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Melatonin and GERD

Jacob Schor ND FABNO

December 27, 2008

Since late spring 2006, five articles have been published in peer reviewed medical journals suggesting a relationship between the hormone melatonin and gastroesophageal reflux disease (GERD).  “Gastroesophageal reflux disease (GERD) is a condition in which food or liquid travels backwards from the stomach to the esophagus ……..”   Many of us still call it by the older description, “Heartburn.”  Yet GERD often causes other symptoms, It “… can also present as supraesophageal symptoms, sleep disturbances and daytime sleepiness. In addition, asthmatic attacks in patients with hyperactive airways can occur if stomach contents migrate into the pharynx and are then aspirated.”

Chart of symptom frequency: http://www.nature.com/nrd/journal/v5/n4/fig_tab/nrd2011_F1.html#figure-title

The “ incidence of nocturnal GERD symptoms …. has been reported to be as high as 10%” Yet many people apparently sleep through their night time symptoms unaware they are having reflux problems.  This hidden or occult disease is only revealed when astute clinicians identify it as the cause of hoarseness, chronic cough, or daytime sleepiness.

The idea of using melatonin to treat GERD goes back to May of 2006. Pereira and de Souza writing in the Journal of Pineal Research, reported on the, “Regression of an esophageal ulcer using a dietary supplement containing melatonin.”   They told the story of a 64 year old woman whose GERD symptoms responded favorably to a formula containing 6 mg of melatonin plus several amino acids and vitamins.  

She weaned off the amino acids and vitamins and did well just taking the 6 mg of melatonin at night.  Her symptoms returned if the melatonin dose was lowered the to only 3 mg.  

That October, the same journal published another paper by Pereira in which he described the results of a study comparing the action of the same melatonin combination formula against omeprazole in treating reflux disease. 

Melatonin was known to inhibit gastric acid secretion and the making of nitric oxide. Nitric oxide acts to temporarily relax the lower esophageal. Others compounds in the formula display anti-inflammatory and analgesic effects. The researchers gave the melatonin containing supplement to 176 patients and 20 mg doses of omeprazole to another 175 patients. All 176 patients receiving the melatonin supplements “reported a complete regression of symptoms after 40 days of treatment.” Only 115 subjects (65.7%) of the omeprazole patients reported similar improvement.

   

In June of the following year, 2007, the Journal of Physiology and  Pharmacology, published an article by Konturek et al from Cracow, Poland.  They tested the effect of melatonin on injured esophageal tissue.  They purposefully chemically induced esophageal lesions in some rats, but let’s not go into the details how they did it.  The important point is that they found that if they pretreated the rats with melatonin, they couldn’t induce the injury.

Melvin Werbach a well-known American writer on nutritional medicine summarized this research last summer in Alternative Therapies in Health and Medicine. He points out that, “The enterochromaffin cells of the gastrointestinal (GI) tract secrete 400 times as much melatonin as the pineal gland; therefore, it is not surprising that research is finding that this indole plays an important role in GI functioning.”

In November 2007, researchers at the Rabin Medical Center in Petak Tikva, Israel announced plans to conduct a clinical trial using just melatonin but in 10 mg doses. According the Clinical Trials listing they have not actually begun the study yet. 

As exciting as all this sounds I must admit this therapy is new to me and I have no clinical experience using melatonin in this context.  We have used much higher doses of melatonin in treating cancer patients.  We have not heard of nor seen major problems from using it.  A small percentage of users complain of either grogginess or insomnia that stops when they stop taking melatonin.  On the other hand, using proton pump inhibitor drugs to treat GERD have several well documented side effects, the most worrisome being the increased osteoporotic fractures. Melatonin seems like a safe and easy enough therapy to try.

This idea makes sense in hindsight though I am the first to admit the thought to use melatonin never once occurred to me before reading these articles.  GERD is a big problem at night.  The body ought to compensate while lying down and sleeping and tighten up the stomach sphincter to prevent reflux. The body signals itself that it is night by secreting melatonin.  We all make less melatonin than our ancestors.  This is because modern lighting suppresses melatonin production.  The artificial lights we us to see at night trigger blue receptors in the eye that stop the brain from making melatonin. 

If melatonin works to treat GERD, we must wonder if things that change melatonin production also change GERD incidence.  We might predict that individuals who work night shifts will have a higher incidence of GERD.  We also might wonder if blue light emitting computer and television screens, because they suppress melatonin production, increase GERD.  At this point I can find no published data that either support or contradict these notions.  Given how new the idea is that melatonin and GERD are even connected, it is unlikely that researchers have even thought to look for such associations.  The absence of data means little.

