The relationship between hemoglobin and V˙O2max: A systematic review and meta-analysis
Kevin L. Webb, Ellen K. Gorman, Olaf H. Morkeberg, Stephen A. Klassen, Riley J. Regimbal, Chad C. Wiggins, Michael J. Joyner, Shane M. Hammer, Jonathon W. Senefeld
Abstract
Objective There is widespread agreement about the key role of hemoglobin for oxygen transport. Both observational and interventional studies have examined the relationship between hemoglobin levels and maximal oxygen uptake ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" id="M3"><mml:mrow><mml:mover accent="true"><mml:mi mathvariant="normal">V</mml:mi><mml:mo>˙</mml:mo></mml:mover><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub><mml:mi mathvariant="normal">m</mml:mi><mml:mi mathvariant="normal">a</mml:mi><mml:mi mathvariant="normal">x</mml:mi></mml:mrow></mml:math> ) in humans. However, there exists considerable variability in the scientific literature regarding the potential relationship between hemoglobin and <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" id="M4"><mml:mrow><mml:mover accent="true"><mml:mi mathvariant="normal">V</mml:mi><mml:mo>˙</mml:mo></mml:mover><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub><mml:mi mathvariant="normal">m</mml:mi><mml:mi mathvariant="normal">a</mml:mi><mml:mi mathvariant="normal">x</mml:mi></mml:mrow></mml:math> . Thus, we aimed to provide a comprehensive analysis of the diverse literature and examine the relationship between hemoglobin levels (hemoglobin concentration and mass) and <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" id="M5"><mml:mrow><mml:mover accent="true"><mml:mi mathvariant="normal">V</mml:mi><mml:mo>˙</mml:mo></mml:mover><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub><mml:mi mathvariant="normal">m</mml:mi><mml:mi mathvariant="normal">a</mml:mi><mml:mi mathvariant="normal">x</mml:mi></mml:mrow></mml:math> (absolute and relative <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" id="M6"><mml:mrow><mml:mover accent="true"><mml:mi mathvariant="normal">V</mml:mi><mml:mo>˙</mml:mo></mml:mover><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub><mml:mi mathvariant="normal">m</mml:mi><mml:mi mathvariant="normal">a</mml:mi><mml:mi mathvariant="normal">x</mml:mi></mml:mrow></mml:math> ) among both observational and interventional studies. Methods A systematic search was performed on December 6 th , 2021. The study procedures and reporting of findings followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Article selection and data abstraction were performed in duplicate by two independent reviewers. Primary outcomes were hemoglobin levels and <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" id="M7"><mml:mrow><mml:mover accent="true"><mml:mi mathvariant="normal">V</mml:mi><mml:mo>˙</mml:mo></mml:mover><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub><mml:mi mathvariant="normal">m</mml:mi><mml:mi mathvariant="normal">a</mml:mi><mml:mi mathvariant="normal">x</mml:mi></mml:mrow></mml:math> values (absolute and relative). For observational studies, meta-regression models were performed to examine the relationship between hemoglobin levels and <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" id="M8"><mml:mrow><mml:mover accent="true"><mml:mi mathvariant="normal">V</mml:mi><mml:mo>˙</mml:mo></mml:mover><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub><mml:mi mathvariant="normal">m</mml:mi><mml:mi mathvariant="normal">a</mml:mi><mml:mi mathvariant="normal">x</mml:mi></mml:mrow></mml:math> values. For interventional studies, meta-analysis models were performed to determine the change in <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" id="M9"><mml:mrow><mml:mover accent="true"><mml:mi mathvariant="normal">V</mml:mi><mml:mo>˙</mml:mo></mml:mover><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub><mml:mi mathvariant="normal">m</mml:mi><mml:mi mathvariant="normal">a</mml:mi><mml:mi mathvariant="normal">x</mml:mi></mml:mrow></mml:math> values (standard paired difference) associated with interventions designed to modify hemoglobin levels or <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" id="M10"><mml:mrow><mml:mover accent="true"><mml:mi mathvariant="normal">V</mml:mi><mml:mo>˙</mml:mo></mml:mover><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub><mml:mi mathvariant="normal">m</mml:mi><mml:mi mathvariant="normal">a</mml:mi><mml:mi mathvariant="normal">x</mml:mi></mml:mrow></mml:math> . Meta-regression models were then performed to determine the relationship between a change in hemoglobin levels and the change in <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" id="M11"><mml:mrow><mml:mover accent="true"><mml:mi mathvariant="normal">V</mml:mi><mml:mo>˙</mml:mo></mml:mover><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub><mml:mi mathvariant="normal">m</mml:mi><mml:mi mathvariant="normal">a</mml:mi><mml:mi mathvariant="normal">x</mml:mi></mml:mrow></mml:math> values. Results Data from 384 studies (226 observational studies and 158 interventional studies) were examined. For observational data, there was a positive association between absolute <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" id="M12"><mml:mrow><mml:mover accent="true"><mml:mi mathvariant="normal">V</mml:mi><mml:mo>˙</mml:mo></mml:mover><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub><mml:mi mathvariant="normal">m</mml:mi><mml:mi mathvariant="normal">a</mml:mi><mml:mi mathvariant="normal">x</mml:mi></mml:mrow></mml:math> and hemoglobin levels (hemoglobin concentration, hemoglobin mass, and hematocrit ( P <0.001 for all)). Prespecified subgroup analyses demonstrated no apparent sex-related differences among these relationships. For interventional data, there was a positive association between the change of absolute <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" id="M13"><mml:mrow><mml:mover accent="true"><mml:mi mathvariant="normal">V</mml:mi><mml:mo>˙</mml:mo></mml:mover><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub><mml:mi mathvariant="normal">m</mml:mi><mml:mi mathvariant="normal">a</mml:mi><mml:mi mathvariant="normal">x</mml:mi></mml:mrow></mml:math> (standard paired difference) and the change in hemoglobin levels (hemoglobin concentration (<j