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.

Evaluation of the antioxidant effect of a new functional food enriched with Sideritis euboea in healthy subjects.

Sideritis euboea is a Greek plant that is traditionally consumed as a beverage (mountain tea). From in vitro studies, its extract has shown antioxidant and estrogenic activities. In our study we used S. euboea as an enriching food factor in order to produce a new functional food, a jelly dessert, in order to explore its antioxidant effects if consumed on a daily basis by healthy subjects. In this placebo-controlled clinical trial, 63 subjects were recruited for a 1-month nutritional intervention. Twelve subjects were excluded. The remaining 51 subjects were randomly classified in the intervention group (daily consumption of the jelly containing 0.3 g of S. euboea extract) or the placebo group (daily consumption of the same jelly without the enrichment). Vitamins C, A, and E, glutathione, coenzyme Q10, total nitrites, nitrates, total nitrogen oxide, nitrites/nitrates ratio, and total antioxidant status were measured in blood samples before and after the intervention. After the intervention, free glutathione and coenzyme Q10 increased, and nitrites decreased significantly in both groups. The other antioxidant markers were not altered. No statistical significant differences were observed between the two groups. The daily consumption of the functional food, for 30 days, had no effects on the antioxidant status of healthy volunteers.

The development and implementation of a software tool and its effect on the quality of provided clinical nutritional therapy in hospitalized patients.

The authors developed "DIET", a computerized system preparing dietary prescriptions in clinical settings. "DIET" has the ability to calculate the nutritional requirements and to produce daily menus of patients automatically. Also, it serves as an electronic medical and dietetic record and it can produce daily reports regarding portions, quantities and cost of meals. The authors also conducted a preliminary evaluation of the system by comparing the design of nutritional plans for 135 patients using "DIET" versus the customary manual methods. Its use resulted in a decrease of the error percentages, concerning appropriate food choices, data recording and calculations of daily nutrient requirements; from 12% to 1.5%. Additionally, there was a reduction by 50% of the time required to obtain and process data as well as design a patient's menu. "DIET" implementation resulted in error decrease and thus in improvement of menu planning, accuracy and recovery of data and decreased the time spent on menu planning.

Alterations in the function of circulating mononuclear cells derived from patients with Crohn's disease treated with mastic.

AIM: To assess the effects of mastic administration on cytokine production of circulating mononuclear cells of patients with active Crohn's disease (CD). METHODS: The study was conducted in patients with established mildly to moderately active CD, attending the outpatient clinics of the hospital, and in healthy controls. Recruited to a 4 wk treatment with mastic caps (6 caps/d, 0.37 g/cap) were 10 patients and 8 controls, all of who successfully completed the protocol. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), macrophage migration inhibitory factor (MIF) and intracellular antioxidant glutathione (GSH) were evaluated in peripheral blood mononuclear cells (PBMC) before and after treatment. RESULTS: Treating CD patients with mastic resulted in the reduction of TNF-alpha secretion (2.1 +/- 0.9 ng/mL vs 0.5 +/- 0.4 ng/mL, P = 0.028). MIF release was significantly increased (1.2 +/- 0.4 ng/mL vs 2.5 +/- 0.7 ng/mL, P = 0.026) meaning that random migration and chemotaxis of monocytes/macrophages was inhibited. No significant changes were observed in IL-6, MCP-1 and GSH concentrations. CONCLUSION: This study shows that mastic acts as an immunomodulator on PBMC, acting as a TNF-alpha inhibitor and a MIF stimulator. Although further double-blind, placebo-controlled studies in a large number of patients is required to clarify the role of this natural product, this finding provides strong evidence that mastic might be an important regulator of immunity in CD.

Chios mastic treatment of patients with active Crohn's disease.

AIM: To evaluate the effectiveness of mastic administration on the clinical course and plasma inflammatory mediators of patients with active Crohn's disease (CD). METHODS: This pilot study was conducted in patients with established mild to moderately active CD, attending the outpatient clinics of the hospital, and in healthy controls. Ten patients and 8 controls were recruited for a 4-wk treatment with mastic caps (6 caps/d, 0.37 g/cap). All patients successfully completed the protocol. CD Activity Index (CDAI), Nutritional Risk Index (NRI), C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), and total antioxidant potential (TAP) were evaluated in the plasma at baseline and at the end of the treatment period. Results were expressed as mean values +/- SE and P < 0.05 was considered to indicate statistical significance. RESULTS: Patients exhibited significant reduction of CDAI (222.9 +/- 18.7 vs 136.3 +/- 12.3, P = 0.05) as compared to pretreament values. Plasma IL-6 was significantly decreased (21.2 +/- 9.3 pg/mL vs 7.2 +/- 2.8 pg/ mL, P = 0.027), and so did CRP (40.3 +/- 13.1 mg/mL vs 19.7 +/- 5.5, P = 0.028). TAP was significantly increased (0.15 +/- 0.09 vs 0.57 +/- 0.15 mmol/L uric acid, P = 0.036). No patient or control exhibited any kind of side effects. CONCLUSION: The results suggest that mastic significantly decreased the activity index and the plasma levels of IL-6 and CRP in patients with mildly to moderately active CD. Further double-blind, placebo-controlled studies in a larger number of patients are required to clarify the role of this natural product in the treatment of patients with CD.