Anabolic Response Cancer

Weight loss and muscle wasting commonly occurs in patients with cancer, negatively influencing their quality of life, treatment response and survival. Weight changes in patients with cancer may be the consequence of energy imbalance and disturbances in protein metabolism, 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. However, in advanced cancer mostly loss of both fat mass and lean mass has been found.

Unfortunately, gains in muscle mass are difficult to achieve. In a previous study of the Investigators, a bolus (15 g) of an essential amino acid mixture as present in milk protein was able to stimulate whole-body protein anabolism equally and effectively in weight-losing patients with lung cancer. This indicates the high potential of proteins with high essential amino acids as therapeutic agents to increase muscle mass in these patients. However, the dose-response effect to reach optimal whole-body protein anabolism is yet unknown and can differ among patients. Therefore, the Investigators would like to study the effects of several dosages of a protein with high essential amino acid levels, administered by sip feeding, on whole-body protein anabolism in patients with cancer in comparison with healthy older adults. Furthermore, the individual protein requirements of cancer patients may be established as this is the cornerstone of nutritional support. Specifically to establish 'the anabolic threshold', when protein breakdown equals synthesis and the response and the relation between protein intake and net protein synthesis are critical.

In this study, the Investigators will test the following hypothesis: A protein meal with high EAA levels will stimulate protein anabolism in a dose-dependent way but the exact relationship differs among cancer patients. The primary endpoint will be the extent of stimulation of net whole-body protein synthesis at each level of protein intake in the individual cancer and control subject. This project will provide important clinical information on the anabolic capacity of dietary protein with high EAA levels and the level of protein intake required to become anabolic in cancer patients on an individual bases. In this way, this study will provide preliminary data for the development of individualized nutritional strategies that will stop the process of ongoing muscle loss in cancer patients.

General aims:

* To study the whole-body protein anabolic effect of several dosages of a high-quality protein sip feeding in cancer subjects as compared to healthy controls.
* To investigate the anabolic threshold in subjects with cancer as compared to healthy controls.

The mechanisms underlying lean tissue loss in cancer remain to be unraveled, which may be because of the complexity of the metabolic alterations that are present when symptoms such as weight loss become obvious. Multiple factors like anorexia and inflammation are present in cancer, all contributing to the loss of lean tissue in these patients by creating a drain on the body protein stores. Previous studies showed that oral supplementation of large amounts of calories in cancer is only partially successful and this indicates that the composition of dietary supplements and meals is important to successfully counteract muscle wasting. Although our previous study supports the concept of supplementing high-quality milk proteins in lung cancer subjects, the dose-response anabolic effects of proteins with high EAA levels are still unclear. Furthermore, there is no insight in the actual protein requirements in cancer. The knowledge gained from this study will benefit our insight in terms of promotion of protein gain after feeding in cancer patients.

Eligibility Criteria:
Inclusion criteria cancer subjects:

* Age 18 years or older
* Ability to lie in supine or elevated position for 8 hours
* Diagnosed with stage III/IV cancer (all solid tumors excluding breast or prostate)
* No chemotherapy/radiotherapy within past month prior to the study day
* Willingness and ability to comply with the protocol

Inclusion criteria healthy subjects:

* Healthy male or female according to the investigator's or appointed staff's judgment
* Age 18 years or older
* Ability to lay in supine or elevated position for 8 hours
* No diagnosis of cancer
* No diagnosis of diabetes
* Willingness and ability to comply with the protocol

Exclusion Criteria all subjects:

* Any condition that may interfere with the definition 'healthy subject' according to the investigator's judgment (for healthy control group only)
* Presence of fever within the last 3 days
* Untreated metabolic diseases including hepatic or renal disorder
* Presence of acute illness or metabolically unstable chronic illness
* BMI of \< 18.5 or ≥ 35 kg/m2 (for healthy control group only)
* Dietary or lifestyle characteristics: Current alcohol or drug abuse, Use of protein or amino acid containing nutritional supplements within 5 days prior to the study day
* Known allergy to milk or milk products
* Failure to give informed consent or Investigator's uncertainty about the willingness or ability of the subject to comply with the protocol requirements
* (Possible) pregnancy
* Any other condition according to the PI or nurse that was found during the screening visit, that would interfere with the study or safety of the patient