Research substantiates dyspeptic relief from the resin of Chios* . . .

Mastic Soothes
Bellyaches

Oddly, benefits do not involve eradication of H. pylori
By Will Block

D

yspepsia affects large numbers of individuals worldwide, especially in the developed world. It is a very common problem and those with dyspepsia problems are typically treated by primary care physicians, gastroenterologists, and themselves (self-medication). Dyspepsia is referred to as functional dyspepsia, with the absence of an identifiable structural lesion in the upper gastrointestinal system. Popularly known as upset stomach or indigestion, it is a medical condition characterized by chronic or recurrent pain or discomfort centered in the upper abdomen. Its effects are often described in terms of gnawing or burning, and often with a sensation of fullness caused by gas buildup. It may also entail bloating, feeling prematurely full (early satiety), belching, nausea, and heartburn. Dyspepsia has many causes, notably peptic ulcers and gastritis, but it can also be caused by several other conditions, including stomach cancer, acid reflux, lactose intolerance, gallbladder inflammation, and even anxiety or depression.


Dioscorides wrote one of the most influential herbal books in history.
Gastroenterologists distinguish dyspepsia from the lower gastrointestinal symptoms of irritable bowel syndrome. While the term dyspepsia is often used synonymously for upper gastrointestinal symptoms, most experts believe that dyspepsia must be distinguished from gastroesophageal reflux disease (GERD). Thus, dyspepsia does not represent all upper gastrointestinal symptoms. It is important to note that burning sensation in the epigastrium, the upper central region of the abdomen, is not heartburn. Rather, heartburn refers to a burning sensation that originates from the epigastric region and radiates up towards the neck. Heartburn alone is not considered dyspepsia, according to this viewpoint.

In a few individuals, dyspepsia may be an initial symptom of peptic ulcer disease (an ulcer of the stomach or duodenum) and, on occasion, of cancer. Thus, newly-onset dyspepsia in people over 55 that cannot be readily explained, especially along with the presence of other alarm symptoms, may require extended testing, and should not be taken lightly.

Mastic is an Ancient Medicine


Galen, considered the most accomplished medical researcher of the Roman period.
Chios mastic gum is resinous exudate from the stem of the plant Pistacia lentiscus var. chia cv. Anacardiaceae, which is principally cultivated on the Greek island of Chios. Its properties have been known from antiquity for a wide variety of medicinal uses. From Dioscorides and Galen, the famous first and second century Roman physicians of Greek origin, (see “Goodbye Pylori” in the March 1999 issue) to the “Jerusalem Balsam” (see “Mastic Kills Colon Cancer Cells" in the September 2005 issue), P. lentiscus has long been considered as a traditional medicine and a food ingredient in the cuisine of the Mediterranean. Presciently, Galen considered Chios mastic as a therapeutic means for hepatic inflammation, and for disorders of the stomach and intestine. Likewise, Dioscorides, in his great work De materia medica, states that mastic positively influences the process of digestion, and also that it offers benefits for the skin (see “Discovering Antibacterial Mastic” in the April 1999 issue) and for teeth (see “Unique Protection Against Gingivitis and Dental Plaque” in the December 2000 issue).

Columbus “Undiscovers” Mastic

Among his other goals in 1492, Christopher Columbus—believing that mastic could cure cholera—set out on his first journey to the New World to find the plant (see “Explorer Columbus, Medicine Procurer” in the April 1999 issue). Curiously, Columbus had drawn much of his crew from the island of Chios, and offered a reward to the first crewman to sight the mastic plant upon landing. Columbus was quite knowledgeable about medicines since he supplemented his readings with trips to famous regional pharmacies.1 Of the many local physicians that he met, he chose two for his three ships, one for the Santa Maria and one for the Niña. Thus he was well equipped for identifying botanicals on his voyages. Indeed, on his last trip to the New World, he enlisted the services of an apothecary, a specialist in botany and pharmacology (such as it then existed). Although he thought he had found mastic, he was mistaken—confusing it with a shrub later identified as gumbo-limbo or turpentine tree (Bursera simaruba). It’s interesting that Columbus was told (in sign language) by the natives that gumbo-limbo—which exudes a resin that bears a striking resemblance to the real mastic tree and like it too has a turpentine-like taste—was “good for a stomach ache.” There have been no clinical trials for gumbo-limbo.

Dyspepsia Remedies Surpassed

While herbal remedies are growing in popularity for treating functional dyspepsia, there has been little or weak substantiation to date. So a new study investigating whether mastic gum might improve symptoms in patients with functional dyspepsia compared to placebo is welcome.2 This study is the first properly designed study to test this hypothesis.


