DNA Damage, n-3 Long-Chain PUFA Levels and Proteomic Profile in Brazilian Children and Adolescents.

Fatty acids play a significant role in maintaining cellular and DNA protection and we previously found an inverse relationship between blood levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and DNA damage. The aim of this study was to explore differences in proteomic profiles, for 117 pro-inflammatory proteins, in two previously defined groups of individuals with different DNA damage and EPA and DHA levels. Healthy children and adolescents (n = 140) aged 9 to 13 years old in an urban area of Brazil were divided by k-means cluster test into two clusters of DNA damage (tail intensity) using the comet assay (cluster 1 = 5.9% ± 1.2 and cluster 2 = 13.8% ± 3.1) in our previous study. The cluster with higher DNA damage and lower levels of DHA (6.2 ± 1.6 mg/dL; 5.4 ± 1.3 mg/dL, p = 0.003) and EPA (0.6 ± 0.2 mg/dL; 0.5 ± 0.1 mg/dL, p < 0.001) presented increased expression of the proteins CDK8-CCNC, PIK3CA-PIK3R1, KYNU, and PRKCB, which are involved in pro-inflammatory pathways. Our findings support the hypothesis that low levels of n-3 long-chain PUFA may have a less protective role against DNA damage through expression of pro-inflammatory proteins, such as CDK8-CCNC, PIK3CA-PIK3R1, KYNU, and PRKCB.

Biomarker-based validity of a food frequency questionnaire estimating intake in Brazilian children and adolescents.

This study evaluated the validity of nutrient and food group intakes estimated by an FFQ against biomarkers. A 71-item semiquantitative FFQ was administered to 210 Brazilian children and adolescents aged 9-13 years. Intakes were correlated with biomarkers in plasma and red blood cells. Correlations between nutrients and their biomarkers were presented for animal protein, myristic acid (C14:0), EPA, DHA, ß-carotene, folate, and vitamins B3, B5 and B6. Food groups and biomarkers were correlated as follows: fish products with EPA and DHA; milk and dairy with C14:0, pyridoxal 5'-phosphate and vitamin B12; total vegetables and dark green and orange vegetables with ß-carotene; 5-methyltetrahydrofolate with green vegetables; and flour products with para-aminobenzoylglutamic acid. This FFQ is a valid tool for ranking Brazilian children and adolescents according to their intake of several nutrients and food groups.

DNA damage is inversely associated to blood levels of DHA and EPA fatty acids in Brazilian children and adolescents.

This study aimed to investigate the association between DNA damage and blood levels of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), retinol, beta-carotene and riboflavin in Brazilian children and adolescents. Subjects (n = 140) were healthy boys and girls aged 9 to 13 years in Ribeirão Preto (SP, Brazil). Data collection included anthropometry, assessment of energy intake and blood sampling. DNA damage was evaluated by single-cell gel electrophoresis (comet assay). Principal component analysis (PCA) was used to verify associations between blood concentrations of vitamins, polyunsaturated fatty acids and DNA damage. Multiple regression analyses, k-means cluster, and analysis of covariance (ANCOVA), adjusted for confounding variables such as age, sex, energy intake, body mass index and total cholesterol (when needed), were applied to confirm the associations. PCA explained 69.4% of the inverse relationships between DNA damage and blood levels of DHA, EPA, retinol, and beta-carotene. Results were confirmed by ANCOVA and multiple regression analyses for DHA and EPA. In conclusion, omega-3-fatty acids were inversely associated with DNA damage in Brazilian children and adolescents and may be a protective factor against the development of future diseases.

Metabo groups in response to micronutrient intervention: Pilot study.

