Iron Absorption in The Low Oxygen Exposure and Weight Status (LOWS) Study

Effects of Energy Restriction and Intermittent Hypoxia on Iron Absorption in Obesity

Declines in iron status are common in those with obesity and may be due to obesity-related chronic inflammation; however, the effects of reducing inflammation following diet-induced weight loss on iron metabolism are poorly understood. Low environmental oxygen exposure increases dietary iron absorption and availability to supply iron for erythropoiesis but has not yet been tested in the context of weight loss. This study is designed to investigate diet-induced weight loss (inflammation reduction) and overnight low oxygen exposure (erythropoiesis stimulating agent) as strategies to improve dietary iron absorption in obesity.

Those with obesity are at increased risk for iron deficiency, which can worsen obesity-related comorbidities and add considerably to national health-care budgets. Declines in iron status in those with obesity may be due to adiposity-related inflammation. Adipokines, such as interleukin 6, increase hepcidin, an iron regulatory hormone secreted by the liver that functions to reduce iron absorption and iron availability. Elevated hepcidin and reduced dietary iron absorption may explain why those with obesity are more susceptible to iron deficiency and more resistant to treatment with iron supplements. However, the effects of reducing inflammation on iron absorption in those with obesity are poorly understood. In addition, low environmental oxygen exposure may be an alternative to optimize iron metabolism in obesity since hypoxia stimulates the synthesis of erythropoietin, which strongly suppresses hepcidin and increases iron absorption. The proposed study aims to capitalize on the ongoing Low Oxygen and Weight Status (LOWS) randomized, double-blind, parallel-arm, controlled-feeding trial (R01DK127162; Berryman) to understand the mechanism by which obesity increases risk for iron deficiency and potential countermeasures. In LOWS, adults with obesity are randomized to 8 weeks of controlled-feeding energy restriction (-500 kcal/day) plus intermittent exposure to normobaric hypoxia (8 h/night, 15% FiO2) or normoxia (8 h/night, 21% FiO2) using a commercially available, in-home tent system. This study aims at assessing dietary iron absorption at baseline and following 8 weeks of energy restriction in normoxia or intermittent hypoxia. Results of this project will serve as a foundation to the development of interventions to prevent and treat declines in iron status in obesity.

Inclusion Criteria:

• Obese (BMI between 30-39.9 kg/m2)
• Born at altitudes below 2,100 meters (~7,000 feet)
• Currently residing in Baton Rouge, Louisiana or surrounding area
• Not taking any medication(s) that interfere with oxygen delivery/transport for 4 weeks prior to and throughout the entire study (e.g., includes sedatives, sleeping aids, tranquilizers and/or any medication that depresses ventilation, diuretics, alpha and beta blockers).
• Willing to refrain from smoking, vaping, chewing tobacco, and dietary supplement use throughout the entire study.
• Willing to have a hypoxic tent set-up in their home and spend 8 consecutive hours per night in the tent for 8 weeks

Exclusion Criteria:

• 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
• Cardiovascular abnormalities, gastrointestinal disorders, or any condition that interferes with oxygen delivery/transport (e.g., kidney disease, cardiovascular disease, etc.)
• Oxygen saturation < 95% while awake or oxygen saturation dips below 88% for a total of ≥ 10 min overnight in normoxic conditions
• Evidence of apnea or other sleeping disorders
• Evidence of prior high-altitude pulmonary edema (HAPE) or high-altitude cerebral edema (HACE) diagnosis
• Diagnosis or family history of sickle cell anemia/trait
• Hematocrit <42% for males, <36% for females
• Hemoglobin <13 g/dL for males, <12 g/dL for females
• Blood donation within 8 weeks of beginning the study
• Present condition of alcoholism, anabolic steroids, or other substance abuse issues
• Women who are pregnant, lactating, planning to become pregnant, or who have had an irregular menstrual cycle in the past 6 mo.
• Weight gain or loss > 10% of body weight during the past 6 months
• Adults unable to consent