Dyspepsia has many causes, notably
peptic ulcers and gastritis, but it can
also be caused by several other
conditions, including stomach cancer,
acid reflux, lactose intolerance,
gallbladder inflammation, and even
anxiety or depression.


Of the different approaches for the treatment of functional dyspepsia, little success has been met. Historically, the use of drugs such as H2-receptor antagonists—a class of drugs used to block the action of histamine on parietal cells in the stomach—have been unsatisfactory. Prokinetics—a type of drug which enhances gastrointestinal motility by increasing the frequency of contractions (or increasing their strength) in the small intestine—have also been used in functional dyspepsia. One such a drug, mosapride, has shown small improvement in symptoms in a small trial.3 Cisapride, a related compound, has shown benefit over placebo but its use is now restricted severely due to cardiac side effects.4 A newer D2-receptor antagonist, itopride, seemed promising but it has failed Phase III trials.5 Proton pump inhibitors (found useful for triple therapy) have shown little efficacy, and Helicobacter pylori eradication (by triple therapy or herbal means) has shown only minor benefit in recent trial and meta-analyses. Finally, alosetron—a 5-HT3 antagonist used for the management of severe diarrhea-predominant irritable bowel syndrome (in women only)—shows some benefit, but its use is restricted in some countries due to serious side effects.

Awaited and Worthy

Given this sorry state of the pharmaceutical armamentarium, any new development has been eagerly awaited, and the new mastic dyspepsia study appears to be worthy. It was recently conducted at the Chios District General Hospital Skyitsion, Chios, Greece. Using 148 male and female subjects (aged 18–75 years; 42 males and 106 females) who met the Rome II criteria* for functional dyspepsia, meaning that they were diagnosed for inclusion if recurrent upper abdominal pain or discomfort was present. The discomfort was characterized by the presence of bloating, nausea, vomiting, belching or loss of appetite. At the same time, these symptoms could be associated with gastroesophageal reflux symptoms such as acid regurgitation and heartburn. However, those with once a week symptoms, or complaints of gastroesophageal reflux only, were excluded from the trial. The subjects were required to have experienced symptoms for at least 12 weeks in the previous 9 months.


* The consensus conference of the American Gastroenterologists’ Association and international medical societies on functional bowel disorders.


Excluding Those With H. Pylori

Still while in the selection process, potential subjects were subjected to physical examinations, laboratory tests, upper gastrointestinal endoscopy, and Helicobacter pylori testing. Patients harboring H. pylori infection were rejected. Upper gastrointestinal endoscopy was performed within the last 2 months before entering the study. Those with a hiatal hernia were permitted to enter the study, but not patients found to have gastritis or duodenitis (inflammation of the duodenum). If the candidates were using medication that altered gastric function—particularly narcotics, tricyclic antidepressants, or calcium channel blockers—they were rejected from the study. Finally, a 4 week washout period was enforced on the use of prokinetics and proton pump inhibitors.

As the trial began in January of 2006, the researchers randomly assigned the volunteers to receive either capsules of Chios mastic gum, 350 mg three times daily (1.05 g/day), or placebo. Seventy-four received Chios mastic gum and seventy-four received placebo. There were no significant differences between baseline characteristics in the two groups. At the end of just 3 weeks of treatment, the researchers measured the change from baseline in the severity of symptoms of functional dyspepsia.

For evaluation, they used the Hong Kong Index of Dyspepsia (HKID), a validated symptom severity questionnaire for patients with dyspepsia. The Index measures twelve dyspepsia symptoms on a five point scale each (0 for absent, 1 for mild, 2 for moderate, 3 for severe, and 4 for very severe). The symptoms measured are stomach pain in general, bloating of the upper abdomen, dull ache of the upper abdomen, stomach pain before meals, stomach pain when anxious, vomiting, nausea, belching, acid regurgitation, heartburn, acidity in the stomach, and loss of appetite. Thus, the possible outcome scores range from 0 to 48, where 0 represents the absence of any symptoms, and 48 represents the high possible severity of the dyspeptic symptoms. The subjects global assessment of efficacy was also evaluated. The last follow-up was completed in November 2008.

Marked Improvement for Mastic

The first specific question asked was: “Did you see any improvement of your symptoms while on the trial medication?” Among the responses given were symptom-free, marked improvement, moderate improvement, no change, and deterioration. Question number two was, “On this five point scale which answer would more accurately describe your symptoms’ improvement?” The dividing line between a positive versus a negative response to treatment was pre-specified as improvement of at least two points in the five point scale. At the end of the study, the subjects returned their mastic or placebos, and the capsules were counted. Those who took at least 75% of the doses were deemed compliant. At this point, a physical examination was performed along with routine laboratory tests that measured full blood count, liver and renal function, blood glucose, cholesterol, triglycerides and uric acid. After one month had passed, the subjects returned to the hospital, when they were asked about side effects and adverse events. The changes measured by the HKID compared to baseline were evaluated. This was judged to be the primary outcome. The global assessment of efficacy as determined by the patients at the end of the study was a second primary outcome.