Micronutrients and their metabolites are cofactors in proteins involved in lipid metabolism. The present study was a subproject of the Harmonized Micronutrient Project (ClinTrials.gov # NCT01823744). Twenty participants were randomly selected from 136 children and adolescents that consumed a daily dose of 12 vitamins and 5 minerals supplementation for 6 weeks. The 20 individuals were divided into two pools of 10 individuals, according to their lipid profile at baseline (Pool 1 with lower triglycerides, LDL, and VLDL). The individuals were analyzed at baseline, after 6 weeks of daily supplementation, and after 6 weeks of a washout period in relation to anthropometric, body composition, food intake, lipid profile, micronutrient levels, and iTRAQ proteomic data. Genetic ancestry and its association with vitamin serum levels were also determined. After supplementation, LDL levels decreased while alpha-tocopherol and pantothenic acid levels increased in pool 2; lipid profiles in pool 1 did not change but had higher plasma levels of pantothenic acid, pyridoxal, and pyridoxic acid. In pool 2, expression of some proteins increased, and expression of other ones decreased after intervention, while in pool 1, the same proteins responded inversely or did not change their levels. Plasma alpha-tocopherol and Native American genetic ancestry explained a significant fraction of LDL plasma levels at baseline and in response to the intervention. After intervention, changes in expression of alpha-1 antitrypsin, haptoglobin, Ig alpha-1 chain C region, plasma protease C1 inhibitor, alpha-1-acid glycoprotein 1, fibrinogen alpha, beta, and gamma-chain in individuals in pool 2 may be associated with levels of LDL and vitamin E. Vitamin E and Native American genetic ancestry may also be implicated in changes of vitamin E and LDL levels. The results of this pilot study must be validated in future studies with larger sample size or in in vitro studies.

Metabolic Groups Related to Blood Vitamin Levels and Inflammatory Biomarkers in Brazilian Children and Adolescents.

Certain B-vitamins and vitamin A may be involved in inflammatory pathways associated with homocysteine and omega-3 fatty acids. The aims of this study were (i) to determine whether different metabolic profiles of B-vitamins and vitamin A in Brazilian children and adolescents were positively or negatively related to homocysteine and omega-3 fatty acids using k-means clustering analysis, (ii) compare nutrient intakes and metabolites between the different metabolic profiles, (iii) evaluate if the statistically significant metabolites found between the metabolic groups, can predict the variation of leukotriene A4 hydrolase (LTA4H) levels, a biomarker of low-grade inflammation, in the total studied population. This cross-sectional study included 124 children and adolescents, aged 9-13 y old. Dietary intake was assessed by the food frequency questionnaire and 24-hour recall. Biomarkers for vitamins B2, B6, B12, folate and vitamin A were measured in plasma. Omega-3 fatty acids and homocysteine were measured in red blood cells (RBC). Two different metabolic profiles were found. Thirty of these individuals had overall average higher riboflavin, pyridoxal, and vitamin B12 plasma levels (metabolic group 1) compared to 94 individuals (group 2). Group 2 had lower dietary intake of vitamin B2, vitamin A, and vitamin B12 and higher RBC levels of homocysteine. EPA and DHA erythrocyte levels were not different between metabolic groups. Multiple linear regression analyses showed that blood cobalamin, riboflavin, pyridoxal and homocysteine combined, explained 9.0% of LTA4H levels variation in the total studied population. The metabolic group that had low plasma levels of riboflavin, pyridoxal, and cobalamin also had a lower dietary intake of B-vitamin and higher RBC homocysteine. The combined levels of the riboflavin, pyridoxal, cobalamin and homocysteine biomarkers can predict the variation of LTA4H in the total population studied, but it is not clear how this regulation occurs.

Homocysteine, folate, hs-C-reactive protein, tumor necrosis factor alpha and inflammatory proteins: are these biomarkers related to nutritional status and cardiovascular risk in childhood-onset systemic lupus erythematosus?

BACKGROUND: Childhood-onset systemic lupus erythematosus (c-SLE) is a chronic autoimmune disease which increases cardiovascular risk factors (CRF) such as elevated homocysteine, TNF-α, and hs-C reactive protein. METHODS: We evaluated BMI, waist circumference (WC), 24-h recalls, SLEDAI-2 K, SLICC/ACR-DI, serum levels of homocysteine, folate, TNF-α, hs-C reactive protein, lipid profile, proteomic data, and duration of corticosteroid therapy in 19 c-SLE and 38 healthy volunteers. Physiological and anthropometric variables of c-SLE and healthy controls were compared by ANCOVA. k-cluster was used to separate c-SLE into two different groups with the best and the worst metabolic profile according to previous analysis showing some metabolites that were statistically different from controls, such as homocysteine, TNF-α, hs-CRP and folate levels. These two clusters were again compared with the control group regarding nutritional parameters, lipid profile and also proteomic data. RESULTS: Individuals with c-SLE presented higher BMI, WC, homocysteine, triglycerides, TNF-α, hs-CRP and lower folate levels when compared to controls. We found 10 proteins whose relative abundances were statistically different between control group and lupus clusters with the best (LCBMP) and the worst metabolic profile (LCWMP). A significant positive correlation was found between TNF-α and triglycerides and between hs-CRP and duration of corticosteroid therapy. CONCLUSION: Cardiovascular disease (CVD) risk parameters were worse in c-SLE. A less protective CVD proteomic profile was found in LCWMP.

