Traditionally, the management and research of inborn errors of metabolism have been primarily overseen by genetic specialists, whose expertise has guided both therapeutic strategies and efforts to identify potential cures. In more recent times, exercise scientists and exercise physiologists have been shown to provide important insights into these conditions from new perspectives. Because exercise and physical activity testing is often used to determine the main outcome variables for interventions designed to improve the lives of those with inborn errors of metabolism, it is logical that exercise specialists are involved in research design and data interpretation.

This article aims to provide important exercise and physical activity testing guidance and advice for researchers of McArdle disease (MD) with evidence-based rationale to help improve data interpretation and the validity of research outcomes for future research. The article presents clear definitions and examples of concepts commonly used in exercise and physical activity research (i.e., absolute and relative intensity) and outlines methodological considerations that may compromise results interpretation (i.e., the use of broad exercise intensity ranges, pretesting liver glycogen standardisation). Additionally, the article discusses important considerations and limitations in using exercise testing metrics in MD populations, and their associated interpretations, that have been previously validated in non-MD populations (i.e., maximal rate of oxygen consumption $\left[\dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{m}\mathrm{a}\mathrm{x}}\right]$, peak rate of oxygen consumption $\left[\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}\right]$, and respiratory exchange ratios [RER]). The information presented will act as an important reference point for future research design and data interpretation for exercise and physical activity testing with MD cohorts.

Inevitably, prior research forms the foundations to future advances which places an important responsibility on all scientists to design robust research methodologies, produce valid and reliable results, identify limitations to their outcomes, and to interpret and apply these results correctly.

McArdle disease (MD) is a rare (1:100000) genetic myopathy whereby the enzyme glycogen phosphorylase is not expressed in skeletal muscle, resulting in the blockage of glycogenolysis and presenting as physical activity intolerance. To circumvent the blockage in glycogenolysis, current clinical practice guidelines advise individuals with MD (IWMD) to ingest 37 ​g of sucrose 5–10 ​minute (min) before undertaking exercise.

The current investigation undertook randomized repeated measure clinical exercise trials on five IWMD to compare exercise tolerance under different timing of sucrose ingestion before exercise.

Results showed significantly higher plasma glucose availability at the beginning of exercise when sucrose was ingested 25-min before exercise ([7.4 ​± ​0.8] mmol⋅L⁻¹) compared to 5-min before exercise ([5.6 ​± ​0.3] mmol⋅L⁻¹, p ​= ​0.024) or a placebo ([5.3 ​± ​0.4] mmol⋅L⁻¹, p ​= ​0.017). Peak heart rates we significantly lower when sucrose was ingested 25-min before exercise ([117 ​± ​14] beats⋅min⁻¹) compared to 5-min before exercise ([129 ​± ​14] beats⋅min⁻¹, p ​= ​0.022) or a placebo ([135 ​± ​20] beats⋅min⁻¹, p ​= ​0.039) which contrasts with recommendations in current clinical practice guidelines.

While the ingestion of sucrose (carbohydrate) before exercise for IWMD may provide statistically significant improvements in exercise tolerance in lab-base settings, its clinical relevance and application to real world settings (RWS) is likely negligible based on the extremely low power outputs IWMD achieve during lab studies. Clinical practice guidelines should be updated to better reflect the magnitude of benefit ingesting carbohydrate before exercise may provide to set realistic expectations for both medical professionals and IWMD.

The ingestion of sucrose (carbohydrate) before exercise for IWMD may provide statistically significant improvements in exercise tolerance in lab-base settings, but its clinical relevance and application to real world settings is likely negligible based on the extremely low power outputs achieved by IWMD during lab studies.