20.4.

2011 The Connection Between GERD and A…

Continue reading →" />

Digestive Health Institute

Your Resource for Digestive Health
I ssues

The Connection Between GERD and Asthma

Posted on August 7, 2010 by Norm Robillard, PhD.

After reading a recent CNN article called “Burgers Hinder Breathing” Linking fast food to asthma, I
commented that I believe the link between fast food and asthma is no different than the link between acid
reflux and asthma. I went on to explain my research findings on the cause of GERD and how GERD,
carbohydrates and asthma may be linked. After several requests, I agreed to publish an excerpt from my
upcoming book Fast Tract Digestion to provide more details on the connection between GERD, carbohydrate
malabsorption and asthma.

On the surface, GERD and asthma appear to be quite separate conditions with little in common. Asthma is a
chronic inflammatory lung disease that causes narrowing of the airways, affecting over 20 million people in
the US including up to 6 million children. Symptoms include: wheezing, coughing, difficulty breathing,
tightness in the chest and flare-ups associated with allergic reactions or following exercise. The exact cause of
asthma is unknown, but both genetic and environmental factors are involved. Flare-ups of asthma appear to be
allergic in nature as most people with asthma have specific allergies. Allergens that can trigger attacks include
cat or dog dander, dust mites, cockroaches, mold and other irritants like cigarette smoke. Asthma diagnosis is
made based on a physical exam, breathing tests and a review of one’s medical history.

GERD, which stands for gastroesophageal reflux disease, is a chronic condition caused by the repeated
refluxing of stomach contents into the esophagus. Approximately sixty million people in the US suffer with
GERD symptoms. The most common symptom is heartburn, described as a burning sensation behind the
breastbone. Other GERD symptoms include abdominal pain, cough, sour taste, sore throat, hoarseness,
laryngitis, asthma like symptoms (one sign of a possible link) and sinus irritation. Smoking, pregnancy,
obesity, hiatal hernia and tight fitting clothes can make symptoms worse.

During acid reflux, the group of muscles at the top of the stomach, called the lower esophageal sphincter or
LES, are unable to keep the stomach’s contents from entering the esophagus. The esophagus is not protected
by the same mucous layer that coats the inside of the stomach. The result is painful damage to the esophagus.
Diagnosis of GERD is generally accomplished by a doctor reviewing a patient’s symptom history in detail
including frequency of heartburn, and related symptoms. If diagnostic tests are required, they may include
upper gastrointestinal endoscopy that allows your doctor to look at the lining of your esophagus, stomach and
first part of your small intestine using a miniature camera. Damage or irritation to the lining of the esophagus
is a common hallmark of GERD. If symptoms persist, additional tests may include manometry to measure how
tightly your LES closes as well as 24 hour pH monitoring to measure how much acid is leaking into your
esophagus and how long it remains there.

For some time a connection between asthma and GERD has been recognized but the reason for the connection
has remained a mystery. As many as 80 percent of asthmatics suffer from abnormal gastroesophageal reflux
compared to about 20 – 30 percent of non asthmatics (1). Some asthmatics have GERD with classic symptoms
digestivehealthinstitute.org/…/the-co… 1/10
20.4.2011 The Connection Between GERD and A…
while others shown to have GERD by pH monitoring don’t have classic symptoms and are considered to have
“silent GERD”(3). A better understanding of the underlying cause of GERD may shed more light on the
connection between GERD and asthma.

What is the true cause of GERD?

As a GERD sufferer myself, I was surprised to find that my symptoms disappeared when I started a
carbohydrate restricted diet. I wondered if carbohydrates somehow caused GERD symptoms and if so, how? I
reviewed the leading theory suggesting that certain (trigger) foods, caffeine, or alcohol could relax or weaken
the LES muscles and trigger reflux. This concept did not make sense to me and didn’t seem to fit the facts. As I
tried to understand how carbohydrates might trigger GERD symptoms, I came up with an idea. If some
carbohydrates were not fully digested and absorbed in the small intestine, they would be available as food for
intestinal bacteria through a process called fermentation. Could bacteria, malabsorbed carbohydrates and
fermentation be causing GERD and perhaps even asthma?

