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Dietary Changes Impact the Gut Microbe Composition in Overweight and Obese Men with Prostate Cancer Undergoing Radical Prostatectomy.
Frugé, AD, Ptacek, T, Tsuruta, Y, Morrow, CD, Azrad, M, Desmond, RA, Hunter, GR, Rais-Bahrami, S, Demark-Wahnefried, W
Journal of the Academy of Nutrition and Dietetics. 2018;(4):714-723.e1
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Abstract
BACKGROUND Diet and obesity influence prostate cancer risk and progression-effects that may be mediated through the gut microbiome. OBJECTIVE Our aim was to explore relationships among diet, gut microbes, and Gleason sum in overweight and obese prostate cancer patients enrolled in a presurgical weight-loss trial. DESIGN Randomized controlled trial (NCT01886677) secondary analysis. PARTICIPANTS/SETTING In 2013-2014, 40 prostate cancer patients in the southeastern United States were randomized and allocated equally to weight-loss and wait-list control arms while they awaited prostatectomy; stool samples were collected on a subset of 22 patients. INTERVENTION Registered dietitian nutritionists and exercise physiologists provided semi-weekly in-person and telephone-based guidance on calorie-restricted diets and exercise to promote an approximate weight loss of 0.91 kg/wk. MAIN OUTCOME MEASURES Baseline and follow-up 24-hour dietary recalls were conducted and analyzed (using the Automated Self-Administered 24-hour dietary recall system; National Cancer Institute, Bethesda, MD) for macronutrients, micronutrients, and food groups. Microbiome analysis targeting the V4 region of the 16S ribosomal RNA gene was performed on fecal samples. Biopsy Gleason sum data were accessed from diagnostic pathology reports. STATISTICAL ANALYSES PERFORMED Associations between dietary factors and operational taxonomic units were determined by β-diversity analysis. Wilcoxon signed rank, and Mann-Whitney U testing assessed within- and between-arm differences. Associations between Gleason sum and operational taxonomic units, and diet and operational taxonomic units, were analyzed using Spearman correlations. RESULTS At baseline, Proteobacteria (median 0.06, interquartile range 0.01 to 0.16) were abundant, with four orders positively associated with Gleason sum. Gleason sum was associated with Clostridium (ρ=.579; P=0.005) and Blautia (ρ=-0.425, P=0.049). Increased red meat consumption from baseline was associated with Prevotella (ρ=-.497; P=0.018) and Blautia (ρ=.422; P=0.039). Men who increased poultry intake had decreased Clostridiales abundance (P=0.009). CONCLUSIONS This hypothesis-generating study provides a starting point for investigating the relationships between the fecal microbiome, diet, and prostate cancer. Adequately powered studies are required to further explore and validate these findings.
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Presurgical weight loss affects tumour traits and circulating biomarkers in men with prostate cancer.
Demark-Wahnefried, W, Rais-Bahrami, S, Desmond, RA, Gordetsky, JB, Hunter, GR, Yang, ES, Azrad, M, Frugé, AD, Tsuruta, Y, Norian, LA, et al
British journal of cancer. 2017;117(9):1303-1313
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Obesity is a risk factor for 13 different cancers and a recent meta-analysis has shown increased weight to be associated with biochemical recurrence in men with prostate cancer. However, few studies have explored whether presurgical intentional weight loss results in improved prostate cancer outcomes. The aim of this trial was to explore the efficacy of weight loss among overweight and obese men with prostate cancer. Forty participants were randomised to either the presurgical weight loss intervention group or control arm, and changes in weight, body composition, quality of life, tumour biology and biomarkers were recorded. This study found that intentional weight loss caused mixed effects on tumour proliferation and gene expression. Based on these results, the authors recommend that more research is needed before effectively recommending presurgical weight loss among overweight men with prostate cancer.
