Gabor Szendi:
Reflux: as for that many things are quite different than you think
Medical sciences blame our old friends for gastroesophageal reflux disease instead of Western pattern diet. This mistake has catastrophic consequences: a disease -could be cured quite easily- may become fatal
Defining reflux, or more specifically gastroesophageal reflux disease (GERD) is not easy because there is a continuous transition between heartburn complaints, sometimes after eating, and reflux disease. For clarity, reflux disease is considered by expert consensus as when gastrointestinal backflow leads to complaints or complications that impair quality of life. Disturbing symptoms occur relatively regularly. Such symptoms are usually heartburn, acid reflux, acid regurgitation, or feelings of chest burning, associated with reflux.
Complications of reflux can be acidic etching in the esophagus, which can lead to esophagitis, Barrett's esophagus (a precancerous condition of the esophagus), or esophageal cancer. These can cause difficulty or painful swallowing. Complications of reflux beyond the esophagus may include a cough due to acid reflux into the trachea, asthma symptoms, persistent hoarseness, tooth surface etching, pharyngitis, inflammation of the sinuses, and recurrent otitis media.
In Western societies, the incidence of reflux disease is estimated at 15-25%, while in Asia it is below 5% (Richter, 2007). The incidence of the disease increases with age. Reflux is increasingly common in the Western world, with a 50% increase in the number of cases since 1995 (El-Serag et al.,2014). Reflux is not even mentioned in the literature before 1930 (Blaser, 2005), and its incidence has been gradually increasing since the mid-1970s, which cannot be attributed simply to diagnostic zeal (Everhart, 2008).
Helicobacter pylori and reflux
Helicobacter pylori was first discovered in the 19th century, but was then forgotten. This bacterium tolerates the acidic medium of the stomach well and is widespread throughout the world: the worse hygiene conditions are, the more common it is, so in Africa and Asia, 70-80% of people are infected, compared to 15-20% in the Western world.
In 1982 two Australian researchers, Robin Warren and Barry Marshall, found that this bacterium was the cause of stomach ulcers, and in 2005 were awarded the Nobel Prize for their work. A gastric ulcer predisposes to stomach cancer, therefore H. pylori is now considered a public enemy and is popularly controlled by antibiotic treatment. However, this negative role is highly questionable as H. pylori has lived in symbiosis with us for at least 100,000 years (Moodley et al.,2012), and studies have shown that ulcers and stomach cancer are very rare in people who are almost 100% infected, but do not consume high glicemic carbohydrates (Datta et al.,2003) (Holcombe, 1992). That is, ulcer and gastric cancer are due to the interaction of H. pylori with Western nutrition.
A special ancient function of the bacterium is the regulation of acid levels in the stomach. The H. pylori researcher Martin Blaser pointed out that the progressive decline of H. pylori in the Western world, due to increasing hygiene and antibiotic use, has altered disease patterns (Blaser, 2005). Reflux, and the resulting Barrett's esophagus and esophageal cancer have become more common.
What causes reflux? To understand reflux disease, it is important to familiarize ourselves with the anatomy of the esophagus. Where the esophagus enters the stomach, there is a closure ring called the lower esophageal closure ring. This ring closes the lower end of the esophagus to prevent stomach contents from flowing backwards.
There is also an external closure ring, which is actually the muscle of the circular opening of the diaphragm surrounding the esophagus. This helps keep the lower esophageal closure ring closed. One theory of reflux is the double closure ring hypothesis. The essence of this is that any effect that weakens the closing capacity of one or the other - or both - of the closure rings, helps the acidic stomach contents return to the esophagus and irritates it. If this is regular, it can slowly lead to burning and inflammation, followed by Barrett's esophagus and finally esophageal cancer.
What can affect the closing function of the two rings? Each time you swallow, the esophagus longitudinally contracts, and in this case the lower closure ring rises slightly above the diaphragm. Because this happens many times in life, the diaphragm ring may become loose and the esophageal-gastric junction may shift over the diaphragm (right figure). This is called diaphragmatic hernia or hiatus hernia. At this point, the two closure rings can no longer "work together" and the stomach contents can enter the esophagus more easily. Diaphragmatic hernia is congenital for many people, or develops over the years. Obesity, heavy lifting, or sports can also help to develop diaphragmatic hernia. There are several types of diaphragmatic hernia, but the most common is shown in the figure. Diaphragmatic hernia can be observed in healthy individuals between 13% and 59%, in varying proportions per test, whereas in patients with reflux this proportion is 50-94% (Hyun and Bak, 2005). In severe cases, surgery may be needed.
