**1. Introduction and Methodology**

In today's global society, the demand for humans to perform work in the heat is increasing [1,2]. Whether affecting manual laborers, military personnel, or athletes, heat stress is responsible for approximately 620 deaths in the United States [3] and thousands globally [4–6] each year. As such, strategies to manage heat stress and prolong exercise or activity in the heat have been explored extensively [7–10]. Broadly, these strategies can be categorized into *physical* and *nutritional* strategies. Physical strategies may include pre-cooling, cold water immersion, misting fans, and/or altering clothing [11]. These strategies have become popular among sports medicine staff and have varying degrees of success. Alternatively, nutritional strategies, largely based upon defending plasma volume (i.e., consuming relatively large doses of electrolytes, carbohydrates, and cold fluids), also play a role in managing heat stress. Among these nutritional strategies of heat stress managemen<sup>t</sup> includes the consumption of betaine.

The articles for this review were collected using the PubMed.gov search engine, searching the term "Betaine" alone and in conjunction with, "Heat Stress", "Heat Shock Proteins", "Hydration", "Gut Permeability", "Osmolytes", "Performance", and "Thermoregulation". Searches were terminated in July of 2020.
