What is Heartburn and gastro-oesophageal reflux disease? (GORD, GERD, Acid reflux)

A friend of mine ask me about GORD and I have to admit I had no idea what it is so after my friend explained what it is I naturally went and did a little research.

Heartburn and gastro-oesophageal reflux disease (GORD) according to NIDirect.gov.uk is:

Gastro-oesophageal reflux disease (GORD) is a common condition, where acid from the stomach leaks up into the oesophagus (gullet). GORD causes symptoms such as heartburn and an unpleasant taste in the back of the mouth. This page has information on GORD for people aged 16 years or older.

So GORD it turns out can cause acid reflux which is what my friend was suffering from and one of the causes is apparently Hiatus hernia because this condition pushes the stomach into the diaphragm opening the related sphincter and allowing stomach acid to flow Bach up the oesophagus. That is the logic so I needed to remind myself about hiatus hernia so I checked YouTube and found this.

What causes GERD

The GERD Diet: What to Eat (and What Not to Eat) this article gives a completely contrasting view on how GERD occurs and thus has different treatment options

Gerd and Insulin resistance

Some of the research findings:

Pathophysiology and treatment options for gastroesophageal reflux disease: looking beyond acid. https://doi.org/10.1111/nyas.14501

Gastroesophageal reflux disease (GERD) is a disorder due to the retrograde flow of refluxate into the esophagus. Although GERD is a common clinical diagnosis, its pathogenesis is quite complex. As a result of its multifactorial development, many patients continue to experience adverse symptoms due to GERD despite prolonged acid suppression with proton pump inhibitor therapy. The pathogenesis of GERD involves an interplay of chemical, mechanical, psychologic, and neurologic mechanisms, which contribute to symptom presentation, diagnosis, and treatment. As such, GERD should be approached as a disorder beyond acid. This review will investigate the major factors that contribute to the development of GERD, including factors related to the refluxate, esophageal defenses, and factors that promote pathologic reflux into the esophagus. In reviewing GERD pathogenesis, this paper will highlight therapeutic advances, with mention of future opportunities of study when approaching GERD.

Diabetes

Diabetes and Acid Reflux: How Are They Linked? I notice that this link is straight to a site run by surgeons who make money through gastric bypass and other surgeries so while the evidence is good I am concerned that the medical industry still resorts so easily to surgery.

lower esophageal valve

• The GERD Diet: What to Eat (and What Not to Eat)

Proton pumps

What are they?

Taken from Ask a biologogist:

If we think of a cell membrane as a dam, we can get a better idea of how the transporters in membranes work. As water builds up on one side of the dam, the concentration gradient is high and has lots of potential energy. If water is let through a spillway or floodgate, it can spin a turbine and create energy. 

In the same way, cell membranes keep the concentration gradient of hydrogen high. When a hydrogen ion passes down the concentration gradient through a transporter, it makes that potential energy available. This energy can be used to take a molecule from inside the cell and move it out or can help make ATP in a specialized enzyme.

However, hydrogen ions can also be moved the other way, toward areas of high concentration. This is how concentration gradients are maintained. In the dam, this is like when pumps are used to keep the water level in a reservoir behind the dam high. To move water up the concentration gradient can take a lot of energy. But when that water level (or concentration gradient) is kept high, more energy is stored that can be used for other things.

For a more indepth explanation refer to the full article at Ask a biologogist:

Wikipedia also has a list of proton pumps and their function. This article also explains the proton pump actions related to cell respiration and therefore its implications for metabolism.