Bacteria in our gut

The human large intestine contains over 100 trillion microbes belonging to more than 50 genera and over 500
species. These organisms live on nutrients from our diet that we are unable to digest, and in exchange, produce
some vitamins and other nutrients that nourish our own cells. Microbes allow us to use food about 30 percent
more efficiently and also compete with disease causing germs that might otherwise gain a foothold making us
ill. Bacteria outnumber other intestinal microbes by far though some protozoa, fungi and other tiny creatures
reside here as well.

While a large diverse population of bacteria is healthy in the large intestine, relatively few bacteria should be
present in our small intestine where our own critical nutrient absorption takes place. Normally, the numbers
range from zero in the stomach and first part of the small intestine to about one million bacteria per milliliter
(mL) in the last part of the small intestine where the large intestine begins. One million bacterial cells is
actually a very small amount compared to the trillions in the large intestine. The number of bacteria in the
upper digestive system is controlled by the constant movement of food, acid produced by the stomach, bile,
intestinal immunity and the production of mucin that make it difficult for bacteria to adhere to the intestinal
surface. Importantly, our efficient digestive process normally limits the amount of nutrients available for
bacterial growth. When this balance is disrupted, resident bacteria can rapidly overgrow in the small intestine.
The term Small Intestinal Bacterial Overgrowth, or SIBO, refers to bacteria, mostly from the large intestine,
invading and overpopulating the small intestine. SIBO is defined as having greater than 100,000 bacteria per
milliliter in the upper part of the small intestine. Despite the many defenses the body has to prevent
overgrowth, SIBO is common and continues to be linked to a growing number of disorders such as irritable
bowel syndrome (IBS), Crohn’s and celiac disease and cystic fibrosis.

When SIBO occurs, normally harmless bacteria overgrow and produce lots of gas (carbon dioxide, hydrogen
and methane). If too much gas is produced but not dissipated by intestinal absorption or metabolism by gas
consuming bacteria, it can create pressure in the small intestine and stomach that actually drives the reflux of
stomach contents past the LES into the esophagus. People with weakened or defective LES muscles will be
more susceptible to reflux because less gas pressure will be required to push open the LES.

digestivehealthinstitute.org/…/the-co… 2/10
20.4.2011 The Connection Between GERD and A…
Can fermentation create enough gas pressure to cause acid reflux? I believe it can. Years ago, as a research
scientist, I routinely grew bacterial cultures often working with intestinal strains of bacteria. The growth
media contained carbohydrate (typically glucose) because gut bacteria prefer to consume carbohydrates for
energy. I was amazed at the amount of gas that most strains could produce. As little as thirty grams (the
weight of six nickels) of carbohydrate can give rise to ten liters of hydrogen gas. So much (flammable) gas can
be produced by intestinal bacteria that there have been well documented cases of explosions during intestinal
surgery (4,5).

The following nine points of evidence convinced me that carbohydrate malabsorption coupled with SIBO may
be the ultimate cause acid reflux and perhaps a factor in asthma:

