This headline may immediately suggest Greek islands, olive oil, and sunshine – all of which can imbue a sense of well-being, but this review is centred on a natural product, utilised for thousands of years and a regular source of contemporary research. Chios Mastic Gum (CMG), an aromatic, white resin derived from the Pistacia lentiscus tree is a Greek health treasure. CMG was first noted by Greeks 2,500 years ago for culinary as well as medicinal applications, and praised by Pedanios Dioscorides, a physician and botanist who wrote the world’s first systematic pharmacopoeia, De Materia Medica, around 70 AD[1].
CMG’s effectiveness in peptic ulcer disease
Peptic ulcers were long thought to be induced solely due to stress, and the typical treatment included the use of antacids[2]. In 1983, however, Australian physician Barry Marshall and his colleague Robin Warren discovered that the bacterium Helicobacter pylori was the cause of many cases of chronic gastritis (inflammation of the stomach lining), peptic ulcer disease, and certain gastric cancers[3]. Marshall and Warren were awarded the Nobel Prize in Physiology or Medicine for this remarkable discovery[4].
Though the standard of care involving the use of multi-pronged antibiotics is effective in eradicating H. pylori, antibiotics are not always well-tolerated and can cause significant alterations to the gut microbiome[5]. According to various studies there is also a direct relationship between the increased use of antibiotics and the creation of resistant bacteria. The appearance of resistant microorganisms to drugs then leads to the currently available treatment regimens becoming less effective or totally ineffective. To overcome this problem, identifying alternative or complementary approaches is urgently needed to prevent and treat microbial infections[6].
“Even low doses of CMG — 1 mg per day for two weeks — can cure peptic ulcers very rapidly,” they noted.
In the late 1990s, scientists reported in the New England Journal of Medicine on the benefits of CMG for six different strains of H. pylori infection: “Even low doses of CMG — 1 mg per day for two weeks — can cure peptic ulcers very rapidly,” they noted[7]. A further study found effective bactericidal activity against nine strains of H. pylori along with other gram-negative and gram-positive bacteria[8]. And research in 2010, found CMG able to safely eradicate H. pylori and alleviate symptoms of chronic gastritis and peptic ulcer disease[9].
The extraintestinal consequences of H. Pylori
Beyond the peptic ulcer story, there is growing evidence that H. pylori infection may be related to numerous extra gastric diseases of various systems throughout the human body in addition to the pathogenetic effects on gastric diseases. These include respiratory, cardiovascular, digestive, liver, diabetic, blood disorders, endocrine and nerve, ophthalmic, reproductive, urinary and dermatological problems. The researchers in this paper published in Frontiers in Microbiology hypothesise the associated disorders can be attributed to the following mechanisms[10]:
- Since pylori can induce several inflammatory factors, such as IL-1/2/6/8/10, TNF-α and IFN-γ, these factors may lead to chronic low-level systemic inflammation in the human body and ultimately represent diseases. Typical disorders due to H. pylori-induced inflammatory factor turbulence include atherosclerosis, insulin resistance, blood-brain barrier damage, brain neurodegenerative disease and decreased sperm motility.
- pylori antigen, like the antigen components of the host leads to molecular mimicry and cross-antigen reactions, which can cause autoimmune attacks and relevant diseases.
CMG and IBD
Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBD) involving the large bowel (UC) or the small and large bowel (CD), in which patients require both induction and maintenance treatment[11]. The pathogenesis of IBD is multifactorial, including genetic predisposition, immune dysregulation, barrier dysfunction, and altered microbial flora, as well as environmental and lifestyle factors. The conventional treatment of IBD includes the use of corticosteroids, immunosuppressants, antibiotics, and biologic agents (anti-tumour necrosis factor (TNF)-α). However, the use of these drugs is accompanied by side effects, with some of them being quite severe.
In a relevant study, the effectiveness of CMG on the clinical course and plasma inflammatory mediators of patients with active CD was evaluated. Recruited to a 4-week treatment with CMG caps (6 caps/d, 0.37 g/cap) were 10 patients and 8 controls. It was found that CMG treatment significantly decreased the CD activity index and the plasma levels of IL-6 and CRP[12].
A further study found that mastic acts as an immunomodulator on peripheral blood mononuclear cells, acting as a TNF-α inhibitor and a migration inhibitory factor stimulator[13]. In particular, the main non-rectal inflammation element that showed improvement was body weight gain, attributed to the decrease in loose stools with the consequent improvement in nutrient absorption, as the daily energy intake remained unchanged during the study.
In 2019, Papada et al.[14], based on the findings of prior animal studies, performed a randomised controlled trial to further investigate the effects of CMG on patients with IBD. The authors’ primary aim was a clinically meaningful improvement in patients’ quality of life assessed using the Inflammatory Bowel Disease Questionnaire (IBDQ), which consists of 32 questions on the bowel, social, systemic, and emotional performances.
A total of 60 patients with endoscopy-proven UC or CD were randomly administered with CMG 2.8 g/day or placebo for 3 months in addition to stable medical treatment. Patients treated with CMG had a significant decrease in faecal lysozyme compared to patients on placebo. In addition to this, a significant improvement in IBDQ scores, reflecting a beneficial effect on patients’ quality of life, was observed in the CMG arm compared to the baseline.
