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Simulated-altitude exercise training may benefit obese breast cancer survivors
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Exercise training under simulated altitude conditions may benefit obese breast cancer survivors who have restricted walking capabilities.
Stephen J. Carter, PhD, cardiovascular physiologist and postdoctoral fellow in the department of nutrition sciences at University of Alabama at Birmingham, and colleagues will assess the feasibility and safety of this approach, also called intermittent normobaric hypoxia.
Additionally, researchers will assess preliminary effect sizes for several physiological factors, including oxygen uptake during treadmill walking, resting blood pressure and markers of insulin resistance.
Results from breast cancer survivors who undergo 8 weeks of exercise training in simulated-altitude conditions — oxygen levels of approximately 16% — or control conditions, with oxygen levels of approximately 21%, will be compared with outcomes from 30 women previously diagnosed with breast cancer.
Carter and colleagues hypothesize that hypoxic-exercise training will lead to more pronounced benefits in cardiometabolic health and the ability to perform activities of independent living.
“The direct and indirect effects of cancer treatment can create, in some, a reinforcing pattern of activity avoidance, which subsequently hastens deconditioning and increases the propensity for weight gain,” Carter said in a press release. “As the benefits of habitual exercise are largely known, we are interested in determining whether we can optimize the exercise stimulus for a given effort in order to elicit favorable cardiometabolic adaptations.”
HemOnc Today spoke with Carter about the trial and the insights he believes it could yield.
Question: What prompted this study?
Answer: When I started my work in cancer research, I was integrated into an NCI-funded, randomized controlled trial that tested a physical activity behavior change intervention for breast cancer survivors compared with usual care. Those in the intervention group had a portion of supervised exercise training, which progressed to home-based workouts. Those in the usual care group did not receive supervised exercise but had periodic follow-up via telephone. During the exercise sessions, I began noticing many of the women would complain of knee or lower-back pain. In some instances, the pain would interfere with their ability to meet the target heart rates. Lower-extremity discomfort coupled with poor systemic conditioning meant many of the women could not sustain the proper walking speed to elicit the desired target heart rate. I thought there had to be a way to circumvent the limitations associated with joint pain and walking speed. During exercise, the introduction of a lower fraction of inspired oxygen leads to a decrease in arterial oxygen saturation, which triggers a compensatory increase in cardiac output for a given walking speed. In this study, we are essentially harnessing a normal physiologic response that enables breast cancer survivors to acquire the more desirable health benefits, consistent with greater levels of physical exertion though walking at speeds within their preferred comfort zone. This has led to a rethinking of the traditional exercise paradigm among cancer survivors.
Q: How will the study be conducted?
A: Our target is to enroll 30 breast cancer survivors in a two-arm, randomized controlled design. We are recruiting women aged 18 to 70 years, with BMI between 30 kg/m2 and 45 kg/m2. Participants are randomly assigned to either the control arm or simulated-altitude arm. For the simulated-altitude exercise regimen, participants are outfitted with an exercise mask connected to a commercial-grade hypoxic generator. A lightweight, corrugated tube from the generator is connected to the exercise mask and secured over the participant’s mouth and nose with neoprene straps. The two groups follow the same exercise progression, matched for relative intensity using a percent of their heart rate reserve. Participants are required to attend two laboratory-based sessions — before exercise training, and again 8 weeks after — so we can assess various aspects of their health.
Q: What is your hypothesis?
A: From a clinical perspective, this approach to exercise training may upregulate nitric oxide bioavailability through changes in the nitrate-nitrite-NO pathway and hypoxia-inducible factors, which then would stimulate a range of favorable cardiovascular/metabolic adaptations, including significantly reduced blood pressure and markers of insulin resistance. However, we also think the simulated-altitude training will lead to more robust improvements in walking economy, which may increase the amount of free-living physical activity, as indexed by accelerometry.
Q: What is your research timeline, and when do you expect results to be available?
A: The study is ongoing, and we are recruiting participants. We anticipate concluding in December, at which point we will begin analyzing data. The preliminary data look promising, but it will be several months before we can draw any tentative conclusions. We likely will be ready for a manuscript submission next year — either by late spring or early summer.
Q: What is next for research?
A: Consistent with the ‘two-hit hypothesis,’ many breast cancer survivors face the direct effects of cancer treatment and the indirect effects resulting from a change in lifestyle following cancer diagnosis. Largely due to the persistent fatigue, many adopt sedentary behaviors that are harmful to physical and psychological well-being. Due to the precipitous decline in cardiorespiratory fitness, many breast cancer survivors encounter feelings of discomfort and pain upon physical exertion, which likely explains why breast cancer survivors generally are inactive. We frequently see a reinforcing pattern in which feelings of fatigue contribute to activity avoidance. This accelerates systemic deconditioning and ultimately increases the level of discomfort during activities of daily living and, thus, fatigue. The net result is a recipe for increased adiposity and cardiometabolic dysfunction. With this in mind, I am interested in strategies that can alleviate the burdens associated with this cycle of physical inactivity. I am especially interested in the link between nitrate-nitrite-NO pathway and cardiovascular function among patients with cancer and survivors. This concept ties in with the explosion of microbiome research, which is still very much in its infancy.
Q: Is there anything else that you would like to mention?
A: Over the past decade, the cancer world has warmed to the idea of using exercise training to offset the deleterious side effects associated with cancer treatment. Indeed, multiple randomized controlled trials have supported the use of exercise training as safe and effective across multiple cancer types. In my mind, the next step is to develop novel strategies to optimize the exercise stimulus on an individual level, which would lend itself favorably to robust improvements in cardiometabolic health. This type of forward thinking may pave the way to more tailored exercise therapies for patients and survivors. This is an exciting time to be researcher in field of exercise oncology, as there is much to be learned. – by Jennifer Southall
For more information:
Stephen J. Carter, PhD, can be reached at The University of Alabama at Birmingham, 1675 University Blvd., Susan Mott Webb Building 248, Birmingham, AL 35233; email: carters@uab.edu.
Disclosure: Carter reports no relevant financial disclosures.