Perhaps this business will serve to teach us a lesson.  Our bodies are well adapted to live in the natural world.  When we create artificial environments, in this case artificial lighting, we run the risk of disrupting well balanced biological homeostatic mechanisms that took millions of years to evolve.  Our professional fixation with nature cure, or just helping patients lead simpler lives that are ‘closer to nature,’ begins to sound more rational and science based when seen in this light.

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REFERENCES:

melatonin 6 mg, 5-hydroxytryptophan 100 mg, D,L-methionine 500 mg, betaine 100 mg, L-taurine 50 mg, riboflavin 1.7 mg, vitamin B6 0.8 mg, folic acid 400 microg, and calcium 50 mg

http://clinicaltrials.gov/ct2/show/NCT00564590

Healthline.com

http://www.nature.com/nrd/journal/v5/n4/full/nrd2011.html

Eur J Gastroenterol Hepatol. 2005 Jan;17(1):113-20.

Related Articles, Links

    Click here to read

    Night-time gastro-oesophageal reflux disease: prevalence, hazards, and management.

    Orr WC.

    Lynn Health Science Institute, Oklahoma City, Oklahoma 73112-5550, USA. okorr@theshop.net

    Patients who complain of symptoms of gastro-oesophageal reflux disease (GORD) that occur at night require special attention. Night-time GORD can profoundly impair quality of life by causing pain, disturbing sleep, and interfering with next-day mental and physical functioning. Sleep impairs oesophageal acid clearance resulting in a prolongation of acid mucosal contact, and nocturnal reflux portends a greater risk of erosive oesophagitis and other significant complications of gastro-oesophageal reflux. Lifestyle changes such as elevating the head of the bed and adjusting the sleeping position can relieve night-time heartburn, and instituting some dietary changes along with occasional use of histamine H2 blockers can also be helpful. Relief of night-time reflux and its attendant symptoms usually requires a medication with acid-suppressing properties that extend into the sleeping interval. In most instances, more powerful acid suppression in the form of proton-pump inhibitors will be required. Clinical studies have shown that 40 mg esomeprazole provides better control of night-time GORD symptoms than 20 mg omeprazole or 30 mg lansoprazole. Furthermore, 40 mg pantoprazole offers even faster relief than 40 mg esomeprazole for night-time GORD symptoms. Of the several proton-pump inhibitors available on the market, esomeprazole and pantoprazole appear to have some advantages, which have been documented in recent studies. Esomeprazole has been shown to be more effective than lansoprazole in relieving GORD symptoms, and esomeprazole and pantoprazole appear to be equally effective in resolving GORD symptoms in a comparative study. Pantoprazole has pharmacokinetic properties that document a longer half-life compared with the other proton-pump inhibitors, and pantoprazole has the slowest inhibition recovery rate. These properties lend credence to pantoprazole as an effective treatment for associated symptoms of night-time reflux.

J Pineal Res. 2006 May;40(4):355-6. 

    Regression of an esophageal ulcer using a dietary supplement containing melatonin.

    de Souza Pereira R.

    PMID: 16635024 [PubMed - indexed for MEDLINE]

J Pineal Res. 2006 Oct;41(3):195-200. 

    Regression of gastroesophageal reflux disease symptoms using dietary supplementation with melatonin, vitamins and aminoacids: comparison with omeprazole.

    Pereira Rde S.

    Depto. de Farmácia-Universidade Estadual da Paraíba, Av das Baraúnas, 351/Campus Universitário, Bodocongó/Campina Grande-PB-Brazil-CEP 58109-753, Brazil. ricardodesouzapereira@yahoo.com.br

    The prevalence of gastroesophageal reflux disease (GERD) is increasing. GERD is a chronic disease and its treatment is problematic. It may present with various symptoms including heartburn, regurgitation, dysphagia, coughing, hoarseness or chest pain. The aim of this study was to investigate if a dietary supplementation containing: melatonin, l-tryptophan, vitamin B6, folic acid, vitamin B12, methionine and betaine would help patients with GERD, and to compare the preparation with 20 mg omeprazole. Melatonin has known inhibitory activities on gastric acid secretion and nitric oxide biosynthesis. Nitric oxide has an important role in the transient lower esophageal sphincter relaxation (TLESR), which is a major mechanism of reflux in patients with GERD. Others biocompounds of the formula display anti-inflammatory and analgesic effects. A single blind randomized study was performed in which 176 patients underwent treatment using the supplement cited above (group A) and 175 received treatment of 20 mg omeprazole (group B). Symptoms were recorded in a diary and changes in severity of symptoms noted. All patients of the group A (100%) reported a complete regression of symptoms after 40 days of treatment. On the other hand, 115 subjects (65.7%) of the omeprazole reported regression of symptoms in the same period. There was statiscally significant difference between the groups (P < 0.05). This formulation promotes regression of GERD symptoms with no significant side effects.

