Mastic gum

Mastic Gum (Pistacia lentiscus var. Chia): A Comprehensive Reference

1. Identity and Botanical Classification

Taxonomic Names and Source Plant

Mastic gum is derived from Pistacia lentiscus L., an evergreen shrub belonging to the Anacardiaceae family, mainly distributed in the Mediterranean region. The plant is also known as lentisk or mastic tree. The latter name derives from the presence of an aromatic resin — mastic — which can be obtained from the P. lentiscus trunk and branches.

The taxonomy of the gum-producing variety has been debated in the scientific literature. De Candolle was the first to formally describe the mastic tree, in 1825, giving it the name Pistacia lentiscus L. var. Chia. Dating back to 1914, Gennadios suggested the name Pistacia chia Desf. for the mastic tree cultivated on Chios island, which is also known as Mastic or Mastix. The variety designation most commonly encountered in the modern scientific literature is Pistacia lentiscus var. Chia, abbreviated in publications as CMG (Chios Mastic Gum).

The mastic tree is a member of the Pistacia genus in the cashew family and is closely related to the pistachio tree. The mastic tree is an evergreen shrub 2–3 metres tall, which grows slowly and reaches full growth after 40–50 years.

Geographic Origin and Exclusivity

Chios mastic gum is exclusively produced by the mastic tree grown on the Greek island of Chios, situated in the northern Aegean Sea. Although the species Pistacia lentiscus L. belonging to the Anacardiaceae family is found all around the eastern Mediterranean coasts, the variety chia is uniquely cultivated in Greece's island of Chios, and especially in the south part. Chios mastiha is the resin obtained from the Pistacia lentiscus L. var. chia (Mastiha tree), which is an endemic plant cultivated exclusively in the southern part of the Greek island of Chios.

In Turkish, the island of Chios is still called Sakiz Adasi, translating to "island of gum." The resin's cultural and harvesting traditions have been recognised internationally: the history, heritage, customs of mastic and its traditional culture are now part of the intangible cultural heritage of UNESCO.

Resin Harvesting and Physical Form

Fine scratches are made on the trunks of the gum trees to allow the resin to flow out. These scratches are usually made during the hot days of summer, and the resin flows drop by drop from the trunk of the tree and hardens. The resin dries into crystal-like beads, reminiscent of teardrops — a quality that has historically given rise to the product's poetic name, "tears of Chios." Mastic gum is obtained as an exudate after "hurting" the trunk and branches of the evergreen shrub, and cutting on the shrub surface results in a congealing excretion, possibly due to a unique combination of climatic and ground conditions.

Etymology

The word "mastic" has the same roots as the English "masticate," and literally means "to gnash one's teeth." This reflects the product's longest-documented use: as a resin chewed directly from the solidified tears of the tree.

Common Forms and Preparations

Mastic gum is available and used in several physical forms:

• Raw resin tears: The hardened, tear-shaped droplets of resin, chewed directly as a natural gum.
• Powder/capsule: Ground mastic in encapsulated form, the primary format used in clinical supplementation studies.
• Essential oil: Distilled from the resin, used in cosmetic, dental, and pharmaceutical applications.
• Food ingredient: Mastiha is widely used in traditional Mediterranean cooking and beverages due to its distinctive aroma and taste.
• Pharmaceutical and dental preparations: Mastiha is also an important dietary supplement, and it has wide application in perfumery, dentistry, and cosmetics.

CMG is highly insoluble in water, and the most appropriate and commonly used solvents for dissolving the resin are non-polar solvents such as diethyl ether, dichloromethane, and ethyl acetate.

The main use of mastiha nowadays is for the production of natural chewing gum, although an approval by the European Medicines Agency for mild dyspeptic disorders and for inflammations of the skin has been given.

2. Traditional and Historical Use

Ancient Greek and Roman Medicine

Chios mastic gum has been used as a traditional medicine over the last 2500 years. Over 2500 years, it has been used in Greek traditional medicine, from Dioscurides to Galenus, in order to cure gastrointestinal inflammatory disorders, such as peptic ulcers.

