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The Dangers of “Gastric” medicine Proton Pump Inhibitors

In Malaysia, any symptoms of epigastric either epigastric pain, discomfort or symptoms of reflux and indigestion that leads to discomfort after taking food the word uses by layman are gastric. More often than not their doctors prescribe them antacids or anti-acid or acid reducing medicine under the group Proton Pump Inhibitors (PPI). PPI come with the word – suffix – pyrazole whatever their trade names. The examples of commonly prescribe are omeprazole (Prilosec), lansoprazole, pantoprazole, esomeprazole (Nexium, esomeprazole).

Many of the people especially elderly vulnerable to serious long-term and chronic adverse effect on their cells and organ systems. I have seen so many people are on these medicine for years. Some continue taking for 4 or 5 years prescribe by their doctors. Quite a number complaints of chronic degenerative symptoms due directly to long-term use of these antacids.

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.  

PPIs have become one of the most commonly prescribed classes of drugs in the industrialized world, despite increasingly frequent warnings by researchers about potential risks and complications. A 2010 study found that of 946 patients receiving PPI therapy in a hospital setting, only 35 percent were prescribed PPIs for an appropriate upper GI diagnosis.

The many roles of proton pumps in the body

 In order to understand the harmful effects associated with PPIs, it’s important to understand what they do in the body at cellular level. PPIs are inhibitors of proton pumps, specifically the proton/potassium pump of parietal cells in the stomach. The theory is that heartburn is caused by excess production of stomach acid by these cells, so inhibiting this proton pump will reduce the acidity of the stomach and prevent the burning sensation of acid reflux or the formation of peptic ulcers.

But proton pumps aren’t limited to the stomach; they are present in just about every cell in your body. All of your cells that have mitochondria that allow your body to metabolize carbohydrates and fat to produce energy (with the exception of red blood cells). They do this by pumping protons across the membrane to generate electric potential that can be harnessed to form ATP, the body’s main energy production. Without an efficient proton-pumping system, the body must rely on anaerobic systems for energy production, leading to rapid fatigue.

Proton pumps are also important in the transport of various substances in the body, as we will see in detail in later sections. And while proton pump inhibitors are designed to interact specifically with the hydrogen/potassium pump in parietal cells of the stomach, research suggests that they likely have nonspecific binding capabilities. In other words, their chemical structure enables them to bind to other proton pumps as well. Though PPIs don’t stay in the blood for very long, their binding to proton pumps is essentially irreversible—they will continue to inhibit the proton pump until the master antioxidant glutathione is able to facilitate dissociation.

PPIs can harm your heart, brain, kidneys, and gut.

PPIs alter the gut

The composition of microbes that inhabit your gut is incredibly sensitive to changes in the local environment. pH, a measure of the acidity of an environment, is an important facet of gut health and a particularly potent regulator of microbial communities. PPI use reduces the amount of acid produced in the stomach, and ultimately the amount of stomach acid that reaches the gut. This causes a significant shift in the pH of the intestines.

Indeed, several recent studies have shown that PPI alters the gut microbiota by reducing its overall diversity. Opportunistic pathogens, including Enterococcus, Streptococcus, Staphylococcus, and E. coli, tended to be more prevalent in the guts of PPI users.

As stomach pH becomes less acidic, many ingested microorganisms that would normally be destroyed are able to make their way into the gut. Those who used acid blockers also had an increased chance of acquiring Clostridium difficile, Campylobacter, Salmonella, Shigella, Listeria, and community-acquired pneumonia than those using other medications.

A 2013 study also found a significantly increased percentage of individuals with small intestinal bacterial overgrowth (SIBO) among PPI users. Together, these studies point to the vital importance of sufficient stomach acid for protecting against bacterial influx into the GI tract and maintaining an intestinal pH that supports GI health.

PPIs impair nutrient absorption

 Another consequence of long-term PPI use is impaired nutrient absorption. Stomach acid is essential for the absorption of many macro- and micronutrients. PPI users have been shown to have an increased risk of vitamin and mineral deficiencies, including vitamin B12, vitamin C, calcium, iron, and magnesium. Achlorhydria (a lack of stomach acid) and atrophic gastritis (stomach inflammation) allow for the overgrowth of bacteria, which compete with the host for consumption of micronutrients like vitamin B12..

