Long-term use of common medications used to help alleviate heartburn have been linked to an increased risk of early death.
Did you catch that?
A recent study published in the British Medical Journal has linked the long-term use of PPI’s (proton pump inhibitors) or acid-suppressing drugs to an increased risk of early death.
In Canada, there were an estimated 4 million prescriptions written in 2010 alone. In the United States, an estimated 15 million patients were prescribed acid-suppressing medication in 2013. (1)
With the number of people taking PPIs continuing to increase, information around their safe use is more important than ever.
What are proton pump inhibitors?
PPIs or proton pump inhibitors are used to suppress the amount of acid secreted by the stomach.
PPIs are prescribed in order to treat many different varieties of stomach acid disease. The most common of which is gastroesophageal reflux disease (GERD); known more commonly as heartburn. Additional diseases that PPIs treat include:
- Peptic ulcer disease
- H-pylori infections
- Zollinger-Ellison syndrome
The stomach is full of small cells called parietal cells. These cells are part of the lining of your stomach. Your stomach contains approximately 1 billion parietal cells. (2) These cells are responsible for excreting hydrochloric acid, or, stomach acid. Proton pump inhibitors irreversibly block the hydrogen/potassium adenosine triphosphate enzyme system (H-K ATPase). (3) This stops hydrogen ions from forming stomach acid.
Taking a PPI daily for 5 days will decrease stomach acid production by 66%. (4) PPIs need to be taken with regularity in order to ensure they are effective. Taking a dose intermittently will not produce any noticeable results.
Common brands of PPI medications include:
- Omeprazole (Losec)
- Esomeprazole (Nexium)
- Lansoprazole (Prevacid)
- Olex (this is an over the counter medication)
What are the risks of taking heartburn medications?
In the short-term, the risks are minimal. And, the benefits far outweigh the potential side-effects. The problems start to compound when PPI use occurs for longer than 2 months. Long-term use of proton pump inhibitors has a lengthy list of serious side effects. Some of the more serious effects include:
- Increased risk of kidney disease
- Clostridium difficile (C-Diff) infection
- Vitamin and mineral deficiencies
- Vitamin B12
- Increased risk of osteoporosis and fractures
- Increased risk of early death
Below, I’ll tackle each of the above risks in more detail.
Chronic kidney disease (CKD) is a long-term, progressive loss of kidney function over a period of months or years. (5) In the early stages, CKD will present with no symptoms. As the disease progresses, symptoms increase in severity. Those suffering from chronic kidney disease may report fatigue, anorexia, nausea, and vomiting. (6)
PPI use has been shown to cause chronic kidney disease. (7) Unfortunately, as the early stage symptoms of CKD are often non-existent, patients often progress further into a disease state without knowing. PPI use was also shown to cause acute kidney injury (AKI) (8). AKI was often shown to precede chronic kidney disease.
At the time of this writing, how PPI use causes kidney disease is unclear. The proposed hypothesis from the quoted study is that PPI use alters the bacteria found in our digestive tract. This is thought to alter the way our body metabolizes foods. Additionally, it is thought that PPI use suppresses the kidney’s ability to heal itself. (9)
Clostridium Difficile Infection
Clostridium difficile is a toxin-producing bacteria that causes antibiotic-associated colitis. It colonizes the human intestinal tract after the normal gut flora has been altered by antibiotic therapy. (10) It is one of the more challenging bacterial infections to treat as the bacteria has adapted to be resistant to many forms of antibiotic therapy.
The hallmark symptom of c-difficile infection is watery diarrhea (>3 bowel movements/day). Other symptoms include lower abdominal pain, nausea, anorexia, and fever. (11)
One study tracked over 300,000 patients risk in developing c-diff infections after PPI use. (12) This study showed that there was a 65% increased risk of developing c-diff after using acid-suppressing medication. (13) The authors of the study strongly recommended limiting the long-term use of PPI medication. Especially in those with a history of gastrointestinal illness.
Vitamin and mineral deficiencies
PPI medication suppresses stomach acid excretion. This lowering of stomach acid can modify the bioavailability and absorption of certain vitamins and minerals. (14) Two of the more serious deficiencies include magnesium and vitamin B12.
Vitamin B12 (cobalamin) is an essential nutrient that we obtain from animal-derived food sources including meats, fish, shellfish, poultry, eggs, and dairy products. Lacto-ovo vegetarians are generally not considered to be at risk for deficiency, while true vegans may risk deficiency unless they consume supplements or vitamin B12 fortified foods. (15) B12 deficiency generally comes on slowly and without symptoms. As the B12 deficiency becomes more severe, symptoms begin to manifest. Some of the more common symptoms of B12 deficiency include weakness, fatigue, tingling or numbness in the fingers/toes, a swollen tongue, and alterations in bowel motility.
Adequate levels of stomach acid are required in order for B12 to be properly absorbed. Without stomach acid, B12 is unable to be removed from dietary proteins and absorbed. (16) Those at the greatest risk for B12 deficiency due to PPI use include the elderly and those with a condition called Zollinger-Ellison syndrome. (17,18)
Magnesium deficiency or hypomagnesemia occurs when there are low levels of magnesium circulating in the blood. Common symptoms include tiredness, generalized weakness, muscle cramps, abnormal heart rhythms, tremors, and palpitations.
A study done in 2012 confirmed that long term use of PPI medication did lower magnesium levels. (19) At the time of writing, researchers have not discovered why PPI use causes lowered magnesium levels.
Increased risk of fractures
A recent review of all the published literature on PPI use from 1970 up to 2010 revealed that there was a significant risk of fractures for those taking PPI medication. (20) There was a 30% increased risk of hip fracture and more than a 50% risk of developing a spinal fracture. (21) The increased risk of hip fracture occurred in both short (<1 year) and long-term (>1 year) use. Though, the risk increased significantly after being on the medication for greater than 5 years.