The earliest references to mastic are made by Herodotus, who claims that the Greeks chewed the dried resinous liquid that dripped from the bark of the mastic tree. In traditional medicine, the oleoresinous gum of Pistacia lentiscus var. chia, so-called mastic gum, has been used to treat multiple conditions such as coughs, sore throats, eczema, dyslipidemia, and diabetes.

Chios mastic gum has a history of traditional use for its beneficial effects on the gastrointestinal system, its anti-inflammatory properties, and its antimicrobial activity.

Dental and Oral Hygiene

Mastic was the world's first natural chewing gum to be used to clean teeth and freshen breath. Ancient Greek and Roman civilizations used mastic gum to protect oral and dental health, heal wounds, and treat respiratory diseases. The practice was widespread: ancient Persians and Indians reportedly filled dental cavities with mastic, and mastic-flavored chewing gum is still found in Greece, Turkey, Syria, and Lebanon.

Byzantine and Ottoman Periods

During the Byzantine and Ottoman empires, mastic from Chios was considered so valuable that it was used to pay taxes and was often reserved for royalty and the elite. During the Ottoman Empire in particular, mastic gum became one of the indispensable flavors of palace kitchens, and it was widely used in desserts and beverages, and the value of mastic gum increased even more.

Spread Through the Mediterranean and Middle East

Mastic is used in cultures throughout the Mediterranean and Arab world, especially in Greek, Cypriot, Syrian, and Lebanese cuisine. The spread of mastic through the Mediterranean and Middle East is due to trade routes which date back to the Byzantine era.

Cultural and Culinary Uses

Mastic has been used for hundreds of years in many Mediterranean and Middle Eastern desserts, including pastries, puddings, ice creams, and cakes. In the Eastern Mediterranean, people have long loved mastic ice cream — the Greek kaimaki or Turkish dondurma — which owes its uniquely stretchy, chewy texture to mastic resin as a stabilizer.

3. Chemical Composition and Key Constituents

Overview

From a chemical point of view, CMG is a very complex natural resin in which, to date, about 120 chemical compounds have been reported, mainly divided into three categories of substances: the polymer, the volatile fraction (essential oil), and the triterpene content.

Triterpene Fraction

Triterpenes, classified into neutral and acidic, constitute the main chemical group of CMG — about 65–70% of the total weight of the resins — and consist mainly of tetracyclic and pentacyclic triterpenes.

Acidic triterpenes are among the most pharmacologically studied compounds. The main constituents of the acidic fraction are oleanonic acid, moronic acid, 24Z-masticadienonic acid, 24Z-isomasticadienonic acid, 24Z-masticadienolic acid, and 24Z-isomasticadienolic acid. CMG's most abundant compounds are the triterpenic acid isomers oleanonic, moronic, masticadienonic, and isomasticadienonic acids, with the last two being the most characteristic constituents of the resin.

Neutral triterpenes identified include: tirucallol, dammaradienone, 28-norolean-12-en-3-one, oleanonic aldehyde, and oleanolic aldehyde.

In total, thirteen triterpenoid acids have been identified in mastic gum by GC-MS as their methyl esters, including moronic acid, oleanonic acid, ursonic acid, oleanolic acid, isomasticadienonic acid, masticadienonic acid, and several related derivatives.

The Natural Polymer

CMG comprises a natural polymer, namely cis-1,4-poly-β-myrcene, the essential oil (composed mostly of α-pinene and myrcene), and the terpene fraction that can be further divided into the acidic and neutral terpenes. The high-molecular-weight polymer constitutes a structurally distinctive component of the resin and may contribute to its mechanical and film-forming properties in dental and gastrointestinal applications.

Volatile Fraction (Essential Oil)

The chemical composition of mastic oil and gum was studied by GC-MS, and α-pinene, β-myrcene, β-pinene, limonene, and β-caryophyllene were found to be the major components. Several trace components that appear to contribute significantly to the antibacterial activity of mastic oil have been identified: verbenone, α-terpineol, and linalool.