If the lower esophageal closure ring opens beyond the swallow or belch, it provides an opportunity for acidic contents to enter the esophagus. It is a common belief that reflux is caused by too much acid in the stomach. That's not true: as long as the esophageal closure ring is working well, acidic content is not released from the stomach, regardless of how much acid is in the stomach. Reflux is a reduction in the tone of the closure ring, and its occasional temporary opening. If the acidity of the stomach is low, it is not disturbing what goes from the stomach to the esophagus, but if the acid level is high then it is.
At this point, it is understandable why H. pylori protects against reflux. H. pylori reduces the acidity of the stomach, and although it does not affect the function of the closure ring, the occasionally upward moving stomach acid is less burning and therefore less irritating to the esophagus, thus protecting against esophageal cancer.
A lot of things can influence the muscle tone of this ring. These may be physical causes, such as excessive stomach tension after overeating, bursting of accumulated air entering the stomach when swallowing, or abdominal compression activities (leaning, lifting, abdominal exercises). Obesity also causes reflux through pressure on the stomach.
Reflux and carbohydrates
Norm Robillard's theory is that the main cause of gas production is the overgrowth of bacteria that enter the small intestine, known in the literature as SIBO (Small Intestinal Bacterium Overgrowth). The small intestine usually contains only stray bacteria. But if bacteria enter the small intestine through the weakened hydrochloric acid barrier of the stomach, or from the large intestine, then the digestion of carbohydrates begins here and the bacteria produce 10 liters of hydrogen out of 30 grams of carbohydrates. Part of this returned to the stomach, increasing its internal pressure, which opens the esophageal closure ring and the acidic contents of the stomach are pressed into the esophagus (Robillard, 2005). SIBO is quite common, and it is estimated at between 2.5% and 22% among healthy people, 17% in obese people (Bures et al.,2010).
Many foods reduce the tone of the lower esophageal closure ring, which people know to cause "heartburn". These include onions, fatty foods, peppermint, citrus fruits, chocolates, sweets, alcohol, tea, coffee, tomatoes and ketchup, and smoking (Hyun and Bak, 2005). Other foods slow down stomach emptying, which can also increase reflux. Hot spices, for example, directly irritate an already damaged esophageal wall. Certain medications also relax the muscles of the esophageal closure ring. These include beta-blockers, calcium channel blockers, diazepam, barbiturates, progesterone and estrogen. (Yancy et al., 2001).
Occasionally, the closure ring can relax spontaneously for 10-45 seconds, and this is also common in reflux patients. The very unpleasant acid reflux at night never occurs in deep sleep, but when we enter a short shallow sleep phase, that is why it seems as if we are waking up to acid reflux (Mittal and Goyal, 2006).
Treatment of reflux
If we look at the risk factors for reflux, one of the most striking factors is obesity, which began in the western world at the same time as the cholesterol hypothesis came to power in the 1970s (Hite and Meguid, 2011). Brian Jacobson et al. showed a consistent relationship between body mass index increase and reflux frequency (Jacobson et al.,2006).
If obesity is one of the main causes of reflux, then dieting should result in significant relief. Mandeep Singh and his group have been slimming down overweight women with reflux. Participants lost 13.6±7.7 kg over six months, with reflux complaints improving in 81% of cases, and within that 65% completely lost their reflux complaints (Singh et al.,2013). In another study, those who had a weight loss index of 2 kg/m2 or more during the study were 2.3 times more likely to have reflux symptoms reduced (Park et al.,2017).
The role of rapidly absorbed carbohydrates is confirmed by lowcarb studies.
In the study of William Yancy et al., symptoms of 5 obese people with reflux resolved within a week with a lowcarb diet (less than 20 grams carbohydrate) (Yancy et al., 2001).
Gregory Austin and his group repeated a lowcarb diet study in 8 people with reflux disease and proved the anti-reflux effect of the diet by lowering esophageal acid levels (Austin et al.,2006).
Keng-Liang Wu and his research team recruited 12 reflux patients for their study. Patients were tested on high and low carbohydrate liquid foods, and the esophageal closure ring opened less frequently and for a shorter period due to lower carbohydrate fluid, therefore less acidic content was returned to the esophagus (Wu et al.,2018).
