Reduced total energy expenditure and physical activity in cachectic patients with pancreatic cancer can be modulated by an energy and protein dense oral supplement enriched with n-3 fatty acids

The aim of the study was to assess the total energy expenditure (TEE), resting energy expenditure (REE) and physical activity level (PAL) in home-living cachectic patients with advanced pancreatic cancer. The influence of an energy and protein dense oral supplement either enriched with or without the n-3 fatty acid eicosapentaenoic acid (EPA) and administered over an 8-week period was also determined. In total, 24 patients were studied at baseline. The total energy expenditure was measured using doubly labelled water and REE determined by indirect calorimetry. Patients were studied at baseline and then randomised to either oral nutritional supplement. Measurements were repeated at 8 weeks. At baseline, REE was increased compared with predicted values for healthy individuals (1387(42) vs 1268(32) kcal day-1, P=0.001), but TEE (1732(82) vs 1903(48) kcal day-1, P=0.023) and PAL (1.24(0.04) vs 1.50) were reduced. After 8 weeks, the REE, TEE and PAL of patients who received the control supplement did not change significantly. In contrast, although REE did not change, TEE and PAL increased significantly in those who received the n-3 (EPA) enriched supplement. In summary, patients with advanced pancreatic cancer were hypermetabolic. However, TEE was reduced and this was secondary to a reduction in physical activity. The control energy and protein dense oral supplement did not influence the physical activity component of TEE. In contrast, administration of the supplement enriched with EPA was associated with an increase in physical activity, which may reflect improved quality of life

Tumor macroenvironment and metabolism

In this review we introduce the concept of the tumor macroenvironment and explore it in the context of metabolism. Tumor cells interact with the tumor microenvironment including immune cells. Blood and lymph vessels are the critical components that deliver nutrients to the tumor and also connect the tumor to the macroenvironment. Several factors are then released from the tumor itself but potentially also from the tumor microenvironment, influencing the metabolism of distant tissues and organs. Amino acids, and distinct lipid and lipoprotein species can be essential for further tumor growth. The role of glucose in tumor metabolism has been studied extensively. Cancer-associated cachexia is the most important tumor-associated systemic syndrome and not only affects the quality of life of patients with various malignancies but is estimated to be the cause of death in 15%–20% of all cancer patients. On the other hand, systemic metabolic diseases such as obesity and diabetes are known to influence tumor development. Furthermore, the clinical implications of the tumor macroenvironment are explored in the context of the patient’s outcome with special consideration for pediatric tumors. Finally, ways to target the tumor macroenvironment that will provide new approaches for therapeutic concepts are described

Effect of the dietary fat quality on insulin sensitivity.

Recent evidence shows that specific fatty acids affect cell metabolism, modifying the balance between fatty acid oxidation and lipogenesis. These effects may have important implications in addressing the present epidemic of nutrition-related chronic disease. Intake of dietary saturated and n-6 PUFA have increased while n-3 fatty acid intake has decreased. Obesity, type 2 diabetes and insulin resistance are highly prevalent, and both are strongly related to disorders of lipid metabolism characterized by an increased plasma and intracellular fatty acid availability. Thus, it has been hypothesized that change in the quality of dietary fat supply is able to modify the degree of insulin sensitivity. Animal studies provide support for this notion. However, there is limited human data either from normal or diabetic subjects. This review aims to analyse human studies that address this question. To this purpose, the experimental design, dietary compliance, insulin-sensitivity method used and confounding variables are discussed in order to identify the role of dietary fat quality as a risk factor for insulin resistance. Most studies (twelve of fifteen) found no effect relating to fat quality on insulin sensitivity. However, multiple study design flaws limit the validity of this conclusion. In contrast, one of the better designed studies found that consumption of a high-saturated-fat diet decreased insulin sensitivity in comparison to a high-monounsaturated-fat diet. We conclude that the role of dietary fat quality on insulin sensitivity in human subjects should be further studied, using experimental designs that address the limitations of existing data sets