The volatile compounds contained in the essential oil and mastic water are obtained by distillation of mastic gum. GC-MS analysis revealed the dominance of α-pinene and trans-verbenol in the volatile fraction and of caryophyllene oxide, mastihadienonic and oleanonic aldehyde among others in the neutral triterpenes' fraction.

4. Mechanisms of Action

Anti-inflammatory Pathways

Anti-inflammatory action is attributed to the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expression by macrophages and the blockage of the expression of the adhesion molecules VCAM-1 and ICAM-1 by TNF-alpha stimulated endothelial cells, ultimately resulting in reduced TNF-α and inflammatory interleukins (ILs) production.

Triterpenes in the medium-polar fraction — such as lupeol, 24Z-masticadienonic acid methyl ester, and 24Z-isomasticadienonic acid methyl ester — are proposed to be the bioactive compounds responsible for mastiha's regulatory actions on energy metabolism and anti-inflammatory activities via interference with GR (glucocorticoid receptor), NF-κB, and AMPK signaling.

Triterpenes have a similar structure to glucocorticoids (GCs), the steroid hormones that exert strong anti-inflammatory activities and play crucial roles in the regulation of cellular metabolism. Findings that CMG potentially promotes beneficial effects through GR and PPARγ/α are of particular interest, especially given the current development of pharmaceuticals that work through those mechanisms to mitigate cardiometabolic disease.

Antioxidant Mechanisms

The antioxidative properties are mainly driven by a downregulation of CD36 expression in macrophages along with an increase in the intracellular antioxidant glutathione levels. This dual mechanism — reducing oxidized LDL (oxLDL) uptake by macrophages while bolstering cellular antioxidant capacity — has been proposed as a key pathway in CMG's anti-atherogenic action.

Antimicrobial Mechanisms

Triterpenes of mastic gum are considered responsible for its anti-microbial and anti-H. pylori properties. The highest overall antimicrobial activity against H. pylori was obtained with isomasticadienolic acid (mean MBC of 0.202 mg/ml), followed by masticadienolic (0.220 mg/ml), oleanonic (0.292 mg/ml), and moronic acid (0.310 mg/ml) tested against 11 strains of H. pylori. The acidic triterpenic fraction was found more effective than the neutral one, while isolated individual triterpenic acids were not as effective, indicating a synergy between all the acidic constituents.

Metabolic and Enzymatic Mechanisms

The main triterpenoids in CMG's acidic fraction, masticadienonic acid and isomasticadienonic acid, were identified to inhibit 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) — up to 50% of enzyme activity — at low micromolar concentrations (2 µM), suggesting these compounds might be contributing to the antidiabetic actions of CMG.

There is evidence of oleanonic acid, a constituent of mastic gum, acting as a peroxisome proliferator-activated receptor γ (PPARγ) agonist, and mastic gum being antidiabetic in mice in vivo.

Anticancer Mechanisms (Preclinical)

The antiprostate cancer effect of mastic gum resin has been shown to be exhibited through targeting of the NF-κB signaling pathway. Cell cycle analysis showed mastic gum resin affects the G1 checkpoint and arrests cells at the G2/M phase, particularly after 48 hours of treatment. There was also a significant decrease in COLO205 cells at the sub-G0/G1 phases with resin treatment, possibly as a result of elimination through apoptosis. These findings are entirely preclinical, derived from cell lines and animal models.

5. Scientific Evidence by Area of Use

5.1 Gastrointestinal Health: Peptic Ulcer and Helicobacter pylori

The antibacterial activity of mastic resin upon Helicobacter pylori (H. pylori) is probably the one that has been more adequately investigated, both in vitro and in clinical trials. H. pylori infection is recognized as one of the main factors for gastritis, peptic ulcer disease, and gastric cancer, with its treatment being of crucial importance for the management and prevention of prevalent digestive disorders.

