In a shockingly rare example of the FDA actually doing its job, a report was issued on Tuesday cautioning against the prolonged use of a class of acid stopping drugs called proton-pump inhibitors (PPIs).

Who knows, maybe someone at the FDA read my series on heartburn and GERD, especially this article and this one detailing the dangers of acid stopping drugs?

This is a really big deal. PPIs are one of the most popular classes of drugs prescribed. Doctors wrote 114 million prescriptions for them last year. Americans spend $5.1 billion on Nexium, the most popular PPI, alone.

The FDA report cautions against high doses or prolonged use of PPIs, because they’ve been shown to increase the risk of infection, bone fractures and dementia.

But the danger doesn’t stop there. As I pointed out in my series, all acid stopping drugs (not just PPIs) inhibit nutrient absorption, promote bacterial overgrowth, reduce resistance to infection and increase the risk of cancer and other serious diseases.

Don’t get me wrong – I’m glad the FDA finally issued this warning. But I can’t help wondering how someone who has been taking a PPI for 20 years is going to feel about it. If I were one of those people, I’d be incredibly angry. Especially because researchers who studied these drugs before they were approved by the FDA years ago sounded a similar warning.

In fact, when the drugs were first approved, it was recommended that they be taken for no longer than six weeks because of these same concerns the FDA is only now warning us about! Looks like someone dropped the ball on that one, because it’s not at all uncommon to encounter people who’ve been on a PPI for two decades. After writing the GERD series, I heard from several people in that group.

So please forward this article to anyone you know who has been taking one of these dangerous drugs for any longer than six weeks. And believe me, you know one of these people. We all do. You may even be one of them.

If you or a loved one wants to get off these drugs and treat GERD naturally, the the series on my blog clearly explains how to do that.

Note: this is the fifth article in a series about heartburn and GERD. If you haven’t done so already, you’ll want to read Part I, Part II, Part III, and Part IVa before reading this article.

In the last article, we discussed the first two of four primary consequences of taking acid stopping drugs:

1. Bacterial overgrowth
2. Impaired nutrient absorption

In this article we’ll cover the remaining two consequences:

3. Decreased resistance to infection
4. 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.

In fact, that’s one of it’s most important roles: to provide a two-way barrier that protects the stomach from pathogenic 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.

A stomach without much acid is in many ways a perfect environment to harbor pathogenic bacteria. It’s dark, warm, moist, and full of nutrients. 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:

• Salmonella
• Campylobacter
• Cholera
• Listeria
• Giardia
• C. Difficile

Other studies have found that acid stopping drugs also increase the risk for:

• Pneumonia
• Tuberculosis
• Typhoid
• Dysentery

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
• Allergies
• 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
• Osteoporosis
• 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.

Stomach cancer

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.

Another theory of what causes stomach cancer involves elevated concentration of nitrites in the gastric fluid. 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.

If pepsin is deficient, the proteins we eat won’t be broken down into these essential amino acid and peptide components. Since many of these essential amino acids, such as phenylalanine and tryptophan, play a crucial role in mental and behavioral health, low stomach acid may predispose people towards developing depression, anxiety or mood disorders.

Autoimmune diseases

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.

Asthma

In the last ten years, more than four hundred scientific articles concerned with the connection between asthma and gastric acidity have been published. One of the most common features of asthma, in addition to wheezing, is gastroesophageal reflux. 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.

Conclusion

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.

Chronic use of acid stopping medication dramatically reduces stomach acid, thus increasing the risk of all of these conditions. What’s more, acid suppressing medications not only do not address the underlying cause of heartburn and GERD, they make it worse.

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.

Note: this is the fourth article in a series about heartburn and GERD. If you haven’t done so already, you’ll want to read Part I, Part II and Part III before reading this article.

Believe it or not, stomach acid isn’t there just to punish you for eating Indian food. Acid is in the stomach because it’s supposed to be there. It is found in all vertebrates. And while it isn’t necessary for life, it is certainly required for health.

Most people have no idea how many vital roles stomach acid plays in our bodies. Such misunderstanding is perpetuated by drug companies who continue to insist that stomach acid is not essential. Meanwhile, millions of people around the world are taking acid suppressing drugs that not only fail to address the underlying causes of heartburn and GERD, but put them at risk of serious (and even life-threatening) conditions.

There are four primary consequences of acid stopping drugs:

1. Increased bacterial overgrowth
2. Impaired nutrient absorption
3. Decreased resistance to infection
4. Increased risk of cancer and other diseases

I had originally intended to cover all four of these issues in this article, but as I started to write I realized it would be far too long. So I will cover increased bacterial overgrowth and impaired nutrient absorption in this article, and decreased resistance to infection and increased risk of cancer and other diseases in the next article.

A stomach full of germs

We’re not going to spend much time on this here since the connection between low stomach acid and bacterial overgrowth was the focus of Part II and Part III.

To review, low stomach acid causes bacterial overgrowth in the stomach and other parts of the intestine. Bacterial overgrowth causes maldigestion of carbohydrates, which in turn produces gas. This gas increases the pressure in the stomach, causing the lower esophageal sphincter (LES) to malfunction. The malfunction of the LES allows acid from the stomach to enter the esophagus, thus producing the symptoms of heartburn and GERD.

