Weight loss and muscle wasting commonly occurs in patients with cancer, negatively influencing their quality of life, treatment response and survival. Weight loss has been reported as a side effect of chemotherapy treatment in cancer. Weight changes may be the consequence of energy imbalance and disturbances in protein metabolism (through different factors linked with chemotherapy), such as reduced caloric and protein intake (partly related to depression), poor treatment tolerance, hormonal alterations, systemic inflammation etc. This results in body composition modifications in favor of fat gain and/or lean body mass loss in early stage cancer and loss of both fat mass and lean mass in advanced cancer. Depletion of lean tissue in cancer patients is related to short survival, and decreased skeletal muscle mass and function may result in fatigue and inactivity, which contributes to fat mass changes and can be responsible for chemo-toxicity and increased mortality. Gains in muscle mass are difficult to achieve in cancer unless specific metabolic abnormalities are targeted. Recently, the investigators observed that essential amino acid mixtures (EAA) are able to induce protein anabolism in patients with stage III and IV non-small cell lung cancer. Previous experimental research and clinical studies in cachectic conditions (including cancer) indicate that polyunsaturated fatty acids (PUFA) are able to attenuate protein degradation by improving the anabolic response to feeding and by decreasing the acute phase response. Eicosapentaenoic acid (EPA) (in combination with docosahexaenoic acid (DHA)) has been shown to effectively inhibit weight loss in several disease states; however, weight and muscle mass gain was not present or minimal. Recent studies examining the effect of fish oil supplementation in relation to chemotherapy have been inconclusive but found potential beneficial effects on physical performance and increased efficacy of first-line chemotherapy in patients with non-small cell lung cancer. It is the investigators' hypothesis that supplementation with milk protein (containing essential amino acids) carbohydrate (CHO) mixture in combination with fish oil supplementation will target the metabolic alterations in cancer patients receiving chemotherapy, attenuating the negative effects of chemotherapy on gut function, muscle mass and muscle function, and cognition; and leading to reduced toxicity from chemotherapy.
For the cancer subjects, the study involves 1 test day prior to a chemotherapy treatment, a 10-week (± 2 weeks) nutritional intervention period at home starting the first day of the chemotherapy treatment, and one test day after this intervention. Chemotherapy in general lasts at least a few months. Recent studies indicate that a 10-week nutritional supplementation period should be long enough to reach significant improvements in nutritional and clinical outcome parameters during chemotherapy. Throughout these 10 weeks the cancer subjects will take the supplements at home. Cancer subjects will be randomly assigned to receive either fish oil or a placebo and protein or a placebo and will take these supplements daily throughout 10 weeks during chemotherapy. For the healthy subjects, the study will involve one test day (approx. 8 hours). On the test days, the response to a protein meal will be examined and subjects will receive a mixture of amino acids which are a little bit heavier than normal, called stable isotopes. Subjects will also ingest a sugar drink to assess gut permeability. In total, approximate 120 ml of blood will be drawn on each test day to assess outcome measures. The investigators' will also collect urine over these 8 hours, and cancer subjects are asked to collect a fecal sample the day before the test day. After completing the nutritional intervention study, cancer subjects will be monitored for up to 6 months via 2 phone calls and through their physician as part of clinical care. Between 6 months and 2 years after completion of the study, information about disease progression (survival) will be obtained from the physician.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
DOUBLE
Enrollment
31
Texas A&M University
College Station, Texas, United States
Net whole-body protein synthesis
The acute change in whole-body protein synthesis rate before and after intake of meal is determined on the first test day for the healthy control group and the cancer group. Secondly, the cancer patients in all 3 intervention arms are also measured after 10 weeks of intervention to examine the effects of fish oil and protein supplementation during chemotherapy on this outcome measure.
Time frame: Acutely before and after 4 hours of feeding and the change after 10 weeks of supplementation
Citrulline Rate of appearance
Plasma enrichment of citrulline is determined on the first test day for the healthy control group and the cancer group. Secondly, the cancer patients in all 3 intervention arms are also measured after 10 weeks of intervention to examine the effects of fish oil and protein supplementation during chemotherapy on this outcome measure.
Time frame: In the postabsorptive state for 4h on the first test day and the change on the second test day after 10 weeks of supplementation
Glucose absorption
Recovery of 3-O-Methyl-D-glucose in the urine is measured on the first test day for the healthy control group and the cancer group. Secondly, the cancer patients in all 3 intervention arms are also measured after 10 weeks of intervention to examine the effects of fish oil and protein supplementation during chemotherapy on this outcome measure.
Time frame: 7 hours during the test day and the change after 10 weeks of supplementation
Gut permeability
Recovery of rhamnose/lactulose in urine is measured on the first test day for the healthy control group and the cancer group. Secondly, the cancer patients in all 3 intervention arms are also measured after 10 weeks of intervention to examine the effects of fish oil and protein supplementation during chemotherapy on this outcome measure.