The first evidence suggesting that mastic has antibacterial activity against H. pylori was published in the New England Journal of Medicine in 1998, providing a possible pathogenetic interpretation of the beneficial effect of mastic on gastric and duodenal ulcers that was already known. Even low doses of mastic gum — 1 mg per day for two weeks — can cure peptic ulcers very rapidly, but the mechanism responsible had not been clear. It was then shown that mastic is active against Helicobacter pylori, which could explain its therapeutic effect in patients with peptic ulcers.

Mastic was shown to kill 90% of isolated H. pylori strains at a concentration of 500 μg/mL. This seems to be attributed to arabinogalactan proteins which inhibit neutrophil activation in the presence of H. pylori neutrophil-activating protein.

Clinical evidence is mixed and limited in scale. Previous studies showed some effect of mastic gum on the healing of peptic ulcers in humans (Al-Habbal et al., 1984; Al Said et al., 1986); however, those studies were conducted before the discovery of H. pylori.

A subsequent small clinical study produced contradictory results: nine patients with H. pylori infection were treated with mastic 1 g four times daily for 14 days; urea breath tests were carried out before and after treatment. Mastic had no effect on H. pylori status in any of the eight completed patients; all remained H. pylori positive, with no change in delta scores (pre-treatment mean 19.1 ± 3.7 vs. post-treatment 18.7 ± 3.8, P = 0.8). The authors concluded that, despite reported anti-H. pylori action in vitro, mastic had no effect on H. pylori in humans in this preliminary study.

A more encouraging result was reported in a randomized controlled trial: in a randomized controlled trial of 180 H. pylori-positive patients, mastic gum was found to be effective in eradicating the bacteria in 83 of 90 patients (92.2%) who received the supplementation along with the triple-drug regimen.

Failure of the combination of mastic with pantoprazole to eradicate H. pylori was observed in one study, attributed to the hypothesis that most of the mastic substances require an acidic environment in the stomach to be effective against H. pylori — a condition that is altered by proton pump inhibitors.

Overall evidence strength: In vitro evidence for activity against H. pylori is solid. Human clinical evidence is small-scale, methodologically heterogeneous, and produces conflicting results. Mastic as a monotherapy for eradication is not established; results as an adjunct to standard triple therapy are more encouraging but require confirmation in larger rigorous trials. Studies have not proven mastic gum can cure any health conditions, and the research on its ability to treat some conditions and infections, such as Helicobacter pylori, has had mixed results on how effective it is.

5.2 Inflammatory Bowel Disease (IBD): Crohn's Disease

Data about the resin's effects on IBD are still limited. Based on the anti-inflammatory properties observed in animal models and in vitro studies, P. lentiscus has been suggested for the treatment of IBD, and a number of preliminary clinical trials have been carried out. The first study evaluated the efficacy of CMG on the clinical course and plasma inflammatory mediators of patients with active Crohn's disease (CD).

In a small clinical study including 10 patients with mild or moderately active CD, recruited for a 4-week treatment with mastic caps (2.2 g/day), it was demonstrated that CMG was effective in the regulation of inflammation, evaluated by C-reactive protein (CRP), IL-6, TNF-α, and MCP-1 in plasma, as well as in the regulation of oxidative stress, evaluated by total antioxidant potential. CMG treatment significantly decreased the CD Activity Index (CDAI).

In this small clinical study including 10 patients with mild or moderately active Crohn's disease, treated with mastic caps (2.2 g/day) for 4 weeks, a significant decrease in the activity index of the disease and the plasma levels of IL-6 and CRP compared to baseline was observed, while no significant side effects were reported. A remarkable reduction in TNF-α secretion following treatment with mastic caps was later reported in the same patient cohort, suggesting an additional inhibitory mechanism of monocyte chemotaxis.

A separate, larger study found: in a clinical trial of 60 IBD patients, 2.8 g/day of mastic gum improved the quality of life and IBD markers (lysozyme, lactoferrin, and calprotectin levels). However, it did not change CRP levels in this study, whereas mastic gum did influence CRP levels in people with Crohn's disease specifically.

