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Lean Mass Improvement from Nutrition Education and Protein Supplementation among Rural Indian Women Living with HIV/AIDS: Results from Cluster Randomized Factorial Trial at 18-Month Follow-Up.
Carpenter, CL, Kapur, K, Ramakrishna, P, Pamujula, S, Yadav, K, Giovanni, JE, Julian, O, Ekstrand, ML, Sinha, S, Nyamathi, AM
Nutrients. 2021;(1)
Abstract
Loss of lean muscle mass impairs immunity and increases mortality risk among individuals with HIV/AIDS. We evaluated the relative contributions of protein supplementation and nutrition education on body composition among 600 women living with HIV/AIDS in rural Andhra Pradesh, India. We conducted a cluster randomized controlled 2 × 2 factorial trial lasting six months with follow up at twelve and eighteen months. Interventions occurred in the Nellore and Prakasam regions of Andhra Pradesh by trained village women, ASHA (Accredited Social Health Activists), and included: (1) the usual supportive care from ASHA (UC); (2) UC plus nutrition education (NE); (3) UC plus nutritional protein supplementation (NS); (4) combined UC plus NE plus NS. A Bioimpedance Analyzer Model 310e measured body composition. SAS 9.4 analyzed all data. Mixed models using repeated measures evaluated lean mass change from baseline as primary and fat weight and total weight as secondary outcomes. Lean mass change was significantly associated with NS (p = 0.0001), NE (p = 0.0001), and combined NS plus NE (p = 0.0001), with similar associations for secondary outcomes. Stronger associations for total weight were observed with greater ART adherence. Nutritional interventions may improve physiologic response to HIV. Significant increases in lean mass resulted from independent and combined protein supplementation and nutrition education.
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Effects of branched-chain amino acids on glucose metabolism in obese, prediabetic men and women: a randomized, crossover study.
Woo, SL, Yang, J, Hsu, M, Yang, A, Zhang, L, Lee, RP, Gilbuena, I, Thames, G, Huang, J, Rasmussen, A, et al
The American journal of clinical nutrition. 2019;(6):1569-1577
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BACKGROUND Recent studies have shown that circulating branched-chain amino acids (BCAAs) are elevated in obese, insulin-resistant individuals. However, it is not known if supplementation of additional BCAAs will further impair glucose metabolism. OBJECTIVES The aim of this pilot study was to determine the effects of BCAA supplementation on glucose metabolism in obese, prediabetic individuals. METHODS This is a randomized crossover study involving 12 obese individuals with prediabetes. Participants were randomly assigned to receive a daily supplement containing either 20 g BCAA or protein low in BCAAs for 4 wk with a 2-wk washout in between. At each visit, an oral-glucose-tolerance test (OGTT) was performed. Collected blood samples were used to measure glucose, insulin, and insulin resistance-associated biomarkers. RESULTS BCAA supplementation tended to decrease the plasma glucose area under the curve (AUC) measured by the OGTT (AUC percentage change from supplementation baseline, BCAA -3.3% ± 3%; low-BCAA: 10.0% ± 6%; P = 0.08). However, BCAA supplementation did not affect plasma insulin during OGTT challenge (BCAA: -3.9% ± 8%; low-BCAA: 14.8% ± 10%; P = 0.28). The plasma concentrations of nerve growth factor (BCAA: 4.0 ± 1 pg/mL; low-BCAA: 5.7 ± 1 pg/mL; P = 0.01) and monocyte chemoattractant protein-1 (BCAA: -0.4% ± 9%; low-BCAA: 29.0% ± 18%; P = 0.02) were significantly lowered by BCAA supplementation compared to low-BCAA control. Plasma interleukin 1β was significantly elevated by BCAA supplementation (BCAA: 231.4% ± 187%; low-BCAA: 20.6% ± 33%; P = 0.05). BCAA supplementation did not affect the circulating concentrations of the BCAAs leucine (BCAA: 9.0% ± 12%; low-BCAA: 9.2% ± 11%), valine (BCAA: 9.1% ± 11%; low-BCAA: 12.0% ± 13%), or isoleucine (BCAA: 2.5% ± 11%; low-BCAA: 7.3% ± 11%). CONCLUSIONS Our data suggest that BCAA supplementation did not impair glucose metabolism in obese, prediabetic subjects. Further studies are needed to confirm the results seen in the present study. This study was registered at clinicaltrials.gov as NCT03715010.