Clinical and Vitamin Response to a Short-Term Multi-Micronutrient Intervention in Brazilian Children and Teens: From Population Data to Interindividual Responses.

SCOPE: Micronutrients are in small amounts in foods, act in concert, and require variable amounts of time to see changes in health and risk for disease. These first principles are incorporated into an intervention study designed to develop new experimental strategies for setting target recommendations for food bioactives for populations and individuals. METHODS AND RESULTS: A 6-week multivitamin/mineral intervention is conducted in 9-13 year olds. Participants (136) are (i) their own control (n-of-1); (ii) monitored for compliance; (iii) measured for 36 circulating vitamin forms, 30 clinical, anthropometric, and food intake parameters at baseline, post intervention, and following a 6-week washout; and (iv) had their ancestry accounted for as modifier of vitamin baseline or response. The same intervention is repeated the following year (135 participants). Most vitamins respond positively and many clinical parameters change in directions consistent with improved metabolic health to the intervention. Baseline levels of any metabolite predict its own response to the intervention. Elastic net penalized regression models are identified, and significantly predict response to intervention on the basis of multiple vitamin/clinical baseline measures. CONCLUSIONS: The study design, computational methods, and results are a step toward developing recommendations for optimizing vitamin levels and health parameters for individuals.

Vitamin A, vitamin E, iron and zinc status in a cohort of HIV-infected mothers and their uninfected infants

Introduction We hypothesized that nutritional deficiency would be common in a cohort of postpartum, human immunodeficiency virus (HIV)-infected women and their infants. Methods Weight and height, as well as blood concentrations of retinol, α-tocopherol, ferritin, hemoglobin, and zinc, were measured in mothers after delivery and in their infants at birth and at 6-12 weeks and six months of age. Retinol and α-tocopherol levels were quantified by high performance liquid chromatography, and zinc levels were measured by atomic absorption spectrophotometry. The maternal body mass index during pregnancy was adjusted for gestational age (adjBMI). Results Among the 97 women 19.6% were underweight. Laboratory abnormalities were most frequently observed for the hemoglobin (46.4%), zinc (41.1%), retinol (12.5%) and ferritin (6.5%) levels. Five percent of the women had mean corpuscular hemoglobin concentrations < 31g/dL. The most common deficiency in the infants was α-tocopherol (81%) at birth; however, only 18.5% of infants had deficient levels at six months of age. Large percentages of infants had zinc (36.8%) and retinol (29.5%) deficiencies at birth; however, these percentages decreased to 17.5% and 18.5%, respectively, by six months of age. No associations between infant micronutrient deficiencies ...

Vitamin A, vitamin E, iron and zinc status in a cohort of HIV-infected mothers and their uninfected infants.

UNLABELLED: Introduction: We hypothesized that nutritional deficiency would be common in a cohort of postpartum, human immunodeficiency virus (HIV)-infected women and their infants. METHODS: Weight and height, as well as blood concentrations of retinol, α-tocopherol, ferritin, hemoglobin, and zinc, were measured in mothers after delivery and in their infants at birth and at 6-12 weeks and six months of age. Retinol and α-tocopherol levels were quantified by high performance liquid chromatography, and zinc levels were measured by atomic absorption spectrophotometry. The maternal body mass index during pregnancy was adjusted for gestational age (adjBMI). RESULTS: Among the 97 women 19.6% were underweight. Laboratory abnormalities were most frequently observed for the hemoglobin (46.4%), zinc (41.1%), retinol (12.5%) and ferritin (6.5%) levels. Five percent of the women had mean corpuscular hemoglobin concentrations < 31g/dL. The most common deficiency in the infants was α-tocopherol (81%) at birth; however, only 18.5% of infants had deficient levels at six months of age. Large percentages of infants had zinc (36.8%) and retinol (29.5%) deficiencies at birth; however, these percentages decreased to 17.5% and 18.5%, respectively, by six months of age. No associations between infant micronutrient deficiencies and either the maternal adjBMI category or maternal micronutrient deficiencies were found. CONCLUSIONS: Micronutrient deficiencies were common in HIV-infected women and their infants. Micronutrient deficiencies were less prevalent in the infants at six months of age. Neither underweight women nor their infants at birth were at increased risk for micronutrient deficiencies.

