Nutritional and Functional Changes in Heart Failure

• Citrulline Rate of appearance [ Time Frame: Postabsorptive state during 2 hours ] [ Designated as safety issue: No ]
  plasma enrichment of citrulline
• Glucose absorption [ Time Frame: 7 hours ] [ Designated as safety issue: No ]
  Recovery of 3-O-Methyl-D-glucose in the urine.
• Gut permeability [ Time Frame: 7 hours ] [ Designated as safety issue: No ]
  recovery of rhamnose/lactulose in urine
• Skeletal and respiratory muscle strength [ Time Frame: 1 day ] [ Designated as safety issue: No ]
  Difference in leg strength and fatigue, handgrip strength and fatigue, and inspiratory and expiratory pressure between heart failure patients and healthy controls.
• Cognitive function [ Time Frame: 1 day ] [ Designated as safety issue: No ]
  Outcome of neuro-psychological tests in heart failure patients and healthy controls in relation to the tryptophan metabolism
• Fatty acid digestion after feeding [ Time Frame: 0,15,30,45,60,75,90,105,120,150,180,210 min post-meal ] [ Designated as safety issue: No ]
  Enrichment in palmitic acid and tripalmitin fatty acids in plasma
• Protein digestion after feeding [ Time Frame: 0,15,30,45,60,75,90,105,120,150,180,210, min post-meal ] [ Designated as safety issue: No ]
  Ratio enrichment free phenylalanine vs phenylalanine from protein spirulina
• Arginine turnover rate [ Time Frame: postabsorptive state during 3 hours ] [ Designated as safety issue: No ]
  Arginine enrichment in plasma
• Whole body collagen breakdown rate [ Time Frame: Postabsorptive state during 3 hours ] [ Designated as safety issue: No ]
  Hydroxyproline enrichment in plasma
• Tryptophan turnover rate [ Time Frame: Postabsorptive state during 3 hours ] [ Designated as safety issue: No ]
  Tryptophan enrichment in plasma
• Insulin response to feeding [ Time Frame: during 3 hours after feeding ] [ Designated as safety issue: No ]
  Acute change from postabsorptive state after intake of meal
• Fat-free mass [ Time Frame: postabsorptive state during 15 min ] [ Designated as safety issue: No ]
  Characteristics of study subjects
• Myofibrillar protein breakdown rate [ Time Frame: 0,15,30,45,60,75,90,105,120,150,180,210 min post-meal ] [ Designated as safety issue: No ]
  3methylhistidine enrichment in plasma
• Glycine rate of appearance [ Time Frame: Postabsorptive state during 3 hours ] [ Designated as safety issue: No ]
  glycine enrichment in plasma
• Taurine turnover rate [ Time Frame: postabsorptive state during 3 hours ] [ Designated as safety issue: No ]
  enrichment of taurine in

