If you ask any average person on the street what causes heartburn, he’ll tell you “too much acid in stomach” or in simple terms he’ll say it as “acidity”,  because the mainstream medical approach to treating heartburn and Gastroesophageal Reflux Disease (GERD) involves taking acid stopping drugs for as long as symptoms are present. Unfortunately, not only do these drugs fail to address the underlying cause of heartburn and GERD, they make it worse, because as soon as the patient stops taking them, the symptoms return. And often they’re worse than they were before the patient started the drug.

Contrary to popular belief, heartburn and GERD are caused by too little (not too much) stomach acid. In 99% of cases, low stomach acid is the underlying cause of acid reflux and GERD. Despite the common sense of how it feels, it’s extremely rare to have too much stomach acid. Besides being the main cause of acid reflux disease and GERD, low stomach acid is also the primary cause of food sensitivities, IBS, colitis, SIBO, osteoporosis, anemia, etc.

But a logical question arises: “If that’s true, then why do my antacid drugs provide relief?” In order to answer that, lets discuss the mechanism of heartburn and GERD.

What Causes Heartburn and GERD?

  • Dysfunction of the Lower Esophageal Sphincter (LES): This is the valve between the stomach and the esophagus. When working correctly, it is only supposed to open when swallowing food, burping or vomiting. If the LES is working properly, it doesn’t matter how much acid we have in our stomachs. It’s not going to make it back up into the esophagus. But if the LES is malfunctioning, as it is in GERD, acid from the stomach gets back into the esophagus and damages its delicate lining. Unlike the stomach, the lining of the esophagus has no protection against acid. So, the question researchers and doctors should have been asking is, “what is causing the LES to malfunction?” rather than “how to reduce stomach acid secretion”.
  • Increased Intra-Abdominal Pressure: Acid reflux occurs when pressure causes gastric distention (stomach bloating) that pushes the stomach contents, including acid, through the LES into the esophagus. According to current thought, factors contributing to this include overeating, obesity, bending over after eating, lying down after eating, and consuming spicy or fatty foods. In his excellent book, Heartburn Cured, microbiologist Dr. Norm Robillard argues that carbohydrate malabsorption leads to bacterial overgrowth, resulting in IAP which drives reflux. But a question arises: What might be causing the carbohydrate malabsorption in the first place, and are there any other causes of bacterial overgrowth that may precede carbohydrate malabsorption?

The answer may be:

# Low Stomach Acid Causes Bacterial Overgrowth: One of the chief roles of stomach acid is to inhibit bacterial overgrowth. At a pH of 3 or less (the normal pH of the stomach), most bacteria can’t survive for more than 15 minutes. But when stomach acid is insufficient and the pH of the stomach rises above 5, bacteria begin to thrive.

Wait a minute??? That means may be, Helicobacter Pylori infection, which can cause gastritis (inflammation of the lining of the stomach), peptic ulcer disease or stomach cancer is due to low stomach acid!!!

Helicobacter Pylori: Friend or foe?

The present doctrine is basically that “the only good H. pylori is a dead H. pylori”. Although it is clear that H. pylori colonization is associated with peptic ulcers, gastric adenocarcinoma and gastric lymphoma (aka maltoma), there is evidence that it also is an “ancient dominion organism”, because it is present in nearly 50% of the world’s population. All mammals have a specific species of helicobacter and these organisms may be essential for proper maturation of the gut immune system. Helicobacter pylori may be harmful to a small subset of patients, but that there is enough evidence to suggest that it is also beneficial. Infection with H. pylori is asymptomatic in approximately 85% of individuals, while 15% develop symptomatic peptic ulcer disease, and less than 1% go on to develop gastric cancer. Research speaks to this organism’s role in prevention of reflux, Barrett’s esophagus and esophageal adenocarcinoma; asthma, eczema and rhinitis; laryngeal carcinoma; celiac disease; Crohn’s disease (Link) (Link) (Link) (Link) (Link) and possibly obesity. These observations suggest that H. pylori may also have a protective effect against the development of autoimmune disease. Epidemiological studies suggest a protective benefit of H. pylori infection against the development of inflammatory bowel disease (IBD). It may also protect against fatal cardiovascular events.

Helicobacter pylori does not behave as a classical bacterial pathogen: disease is not solely mediated by production of toxins. Instead, disease seems to result from a complex interaction between the bacterium, the host, and the environment. This teaches us to look more deeply at our resident microbiome and the complexity of its interactions, both in this complex population and within our own tissues, to gain a better understanding of health and disease.