Presciently, Galen considered
Chios mastic as a therapeutic means
for hepatic inflammation, and for
disorders of the stomach and
intestine.


The most important finding was that the symptom score after treatment was significantly lower in the mastic group than in the placebo group. There was a significant difference at the end of treatment in HKID scores in favor of the mastic treatment (symptoms in the mastic group were 26% lower than the placebo group). In within-group comparison in the actively treated group, there was significant improvement from baseline (improvement in the mastic group increase by 60%). There was no significant improvement in the placebo group of this comparison type.

Individual Assessment of Efficacy

Regarding the subjects’ own global assessment of efficacy, only 40% (30/74) of patients showed improvement on the placebo arm, while 77% (57/74) of patients in the active treatment (mastic) group showed improvement of symptoms. Of twelve symptoms influenced by treatment, eight were not significant. Those symptoms that showed significant improvement with mastic compared to placebo were: stomach pain in general (improved by 144%), stomach pain when anxious (improved by 176%), dull ache in the upper abdomen (improved by 278%), and heartburn (improved by 267%).

Of subjects who had some element of gastro-esophageal reflux in the initial assessment—32 patients in the placebo group had either acid reflux or heartburn or both and 33 patients in the mastic arm had either acid reflux or heartburn or both—only 6 patients in the placebo group showed some improvement, whereas 25 patients in the mastic group reported benefit from the treatment. There were no dropouts because of adverse events, although there was one complaint of mild side effects in each group. Mastic was well tolerated by the subjects who took it.


To our knowledge this is the first
double-blind placebo controlled trial
to assess the effects of natural mastic
for functional dyspepsia.


Due to the paucity of effective conventional medication for the treatment of functional disorders of the alimentary tract, natural remedies and herbal preparations have been tested for these conditions during the past few years. And some efficacy has been shown. For irritable bowel syndrome, tested remedies include compounds such as peppermint oil, iberogast and Chinese herbal preparations. With these showings, however small, there is growing acceptance for complementary approaches that these herbs have some role for treatment.

In fact, treatment of functional dyspepsia has recently been a preferential niche for natural remedies, especially since, as previously mentioned, drugs have done so poorly, and have unconscionable adverse effects in some instances. So there is promise for herbal preparations as reliable alternatives in the treatment of functional dyspepsia. To our knowledge, the current study is the first double-blind placebo controlled trial to assess the effects of natural mastic for functional dyspepsia. And the finding—that mastic significantly improved the perception of symptoms in patients with functional dyspepsia over 3 weeks of treatment compared to placebo—is impressive.

What Causes Mastic to Relieve Dyspepsia?

Many constituents of mastic have been identified. Nearly 25% of its weight consists of a polymer which in an acid environment becomes a runny resin which could have cytoprotectant effects in patients.6 More than 20% of its weight comprises the neutral fraction; this doesn’t seem to have any medicinal properties. The balance constitutes the acid fraction, and it is here that triterpenoid acids seem to have both antimicrobial and antioxidant effects. Of these, moronic acid appears to have antimicrobial activity against E. coli, Staphylococcus species and Ozava muconata.7,8 This constituent could be the cause responsible for the effect that mastic has on H. pylori in vitro.9,10 Then there is masticadienonic acid, which has been found to inhibit bradykinin and phospholipase A2.11 Two other acids, iso-masticadienonic acid and oleanolic inhibit leukotriene B4.12


“It is worth noting that three quarters
of the patients receiving Chios mastic
gum reported improvement …
which is one of the best results
ever obtained by a medication
[herbal or drug] in a
placebo controlled trial of
functional dyspepsia.”


Altogether, 69 components have been isolated from mastic gum.13 But it is not known whether these any of these triterpenoid acids could be responsible for the effect of mastic gum on functional dyspepsia remains. Other active substances in the resin of Chios mastic gum could be causal.

Seventy-Five Percent Improvement in Dyspepsia Symptoms

Despite the study’s relatively small sample size, the researchers believe that it achieves statistically significant results. The authors wrote: “It is worth noting that three quarters of the patients receiving Chios mastic gum reported improvement which is one of the best results ever obtained by a medication [herbal or drug] in a placebo controlled trial of functional dyspepsia.”

Mastic had almost double the improvement compared to placebo. Looking at each of the symptom's scores, all twelve improved in the treatment group compared to the baseline. Grouping the symptoms into three major categories—i.e. pain, reflux and fullness—mastic showed a greater improvement of symptoms’ scores in the three symptoms of the pain group and in heartburn. Only postprandial fullness did not show significantly better than placebo.

