Additional covariates that can influence the outcome of a given trial also include concomitant pathology (such as X-linked creatine transporter deficiency) and nutritional status of participants (e.g., vitamin D deficiency, creatine-free diet), along with other factors (including age, physical exercise, and level of education) that could play important role on CT1 and Klotho protein function and/or creatine homeostasis in the brain. This evidence concerns the gene SLC6A8 and X-linked creatine transporter deficiency.