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The insertion/deletion (I/D) polymorphism in the gene for the major regulator of vascular tone, angiotensin-converting enzyme-insertion/deletion (ACE-I/D) affects muscle capillarization and mitochondrial biogenesis with endurance training. We tested whether changes of leg muscle oxygen saturation (SmO 2 ) during exhaustive exercise and recovery would depend on the aerobic fitness status and the ACE I/D polymorphism.    Methods  In total, 34 healthy subjects (age: 31.8 ± 10.2 years, 17 male, 17 female) performed an incremental exercise test to exhaustion. SmO 2  in  musculus vastus lateralis  (VAS) and musculus gastrocnemius (GAS) was recorded with near-IR spectroscopy. Effects of the aerobic fitness status (based on a VO 2peak  cutoff value of 50 ml O 2  min −1  kg −1 ) and the ACE-I/D genotype (detected by PCR) on kinetic parameters of muscle deoxygenation and reoxygenation were assessed with univariate ANOVA.    Results  Deoxygenation with exercise was comparable in VAS and GAS ( p  = 0.321). In both leg muscles, deoxygenation and reoxygenation were 1.5-fold higher in the fit than the unfit volunteers. Differences in muscle deoxygenation, but not VO 2 peak, were associated with gender-independent ( p  &amp;gt; 0.58) interaction effects between aerobic fitness × ACE-I/D genotype; being reflected in a 2-fold accelerated deoxygenation of VAS for aerobically fit than unfit ACE-II genotypes and a 2-fold higher deoxygenation of GAS for fit ACE-II genotypes than fit D-allele carriers.    Discussion  Aerobically fit subjects demonstrated increased rates of leg muscle deoxygenation and reoxygenation. Together with the higher muscle deoxygenation in aerobically fit ACE-II genotypes, this suggests that an ACE-I/D genotype-based personalization of training protocols might serve to best improve aerobic performance.

Accelerated Muscle Deoxygenation in Aerobically Fit Subjects During Exhaustive Exercise Is Associated With the ACE Insertion Allele