Management of dietary carbohydrates improves GERD symptoms and reduces esophageal acid exposure.
(6,7,8). I believe reducing carbs is an effective treatment because intestinal bacteria are denied fuel which
limits their growth and ability to produce gas.
Treatment of GERD patients with the antibiotic erythromycin decreases gastro esophageal reflux and
increases apparent LES pressure (9,10). The authors suggested that erythromycin had increased the lower
esophageal sphincter (LES) pressure in the GERD patients. But how can an antibiotic tighten these
muscles? LES pressure is measured by inserting a tube through the LES that detects how tightly the LES
closes. In this case the LES appeared be closing more tightly after treatment with erythromycin. Possibly,
the authors failed to recognize the growth inhibiting effect of erythromycin on intestinal bacteria and how
that would limit reflux causing gas. What appears to the authors as “strengthening the defective LES in
GERD patients” is, in my opinion, a decrease in intragastric (stomach) gas pressure because erythromycin
is inhibiting the intestinal microbes that were producing the gas in the first place. The LES appears to
exhibit increased pressure but the effect is actually caused by a decrease in intragastric pressure that no
longer pushes as hard on the LES.
Consumption of the carbohydrate fructose oligosaccharide (FOS), which is indigestible by humans, but
fermented by gut bacteria produces intestinal gas and increases the number of reflux episodes and
symptoms of GERD (11). The authors noted an increase in something called transient lower esophageal
sphincter relaxations (TLESRs). In other words, the LES opened more as if it was relaxing. I believe these
“Lower esophageal sphincter relaxations” described by the authors actually represent the LES being
“forced” open by gas pressure. Consuming FOS ensures 100% malabsorption. The fermentation of FOS by
gut microbes makes enough gas to pressurize the small intestine and stomach and force open the LES
causing reflux and heartburn in susceptible people.
In GERD patients, reflux was associated with an increase in intra-abdominal (gas) pressure and belching
(12,13). The increase in intra-abdominal gas pressure and belching is consistent with the idea that gas
produced in the small intestine from carbohydrate fermentation can create gas pressure in the stomach
and cause belching as the gas escapes into the esophagus. The only difference between belching and acid
reflux is that the gas pushes stomach contents into the esophagus in the later case and escapes on its own
in the former.
Cystic fibrosis (CF) patients have a very high (up to 80%) prevalence for GERD and exhibit well
documented carbohydrate malabsorption and bacterial overgrowth associated with pancreatic digestive
enzyme deficiency due to blockage of pancreatic ducts with thick mucus (14,15,16). After studying the
connection between GERD and CF as well as the details of carbohydrate malabsorption in CF, I am
convinced that pancreatic enzyme insufficiency leads to malabsorption, SIBO and the GERD related
symptoms so prevalent in cystic patients.
digestivehealthinstitute.org/…/the-co… 3/10
20.4.2011 The Connection Between GERD and A…
The prevalence of GERD in IBS patients (39%) and IBS in GERD patients (49%) is much higher than the
prevalence of GERD (19%) or IBS (12%) in the general population indicating a relationship between the two
conditions (17). IBS has been clearly linked to small intestinal bacterial overgrowth via hydrogen breath
testing and, like GERD, has been treated successfully with carbohydrate restriction as well as antibiotics
(18,19,20,21,22). This evidence is consistent with SIBO playing a role in both conditions.
Half of GERD patients taking PPI drugs showed evidence of SIBO by glucose breath testing compared to
only 25% of IBS patients not taking PPIs. Eighty-seven to ninety percent of SIBO-positive patients (with
GERD or IBS) showed improvement after antibiotic treatment (23). I believe the SIBO-positive results in
both groups would have been higher if the study employed the lactulose breath test instead of the glucose
breath test. Lactulose is not digested or absorbed in the small intestine and can detect bacteria (fermenting
the lactulose and producing hydrogen) throughout the entire length of the small intestine. Glucose is
rapidly absorbed in the first part of the small intestine and will only detect bacteria if they are present in
this region. Dr. Pimentel found that 78 percent of IBS patients tested at the Cedars-Sinai Medical Center
had SIBO as indicated by a positive lactulose breath test (18).
GERD is associated with obesity and carbohydrate restriction improved symptoms and reduced esophageal
acid exposure in obese patients regardless of weight loss (24,25,26). Obese people consume more food,
especially carbohydrates, which I believe can lead to “volume based” malabsorption causing SIBO and
reflux.
A significant number of GERD patients report new symptoms following fundoplication surgery that include
excessive gas (abdominal gas and flatulence), bloating, diarrhea and abdominal pain (27, 28,29). The
procedure is aimed at preventing reflux, but the side effects are indicative of trapped stomach and
intestinal gas as would be expected with malabsorption and SIBO.

