High Altitude and Exogenous Carbohydrate Oxidation



Status:Recruiting
Healthy:No
Age Range:18 - 39
Updated:2/24/2019
Start Date:November 28, 2018
End Date:November 1, 2020
Contact:Lee M Margolis, PhD
Email:lee.m.margolis.ctr@mail.mil
Phone:508-233-4591

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The Mechanistic Effects of Acute Hypobaric Hypoxia on Exogenous Carbohydrate Utilization During Steady-state Aerobic Exercise

Recent studies have reported that oxidation of exogenous carbohydrate is reduced under acute
hypobaric hypoxic (high altitude; HA) conditions compared to normoxia (sea level; SL) in
native lowlanders. However, the mechanisms by which HA suppresses exogenous carbohydrate
oxidation are not known. This study will seek to confirm that acute HA exposure decreases
exogenous carbohydrate oxidation during steady-state aerobic exercise compared to SL, and
explore if the mechanism inhibiting plasma glucose uptake is insulin dependent or
independent.

This randomized crossover study will examine substrate metabolic responses to ingesting
supplemental carbohydrate during steady-state aerobic-type exercise at sea level (SL) and
following acute (~5 h) exposure to HA (4,300 m) conditions in 10 healthy, recreationally
active adults between the ages of 18-39 yrs. Following a 48-hr muscle glycogen normalization
period, volunteers will complete 80-min of metabolically-matched, steady-state aerobic
exercise on a treadmill, and consume 145 g of glucose (1.8 g·min-1) at SL and HA. Treadmill
exercise will be performed at the same absolute workload, with speed and grade being the same
at SL and HA to induce the same absolute workload between phases. SL and HA trials will occur
in the US Army Research Institute of Environmental Medicine (USARIEM) hypobaric chamber and
will be separated by a minimum 7-d washout period between each protocol day. 6-6-[2H2]
glucose will be used as a tracer to assess glucose turnover. Indirect calorimetry, breath
sampling for 13C/12C expired in CO2, and urine collections will be used to determine
carbohydrate, fat, and protein oxidation during exercise at SL and HA. Serial blood draws
will be collected during each trial to assess endocrine and circulating substrate responses
to exercise, carbohydrate, and hypoxia. Muscle biopsies will be collected before and after
steady-state exercise to examine intramuscular glucose transport expression and
translocation, glycogen status, and activity enzyme intermediates in aerobic and anaerobic
energy metabolism.

Inclusion Criteria:

- Men aged 18 - 39 years

- Born at altitudes less than 2,100 m (~7,000 feet; Examples include Santa Fe, New
Mexico; Laramie, Wyoming; Etc.)

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

- Have supervisor approval (permanent party military and civilians)

- Willing to refrain from alcohol, smokeless nicotine products and dietary supplement
use during study periods

- 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; Examples include Santa Fe, New
Mexico; Laramie, Wyoming; Etc.)

- 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 months (Examples
include Ft. Huachuca, Arizona; Lima, Peru; Feldberg, Germany, Etc.)

- Musculoskeletal injuries that compromise exercise capability

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

- Medication that affects macronutrient metabolism (i.e., diabetes medications, statins,
corticosteroids, etc) and/or the ability to participate in strenuous exercise

- Evidence of apnea or other sleeping disorders

- Prior diagnosis of high altitude pulmonary edema (HAPE) or high altitude cerebral
edema (HACE)

- Presence of asthma or respiratory tract infections (< 1 month prior)

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

- Smoking or vaping

- 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 the Office of Medical
Support and Oversight

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

- Anemia (hematocrit <38% and hemoglobin <12.5 g/dL) and Sickle Cell Anemia/Trait

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

- Blood donation within 8 weeks of beginning the study
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Phone: 508-233-4591
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