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

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.

Study Overview

• Status: Recruiting
• Conditions: Obesity (Disorder)
• Intervention / Treatment: Other: Normobaric normoxia (NN); Other: Normobaric hypoxia (NH)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Recruitment Core; Phone Number: 225-763-3000; Email: clinicaltrials@pbrc.edu

Study Locations

• United States
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Recruiting
      • Pennington Biomedical Research Center
      • Contact: Recruitment Core; Phone Number: 225-763-3000; Email: clinicaltrials@pbrc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Normobaric hypoxia (NH); 8 weeks of overnight exposure (8 hrs/night) to NH conditions (~15% oxygen; achieved with nitrogen dilution, equivalent to ~8500 feet elevation) using a commercially available tent and generator system (Hypoxico, Inc., New York, NY).	Other: Normobaric hypoxia (NH); Low oxygen exposure to mimic ~8500 feet elevation (experimental)
Sham Comparator: Normobaric normoxia (NN); 8 weeks of overnight exposure (8 hrs/night) to NN conditions (~21% oxygen; sea level) using a commercially available tent and generator system (Hypoxico, Inc., New York, NY).	Other: Normobaric normoxia (NN); Normal oxygen exposure to mimic sea level conditions (sham comparator).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in iron absorption	Fractional iron absorption will be measured during the baseline weight maintenance phase (day -7) and at the end of the study (day 42). Change in fractional iron absorption will be calculated as: fractional iron absorption on day 42 - fractional iron absorption on day -7.	7 weeks

Collaborators and Investigators

• Sponsor: Pennington Biomedical Research Center
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Camila Weschenfelder, PhD, Pennington Biomedical Research Center

Publications and helpful links

General Publications

• Riley TM, Weschenfelder C, Ravussin E, Rood JC, Greenway F, Taff S, Hickner RC, Cao H, Sutin AR, Todd G, Hennigar SR, Berryman CE. Effects of daily low oxygen exposure on weight status, body composition, and metabolic health in adults with obesity: protocol for a randomized, double-blind, controlled-feeding study. Contemp Clin Trials. 2026 Jan;160:108167. doi: 10.1016/j.cct.2025.108167. Epub 2025 Nov 26.

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: April 14, 2026
• First Submitted That Met QC Criteria: April 14, 2026
• First Posted (Actual): April 21, 2026

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Energy expenditure; Body weight; Iron absorption; Energy intake; Iron metabolism; Normobaric hypoxia; Negative energy balance
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Body Weight
• Other Study ID Numbers: 2022-046-PBRC; U24DK132740 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No