Planetary Habitat Simulation: Nutrition Studies
Planetary Habitat Simulation: Nutrition Studies
A loss of body weight has been documented in lowland-living individuals when exposed to
 hypoxic environments, such as at high altitude, or under laboratory conditions. A reduction
 in appetite and energy intake has also been reported during conditions of microgravity, such
 as during space flight. Fourteen normal or over-weight men, who are otherwise healthy, will
 undergo 3x 21-day interventions; normobaric normoxic bed rest (NBR; FiO2=21%), normobaric
 hypoxic ambulatory confinement (HAMB; FiO2=14%; ~4000 m simulated altitude), and normobaric
 hypoxic bed rest (HBR; FiO2=14%). The effects of hypoxia and bedrest on appetite and its
 hormonal control will be assessed before and at day 17 of each intervention using a mixed
 meal tolerance test.
A loss of body weight has been documented in lowland-living individuals when exposed to
 hypoxic environments, such as at high altitudes, or under laboratory conditions. This weight
 loss has been attributed both to a reduced appetite (and subsequent fall in dietary energy
 intake), and to an increase in resting energy expenditure. Interestingly, a reduction in
 appetite and energy intake has also been reported during space flight, although the mechanism
 for this has not been explained. As the gas inside future planetary habitats is likely to
 have lower partial pressure of oxygen than in Earth's atmospheric air, hypoxia induced
 appetite reduction could pose a challenge for individuals in these environments. For example,
 persistent under-eating could compromise long term health due to inadequate intake of
 essential micronutrients, especially in the presence of altered nutrient metabolism and
 requirements seen during space flight. Moreover, inadequate macronutrient intake could
 exacerbate the loss of lean body tissue which occurs in situations (such as microgravity,
 inactivity and bed rest) where muscles are unloaded. Indeed, a protein intake greater than
 normal could be required in situations where there is muscle inactivity, to achieve the same
 postprandial anabolic effect of amino acids seen in ambulatory individuals.

 The mechanism for the reduction in appetite observed in hypoxia is not well established.
 Several incretin hormones and adipokines have been implicated in the control of appetite and
 may be candidates for inducing this alteration in appetite observed in hypoxia. However,
 reports in the literature present contradictory findings, perhaps due to the use of different
 experimental paradigms (hypobaric and normobaric hypoxia, active and resting subjects,
 variability in the degree and duration of hypoxia).

 The protocol of the current study standardises physical activity, ambient temperature,
 hypoxic stimulus and nutritional composition of the diet, and aims to extend our knowledge of
 the effects of hypoxia and bedrest on appetite and its hormonal control.

 In order to discern the separate and combined effects of microgravity and hypoxia, fourteen
 normal or over-weight men, who are otherwise healthy, will be recruited following medical and
 psychological screening. They will be invited to attend the Olympic Sport Centre, Planica,
 Slovenia on 3 occasions, with each visit being 31 days in duration and separated by 5 months.
 Each 31-day visit ('campaign') includes a baseline recording period (5 days), 21 days of
 intervention and a recovery period (5 days), with the 3 interventions allocated in a
 randomized, cross over design: i) Normobaric normoxic bed rest (NBR; FiO2=21%), ii)
 Normobaric hypoxic ambulatory confinement (HAMB; FiO2=14%; ~4000 m simulated altitude), and
 iii) Normobaric hypoxic bed rest (HBR; FiO2=14%). A standardized, repeating, 14-day dietary
 menu, comprised of foods commonly consumed in the Slovenian diet, will be applied during all
 campaigns, the targeted energy intakes being calculated individually using a modified
 Benedict-Harris formula with physical activity factor multipliers of 1.2 for the HBR and NBR
 campaigns and 1.4 for the HAMB campaign. Food will be provided in weighed portions and
 subjects will be encouraged to eat all food supplied. However, any food not eaten will be
 weighed and actual amount consumed recorded in a diet analysis programme. Body mass will be
 assessed daily during the campaigns using a gurney incorporating load cells, and whole body
 composition will be determined before and immediately after each intervention using fan beam
 dual-emission X-ray absorptiometry.

