Substrate Utilization, Exercise Performance, and Skeletal Muscle Response to Energy Deficit and Altitude Acclimatization



Status:Enrolling by invitation
Healthy:No
Age Range:18 - 42
Updated:4/21/2016
Start Date:March 2016
End Date:September 2017

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This research will evaluate nutrition requirements for missions at high altitude (i.e. >7800
feet above sea level) and the information obtained can be used to optimize nutrient content
specifications for combat rations.

The objectives are:

1. Determine whether loss of lean body mass resulting from negative calorie balance over a
22-d period at high altitude can be prevented by increasing dietary protein intake.

2. Determine the efficacy of carbohydrate (glucose and fructose) supplementation on
aerobic exercise performance at sea level, acute exposure to high altitude, and in
response to 22-d period of negative calorie balance at high altitude.

3. Determine cognitive function, sleep patterns, and behavioral responses to high altitude
and underfeeding.

4. Determine appetite and eating behavior in response to high altitude and sustained
underfeeding.

5. Examine the effects of high altitude, negative calorie balance, dietary intake
manipulations on gut health.

Twenty-four, normal to overweight (body mass index of 18.5-29.9 kg/m2), physically active
adult civilians or active duty military personnel will be recruited for the 44-d protocol,
22-d at sea level and 22-d at high altitude (HA). During the 22-d sea level phase,
volunteers will receive dietary counseling to maintain baseline weight and consume protein
at levels consistent with recommendations for periods of low physical activity (1.0 g/kg/d).
During the 22-d at HA, all meals and beverages (water ad libitum) will be prepared and
provided to volunteers by research staff. Physical activity will be increased at HA and
calorie intake will be reduced 40% to create a state of negative calorie balance.

Changes in total body, lean body, and fat mass will be assessed at sea level and after a
22-d energy deficit at HA. Regulation of muscle mass will be assessed using stable isotope
methodology, muscle biopsies, and various molecular techniques, to directly measure muscle
protein synthesis, whole body protein balance, and the cellular mechanisms that regulate
these processes. Furthermore, exercise testing, substrate oxidation rates, and expired
carbon dioxide labeled with the stable isotope of carbon dioxide (one extra neutron) will be
used to assess total, exogenous, and endogenous carbohydrate oxidation and performance
capacity.

A comprehensive cognitive/behavioral test battery will be performed at sea level and HA.
Sleep will be assessed by actigraphy. Eating behavior and appetite will be assessed at sea
level, acute HA, and after the 22-d energy deficit at HA using validated measures. Gut
health will be assessed using sugar absorption tests and the bacterial composition of the
gut will be characterized using advanced molecular techniques.

Inclusion Criteria:

- Born at altitudes less than 2,100 m (~7,000 feet)

- Physically active based on assessment of physical activity history (2-4 days per week
aerobic and/or resistance exercise)

- Body weight ≥ 110 lbs.

- Body mass index (BMI) between 18.5-29.9 kg/m2

- Females must be on contraception (e.g., oral birth control, NuvaRing®, Depo Provera®,
etc.)

- Have supervisor approval (permanent party military)

- Not taking any medications and/or willing to refrain from all medication use 4 wk
prior to and throughout the entire study period, unless provided/approved by the US
Army Research Institute of Environmental Medicine (USARIEM) Office of Medical Support
and Oversight (OMSO) or medical oversight at Pikes Peak, Colorado organized through
OMSO.

- Willing to refrain from alcohol, smoking any nicotine product (includes
e-cigarettes), electronic cigarettes, chewing tobacco, caffeine, and dietary
supplement use throughout the entire study period

- Willing to travel to USARIEM's Altitude Laboratory at Pikes Peak and live there for
22 consecutive days

- Refrain from taking any nonsteroidal anti-inflammatory drugs (NSAIDs; e.g. aspirin,
Advil®, Aleve®, Naprosyn®, or any aspirin-containing product) for 10 days before and
at least 5 days AFTER each muscle biopsy. (*Tylenol® or acetaminophen is ok to use if
needed for discomfort)

Exclusion Criteria:

- Born at altitudes greater than 2,100 m (~7,000 feet)

- Living in areas that are more than 1,200 m (~4,000 feet), or have traveled to areas
that are more than 1,200 m for five days or more within the last 2 mo

- Musculoskeletal injuries that compromise exercise capability

- Metabolic or cardiovascular abnormalities, gastrointestinal disorders (e.g., kidney
disease, diabetes, cardiovascular disease, etc.)

- Disease or medication that affects macronutrient metabolism and/or the ability to
participate in strenuous exercise

- Evidence of apnea or other sleeping disorders

- Evidence of prior high altitude pulmonary edema or high altitude cerebral edema
diagnosis

- Allergies or intolerance to foods (including but not limited to lactose
intolerance/milk allergy), vegetarian practices, or medications (including, but not
limited to, lidocaine or phenylalanine) to be utilized in the study

- History of complications with lidocaine

- Taking medications that interfere with oxygen delivery and transport (Includes
sedatives, sleeping aids, tranquilizers and/or any medication that depresses
ventilation, diuretics, alpha and beta blockers)

- Evidence of any physical, mental, and/or medical conditions that would make the
proposed studies relatively more hazardous as determined by OMSO

- Present condition of alcoholism, anabolic steroids, or other substance abuse issues

- Anemia (hematocrit <38% for males, <36% for females, and hemoglobin >12.5 g/dL for
all subjects) or Sickle Cell Anemia/Trait

- Abnormal prothrombin time/partial thromboplastin time (PT/PTT) test or problems with
blood clotting

- Blood donation within 8 weeks of beginning the study

- Pregnancy and women not on contraceptives

- Any use of antibiotics, except topical antibiotics, within 3 months of study
participation.

- Colonoscopy within 3 months of study participation

- Use of laxatives, stool softeners, or anti-diarrheal medications at least once a
week.
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