Lipolysis and lipid oxidation in weight-losing cancer patients and healthy subjects

increased lipolysis has been suggested as one of the possible mechanisms underlying cancer cachexia, The study aim was to assess whether lipolysis is increased in weight-losing cancer patients, considering their differences in food intake and body composition. Sixteen healthy subjects and 18 cancer patients with different tumor types and a weight loss of at least 5% in the previous 6 months were included in the study. Food intake was recorded for 4 days. After an overnight fast, [1,1,2,3,3-H-2(5)]glycerol was infused to determine the rate of appearance (Ra) of glycerol as a measure of whole-body lipolysis, and [1-C-13]palmitic acid was infused to determine the Pa of palmitate as a measure of adipocyte fatty acid release, Palmitate oxidation was determined by measuring (CO2)-C-13 enrichment in breath samples, and body composition was measured by bioelectrical impedance analysis, After adjustment for energy intake, whore-body lipolysis was significantly higher in cancer patients versus healthy subjects (6.46 +/- 0.63 and 4.67 +/- 0.46 (mu mol/kg +/- min, respectively, P <.05). The difference in adipocyte fatty acid release did not reach statistical significance. The rate of palmitate oxidation was also significantly higher in patients than in healthy subjects (1.15 +/- 0.10 and 0.93 +/- 0.07 mu mol/kg . min, respectively, P <.05). No differences in body composition were observed between groups. In conclusion, whole-body lipolysis las measured by the Pa of glycerol) and palmitate oxidation were elevated in weight-losing cancer patients, but fatty acid release was not significantly different. by W.B. Saunders Company

Eicosapentaenoic acid ethyl ester supplementation in cachectic cancer patients and healthy subjects: effects on lipolysis and lipid oxidation

Background & aims: Recent reports suggest that weight loss in cachectic cancer patients may be inhibited by supplementation of the n-3 fatty acid eicosapentaenoic acid (20.5n-3, EPA), presumably due to inhibition of lipolysis. The aim of the present double-blind, randomized trial was to assess whether short-term oral EPA ethyl ester (EE) supplementation inhibits lipolysis and lipid oxidation in weight-losing cancer patients and in healthy subjects. Methods: Seventeen weight losing, cancer patients of different tumor types, and 16 healthy subjects were randomized to receive EPA-EE (6 g/d) or placebo (oleic acid (OA)-EE; 6 g/d) for seven days. At baseline (day 0) and during supplementation (days 2 and 7) whole-body lipolysis and palmitic acid release were measured in the overnight fasting state using [1, 1, 2, 3, 3-H-2(5)] glycerol and [1-C-13] palmitic acid. Palmitate oxidation was determined by measuring (CO2)-C-13 enrichment in expired breath. Results: No significant effects of EPA-EE on whole-body lipolysis, palmitic acid release, or palmitate oxidation were detected in cancer patients nor in healthy subjects in comparison with OA-EE. EPA-EE supplementation reduced plasma-free fatty acid and triacylglycerol concentrations significantly in healthy subjects bur not in cancer patients. Conclusion: We conclude that supplementation of EPA-EE does not significantly inhibit lipolysis or lipid oxidation in weight-losing cancer patients or in healthy subjects during short-term supplementation when using OA-EE as a placebo supplement

Fatty acid composition of plasma lipids in patients with pancreatic, lung and oesophageal cancer in comparison with healthy subjects

Institute of Internal Medicine II, Rotterdam, The Netherlands. BACKGROUND & AIMS: Despite the general notion of impaired nutritional status in cancer patients, studies on fatty acid status in cancer patients are limited. The aim of the present study was to investigate whether plasma n-3 fatty acids concentrations are reduced in patients with different tumour types. METHODS: We measured fatty acid composition in plasma phospholipids (PLs) and cholesteryl esters (CEs) in 71 newly diagnosed, untreated cancer patients of three tumour types: oesophageal or cardia cancer (n = 35), non-small cell lung cancer (n = 22) and pancreatic cancer (n = 15) and in 45 healthy subjects. RESULTS: In pancreatic cancer, plasma n-3 fatty acids showed a substantial reduction in both plasma PLs and CES. Although n-3 fatty acids in lung cancer also tended to be reduced, this difference failed to reach statistical significance. n-3 Fatty acid levels were especially reduced in pancreatic cancer patients without diabetes mellitus, and in lung cancer patients with weight loss. In oesophageal cancer, n-3 fatty acid concentrations were comparable to those in healthy subjects. CONCLUSION: We conclude that plasma n-3 fatty acid levels were reduced in pancreatic cancer, tended to be reduced in lung cancer, but were not altered in oesophageal cancer. Further studies are needed to assess the mechanisms underlying the observed changes in n-3 fatty acid concentrations