Current treatments for GERD

Standard treatment of GERD falls into three basic categories: acid reducing medications, surgery and dietary
changes. Medications in order of increasing potency include antacids, such as Tums, Rolaids, Gaviscon and
Maalox, histamine antagonists (H2 antagonists) such as famotidine (Pepcid), cimetidine (Tagamet),
nizatidine (Axid), and ranitadine (Zantac), and prescription strength proton pump inhibitors (PPIs) such as
esomeprazole (Nexium), omeprazole (Prilosec and Zegerid), lansoprazole (Prevacid), pantoprazole (Protonix)
and rabeprazole (Aciphex). Antacids neutralize stomach acid while H2 antagonists and PPI drugs block the
production of acid by specialized parietal cells that line the stomach. The less potent H2 antagonists, widely
available over the counter, are used to treat milder reflux symptoms while PPIs are often prescribed for more
severe symptoms. One PPI drug, omeprazole (Prilosec and Zegerid) is now available over the counter without a
prescription. Potent PPI drugs are intended for short term use but since they don’t correct the underlying
cause of the GERD, people end up taking these drugs permanently. With so many people taking acid reducing
drugs long term, several studies have looked more closely at the side effects associated with long term acid
suppression.

Acid reducing medications significantly reduce the amount of acid in one’s stomach. Thus, if stomach contents
escape into the esophagus, much of the burning and damage from acid will be reduced. While this approach
can be effective at controlling heartburn symptoms, acid reducing drugs are increasingly being linked to side
effects and long term health risks. Because these drugs neutralize stomach acid, the absorption of vitamins,
minerals and nutrients can be negatively affected (30,31). According to a study conducted in the United
Kingdom and published in the Journal of the American Medical Association (JAMA), the long term use of PPIs
digestivehealthinstitute.org/…/the-co… 4/10
20.4.2011 The Connection Between GERD and A…
can also lead to weakened bones and more fractures (32). The authors suggest that the increase risk of facture
may be due to PPIs interfering with calcium absorption. Calcium is absorbed efficiently only when the stomach
is acidic. It makes sense that PPI drugs like Nexium neutralize your stomach acid making it difficult for your
body to absorb enough calcium to keep your bones strong. A separate Canadian study confirmed the findings
(33).

Another problem with acid reducing medicines is the loss of stomach acid allows bacteria to more easily
colonize the stomach and small intestine leading to deconjugation of bile acids which are needed for fat
digestion as well as their antibacterial properties (34,35,36,37,38).

And what about the widespread reports of a PPI induced rebound effect? Many people indicate that their
symptoms become worse when they stop taking PPI drugs effectively keeping them addicted to the drugs. This
phenomenon has been studied in people with GERD (39), but even more interestingly, the rebound effect was
evident in healthy people (without GERD) who were given PPI drugs (40). The authors suggest that a
phenomenon called drug induced “rebound acid hypersecretion” (RAHS) may be responsible, but I wonder if
there is more to this picture. We know that PPI drugs block the production of stomach acid which allows
bacteria an opportunity to grow and produce reflux causing gas. If this were the case, PPI drugs might actually
perpetuate the problem they are supposed to resolve because of PPI-induced SIBO.

The connection between gut and lungs

Normally, stomach acid forms a barrier between bacteria in your intestines and your esophagus, lungs and
sinuses because bacteria are killed by stomach acid. Acid reflux can surpass this protective mechanism,
especially if stomach acid is neutralized. When acid neutralizing drugs are used (PPIs, H2 blockers and even
antacids), bacteria from the intestines are more likely to overgrow and survive in the small intestine and
stomach. Reflux can cause these bacteria to enter the esophagus and potentially the lungs and sinuses. People
on acid blocking meds are more susceptible to respiratory infections most likely from bacteria originating in
their own intestines.

This connection has been proven in a large study linking acid reducing medications to pneumonia. A study of
more than 364,000 people led by Robert J.F. Laheij at the University Medical Center St. Radboud in Nijmegen
, the Netherlands , found that the risk of pneumonia was almost double for people taking proton-pump
inhibitors for prolonged periods compared to people not taking such drugs (41). The increased risk of
respiratory infection was also seen in children taking acid reducing medication (42).

