In the last article, we discussed the first two of four primary consequences of taking acid stopping drugs:
- Bacterial overgrowth
- Impaired nutrient absorption
In this article we’ll cover the remaining two consequences:
- Decreased resistance to infection
- Increased risk of cancer and other diseases
Our first line of defense
The mouth, esophagus and intestines are home to between 400-1,000 species of bacteria. However, a healthy stomach is normally almost completely sterile. Why? Because stomach acid kills bacteria.
First, stomach acid prevents harmful bacteria that may be present in the food or liquid we consume or the air we breathe from entering the intestine. At the same time, stomach acid also prevents normal bacteria from the intestines to move into the stomach and esophagus, where they could cause problems.
The low pH (high acid) environment of the stomach is one of the major non-specific defense mechanisms of the body. When the pH of the stomach is 3 or lower, the normal between-meal “resting” level, bacteria don’t last more than fifteen minutes. But as the pH rises to 5 or more, many bacterial species can avoid the acid treatment and begin to thrive.
Unfortunately, this is exactly what happens when you take acid stopping drugs. Both Tagamet and Zantac significantly raise the pH of the stomach from about 1 to 2 before treatment to 5.5 to 6.5 after, respectively.
Prilosec and other PPIs are even worse. Just one of these pills is capable of reducing stomach acid secretion by 90 to 95 percent for the better part of a day. Taking higher or more frequent doses of PPIs, as is often recommended, produces a state of achlorydia (virtually no stomach acid). In a study of ten healthy men aged 22 to 55 years, a 20 or 40 mg dose of Prilosec reduced stomach acid levels to near-zero.
Most of the time these bacteria won’t kill us – at least not right away. But some of them can. People who have a gastric pH high enough to promote bacterial overgrowth are more vulnerable to serious bacterial infections.
A recent systematic review of gastric acid-suppressive drugs suggested that they do in fact increase susceptibility to infections (PDF). The author found evidence that using acid stopping drugs can increase your chances of contracting the following nasty bugs:
- C. Difficile
Other studies have found that acid stopping drugs also increase the risk for:
Not only do acid stopping drugs increase our susceptibility to infection, they weaken our immune system’s ability to fight off infections once we have them. In vitro studies have shown that PPIs impair nuetrophil function, decrease adhesion to endothelial cells, reduce bactericidal killing of microbes, and inhibit neutrophil phagocytosis and phagolysosome acidification.
A gateway to other serious diseases
As we discussed in the first article in this series, a decline in acid secretion with age has been well documented. As recently as 1996, a British physician noted that age-related stomach acid decline is due to a loss of the cells that produce the acid. This condition is called atrophic gastritis.
In particular relevance to our discussion here, atrophic gastritis (a condition where stomach acid is very low) is associated with a wide range of serious disorders that go far beyond the stomach and esophagus. These include:
- Stomach cancer
- Bronchial asthma
- Depression, anxiety, mood disorders
- Pernicious anemia
- Skin diseases, including forms of acne, dermatitis, eczema, and urticaria
- Gall bladder disease (gallstones)
- Autoimmune diseases, such as Rheumatoid arthritis and Graves disease
- Irritable bowel syndrome (IBS), Crohn’s disease (CD), Ulcerative colitis (UC)
- Chronic hepatitis
- Type 1 diabetes
And let’s not forget that low stomach acid can cause heartburn and GERD!
In the interest of keeping this article from becoming a book, I’m going to focus on just a few of the disorders on the list above.
Atrophic gastritis is a major risk factor for stomach cancer. H. pylori is the leading cause of atrophic gastritis. Acid suppressing drugs worsen H. pylori infections and increase rates of infection.
Therefore, it’s not a huge leap to suspect that acid suppressing drugs increase the risk of stomach cancer in those infected with H. pylori (which, as we saw in Part III, is one in two people).
In a recent editorial, Julie Parsonnet, M.D. of Standford University Medical School writes:
In principle, current [acid suppressing drug] therapies might be advancing the cancer clock by converting relatively benign gastric inflammation into a more destructive, premalignant process.
One way PPIs increase the risk of cancer is by inducing hypergastrinemia, a condition of above-normal secretion of the hormone gastrin. This is a potentially serious condition that has been linked to adenocarcinoma – a form of stomach cancer.
Taking a standard 20 mg daily dose of Prilosec typically results in up to a three-to-fourfold increase in gastrin levels. In people whose heartburn fails to respond to the standard dose, long-term treatment with doses as high as 40 or 60 mg has produced gastrin levels as much as tenfold above normal.
In a healthy stomach, ascorbic acid (vitamin C) removes nitrite from gastric juice by converting it to nitric oxide. However, this process is dependent upon the pH of the stomach being less than 4. As I discussed earlier in this article, most common acid stopping medications have no trouble increasing the pH of the stomach to 6 or even higher.
