Effect of dietary patterns differing in carbohydrate and fat content on blood lipidand glucose profiles based on weight-loss success of breast-cancer survivors

INTRODUCTION: Healthy body weight is an important factor for prevention of breast cancer recurrence. Yet, weight loss and weight gain are not currently included in clinical-practice guidelines for posttreatment of breast cancer. The work reported addresses one of the questions that must be considered in recommending weight loss to patients: does it matter what diet plan is used, a question of particular importance because breast cancer treatment can increase risk for cardiovascular disease. METHODS: Women who completed treatment for breast cancer were enrolled in a nonrandomized, controlled study investigating effects of weight loss achieved by using two dietary patterns at the extremes of macronutrient composition, although both diet arms were equivalent in protein: high fat, low carbohydrate versus low fat, high carbohydrate. A nonintervention group served as the control arm; women were assigned to intervention arms based on dietary preferences. During the 6-month weight-loss program, which was menu and recipe defined, participants had monthly clinical visits at which anthropometric data were collected and fasting blood was obtained for safety monitoring for plasma lipid profiles and fasting glucose. Results from 142 participants are reported. RESULTS: Adverse effects on fasting blood lipids or glucose were not observed in either dietary arm. A decrease in fasting glucose was observed with progressive weight loss and was greater in participants who lost more weight, but the effect was not statistically significant, even though it was observed across both diet groups (P = 0.21). Beneficial effects of weight loss on cholesterol (4.7%; P = 0.001), triglycerides (21.8%; P = 0.01), and low-density lipoprotein (LDL) cholesterol (5.8%; P = 0.06) were observed in both groups. For cholesterol (P = 0.07) and LDL cholesterol (P = 0.13), greater reduction trends were seen on the low-fat diet pattern; whereas, for triglycerides (P = 0.01) and high-density lipoprotein (HDL) cholesterol (P = 0.08), a decrease or increase, respectively, was greater on the low-carbohydrate diet pattern. CONCLUSIONS: Because an individual's dietary preferences can affect dietary adherence and weight-loss success, the lack of evidence of a negative effect of dietary pattern on biomarkers associated with cardiovascular risk is an important consideration in the development of breast cancer practice guidelines for physicians who recommend that their patients lose weight. Whether dietary pattern affects biomarkers that predict long-term survival is a primary question in this ongoing clinical trial

Metabolically-Defined Body Size Phenotypes and Risk of Endometrial Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Background: Obesity is a risk factor for endometrial cancer but whether metabolic dysfunction is associated with endometrial cancer independent of body size is not known. Methods: The association of metabolically defined body size phenotypes with endometrial cancer risk was investigated in a nested case-control study (817 cases/ 817 controls) within the European Prospective Investigation into Cancer and Nutrition (EPIC). Concentrations of C-peptide were used to define metabolically healthy (MH; _1st tertile) status among the control participants. These metabolic health definitions were combined with normal weight (NW); body mass index (BMI)_25 kg/m2 or WC >_80 cm or WHR >_0. 8) status, generating four phenotype groups for each anthropometric measure: (i) MH/NW, (ii) MH/OW, (iii) MU/ NW, and (iv) MU/OW. Results: In a multivariable-adjusted conditional logistic regression model, compared with MH/NW individuals, endometrial cancer risk was higher among those classified as MU/NW [ORWC, 1.48; 95% confidence interval (CI), 1.05-2.10 and ORWHR, 1.68; 95% CI, 1.21- 2.35] and MU/OW (ORBMI, 2.38; 95% CI, 1.73-3.27; ORWC, 2.69; 95% CI, 1.92-3.77 and ORWHR, 1.83; 95% CI, 1.32-2.54). MH/OW individuals were also at increased endometrial cancer risk compared with MH/NW individuals (ORWC, 1.94; 95% CI, 1.24-3.04). Conclusions: Women with metabolic dysfunction appear to have higher risk of endometrial cancer regardless of their body size. However, OW status raises endometrial cancer risk even among women with lower insulin levels, suggesting that obesity related pathways are relevant for the development of this cancer beyond insulin. Impact: Classifying women by metabolic health may be of greater utility in identifying those at higher risk for endometrial cancer than anthropometry per se