J Physiol Pharmacol. 2007 Jun;58(2):361-77. 

    Protective influence of melatonin against acute esophageal lesions involves prostaglandins, nitric oxide and sensory nerves.

    Konturek SJ, Zayachkivska O, Havryluk XO, Brzozowski T, Sliwowski Z, Pawlik M, Konturek PC, Cze?nikiewicz-Guzik M, Gzhegotsky MR, Pawlik WW.

    Department of Physiology, Jagiellonian University Medical College, Cracow, Poland. mpkontur@cyf-kr.edu.pl

    Melatonin (MT) is known to protect gastrointestinal mucosa against various types of injury but its effects on esophageal damage have not been studied. We examined the effects of MT on acute esophageal injury and the mechanism involved in the action of this indole. Acute esophageal lesions were induced by perfusion with acid-pepsin solution using tube inserted through the oral cavity into the mid of esophagus of anaesthetized rats with or without inhibition of prostaglandin (PG) generation by indomethacin (5 mg/kg/day), nitric oxide (NO) formation by N(G)-nitro-L-arginine (L-NNA, 20 mg/kg/day) or sensory nerves deactivation by capsaicin (125 mg/kg, sc). The esophageal injury was assessed by macroscopic score and histologic activity index. The esophageal mucosal blood flow (EBF) was determinated by H(2)-gas clearance method. The plasma TNF-alpha and nitrate/nitrite (NOx) levels and mucosal PGE(2) contents were assessed by immunoassays. Esophageal acid-pepsin perfusion induced noticeable esophageal mucosal injury as compared to perfusion with vehicle saline. The pretreatment with MT prevented significantly esophageal injury, raised EBF and mucosal content of PGE(2), while decreasing the levels of TNF-alpha. Inhibition of COX/PG and NOS/NO systems by indomethacin and L-NNA, respectively, or inactivation of sensory nerves by capsaicin, that manifested in further increase of esophageal injury, reduced the levels of EBF, markedly raised the levels TNF-alpha and reduced mucosal PGE(2), but the pretreatment with MT prevented significantly esophageal injury, improved EBF and raised mucosal PGE(2) contents. These studies suggest that MT can be considered as a novel esophagoprotector, acting, at least in part, through the COX/PG and NOS/NO systems and activation of sensory nerves.

Altern Ther Health Med. 2008 Jul-Aug;14(4):54-8.Links

    Melatonin for the treatment of gastroesophageal reflux disease.

    Werbach MR.

    The enterochromaffin cells of the gastrointestinal (GI) tract secrete 400 times as much melatonin as the pineal gland; therefore, it is not surprising that research is finding that this indole plays an important role in GI functioning. In animal studies, it protects against GI ulcerations, and randomized clinical trials suggest its efficacy in treating functional dyspepsia and irritable bowel syndrome. Melatonin administration has been shown to protect against esophageal lesions in animals. Moreover, in a randomized, single-blind clinical trial of subjects with gastroesophageal reflux disease (GERD), the combination of melatonin with other natural supplements was found to be superior to omeprazole, a proton pump inhibitor (PPI). Its administration as a single treatment for GERD has not been previously reported. A 64-year-old Caucasian female who required treatment with a PPI for symptoms of GERD wished to substitute a natural treatment because of the risk of worsening her osteoporosis. She experienced a return of symptoms following each of three 20-day trials of a proprietary blend of D-limonene when attempts were made to discontinue the PPI. She then underwent a trial of a natural formula consisting of melatonin 6 mg, 5-hydroxytryptophan 100 mg, D,L-methionine 500 mg, betaine 100 mg, L-taurine 50 mg, riboflavin 1.7 mg, vitamin B6 0.8 mg, folic acid 400 microg, and calcium 50 mg. After 40 days, the PPI was withdrawn without a return of symptoms. Subsequently, an attempt to reduce melatonin to 3 mg resulted in symptoms, while all other ingredients were withdrawn with minimal symptoms during 10 months of follow-up.