IMPACT OF SIMULATED CALORIC REDUCTION ON NUTRIENT ADEQUACY AMONG US ADULTS WITH OVERWEIGHT OR OBESITY (NHANES 2015-2018).

BACKGROUND: Current guidelines for the treatment of obesity recommend dietary restriction to create a caloric deficit, and caloric reductions of 16-68% have been achieved in adults with overweight or obesity engaging in intentional weight loss programs. OBJECTIVE: This study models the impact of simulated caloric reduction on nutrient adequacy among US adults 19+ y with overweight or obesity using National Health and Nutrition Examination Survey data (2015-2018). METHODS: Four levels of caloric reduction (20, 30, 40 and 50%) were modeled by pro-rating daily calorie intake such that usual intakes of 14 nutrients were reduced proportional to caloric reduction. The percentages below the estimated average requirement (EAR) or above the adequate intake (AI) were estimated at each level of caloric reduction, with and without dietary supplement use. Differences across percentages of simulated caloric reductions were determined using non-overlapping confidence intervals of the means (97.5th percentile confidence intervals were used to approximate p<0.05). RESULTS: There were meaningful differences (p<0.05) in percentages below the EAR (above the AI) between sequential levels of simulated caloric reduction for most of the nutrients analyzed (protein, vitamins A, B6, folate and C, calcium, iron, magnesium, potassium and zinc). For example, after a simulated 30% caloric reduction, 25-40% of the population had intakes below the EAR for protein, vitamin B6 and zinc, and 75-91% of the population had intakes below the EAR for vitamin A, calcium and magnesium (versus 4-18% and 45-56%, respectively, without caloric reduction). With the inclusion of dietary supplements, percentages below the EAR for all nutrients (except protein) were lower than those for food alone. CONCLUSIONS: Caloric reduction may exacerbate nutrient inadequacies among adults with overweight or obesity. Inclusion of nutrient-dense foods, fortified foods, specially formulated products and/or dietary supplements should be considered for those on calorie-restricted diets for long-term weight loss.

Change in plasma α-tocopherol associations with attenuated pulmonary function decline and with CYP4F2 missense variation.

BACKGROUND: Vitamin E (vitE) is hypothesized to attenuate age-related decline in pulmonary function. OBJECTIVES: We investigated the association between change in plasma vitE (∆vitE) and pulmonary function decline [forced expiratory volume in the first second (FEV1)] and examined genetic and nongenetic factors associated with ∆vitE. METHODS: We studied 1144 men randomly assigned to vitE in SELECT (Selenium and Vitamin E Cancer Prevention Trial). ∆vitE was the difference between baseline and year 3 vitE concentrations measured with GC-MS. FEV1 was measured longitudinally by spirometry. We genotyped 555 men (vitE-only arm) using the Illumina Expanded Multi-Ethnic Genotyping Array (MEGAex). We used mixed-effects linear regression modeling to examine the ∆vitE-FEV1 association. RESULTS: Higher ∆vitE was associated with lower baseline α-tocopherol (α-TOH), higher baseline γ-tocopherol, higher baseline free cholesterol, European ancestry (as opposed to African) (all P < 0.05), and the minor allele of a missense variant in cytochrome P450 family 4 subfamily F member 2 (CYP4F2) (rs2108622-T; 2.4 µmol/L higher ∆vitE, SE: 0.8 µmol/L; P = 0.0032). Higher ∆vitE was associated with attenuated FEV1 decline, with stronger effects in adherent participants (≥80% of supplements consumed): a statistically significant ∆vitE × time interaction (P = 0.014) indicated that a 1-unit increase in ∆vitE was associated with a 2.2-mL/y attenuation in FEV1 decline (SE: 0.9 mL/y). The effect size for 1 SD higher ∆vitE (+4 µmol/mmol free-cholesterol-adjusted α-TOH) was roughly one-quarter of the effect of 1 y of aging, but in the opposite direction. The ∆vitE-FEV1 association was similar in never smokers (2.4-mL/y attenuated FEV1 decline, SE: 1.0 mL/y; P = 0.017, n = 364), and current smokers (2.8-mL/y, SE: 1.6 mL/y; P = 0.079, n = 214), but there was little to no effect in former smokers (-0.64-mL/y, SE: 0.9 mL/y; P = 0.45, n = 564). CONCLUSIONS: Greater response to vitE supplementation was associated with attenuated FEV1 decline. The response to supplementation differed by rs2108622 such that individuals with the C allele, compared with the T allele, may need a higher dietary intake to reach the same plasma vitE concentration.

Association between Ready-to-Eat Cereal Consumption and Nutrient Intake, Nutritional Adequacy, and Diet Quality in Adults in the National Health and Nutrition Examination Survey 2015-2016.