Metabolomics Analytics Workflow for Epidemiological Research: Perspectives from the Consortium of Metabolomics Studies (COMETS)

The application of metabolomics technology to epidemiological studies is emerging as a new approach to elucidate disease etiology and for biomarker discovery. However, analysis of metabolomics data is complex and there is an urgent need for the standardization of analysis workflow and reporting of study findings. To inform the development of such guidelines, we conducted a survey of 47 cohort representatives from the Consortium of Metabolomics Studies (COMETS) to gain insights into the current strategies and procedures used for analyzing metabolomics data in epidemiological studies worldwide. The results indicated a variety of applied analytical strategies, from biospecimen and data pre-processing and quality control to statistical analysis and reporting of study findings. These strategies included methods commonly used within the metabolomics community and applied in epidemiological research, as well as novel approaches to pre-processing pipelines and data analysis. To help with these discrepancies, we propose use of open-source initiatives such as the online web-based tool COMETS Analytics, which includes helpful tools to guide analytical workflow and the standardized reporting of findings from metabolomics analyses within epidemiological studies. Ultimately, this will improve the quality of statistical analyses, research findings, and study reproducibility

Effect of a low fat versus a low carbohydrate weight loss dietary intervention on biomarkers of long term survival in breast cancer patients ('CHOICE'): study protocol

<p>Abstract</p> <p>Background</p> <p>Weight loss in overweight or obese breast cancer patients is associated with an improved prognosis for long term survival. However, it is not clear whether the macronutrient composition of the chosen weight loss dietary plan imparts further prognostic benefit. A study protocol is presented for a dietary intervention to investigate the effects of weight loss dietary patterns that vary markedly in fat and carbohydrate contents on biomarkers of exposure to metabolic processes that may promote tumorigenesis and that are predictive of long term survival. The study will also determine how much weight must be lost for biomarkers to change in a favorable direction.</p> <p>Methods/Design</p> <p>Approximately 370 overweight or obese postmenopausal breast cancer survivors (body mass index: 25.0 to 34.9 kg/m²) will be accrued and assigned to one of two weight loss intervention programs or a non-intervention control group. The dietary intervention is implemented in a free living population to test the two extremes of popular weight loss dietary patterns: a high carbohydrate, low fat diet versus a low carbohydrate, high fat diet. The effects of these dietary patterns on biomarkers for glucose homeostasis, chronic inflammation, cellular oxidation, and steroid sex hormone metabolism will be measured. Participants will attend 3 screening and dietary education visits, and 7 monthly one-on-one dietary counseling and clinical data measurement visits in addition to 5 group visits in the intervention arms. Participants in the control arm will attend two clinical data measurement visits at baseline and 6 months. The primary outcome is high sensitivity C-reactive protein. Secondary outcomes include interleukin-6, tumor necrosis factor-α, insulin-like growth factor-1 (IGF), IGF binding protein-3, 8-isoprostane-F2-alpha, estrone, estradiol, progesterone, sex hormone binding globulin, adiponectin, and leptin.</p> <p>Discussion</p> <p>While clinical data indicate that excess weight for height is associated with poor prognosis for long term survival, little attention is paid to weight control in the clinical management of breast cancer. This study will provide information that can be used to answer important patient questions about the effects of dietary pattern and magnitude of weight loss on long term survival following breast cancer treatment.</p> <p>Clinical Trial Registration</p> <p>CA125243</p

Dietary Oncopharmacognosy as a Crosswalk between Precision Oncology and Precision Nutrition