Helicobacter pylori is dependent on temporal hypoacidity or anacidity for its primary infection, but acidity to survive for a long time. If low stomach acid is a prerequisite to H. pylori infection, we might expect acid suppressing drugs to worsen current H. pylori infections and increase rates of infection. That’s exactly what studies suggest. Prilosec and other acid suppressing drugs increase gastritis (inflammation of the stomach) and epithelial lesions in the corpus of the stomach in people infected with H. pylori.

The connection between low stomach acid, h. pylori and acid suppressing drugs induce a nasty vicious cycle: Low Stomach Acid >>> Heartburn >>> Acid Suppressing Drugs >>> H. Pylori Infection >>> Further Reduction of Stomach Acid >>> Chronic Heartburn & GERD

If we look at H. pylori as a good bacterium with bad side effects as opposed to a bad bacterium with good side effects, perhaps we can gain something from this bug.

# Low Stomach Acid Causes Maldigestion Of Carbohydrates: Stomach acid (HCL) supports the digestion and absorption of carbohydrates by stimulating the release of pancreatic enzymes into the small intestine. If the pH of the stomach is too high (due to insufficient stomach acid), the pancreatic enzymes will not be secreted and the carbohydrates will not be broken down properly.

# Bacterial Overgrowth + Maldigested Carbohydrates = Gas!

To summarize, low stomach acid contributes to bacterial overgrowth in the bowel which in turn can lead to carbohydrate malabsorption (due to decreased pancreatic enzyme secretion) which increases intra-abdominal pressure and causes GERD.

So, treating low stomach acid (the main cause of Heartburn and GERD) with acid stopping drugs is like giving alcohol to an alcoholic to cure alcoholism!!!

Why Acid Stopping Drugs to Treat Heartburn and GERD are Useless?

Acid stopping drugs promote bacterial overgrowth, weaken our resistance to infection, reduce absorption of essential nutrients, and increase the likelihood of developing IBS, other digestive disorders, and cancer.

Antacids have a quick but not sustainable effect on acid‐related symptoms. Histamine‐2‐receptor antagonists (H2RAs) inhibit gastric acid secretion, but their effects may diminish over time (and they do not block the stimulatory effects of other hormones on acid secretion). To inhibit gastric acid secretion more powerfully, the proton pump inhibitors (PPIs) were developed.

Proton pump inhibitors (Omeprazole, Lansoprazole, Esomeprazole, Pantoprazole, and Rabeprazole) are one of the most prescribed class of drugs today and are used mainly for acid-related conditions such as gastroesophageal reflux disease and peptic ulcer, but they are also frequently prescribed for management of dyspepsia, as part of Helicobacter pylori eradication therapy, and for prevention of peptic ulcer bleeding in high-risk patients on aspirin and/or non-steroidal anti-inflammatory drugs. Unfortunately, numerous studies in Western populations have documented prevalent PPI prescription and use without evidence-based indication; hence, in many populations, patients without indication may be the largest group of users.

By the way, PPIs are generally supposed to be taken for two to eight weeks, depending on the condition being treated. The U.S. Food and Drug Administration states that over-the-counter PPIs should only be taken for a single 14-day treatment up to 3 times a year, but not more often than every 4 months. Doctors are aware of this, but most patients continue to take these drugs on a permanent basis.

A single dose of PPIs can inhibit acid production by about 90% for 24 hours, according to the textbook (Medical Pharmacology and Therapeutics).

Regular Acid-Reflux Drug Use Linked to Higher Risk of Type 2 Diabetes

People who regularly use acid reflux drugs are 24% more likely to develop type 2 diabetes. Use of up to two years was linked to a 5% increased risk and for more than two years was linked to a 26% increased risk. 

Results from 3 prospective cohort studies in May 2021 found that, regular use of PPIs was associated with a higher risk of type 2 diabetes and the risk increased with longer duration of use.

Side Effects of PPIs (Omeprazole, Lansoprazole, Esomeprazole, Pantoprazole, and Rabeprazole) 

Since 2010, the FDA has issued various safety warnings regarding the potential effects of long-term use of PPIs: risk of fractures, hypomagnesemia, Clostridium difficile–associated diarrhea, vitamin B12 deficiency, acute interstitial nephritis (AIN), and cutaneous and systemic lupus erythematosus events.

Proton pump inhibitor side effects range from minor to life-threatening. The most common side effects include constipation, headache, diarrhea and vomiting.