Abstract
BACKGROUND Obesity is associated with aggressive prostate cancer. To explore whether weight loss favourably affects tumour biology and other outcomes, we undertook a presurgical trial among overweight and obese men with prostate cancer. METHODS This single-blinded, two-arm randomised controlled trial explored outcomes of a presurgical weight loss intervention (WLI) that promoted ∼1 kg per week loss via caloric restriction and increased physical activity (PA). Forty overweight/obese men with clinically confirmed prostate cancer were randomised to the WLI presurgery or to a control arm; changes in weight, body composition, quality-of-life, circulating biomarkers, gene expression, and immunohistochemical markers in tumour and benign prostatic tissue were evaluated. RESULTS The study period averaged 50 days. Mean (s.d.) change scores for the WLI vs control arms were as follows: weight: -4.7 (3.1) kg vs -2.2 (4.4) kg (P=0.0508); caloric intake: -500 (636) vs -159 (600) kcal per day (P=0.0034); PA: +0.9 (3.1) vs +1.7 (4.6) MET-hours per day (NS); vitality: +5.3 (7.l4) vs -1.8 (8.1) (P=0.0491); testosterone: +55.1 (86.0) vs -48.3 (203.7) ng dl-1 (P=0.0418); sex hormone-binding globulin: +14.0 (14.6) vs +1.8 (7.6) nmol l-1 (P=0.0023); and leptin: -2.16 (2.6) vs -0.03 (3.75) (P=0.0355). Follow-up Ki67 was significantly higher in WLI vs control arms; median (interquartile range): 5.0 (2.5,10.0) vs 0.0 (0.0,2.5) (P=0.0061) and several genes were upregulated, for example, CTSL, GSK3B, MED12, and LAMC2. CONCLUSIONS Intentional weight loss shows mixed effects on circulating biomarkers, tumour gene expression, and proliferative markers. More study is needed before recommending weight loss, in particular rapid weight loss, among men with prostate cancer.
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Feasibility outcomes of a presurgical randomized controlled trial exploring the impact of caloric restriction and increased physical activity versus a wait-list control on tumor characteristics and circulating biomarkers in men electing prostatectomy for prostate cancer.
Demark-Wahnefried, W, Nix, JW, Hunter, GR, Rais-Bahrami, S, Desmond, RA, Chacko, B, Morrow, CD, Azrad, M, Frugé, AD, Tsuruta, Y, et al
BMC cancer. 2016;16:61
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There is a strong body of evidence associating obesity and increased risk for more aggressive and progressive cancer. This paper aims to assess the feasibility of a presurgical diet and exercise weight loss intervention in men with newly-diagnosed prostate cancer who elected for prostatectomy. It also aims to explore the intervention’s effects on tumour proliferation rates and other biomarkers. The 3-weeks randomised controlled study included 40 overweight or obese men newly-diagnosed with prostate cancer. Participants in experimental arm were assigned to a healthy energy-restricted diet versus wait-list control arm. All feasibility endpoints were achieved with accrual completed within 2 years, retention of 85%, adherence of 95% and no adverse events. Biologic outcomes were not included in this paper, as biological testing was still ongoing. Authors concluded that this study’s methods and data on feasibility could provide useful framework for the design of future trials. They also highlighted the importance of presurgical trials as a feasible and safe means to assess the impacts of diet and exercise on tumour tissue.
Abstract
BACKGROUND Obesity is associated with tumor aggressiveness and disease-specific mortality for more than 15 defined malignancies, including prostate cancer. Preclinical studies suggest that weight loss from caloric restriction and increased physical activity may suppress hormonal, energy-sensing, and inflammatory factors that drive neoplastic progression; however, exact mechanisms are yet to be determined, and experiments in humans are limited. METHODS We conducted a randomized controlled trial among 40 overweight or obese, newly-diagnosed prostate cancer patients who elected prostatectomy to explore feasibility of a presurgical weight loss intervention that promoted a weight loss of roughly one kg. week(-1) via caloric restriction and physical activity, as well as to assess effects on tumor biology and circulating biomarkers. Measures of feasibility (accrual, retention, adherence, and safety) were primary endpoints. Exploratory aims were directed at the intervention's effect on tumor proliferation (Ki-67) and other tumor markers (activated caspase-3, insulin and androgen receptors, VEGF, TNFβ, NFκB, and 4E-BP1), circulating biomarkers (PSA, insulin, glucose, VEGF, TNFβ, leptin, SHBG, and testosterone), lymphocytic gene expression of corresponding factors and cellular bioenergetics in neutrophils, and effects on the gut microbiome. Consenting patients were randomized in a 1:1 ratio to either: 1) weight loss via a healthful, guidelines-based diet and exercise regimen; or 2) a wait-list control. While biological testing is currently ongoing, this paper details our methods and feasibility outcomes. RESULTS The accrual target was met after screening 101 cases (enrollment rate: 39.6%). Other outcomes included a retention rate of 85%, excellent adherence (95%), and no serious reported adverse events. No significant differences by age, race, or weight status were noted between enrollees vs. non-enrollees. The most common reasons for non-participation were "too busy" (30%), medical exclusions (21%), and "distance" (16%). CONCLUSIONS Presurgical trials offer a means to study the impact of diet and exercise interventions directly on tumor tissue, and other host factors that are feasible and safe, though modifications are needed to conduct trials within an abbreviated period of time and via distance medicine-based approaches. Pre-surgical trials are critical to elucidate the impact of lifestyle interventions on specific mechanisms that mediate carcinogenesis and which can be used subsequently as therapeutic targets. TRIAL REGISTRATION NCT01886677.
