Estimating the dosage and feasibility of intranasal administration of creatine.

Abstract

Creatine dysregulation is present in many psychiatric and neurocognitive conditions, supporting the notion that oral creatine supplementation could constitute a viable treatment for conditions such as dementia, depression, and concussion. We recently proposed an intranasal route of administration (ROA) of creatine as a means of efficiently dosing creatine to achieve absorption across the blood brain barrier while targeting preferential delivery to the brain. Indeed, a subsequent murine study supports that creatine can be absorbed via the nasal ROA. The objective of this project is to refine this ROA and estimate appropriate dosage for research trials.    The amount of creatine needed to directly supply the brain is but a small portion of the dose that is administered orally for whole-body saturation. A single dose of creatine is typically 5 g, which results in a calculated blood concentration of 80 mg/dL based upon average adult blood volume. Evidence suggests this is sufficient to raise brain creatine levels. Given the adult brain blood volume of 100‒130 mL, we estimate that a minimum of 80 mg of nasally-administered creatine would need to pass from the nasal cavity across the blood-brain barrier. Even if the nasal columnar epithelium or mucus were to pose a barrier, doubling or tripling the dose would still represent a relatively modest amount of nasally-delivered creatine (e.g., 160‒240 mg) in solution. We predict that the amount of nasally-administered creatine to theoretically raise brain blood concentration to a therapeutic level would be modest and practical.