THE EFFECTS OF CURCUMIN ON BODY COMPOSITION OF PATIENTS WITH ADVANCED PANCREATIC CANCER

Cachexia is very common among patients with advanced pancreatic cancer and is a marker of poor prognosis. Weight loss in cachexia is due to both adipose and muscle compartments, and sarcopenia (severe muscle depletion) is associated with worse outcomes. Curcumin has shown a myriad of biological effects, including anti-cancer and anti-inflammatory. The ability of curcumin to attenuate cachexia and muscle loss has been tested in animal models, with conflicting results so far. The hypothesis of this study was that patients with advanced pancreatic cancer treated with curcumin for two months have less fat and muscle loss as compared to matched controls not treated with this compound. A matched 1:2 case-control retrospective study was conducted with 22 patients with pancreatic cancer who were treated with curcumin on a previous protocol and 44 untreated controls with the same diagnosis matched by age, gender, time from advanced cancer, body mass index, and number of prior therapies. Data was collected regarding oncologic treatment, medication use, weights, heights, and survival. Body composition was determined by computerized tomography analyses at two timepoints separated by 60±20 days. For treated patients, the first image was at the beginning of treatment and for controls it was determined by the matching time from advanced cancer. The evolution of body composition over time was quantitatively analyzed comparing both groups. All patients lost weight both due to fat and muscle losses, and patients treated with curcumin presented greater losses both in lean adipose body mass. Use of medications, chemotherapy, age, time from advanced cancer, baseline albumin, performance status, and number of prior therapies were not independently correlated with changes in body composition variables. Patients treated with curcumin had borderline shorter survival when compared with untreated patients. Sarcopenic treated patients had significantly shorter survival than non-sarcopenic counterparts, and sarcopenia status was not associated with survival among the controls. Treated patients with shorter survival showed a tendency to lose more lean and especially fat body mass as compared to untreated patients, maybe suggesting an effect of curcumin on shifting weight loss towards the end of life by impacting its mechanisms.

Systematic review of worksite-based behavior change programs that target metabolic syndrome risk factors

Approximately one-third of US adults have metabolic syndrome, the clustering of cardiovascular risk factors that include hypertension, abdominal adiposity, elevated fasting glucose, low high-density lipoprotein (HDL)-cholesterol and elevated triglyceride levels. While the definition of metabolic syndrome continues to be much debated among leading health research organizations, the fact is that individuals with metabolic syndrome have an increased risk of developing cardiovascular disease and/or type 2 diabetes. A recent report by the Henry J. Kaiser Family Foundation found that the US spent $2.2 trillion (16.2% of the Gross Domestic Product) on healthcare in 2007 and cited that among other factors, chronic diseases, including type 2 diabetes and cardiovascular disease, are large contributors to this growing national expenditure. Bearing a substantial portion of this cost are employers, the leading providers of health insurance. In lieu of this, many employers have begun implementing health promotion efforts to counteract these rising costs. However, evidence-based practices, uniform guidelines and policy do not exist for this setting in regard to the prevention of metabolic syndrome risk factors as defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III). Therefore, the aim of this review was to determine the effects of worksite-based behavior change programs on reducing the risk factors for metabolic syndrome in adults. Using relevant search terms, OVID MEDLINE was used to search the peer-reviewed literature published since 1998, resulting in 23 articles meeting the inclusion criteria for the review. The American Dietetic Association's Evidence Analysis Process was used to abstract data from selected articles, assess the quality of each study, compile the evidence, develop a summarized conclusion, and assign a grade based upon the strength of supporting evidence. The results revealed that participating in a worksite-based behavior change program may be associated in one or more improved metabolic syndrome risk factors. Programs that delivered a higher dose (>22 hours), in a shorter duration (<2 years) using two or more behavior-change strategies were associated with more metabolic risk factors being positively impacted. A Conclusion Grade of III was obtained for the evidence, indicating that studies were of weak design or results were inconclusive due to inadequate sample sizes, bias and lack of generalizability. These results provide some support for the continued use of worksite-based health promotion and further research is needed to determine if multi-strategy, intense behavior change programs targeting multiple risk factors are able to sustain health improvements in the long-term.^

Metabolic Regulation of mTOR Activation and Endoplasmic Reticulum Stress in the Heart

When subjected to increased workload, the heart responds metabolically by increasing its reliance on glucose and structurally by increasing the size of myocytes. Whether changes in metabolism regulate the structural remodeling process is unknown. A likely candidate for a link between metabolism and growth in the heart is the mammalian target of rapamycin (mTOR), which couples energy and nutrient metabolism to cell growth. Recently, sustained mTOR activation has also been implicated in the development of endoplasmic reticulum (ER) stress. We explored possible mechanisms by which acute metabolic changes in the hemodynamically stressed heart regulate mTOR activation, ER stress and cardiac function in the ex vivo isolated working rat heart. Doubling the heart’s workload acutely increased rates of glucose uptake beyond rates of glucose oxidation. The concomitant increase in glucose 6-phosphate (G6P) was associated with mTOR activation, endoplasmic reticulum (ER) stress and impaired contractile function. Both rapamycin and metformin restored glycolytic homeostasis, relieved ER stress and rescued contractile function. G6P and ER stress were also downregulated with mechanical unloading of failing human hearts. Taken together, the data support the hypothesis that metabolic remodeling precedes, triggers, and sustains structural remodeling of the heart and implicate a critical role for G6P in load-induced contractile dysfunction, mTOR activation and ER stress. In general terms, the intermediary metabolism of energy providing substrates provides signals for the onset and progression of hypertrophy and heart failure.