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Light-intensity activity attenuates functional decline in older cancer survivors.
Blair, CK, Morey, MC, Desmond, RA, Cohen, HJ, Sloane, R, Snyder, DC, Demark-Wahnefried, W
Medicine and science in sports and exercise. 2014;(7):1375-83
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Abstract
UNLABELLED While moderate- to vigorous-intensity physical activities (MVPA) confer the greatest health benefits, evidence suggests that light-intensity activities are also beneficial, particularly for older adults and individuals with moderate to severe comorbidities. PURPOSE To examine cross-sectional and longitudinal associations between light-intensity activity and physical function in older cancer survivors at increased risk for age- and treatment-related comorbidities, including accelerated functional decline. METHODS The analysis included data from 641 breast, prostate, and colorectal cancer survivors (54% female) age 65 yr and older who participated in a 1-yr home-based diet and exercise intervention designed to reduce the rate of physical function decline. ANCOVA was used to compare means of physical function across levels of PA intensity (low-light [LLPA]: 1.5-2.0 METs; high-light [HLPA]: 2.1-2.9 METs; MVPA ≥3.0 METs). RESULTS In cross-sectional analyses, increasing tertiles of light-intensity activity were associated with higher scores for all three measures of physical function (all P values <0.005), after adjusting for age, sex, body mass index, comorbidity, symptoms, and MVPA. Associations were stronger for HLPA than for LLPA. Compared with survivors who had decreased MVPA or maintained stable MVPA and HLPA at the postintervention follow-up, those who had increased HLPA, but had decreased MVPA or maintained stable MVPA, reported higher physical function scores (LS means [95% confidence interval]: SF-36 Physical Function Subscale: -5.58 [-7.96 to -3.20] vs -2.54 [-5.83 to 0.75], P = 0.14; Basic Lower Extremity Function: -2.00 [-3.45 to -0.55] vs 0.28 [-1.72 to 2.28], P = 0.07; Advanced Lower Extremity Function: -2.58 [-4.00 to -1.15] vs 0.44 [-1.52 to 2.40], P = 0.01). CONCLUSIONS Our findings suggest that increasing light-intensity activities, especially HLPA, may be a viable approach to reducing the rate of physical function decline in individuals who are unable or reluctant to initiate or maintain adequate levels of moderate-intensity activities.
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Harvest for health gardening intervention feasibility study in cancer survivors.
Blair, CK, Madan-Swain, A, Locher, JL, Desmond, RA, de Los Santos, J, Affuso, O, Glover, T, Smith, K, Carley, J, Lipsitz, M, et al
Acta oncologica (Stockholm, Sweden). 2013;(6):1110-8
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BACKGROUND Cancer survivors are at increased risk for second malignancies, cardiovascular disease, diabetes, and functional decline. Evidence suggests that a healthful diet and physical activity may reduce the risk of chronic disease and improve health in this population. METHODS We conducted a feasibility study to evaluate a vegetable gardening intervention that paired 12 adult and child cancer survivors with Master Gardeners to explore effects on fruit and vegetable intake, physical activity, quality-of-life, and physical function. Throughout the year-long study period, the survivor-Master Gardener dyads worked together to plan/plant three gardens, harvest/rotate plantings, and troubleshoot/correct problems. Data on diet, physical activity, and quality-of-life were collected via surveys; anthropometrics and physical function were objectively measured. Acceptability of the intervention was assessed with a structured debriefing survey. RESULTS The gardening intervention was feasible (robust enrollment; minimal attrition) and well-received by cancer survivors and Master Gardeners. Improvement in three of four objective measures of strength, agility, and endurance was observed in 90% of survivors, with the following change scores [median (interquartile range)] noted between baseline and one-year follow-up: hand grip test [+ 4.8 (3.0, 6.7) kg], 2.44 meter Get-Up-and-Go [+ 1.0 (+ 1.8, + 0.2) seconds], 30-second chair stand [+ 3.0 (+ 1.0, 5.0) stands], and six-minute walk [+ 11.6 (6.1, 48.8) meters]. Increases of ≥ 1 fruit and vegetable serving/day and ≥ 30 minutes/week of physical activity were observed in 40% and 60%, respectively. CONCLUSION These preliminary results support the feasibility and acceptability of a mentored gardening intervention and suggest that it may offer a novel and promising strategy to improve fruit and vegetable consumption, physical activity, and physical function in cancer survivors. A larger randomized controlled trial is needed to confirm our results.