These micronutrients are particularly important for bone health. Studies have found an association between PPI use and total bone fractures in the elderly. While the association was modest, the findings were significant enough that the FDA felt it necessary to issue a news release in 2010 warning of the possible increased fracture risk. The effects of PPIs on bone health may be more nuanced than simply causing nutrient deficiency. Osteoclasts, the bone cells responsible for the resorption of calcium, also possess proton pumps, and their activity is thought to be directly affected by PPIs.

PPIs increase the risk of cardiovascular events

 Several recent studies have also shed light on PPIs and the cardiovascular system. PPI users have been shown to have a significantly greater risk of heart attack than those on other antacid medication. PPIs also reduce production of nitric oxide, a natural substance that promotes the dilation of blood vessels and improves blood flow.

PPIs may also damage blood vessel cells, as shown by a study published in May 2016. When researchers exposed cultured human blood vessel endothelial cells to esomeprazole, the cells seemed to age much more quickly, losing their ability to split into new cells.

PPIs harm the kidneys

 The kidneys are also affected by PPIs. A study published in 2016 compared patients using PPIs to patients using H2 blockers, another common antacid drug. They showed that over the course of five years, those in the PPI group were 28 percent more likely to develop chronic kidney disease and 96 percent more likely to develop end-stage renal disease.

While the mechanism by which this occurs is unclear, we do know that proton pumps are present in the intercalated cells of the kidney. These proton pumps are responsible for moving protons into the urine, creating a gradient that allows for bicarbonate reabsorption into the blood. Bicarbonate is vitally important to maintaining proper blood pH.

PPIs negatively affect cognitive function

 PPIs also impair cognitive function. A 2016 study found that regular PPI users had a 44 percent increased risk of dementia compared with those not using the drugs. A different study published in 2015 that assessed cognitive function in PPI users versus controls found statistically significant impairment in visual memory, attention, executive function, and working and planning function among PPI users.

Several commonly prescribed PPIs, such as lansoprazole and omeprazole, have been reported to cross the blood-brain barrier. In mice, PPIs were observed to affect ?- and ?-secretase enzymes, resulting in increased levels of amyloid ?, a protein fragment that forms the plaques characteristic of Alzheimer’s disease.

Furthermore, communication between brain cells requires the action of proton pumps. Simplistically, neuron cells contain small vesicles, or pockets, of neurotransmitters. When a neuron is stimulated, the vesicle releases these neurotransmitters into the synaptic space, where they can then interact with receptors on other nearby neurons, transmitting the signal down the line. The neurotransmitters must then be taken back up by the neuron so that they can be released again in response to the next stimulus. The energy required for this reuptake process is driven by proton pumps. If PPIs bind to these proton pumps, cognitive abilities would certainly be impaired.

PPI withdrawal can lead to rebound reflux

 Your body is acutely sensitive changes in your physiology and is constantly trying to maintain a stable equilibrium, often termed homeostasis. In the case of PPIs, when it senses reduced stomach acid production, your body produces the hormone gastrin to try to compensate. Gastrin normally stimulates gastric (stomach) acid production. Parietal cells undergo hypertrophy, or an expansion in the size of each cell with PPIs use, once PPI stop there will be rebound of symptoms.

Larger parietal cells have more proton pumps and can produce larger amounts of stomach acid. This is termed “rebound hypersecretion,” or an overproduction of stomach acid after taking PPIs. This is why getting off PPI therapy is so difficult, because long-term use fundamentally changes the physiology of stomach cells. It also points to yet another instance where simply treating the symptoms of a condition fails to recognize and treat the underlying root cause.

Stomach acid is the basis of natural physiology

 Now I’d like to hear from you. Have you taken PPIs? Did you know about the long-term dangers? Did you notice improvement in your acid reflux by switching to a Paleo diet or reducing your carbohydrate intake? Share your experience in the comments section!

Acid in the stomach is supposed to be there. 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. Proton pumps inhibitor drugs were created with sale of USD2 million per minute all over the world!

Meanwhile, millions of people around the world are taking acid suppressing drugs that not only fail to address the underlying causes of heartburn and Gastro-esophageal reflux disease (GERD), but put them at risk of serious (and even life-threatening) conditions. It cost your health so much, let see how.

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

A stomach full of germs

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 found out 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 is co-factor for no less than 200 enzymes and takes part in 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 intra-gastric 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.

References