 Participants will undergo a mixed meal tolerance test before and on day 17 of each
 intervention period, in the morning, after a 12 hour fast, with the time of assessment
 replicated on each study day at every campaign. On arrival, participants will rest supine on
 a hospital bed and place their hand in a heated hand warming unit (air temperature 50-55oC).
 An intravenous cannula will then be inserted retrograde into a dorsal hand vein for
 arterialised-venous blood sampling. After 15mins rest, a baseline, fasting blood sample will
 be taken for determination of serum insulin, total cholesterol, high density lipoprotein
 (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, adiponectin and leptin, whole
 blood glucose and lactate, and plasma catecholamines, ghrelin, PeptideYY (PYY), glucagon-like
 peptide-1(GLP-1), triglycerides, and non-esterified fatty acid concentration. An expired
 breath sample will be collected into evacuated tubes for 13 labelled carbon dioxide (13CO2)
 determination, and a 20min baseline measurement of resting energy expenditure (REE) and
 respiratory exchange ratio (RER) will be then made using indirect calorimetry, with subjects
 wearing a mask, and both inspired and expired air being measured on every breath. Appetite
 assessment will be made by asking subjects to rate their hunger, desire to eat, fullness, and
 their prospective food intake, by placing a vertical mark on a 0-100mm linear scale. This
 visual analogue scale will be measured from left to right, with 0 indicating no experience of
 the variable (e.g. not hungry, unable to eat anything) and 100 indicating the most of each
 variable that they can imagine experiencing (e.g. intense desire to eat, or completely full).
 Values for these 4 variables will be combined to calculate a combined appetite score (CAS).
 Once baseline measurements have been completed, subjects will consume a mixed nutrient
 milkshake (Ensure Plus, Abbott Nutrition) at 5ml/kg body weight, which will be supplemented
 (at 1% of carbohydrate content) with 13-Carbon labelled (13C) Glucose. Arterialised venous
 blood samples will subsequently be taken every 10min for glucose and lactate assessment, and
 every 20min for assessment of serum insulin and incretin hormones. A measurement of REE and
 RER will be performed in the last 15min of every 30min period for the following 2 hours to
 assess fuel oxidation and metabolic rate, and an expired breath sample will be collected into
 evacuated tubes for 13CO2 determination at a later date. Subjective appetite will be assessed
 every 15minutes throughout using visual analogue scales, as described above, and at the end
 of the 2hr postprandial period subjects will be given an ad libitum pasta-based test meal and
 will be instructed to eat until they feel comfortably full. This meal will be comprised of
 cooked dried white pasta, commercially available tomato-based pasta sauce, olive oil and
 grated hard cheese, with a composition of 37% of total energy derived from fat, 48%
 carbohydrate, and 16% protein. The amount eaten will be recorded and related to subjective
 appetite ratings.
Inclusion Criteria:

 -  Physically and mentally healthy subjects

 -  Body mass index < 25 kg/m2

 -  Height 158 - 190 cm

 -  Waist circumference < 94 cm

 -  Volunteers that are able to declare their willingness to participate in the entire
 study

 -  Willing to be assigned randomly to the three groups

 -  Successfully passing the psychological and medical screening

 -  competent to sign informed consent

 -  Slovenian social insurance

 -  English language fluency

 Exclusion Criteria:

 -  Medication required that may interfere with the interpretation of the results

 -  Bone mineral density (as measured by DEXA) more than 1.5 standard deviations < t score

 -  Recent sub-standard nutritional status

 -  Family history of thrombosis or positive response in thrombosis screening procedure.

 (Biochemical analysis of the following parameters: ATIII, High sensitive C-reactive
 protein, S-Akt., Factor V-Leiden, Prothrombin, Lupus-partial thromboplastin time, Factor
 II)

 -  History of: thyroid dysfunction, renal stones, diabetes, allergies, hypertension,
 hypocalcemia, uric acidaemia, lipidaemia, or hyperhomocysteinaemia

 -  Gastro-esophageal reflux disease or renal function disorder, Hiatus hernia

 -  History of medical illness

 -  Smoker within six months prior to the start of the study

 -  Abuse of drugs, medicine or alcohol

 -  Participation in another study up to two months before study onset

 -  No signed consent form before the onset of the experiment

 -  Blood donors in the past three months before the onset of the experiment

 -  Vegetarian and Vegans

 -  Migraines

 -  History of orthostatic intolerance

 -  History of vestibular disorders

 -  Claustrophobia

 -  metallic implants, osteosynthesis material

 -  Chronic back pain