Overall evidence strength: Some evidence suggests that mastic gum could help with IBDs such as Crohn's disease. However, a 2023 review notes that most of the evidence to support this so far has come from animal studies, and data in humans is limited. That said, a few small clinical trials show some promise, finding that taking oral mastic gum helped reduce symptoms and inflammatory substances known as cytokines in the body. More research with larger groups of participants is necessary to confirm these findings.

5.3 Lipid Metabolism and Cardiovascular Health

The effects of CMG supplementation on lipids and lipoproteins, hepatic, cardiovascular, and general metabolic health have been explored in clinical trials. One of the earliest reports evaluated the hypolipidemic effects of CMG when given at a high dose (5 g/d) in 48 patients and observed decreases in plasma total cholesterol (TC), triglycerides (TG), TC/HDL ratio, lipoprotein (a), apolipoprotein A-1, and apolipoprotein B after 18 months. In contrast, a group of patients who received a low dose (~0.7 g/d) for 12 months exhibited no changes in lipids.

As a result of high-dose CMG supplementation, decreases in serum alanine aminotransferase (ALT), aspartate transaminase (AST), and gamma-glutamyl transferase were also observed, indicating the hepatoprotective properties of CMG.

After 8 weeks of treatment, only patients treated with 1 g of crude mastic per day exhibited a significant reduction in total cholesterol values of about 11.5 mg/dl compared to baseline, with this effect being more pronounced in overweight and obese patients. This was accompanied by a decrease in free plasma glucose levels of about 4.5 mg/dl. Nonetheless, these findings should be interpreted with caution, given that no effects on LDL, HDL, triglycerides, or CRP were observed.

Clinical evidence on the anti-atherogenic or cardioprotective effects of mastic is limited, and mainly derived from studies assessing surrogate markers of atherosclerosis.

Differential sex effects were discovered, where beneficial effects of CMG on total cholesterol, lipoprotein (a), and serum glucose occurred in males. Other lifestyle factors — such as smoking, alcohol consumption, sleep patterns — the dosing regimen of CMG, interactions with potential medications, and underlying health conditions are additional confounders that have yet to be fully acknowledged and addressed in these clinical trials. These mixed results and study designs underscore the need for more rigorous research to validate the therapeutic efficacy of CMG.

Overall evidence strength: Preliminary and suggestive. Clinical trials are small to moderate in size, show dose-dependent effects, and results are mixed across doses and populations. No adequately powered, double-blind, placebo-controlled trial has established robust cardiovascular endpoints. Despite the relatively limited studies with mixed results, they have provided the foundation to understand the strengths, weaknesses, and opportunities moving forward that may help to establish CMG and its bioactives as viable therapeutics for cardiometabolic disease.

5.4 Oral and Dental Health

Chios mastic gum is a resin procured from the trunk as well as leaves of Pistacia lentiscus. It has antioxidant properties in addition to teeth-cleaning properties. Applying mastic oil in the form of mastic gum to the oral cavity has been shown to prevent the formation of dental plaques and promote the secretion of a greater amount of saliva to treat xerostomia.

The essential oil fraction is particularly active against oral pathogens. The essential oil and gum of Pistacia lentiscus var. chia are natural antimicrobial agents that have found extensive uses in medicine in recent years.

Overall evidence strength: There is plausible mechanistic (antimicrobial, antiplaque) and some clinical support for oral health applications, but large, randomized controlled trials specifically targeting periodontal endpoints are limited. The European Medicines Agency's approval for mild dyspeptic disorders and skin inflammations does not extend to formal dental indications. The oral health area warrants further rigorous clinical investigation.

5.5 Antioxidant and Anti-inflammatory Effects

In recent years, many in vitro and clinical studies have revealed a wide variety of the biological properties of Chios mastiha, such as anti-inflammatory, antioxidant, anti-microbial, hypolipidemic, and anti-cancer properties. There is now substantial evidence to suggest that mastiha demonstrates a plethora of favorable effects, mainly attributed to the anti-inflammatory and anti-oxidative properties of its components.

