Planetary Habitat Simulation: Nutrition Studies
Condition: Hypoxia
MeSH terms: Hypoxia
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Hypoxic ambulatory; Hypoxic Bedrest; Normoxic Bedrest
Intervention type(s): Other; Other; Other
Intervention description(s): 21 days confinement in normobaric hypoxic (FiO2 = 14%) environment; 21 days supine bedrest in normobaric hypoxic (FiO2 = 14%) environment; 21 days supine bedrest in normobaric normoxic (FiO2 = 21%) environment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Bedrest; Appetite