Chios mastiha essential oil exhibits antihypertensive, hypolipidemic and anti-obesity effects in metabolically unhealthy adults - a randomized controlled trial.

The essential oil of the resinous exudate from Pistacia lentiscus of Chios namely Chios Mastiha Essential Oil (CMEO), is a natural volatile oil rich in monoterpenes α-pinene, ß-myrcene, ß-pinene. In the present randomized controlled trial, we investigated the effects of CMEO on individuals with abdominal obesity and metabolic abnormalities i.e., dyslipidemia, hypertension, insulin resistance. Eligible patients (N = 94) were randomly assigned to either the intervention group, receiving capsules containing 200 mg of CMEO daily for 3 months adjunct to current treatment for metabolic disorder(s), or the control group. Anthropometric measurements, blood markers, and quality of life (QoL) were assessed. Statistical analysis was performed on an intention-to-treat basis. A significant improvement in blood lipid profile, namely triglycerides (p = 0.026) and low-density lipoprotein (p = 0.05) of the CMEO group versus controls was observed. Systolic blood pressure (p = 0.05) and alanine aminotransferase (p = 0.022) significantly decreased only after CMEO intake. Alike, weight decreased only in CMEO (p = 0.02), while mean changes in % body fat (p = 0.005) and visceral fat (p = 0.045) were significantly different between groups post-intervention. Lower oxidized LDL (p = 0.044) and higher adiponectin (p = 0.007) were recorded in CMEO with significant different mean changes between groups post-intervention. QoL, as assessed by Short Form-12 questionnaire was improved in the CMEO compared to control (p = 0.041 for Physical Composite Score, p = 0.035 for Mental Composite Score). No adverse effects were reported. An anti-obesity effect of CMEO, probably attributed to modulation of inflammatory and antioxidant processes, is suggested. Conclusively, CMEO can be safe and effective in regulating metabolic abnormalities, adjunct to treatment. (ClinicalTrials.gov. The effect of Mastiha oil in Metabolic Syndrome, ID Number: NCT04785573).

Mastiha has efficacy in immune-mediated inflammatory diseases through a microRNA-155 Th17 dependent action.

Mastiha is a natural nutritional supplement with known anti-inflammatory properties. Non-alcoholic fatty liver disease (NAFLD) and Inflammatory bowel disease (IBD) are immune mediated inflammatory diseases that share common pathophysiological features. Mastiha has shown beneficial effects in both diseases. MicroRNAs have emerged as key regulators of inflammation and their modulation by phytochemicals have been extensively studied over the last years. Therefore, the aim of this study was to investigate whether a common route exists in the anti-inflammatory activity of Mastiha, specifically through the regulation of miRNA levels. Plasma miR-16, miR-21 and miR-155 were measured by Real-Time PCR before and after two double blinded and placebo-controlled randomized clinical trials with Mastiha. In IBD and particularly in ulcerative colitis patients in relapse, miR-155 increased in the placebo group (p = 0.054) whereas this increase was prevented by Mastiha. The mean changes were different in the two groups even after adjusting for age, sex and BMI (p = 0.024 for IBD and p = 0.042). Although the results were not so prominent in NAFLD, miR-155 displayed a downward trend in the placebo group (p = 0.054) whereas the levels did not changed significantly in the Mastiha group in patients with less advanced fibrosis. Our results propose a regulatory role for Mastiha in circulating levels of miR-155, a critical player in T helper-17 (Th17) differentiation and function.

Regulation of faecal biomarkers in inflammatory bowel disease patients treated with oral mastiha (Pistacia lentiscus) supplement: A double-blind and placebo-controlled randomised trial.

There is a keen research upon the effects of nutraceuticals on inflammatory bowel disease. The purpose of this study was to explore the effect of mastiha supplement, rich in bioactive nutraceuticals, in active inflammatory bowel disease. This is a randomised, double-blind, placebo-controlled clinical trial. Α total of 60 inflammatory bowel disease patients were enrolled and randomly allocated to mastiha (2.8 g/day) or placebo groups for 3 months adjunct to stable medical treatment. Medical and dietary history, Inflammatory Bowel Disease Questionnaire (IBDQ), Harvey-Bradshaw index, partial Mayo score, biochemical indices, faecal, and blood inflammatory markers were assessed. A clinically important difference between groups in IBDQ was defined as primary outcome. Inflammatory Bowel Disease Questionnaire score significantly improved in verum compared with baseline (p = 0.004). There was a significant decrease in faecal lysozyme in mastiha patients (p = 0.018) with the mean change being significant (p = 0.021), and significant increases of faecal lactoferrin (p = 0.001) and calprotectin (p = 0.029) in the placebo group. Fibrinogen reduced significantly (p = 0.006) with a significant mean change (p = 0.018), whereas iron increased (p = 0.032) in mastiha arm. Our results show regulation of faecal lysozyme by mastiha supplement adjunctive to pharmacological treatments in active inflammatory bowel disease. An effect secondary to a prebiotic potency is proposed.

