**8. Future Research**

In light of this review, several lines of research become overtly clear. First, scholars should aim to translate the data from mammalian cell cultures of other species to humans. Specifically, future research should measure the e ffects of betaine on di fferent types of cellular stressors (i.e., hypertonic, thermal, oxidative, acidic, etc.) in isolation and in combination, using specific tissues or tissue analogs (i.e., human enterocytes, hepatocytes, and skeletal muscle). Secondly, future researchers should test the impact of pre-loaded betaine on humans during passive and active heat stress, conditions where each of these cellular stressors are anticipated to be present. Specifically, future researchers should measure indications of thermal stress, hypertonic stress, and changes in metabolism. Lastly, future research should examine the impact of pre-loaded betaine on immune response during exercise in the heat to determine if the proposed pathway for endotoxin translocation can be improved upon through a series of exposures and adaptations (i.e., training the gut). All of these considerations will lead to a greater understanding of how athletes may use betaine supplementation to increase safety and performance in events where heat and humidity may pose a problem.

**Author Contributions:** Conceptualization, B.D.W. and M.J.O.; data curation, B.D.W. and T.J.R.; writing—original draft preparation, B.D.W. and T.J.R.; writing—review and editing, B.D.W., T.J.R. and M.J.O. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Conflicts of Interest:** The authors declare no conflict of interest.