The primary anti-inflammatory mechanism involves interference with multiple inflammatory cascades. The clinical effects of mastic represent the result of anti-inflammatory and antioxidant action and include a hypolipidemic action with a decrease in oxidized-LDL particles and foam cell formation, beneficial effects in inflammatory bowel disease, dermatitis and periodontal inflammation, and antimicrobial and anticancer properties.

Overall evidence strength: Anti-inflammatory and antioxidant mechanisms are well-characterized in vitro and supported by animal models. Human clinical evidence demonstrating meaningful reductions in systemic inflammation biomarkers is emerging but remains preliminary and small-scale.

5.6 Anticancer Properties

Chios mastic gum has been shown to exert beneficial effects on a wide range of human disorders. The most comprehensive data so far have indicated that mastic gum provides protection against gastrointestinal malfunctions and bacterial infections. Substantial evidence has also suggested that mastic gum exhibits hepatoprotective and cardioprotective, anti-inflammatory/antioxidant, and antiatherogenic properties. In the last decade, an increasing number of studies further evaluated the potential antiproliferative properties of mastic gum against several types of human neoplasia.

Mastic gum is known to induce apoptosis by activation of caspase-3, which is a key mediator in apoptosis. The antiprostate cancer effect of mastic gum resin has been shown to be exhibited through targeting of the NF-κB signaling pathway. It was confirmed that the antiproliferative efficacy of the resin is positively correlated with its polyphenolic contents, suggesting a causal link related to the exudate content of phenolic acid and flavonoids.

Overall evidence strength: All anticancer evidence is currently preclinical — derived from cell lines and animal models. There are no published human clinical trials evaluating mastic gum as a cancer treatment or preventive. These findings, while mechanistically informative, cannot be extrapolated to clinical recommendations.

5.7 Metabolic Effects: Glucose Metabolism and Diabetes

Mastic gum is commonly used in traditional medicine for the treatment of several diseases, including diabetes. Mastic gum is rich in triterpenes, which have been postulated to exert antidiabetic effects and improve lipid metabolism.

Mechanistically, there is evidence of oleanonic acid, a constituent of mastic gum, acting as a PPARγ agonist, and mastic gum being antidiabetic in mice in vivo. Despite these findings, the exact antidiabetic mechanism of mastic gum remains unknown.

The results of clinical trials and in vivo, in vitro, and in silico studies provide accumulating evidence of the mechanisms underlying CMG's impacts on lipid and glucose metabolism, cardiovascular and hepatic health, inflammation, oxidative stress, body composition, and microbiota. However, robust human clinical trial data specifically targeting glycemic outcomes as primary endpoints are lacking, and findings in this domain remain preliminary.

Overall evidence strength: Mechanistic evidence from cell and animal studies is promising. Human clinical data on glucose lowering are limited to secondary observations within cardiovascular and lipid-focused trials. Purpose-designed antidiabetic trials in humans are needed.

6. Body Systems and Health Areas Associated with Mastic Gum

• Gastrointestinal system: Peptic ulcer, gastritis, H. pylori infection, dyspepsia, inflammatory bowel disease (Crohn's disease, ulcerative colitis). EMA has granted approval for the indication of mild dyspeptic disorders.
• Oral and dental health: Antibacterial plaque reduction, breath freshening, reduction of gingivitis; traditional application as the world's first natural chewing gum.
• Cardiovascular and lipid metabolism: Total cholesterol reduction (at high doses), anti-atherogenic effects, hepatoprotective action (ALT, AST, GGT reduction).
• Inflammatory and immune pathways: Reduction of pro-inflammatory cytokines (IL-6, TNF-α, CRP), COX-2 and iNOS inhibition, modulation of NF-κB and GR signaling.
• Metabolic health: Glucose metabolism modulation, PPARγ agonism, 11β-HSD1 inhibition; antidiabetic potential demonstrated preclinically.
• Skin and integumentary system: EMA approval for skin inflammation; traditional use for wound healing; allergic contact dermatitis has been noted as an adverse reaction in some users.
• Oncology (preclinical only): Antiproliferative and pro-apoptotic effects demonstrated in cell lines for prostate, colon, oral, and hepatic cancers.