Reflux and antacids
Reflux disease is not caused by high acid levels, but by the occasional relaxation of the esophageal closure ring, where acidic contents enter the esophagus. People have long been solving their occasional "heartburn" with various acid reducing agents. With the spread of reflux, the pharmaceutical industry saw the business in this as well.
At first, a histamine2 receptor blocker, cimetidine, appeared on the market in 1972, followed by another type of drug called a proton pump inhibitor (PPI) in the late 1980s. Today PPIs generate $10 billion in annual sales. Business success is enhanced by the fact that 25-70% of those taking PPIs do not even need to take the drug (Forgacs and Loganayagam, 2008).
However, the widespread use of PPIs has revealed a growing number of problems and dangers. One is that after a while, reflux reappears in 40% of patients despite taking the medicine (Fass and Gasiorowska, 2008). PPIs should only be taken for a short time, but when the patient wants to leave the medication, reflux returns, often in more severe forms (Reimer et al.,2009). For many, gradual withdrawal does not help (Moon, 2009), so many continue to take medication out of necessity.
People have also hoped PPIs will reduce the incidence of Barrett's esophagus and esophageal cancer. However, since PPIs have been in circulation, the number of people suffering from Barrett's esophagus has been steadily increasing (Alsalahi and Dobrian, 2015) and prolonged use in a Danish study showed a 3.4 times risk of gastric cancer (Hvid-Jensen et al., 2014). In a Hong Kong study, there was a 5-8 times risk of gastric cancer depending on the time of taking medication (Cheung et al.,2018b). There was no evidence of an increased risk of gastric cancer in those taking H2 blocker.
90% of refluxes can be eliminated by lifestyle changes (weight loss, lowcarb or paleo diets), with no reflux-provoking foods. Therefore, it is not worth choosing a medication that involves more risks than benefits.
Risks of taking PPIs
1. It causes magnesium deficiency, which can lead to severe muscle spasms, epileptic seizures and cardiac arrest (Nehra et al.,2018).
2. B12 deficiency develops (Nehra et al.,2018). It also increases the risk of vitamin C deficiency (Heidelbaugh, 2013).
3. Regular users are 7.5 times more likely to develop SIBO (Nehra et al.,2018).
4. It increases the risk of fracture in general by 33%, but this risk is 58% higher in the vertebrae and 26% higher in the hip (Nehra et al.,2018).
5. Taking PPIs regularly increases the risk of Clostridium difficile infection by 1.7 to 2.5 times (Nehra et al.,2018).
6. PPIs increase the risk of acute and chronic kidney disease: 3 times the risk for acute kidney disease and 2 times the risk for end-stage renal disease (Nehra et al.,2018).
7. It increases the risk of dementia by 38-44% (Nehra et al.,2018).
8. It can increase the risk of pneumonia by up to 70-100% (Eom et al.,2011).
9 It increases the risk of a heart attack by 16%, and 2 times increase in cardiovascular mortality (Shah et al.,2015). In another study, the risk of ischemic stroke was 77% higher in the first month of taking PPI (Wang et al.,2017).
10. Both PPIs and H2 blockers increase the risk of total death. There is a 25% increase in risk in the first 90 days and a 57% increase in continued use (Xie et al.,2017).
References
Alsalahi O, Dobrian AD. Proton Pump Inhibitors: The Culprit for Barrett's Esophagus? Front Oncol. 2015 Jan 9;4:373.
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.
Blaser MJ. An endangered species in the stomach. Sci Am 2005; 292: 38-45.
Bures J, Cyrany J, Kohoutova D, Förstl M, Rejchrt S, Kvetina J, Vorisek V, Kopacova M. Small intestinal bacterial overgrowth syndrome. World J Gastroenterol. 2010 Jun 28;16(24):2978-90.
Cheung KS, Chan EW, Wong AYS, Chen L, Wong ICK, Leung WK. Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-based study. Gut. 2018b Jan;67(1):28-35.
Datta S, Chattopadhyay S, Balakrish Nair G, Mukhopadhyay AK, Hembram J, Berg DE, Rani Saha D, Khan A, Santra A, Bhattacharya SK, Chowdhury A. Virulence genes and neutral DNA markers of Helicobacter pylori isolates from different ethnic communities of West Bengal, India. J Clin Microbiol. 2003 Aug;41(8):3737-43.
El-Serag HB, Sweet S, Winchester CC, Dent J. Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut. 2014 Jun;63(6):871-80.