The above study found the risk of fractures to be equal amongst men and women taking PPI medication. Researchers believe that the lowered stomach acid concentration results in a lowered absorption of calcium carbonate. (22) In animal models, it has been confirmed that Omeprazole lowers calcium absorption. (23)
Increased risk of early death
The most recent study on PPI medication has shown that there is a 25% increased risk of early death. (24) In research terms, that doesn’t mean that 1 in 4 people taking PPI medication will die early. Instead, in shows that 1 in 500 people’s death will be the result of PPI use.
While that may not seem like much, consider that in the United States, PPI use increased from 3.9% of the population to 7.8% between 1999 and 2012. (25) That’s over 25 million people taking PPI medication. Which results in over 50,000 people likely to suffer an early death because of this medication.
This becomes even more alarming when studies estimate that somewhere between 53%-69% of PPI medication is prescribed for inappropriate conditions. (26, 27) These are conditions that will likely not benefit (at all) from the use of PPI medication.
The above study showed that the risk of early death increased based on the duration the PPI medication was taken for. There was no risk for those taking medication less than 30 days. The risk increased substantially for each additional month one was taking the medication. (28)
Why PPI use causes early death is still not clear. In rat models, PPI use stopped the liver from being able to regenerate. (29) New research is suggesting that PPI use alters the way our genes are able to be expressed. (30, 31) Though how these changes in gene expression contribute to early death is still not clear.
What is clear is that PPI use does increase the risk for fractures, kidney disease, vitamin/mineral deficiencies, and Clostridium difficile infections. The above are certain risk factors for early death.
Risk factors for GERD
Common risk factors that contribute to GERD include:
- Obesity (32)
- The higher your BMI, the more likely you are to develop GERD.
- Smoking (33)
- Cigarette smoking has been shown to increase the risk of GERD.
- Physical activity (34)
- Moderate physical activity and a diet high in dietary fiber are beneficial for GERD.
- Psychological stress (35)
- Psychological stress has been linked to a heightened perception of pain related to GERD.
- Sleep disturbance (36)
- GERD has shown to disturb sleep. Consequently, lack of sleep has shown to increase the symptoms of GERD.
Medical alternatives to PPI medication
A thorough investigation into the root cause of your heartburn or GERD is essential. Once the root cause is identified, it can be remedied and the continued use of PPI medication will no longer be necessary.
While the search for the root cause is underway, there are other medications that have fewer risk factors associated with them. These include histamine receptor antagonists (H2RA’s) and prokinetic medications.
Histamine receptor antagonists can provide symptomatic relief from heartburn and GERD. However, their long-term use is not recommended because the body builds up a tolerance to them. In 1-2 weeks, they are no longer useful in stopping the erosion of the esophagus from stomach acid.
Prokinetic drugs speed up the time it takes for food to move from your esophagus to your stomach and finally into your intestinal tract. This can decrease the acid build up and thus decrease the symptoms associated with GERD. Unfortunately, prokinetic medications have unfavorable side effects including tremors, fatigue, and an increased risk of cardiac events.
It is clear the medications are not the ideal solution for heartburn and GERD. In the long run, the risks certainly outweigh the proposed benefits.
Natural remedies for heartburn and GERD
At the risk of sounding redundant, I’m going to reiterate how important it is to determine the underlying or root cause of your heartburn/GERD. While the below remedies are natural, they may not get to the cause of your symptoms. Working with a knowledgeable practitioner can be invaluable in solving this problem (for good!).
The below lifestyle alterations may be helpful to those suffering from GERD. They have not been evaluated through peer-review scientific literature (yet). (37)
- Elevate the head of the bed 6 inches. Use blocks under the bed posts rather than extra pillows.
- Use of extra pillows may increase the intra-abdominal pressure. Thus, exacerbating symptoms.
- Diet and exercise to obtain a healthy weight.
- Eat smaller meals. Additionally, avoid consuming large quantities of fluids with meals.
- Avoid large meals close to bedtime.
- Avoid lying down after eating.
- Avoid foods high in saturated fats and simple sugars.
- Avoid caffeine.
- Avoid beverages containing acid (red wine, carbonated beverages, orange juice, tomato juice, citrus fruit juices).
- Increase fiber intake.
- Decrease alcohol intake.
- Avoid strong mints. These relax the lower esophageal sphincter.
- Avoid wearing tight clothing around the abdomen.
Recent research has shown that those with GERD have reduced melatonin levels. (38) Remember, melatonin is a hormone our body produces to regulate our sleep-wake cycle. Melatonin helps to synchronize our body with the light-dark cycle. It is also commonly used as a sleep-aid.
But did you also know that melatonin is important in gut motility? Melatonin has been shown to decrease stomach acid production. (39) Melatonin has also been shown to help stimulate bicarbonate excretion (this neutralizes stomach acid) which helps protect our digestive tract from excessive amounts of acid.
More surprisingly, melatonin may help prevent relaxation of the lower esophageal sphincter. The relaxation of this sphincter allows stomach acid to move up the stomach, into the esophagus – this is often the cause of GERD. (40)
Demulcent herbs are the remedy of choice for heartburn and GERD. Demulcent herbs are known to relieve both inflammation and irritation – two common symptoms of GERD. Common herbal recommendations include: (41)
- Licorice root (ensure the supplement is deglycyrrhizinated)
- Slippery elm bark
- Marshmallow root
Diet and lifestyle interventions should be the first step in treatment. If alterations do not lead to resolution of GERD symptoms, a thorough examination of the digestive tract is in order.
Now, I want to hear from you!
What have you used to cure heartburn?
Also published on Medium.