7. Dosage Forms and Dosages Reported in Studies

The following dosages reflect those employed in clinical studies and should not be interpreted as endorsements or recommendations:

• Crohn's disease (pilot study): Patients with mild to moderately active CD were recruited for a 4-week treatment with mastic caps at 6 capsules per day (0.37 g/cap), totalling 2.2 g/day.
• IBD markers trial: 2.8 g/day of mastic gum in a clinical trial of 60 IBD patients.
• Hypolipidemic study: High dose: 5 g/day in 48 patients for 18 months; low dose: approximately 0.7 g/day in 85 patients for 12 months. Only the high-dose group showed significant lipid changes.
• Cholesterol/glucose study: 1 g of crude mastic per day for 8 weeks, demonstrating significant reduction in total cholesterol in patients with cholesterol over 200 mg/dL.
• Peptic ulcer study (historical): 1 mg per day for two weeks was reported to cure peptic ulcers, though the mechanism at the time was not fully characterized.
• H. pylori pilot study (negative result): 1 g of mastic, four times daily (4 g/day total), for 14 days.
• General supplement use: Mastic gum or powder have most often been used by adults in doses of 1–2.8 grams by mouth daily for up to 3 months.
• Tolerability ceiling (reported): Mastic gum at up to 10 g/day was generally well-tolerated with no reported side effects in one study.

8. Safety Considerations and Known Interactions

General Safety Profile

Mastic gum consumption is generally considered safe, although the long-term safety has not been sufficiently investigated, and the maximum safe dose remains unknown. Beyond some cases of allergic contact dermatitis following postoperative use of patches containing mastic, there are hardly any reports of remarkable side effects. High doses of mastic have also been well tolerated in clinical trials, and no adverse effects have been recorded.

When taken by mouth, mastic is possibly safe when used for up to 3 months. It seems to be well-tolerated. Side effects might include constipation.

Allergic Reactions

Most adverse reactions are associated with hypersensitivity to the plant species or with allergic reactions. Most toxic effects related to mastic or P. lentiscus involve allergic reactions. The plant pollen is a major source of allergic reactions, and the first report of immunological reactions to pollen extracts of the Pistacia genus occurred in 1987. People who are allergic to a plant called Schinus terebinthifolius or to Pistacia species might also be allergic to the mastic tree.

Skin Reactions

When applied to the skin, there is not enough reliable information to know if mastic is safe. Some people might experience an itchy rash after using mastic gum topically.

Pregnancy and Lactation

No studies prove mastic gum is safe for children, pregnant people, or those who are breastfeeding. There isn't enough reliable information to know if mastic is safe to use when pregnant or breastfeeding.

Potential Drug Interactions

In one study, people who took mastic gum with the conventional anti-ulcer medication pantoprazole were not cured of H. pylori infections. Those taking mastic gum who have been prescribed pantoprazole (Protonix) or any other proton pump inhibitor for ulcers should be aware of this potential antagonism. The mechanism proposed is that pantoprazole raises gastric pH, reducing the acidic environment needed for mastic's active constituents to function effectively against H. pylori.

It is also unclear whether mastic gum interacts with other medical conditions or drugs. In one study, some people who took just mastic gum eradicated H. pylori infections while those who combined it with antibiotics (amoxicillin or clarithromycin) were all cured in a clinical trial of 52 people. Based on this single study, mastic gum does not appear to reduce the effects of antibiotics, but these data are limited.

Regulatory Status

The Food and Drug Administration (FDA) does not test mastic gum supplements for safety or effectiveness. An approval by the European Medicines Agency for mild dyspeptic disorders and for inflammations of the skin has been given, representing the highest-level regulatory recognition to date for specific therapeutic indications.

Long-term Safety

Current research indicates that mastic gum is safe for use up to three months, though long-term safety data beyond this period is limited. There are only specific reports of possible side effects of mastic originating from animal studies. Well-designed long-duration safety studies in humans have not been published.

References

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