Medium-term Bedrest Whey Protein (MEP)

Study Overview
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Brief Summary
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The human being has shown that he can live and work in the space environment, but due to the lack of essential mechanical load on muscle and bone, the fluid-shift as well as alterations in the acid-base balance (mainly on account of nutritional factors), the exposure to microgravity results in a gradual degradation of muscle, bone and cartilage, deconditioning of the cardiovascular system and metabolic changes. Countermeasures to prevent all the deconditioning of the physiological systems are not yet fully effective and require further investigation. A commonly utilized model of simulating the physiological effects of microgravity on the human organism on ground is the 6° head-down-tilt bed rest. In the present study the model has been used to study potential countermeasures to spaceflight-associated deconditioning. One of the most constrictive changes appearing during space flight as well as during bed rest, are disuse-induced muscle losses. These are associated with a decrease in muscle protein synthesis, rather then an increase in muscle protein breakdown. Besides an effective training countermeasure, nutritional countermeasures gain respect in this context: supplementing conventional diets with whey protein or essential amino acids has been shown to increase muscle protein synthesis. Due to these anabolic properties whey protein seems promising to counteract disuse-induced muscle wasting. Drawbacks of a high protein intake are calciuric effects, ascribed to the proton-release when metabolizing sulfur-containing amino acids. The so called 'low grade metabolic acidosis' has also shown to activate osteoclastic bone resorption and muscle protein degradation. Therefore, to maximize the anabolic potential of a whey protein supplementation, the acidogenic properties need to be compensated. As previous works suggest, a shift of acid base balance into the acid direction and the resulting changes in bone and protein turnover may be hindered by supplementing alkaline mineral salts. In this regard, a mid-term bed rest study was performed in order to investigate the effect of a combined whey protein (0.6 g/kg body weight/day) and potassium bicarbonate (90 mmol/day) supplementation as a potential countermeasure to multiple physiological and metabolic alterations on the human body resulting from real and simulated microgravity.

Conditions
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Countermeasure Evaluation

Intervention / Treatment
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* Dietary Supplement: Whey Protein + Potassium bicarbonate
* Other: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males, 20 -45 years BMI: 20 - 25 kg/m2 Height: 158 - 190 cm Weight: 65 - 85 kg maximum relative oxygen uptake: 30 - 60 ml/min/kg non-smokers successful medical and psychological screening Willingness to participate in the entire study signed informed consent social insurance Clear criminal background check Exclusion Criteria: Abuse of drugs, medicine or alcohol Vegetarians, Vegans Migraines History of mental illness Claustrophobia History of: thyroid dysfunction, renal stones, diabetes, allergies, hypertension, hypocalcaemia, uric acidaemia, lipidaemia, hyperhomocysteinaemia Rheumatism Muscle-, Cartilage- or Joint Injuries Gastro-esophageal reflux disease, renal function disorder, Hiatus hernia Chronic back pain Bone diseases Herniated discs Achilles tendon injuries Cruciate ligament rupture or any other severe knee injury BMD more than 1.5 SD < t-score History of orthostatic intolerance or vestibular disorders Anaemia Vitamin D Deficiency Positive response in thrombosis screening Use of metallic implants, osteosynthesis material Porphyria, Blood dyscrasia HIV, Hepatitis Increased Inner Eye pressure Intolerance to local anesthetics Participation in another study up to three month before study onset

