The relationship between hemoglobin and : A systematic review and meta-analysis

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 ($$) in humans. However, there exists considerable variability in the scientific literature regarding the potential relationship between hemoglobin and $$. Thus, we aimed to provide a comprehensive analysis of the diverse literature and examine the relationship between hemoglobin levels (hemoglobin concentration and mass) and $$ (absolute and relative $$) among both observational and interventional studies.

A systematic search was performed on December 6th, 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 $$ values (absolute and relative). For observational studies, meta-regression models were performed to examine the relationship between hemoglobin levels and $$ values. For interventional studies, meta-analysis models were performed to determine the change in $$ values (standard paired difference) associated with interventions designed to modify hemoglobin levels or $$. Meta-regression models were then performed to determine the relationship between a change in hemoglobin levels and the change in $$ values.

Data from 384 studies (226 observational studies and 158 interventional studies) were examined. For observational data, there was a positive association between absolute $$ and hemoglobin levels (hemoglobin concentration, hemoglobin mass, and hematocrit (P<0.001 for all)). Prespecified subgroup analyses demonstrated no apparent sex-related differences among these relationships. For interventional data, there was a positive association between the change of absolute $$ (standard paired difference) and the change in hemoglobin levels (hemoglobin concentration (P<0.0001) and hemoglobin mass (P = 0.006)).

These findings suggest that $$ values are closely associated with hemoglobin levels among both observational and interventional studies. Although our findings suggest a lack of sex differences in these relationships, there were limited studies incorporating females or stratifying results by biological sex.