Approved by the EMA
Since July 2015 the European Medicines Agency, EMA, has approved Chios mastic gum for traditional medicinal use with the following 2 indications:
Indication 1. Traditional herbal medicinal product used in mild dyspeptic disorders (functional dyspepsia).
Indication 2. Traditional herbal medicinal product used for the symptomatic treatment of minor inflammations of the skin and as an aid in healing of minor wounds.
Introduction
Mastic is the product of mastic tree (Pistacia lentiscus var. Chia) which grows exclusively in southern Chios Island, Greece. It is excreted in the form of “tears” from the trunk and large branches, by causing superficial cuts with sharp tools. The fresh resin, after a few days of standing under the bush, solidifies by the hot summer weather (intense sunshine and drought) prevailing in the area.
Subsequently, the solidified product is collected and purified. While mastic trees exist throughout the Mediterranean, only in southern Chios are they systematically cultivated to produce the highest-quality mastic resin, probably owing to three factors: the special microclimate of the area, the unique variety of the species, and the good management since antiquity, when the ancestor Chios inhabitants systematized the cultivation of mastic trees, and imposed the product on the market.
Historical perspective
Ancient Greek physicians (Hippocrates, Dioscorides, Galen) reported for the first time the properties of Chios Mastic gum and recommended its use for its distinctive flavor and its therapeutic properties. Documents show that it was the first natural chewing gum of the ancient world, used to clean the teeth and to freshen the breath. It was even used in cosmetology for cleansing the face and body. Then the resin was used as an active ingredient in a series of pharmaceutical formulas and nostrums, many of which have been recorded from time to time in international pharmacopeias.
Dioscorides (1st century AD.) in Materia Medica referred the therapeutic properties of mastic from the island of Chios (Chios Mastiha), mentioning that it helps in the cases of indigestion, in blood problems, in chronic coughing, while at the same time it acted as a tranquilizer. He proposed the healing properties of chewing mastic resin to support oral hygiene as well as to clean and fresh breath. He mentioned the use of Mastiha oil, the essential oil of mastic, to be applied in multiple ways for affections of the uterus, as well as for its styptic activities.
From the 1st until the 7th century AD mastic was used by medical practitioners and botanists mainly for the treatment of stomach disorders like stomach pain, dyspepsia and peptic ulcer for more than 2500 years. Ancient Greek physicians, such as Hippocrates, Dioscorides, Theophrastos and Galen mentioned its properties and recommended its use. In the view of the people at that time, the use of mastic contributed to the smooth function of the gastrointestinal system.
More specifically and from the various sources results that the Mastiha was used for soothing the pain of the stomach as well as indigestion and stomach disorders. The effect of mastic in atonic and inflammation of the stomach, intestine and liver, and the emollient properties, is reported by Galen in «Simpliciun medicamentorum temperamentis ac faculatibus libri XI».
Chios mastic gum composition
While the exact composition of Chios mastic gum has not been fully identified, it has been found that it contains more than 120 active ingredients, such as: a natural polymer, volatile and flavor components that make up the essential oil (mastic oil), terpene acids, phytosterols, polyphenylene molecules and a large number of other active substances.
According to published studies, it appears that the essential oil and the purified mastic resin are natural antibiotics with therapeutic properties (antimicrobial, antioxidant, hepato-protective).
Chios mastic gum and gastroesophageal reflux disease / functional dyspepsia
In a clinical study of Dabos et al the symptoms of gastroesophageal reflux disease were evaluated after treatment with mastic gum. Patients received 350 mg mastic gum three times daily or placebo. After 3 weeks of treatment the severity of the symptoms was assessed using the Hong Kong index of dyspepsia. Patient’s global assessment of efficacy was also evaluated. At the placebo group 32 patients had either acid reflux or heartburn or both and 32 patients in the treatment arm had either acid reflux or heartburn or both. Only 6 patients in the placebo group showed some improvement of their symptoms at the end of the study period, whereas 25 patients in the treatment group reported benefit from the treatment (p<0.01).
In 2010 Dabos et al performed the first double-blind placebo controlled trial to assess the effects of Chios mastic gum in functional dyspepsia. 148 patients fulfilling Rome II criteria for functional dyspepsia were randomly assigned to receive either Chios mastic gum 350 mg three times daily or placebo. After 3 weeks of treatment the change from baseline in the severity of symptoms of functional dyspepsia was assessed using the Hong Kong index of dyspepsia. The symptom score after treatment was significantly lower in the Chios mastic gum than in the placebo group. Individual symptoms that showed a significant improvement with Chios mastic gum were: stomach pain in general, stomach pain when anxious, dull ache in the upper abdomen and heartburn (<0.05 for all four symptoms). It was proved that Chios mastic gum significantly improved the perception of symptoms in patients with functional dyspepsia over 3 weeks of treatment compared to placebo.
Safety
Chios mastic gum was well tolerated by the patients and no adverse effects were recorded.
Chios mastic gum and Helicobacter pylori
Helicobacter pylori eradication regimens with antibiotics have proven sufficiently effective. However, there are problems with the patient compliance and increasing worldwide bacterial resistance to the administered antibiotics (particularly clarithromycin) thereby warranting further and continuous research with novel effective substances. The antibacterial properties of Chios mastic gum in vitro against Helicobacter pylori were first mentioned in the New England Journal of Medicine by Huwez et al, who concluded that the Chios mastic gum can be a cheap alternative therapy against Helicobacter pylori infection in the developing countries.