As further proof of the connection between reflux and lung problems, Belgium researchers found that the
potent antibiotic azithromycin reduced gastroesophageal reflux as well as esophageal acid exposure and the
concentration of bile acids in fluid removed from the lungs of lung transplant patients (43). Similar to the
erythromycin studies cited above, the authors did not consider that the profound effect might be due to the
antibiotic treatment inhibiting gut microorganisms. In this case, stomach acid and bile were being refluxed
not only into the esophagus, but directly into the lungs. Azithromycin treatment helped prevent reflux into the
esophagus and lungs likely via its effect on SIBO inhibition. The results were quite beneficial for the patients.

Asthma and GERD

digestivehealthinstitute.org/…/the-co… 5/10
20.4.2011 The Connection Between GERD and A…
In an attempt to understand the connection between GERD and asthma, large multicenter studies were
conducted to determine if treatment of GERD with potent PPI drugs would reduce asthma symptoms and
improve lung function in poorly controlled asthmatics that had GERD or silent GERD. Studies with the PPI
drugs lansoprazole and esomeprazole were conducted to determine if the treatment of GERD with these drugs
would have a positive impact on asthma. In each case, the drugs did not improve asthma symptoms or lung
function (44,45).

The study employing esomeprazole (Nexium), called the SARA study (for study of acid reflux and asthma),
concluded that “gastroesophageal reflux is not a likely cause of poorly controlled asthma”. The authors
reasoning was that Nexium “treated the GERD” and the asthma did not improve, therefore GERD can’t be a
cause of asthma. It should come as no surprise that I disagree with this conclusion and find myself surprised
that no one caught the flaw in this logic. The flaw is making the assumption that Nexium (or any other acid
reducing drug) eliminates any threat from GERD. There is no evidence I am aware of that shows that Nexium
and other PPI drugs stop reflux. The drugs simply shut down the production of stomach acid. The above
studies suggest that acid alone is not the cause of difficult to treat asthma. But uncontrolled reflux ensures that
digestive enzymes, bile and bacteria continue to insult the esophagus, lungs and sinuses. One or more of these
substances may play a role in the continued exacerbation of asthma even when patients are given PPI drugs.
Prolonged use of PPI drugs may actually make things worse by blocking the production of stomach acid that
prevents gut bacteria from entering the esophagus, lungs and sinuses.

Research led by Sebastian Johnston at Emperial College London points to bacteria as one likely suspect in the
exacerbation of asthma. The team treated 278 adults diagnosed with asthma with either placebo or
telithromycin, an antibiotic used to treat bacterial pneumonia. Treatment was initiated within 24 hours after
an acute exacerbation of asthma requiring short-term medical care (46). The results of the study showed the
group treated with the antibiotic had a significant improvement in symptoms. Though the other endpoint -
peak expiratory flow in the morning at home – was not significantly different, the researchers concluded that
there was evidence of the benefit of telithromycin in patients with acute exacerbations of asthma. They also
noted that the mechanisms of benefit remain unclear. The contribution of gut bacteria via reflux appears to be
the most promising candidate to explain these findings.

What should GERD sufferers and asthmatics do?

Clearly GERD and asthma are very different and complex conditions that share a link. People undergoing
treatment for either condition should not make any immediate changes before consulting their own health
care provider. Your own health care provider may offer diagnostic tests to determine if you suffer from various
types of carbohydrate malabsoption such as lactose or fructose intolerance. Some health care providers provide
screening for SIBO itself. If your doctor suggests that you taper off PPI drugs, a low carbohydrate diet will
certainly help and may allow any underlying condition responsible for carbohydrate malabsorption to heal. I
do not recommend people with SIBO undergo antibiotic treatments without first trying to control the
overgrowth of bacteria by limiting carbohydrates. I believe the benefits of controlling SIBO and GERD by
carbohydrate restriction may extend to lessoning the symptoms and severity of asthma, but only clinical
testing can provide proof.