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Mixed Spices at Culinary Doses Have Prebiotic Effects in Healthy Adults: A Pilot Study.
Lu, QY, Rasmussen, AM, Yang, J, Lee, RP, Huang, J, Shao, P, Carpenter, CL, Gilbuena, I, Thames, G, Henning, SM, et al
Nutrients. 2019;11(6)
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An increasing body of evidence suggests that the gut microbiota has a profound impact on human health. While the microbiome of a healthy individual is relatively stable, gut microbial dynamics can be influenced by host lifestyle and dietary choices. The aim of this study was to investigate the effects of mixed spices (cinnamon, oregano, ginger, black pepper, and cayenne pepper) at culinary doses consumed over 2 weeks in a standardized 5g capsule on the production of gut microbiota and short-chain fatty acids The study is a randomised, placebo-controlled, double-blind pilot study carried out with a total of 31 healthy women and men aged between 18 and 65. The subjects were randomly allocated to one of the two intervention groups. Results indicate that daily intake of 5g of mixed spices for 2 weeks in healthy subjects resulted in a significant reduction in the relative abundance of the phylum Firmicutes (bacteria), and a trend of increasing in phylum Bacteroidetes (bacteria) as compared with a matched control group. Authors conclude that a mixture of spices at culinary doses affects the composition of gut microbiota.
Abstract
Spices were used as food preservatives prior to the advent of refrigeration, suggesting the possibility of effects on microbiota. Previous studies have shown prebiotic activities in animals and in vitro, but there has not been a demonstration of prebiotic or postbiotic effects at culinary doses in humans. In this randomized placebo-controlled study, we determined in twenty-nine healthy adults the effects on the gut microbiota of the consumption daily of capsules containing 5 g of mixed spices at culinary doses by comparison to a matched control group consuming a maltodextrin placebo capsule. The 16S ribosomal RNA sequencing data were used for microbial characterization. Spice consumption resulted in a significant reduction in Firmicutes abundance (p < 0.033) and a trend of enrichment in Bacteroidetes (p < 0.097) compared to placebo group. Twenty-six operational taxonomic units (OTUs) were different between the spice and placebo groups after intervention. Furthermore, there was a significant negative correlation between fecal short-chain fatty acid propionate concentration and Firmicutes abundance in spice intervention group (p < 0.04). The production of individual fecal short-chain fatty acid was not significantly changed by spice consumption in this study. Mixed spices consumption significantly modified gut microbiota, suggesting a prebiotic effect of spice consumption at culinary doses.
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Sustained Effect of a Community-based Behavioral and Nutrition Intervention on HIV-related Outcomes Among Women Living With HIV in Rural India: A Quasi-experimental Trial.
Nyamathi, AM, Shin, SS, Sinha, S, Carpenter, CL, Garfin, DR, Ramakrishnan, P, Yadav, K, Ekstrand, ML
Journal of acquired immune deficiency syndromes (1999). 2019;(4):429-438
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BACKGROUND Women living with HIV (WLH) in rural communities face challenges to obtaining treatment and accurate disease-related information. Nutritional deficits exacerbate disease progression. SETTING WLH were recruited from primary health centers in rural India. METHOD A quasi-experimental trial of a comprehensive Accredited Social Health Activist (Asha)-supported intervention compared 4 distinct Asha-based programs [(1) standard education (SE) alone; (2) nutrition education (+NE); (3) nutrition supplements (+NS); or (4) nutrition education and nutrition supplements (+NENS)] on key disease and nutrition-related outcomes [CD4 count, body mass index (BMI), serum albumin, and hemoglobin]. Assessments occurred at baseline, and months 6 (immediately after intervention), 12, and 18. Multilevel modeling examined effects of program (group) over time. FINDINGS Among 600 WLH enrolled (n = 150 per arm), mean age, CD4 count, and BMI (kg/m) were 34.31, 447.42, and 20.09, respectively, at baseline. At 18-month follow-up, program 4 (+NENS) experienced greatest improvements in CD4 counts compared with program 1 (+SE) [adjusted difference = 223.81, 95% confidence interval (CI): 170.29 to 277.32]. For BMI, programs 3 (+NS; adjusted difference = 2.33, 95% CI: 1.39 to 3.26) and 4 (+NENS; adjusted difference = 2.14, 95% CI: 1.17 to 3.12) exhibited greater gains compared with program 1 (+SE). Programs 3 and 4 were not significantly different from each other (adjusted difference = -0.18, 95% CI: -1.12 to 0.76). Hemoglobin and serum albumin also improved over time; program 4 (+NENS) exhibited the greatest gains. CONCLUSIONS A low-cost Asha-supported behavioral and nutritional intervention improved outcomes for WLH. Gains were sustained at 18-month follow-up. Similar approaches may help improve HIV and other infectious disease-related outcomes in vulnerable populations.