This study examined differences in dietary intake between ready-to-eat cereal eaters and non-eaters in adults from the United States. Participants (n = 5163) from the National Health and Nutrition Examination Survey 2015-2016 were included. One-day dietary recall was used to define ready-to-eat cereal consumption status and estimate dietary intake in eaters and non-eaters. Data from Food Patterns Equivalent Database 2015-2016 were used to compare intakes of food groups by consumption status. Diet quality was assessed by Healthy Eating Index 2015. Nineteen percent of US adults were ready-to-eat cereal eaters; they had a similar level of energy intake as non-eaters, but they had significantly higher intake of dietary fiber, and several vitamins and minerals, such as calcium, iron, magnesium, potassium, zinc, vitamin A, thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, and vitamin D. They were also more likely to meet nutrient recommendations. Compared to non-eaters, ready-to-eat cereal eaters had the same level of added sugar intake but they had significantly higher intake of whole grains, total fruits, and dairy products. The diet quality of ready-to-eat cereal eaters was significantly higher than that of non-eaters. The study supports that ready-to-eat cereal eaters have better dietary intake with a healthier dietary pattern than non-eaters in the United States.

Association between Ready-to-Eat Cereal Consumption and Nutrient Intake, Nutritional Adequacy, and Diet Quality among Infants, Toddlers, and Children in the National Health and Nutrition Examination Survey 2015-2016.

Ready-to-eat (RTE) cereal is a popular food among children. However, there are no recent data on the associations between RTE cereal consumption and dietary outcomes in the U.S. Therefore, we sought to investigate how RTE cereal was associated with nutrient and food group intakes and overall dietary quality among children aged 0.5 to 17 years using the latest data from the National Health and Nutrition Examination Survey (NHANES 2015-2016). Thirty-six percent of children reported consuming RTE cereal. RTE cereal eaters consumed the same number of calories as non-eaters but had higher intakes of total carbohydrates, total sugar, fiber, calcium, iron, magnesium, potassium, zinc, vitamin A, thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, and vitamin D, as well as lower intakes of total fat and saturated fat (p ≤ 0.0007). We also found that children who consumed RTE cereal had 29% higher total dairy intake (p < 0.0001) and 61% higher whole grain intake (p < 0.0001). Lastly, children who ate RTE cereal had higher diet quality than the children that did not eat RTE cereal, as shown by Healthy Eating Index 2015 total score (52.6 versus 47.7, p < 0.0001). Therefore, consumption of whole-grain fortified RTE cereals should be encouraged as part of healthy dietary patterns for children.

AKT network of genes and impaired myocardial contractility during murine acute Chagasic myocarditis.

Chagasic disease is associated with high morbidity in Latin America. Acute Chagasic myocarditis is consistently found in acute infections, but little is known about its contribution to chronic cardiomyopathy. The aim of the study was to phenotypically characterize two strains of mice with differential Chagas infection susceptibility and correlate strain myocarditis phenotypes with heart tissue gene expression. C57BL/6J and Balb/c mice were injected intraperitoneally with 0 or 150-200 tissue-derived trypomastigotes (Tulahuen strain). Echocardiograms, brain natriuretic peptide, and troponin were measured. Heart tissue was harvested for histopathological analysis and gene expression profiling on microarrays. Genes differently expressed between infected Balb/c and C57BL/6J mice were identified. Echocardiograms showed differences in Balb/c versus C57BL/6J infected mice in heart rate (413 versus 476 beats per minute; P = 0.0001), stroke volume (31.9 ± 9.3 versus 39.2 ± 5.5 µL; P = 0.03), and cardiac output (13.1 ± 3.5 versus 18.7 ± 3.2 µL/min; P = 0.002). Gene expression at 4 weeks analysis showed 32 statistically significant (q value < 0.05) differentially expressed genes between infected Balb/c and C57BL/6J mice that were enriched for genes related to the protein kinase B (AKT) pathway. These specific phenotypic features of cardiac response during acute Chagasic myocarditis may, in part, be related to host AKT network regulation.

Differential expression of vitamin E and selenium-responsive genes by disease severity in chronic obstructive pulmonary disease.