Nutritional status and lipid profile of HIV-positive children and adolescents using antiretroviral therapy.

OBJECTIVE: To describe nutritional status, body composition and lipid profile in children and adolescents receiving protease inhibitors. METHODS: Fifty-nine patients, 23 treated with protease inhibitors (group 1) and 36 not using protease inhibitors (group 2). Their dietary intake, anthropometry, bioimpedance analysis and lipid profile variables were measured. RESULTS: There was no difference in nutritional status or body composition between groups at the beginning of the study. After 6 months of follow-up, there was an increase in weight and height in both groups, as well as in waist circumference and subscapular skinfold thickness. In group 2, body mass index and triceps skinfold thickness adequacy were significantly higher after 6 months of follow-up. The groups had similar energy and macronutrient intake at any time point. After 6 months, group 1 had a higher cholesterol intake and group 2 had a higher fiber intake. Triglyceride serum levels were significantly different between the groups, with higher values in G1, at any time point [G1: 153 mg/dl (30-344); 138 (58-378) versus G2: 76 mg/dl (29-378); 76 (29-378)]. After 6 months of follow-up, G1 had higher LDL-cholesterol than G2 [104 mg/dl (40-142) versus 82 (42-145)]. CONCLUSION: The use of protease inhibitors, per se, does not seem to significantly interfere with anthropometric measures, body composition and food intake of HIV-infected children and adolescents. However, this antiretroviral therapy was associated with a significant increase in triglyceride and LDL-cholesterol in our subjects.

Nutritional assessment and lipid profile in HIV-infected children and adolescents treated with highly active antiretroviral therapy.

INTRODUCTION: HIV-infected children and adolescents treated with highly active antiretroviral therapy (HAART) regimens that include a protease inhibitor (PI) can show significant improvements in clinical outcomes, nutritional status and quality of life. The study aimed to report nutritional and metabolic alterations for pediatric patients continuously exposed to HAART and for healthy controls for up to 1 year. METHODS: Clinical, anthropometric, lipid profile and food intake data were collected prospectively over approximately 12-months for each patient. RESULTS: Fifty-one individuals were studied, of these, 16 were healthy. After 12 months follow-up, HIV-positive individuals remained below the healthy control group parameters. No change was observed concerning food intake. Triglyceride serum levels were higher in patients using protease inhibitor at the onset of the study [PI groups: 114 (43 - 336), and 136 (63 - 271) versus control group: 54.5 (20 - 162); p = 0.003], but after twelve months follow-up, only the group using protease inhibitor for up to two months presented higher values [140 (73 - 273) versus 67.5 (33 - 117); p = 0.004]. HDL-cholesterol was lower in HIV-positive individuals [HIV-positive groups: 36 (27 - 58) and 36 (23 - 43); control 49.5 (34 - 69); p = 0.004]. CONCLUSIONS: HIV-infected children and adolescents treated with highly active antiretroviral therapy showed compromised nutritional parameters compared to a paired healthy control group. Individuals using protease inhibitor presented worse triglyceride serum levels compared to their healthy counterparts.