References

digestivehealthinstitute.org/…/the-co… 6/10
20.4.2011 The Connection Between GERD and A…
1. Sontag SJ, O’Connell S, Khandelwal S, Miller T, Nemchausky B, Schnell TG, Serlovsky R. Most asthmatics
have gastroesophageal reflux with or without bronchodilator therapy. Gastroenterology. 1990 Sep;99(3):613-
20.

2. Leggett JJ, Johnston BT, Mills M, Gamble J, Heaney LG. Prevalence of gastroesophageal reflux in difficult
asthma: relationship to asthma outcome. Chest. 2005 Apr;127(4):1227-31.

3. Parsons JP, Mastronarde JG. Gastroesophageal reflux disease and asthma. Curr Opin Pulm Med. 2010
Jan;16(1):60-3.

4. Dener IA, Demirci C. Explosion during diathermy gastrotomy in a patient with carcinoma of the antrum. Int
J Clin Pract. 2003 Oct; 57(8):737-8.

5. Bigard M-A, Gaucher P, Lassalle C. Fatal colonic explosion during colonoscopic polypectomy.
Gastroenterology 1979; 77: 1307-1310.

6. Yancy WS Jr, Provenzale D, Westman EC. Improvement of gastroesophageal reflux disease after initiation of
a low-carbohydrate diet: five brief cased reports. Altern Ther health med. 2001. Nov-Dec; 7(6):120,116-119.

7. Austin GL, Thiny MT , Westman EC, Yancy WS Jr, Shaheen NJ . A very low-carbohydrate diet improves
gastroesophageal reflux and its symptoms. Dig Dis Sci. 2006 Aug;51(8):1307-12.

8. Eades M. Protein Power. 1996 Bantam Books.

9. Pennathur A, Tran A, Cioppi M, Fayad J, Sieren GL, Little AG. Erythromycin strengthens the defective lower
esophageal sphincter in patients with gastroesophageal reflux disease. Am J Surg. 1994 Jan;167(1):169-173.

10. Pehl C, Pfeiffer A, Wendl B, Stellwag B, Kaess H. Effect of erythromycin on postprandial gastroesophageal
reflux in reflux esophagitis. Dis Esophagus. 1997 Jan;10(1):34-37.

11. Piche T, des Varannes SB, Sacher-Huvelin S, Holst JJ, Cuber JC, Galmiche JP. Colonic fermentation
influences lower esophageal sphincter function in gastroesophageal reflux disease. Gastroenterology. 2003
Apr;124(4):894-902.

12. Dodds WJ, Dent J, Hogan WK, Helm JF, Hauser R, Patel GK, Egide MS, Mechanisms of gastroesophageal
reflux in patients with reflux esophagitis. N. Engl J Med. 1982. Dec 16;307(25):1547-52.

13. Lin M, Triadafilopoulos G. Belching: dyspepsia or gastroesophageal reflux disease? Am J Gastroenterol.

2003 Oct;98(10):2139-45.

14. Ledson MJ, Tran J, Walshaw MJ. Prevalence and mechanisms of gastro-oesophageal reflux in adult cystic
fibrosis patients. J R Soc Med. 1998 Jan;91(1):7-9.

15. Vic P, Tassin E, Turck D, Gottrand F, Launay V, Farriaux JP. Frequency of gastroesophageal reflux in
infants and in young children with cystic fibrosis. Arch Pediatr. 1995 Aug;2(8):742-6.

16. Fridge JL, Conrad C, Gerson L, Castillo RO, Cox K. Risk factors for small bowel bacterial overgrowth in

digestivehealthinstitute.org/…/the-co… 7/10
20.4.2011 The Connection Between GERD and A…
cystic fibrosis. J Pediatr Gastroenterol Nutr. 2007 Feb;44(2):212-8.

17. Nastaskin I, Mehdikhani E, Conklin J, Park S, Pimentel M. Studying the overlap between IBS and GERD: a
systematic review of the literature. Dig Dis Sci. 2006. Dec;51(12):2113-20.