While none of the subjects had mainly reflux symptoms, there was a significant overlap between functional dyspepsia and gastroesophageal reflux, and mastic was effective in alleviating concomitant heartburn in patients with functional dyspepsia. The researchers speculated that the effect of mastic on heartburn could have been caused by a gel formed by the polymer in acid conditions that can be caused by a prokinetic effect.

More Women Than Men

Recall that a high proportion of the study subjects were women (106 females compared to 42 males). This probably reflects a real life scenario, because women generally complain of functional gastrointestinal problems more than men, or at least to their physicians.


Mastic is efficacious for treating a
common condition, namely dyspepsia,
for which few effective therapies are
currently available.


Summing up, in all appearances mastic is efficacious for treating a common condition for which few effective therapies are currently available. While further trials are needed to confirm the findings, no drugs or other herbals come even close. Future research should focus on identifying the active substances from mastic that alleviate symptoms of functional dyspepsia. But given this study, when you consider the pain and suffering of functional dyspepsia, not to mention the safety of mastic, why wait?


* In last month’s issue, in the article “Mastic: Curtains for Ulcer-Causing Bacteria,” we made reference to a poster-session abstract, “Is Chios mastic gum effective in the treatment of functional dyspepsia? A prospective randomized double-blind placebo control study.”2 As is occasionally the case, when authors are excited enough to present a clear finding, the details are in flux, because the study is still in process, and the final calculations have not been done. So now we present the published findings, which are still uncorrected, for publication, because the thrust is so positive. The conclusions still portray the reasons for our enthusiasm: mastic gum significantly relieves dyspepsia, a curse that has been with us from the dawn of our species.


References

  1. Griffenhagen G. Materia medica of Columbus. Int Pharm J 1990;4:271-2.
  2. Dabos KJ, Sfika E, Vlatta LJ, Frantzi D, Amygdalos GI, Giannikopoulos G. Is Chios mastic gum effective in the treatment of functional dyspepsia? A prospective randomised double-blind placebo controlled trial. J Ethnopharmacol 2009 Dec 2 doi:10.1016/j.jep.2009.11.021. [Epub ahead of print]
  3. Wu ZY, Wang YP, Chao Z. Mosapride for functional dyspepsia: a systematic review. Chin J Evid Based Med 2006;6:790–803.
  4. Veldhuyzen van Zanten SJ, Jones MJ, Verlinden M, Talley NJ. Efficacy of cisapride and domperidone in functional (non-ulcer) dyspepsia: a meta-analysis. Am J Gastroenterol 2001;96:689–96.
  5. Talley NJ, Tack J, Ptak T, Gupta R, Giguere M. Itopride in functional dyspepsia: results of two phase III multicenter, randomized, double-blind, placebo-controlled trials. Gut 2008; 57:740-6.
  6. Dimas K, Hatziantoniou S, Wyche JH, Pantazis P. A mastic gum extract induces suppression of growth of human colorectal tumour xenografts in immunodefficient mice. In Vivo 2009;23, 63-8.
  7. Hostettmann-Kaldas M, Nakanishi K, 1979. Moronic acid, a simple triterpenoid keto acid with antimicrobial activity isolated from Ozoroa mucronata. Planta Medica 1979;37, 358-60.
  8. Koutsoudaki C, Krsek M, Rodger A. Chemical composition and antibacterial activity of the essential oil and the gum of Pistacia lentiscus var. Chia. J Agri Food Chem 2005;53:7681-5.
  9. Huwez FU, Thirlwell D, Cockayne A, Ala'Aldeen DA. Mastic gum kills Helicobacter pylori. N Engl J Med 1998 Dec 24;339(26):1946.
  10. Marone P, Bono L, Leone E, Bona S, Carretto E, Perversi L. Bactericidal activity of Pistacia lentiscus mastic gum against Helicobacter pylori. J Chemother 2001;13, 611-4.
  11. Giner-Larza EM, Manez S, Giner RM, Recio MC, Prieto JM, Cerda-Nicolas M, Rios JL. Anti-inflammatory triterpenes from Pistacia terebinthus gals. Planta Medica 2002;68, 311-5.
  12. Giner-Larza EM, Máñez S, Recio MC, Giner RM, Prieto JM, Cerdá-Nicolás M, Ríos JL. Oleanonic acid, a 3-oxotriterpene from Pistacia, inhibits leukotriene synthesis and has anti-inflammatory activity. Eur J Pharmacol 2001 Sep 28;428(1):137-43.
  13. Kaliora AC, Mylona A, Chiou A, Petsios DG, Andrikopoulos NK. Detection and identification of simple phenolics in Pistacia lentiscus resin. J Liq Chromatogr Relat Technol 2004;27,289-300.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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