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Favourable metabolic effects of a eucaloric lower-carbohydrate diet in women with PCOS.
Gower, BA, Chandler-Laney, PC, Ovalle, F, Goree, LL, Azziz, R, Desmond, RA, Granger, WM, Goss, AM, Bates, GW
Clinical endocrinology. 2013;(4):550-7
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OBJECTIVE Diet-induced reduction in circulating insulin may be an attractive nonpharmacological treatment for women with polycystic ovary syndrome (PCOS) among whom elevated insulin may exacerbate symptoms by stimulating testosterone synthesis. This study was designed to determine whether a modest reduction in dietary carbohydrate (CHO) content affects β-cell responsiveness, serum testosterone concentration and insulin sensitivity in women with PCOS. DESIGN In a crossover design, two diets ('Standard,' STD, 55:18:27% energy from carbohydrate/protein/fat; lower-carbohydrate, 41:19:40) were provided for 8 weeks in random order with a 4-week washout between. PATIENTS Thirty women with PCOS. MEASUREMENTS β-cell responsiveness assessed as the C-peptide response to glucose during a liquid meal test; insulin sensitivity from insulin and glucose values throughout the test; insulin resistance (HOMA-IR); and total testosterone by immunoassay. RESULTS Paired t-test indicated that the lower-CHO diet induced significant decreases in basal β-cell response (PhiB), fasting insulin, fasting glucose, HOMA-IR, total testosterone and all cholesterol measures, and significant increases in insulin sensitivity and dynamic ('first-phase') β-cell response. The STD diet induced a decrease in HDL-C and an increase in the total cholesterol-to-HDL-C ratio. Across all data combined, the change in testosterone was positively associated with the changes in fasting insulin, PhiB and insulin AUC (P < 0·05). CONCLUSIONS In women with PCOS, modest reduction in dietary CHO in the context of a weight-maintaining diet has numerous beneficial effects on the metabolic profile that may lead to a decrease in circulating testosterone.
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Self-efficacy as a predictor of weight change and behavior change in the PREMIER trial.
Wingo, BC, Desmond, RA, Brantley, P, Appel, L, Svetkey, L, Stevens, VJ, Ard, JD
Journal of nutrition education and behavior. 2013;(4):314-21
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OBJECTIVES Determine whether self-efficacy independently predicted weight loss in a behavioral intervention and explore factors that influence the path between self-efficacy and weight change. DESIGN Secondary analysis of the PREMIER trial, a randomized controlled trial testing effects of lifestyle interventions on blood pressure. SETTING Four academic medical centers. PARTICIPANTS PREMIER recruited adults (n = 810) with pre-hypertension/stage 1 hypertension, not currently receiving medication. This analysis excluded participants in the control arm, resulting in n = 537. INTERVENTIONS Participants were randomly assigned to 1 of 3 groups: advice only, established lifestyle recommendations, or established lifestyle recommendations plus Dietary Approaches to Stop Hypertension dietary pattern. MAIN OUTCOME MEASURES Self-efficacy (dietary self-efficacy [DSE], exercise self-efficacy [ESE]), dietary intake, fitness. ANALYSIS Pearson correlations, 1-way analysis of variance, mediation analyses. RESULTS Despite an overall decrease in DSE/ESE, change in DSE/ESE significantly predicted weight change at 6 (β = -.21, P < .01; β = -.19, P < .01, respectively) and 18 months (β = -.19, P < .01; β = -.35, P < .01). Change in percent calories from fat partially mediated the DSE/weight change relationship at 6 months. Change in fitness partially mediated the ESE/weight change relationship at 18 months. CONCLUSIONS AND IMPLICATIONS Changes in DSE/ESE were not associated with behavior change as hypothesized. Additional research is needed to identify mediators between self-efficacy and adoption of behaviors that influence weight loss.
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Missing data in randomized clinical trials for weight loss: scope of the problem, state of the field, and performance of statistical methods.
