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, [1,1,2,3,3-2H5]glycerol was infused to determine the rate of appearance (Ra) of glycerol as a measure of whole-body lipolysis, and [1-13C]palmitic acid was infused to determine the Ra of palmitate as a measure of adipocyte fatty acid release. Palmitate oxidation was determined by measuring 13CO2 enrichment in breath samples, and body composition was measured by bioelectrical impedance analysis. After adjustment for energy intake, whole-body lipolysis was significantly higher in cancer patients versus healthy subjects (6.46 +/- 0.63 and 4.67 +/- 0.46 micromol/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 )micromol/kg x min, respectively, P < .05). No differences in body composition were observed between groups. In conclusion, whole-body lipolysis (as measured by the Ra of glycerol) and palmitate oxidation were elevated in weight-losing cancer patients, but fatty acid release was not significantly different.

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-(2)H(5)]glycerol and [1-(13)C]palmitic acid. Palmitate oxidation was determined by measuring(13)CO(2)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 but 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.

Incorporation and washout of orally administered n-3 fatty acid ethyl esters in different plasma lipid fractions.

The aim of the present study was to quantify the incorporation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) into plasma lipids after oral administration of n-3 fatty acid ethyl esters, since little is known about the rate and pattern of incorporation into plasma lipid fractions. In addition, we aimed to obtain preliminary information regarding EPA half-life, which is needed to establish an optimal dosing schedule. Five healthy volunteers ingested two 8.5 g doses of n-3 fatty acid ethyl esters daily for 7 d, supplying 6.0 g EPA/d and 5.3 g DHA/d. The fatty acid compositions of plasma phospholipids (PL), cholesteryl esters (CE) and triacylglycerols (TAG) were determined during supplementation and during a washout period of 7 d. Half-lives of EPA and DHA were calculated. The proportion of EPA in PL showed a 15-fold increase after 7 d (P < 0.001), while DHA showed a smaller increase (P < 0.01). In CE, EPA also increased (P < 0.05), while DHA did not increase at all. Remarkably, incorporation of DHA into TAG was even higher than that of EPA. Half-life of EPA in PL ranged from 1.63 to 2.31 d (mean 1.97 (SE 0.15) d), whereas mean half-life of EPA in CE was 3.27 (SE 0.56) d. In three subjects, washout of EPA and DHA from TAG seemed to follow a bi-exponential pattern, with a short half-life (< 1 d) in the initial phase and a half-life of several days in the second phase. In conclusion, EPA ethyl esters are rapidly incorporated into plasma lipids, especially into PL. The relatively long half-life of EPA in plasma would permit a dosing schedule with intervals of > or = 12 h in supplementation studies.