Antihypertensive Potential of Pistacia lentiscus var. Chia: Molecular Insights and Therapeutic Implications.

Background: Hypertension poses a significant global health burden and is associated with cardiovascular morbidity. Chios mastic gum (CMG), derived from Pistacia lentiscus var. Chia, shows potential as a phytotherapeutic agent, due to its multifaceted beneficial effects. However, its anti-hypertensive effects and vascular, circulatory, and renal-related dysfunction, have not been thoroughly investigated. Herein, we aimed to explore the antihypertensive potential of CMG, focusing on vascular and renal endothelium, in vivo. Methods: Two models of hypertension in male rats, induced by Angiotensin II and Deoxycorticosterone acetate (DOCA)-high-salt administration, were utilized. CMG was administered at 220 mg/kg daily for four weeks after hypertension onset and blood pressure was measured non-invasively. Whole blood RNA sequencing, metabolomics, real-time PCR, and Western blot analyses of kidney and aorta tissues were additionally performed. Results: CMG significantly lowered systolic, diastolic, and mean blood pressure in both models. RNA sequencing revealed that CMG modulated immunity in the Angiotensin II model and metabolism in the DOCA-HS model. CMG downregulated genes related to oxidative stress and endothelial dysfunction and upregulated endothelial markers such as Vegfa. Metabolomic analysis indicated improved endothelial homeostasis via lysophosphatidylinositol upregulation. Conclusions: CMG emerges as a potent natural antihypertensive therapy, demonstrating beneficial effects on blood pressure and renal endothelial function.

Effects of Chios Mastiha essential oil on cholesterol levels of healthy volunteers: A prospective, randomized, placebo-controlled study (MASTIHA-OIL).

INTRODUCTION: Chios Mastiha essential oil (CMO) is a natural product extracted from the resin of Mastiha, possessing antioxidant, anti-microbial, anti-ulcer, anti-neoplastic, and cholesterol-lowering capabilities in vitro, and its hypolipidemic effect was confirmed in animal studies. Yet, there are no randomized, placebo-controlled clinical studies in the literature regarding CMO's hypolipidemic effects in humans. A prospective, randomized, placebo-controlled study was designed to study the hypolipidemic effect of CMO capsules on healthy volunteers with elevated cholesterol. METHODS: 192 healthy volunteers were screened and 160 of them with total cholesterol> 200 mg/dl participated in the study. They were randomized with a 2:1 ratio of receiving CMO capsules (200 mg mastiha-oil/capsule) and placebo for 8 weeks respectively. 113 patients received CMO and 47 were randomized in the control group, and all of them completed the follow-up period. RESULTS: After 8 weeks of CMO administration, total and LDL cholesterol were significantly lower in the CMO compared to the placebo group 215.2 ± 27.5 vs 237.0 ± 27.9 mg/dl (p < 0.001) and 135.0 ± 26.1 vs 153.0 ± 23.3 mg/dl (p < 0.001) respectively. No gastrointestinal adverse events or liver or renal toxicity were reported. Additionally, in the CMO group total cholesterol was significantly decreased by 20.6 mg/dl (9%), LDL by 18.1 mg/dl (12%), triglycerides by 21.8 mg/dl (15%), and glucose by 4.6 mg/dl (5%) and HDL was increased by 2.4 mg/dl (5%), compared to their baseline values. CONCLUSION: The MASTIHA-OIL study showed the efficacy and safety of CMO in reduction of total and LDL cholesterol after 8 weeks of administration in healthy volunteers with elevated cholesterol levels.

Association of Dietary Patterns with MRI Markers of Hepatic Inflammation and Fibrosis in the MAST4HEALTH Study.