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Eosinophilic oesophagitis endotype classification by molecular, clinical, and histopathological analyses: a cross-sectional study.
Shoda, T, Wen, T, Aceves, SS, Abonia, JP, Atkins, D, Bonis, PA, Caldwell, JM, Capocelli, KE, Carpenter, CL, Collins, MH, et al
The lancet. Gastroenterology & hepatology. 2018;(7):477-488
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BACKGROUND Eosinophilic oesophagitis is understood in terms of quantifiable histological, endoscopic, and molecular features. Data are scant for inter-relations of these features and their potential to identify distinct disease endotypes. We aimed to identify clinical-pathological correlations between endoscopic and histological disease variables by transcription profiling of the oesophagus of patients with eosinophilic oesophagitis of varying severity and disease activity states. METHODS We did a cross-sectional study across ten hospital sites in the USA associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers. We analysed oesophageal biopsy specimens taken from paediatric and adult patients with eosinophilic oesophagitis (discovery cohort), using the eosinophilic oesophagitis diagnostic panel (EDP), a set of 96 informative transcripts. Histological and endoscopic features were assessed by quantification of oesophageal eosinophils and use of the eosinophilic oesophagitis histology scoring system (HSS) and the eosinophilic oesophagitis endoscopic reference score (EREFS). Associations among the various histological, endoscopic, and molecular features were analysed by Spearman correlation. Results were replicated in a biologically independent, single-centre, validation cohort of patients with active eosinophilic oesophagitis. FINDINGS The discovery cohort contained 185 samples and the validation cohort comprised 100 specimens. In the discovery cohort, EDP showed intersite consistency, significant correlation with oesophageal eosinophils (p<0·0001), and similar findings between paediatric and adult patients. Of eight HSS domains, basal zone hyperplasia correlated with the EDP (median Spearman ρ 0·47 [IQR 0·36-0·60]). Of five EREFS features, distal furrows correlated with the EDP (median Spearman ρ 0·42 [0·32-0·50]). By analysing active eosinophilic oesophagitis in the discovery cohort, the EDP identified three clusters associated with distinct endotypes (termed EoEe1-3) despite similar eosinophil levels. EoEe1 was associated with a normal-appearing oesophagus (risk ratio [RR] 3·27, 95% CI 1·04-10·27; p=0·0443), an inverse association with a history of oesophageal dilation (0·27, 0·09-0·82; p=0·0105) and showed relatively mild histological, endoscopic, and molecular changes. EoEe2 showed an inflammatory and steroid-refractory phenotype (RR 2·77, 95% CI 1·11-6·95; p=0·0376) and had the highest expression of inflammatory cytokines and steroid-responding genes. EoEe3 was associated with a narrow-calibre oesophagus (RR 7·98, 95% CI 1·84-34·64; p=0·0013) and adult onset (2·22, 1·19-4·12; p=0·0155), and showed the highest degree of endoscopic and histological severity and the lowest expression of epithelial differentiation genes. These endotypes were replicated in the validation cohort by clustering and with an eosinophilic oesophagitis endotype-prediction algorithm. INTERPRETATION Our new disease classification stratifies patients with eosinophilic oesophagitis into subgroups with potential clinical and therapeutic significance and provides a framework for a precision medicine approach to eosinophilic oesophagitis. FUNDING National Institutes of Health.
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Alignment of parent- and child-reported outcomes and histology in eosinophilic esophagitis across multiple CEGIR sites.