Antioxidant nutritional status is hypothesized to influence chronic obstructive pulmonary disease (COPD) susceptibility and progression. Although past studies relate antioxidants to gene expression, there are no data in patients with COPD. This study investigated the hypothesis that antioxidant status is compromised in patients with COPD, and antioxidant-responsive genes differentially express in a similar pattern. Lung tissue samples from patients with COPD were assayed for vitamin E and gene expression. Selenium and vitamin E were assayed in corresponding plasma samples. Discovery based genome-wide expression analysis compared moderate, severe, and very severe COPD (GOLD II-IV) patients to mild and at-risk/normal (GOLD 0-I). Hypotheses-driven analyses assessed differential gene expression by disease severity for vitamin E-responsive and selenium-responsive genes. GOLD II-IV COPD patients had 30% lower lung tissue vitamin E levels compared to GOLD 0-I participants (p = 0.0082). No statistically significant genome-wide differences in expression by disease severity were identified. Hypothesis-driven analyses of 109 genes found 16 genes differentially expressed (padjusted < 0.05) by disease severity including 6 selenium-responsive genes (range in fold-change -1.39 to 2.25), 6 vitamin E-responsive genes (fold-change -2.30 to 1.51), and 4 COPD-associated genes. Lung tissue vitamin E in patients with COPD was associated with disease severity and vitamin E-responsive genes were differentially expressed by disease severity. Although nutritional status is hypothesized to contribute to COPD risk, and is of therapeutic interest, evidence to date is mainly observational. The findings reported herein are novel, and support a role of vitamin E in COPD progression.

Polymorphisms in the SUFU gene are associated with organ injury protection and sepsis severity in patients with Enterobacteriacea bacteremia.

BACKGROUND: Organ injury including acute kidney injury (AKI) and acute lung Injury (ALI) are major contributors to mortality and morbidity in the setting of sepsis. Hedgehog pathway has been recognized as an important mediator in repair of organ injury. There are some clinical predictors associated with the development of organ injury in sepsis; however few host genetic risk factors have been identified and candidate genes for organ injury susceptibility and severity are largely unknown. METHODS: A prospective cohort study in a tertiary care hospital included 250 adult hospitalized patients with Enterobacteriacea bacteremia. We selected a panel of 69 tagging SNPs for genes in the Hedgehog signaling pathway using the TagSNP functionality of the SNPInfo web server and designed a panel on the GoldenGate Veracode genotyping assay (Illumina). We confirmed Illumina data using Taqman allelic discrimination assays. We assessed SNPs in combination with clinical variables for associations with outcomes and organ injury. RESULTS: Significant associations were identified using logistic regression models, controlling for age, race and gender. From the 69 tagging SNPs, 5 SNPs were associated with renal function and 2 with APACHEII score after false discovery rate correction. After multivariate analysis SNPs rs10786691 (p=0.03), rs12414407 (p=0.026), rs10748825 (p=0.01), and rs7078511 (p=0.006), all in the suppressor of fused homolog (SUFU) gene, correlated with renal function. Likewise, SUFU SNPs rs7907760 (p=0.009) and rs10748825 (p=0.029) were associated with APACHEII score. SNPs rs12414407 and rs1078825 are in linkage disequilibrium (LD) with rs2296590, a SNP in the 5'-UTR region that is within a predicted transcription factor bind site for CCAAT-enhancer-binding proteins. In multivariate analyses functional SNP rs2296590 was correlated with renal function (p=0.004) and APACHEII score (p=0.049). CONCLUSIONS: Host susceptibility factors play an important role in sepsis development and sepsis related organ injury. Polymorphisms in the SUFU gene (encoding for a negative regulator of the hedgehog signaling pathway) are associated with protection from Enterobacteriacea bacteremia related organ injury and sepsis severity.

Randomised vitamin E supplementation and risk of chronic lung disease in the Women's Health Study.

BACKGROUND: The oxidant/antioxidant balance in lung tissue is hypothesised to contribute to the risk of chronic obstructive pulmonary disease (COPD). Observational studies consistently report higher antioxidant status associated with lower COPD risk, but few randomised studies have been reported. METHODS: A post hoc analysis of 38,597 women without chronic lung disease at baseline was conducted in the Women's Health Study (WHS) to test the effect of vitamin E on the risk of incident chronic lung disease. The WHS is a randomised double-blind placebo-controlled factorial trial of vitamin E (600 IU every other day) and aspirin (100 mg every other day) in female health professionals aged≥45 years. Using Cox proportional hazards models, the effect of randomised vitamin E assignment on self-reported physician-diagnosed chronic lung disease was evaluated. RESULTS: During 10 years of follow-up (376,710 person-years), 760 first occurrences of chronic lung disease were reported in the vitamin E arm compared with 846 in the placebo arm (HR 0.90; 95% CI 0.81 to 0.99; p=0.029). This 10% reduction in the risk of incident chronic lung disease was not modified by cigarette smoking, age, randomised aspirin assignment, multivitamin use or dietary vitamin E intake (minimum p for interaction=0.19). Current cigarette smoking was a strong predictor of chronic lung disease risk (HR 4.17; 95% CI 3.70 to 4.70; vs. never smokers). CONCLUSIONS: In this large randomised trial, assignment to 600 IU vitamin E led to a 10% reduction in the risk of chronic lung disease in women.