Acid reflux or heartburn has always been treated as a condition of too much stomach acid when the opposite is in fact true. Bad eating habits formed over years such as eating on the run, eating when you’re stressed or stimulated, drinking during meals, eating highly processed/high carbohydrate/high fat meals, not eating enough protein, using too many over-the-counter medications such as NSAIDs and antacids that interfere with digestion…all of this can trigger the start of chronic acid reflux or make it worse. If this goes on for a long time it will affect how well the valve between the stomach and esophagus will close which may contribute to problems such as Barrett’s esophagus and persistent cough that refuses to go away despite many efforts. The key here is to INCREASE stomach acid production which seems counterintuitive so we’ll explain how this works.
GERD (GastroeEsophageal Reflux Disease) is a more serious form of acid indigestion that can be linked to chronic cough that can last for months and months. GERD can occur with or without heartburn and is harder to diagnose when heartburn is absent.
Esophagotracheobronchial Cough Reflex
When you have acid in the furthest part of the esophagus or throat, closest to the stomach, it can trigger this cough reflex. The valve between the esophagus and stomach just needs to be open a tiny bit to allow a small amount of acid through to set this cough reflex off. If the acid was significant there would usually be heartburn or reflux associated with the cough. The reflex that is set off seems to involved both stimulation of the mucosal wall of the esophagus and the vagus nerve linked to the esophagus. This theory is based on treatments that were effective for this type of cough discussed below:
- Esophageal lidocaine – this blocks the afferent limb of the cough reflex involving mucosa
- Inhaled ipratropium (anticholinergic agent) – this blocks the efferent limb of the cough reflex and is part of vagal nerve stimulation
Symptoms of chronic cough caused by GERD include:
- Non-productive cough mostly during the day while you are in an upright position
- Coughing when chest x-rays are normal
- Coughing without asthma or postnasal drip
- Lower cough threshold – anything can set of a cough
Differentiation Between Cough-GERD and Non-Cough GERD
Looking at GERD, the following may be present in those with chronic cough, but not necessarily in those without cough:
- Decreased lower esophageal sphincter (LES) pressures
- Decreased upper esophageal sphincter (UES) pressures
- Higher esophageal acid contact times
- Took longer for acid to clear out of the esophagus
- Airway inflammation with high monocytes and epithelial desquamation (when surface cells loose their differentiation and become smooth)
In short, this means the valve between the stomach and esophagus that keeps the stomach acid and content inside the stomach and prevents it from coming up into the throat becomes flimsy or weak. This allows the valve to open more easily and allow stomach acid or content to come back up. Even in small amounts this may not be enough to present as reflux or heartburn, but enough to stimulate the vagus nerve in the esophagus or irritate the esophagus wall. If this is a chronic occurrence it may set of episodes of cough that just doesn’t seem to go away without any obvious lung involvement.
How To Increase LES Pressure
- Stimulate gastrin production
- High protein diet – stimulates gastrin production
- Respiratory physiotherapy
Avoid Things That Decrease LES Pressure
- Cholecystokinin – released from the small intestine in response to fatty foods
- Fatty meals
- Chocolate – via methyl xanthine content (caffeine and theobromine). This inhibits phosphodiesterase and result in cyclic AMP accumulation.
- Caffeine – via methyl xanthine but also due to increased gastric acid secretion in the 1st 30 – 45 min. after ingestion.
- Alcohol – also interferes with esophageal motility and delays the clearing of acid from the esophagus.
- Acid foods such as orange juice and tomato – acts like stomach acid, irritates lower esophagus and stimulates cough reflex.
- Spicy foods – same reason as acid foods.
- Smoking – nicotine
- Peppermint, spearmint
- Carbonated drinks
Acetylcholine through vagal stimulation increase gastrin release from the G cells by activating M3 receptors. It can also have a direct stimulation on the parietal cells. It alters histamine concentrations in the stomach by inhibiting the release of somatostatin and so increases histamine (somatostatin inhibits histamine). In order to make acetylcholine we need choline (from the diet) and acetyl-CoA (from the pyruvate glucose cycle or acetyl-carnitine). We also need to inhibit excessive acetylcholinesterase activity (an enzyme that breaks down acetylcholine). Holy basil helps to decrease acetylcholinesterase activity.
Acetylcholine is responsible for about 20% of total acid secretion under stimulated conditions.
Gastrin is a peptide hormone released by G cells in the stomach in response to acetycholine and facilitates movement of food through the stomach. It is blocked by long-term antacid use which will make GERD worse in the long run. Gastrin is released in response to protein in the stomach, food in the stomach (through distension), vagal nerve stimulation (via GRP) and calcium (via calcium-sensing receptors). It is inhibited by stomach acid (negative feedback), somatostatin, secretin, glucagon, calcitonin, vasoactive intestinal peptide and gastroinhibitory peptide (GIP). Gastrin secretion can be stimulated by herbs such as gentian and valerian, as well as other ‘bitter’ herbs, but also amino acids. When peptones or amino acids such as phenylalanine is added to the stomach, gastrin mRNA can increase within about 15 minutes. The same effect is not seen with fat or glucose so this is quite significant.
Gastrin then binds to ECL (enterochromaffin-like) cells via CCK2 (cholecystokinin-2) receptors which secretes histamine. In those with auto-immune gastritis the immune system can attack the parietal cells. Here you will typically see an initial increase in gastrin production as the body is trying its hardest to get stomach acid production stimulated, but eventually it will drop off due to the loss of parietal cells and lack of negative feedback.