Nutritional assessment and lipid profile in HIV-infected children and adolescents treated with highly active antiretroviral therapy / Avaliação nutricional e do perfil lipídico em crianças e adolescentes infectadas pelo HIV tratadas com terapia antirretroviral de alta potência

INTRODUCTION: HIV-infected children and adolescents treated with highly active antiretroviral therapy (HAART) regimens that include a protease inhibitor (PI) can show significant improvements in clinical outcomes, nutritional status and quality of life. The study aimed to report nutritional and metabolic alterations for pediatric patients continuously exposed to HAART and for healthy controls for up to 1 year. METHODS: Clinical, anthropometric, lipid profile and food intake data were collected prospectively over approximately 12-months for each patient. RESULTS: Fifty-one individuals were studied, of these, 16 were healthy. After 12 months follow-up, HIV-positive individuals remained below the healthy control group parameters. No change was observed concerning food intake. Triglyceride serum levels were higher in patients using protease inhibitor at the onset of the study [PI groups: 114 (43 - 336), and 136 (63 - 271) versus control group: 54.5 (20 - 162); p = 0.003], but after twelve months follow-up, only the group using protease inhibitor for up to two months presented higher values [140 (73 - 273) versus 67.5 (33 - 117); p = 0.004]. HDL-cholesterol was lower in HIV-positive individuals [HIV-positive groups: 36 (27 - 58) and 36 (23 - 43); control 49.5 (34 - 69); p = 0.004]. CONCLUSIONS: HIV-infected children and adolescents treated with highly active antiretroviral therapy showed compromised nutritional parameters compared to a paired healthy control group. Individuals using protease inhibitor presented worse triglyceride serum levels compared to their healthy counterparts.

INTRODUÇÃO: Crianças e adolescentes infectadas pelo HIV e tratadas com terapia antirretroviral de alta potência (TAAP), que inclui inibidor de protease (IP) podem apresentar significante melhora clínica no estado nutricional e na qualidade de vida. O objetivo é relatar as alterações nutricionais e metabólicas em pacientes pediátricos expostos a TAAP e controles saudáveis durante 1 ano. MÉTODOS: O perfil clínico, antropométrico e lipídico, bem como dados da ingestão alimentar foram coletados prospectivamente durante aproximadamente 12 meses. RESULTADOS: Cinquenta e um indivíduos foram estudados. Dezesseis eram saudáveis. Após 12 meses de acompanhamento, indivíduos HIV-positivo permaneceram abaixo dos parâmetros do grupo controle saudável. Nenhuma mudança foi observada em relação à ingestão alimentar. Níveis séricos de triglicerídeos foram maiores em pacientes usando inibidor de protease no começo do estudo [IP grupo: 114 (43 - 336), e 136 (63 - 271) versus grupo controle: 54.5 (20 - 162); p = 0.003], porém após doze meses de acompanhamento, apenas o grupo que recebeu inibidor de protease por não mais do que dois meses apresentou maiores valores [140 (73 - 273) versus 67.5 (33 - 117); p = 0.004]. HDL-colesterol foi menor nos indivíduos HIV-positivos [grupo HIV-positivo: 36 (27 - 58) e 36 (23 - 43); controle 49.5 (34 - 69); p=0.004]. CONCLUSÕES: Crianças e adolescentes infectadas pelo HIV e tratadas com terapia antirretroviral de alta potência tiveram seus parâmetros nutricionais comprometidos quando comparados com o pareado grupo controle. Indivíduos usando inibidor de protease apresentaram piores níveis séricos de triglicerídeos quando comparados com os saudáveis.

Nutritional and metabolic status of HIV-positive patients with lipodystrophy during one year of follow-up.

OBJECTIVES: The aim of this prospective study was to compare changes in lipid metabolism and nutritional status after either 6 and 12 months of follow-up in subjects with lipodystrophy syndrome after traditional lifestyle therapy with or without fibric acid analogue intervention (bezafibrate and clofibrate). METHODS: Food intake, alterations in body composition and metabolic abnormalities were assessed in subjects with lipodystrophy syndrome at the beginning of the study. The nutritional status and metabolic alterations of the subjects were monitored, and the subjects received nutritional counseling each time they were seen. The subjects were monitored either two times over a period no longer than six months (Group A; n = 18) or three times over a period of at least 12 months (Group B; n = 35). All of the subjects underwent nutrition counseling that was based on behavior modification. The fibric acid analogue was only given to patients with serum triglyceride levels above 400 mg/dL. RESULTS: After six months of follow-up, Group A showed no alterations in the experimental parameters. After twelve months, there was a decrease in serum triglyceride levels (410.4 ± 235.5 vs. 307.7 ± 150.5 mg/dL, p < 0.05) and an increase in both HDLc levels (37.9 ± 36.6 vs. 44.9 ± 27.9 mg/dL, p,0.05) and lean mass (79.9 ± 7.8 vs. 80.3 ± 9.9 %, p < 0.05) in Group B. CONCLUSION: After one year of follow-up (three sessions of nutritional and medical counseling), the metabolic parameters of the subjects with lipodystrophy improved after traditional lifestyle therapy with or without fibric acid analogue intervention.