• Citrulline Rate of appearance [ Time Frame: Postabsorptive state during 2 hours ] [ Designated as safety issue: No ]
  plasma enrichment of citrulline
• Glucose absorption [ Time Frame: 7 hours ] [ Designated as safety issue: No ]
  Recovery of 3-O-Methyl-D-glucose in the urine.
• Gut permeability [ Time Frame: 7 hours ] [ Designated as safety issue: No ]
  recovery of rhamnose/lactulose in urine
• Skeletal and respiratory muscle strength [ Time Frame: 1 day ] [ Designated as safety issue: No ]
  Difference in leg strength and fatigue, handgrip strength and fatigue, and inspiratory and expiratory pressure between heart failure patients and healthy controls.
• Cognitive function [ Time Frame: 1 day ] [ Designated as safety issue: No ]
  Outcome of neuro-psychological tests in heart failure patients and healthy controls in relation to the tryptophan metabolism
• Fatty acid digestion after feeding [ Time Frame: 0,15,30,45,60,75,90,105,120,150,180,210,240 post-meal ] [ Designated as safety issue: No ]
  Enrichment in palmitic acid and tripalmitin fatty acids in plasma
• Protein digestion after feeding [ Time Frame: 0,15,30,45,60,75,90,105,120,150,180,210,240 post-meal ] [ Designated as safety issue: No ]
  Ratio enrichment free phenylalanine vs phenylalanine from protein spirulina
• Arginine turnover rate [ Time Frame: postabsorptive state during 2 hours ] [ Designated as safety issue: No ]
  Arginine enrichment in plasma
• Whole body collagen breakdown rate [ Time Frame: Postabsorptive state during 2 hours ] [ Designated as safety issue: No ]
  Hydroxyproline enrichment in plasma
• Tryptophan turnover rate [ Time Frame: Postabsorptive state during 2 hours ] [ Designated as safety issue: No ]
  Tryptophan enrichment in plasma
• Insulin response to feeding [ Time Frame: during 4 hours after feeding ] [ Designated as safety issue: No ]
  Acute change from postabsorptive state after intake of meal
• Fat-free mass [ Time Frame: postabsorptive state during 15 min ] [ Designated as safety issue: No ]
  Characteristics of study subjects
• Myofibrillar protein breakdown rate [ Time Frame: 0,15,30,45,60,75,90,105,120,150,180,210,240min post-meal ] [ Designated as safety issue: No ]
  3methylhistidine enrichment in plasma
• Glycine rate of appearance [ Time Frame: Postabsorptive state during 2 hours ] [ Designated as safety issue: No ]
  glycine enrichment in plasma

Weight loss commonly occurs in patients with chronic heart failure (CHF), negatively influencing their quality of life, treatment response and survival. Loss of muscle protein is generally a central component of weight loss in CHF patients but patients also have reductions in fat mass and bone density, independent of the severity of the disease state. The purpose of this cross-sectional study is to provide detailed insight in disease related gut function by obtaining information on gut permeability, digestion and absorption of glucose, fat and protein in CHF patients compared to matched healthy controls. This will provide required information that is necessary to implement new strategies to develop optimal nutritional regimen in CHF. The hypothesis is that CHF is related to decreased gut function and absorption, leading to decreased anabolic response. Second, this decreased nutritional status is linked to reduced muscle functioning and possibly decreased cognition. In addition, we will examine the effect of aging on by comparing gut function digestion and absorption of the CHF aged matched healthy controls to a group of young healthy subjects.

This study involves one test day of approximately 7-8 hours. On this test day subjects will ingest a sugar drink to assess gut permeability and gut function, and a protein meal to measure digestion/absorption and the anabolic response to food intake. Subjects will also receive a mixture of amino acids that are made a little heavier than normal, called stable isotopes. This stable isotopes is used to investigate protein behavior in the body (protein kinetics). Blood (100-120 ml in total) and urine samples will be collected over 7 hours.

Inclusion criteria CHF subjects:

• Ability to walk, sit down and stand up independently
• Age 45 years or older
• Ability to lie in supine or elevated position for 6 hours
• Diagnosis of CHF; under regular care by cardiologist
• NYHA class II-IV
• Reduced Ejection Fraction (<45%)
• Clinically stable condition; no hospitalization 4 weeks preceding the first study day
• Willingness and ability to comply with the protocol

Inclusion criteria healthy control subjects:

• Healthy male or female according to the investigator's or appointed staff's judgment
• Ability to walk, sit down and stand up independently
• Age 45 years or older
• Age between 20 and 30 years
• Ability to lay in supine or elevated position for 6 hours
• No diagnosis of CHF
• 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 (healthy subjects only)
• Established diagnosis of malignancy
• Established diagnosis of Insulin Dependent Diabetes Mellitus
• History of untreated metabolic diseases including hepatic or renal disorder
• Presence of acute illness or metabolically unstable chronic illness
• Presence of fever within the last 3 days
• Body mass index >40 kg/m2
• 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
• Use of protein or amino acid containing nutritional supplements within 5 days of first study day
• Use of long-term oral corticosteroids or short course of oral corticosteroids within 4 weeks preceding first study day
• 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