18. Pimentel M, Chow EJ, Lin HC. Eradication of small intestinal bacterial overgrowth reduces symptoms of
irritable bowel syndrome. Am J Gastroenterol. 2000;95:3503-6.

19. Austin GL, Dalton CB, Hu Y, Morris CB, Hankins J, Weinland SR, Westman EC, Yancy WS Jr, Drossman
DA. A very low-carbohydrate diet improves symptoms and quality of life in diarrhea-predominant irritable
bowel syndrome. Clin Gastroenterol Hepatol. 2009 Jun;7(6):706-708.

20. Majewski M, Reddymasu SC, Sostarich S, Foran P, McCallum RW. Efficacy of rifaximin, a non absorbed
oral antibiotic, in the treatment of small intestinal bacterial overgrowth. Am J Med Sci. 2007 May;333(5):266-
70.

21. Pimentel M. Review of rifaximin as treatment for SIBO and IBS. Expert Opin Investig Drugs. 2009
Mar;18(3):349-58.

22. Yang J, Lee HR, Low K, Chatterjee S, Pimentel M. Rifaximin versus other antibiotics in the primary
treatment and retreatment of bacterial overgrowth in IBS. Dig Dis Sci. 2008 Jan;53(1):169-74.

23. Lombardo L, Foti M, Ruggia O, Chiecchio A. Increased incidence of small intestinal bacterial overgrowth
during proton pump inhibitor therapy. Clin Gastroenterol Hepatol. 2010 Jun;8(6):504-8.

24. Hagen J, Deitel M, Khanna RK, Ilves R. Gastroesophageal reflux in the massively obese. Int. Surg. 1987
Jan-Mar;72(1):1-3.

25. Fisher BL, Pennathur A, Mutnick JL, Little AG. Obesity correlates with gastroesophageal reflux. Dig Dis
Sci. 1999 Nov;44(11):2290-4.

26. Austin GL, Thiny MT , Westman EC, Yancy WS Jr, Shaheen NJ . A very low-carbohydrate diet improves
gastroesophageal reflux and its symptoms. Dig Dis Sci. 2006 Aug;51(8):1307-12.

27. Vakil N, Shaw M, Kirby R. Clinical effectiveness of laparoscopic fundoplication in a US community. Am J

Med. 2003 Jan;114(1):1-5.

28. Klaus A, Hinder RA, DeVault KR, Achem SR. Bowel dysfunction after laparoscopic anti reflux surgery:
incidence, severity, and clinical course. Am J Med. 2003 Jan;114(1):6-9.

29. Beldi G, Gláttli A. Long-term gastrointestinal symptoms after laparoscopic nissen fundoplication. Surg
Laparosc Endosc Percutan Tech. 2002 Oct;12(5):316-9.

30. Hirschowitz BI, Worthington J, Mohnen J. Vitamin B12 deficiency in hypersecretors during long-term acid
suppression with proton pump inhibitors. Aliment Pharmacol Ther. 2008. Jun 1;27(11):1110-21.

31. Marcuard SP, Albernaz L, Khazanie PG. Omeprazole therapy causes malabsorption of cyanocobalamin

digestivehealthinstitute.org/…/the-co… 8/10
20.4.2011 The Connection Between GERD and A…
(vitamin B12). Ann Intern Med. 1994 Feb 1;120(3):211-5.

32. Yang YX, Lewis JD, Epstein S, Metz DC . Long-term proton pump inhibitor therapy and risk of hip
fracture. JAMA. 2006 Dec 27;296(24):2947-53.

33. Targownik LE , Lix LM , Metge CJ , Prior HJ , Leung S , Leslie WD . Use of proton pump inhibitors and risk
of osteoporosis-related fractures. CMAJ. 2008 Aug 12;179(4):319-26.

34. Patel TA, Abraham P, Ashar VJ, Bhatia SJ, Anklesaria PS. Gastric bacterial overgrowth accompanies
profound acid suppression. Indian J Gastroenterol. 1995 Oct;14(4):134-6.