Eom CS, Jeon CY, Lim JW, Cho EG, Park SM, Lee KS. Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis. CMAJ. 2011 Feb 22;183(3):310-9.
Everhart, JE: Gastroesophageal reflux disease. In: Everhart JE, (ed.): The burden of digestive diseases in the United States. US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Washington, DC: US Government Printing Office, 2008; NIH Publication No. 09-6443 pp:69-72.
Fass R, Gasiorowska A. Refractory GERD: what is it? Curr Gastroenterol Rep. 2008 Jun;10(3):252-7.
Forgacs I, Loganayagam A. Overprescribing proton pump inhibitors. BMJ. 2008 Jan 5;336(7634):2-3.
Heidelbaugh JJ. Proton pump inhibitors and risk of vitamin and mineral deficiency: evidence and clinical implications. Ther Adv Drug Saf. 2013 Jun;4(3):125-33.
Hite, A.H.; Meguid, M.M.: Destined for greater obesity. Nutrition, 2011, 27(10):1078-9.
Holcombe C. Helicobacter pylori: the African enigma. Gut. 1992 Apr;33(4):429-31.
Hvid-Jensen F, Pedersen L, Funch-Jensen P, Drewes AM. Proton pump inhibitor use may not prevent high-grade dysplasia and oesophageal adenocarcinoma in Barrett's oesophagus: a nationwide study of 9883 patients. Aliment Pharmacol Ther. 2014 May;39(9):984-91.
Hyun JJ, Bak YT. Clinical significance of hiatal hernia. Gut Liver. 2011 Sep;5(3):267-77.
Jacobson BC, Somers SC, Fuchs CS, Kelly CP, Camargo CA Jr. Body-mass index and symptoms of gastroesophageal reflux in women. N Engl J Med. 2006 Jun 1;354(22):2340-8.
Mittal, RK; Goyal,RK: Sphincter mechanisms at the lower end of the esophagus. GI Motility online, 2006. doi:10.1038/gimo14
Moon, MA: PPI Withdrawal Triggers Acid Hypersecretion July 1, 2009 Family Practice News. web: https://www.mdedge.com/familypracticenews/article/29604/gastroenterology/ppi-withdrawal-triggers-acid-hypersecretion letöltve: 2018-02-20
Nehra AK, Alexander JA, Loftus CG, Nehra V. Proton Pump Inhibitors: Review of Emerging Concerns. Mayo Clin Proc. 2018 Feb;93(2):240-246.
Park SK, Lee T, Yang HJ, Park JH, Sohn CI, Ryu S, Park DI. Weight loss and waist reduction is associated with improvement in gastroesophageal disease reflux symptoms: A longitudinal study of 15 295 subjects undergoing health checkups. Neurogastroenterol Motil. 2017 May;29(5).
Reimer C, Sondergaard 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,
Richter JE. The many manifestations of gastroesophageal reflux disease: presentation, evaluation, and treatment. Gastroenterol Clin North Am. 2007 Sep;36(3):577-99
Robillard, N: Heartburn cured: the low carb miracle. Self Health Publishing, 2005.
Singh M, Lee J, Gupta N, Gaddam S, Smith BK, Wani SB, Sullivan DK, Rastogi A, Bansal A, Donnelly JE, Sharma P. Weight loss can lead to resolution of gastroesophageal reflux disease symptoms: a prospective intervention trial. Obesity (Silver Spring). 2013 Feb;21(2):284-90.
Wang YF, Chen YT, Luo JC, Chen TJ, Wu JC, Wang SJ. Proton-Pump Inhibitor Use and the Risk of First-Time Ischemic Stroke in the General Population: A Nationwide Population-Based Study. Am J Gastroenterol. 2017 Jul;112(7):1084-1093.
Wu KL, Kuo CM, Yao CC, Tai WC, Chuah SK, Lim CS, Chiu YC. The effect of dietary carbohydrate on gastroesophageal reflux disease. J Formos Med Assoc. 2018 Jan 12.
Xie Y, Bowe B, Li T, Xian H, Yan Y, Al-Aly Z. Risk of death among users of Proton Pump Inhibitors: a longitudinal observational cohort study of United States veterans. BMJ Open. 2017 Jul 4;7(6):e015735.
Yancy WS, Jr., Provenzale D, Westman EC () Improvement of gastroesophageal reflux disease after initiation of a lowcarbohydrate diet: five brief case reports. Altern Ther Health Med 2001, 7(6):120, 116-119