Thank you for providing detailed information on PPIs and their alternatives. As you’ve mentioned in your post, PPIs affect proton pumps not only in the stomach. It was interesting to learn this week that an impairment of lysosomal acidification caused by PPI drugs reduces lysosomal enzyme activity, which results in an accumulation of protein aggregates. Today, PPIs are the main medication used to reduce stomach acid and relieve GERD symptoms. Due to numerous side effects of PPIs drugs, especially when used long-term, health care provides recommend other alternatives, and melatonin is one of them. Although, melatonin is mainly used to treat sleep disorders, it was found that low levels of this hormone produced in the body by the pineal gland can lead to gastroesophageal reflux disease (GERD). Studies also determined that melatonin has an inhibitory effect on the secretion of gastric acid, and participates in the controlling of the lower esophageal sphincter. The first mechanism of melatonin’s action is the strengthening of the lower esophageal sphincter. Since relaxation of this sphincter is the main cause of acid reflux, its strengthening helps to prevent stomach contents from coming back up into the esophagus. Besides that, melatonin inhibits the production of nitric oxide – a chemical compound that relaxes the lower esophageal sphincter and allows for acidic contents to enter the esophagus and cause heartburn.