Elobeid, MA, Padilla, MA, McVie, T, Thomas, O, Brock, DW, Musser, B, Lu, K, Coffey, CS, Desmond, RA, St-Onge, MP, et al
PloS one. 2009;(8):e6624
Abstract
BACKGROUND Dropouts and missing data are nearly-ubiquitous in obesity randomized controlled trails, threatening validity and generalizability of conclusions. Herein, we meta-analytically evaluate the extent of missing data, the frequency with which various analytic methods are employed to accommodate dropouts, and the performance of multiple statistical methods. METHODOLOGY/PRINCIPAL FINDINGS We searched PubMed and Cochrane databases (2000-2006) for articles published in English and manually searched bibliographic references. Articles of pharmaceutical randomized controlled trials with weight loss or weight gain prevention as major endpoints were included. Two authors independently reviewed each publication for inclusion. 121 articles met the inclusion criteria. Two authors independently extracted treatment, sample size, drop-out rates, study duration, and statistical method used to handle missing data from all articles and resolved disagreements by consensus. In the meta-analysis, drop-out rates were substantial with the survival (non-dropout) rates being approximated by an exponential decay curve (e(-lambdat)) where lambda was estimated to be .0088 (95% bootstrap confidence interval: .0076 to .0100) and t represents time in weeks. The estimated drop-out rate at 1 year was 37%. Most studies used last observation carried forward as the primary analytic method to handle missing data. We also obtained 12 raw obesity randomized controlled trial datasets for empirical analyses. Analyses of raw randomized controlled trial data suggested that both mixed models and multiple imputation performed well, but that multiple imputation may be more robust when missing data are extensive. CONCLUSION/SIGNIFICANCE Our analysis offers an equation for predictions of dropout rates useful for future study planning. Our raw data analyses suggests that multiple imputation is better than other methods for handling missing data in obesity randomized controlled trials, followed closely by mixed models. We suggest these methods supplant last observation carried forward as the primary method of analysis.
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The impact of cost on the availability of fruits and vegetables in the homes of schoolchildren in Birmingham, Alabama.
Ard, JD, Fitzpatrick, S, Desmond, RA, Sutton, BS, Pisu, M, Allison, DB, Franklin, F, Baskin, ML
American journal of public health. 2007;(2):367-72
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OBJECTIVES Fruit and vegetable cost is a presumed barrier to intake. We sought to determine whether fruit and vegetable cost and consumers' race and income would predict availability of fruits and vegetables in homes of schoolchildren in the Birmingham, Ala, area. METHODS Data on availability of 27 fruit and vegetable items were obtained from homes of 1355 children (32% African American) in the Birmingham area. Fruit and vegetable costs were obtained from the US Department of Agriculture. We used discrete choice analysis with the dependent variable represented as presence or absence of the fruit or vegetable item. Explanatory variables included fruit and vegetable price per serving; child's gender, race, and age; and parent's body mass index and income. RESULTS Higher cost was inversely related to fruit and vegetable availability. Higher income, African American race, and female gender were positively related to availability. Cost per serving was stratified into 3 categories-low, medium, and high. Relative to low-cost items, only high-cost items decreased the odds of availability significantly. CONCLUSIONS Fruit and vegetable cost does impact availability and has the greatest impact for high-cost items. Although cost was inversely related to availability, African Americans reported higher fruit and vegetable availability than Whites. Additional studies are needed to determine whether food items of lower nutritive value and comparable cost impact availability.
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Effect of folic acid fortification of foods on folate intake in female smokers with cervical dysplasia.
Shikany, JM, Heimburger, DC, Piyathilake, CJ, Desmond, RA, Greene, PG
Nutrition (Burbank, Los Angeles County, Calif.). 2004;(5):409-14
Abstract
OBJECTIVE We investigated the effect of folic acid fortification of enriched cereal grains on folate intake in women of predominantly childbearing age at high risk for cervical cancer. METHODS Subjects in this cross-sectional study were 77 women randomized between November 1999 and December 2000 in the Women's Intervention to Stay Healthy (WISH), a clinical trial evaluating the effect of a tobacco control intervention on the progression of cervical dysplasia. All subjects were cigarette smokers, had a previously abnormal Papanicolaou test, and were positive for high-risk human papillomavirus at entry. Dietary intake was assessed with food-frequency questionnaires completed at the baseline visit for WISH. The effect of folic acid fortification on folate intake was assessed by using pre- and postfortification folate databases to estimate folate intake. RESULTS Mean folate intake assessed with the postfortification database was 63% higher than intake assessed with the prefortification database: 417 versus 256 microg/d of dietary folate equivalents (P < 0.0001). The proportion of subjects below the estimated average requirement for folate was smaller after fortification than before fortification: 40.3% versus 75.3% (P < 0.0001). Several foods, including white bread, cheese dishes, spaghetti, and rice, became major sources of folate as a result of fortification. CONCLUSIONS Folic acid fortification resulted in an increased intake of folate in these subjects. However, even with fortification, folate intake in a large proportion of these women remained below recommended levels. These results should be considered before decisions regarding future levels of folic acid fortification are made.