Time frame: 7 hours during the test day and the change after 10 weeks of supplementation
Skeletal and respiratory muscle strength
Difference in leg strength and fatigue, handgrip strength and fatigue, and inspiratory and expiratory pressure between heart failure patients and healthy controls on test day 1. The cancer patients in all 3 intervention arms are also measured after 10 weeks of intervention to examine the effects of fish oil and protein supplementation during chemotherapy on this outcome measure.
Time frame: In the postabsorptive state on the first test day and the change on the second test day after 10 weeks of supplementation
Cognitive function
Outcome of neuro-psychological tests in heart failure patients and healthy controls in relation to the tryptophan metabolism. The cancer patients in all 3 intervention arms are also measured after 10 weeks of intervention to examine the effects of fish oil and protein supplementation during chemotherapy on this outcome measure.
Time frame: On the first test day and the change on the second test day after 10 weeks of supplementation
Fatty acid digestion after feeding
Enrichment in palmitic acid and tripalmitin fatty acids in plasma in response to a meal is measured on the first test day in for the healthy control group and the cancer group. Secondly, the cancer patients in all 3 intervention arms are also measured after 10 weeks of intervention to examine the effects of fish oil and protein supplementation during chemotherapy on this outcome measure.
Time frame: Acutely after 4 hours of feeding and the change after 10 weeks of supplementation
Protein digestion after feeding
Ratio enrichment free phenylalanine vs phenylalanine from protein spirulina in response to a meal is measured on the first test day for the healthy control group and the cancer group. Secondly, the cancer patients in all 3 intervention arms are also measured after 10 weeks of intervention to examine the effects of fish oil and protein supplementation during chemotherapy on this outcome measure.
Time frame: Acutely after 4 hours of feeding and the change after 10 weeks of supplementation
Whole body collagen breakdown rate
Hydroxyproline enrichment in plasma is measured on the first test day for the healthy control group and the cancer group. Secondly, the cancer patients in all 3 intervention arms are also measured after 10 weeks of intervention to examine the effects of fish oil and protein supplementation during chemotherapy on this outcome measure.
Time frame: In the postabsorptive state on the first test day and the change on the second test day after 10 weeks of supplementation
Tryptophan turnover rate
Tryptophan enrichment in plasma is measured on the first test day for the healthy control group and the cancer group. Secondly, the cancer patients in all 3 intervention arms are also measured after 10 weeks of intervention to examine the effects of fish oil and protein supplementation during chemotherapy on this outcome measure.
Time frame: In the postabsorptive state on the first test day and the change on the second test day after 10 weeks of supplementation
Insulin response to feeding
The acute change in insulin levels before and after intake of meal is determined on the first test day for the healthy control group and the cancer group. Secondly, the cancer patients in all 3 intervention arms are also measured after 10 weeks of intervention to examine the effects of fish oil and protein supplementation during chemotherapy on this outcome measure.
Time frame: Before and acutely after 4 hours of feeding and the change after 10 weeks of supplementation
Fat-free mass
Fat free mass is measured on the first test day for the healthy control group and the cancer group. Secondly, the cancer patients in all 3 intervention arms are also measured after 10 weeks of intervention to examine the effects of fish oil and protein supplementation during chemotherapy on this outcome measure.
Time frame: In postabsorptive state on test day 1 and the difference on test day 2, after 10 weeks of supplementation
Myofibrillar protein breakdown rate
The acute change 3-methylhistidine enrichment in plasma before and after intake of meal is determined on the first test day for the healthy control group and the cancer group. Secondly, the cancer patients in all 3 intervention arms are also measured after 10 weeks of intervention to examine the effects of fish oil and protein supplementation during chemotherapy on this outcome measure.
Time frame: Before and acutely after 4 hours of feeding and the change after 10 weeks of supplementation
Glycine rate of appearance
Glycine enrichment in plasma is measured on the first test day for the healthy control group and the cancer group. Secondly, the cancer patients in all 3 intervention arms are also measured after 10 weeks of intervention to examine the effects of fish oil and protein supplementation during chemotherapy on this outcome measure.
Time frame: In the postabsorptive state on the first test day and the change on the second test day after 10 weeks of supplementation
Taurine turnover rate
Enrichment of taurine in plasma is measured on the first test day for the healthy control group and the cancer group. Secondly, the cancer patients in all 3 intervention arms are also measured after 10 weeks of intervention to examine the effects of fish oil and protein supplementation during chemotherapy on this outcome measure.
Time frame: In the postabsorptive state on the first test day and the change on the second test day after 10 weeks of supplementation
Functional Status
Functional status will be assessed by the Karnofsky Performance Score, a widely used method to assess the functional status of a cancer patient. It describes a patient's functional status as a comprehensive 11-point scale ranging from 0% to 100%.
Time frame: On the first test day and the change on the second test day after 10 weeks of supplementation
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