Bacterial overgrowth has a number of other undesirable effects, including reducing nutrient absorption, increasing inflammation, and raising the risk of stomach cancer. Studies have confirmed that proton-pump inhibitors (PPIs) can profoundly alter the gastrointestinal bacterial population by suppressing stomach acid. Researchers in Italy detected small bowel bacterial overgrowth (SIBO) in 50% of patients using PPIs, compared to only 6% of healthy control subjects. The prevalence of SIBO increased after one year of treatment with PPIs.

Well-fed but undernourished

Stomach acid is a prerequisite to healthy digestion. The breakdown and absorption of nutrients occurs at an optimum rate only within a narrow range of acidity in the stomach. If there isn’t enough acid, the normal chemical reactions required to absorb nutrients is impaired. Over time this can lead to diseases such as anemia, osteoporosis, cardiovascular disease, depression, and more.

Macronutrients

Stomach acid plays a key role in the digestion of protein, carbohydrates and fat. When food is eaten, the secretion of stomach acid (HCL) triggers the production of pepsin. Pepsin is the enzyme required to digest protein. If HCL levels are depressed, so are pepsin levels. As a result, proteins don’t get broken down into their component amino acids and peptides. This can lead to a deficiency of essential amino acids, which in turn may lead to chronic depression, anxiety and insomnia.

At the same time, proteins that escape digestion by pepsin may end up in the bloodstream. Since this is not supposed to happen, the body reacts to these proteins as if they were foreign invaders, causing allergic and autoimmune responses. I’ll discuss this more below.

Micronutrients

We can eat the most nutritious diet imaginable, packed with vitamins, minerals and other essential nutrients, but if we aren’t absorbing those nutrients we won’t benefit from them.

As acid declines and the pH of the stomach increases, absorption of nutrients becomes impaired. Decades of research have confirmed that low stomach acid – whether it occurs on its own or as a result of using antacid drugs – reduces absorption of several key nutrients such as iron, B12, folate, calcium and zinc.

IRON

Iron deficiency causes chronic anemia, which means that the body’s tissues are literally starving for oxygen.

In one study, 35 of 40 people (80 percent) with chronic iron-deficiency anemia were found to have below normal acid secretion. Iron-deficiency anemia is a well-known consequence of surgical procedures that remove the regions of the stomach where acid is produced.

Researchers have found that inhibition of acid secretion by Tagamet, a popular acid stopping drug, resulted in a significant reduction of iron. At the same time, studies have shown that adding acid has improved iron absorption in patients with achlorydia (no stomach acid production).

B12

Vitamin B12 (cobalamin) is needed for normal nerve activity and brain function. B12 enters the body bound to animal-derived proteins. In order for use to absorb it, the vitamin molecules must first be separated from these proteins with the help of – you guessed it – stomach acid.

If stomach acid is low, B12 can’t be separated from its carrier proteins and thus won’t be absorbed. In one study of 359 people aged 69-79 years with serious atrophic gastritis, a disease characterized by low stomach acid, more than 50 percent had low vitamin B12 levels.

A number of studies have examined the negative effect of PPI therapy on B12 absorption. In a study on healthy subjects treated with 20 mg and 40 mg of Prilosec per day for two weeks, B12 absorption was reduced by 72% and 88% respectively.

FOLATE

Among other things, folate (folic acid) is vital for keeping the cardiovascular system healthy and for preventing certain birth defects. Low stomach acid levels can interfere with folate absorption by raising the pH in the small intestine. At the same time, when folate is given to achlorydric patients (with no stomach acid) along with an HCL supplement, absorption of the vitamin increases by 54 percent.

Both Tagamet and Zantac reduced folate absorption in another study, though the reduction in the Zantac group was not statistically significant. The overall reduction of folate absorption was sixteen percent. This modest reduction is probably not enough to harm a healthy person consuming adequate levels of folate, but it may cause problems in those with folate deficiency (relatively common) or other health problems.

CALCIUM

Calcium makes our bones and teeth strong and is responsible for hundreds, if not thousands, of other functions in our body. The importance of stomach acid in the absorption of calcium has been known since the 1960s, when one group of researchers noted that some ulcer patients were barely absorbing any calcium at all (just 2 percent). When they investigated they found that these subjects had a high gastric pH (6.5) and very little stomach acid. However, when the researchers gave them HCL supplements, lowering the pH to 1, calcium absorption rose five-fold.

ZINC

Zinc takes part in several metabolic processes related to keeping cell membranes stable, forming new bone, immune defense, night vision, and tissue growth. In one controlled trial, Tagamet treatment reduced zinc absorption by about 50 percent. Another study found that Pepcid, which raises intragastric pH to over 5, had the same effect.

Although there is little systemic research on the absorption of other nutrients, there is good reason to believe that low acid levels may also effect levels of vitamin A, vitamin E, thiamine (vitamin B1), riboflavin (vitamin B2), and niacin (vitamin B3). Theoretically, the absorption of any nutrient that is bound to protein will be inhibited (PDF).

In Part B of this article I will explain how acid stopping drugs decrease our resistance to infection and increase our risk of stomach cancer and other diseases.