Life-threatening infections:

Iatrogenic gastric hypo/achlorhydria due to the widely use of antisecretagous drugs as H2RBs and PPI has repeatedly been shown to increase the susceptibility to several bacterial and parasitic infections. Proton pump inhibitors (PPIs) do not have a large effect on microbial diversity of the colon, but do affect specific taxa, including Streptococcaceae and Enterococcaceae, which mediate resistance to Clostridium difficile infection (CDI), researchers report in the October issue of Gastroenterology. PPIs have correlations with an increased amount of Clostridium difficile infections, other enteric foodborne infections, and potentially increased risk of community-acquired pneumonia. While it is still unclear as to the exact mechanism for this increased infection risk, one hypothesis proposed that the decreased acidic environment of the stomach leads to bacterial overgrowth and increased risk of bacterial aspiration.

Proton pump inhibitor use is associated with increased risk of severity and mortality from coronavirus disease 2019 (COVID-19) infection.

The use of PPI moderately increases the risk of small intestinal bacterial overgrowth (SIBO), thereby highlighting the need for appropriate prescribing of PPIs.

Iron Deficiency:

PPI use is associated with lower iron status and iron deficiency, indicating impaired intestinal absorption of iron potentially related to reduced gastric acid secretion. Among patients without known risk factors for iron deficiency, gastric acid inhibitor use for ≥2 years was associated with an increased subsequent risk of iron deficiency. The risk increased with increasing potency of acid inhibition and decreased after medication discontinuation.

Low Magnesium Levels:

PPIs may result in a clinically significant decrease in serum magnesium levels with potentially harmful and even deadly effects. Hypomagnesemia is a serious complication that predisposes the patient to tetany, seizure, muscle weakness, delirium, and cardiac arrhythmias. It is not yet entirely clear what causes this adverse effect, but one hypothesis suggests that it may be due to decreased active intestinal absorption of magnesium by the transient receptor protein channels (TRPM 6/7) that are stimulated by extracellular protons.

Low vitamin B12 levels: 

PPIs can interfere with the body’s absorption of vitamin B12 from food, because stomach acid is needed to separate the vitamin from food. Taking proton pump inhibitors (PPIs) for more than two years was linked to a 65 percent increase in the risk of vitamin B-12 deficiency

Liver Damage:

Researchers have found evidence that use of proton pump inhibitors (PPIs) may cause changes to gut bacteria that can promote liver disease. They also showed a link between liver damage from alcohol abuse and use of PPIs. Cases of PPI induced liver injury with minor elevation of liver enzymes which normalized after discontinuation of PPI have been documented. Meta-analyses of existing studies suggest that use of PPIs is associated with an increased risk of Spontaneous Bacterial Peritonitis (SBP), which is a common but serious complication in patients with cirrhosis.

Cardiac Events:

A 2019 study done by US Department of Veterans Affairs found that, taking PPIs is associated with an excess of mortality due to cardiovascular disease, chronic kidney disease, and upper gastrointestinal cancer.

Risk of Stroke:

In a large cohort of more than 200,000 patients, PPI use increased the risk of first-time ischemic stroke, according to an abstract presented at the 2016 American Heart Association meeting. PPIs reduce production of nitric oxide, which promotes the dilation of blood vessels and improves blood flow. They also inhibit cellular lysosomes, which leads to aging of the blood vessel endothelial cells.

Myopathy (Muscle Weakness):

PPI use may be associated with occurrence of myopathies, including polymyositis and the serious reaction rhabdomyolysis. 

Risk of Cancer: Emerging evidence from multiple observational studies suggests long-term use of PPIs is associated with a higher risk of gastric cancer development. There is concern that use of PPIs may mask gastric cancers or other serious gastric problems. Long-term use of PPIs is associated with the development of benign polyps from fundic glands but do not cause cancer and resolve when PPIs are discontinued.

Dementia & Memory Loss: 

There is a direct association between the onset of dementia and depression on one side and the long-term use of PPIs on the other. Although the mechanism of action of the PPI use in dementia is not that clear, one of the factors can be deficiency of vitamin B12. Proton pump inhibitors (PPIs) significantly increase the risk of dementia by acting as inhibitors of ChAT, with high selectivity and unprecedented potencies that lie far below their in vivo plasma and brain concentrations. This call for restrictions for prolonged use of PPIs in elderly, and in patients with dementia or amyotrophic lateral sclerosis.

Drug-drug Interactions: 

PPI interactions can occur with at least 290 medicines. Studies have found that taking the PPI omeprazole with the blood thinner clopidogrel (Plavix) reduces the effectiveness of this blood thinner by nearly 50%. Omeprazole and esomeprazole block the enzyme CYP2C19. The enzyme is needed to activate clopidogrel. This can decrease the blood thinner’s presence in the blood. 

