posted on 2019-03-05, 00:00authored byMichelle Saoi, Michael Percival, Carine Nemr, Alice Li, Martin Gibala, Philip Britz-McKibbin
Bicarbonate
has long been touted as a putative ergogenic aid that
improves exercise performance and blood buffering capacity during
strenuous exercise. However, the underlying mechanisms of action of
bicarbonate intake on skeletal muscle metabolism have yet to be fully
elucidated. Herein, we apply two orthogonal analytical platforms for
nontargeted profiling of metabolites and targeted analysis of electrolytes
from mass-limited muscle tissue biopsies (∼2 mg dried mass)
when multisegment injection-capillary electrophoresis-mass spectrometry
(MSI-CE-MS) and CE with indirect UV detection are used, respectively.
Seven untrained men performed a standardized bout of high-intensity
interval exercise trial following either bicarbonate (0.40 g/kg) or
placebo ingestion in a double-blinded, placebo-controlled, crossover
study design, where paired skeletal muscle tissue and plasma specimens
were collected at three time intervals at rest, postexercise, and
recovery. Optimization of a quantitative microextraction procedure
was first developed for lyophilized tissue prior to characterization
of the human muscle metabolome, which resulted in the identification
and quantification of more than 80 polar/ionic metabolites reliably
(CV < 30%) detected in a majority (>75%) of samples with quality
control. Complementary univariate and multivariate statistical methods
were used to identify biomarkers associated with strenuous exercise
and/or bicarbonate treatment responses, whereas structural elucidation
of biologically significant intramuscular metabolites was performed
using high-resolution MS/MS. Importantly, bicarbonate ingestion prior
to strenuous interval exercise was found to elicit a modest treatment
effect (p < 0.05) in comparison to placebo on
metabolic pathways associated with ionic homeostasis (potassium),
purine degradation (uric acid), and oxidative stress as regulated
by glutathione metabolism (oxidized mixed glutathione disulfide) and
histidine-containing dipeptides (anserine) within muscle tissue that
was distinctive from dynamic metabolic changes measured in circulation.
This work provides deeper biochemical insights into the effect of
acute alkalosis in preserving contracting muscle function during high-intensity
exercise, which is also applicable to the study of muscle-related
pathologies relevant to human health and aging.