Whereas the etiology of non-alcoholic fatty liver disease (NAFLD) is complex, the role of nutrition as a causing and preventive factor is not fully explored. The aim of this study is to associate dietary patterns with magnetic resonance imaging (MRI) parameters in a European population (Greece, Italy, and Serbia) affected by NAFLD. For the first time, iron-corrected T1 (cT1), proton density fat fraction (PDFF), and the liver inflammation fibrosis score (LIF) were examined in relation to diet. A total of 97 obese patients with NAFLD from the MAST4HEALTH study were included in the analysis. A validated semi-quantitative food frequency questionnaire (FFQ) was used to assess the quality of diet and food combinations. Other variables investigated include anthropometric measurements, total type 2 diabetes risk, physical activity level (PAL), and smoking status. Principal component analysis (PCA) was performed to identify dietary patterns. Six dietary patterns were identified, namely "High-Sugar", "Prudent", "Western", "High-Fat and Salt", "Plant-Based", and "Low-Fat Dairy and Poultry". The "Western" pattern was positively associated with cT1 in the unadjusted model (beta: 0.020, p-value: 0.025) and even after adjusting for age, sex, body mass index (BMI), PAL, smoking, the center of the study, and the other five dietary patterns (beta: 0.024, p-value: 0.020). On the contrary, compared with low-intake patients, those with medium intake of the "Low-Fat Dairy and Poultry" pattern were associated with lower values of cT1, PDFF, and LIF. However, patients with a "Low-Fat Dairy and Poultry" dietary pattern were negatively associated with MRI parameters (cT1: beta: -0.052, p-value: 0.046, PDFF: beta: -0.448, p-value: 0.030, LIF: beta: -0.408, p-value: 0.025). Our findings indicate several associations between MRI parameters and dietary patterns in NAFLD patients, highlighting the importance of diet in NAFLD.

Nutrigenetic Interactions Might Modulate the Antioxidant and Anti-Inflammatory Status in Mastiha-Supplemented Patients With NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease with no therapeutic consensus. Oxidation and inflammation are hallmarks in the progression of this complex disease, which also involves interactions between the genetic background and the environment. Mastiha is a natural nutritional supplement known to possess antioxidant and anti-inflammatory properties. This study investigated how a 6-month Mastiha supplementation (2.1 g/day) could impact the antioxidant and inflammatory status of patients with NAFLD, and whether genetic variants significantly mediate these effects. We recruited 98 patients with obesity (BMI ≥ 30 kg/m2) and NAFLD and randomly allocated them to either the Mastiha or the placebo group for 6 months. The anti-oxidative and inflammatory status was assessed at baseline and post-treatment. Genome-wide genetic data was also obtained from all participants, to investigate gene-by-Mastiha interactions. NAFLD patients with severe obesity (BMI > 35kg/m2) taking the Mastiha had significantly higher total antioxidant status (TAS) compared to the corresponding placebo group (P value=0.008). We did not observe any other significant change in the investigated biomarkers as a result of Mastiha supplementation alone. We identified several novel gene-by-Mastiha interaction associations with levels of cytokines and antioxidant biomarkers. Some of the identified genetic loci are implicated in the pathological pathways of NAFLD, including the lanosterol synthase gene (LSS) associated with glutathione peroxidase activity (Gpx) levels, the mitochondrial pyruvate carrier-1 gene (MPC1) and the sphingolipid transporter-1 gene (SPNS1) associated with hemoglobin levels, the transforming growth factor-beta-induced gene (TGFBI) and the micro-RNA 129-1 (MIR129-1) associated with IL-6 and the granzyme B gene (GZMB) associated with IL-10 levels. Within the MAST4HEALTH randomized clinical trial (NCT03135873, www.clinicaltrials.gov) Mastiha supplementation improved the TAS levels among NAFLD patients with severe obesity. We identified several novel genome-wide significant nutrigenetic interactions, influencing the antioxidant and inflammatory status in NAFLD. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03135873.

Effect of Mastiha supplementation on NAFLD: The MAST4HEALTH Randomised, Controlled Trial.

SCOPE: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease with poor therapeutic strategies. Mastiha possesses antioxidant/anti-inflammatory and lipid-lowering properties. The authors investigate the effectiveness of Mastiha as a nonpharmacological intervention in NAFLD. METHODS AND RESULTS: Ninety-eight patients with NAFLD in three countries (Greece, Italy, Serbia) are randomly allocated to either Mastiha or Placebo for 6 months, as part of a multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The authors assess NAFLD severity via magnetic resonance imaging (MRI) scanning and LiverMultiScan technique and evaluate the effectiveness of Mastiha through medical, anthropometric, biochemical, metabolomic, and microbiota assessment. Mastiha is not superior to Placebo on changes in iron-corrected T1 (cT1) and Liver Inflammation Fibrosis score (LIF) in entire patient population; however, after BMI stratification (BMI ≤ 35 kg m-2 and BMI > 35 kg m-2 ), severely obese patients show an improvement in cT1 and LIF in Mastiha versus Placebo. Mastiha increases dissimilarity of gut microbiota, as shown by the Bray-Curtis index, downregulates Flavonifractor, a known inflammatory taxon and decreases Lysophosphatidylcholines-(LysoPC) 18:1, Lysophosphatidylethanolamines-(LysoPE) 18:1, and cholic acid compared to Placebo. CONCLUSION: Mastiha supplementation improves microbiota dysbiosis and lipid metabolite levels in patients with NAFLD, although it reduces parameters of liver inflammation/fibrosis only in severely obese patients.