35. Fried M, Siegrist H, Frei R, Froehlich F, Duroux P, Thorens J, Blum A, Bille J, Gonvers JJ, Gyr C. Duodenal
bacterial overgrowth during treatment in outpatients with omeprazole. Gut 1994; 35:23-26.

36. Shindo K, Machida M, Fukumura M, Koide K, Yamazaki R. Omeprazole induces altered bile acid
metabolism. Gut. 1998 Feb;42(2):266-71.

37. Theisen J, Nehra D, Citron D, Johansson J, Hagen JA, Crookes PF, DeMeester SR, Bremner CG, DeMeester
TR, Peters JH. Suppression of gastric acid secretion in patients with gastroesophageal reflux disease results in
gastric bacterial overgrowth and deconjugation of bile acids. J Gastrointest. Surg. 2000 Jan-Feb;4(1):50-4.

38. Lombardo L, Foti M, Ruggia O, Chiecchio A. Increased incidence of small intestinal bacterial overgrowth
during Proton Pump Inhibitor therapy. Clin Gastroenterol Hepatol. 2010 Jun;8(6):504-8.

39. Fossmark R , Johnsen G , Johanessen E , Waldum HL . Rebound acid hypersecretion after long-term
inhibition of gastric acid secretion. Aliment Pharmacol Ther. 2005 Jan 15;21(2):149-54.

40. Reimer C, Søndergaard B, Hilsted L, Bytzer P. Proton-pump inhibitor therapy induces acid-related
symptoms in healthy volunteers after withdrawal of therapy. Gastroenterology. 2009 Jul;137(1):80-7.

41. Laheij RJ , Sturkenboom MC , Hassing RJ , Dieleman J , Stricker BH , Jansen JB . Risk of community-

acquired pneumonia and use of gastric acid-suppressive drugs. JAMA. 2004 Oct 27;292(16):1955-60.

42. Canani RB, Cirillo P, Roggero P, Romano C, Malamisura B, Terrin G, et al. Therapy with gastric acidity
inhibitors increases the risk of acute gastroenteritis and community-acquired pneumonia in children.
Pediatrics 2006;117:e817-20.

43. Mertens V, Blondeau K, Pauwels A, Farre R, Vanaudenaerde B, Vos R, Verleden G, Van Raemdonck DE,
Dupont LJ, Sifrim D. Azithromycin reduces gastroesophageal reflux and aspiration in lung transplant
recipients. Dig Dis Sci. 2009 May;54(5):972-9.

44. Littner MR, Leung FW, Ballard ED 2nd, Huang B, Samra NK Effects of 24 weeks of therapy on asthma
symptoms, exacerbations, quality of life, and pulmonary function in adult asthmatic patients with acid reflux
symptoms. Chest. 2005 Sep;128(3):1128-35.

45. Mastronarde JG, Anthonisen NR, Castro M, Holbrook JT, Leone FT, Teague WG, Wise RA. Efficacy of
esomeprazole for treatment of poorly controlled asthma. N Engl J Med. 2009 Apr 9;360(15):1487-99.
digestivehealthinstitute.org/…/the-co… 9/10
20.4.2011 The Connection Between GERD and A…
46. Johnston SL, Blasi F, Black PN, Martin RJ, Farrell DJ, Nieman RB; TELICAST Investigators. The effect of
telithromycin in acute exacerbations of asthma. N Engl J Med. 2006 Apr 13;354(15):1589-600.

About Norm Robillard, PhD.

The overall goal of the Digestive Health Institute is to improve digestive health through collaborative research, communication
and education. DHI's research goals include both basic and clinical research on diet, overall digestive health and specific
diseases. Research findings will be published in peer review journals and other appropriate print and digital media. DHI will
conduct charitable and educational activities to promote increased awareness of digestive health issues, research findings and
the latest treatments. To support DHI's primary goals, the organization will seek to secure funding through government and
local grants, fund raising events, and private donations.
View all posts by Norm Robillard, PhD. →

This entry was posted in GERD Research. Bookmark the permalink.

Digestive Health Institute

Proudly powered by WordPress.

digestivehealthinstitute.org/…/the-co… 10/10