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MEP-1<br> | Dietary Supplement: Whey Protein + Potassium bicarbonate<br>* 0.6 mmol WP/kg body weight + 90 mmol KHCO3 during bed rest<br>Other: Control<br>* Bed rest without dietary supplement<br>|
| Experimental: MEP-2<br> | Dietary Supplement: Whey Protein + Potassium bicarbonate<br>* 0.6 mmol WP/kg body weight + 90 mmol KHCO3 during bed rest<br>Other: Control<br>* Bed rest without dietary supplement<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in body composition |  | Baseline, after 21 days of bed rest | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Volume |  | Baseline, after 21 days of bed rest | 
| Maximum volume of oxygen uptake |  | Baseline, after 21 days of bed rest | 
| Isometric torque | During a an Isometric Maximum Voluntary Contraction Test on the knee extensors & flexors, the plantarflexors and dorsiflexors, the elbow extensors & flexors the Isometric Torque will be measured in Nm. | Baseline, after 21 days of bed rest | 
| Muscle fatigue |  | Baseline, after 21 days of bed rest | 
| Bone metabolism |  | Baseline, after 2,5,14,21 days of bed rest, 1, 5, 14, 28 days after finishing bed rest | 
| Bone mineral density + content |  | Baseline, after 21 days of bed rest | 
| Standing balance |  | Baseline, after 21 days of bed rest | 
| Locomotion | Locomotion will be assessed by Dynamic Gait Index, specific parameters are: total Score and Subscore | Baseline, after 21 days of bed rest | 
| Body mass |  | Daily for a duration of 35 days | 
| Intracranial pressure |  | Baseline, after 1,4, 7,10,13,14,15,16,17,18,19,20,21 days of bed rest,1,2,4 days after finishing bed rest | 
| Monitoring of Vitamin K status |  | Baseline, after 2,5,14,21 days of bed rest, 1, 5 days after finishing bed rest | 
| Fat metabolism |  | Baseline, after 21 days of bed rest | 
| Glucose metabolism |  | Baseline, after 21 days of bed rest, 4 days after finishing bed rest | 
| Nitrogen balance |  | Daily for a duration of 33 days | 
| Energy metabolism |  | Baseline, after 21 days of bed rest | 
| Glucocorticoid activity |  | Baseline, after 2,3,7,8,12,13,16,17 days of bed rest, 2,3 days after finishing bed rest | 
| Muscle metabolism |  | Baseline, after 21 days of bed rest | 
| Acid base balance |  | Baseline, after 2, 14, 21 days of bed rest, 5 days after finishing bed rest | 
| Sympathetic activity during orthostatic stress | Muscle sympathetic nerve activity is measured by MSNA recording by microneurography technique. | Baseline, after 21 days of bed rest | 
| Visual Orientation | Visual Orientation is assessed by 'Oriented Character Recognition Test' and Luminous Line Test. The main parameter is Score. | Baseline, after 6,12,20 days of bed rest, 2,4 days after finishing bed rest | 
| Plasma galanin and adrenomedullin responses during head up tilt test (orthostatic stress) |  | Baseline, after 21 days of bed rest | 
| Cartilage metabolism and -thickness |  | Baseline, after 2,3,5,7,14,21 days of bed rest, 5 days after finishing bed rest | 
| Hematopoetic system | Blood cell count, reticulocytes, Haptoglobin, Bilirubin, Ferritin, EPO, Thrombopoietin, Urinary Urobilinogen and Fecal Urobilinogen (markers of blood cell degradation) | Baseline, after 10, 21 days of bed rest, 1, 28 days after finishing bed rest | 
| Fat accumulation in bone marrow |  | Baseline, after 10, 21 days of bed rest, 3, 28 days after finishing bed rest | 
| Achilles tendon structure |  | Baseline, after 21 days of bed rest, 2, 28 days after finishing bed rest | 
| Headache - frequency and quality |  | Baseline, daily during 21 days of bed rest | 
| Muscle volume |  | Baseline, after 20, 21 days of bed rest, 3 days after finishing bed rest | 
| Free water and fat content in muscle |  | Baseline, after 20, 21 days of bed rest, 3 days after finishing bed rest | 
| Orthostatic tolerance | Orthostatic tolerance will be assessed by Head up tilt test. The following parameters are assessed to measure orthostatic tolerance: beat-to-beat heart rate [bpm], beat-to-beat blood pressure [bpm] time to presyncope [min, s] | Baseline, after 21 days of bed rest |