Taking benzodiazepines and PPIs together can lead to mental impairment,  dizziness, and loss of coordination due to the fact that, they both are metabolized by CYP450 enzymes. This leads to an interaction in which the effects of benzodiazepines are amplified – in some cases, to a dangerous degree. 

A warning added in May 2012 cautions that using certain PPIs with methotrexate, a drug commonly used to treat certain cancers and autoimmune conditions, can lead to elevated levels of methotrexate in the blood, causing toxic side effects.

Increased Risk of Developing Osteoporosis:

Long-term use of PPIs is associated with lower bone mineral content and higher rate of osteopenia/osteoporosis.The most widely assumed mechanism is that long-term PPI use leads to decreased intestinal absorption of calcium resulting in negative calcium balance, increased osteoporosis, development of secondary hyperparathyroidism, increased bone loss and increased fractures.

Increased risk of hip, wrist, and spine fractures:

Be aware that an increased risk of fractures of the hip, wrist, and spine has been reported in some studies of patients using proton pump inhibitors. The greatest increased risk for these fractures was seen in patients who receive high doses of these medications or use them longer (a year or more). A study published in JAMA (2006; 296:2947-2953) was conducted to determine whether there is an association between long-term proton pump inhibitor (PPI) therapy and the risk of hip fracture. The study concluded that long-term PPI therapy, particularly at high doses, is associated with an increased risk of hip fracture.

Kidney Damage:

Several studies have suggested an association between PPI exposure and acute interstitial nephritis. PPI-induced acute interstitial nephritis is thought to be a cell-mediated immune response that maybe idiosyncratic, and likely represents a class effect and does not seem dose-dependent. It has been reported that 30–70% of patients with acute interstitial nephritis did not fully recover renal function, likely due to rapid development of interstitial fibrosis shortly after onset of the acute inflammatory process, especially in the setting of delayed diagnosis or treatment. This incomplete recovery of renal function, possibly along with chronic interstitial nephritis, leads to CKD and potentially CKD progression and ESRD. So, PPI exposure  highly associates with increased risk of incident CKD, CKD progression, and ESRD. A study published by the US-based National Institute of Health had demonstrated how use of PPIs was independently associated with a “20–50 per cent higher risk of incident chronic kidney disease”.

According to the results of a retrospective study published in PLOS ONE, in 199 patients with CKD, 70.6% of patients who used omeprazole experienced CKD progression versus 10.5% of non-users. Moreover, there was a higher risk of progression to more severe disease in those using omeprazole. The authors noted that renal damage induced by PPI use may be caused by “the deposition of the drug and its metabolites in renal tissue, which may culminate in renal interstitial fibrosis, leading to chronicity of the lesion and onset of CKD; reduced nitric oxide synthesis, caused by inhibition of the proton pump of cell lysosomes, and thus production of highly reactive superoxide anion, which causes renal endothelial dysfunction; and hypomagnesemia, as low magnesium levels are able to increase secretion of atherogenic and inflammatory substances, producing endothelial dysfunction of the renal tissue.”

May Increase Childhood Asthma during Pregnancy:

A systematic review published in June 2017 found that children born to mothers who took acid-suppressing medications had a 1.3 times greater risk of developing asthma. PPIs also interfere with protein digestion, which may increase the number of allergens that the fetus is exposed to through the placenta. Early exposure to allergens could induce Th2 immune dominance and sensitization of the immune system.

Increased Risk of Death: 

A large scale observational cohort study of 3.5 million U.S. veterans found that PPI use was associated with a 1.23 times increased risk of death compared to non-use. Risk increased with time of use, and those who had used PPIs for over a year had a 1.5 times increased risk of death.

The Rebound Effect: 

One potential effect of PPI use is an increase in gastrin, a hormone involved in the secretion of stomach acid. That hormone surge could lead to a dangerous spike in acid if you suddenly stop taking a PPI.

So, Long-term use of PPI medications have noted potential adverse effects, including risk of fractures, pneumonia, Clostridium difficile diarrhea, hypomagnesemia, vitamin B12 deficiency, chronic kidney disease, and dementia.

Given the potential risk of diabetes and other adverse effects, clinicians should carefully balance the benefits and harms in prescribing PPIs, particularly for long-term continuous use. For patients who have to receive long-term PPI treatment, screening for abnormal blood glucose and type 2 diabetes is recommended.

Get Rid of Heartburn and GERD by following 2 simple dietary guidelines:

  • Eat all your food for the day in an 8-hour period (Time-restricted eating).
  • Eat anything ad libitum in this 8-hour window, but try to eat 50% RAW Water Rich Foods.