Aceves, SS, King, E, Collins, MH, Yang, GY, Capocelli, KE, Abonia, JP, Atkins, D, Bonis, PA, Carpenter, CL, Dellon, ES, et al
The Journal of allergy and clinical immunology. 2018;(1):130-138.e1
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BACKGROUND Patient-reported outcome metrics for eosinophilic esophagitis (EoE) have been developed and validated but not used in a multicenter pediatric population or systematically aligned with histology. OBJECTIVE We sought to understand (1) the potential of caregiver report to predict patient self-reported symptoms and (2) the correlation of patient-reported outcome domains with histology. METHODS Patients with EoE (n = 310) and their parents participating in the Consortium of Gastrointestinal Eosinophilic Disease Researchers (CEGIR) observational clinical trial were queried for baseline patient symptoms and quality of life (QOL) by using the Pediatric Eosinophilic Esophagitis Symptom Score, version 2 (PEESSv2.0), and the Pediatric QOL EoE module (PedsQL-EoE), and biopsy specimens were analyzed by using the EoE Histology Scoring System. RESULTS PEESSv2.0 parental and child reports aligned across all domains (r = 0.68-0.73, P < .001). PedsQL-EoE reports correlated between parents and children across ages and multiple domains (r = 0.48-0.79, P < .001). There was a tight correlation between symptoms on PEESSv2.0 and their effects on QOL both on self-report and parental report (P < .001). Self-reported symptoms on PEESSv2.0 (positively) and PedsQL-EoE (inversely) showed a weak correlation with proximal, but not distal, peak eosinophil counts and features and architectural tissue changes on the EoE Histology Scoring System (P < .05). CONCLUSIONS Parents of children with EoE aged 3 to 18 years accurately reflected their children's disease symptoms and QOL. Self- and parent-reported symptoms correlate with proximal esophageal histology. Our data suggest that parental report in young children can function as an adequate marker for self-reported symptoms and that self-reported symptoms can reflect changes in tissue histology in the proximal esophagus. These findings should be considered during clinical trials for drug development.
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Randomized clinical trial of brewed green and black tea in men with prostate cancer prior to prostatectomy.
Henning, SM, Wang, P, Said, JW, Huang, M, Grogan, T, Elashoff, D, Carpenter, CL, Heber, D, Aronson, WJ
The Prostate. 2015;(5):550-9
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BACKGROUND Preclinical and epidemiologic studies suggest chemopreventive effects of green tea (GT) and black tea (BT) in prostate cancer. In the current study we determined the effect of GT and BT consumption on biomarkers related to prostate cancer development and progression. METHODS In this exploratory, open label, phase II trial 113 men diagnosed with prostate cancer were randomized to consume six cups daily of brewed GT, BT or water (control) prior to radical prostatectomy (RP). The primary endpoint was prostate tumor markers of cancer development and progression determined by tissue immunostaining of proliferation (Ki67), apoptosis (Bcl-2, Bax, Tunel), inflammation (nuclear and cytoplasmic nuclear factor kappa B [NFκB]) and oxidation (8-hydroxydeoxy-guanosine [8OHdG]). Secondary endpoints of urinary oxidation, tea polyphenol uptake in prostate tissue, and serum prostate specific antigen (PSA) were evaluated by high performance liquid chromatography and ELISA analysis. RESULTS Ninety three patients completed the intervention. There was no significant difference in markers of proliferation, apoptosis and oxidation in RP tissue comparing GT and BT to water control. Nuclear staining of NFκB was significantly decreased in RP tissue of men consuming GT (P = 0.013) but not BT (P = 0.931) compared to water control. Tea polyphenols were detected in prostate tissue from 32 of 34 men consuming GT but not in the other groups. Evidence of a systemic antioxidant effect was observed (reduced urinary 8OHdG) only with GT consumption (P = 0.03). GT, but not BT or water, also led to a small but statistically significant decrease in serum prostate-specific antigen (PSA) levels (P = 0.04). CONCLUSION Given the GT-induced changes in NFκB and systemic oxidation, and uptake of GT polyphenols in prostate tissue, future longer-term studies are warranted to further examine the role of GT for prostate cancer prevention and treatment, and possibly for other prostate conditions such as prostatitis.
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Phenolic acid concentrations in plasma and urine from men consuming green or black tea and potential chemopreventive properties for colon cancer.