While diet and nutrition are modifiable risk factors for many chronic and infectious diseases, their role in cancer prevention and control remains under investigation. The lack of clarity of some diet–cancer relationships reflects the ongoing debate about the relative contribution of genetic factors, environmental exposures, and replicative errors in stem cell division as determinate drivers of cancer risk. In addition, dietary guidance has often been based upon research assuming that the effects of diet and nutrition on carcinogenesis would be uniform across populations and for various tumor types arising in a specific organ, i.e., that one size fits all. Herein, we present a paradigm for investigating precision dietary patterns that leverages the approaches that led to successful small-molecule inhibitors in cancer treatment, namely understanding the pharmacokinetics and pharmacodynamics of small molecules for targeting carcinogenic mechanisms. We challenge the scientific community to refine the paradigm presented and to conduct proof-in-concept experiments that integrate existing knowledge (drug development, natural products, and the food metabolome) with developments in artificial intelligence to design and then test dietary patterns predicted to elicit drug-like effects on target tissues for cancer prevention and control. We refer to this precision approach as dietary oncopharmacognosy and envision it as the crosswalk between the currently defined fields of precision oncology and precision nutrition with the goal of reducing cancer deaths

Impaired fasting glucose with or without impaired glucose tolerance: progressive or parallel states of prediabetes?

Our objective was to determine whether defects underlying impaired fasting glucose (IFG) are maintained and additive when combined with impaired glucose tolerance (IGT) (representing a progressive form of prediabetes) or are distinct in IFG/IGT (reflecting a parallel form of prediabetes). Volunteers with IFG (n = 10), IFG/IGT (n = 14), or normal glucose tolerance (NGT; n = 15) were matched for demographics and anthropometry. Insulin secretion was assessed using the glucose step-up protocol and insulin action through the use of a two-stage hyperinsulinemic euglycemic clamp with infusion of [6,6-2H2]glucose. Modeling of insulin secretory parameters revealed similar basal (Φb) but diminished dynamic (Φd) components in both IFG and IFG/IGT (P = 0.05 vs. NGT for both). Basal glucose rate of appearance (Ra) was higher in IFG compared with NGT (P < 0.01) and also, surprisingly, with IFG/IGT (P < 0.04). Moreover, glucose Ra suppressed more during the low-dose insulin clamp in IFG (P < 0.01 vs. NGT, P = 0.08 vs. IFG/IGT). Insulin-stimulated glucose uptake [glucose rate of disappearance (Rd)] was similar in IFG, IFG/IGT, and NGT throughout the clamp. We conclude that nuances of β-cell dysfunction observed in IFG were also noted in IFG/IGT. A trend for additional insulin secretory defects was observed in IFG/IGT, possibly suggesting progression in β-cell failure in this group. In contrast, basal glucose Ra and its suppressability with insulin were higher in IFG, but not IFG/IGT, compared with NGT. Together, these data indicate that IFG/IGT may be a distinct prediabetic syndrome rather than progression from IFG

Weight loss interventions for breast cancer survivors: impact of dietary pattern.

Body weight management is not emphasized in clinical practice guidelines for breast cancer survivors, reflecting the lack of evidence that weight loss improves prognosis. Even if this situation changes, the optimal design for weight loss interventions is unclear. We conducted a 6-month non-randomized, controlled weight loss intervention in 249 post-menopausal breast cancer survivors. This paper reports effects on two secondary endpoints, change in body weight and composition. Participants were predominantly non-Hispanic whites (89%) with a mean age of 54.9 ± 9.2 years, a mean BMI of 29.0 ± 2.6 kg/m: (2) and an average of 43 ± 5% body fat. Two dietary interventions, low fat or low carbohydrate, were investigated and consisted of a 42 day cycle of menus and recipes. Weight loss counseling and anthropometric assessment were provided at monthly clinic visits. One hundred ninety-two women completed the trial (77% retention). In comparison to the nonintervention control, both intervention arms achieved significant decreases in body weight (12.5%), body fat (27.5%), waist circumference (9.5%), and hip circumference (7.8%) (all p < 0.001) with minimal effects on lean mass (1.3% decrease). Median time to 5 and 10% weight loss was 2 (95% confidence interval = 1 to 3) and 4 (95% confidence interval = 3 to 5) months, respectively, and 23% of participants experienced ≥ 15% weight loss. Loss of body weight and fat mass was rapid and substantial irrespective of dietary approach when a structured program was provided with monthly anthropometric assessment and weight loss counseling.ClinicalTrials.gov NCT01315483