The vagus nerve has a hepatic (liver) branch. When the liver is stimulated there is an increase of bile production and release, which helps in cleansing the liver so it will be able to perform more efficiently. In short the bitters kick the liver and gallbladder in to high hear, while also increasing stomach acidity and digestive enzymes. The effect is pretty quick, but generally not very drastic. Most people will develop mild flu-like symptoms (fatigue, diarrhea, mild fever, minor aches, etc.) during the initial detox. This is why the water throughout the day is so important. This usually does not last more than a day or two of using the bitters. Though everyone is different so some will have no detox symptoms, some will have mild detox symptoms, and rarely people can have more severe detox symptoms. This is why it is best to start out slow and work up to three times daily.