The Necessary Role of Stomach Acid

"All disease starts in the gut"- Hippocrates

Conventional wisdom proposes that acid reflux is the consequence of too much stomach acid and that acid suppression is necessary when reflux occurs; it is imperative to examine the mechanisms of this process and the repercussions of a reduced acidic environment in the stomach. The process of digestion is highly complex, requiring coordination between the compartmentalized gastrointestinal tract and associated organs (liver, gallbladder, and pancreas). Disruption at any location can trigger severe health consequences, some that occur immediately and others that are more latent. Functioning as a coordinated ecosystem, it is important to maintain each partitioned microenvironment to maximize nutrient absorption, protect the delicate small intestinal brush border, and nourish a diverse, healthy microbiome (beneficial intestinal bacteria). Stomach acid performs multiple functions including initiating nutrient absorption, reducing pathogenic microorganism burden1, and triggering pancreatic enzyme excretion. Medication aimed at suppressing acid in the stomach interrupts nutrient digestion and absorption through numerous mechanisms. Prolonged use may negatively impact many organ systems including the liver, stomach, brain, bones, and kidneys2.

Gastroesophageal reflux is characterized by a burning sensation in the chest, usually associated with recent food intake, but not always, and exacerbated when lying down. The lower esophageal sphincter (LES) is a circular smooth muscle at the terminal aspect of the esophagus, just above the stomach, that tightens, to prevent stomach acid from spill-over into the esophagus, in normal physiologic conditions. There are two main scenarios that may interrupt this normal physiologic state; reduced sphincter tone or increased intra-gastric pressure, exceeding the manometric pressure of the LES. Increased abdominal adiposity, overeating, pyloric stenosis (small opening at the distal end of the stomach), gas-producing bacteria in the small intestine, transient lower esophageal sphincter relaxation, and hiatal herniation (the upper part of the stomach herniates through the thoracic diaphragm) are some conditions that can lead to reflux symptoms. Episodic use of acid-suppressing medication will help eliminate these symptoms at the moment, but it is important to find and address the underlying cause of these symptoms with frequent recurrence.

The stomach is often regarded as a hollow sac for mechanical and chemical digestion only. However, the stomach is a highly sophisticated physiological organ with endocrine, immunological, biochemical, and microbiological influences3. In order to maintain the proper coordinated physiological functioning, it is necessary that the environment be regulated appropriately. Parietal cells in the stomach produce hydrochloric acid and the pH can be as low as 0.8. Acid secretion, in the stomach, is under continuous endocrine and nervous system regulatory control and is often not maximally acidic. Secretion of gastric acid is not continuous either, but rather, triggered in response to fed-state physiology. Production of hydrochloric acid is an expensive energetic process, requiring more than 1,500 calories of energy per liter of gastric juice created. Our bodies choose efficiency and only create acid when it is needed, in order to conserve energy.

Digestion of protein requires an acidic environment in the stomach. Adequate protein intake is crucial for structural growth, maintenance of adequate muscle mass, proper immune function, production of enzymes, and cellular signaling pathways. Proteins have a unique 3-dimensional structure commensurate to their function. In order to digest protein, stomach acid is necessary to disrupt the 3-dimensional architecture to produce a linear polypeptide in order for cleavage into individual amino acids (building blocks of protein) for absorption. Without denaturing the protein into a linear form, digestive enzymes (peptidases) are unable to fully break down these proteins for absorption. Pepsin, a protein-digesting enzyme, secreted from the Chief cells in the stomach, requires stomach acid for conversion from its inactive proenzyme form, pepsinogen, to its active form, pepsin.

Several key vitamins and minerals also require stomach acid for absorption including vitamin B12, vitamin C, calcium, iron, and magnesium4. Vitamin B12 malabsorption5 is a result of the inactivation of pepsinogen to pepsin; pepsin acts to cleave B12 from the food-carrier proteins. Absorption of vitamin B12 requires a complicated interaction and reliance on the production and degradation of carrying molecules. Stomach acid plays a vital role in the activation and excretion of these key enzymes. Deficiency in vitamin B12 can lead to irreversible nerve damage as well as many diseases associated with aging6.

In addition to vitamin and mineral deficiencies, prolonged hypochlorhydria (low stomach acid) has been associated with gastric cancer, kidney disease, bone fracture risk, dementia, and liver disease. While proton pump inhibitors (omeprazole, pantoprazole, etc.), histamine-2 antagonists (famotidine, cimetidine, etc.), and other oral antacids are efficacious in treating symptomatic pathologies, their negative side effects should be weighed against the benefit of their long-term use. Peptic ulcer disease and erosive esophagitis are clear indications of their benefit and should be used in these scenarios. Even episodic use for gastroesophageal reflux may be necessary, but better discernment is needed to avoid the myriad complicating factors associated with long-term use. While these medications often provide the elimination of unwanted reflux symptoms, judicious use is important to avoid long-term, irreversible consequences. Adequate nutrient digestion and absorption require the production of stomach acid; chronically suppressing this normal physiologic response will lead to many unintended negative consequences.

Resources:

1. https://www.sciencedirect.com/science/article/pii/S0362028X2203201X
2. https://www.mdpi.com/1422-0067/20/20/5203/htm
3. https://gut.bmj.com/content/64/10/1650.long
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110863/pdf/10.1177_2042098613482484.pdf
5. https://www.sciencedirect.com/science/article/abs/pii/S0083672922000164?via%3Dihub
6. https://journals.sagepub.com/doi/epub/10.1177/0004563212473279