A 1998 study found histamine, HDC (histamine decarboxylase) an VMAT1 (type 1 vesicular monoamine transporter that moves histamine into storage vesicles) in the G-cells of the stomach. It was always assumed that histamine is only secreted by the ECL cells. I don’t know if this study was replicated and there are other studies that seem to say the exact opposite, but it’s an interesting theory.
Gastrin and histamine combined are responsible for about 40% of total acid secretion under stimulated conditions.
Ghrelin is a growth hormone-peptide found in the stomach that stimulates acid secretion and improves stomach motility via nitric oxide (possibly due to increased mucosal blood flow). It stimulates HDC (histamine decarboxylase) and thus histamine production and release from gastric ECL cells, but it does so mainly via the vagus nerve. This mechanism will not work properly in those with poor vagal tone. Ghrelin is usually increased during fasting to signal that it is time to eat.
Histamine is released from the ECL cells in response to gastrin (from G cells) or ghrelin (via vagus nerve), binds to H2 receptors (histamine receptors) on the parietal cells and secrete gastric acid. A feedback mechanism exists where high histamine will suppress gastrin production. So it makes sense that if you want to increase gastrin production in order to increase LES pressure and improve GERD that you may have to look for high histamine production in the stomach and possibly suppress this through anti-histamines. Yet, LES pressure seems to increase in response to intravenous histamine phosphate. H1 receptors occur on the LES and has a spasmodic effect. H2 receptors which are muscle relaxants do not occur on the LES. This may indicate that the reason why gastrin stimulation increases LES pressure is not a direct action, but more through its role in histamine release.
Histamine and gastrin combined are responsible for about 40% of total acid secretion under stimulated conditions.
Somatostatin inhibits histamine release, parietal cell function and gastric acid release. So it reduces stomach acid. We would expect that when stomach acid is chronically reduced such as with the longterm use of PPI’s and other antacids that somatostatin levels will reduce as well (feedback mechanism) to allow for increased stomach acid production. However, it was found that after use of gastric acid inhibitors somatostatin mRNA was increased. This would indicate that somatostatin is regulated by stomach pH as a protective mechanism against ulcer formation or reflux.
Gastric acid inhibitors also increase gastrin production, probably because the drop in stomach acid brought on by the drugs triggers the body to try and make more acid through gastrin stimulation. High gastrin will trigger somatostatin release.
Proton Pump Inhibitors and Antacids
These function either to stop the body’s production of stomach acid or neutralize the acid already produced inside the stomach. Using these over a period of time will result in nutrient malabsorption and a gradual decline in health as a result. Common nutritional deficiencies linked to the use of these drugs include calcium, vitamin B12, other B vitamins, zinc, folate, selenium, iron and magnesium, just to name a few. The folate transporter SLC46A1 needs a low pH environment in the small intestine (when food arrives from the stomach) to become activated and transport folate from food into the bloodstream. Deficiencies in these nutrients will have huge implications for methylation as the driving mechanism in the development of chronic disease.
Because it inhibits gastric acid production, longterm use will have the body respond in a compensatory way by producing more gastrin. Gastric acid levels drop, stomach pH increases (becomes more alkaline), somatostatin levels drop and gastrin levels increase. This excessive gastrin production in response to low stomach acid has been linked to the growth of esophageal (Barrett’s esophagus), pancreatic and gastric cancer cells.
Lowering stomach acid also removes the body’s natural defense mechanism against H. pylori, bacteria, viruses and other pathogens that usually don’t make it past the low pH environment of the stomach. PPI’s and antacids create conditions where they can happily bypass this mechanism and move further down the digestive tract to inhabit, grow and cause other gastrointestinal symptoms.
This Raises A Few Questions
What about those where blood tests show very low gastrin levels and yet anti-histamines make them worse? This may indicate a complete failure of the whole system possibly starting from low acetylcholine or autonomic nervous system dysfunction (vagus nerve).
Does it mean if GERD symptoms are more pronounced with eating that it is more related to low gastrin, and if it occurs independent of eating or not eating that it is more related to low histamine (as a combination of low gastrin and ghrelin)?
How To Increase LES Pressure and Improve Digestion
- Avoid foods that would decrease LES pressure
- Drink liquids away from meals, at least 30 minutes before or after meals, so as not to dilute stomach acid.
- Think about lemons or drink a small amount of lemon juice or apple cider vinegar in a small amount of water before a meal. This starts the salivation process. Salivation is the first sign of digestion.
- Take 20 drops of bitters in a small amount of water before meals.
- Eat when you are relaxed or in a relaxed environment. You will salivate when you are relaxed, not when you are stressed, so use this as a sign.
- Make sure meals contain protein to stimulate gastrin production.
If you need guidance in the treatment of this or any other condition, please make an appointment with one of our practitioners.
This article is for information purposes only. Please refer to our Medical Disclaimer policy for more information. The opinions expressed here represents the author’s and not necessarily those of Realize Health. In addition, thoughts and opinions change from time to time due to updates in research and as a necessary consequence of having an open mind. Views expressed in out-of-date posts may not be the same to those we hold today.
Nutrition and Gene Expression by Carolyn D. Berdanier and James L. Hargrove