In cell respiration, the proton pump uses energy to transport protons from the matrix of the mitochondrion to the inter-membrane space.^[1] It is an active pump that generates a proton concentration gradient across the inner mitochondrial membrane because there are more protons outside the matrix than inside. The difference in pH and electric charge (ignoring differences in buffer capacity) creates an electrochemical potential difference that works similar to that of a battery or energy storing unit for the cell.^[2] The process could also be seen as analogous to cycling uphill or charging a battery for later use, as it produces potential energy. The proton pump does not create energy, but forms a gradient that stores energy for later use.^[3]

Proton pumps and activity

Given the success of proton pump inhibitors I am investigating the link between proton pumps and physical activity and asking questions like; is the proton pump improved through activity. The reason being that the functioning of all energy pathways is improving through activity so is there any evidence that the proton pump energy pathway is improved through activity

Taking this argument further lead me to link insulin resistance and GERD and therefore ask if an increase insulin sensitivy will reduce GERD symptoms for example by improving the proton pump.

• Association of Proton Pump Inhibitor (PPI) Use with Energy Intake, Physical Activity, and Weight Gain Jennifer L Czwornog ¹, Gregory L Austin ² PMID: 26492268 PMCID: PMC4632436 DOI: 10.3390/nu7105416
• Gastroesophageal reflux disease and physical activity Sports Med. 2006;36(5):385-91. doi: 10.2165/00007256-200636050-00002.
• The Dangers of Proton Pump Inhibitors A summary of the risk of long term use of proton pump inhibitors. Proton pump inhibitors rank among the top 10 prescribed classes of drugs and are commonly used to treat acid reflux, indigestion, and peptic ulcers. Although generally assumed to be safe, recent studies have shown that they have numerous side effects, from an altered gut environment and impaired nutrient absorption to an increased risk for cardiovascular events, kidney disease, and dementia.  
• The Lysosomal Proton Pump lysosoms are the cells garbage collectors

Prolonged Use of Proton Pump Inhibitors and Risk of Type 2 Diabetes

• Prolonged Use of Proton Pump Inhibitors and Risk of Type 2 Diabetes: Results From a Large Population-Based Nested Case-Control Study Stefano Ciardullo, Federico Rea, Laura Savaré, Gabriella Morabito, Gianluca Perseghin, and Giovanni Corrao: J Clin Endocrinol Metab. 2022 Jul; 107(7): e2671–e2679. : Regular and prolonged use of PPIs is associated with a higher risk of diabetes. Physicians should therefore avoid unnecessary prescription of this class of drugs, particularly for long-term use.
• Proton pump inhibitors are associated with incident type 2 diabetes mellitus in a prospective population-based cohort study Petra Czarniak, Fariba Ahmadizar, Jeff Hughes, Richard Parsons, Maryam Kavousi, Mohammad Ikram, Bruno H. Stricker: https://doi.org/10.1111/bcp.15182 New users of PPIs during follow-up had a significantly higher dose-dependent risk of incident diabetes. We suggest vigilance regarding their potential adverse effect on glucose homeostasis.
  • What is already known about this subject
    • Previous studies reported that gastrin promotes beta-cell proliferation in rodents.
    • Proton pump inhibitors (PPIs) can lead to hypergastrinaemia, and some studies reported improved glycaemic control in patients with diabetes on PPI.
    • Counterintuitively, studies in people without diabetes suggest an association between PPI and onset of diabetes, but results were contradictory.
  • What this study adds
    • Incident use of PPI was associated with a significantly increased risk of incident diabetes.
    • The effect was dependent on dosage and duration of PPI use.
    • Whilst the mechanism of glycaemic dysregulation associated with PPI use requires further investigation, low magnesium and glucagon-like peptide-1 are potential contributors.
• Proton pump inhibitors linked to higher risk of diabetes A study from Italy reports that “regular and prolonged use of proton pump inhibitors is associated with a higher risk of diabetes”. The authors of the study suggest avoiding “unnecessary prescription” of PPIs — “particularly for long-term use”.
• Effect of proton pump inhibitors on glycemic control in patients with diabetes

Appedicitis

• Association between Gastroesophageal Reflux Disease and Appendicitis: A Population-Based Case-Control Study:. I can’t help but search for correlations and see what is likely to go wrong.