Accurate determination of energy needs in children and adolescents with cancer.

Studies on children with cancer have suggested that energy expenditure may indeed be greater than predicted for healthy children. Nutritional assessment is important for intervention and for the prevention of complications associated with malnutrition. The present study aimed to describe the nutritional status, energy expenditure, and substrate utilization of children and adolescents with cancer compared to healthy children matched for age, sex, and body mass index. Subjects were evaluated by anthropometry, food intake pattern, and body composition analysis. Energy expenditure and substrate oxidation were measured by indirect calorimetry. Indirect calorimetry data, energy, and macronutrient intake, anthropometry, and body composition parameters showed no significant differences between groups. There was no evidence of increased energy expenditure or of a change in substrate utilization in children with cancer compared to the healthy group. The data regarding usual food consumption showed no significant differences between groups.

Nutritional and metabolic status of HIV-positive patients with lipodystrophy during one year of follow-up

OBJECTIVES: The aim of this prospective study was to compare changes in lipid metabolism and nutritional status after either 6 and 12 months of follow-up in subjects with lipodystrophy syndrome after traditional lifestyle therapy with or without fibric acid analogue intervention (bezafibrate and clofibrate). METHODS: Food intake, alterations in body composition and metabolic abnormalities were assessed in subjects with lipodystrophy syndrome at the beginning of the study. The nutritional status and metabolic alterations of the subjects were monitored, and the subjects received nutritional counseling each time they were seen. The subjects were monitored either two times over a period no longer than six months (Group A; n = 18) or three times over a period of at least 12 months (Group B; n = 35). All of the subjects underwent nutrition counseling that was based on behavior modification. The fibric acid analogue was only given to patients with serum triglyceride levels above 400 mg/dL. RESULTS: After six months of follow-up, Group A showed no alterations in the experimental parameters. After twelve months, there was a decrease in serum triglyceride levels (410.4 ± 235.5 vs. 307.7 ± 150.5 mg/dL, p< 0.05) and an increase in both HDLc levels (37.9±36.6 vs. 44.9 ±27.9 mg/dL, p,0.05) and lean mass (79.9 ± 7.8 vs. 80.3 ± 9.9 percent, p< 0.05) in Group B. CONCLUSION: After one year of follow-up (three sessions of nutritional and medical counseling), the metabolic parameters of the subjects with lipodystrophy improved after traditional lifestyle therapy with or without fibric acid analogue intervention.

Nutritional status and lipid profile of HIV-positive children and adolescents using antiretroviral therapy

OBJECTIVE: To describe nutritional status, body composition and lipid profile in children and adolescents receiving protease inhibitors. METHODS: Fifty-nine patients, 23 treated with protease inhibitors (group 1) and 36 not using protease inhibitors (group 2). Their dietary intake, anthropometry, bioimpedance analysis and lipid profile variables were measured. RESULTS: There was no difference in nutritional status or body composition between groups at the beginning of the study. After 6 months of follow-up, there was an increase in weight and height in both groups, as well as in waist circumference and subscapular skinfold thickness. In group 2, body mass index and triceps skinfold thickness adequacy were significantly higher after 6 months of follow-up. The groups had similar energy and macronutrient intake at any time point. After 6 months, group 1 had a higher cholesterol intake and group 2 had a higher fiber intake. Triglyceride serum levels were significantly different between the groups, with higher values in G1, at any time point [G1: 153 mg/dl (30-344); 138 (58-378) versus G2: 76 mg/dl (29-378); 76 (29-378)]. After 6 months of follow-up, G1 had higher LDL-cholesterol than G2 [104 mg/dl (40-142) versus 82 (42-145)]. CONCLUSION: The use of protease inhibitors, per se, does not seem to significantly interfere with anthropometric measures, body composition and food intake of HIV-infected children and adolescents. However, this antiretroviral therapy was associated with a significant increase in triglyceride and LDL-cholesterol in our subjects.