adolescence; specifically, higher unsaturated fat intake predicted abdominal subcutaneous adipose tissue, higher animal protein intake predicted visceral adipose tissue, and higher starch intake predicted hepatic fat.

A previous study found that decreases in fiber and vegetable protein and increases in saturated fat intake between childhood and adolescence interact with the PNPLA3 variant risk allele (a strong genetic risk factor for hepatic fat) to predict higher hepatic fat in adolescence [31]. However, Cohen et al. did not find an association between childhood fiber intake and adolescent hepatic fat, but this may be biased by the higher starch intake that is usually low in fiber. Interestingly, they also did not find associations between childhood total sugar intake and adolescent abdominal visceral adipose tissue or hepatic fat, which conflicts with studies in children showing that dietary sugar restriction was associated with reductions in these body fat depots [32,33]. These discrepancies may be due to differences in sample characteristics, because most previous studies have focused on youth with obesity, compared with the generally healthy sample of youth in the current study. It may also suggest that intakes of the different nutrients (i.e., sugar, fiber) more proximal to adolescence may be more relevant to body fat partitioning patterns than intakes earlier in childhood.

The strengths of the study are the prospective design with the longitudinal of approximately 6 years follow-up between exposure and outcome and the assessment of abdominal and hepatic fat mass by magnetic resonance imaging. Its limitations include the reliance on self-reported dietary intake data, which can be prone to social desirability bias, particularly in individuals with obesity and may contribute to dietary underreporting; and also, the observational nature of this study, which limits causal inference.

Nevertheless, the findings of this study may be used to plan dietary interventions aiming to promote a healthier body fat distribution in youth

Mediterranean diet and genetic determinants of obesity and metabolic syndrome in European children and adolescents

Comments: MD is characterized by the prevalent consumption of fruits, vegetables, whole grain cereals, legumes, nuts, and seeds, with olive oil as the main source of added fat. The MD is associated with significant health benefits, with higher MD adherence at early ages associated with a lower risk of developing obesity during childhood [34]. Research indicates a major role for genetic susceptibility to obesity and the MetS. Therefore, predisposing genetic factors for development of obesity and the associated metabolic complications may change the “protecting effect” of the MD. Understanding The biological impact of gene-nutrient interactions can provide a key insight into the pathogenesis and progression of diet-related polygenic disorders, including MetS. Indeed, in European youth, the individual’s genetic profile has been previously observed to modulate the effect of MD in terms of obesity and MetS [35].

The current study is based on a systematic literature search with evaluation of the impact of genetic factors in the ability of MD to reduce the obesity and MetS risk, and to observe the impact of MD on the genetic predisposition to obesity and MetS. The present review has shown that gene-diet interaction effects in early life remain deeply understudied in young individuals of European origin. Only one study evaluated these issues in the pediatric age group [35]. This study was carried out under the HELENA study, a cross-sectional multicentric study in European adolescents. Its main findings showed that the influence of high MD adherence on adiposity and MetS was only observed if a limited number of risk alleles were present. In addition, the gene-interaction effect showed sex-specific differences, being higher in females than males.

The strengths of that study are the large sample of patients (n = 605) included and, due to the multicenter design including participants from 10 European cities, the researchers have been provided with large datasets from diversely distributed adolescent populations across Europe. Its limitation was the cross-sectional design that does not allow to establish a cause-effect relationship. Moreover, only selected risk loci were available in the HELENA study. The constructed obesity genetic risk score of the HELENA study does not include potential rarer variants that may emerge when genome-wide association studies are carried out.

Since the majority of the studies evaluated in the present review were conducted in European adults, it is hard to get to conclusion about the pediatric population. Nevertheless, as MetS and obesity may occur from childhood to adulthood, early detection is essential to elaborate on health prevention programs among the young population to effectively reduce the risk of cardiometabolic diseases, and the adherence to MD can modify the risk. The genes-diet interaction effect on MetS is gender dependent with a stronger effect in females than in males. Thus, personalized nutritional approach, wherein the genetic profile may determine the responsiveness of patients to a specific diet, may be recommended as a possible therapeutic measure to reduce the risk of MetS.

Vitamin D supplementation and cardiometabolic risk factors among diverse school children: a randomized clinical trial

Comments: Along with the high prevalence of obesity and MetS in pediatric patients, children and adolescents in the majority of countries are diagnosed with vitamin D deficiency. There is growing evidence linking vitamin D deficiency to various negative health outcomes including hypertension, diabetes, and cardiovascular diseases. Low vitamin D concentrations are associated with markers of subclinical arteriosclerosis, including arterial endothelial dysfunction and increased arterial stiffness [36] that are predictors for future cardiovascular events [37]. Therefore, an increasing attention to the effect of vitamin D supplementation on cardiometabolic risk markers in children and adolescents has been gained recently. A new meta-analysis of randomized controlled trials examined the effect of vitamin D supplementation (for 6 weeks to 6 months) on cardiometabolic risk markers in children and adolescents. It indicates that vitamin D supplementation appeared to have a beneficial effect on reducing fasting glucose and triglycerides level with total vitamin D supplementation ≥200,000 IU but without a significant effect on HDL cholesterol, LDL cholesterol, TC, BMI, blood pressure, and waist circumferences levels in children and adolescents [38].

The recent reviewed randomized clinical trial study examined the effect of 3 different daily dosages of vitamin D (600, 1,000, or 2,000 IU) for 6 months, with subsequent follow-up of another 6 months on cardiometabolic risk factors among children at risk of deficiency. Of note, over one third (39.6%) of the children were vitamin D inadequate (<20 ng/mL). In contrast to the findings of the meta-analysis, the researchers of this study found that vitamin D supplementation demonstrated generally positive effects on HDL cholesterol, LDL cholesterol, and TC, especially at the lower dosage of600 IU/day, with several significant changes persisting during the post supplementation period.

The strengths of the study include its randomized controlled design and the large sample of participants of healthy children of diverse racial/ethnic backgrounds who are at risk of poor cardiometabolic health. The limitation of the study includes the self reported dietary vitamin D intake that may be subject to reporting error. Yet, together with the other advantages of vitamin D supplementation, optimization of children’s vitamin D status may improve their cardiovascular health

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