Henning, SM, Wang, P, Abgaryan, N, Vicinanza, R, de Oliveira, DM, Zhang, Y, Lee, RP, Carpenter, CL, Aronson, WJ, Heber, D
Molecular nutrition & food research. 2013;(3):483-93
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SCOPE Tea polyphenols are metabolized by the colonic microflora yielding phenolic metabolites, which may contribute to the health benefits of tea. We determined the serum and urine concentrations of phenolic acids, hippuric acid, and polyhydroxyphenyl-γ-valerolactones during green tea (GT) and black tea (BT) administration. The effects of (-)-epigallocatechin gallate (EGCG) and 3,4-dihydroxyphenylacetic acid (3,4-DHPAA) alone and in combination on bioavailability, intracellular metabolism, and antiproliferative activity were determined in HCT-116 colon cancer cells. METHODS AND RESULTS The concentration of phenolic metabolites was quantified by HPLC with electrochemical detection and MS. Urine concentrations of 4-hydroxyphenylacetic acid (4-HPAA), 3-hydroxyphenylacetic acid (3-HPAA), and polyhydroxy-γ-valerolactones were increased significantly in men drinking GT compared to control. Urine concentration of 3-O-methylgallic acid (3OMGA) was significantly increased in men drinking BT compared to control. Serum 3,4-DHPAA was significantly increased after consumption of GT and BT and 4-HPAA after GT consumption. In vitro treatment of HCT-116 colon cancer cells with 3,4-DHPAA and EGCG exhibited an additive antiproliferative effect, while methylation of 3,4-DHPAA was significantly decreased. 3OMGA exhibited the strongest antiproliferative activity among the phenolic acids. CONCLUSION The consumption of both, GT and BT, was associated with a significant increase in urinary and serum phenolic acids.
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Impact of protein supplementation and care and support on body composition and CD4 count among HIV-infected women living in rural India: results from a randomized pilot clinical trial.
Nyamathi, A, Sinha, S, Ganguly, KK, Ramakrishna, P, Suresh, P, Carpenter, CL
AIDS and behavior. 2013;(6):2011-21
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Body composition in HIV-infected individuals is subject to many influences. We conducted a pilot 6-month randomized trial of 68 women living with AIDS (WLA) from rural India. High protein intervention combined with education and supportive care delivered by HIV-trained village women (activated social health activist [Asha] life [AL]) was compared to standard protein with usual care delivered by village community assistants (usual care [UC]). Measurements included CD4 counts, ART adherence, socio-demographics, disease characteristics (questionnaires); and anthropometry (bioimpedance analyzer). Repeated measures analysis of variance modeled associations. AL significantly gained in BMI, muscle mass, fat mass, ART adherence, and CD4 counts compared to UC, with higher weight and muscle mass gains among ART adherent (≥66%) participants who had healthier immunity (CD4 ≥450). BMI of WLA improved through high protein supplementation combined with education and supportive care. Future research is needed to determine which intervention aspect was most responsible.
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Addictive genes and the relationship to obesity and inflammation.
Heber, D, Carpenter, CL
Molecular neurobiology. 2011;(2):160-5
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There is increasing evidence that the same brain reward circuits involved in perpetuating drug abuse are involved in the hedonic urges and food cravings observed clinically in overweight and obese subjects. A polymorphism of the D2 dopamine receptor which renders it less sensitive to dopamine stimulation has been proposed to promote self-stimulatory behavior such as consuming alcohol, abusing drugs, or binging on foods. It is important to determine how this polymorphism may interact with other well-known candidate genes for obesity including polymorphisms of the leptin receptor gene and the opiomelanocortin gene. Leptin is a proinflammatory cytokine as well as a long-term signal maintaining body fat. Upper-body obesity stimulates systemic inflammation through the action of multiple cytokines including leptin throughout many organs including the brain. The association of numerous diseases including diabetes mellitus, heart disease, as well as depression with chronic low-grade inflammation due to abdominal obesity has raised the possibility that obesity-associated inflammation affecting the brain may promote addictive behaviors leading to a self-perpetuating cycle that may affect not only foods but addictions to drugs, alcohol, and gambling. This new area of interdisciplinary research holds the promise of developing new approaches to treating drug abuse and obesity.