Therefore, it’s entirely plausible that acid stopping medications increase the risk of stomach cancer by at least two distinct mechanisms.
Gastric and duodenal ulcers
An estimated 90% of duodenal (intestinal) and 65% of gastric ulcers are caused by H. pylori. It is also recognized that the initial H. pylori infection probably only takes place when the acidity of the stomach is decreased. In a human inoculation experiment, infection could not be established unless the pH of the stomach was raised (thus lowering the acidity) by use of histamine antagonists.
By lowering stomach acid and increasing stomach pH, acid suppressing drugs increase the risk of H. pylori infection and subsequent development of duodenal or gastric ulcers.
Irritable bowel syndrome, Crohn’s disease and ulcerative colitis
Adenosine is a key mediator of inflammation in the digestive tract, and high extracellular levels of adenosine suppress and resolve chronic inflammation in both Crohn’s disease and ulcerative colitis. Chronic use of PPIs has been shown to decrease extracellular concentration of adenosine, resulting in an increase in inflammation in the digestive tract. Therefore, it is possible that long-term use of acid stopping medications may predispose people to developing serious inflammatory bowel disorders.
It has become increasingly well established that irritable bowel syndrome (IBS) is caused at least in part by small bowel bacterial overgrowth (SIBO). It is also well known that acid suppressing drugs contribute to bacterial overgrowth, as I explained in Part II and Part III. It makes perfect sense, then, that chronic use of acid suppressing drugs could contribute to the development of IBS in those that didn’t previously have it, and worsen the condition in those already affected.
Depression, anxiety and mood disorders
While there is no specific research (that I am aware of) linking acid suppressing drugs to depression or mood disorders, a basic understanding of the relationship between protein digestion and mental health suggests that there may be a connection.
During the ingestion of food stomach acid secretion triggers the release of pepsin. Pepsin is the enzyme responsible for breaking down protein into its component amino acids and peptides (two or more linked amino acids). Essential amino acids are called “essential” because we cannot manufacture them in our bodies. We must get them from food.
Low stomach acid and consequent bacterial overgrowth cause the intestine to become permeable, allowing undigested proteins to find their way into the bloodstream. This condition is often referred to as “leaky gut syndrome”. Salzman and colleagues have shown that both transcellular and paracellular intestinal permeability are substantially increased in atrophic gastritis sufferers compared to control patients.
When undigested proteins end up in the bloodstream, they are considered as “foreign” by the immune system. The resulting immune response is similar to what happens when the body mobilizes its defenses (i.e. T cells, B cells and antibodies) to eradicate a viral or bacterial infection.
This type of immune response against proteins we eat contributes to food allergies. A similar mechanism that is not fully understood predisposes people with a leaky gut to develop more serious autoimmune disorders such as lupus, rheumatoid arthritis, type 1 diabetes, Graves disease, and inflammatory bowel disorders like Crohn’s and ulcerative colitis.
The connection between rheumatoid arthritis (RA) and low stomach acid in particular has been well established in the literature. Examining the stomach contents of 45 RA patients, Swedish researchers found that 16 (36 percent) had virtually no stomach acid. Those people who had suffered from RA the longest had the least acid. A group of Italian researchers also found that people with RA have an extremely high rate of atrophic gastritis associated with low stomach acid when compared with normal individuals.
It is estimated that between up to 80 percent of people with asthma also have GERD. Compared with healthy people, those with asthma also have significantly more reflux episodes and more acid-induced irritation of their esophageal lining.
When acid gets into the windpipe, there is a tenfold drop in the ability of the lungs to take in and breathe out air. Physicians who are aware of this association have begun prescribing acid stopping drugs to asthma patients suffering from GERD. While these drugs may provide temporary symptomatic relief, they do not address the underlying cause of the LES dysfunction that permitted acid into the esophagus in the first place.
In fact, there is every reason to believe that acid suppressing drugs make the underlying problem (too little stomach acid and overgrowth of bacteria) worse, thus perpetuating and exacerbating the condition.
As we have seen in the previous articles in the series, heartburn and GERD are caused by too little – and not too much – stomach acid. Unfortunately, insufficient stomach acid is also associated with bacterial overgrowth, impaired nutrient absorption, decreased resistance to infection, and increased risk of stomach cancer, ulcers, IBS and other digestive disorders, depression and mood disorders, autoimmune disease, and asthma.
Is the temporary symptom relief these drugs provide worth the risk? That’s something only you can decide. I hope the information I’ve provided here can help you make an educated decision.
In the next and final article of the series, I will present a plan for getting rid of heartburn and GERD once and for all without drugs.