Modulation of Free Amino Acid Profile in Healthy Humans Administered with Mastiha Terpenes. An Open-Label Trial.

We aimed to explore whether plasma-free amino acids are modified in response to terpenes administration in healthy humans. In this open-label, single-arm acute trial, seventeen healthy male volunteers were administered with a naturally occurring product of known terpenes-namely mastiha-after overnight fasting. Blood samples were collected at different time points before and after ingestion. We aimed at identifying and quantifying 60 free amino acids in plasma applying Gas Chromatography-Mass Spectrometry. A total of 24 free amino acids were quantified. Branched-chain valine significantly decreased 4 h post-ingestion, whereas proline decreased at 6 h and ornithine at 2 h, compared to 0 h. These novel findings demonstrate that free amino acids levels are modulated in response to terpenes intake in healthy subjects.

Effects of Chios mastic gum and exercise on physical characteristics, blood lipid markers, insulin resistance, and hepatic function in healthy Japanese men.

The effects of Chios mastic gum (Pistacia lentiscus var. Chia) and exercise on physical characteristics, blood lipid markers, insulin resistance, and hepatic function were investigated in healthy, non-smoking Japanese men aged ≥ 40 years. Participants were allocated to control (C, 5 g/day placebo powder, n = 7), mastic (M, 5 g/day mastic powder, n = 7), or mastic plus physical activity groups (M + PA, 5 g/day mastic powder and 30-min exercise three times/week, n = 7), and measurements were taken at baseline, 3 and 6 months. Serum triglycerides were significantly reduced at 3 months in M and M + PA compared with C (P < 0.05). Serum insulin and homeostatic model assessment of insulin resistance values were significantly reduced at 3 and 6 months in M + PA, and at 6 months in M, compared with C (P < 0.05). These results indicate that Chios mastic gum intake for 6 months reduced serum triglyceride and insulin concentrations, and additional exercise enhanced the effect on insulin.

Bioavailability of Terpenes and Postprandial Effect on Human Antioxidant Potential. An Open-Label Study in Healthy Subjects.

SCOPE: To assess bioavailability of terpenes in human plasma and their effect on oxidative stress biomarkers. METHODS AND RESULTS: In this open-label and single arm postprandial trial, seventeen healthy male volunteers (20-40 years old) follow a low-phytochemical diet for 5 days. Next, after overnight fasting, volunteers consume Mastiha powder (a natural resin rich in terpenes) dispersed in water. Blood samples are collected on time points 0 h (before ingestion) and 0.5, 1, 2, 4, 6, and 24 h (post-ingestion). Ultra-high-pressure liquid chromatography high-resolution MS (UHPLC-HRMS/MS) is applied for high throughput analysis of plasma. Serum resistance to oxidation and oxidized LDL (oxLDL) levels are measured. UHPLC-HRMS/MS analysis shows that major terpenes are bioavailable since 0.5 h after administration, reaching a peak between 2 h and 4 h. Serum resistance to oxidation, expressed as difference of tLAG (time point-0 h), starts to increase from 0.5 h. This increase reaches statistical significance at 4 h (402.3 ± 65.0 s), peaks at 6 h (524.6 ± 62.9 s), and remains statistically significant until 24 h (424.2 ± 48.0 s). oxLDL levels, expressed as %change from 0 h, are reduced significantly from time point-1 h until time point-6 h. CONCLUSION: Results demonstrate the terpene bioavailability pattern after oral administration of Mastiha. Terpenes are potential mediators of antioxidant defense in vivo.

Quality profile determination of Chios mastic gum essential oil and detection of adulteration in mastic oil products with the application of chiral and non-chiral GC-MS analysis.

The determination of mastic oil profile, with emphasis on its chiral characteristics, could serve as a method for detecting adulteration in products found in the market with a claim of mastic oil content aiming towards protecting it from counterfeiting. Furthermore the evaluation of the raw material is crucial, as the profile is potentially affected by factors as mastic origin and storage time. Thus 45 authentic mastic oil samples were analyzed by GC-MS employing a chiral column and content limits for all major constituents were determined. The chiral GC-MS analysis proved that selected concentration ratios between these constituents, namely those of (-)/(+)-α-pinene (≤1:100) and (-)-α-pinene/myrcene (1.9:100-11:100) could serve as markers for the determination of mastic oil authenticity. Employing this methodology, the analysis of 25 mastic oils contained in cosmetic and dietary products, as well as an artificial mastic oil sample, exhibited several differentiations that could indicate adulteration either with artificial essential oils or volatile compounds, or the use of aged mastic oil.