The data from the literature to date (more studies will be beneficial) show that CMG reduces pro-inflammatory cytokines such as IL-6 and TNF-α and increases the levels of interleukin-a17A , which is considered a protective key factor in the development and relapse of IBD[15]. These data have been corroborated by randomised controlled studies showing that CMG may also reduce free amino acids in plasma[16], a surrogate for inflammation and cell homeostasis[17], and may play a key role in pathways regulating intestinal health.
Because of these and other studies, CMG may be used as a supplement to decrease disease activity, improve nutritional status, maintain clinical remission in IBD patients and resolve H. Pylori infections.
It has other beneficial effects on Functional dyspepsia, obesity, blood sugar regulation, hypertension, lipid management, NAFLD and some types of cancerous changes[18]. CMG is a safe multifactorial food supplement with a wide range of mechanistic actions and may be utilised alone or in conjunction with probiotics and other inflammation interventions such as Turmeric or Aloe vera[19].
References
[1] Paraschos S. Chios gum mastic: A review of its biological activities. Curr Med Chem. 2012;19(14):2292-302
[2] Abbasi J. Barry Marshall, MD: H pylori 35 Years Later. JAMA. 2017 Apr 11;317(14):1400-1402
[3] Warren JR, Marshall B. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. 1983. Lancet 321:1273-1275.
[4] Marshall, B. Helicobacter connections. Chem Med Chem. 2006;1: 783-802
[5] Langdon A, et al. The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation. Genome Medicine. 2016;8:39.
[6] Khameneh B, Iranshahy M, Soheili V, Fazly Bazzaz BS. Review on plant antimicrobials: a mechanistic viewpoint. Antimicrob Resist Infect Control. 2019 Jul 16;8:118.
[7] Huwez FA, et al. Mastic gum kills Helicobacter pylori. New Eng J Med 1998;339:1946
[8] Francis NA, et al. Oral and Topical Antibiotics for Clinically Infected Eczema in Children: A Pragmatic Randomized Controlled Trial in Ambulatory Care. Ann Fam Med. 2017 Mar;15(2):124-130
[9] Dabos KJ, et al. The effect of mastic gum on Helicobacter pylori: a randomized pilot study. Phytomedicine. 2010 Mar;17(3-4):296-9. 2009 Oct 29
[10] He J, Liu Y, Ouyang Q, Li R, Li J, Chen W, Hu W, He L, Bao Q, Li P and Hu C (2022) Helicobacter pylori and unignorable extragastric diseases: Mechanism and implications. Front. Microbiol. 13:972777.
[11] Triantafillidis JK, Stanciu C, editors. 4th Edition. Athens, Greece: “Technogramma”; 2012. Inflammatory bowel disease: etiopathogenesis, diagnosis, treatment.
[12] Kaliora AC, Stathopoulou MG, Triantafillidis JK, Dedoussis GV, Andrikopoulos NK. Chios mastic treatment of patients with active Crohn’s disease. World J Gastroenterol. 2007;13:748–753
[13] Kaliora AC, Stathopoulou MG, Triantafillidis JK, Dedoussis GV, Andrikopoulos NK. Alterations in the function of circulating mononuclear cells derived from patients with Crohn’s disease treated with mastic. World J Gastroenterol. 2007;13:6031–6036.
[14] Papada E., Gioxari A., Amerikanou C., Forbes A., Tzavara C., Smyrnioudis I., Kaliora A.C. (Regulation of faecal biomarkers in inflammatory bowel disease patients treated with oral mastiha (Pistacia lentiscus) supplement: A double-blind and placebo-controlled randomised trial. Phytother. Res. 2019;33:360–369
[15] Amerikanou C., Dimitropoulou E., Gioxari A., Papada E., Tanaini A., Fotakis C., Zoumpoulakis P., Kaliora A.C. Linking the IL-17A immune response with NMR-based faecal metabolic profile in IBD patients treated with Mastiha. Biomed. Pharmacother. 2021;138:111535
[16] Papada E., Forbes A., Amerikanou C., Torović L., Kalogeropoulos N., Tzavara C., Triantafillidis J.K., Kaliora A.C. Antioxidative Efficacy of a Pistacia lentiscus Supplement and Its Effect on the Plasma Amino Acid Profile in Inflammatory Bowel Disease: A Randomised, Double-Blind, Placebo-Controlled Trial. Nutrients. 2018;10:1779
[17] Nakaya M., Xiao Y., Zhou X., Chang J.-H., Chang M., Cheng X., Blonska M., Lin X., Sun S.-C. Inflammatory T cell responses rely on amino acid transporter ASCT2 facilitation of glutamine uptake and mTORC1 kinase activation. Immunity. 2014;40:692–705
[18] Soulaidopoulos S, Tsiogka A, Chrysohoou C, Lazarou E, Aznaouridis K, Doundoulakis I, Tyrovola D, Tousoulis D, Tsioufis K, Vlachopoulos C, Lazaros G. Overview of Chios Mastic Gum (Pistacia lentiscus) Effects on Human Health. Nutrients. 2022 Jan 28;14(3):590.
[19] Triantafyllidi A, Xanthos T, Papalois A, Triantafillidis JK. Herbal and plant therapy in patients with inflammatory bowel disease. Ann Gastroenterol. 2015 Apr-Jun;28(2):210-220.
