NATICK, Mass. -- It's old news that warfighters conducting combat operations in mountainous regions like Afghanistan can experience significant loss of weight and muscle mass.

Yet the loss may not be due entirely to a lack of food or high physical activity levels. Hypoxia, a condition that leads to acute mountain sickness, or AMS, can play a major role in muscle loss during high-altitude missions.

For the past 10 years, researchers from the Army Research Institute of Environmental Medicine have conducted a series of underfeeding studies in order to evaluate nutrition requirements for working in extreme environments. Last summer, USARIEM's Military Nutrition Division began exploring the problem of high altitude -- an altitude higher than 11,500 feet.

MND researchers conducted a six-week underfeeding study with 17 test volunteers at the Institute's Maher Memorial Altitude Laboratory, which is located 14,115 feet above sea level on the Pikes Peak summit in Colorado.

According to Dr. Stefan Pasiakos, the study's principal investigator, the purpose was to conduct research that could guide the optimization of the modular operational ration enhancement, or MORE, a food ration developed by the Natick Soldier Research, Development and Engineering Center's Combat Feeding Directorate for high-altitude missions.

"The most consistent issue we see during operations is that warfighters are not eating enough, which causes a negative calorie balance and, ultimately, a loss of muscle mass," Pasiakos said. "USARIEM researchers want to ensure that warfighters are consuming the right blend of macronutrients, particularly carbohydrates and protein, during periods of negative calorie balance to protect against muscle wasting, physical performance declines and cognitive deterioration."

Researchers executed a highly controlled diet and exercise intervention at the Pikes Peak lab. They assessed body composition, muscle protein and carbohydrate metabolism measurements, appetite, gut microbiome, exercise and cognitive performance at sea level, during and after 21 days of high-altitude exposure.

According to Pasiakos, the study was not the first time researchers have explored the effects of hypoxia and underfeeding, but it was the first comprehensive and systematic approach to identifying how hypoxia elicits muscle wasting and how a warfighter's diet during high-altitude missions can either contribute to muscle loss or protect muscle and performance.

What may explain the loss of body weight and muscle during high-altitude missions? According to Pasiakos, hypoxia diminishes the body's ability to deliver oxygen, causing the metabolism to ramp up because the body still requires the same amount of oxygen to function.

"Warfighters need to eat more to maintain body weight. But appetite is also suppressed," Pasiakos said. "While these symptoms improve as warfighters acclimatize to high altitude, the higher amount of calories needed versus the lower amount of calories consumed [will] cause warfighters to lose weight. Warfighters' abilities to maintain muscle mass, prevent injury and sustain physical and cognitive performance are at greater risk of being compromised."

During the study, volunteers ate either a standard-protein diet or a higher-protein diet that was consistent with recommendations for periods of high physical activity. Researchers wanted to see how well the volunteers maintained their muscle mass when losing weight.

Researchers also fed volunteers either a multi-carbohydrate blended drink or a placebo to test how efficiently they burned carbohydrates during endurance exercise and how fast they were able to complete a two-mile run.

Pasiakos said that, while the volunteers underwent the stress of being underfed and performed high levels of physical activity, they were closely monitored by a "research staff with over 100 years of combined physiology research at high altitude."

"The practical experience and can-do attitude of our staff enabled the team to tightly control physical activity and diet and execute complex experiments throughout this six-week study," Pasiakos said.

The underfeeding endured by the volunteers should ensure that warfighters on future high-altitude missions will be better fed.

"The knowledge [gained] from this study will improve Soldier readiness by advancing our understanding of the nutritional requirements ... in extreme high-altitude environments," Pasiakos said. "Recommending dietary changes to the ration composition is one method to help prevent muscle loss and maintain physical and mental performance during high-altitude stress."

Researchers are currently "digesting the results" Pasiakos said. Eventually, the study outcomes will be shared with the ration developer to optimize the dietary composition of future combat rations.

"Nutrition recommendations for athletic performance are available, but they do not necessarily apply, [nor are they] practical for warfighters operating in environmental extremes, due to limited access to foods or mission constraints on eating," Pasiakos said.

"It is our job to define nutrition requirements and identify solutions specific to our warfighters under the multiple circumstances they operate in."