Additional in vitro studies supported those initial findings, which showed that Chios mastic resin powder at concentrations of 125 micrograms / mL and 500 mg / mL could neutralize 50% and 90% of strains of Helicobacter pylori, respectively.
Initial in vivo experimental studies showed that the monotherapy with mastic was not able to eradicate Helicobacter pylori. In another study involving 9 patients with Helicobacter pylori infection without gastroduodenal ulcer who received mastic gum 1 g four times daily for 14 days, no successful eradication of the bacterium was achieved either.
However, it was noted that these initial unsuccessful studies in rats and humans had used crude, unprocessed mastic gum containing a high content (25%) of an insoluble and sticky polymer (poly-beta-myrcene) possibly leading to a reduced absorption and bioavailability of the active components of mastic. In order to circumvent the above-mentioned problem, Chios mastic extract without the polymer (TMEWP) was tested against Helicobacter pylori in mice infected with Helicobacter pylori SS1 strain, showing a significant decrease (30-fold) in the number of colonies of Helicobacter pylori which had been inoculated. Therefore, administration of TMEWP significantly reduced the colonization of Helicobacter pylori in vivo.
A recent clinical study from Chios Island included 52 patients with Helicobacter pylori infection treated purified mastic gum (without the polymer) 350 mg three times daily for 14 days (group A), 1.05 g three times daily for 14 days (Group B), 20 mg pantoprazole twice daily, 350 mg of mastic gum three times daily for 14 days (group C), or antibiotic eradication regimen (pantoprazole, amoxicillin, clarithromycin) for 10 days (group D). The study showed that Helicobacter pylori eradication was achieved in 4/13 patients in group A, 5/13 patients in group B, 0/13 patients in group C, and 10/13 patients in Group D. While the antibiotic eradication regimen proved superior, however, it was shown for the first time that the purified Chios mastic gum has a bactericidal effect against Helicobacter pylori in humans. The authors recommended administering Chios mastic at a high dose for eradication of Helicobacter pylori in patients who refuse to take or experience side effects from the eradication therapy with antibiotics.
Our clinical experience indicates that only natural purified Chios mastic gum coadministration with the antibiotic eradication regimen adds clinical benefits against Helicobacter pylori-associated gastric pathologies, also improving the outcome of the antibiotic eradication regimen (optimization).
Conclusions
Chios mastic gum seems to possess significant antimicrobial properties against Helicobacter pylori infection in in vitro experiments. In contrast, monotherapy with mastic in in vivo studies did not initially achieve a significant eradication of Helicobacter pylori, probably due to a low dose or the administration of crude unprocessed Mastic gum containing a high concentration of the insoluble and sticky polymer (poly-beta-myrcene) which may have impacted negatively the absorption and bioavailability of the active ingredients of Chios mastic gum against Helicobacter pylori.
Finally, we propose the concurrent use of natural purified Chios mastic gum along with the conventional antibiotic eradication treatment regimen, or possibly the use of high-dose purified Chios mastic gum in patients with side effects or who are unwilling to take the antibiotic eradication regimen.
Natural purified Chios mastic gum is manufactured by the Greek Pharmaceutical company Iasis and is distributed by the company Pharma Q in the form of capsules (Mastiha var. Chia caps). The recommended daily dose is 2-4 capsules divided in 2-3 times daily. It should be taken half an hour before the meal.
Although there is no maximum duration of use, patients are advised to consult with their gastroenterologist if symptoms persist.
References
- Paraschos S, Magiatis P, Mitakou S, et al. In vitro and in vivo activities of Chios mastic gum extracts and constituents against Helicobacter pylori. Antimicrob Agents Chemother 2007;51:551-559.
- Huwez FU, Thirlwell D, Cockayne A, Ala’Aldeen DA. Mastic gum kills Helicobacter pylori. N Engl J Med 1998;339:1946.
- 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;13:611-614.
- Loughlin MF, Ala’Aldeen DA, Jenks PJ. Monotherapy with mastic does not eradicate Helicobacter pylori infection from mice. J Antimicrob Chemother 2003;51:367-371.
- Bebb JR, Bailey-Flitter N, Ala’Aldeen D, Atherton JC. Mastic gum has no effect on Helicobacter pylori load in vivo. J Antimicrob Chemother 2003;52:522-3.
- Dabos KJ, Sfika E, Vlatta LJ, Giannikopoulos G. The effect of mastic gum on Helicobacter pylori: a randomized pilot study. Phytomedicine 2010;17:296-299.
- Kountouras J, Zavos C, Deretzi G, et al. Potential implications of Helicobacter pylori-related neutrophil-activating protein. World J Gastroenterol 2012;18:489-490.
- Kottakis F, Befani C, Asiminas A, Kontou M, Koliakos G, Choli-Papadopoulou T. The C-terminal region of HPNAP activates neutrophils and promotes their adhesion to endothelial cells. Helicobacter 2009;14:177-179.
- Kottakis F, Kouzi-Koliakou K, Pendas S, Kountouras J, Choli-Papadopoulou T. Effects of mastic gum Pistacia lentiscus var. Chia on innate cellular immune effectors. Eur J Gastroenterol Hepatol 2009;21:143-149.
- Choli-Papadopoulou T, Kottakis F, Papadopoulos G, Pendas S. Helicobacter pylori neutrophil activating protein as target for new drugs against H. pylori inflammation. World J Gastroenterol 2011;17:2585-2591.