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.

Medium-term effect of sublingual l-glutathione supplementation on flow-mediated dilation in subjects with cardiovascular risk factors.

OBJECTIVE: Supplementation of glutathione (GSH) may be a positive strategy to improve the endogenous antioxidant defense required to counteract many acute and chronic diseases. However, the efficacy of GSH treatment seems to be closely related to type of administration, degree of absorption, and increase of its concentrations. The aim of this study was to test a new sublingual formulation of L-GSH, which enters directly the systemic circulation, to assess its efficacy on circulating biochemical markers of hepatic metabolism, lipid profile, and oxidative stress and on peripheral vascular function compared with placebo in patients with cardiovascular risk factors (CVRF). METHODS: We enrolled 16 healthy men with CVRF in a double-blinded, randomized placebo-controlled crossover study. At each visit, blood samples were collected for biochemistry analyses and peripheral endothelial function (reactive hyperemia index [RHI]) and stiffness were measured by Endo-PAT2000. RESULTS: In the overall population, a decrease in total and low-density lipoprotein cholesterol was highlighted after L-GSH supplementation compared with placebo (P = 0.023 and P = 0.04, respectively). On the contrary, no difference was observed in RHI and oxidative stress markers between L-GSH and placebo in the study population. However, seven participants with baseline abnormal RHI (≤1.67) compared with those with normal RHI showed a significant reduction of arterial stiffness after L-GSH administration, (P = 0.007 and P = 0.037, respectively). CONCLUSIONS: Supplementation of L-GSH compared with placebo influences the lipid profile of patients with CVRF. Sublingual L-GSH may represent a valid prevention of vascular damage in patients with CVRF and endothelial dysfunction.

A single portion of blueberry (Vaccinium corymbosum L) improves protection against DNA damage but not vascular function in healthy male volunteers.

It has been suggested that anthocyanin-rich foods may exert antioxidant effects and improve vascular function as demonstrated mainly in vitro and in the animal model. Blueberries are rich sources of anthocyanins and we hypothesized that their intake could improve cell protection against oxidative stress and affect endothelial function in humans. The aim of the study was to investigate the effect of one portion (300 g) of blueberries on selected markers of oxidative stress and antioxidant protection (endogenous and oxidatively induced DNA damage) and of vascular function (changes in peripheral arterial tone and plasma nitric oxide levels) in male subjects. In a randomized cross-over design, separated by a wash out period ten young volunteers received one portion of blueberries ground by blender or one portion of a control jelly. Before and after consumption (at 1, 2, and 24 hours), blood samples were collected and used to evaluate anthocyanin absorption (through mass spectrometry), endogenous and H(2)O(2)-induced DNA damage in blood mononuclear cells (through the comet assay), and plasma nitric oxide concentrations (through a fluorometric assay). Peripheral arterial function was assessed by means of Endo-PAT 2000. Blueberries significantly reduced (P < .01) H(2)O(2)-induced DNA damage (-18%) 1 hour after blueberry consumption compared to control. No significant differences were observed for endogenous DNA damage, peripheral arterial function and nitric oxide levels after blueberry intake. In conclusion, one portion of blueberries seems sufficient to improve cell antioxidant defense against DNA damage, but further studies are necessary to understand their role on vascular function.

Effect of a wild blueberry (Vaccinium angustifolium) drink intervention on markers of oxidative stress, inflammation and endothelial function in humans with cardiovascular risk factors.

PURPOSE: Wild blueberries (WB) (Vaccinium angustifolium) are rich sources of polyphenols, such as flavonols, phenolic acids and anthocyanins (ACNs), reported to decrease the risk of cardiovascular and degenerative diseases. This study investigated the effect of regular consumption of a WB or a placebo (PL) drink on markers of oxidative stress, inflammation and endothelial function in subjects with risk factors for cardiovascular disease. METHODS: Eighteen male volunteers (ages 47.8 ± 9.7 years; body mass index 24.8 ± 2.6 kg/m²) received according to a cross-over design, a WB (25 g freeze-dried powder, providing 375 mg of ACNs) or a PL drink for 6 weeks, spaced by a 6-week wash-out. Endogenous and oxidatively induced DNA damage in blood mononuclear cells, serum interleukin levels, reactive hyperemia index, nitric oxide, soluble vascular adhesion molecule concentration and other variables were analyzed. RESULTS: Wild blueberry drink intake significantly reduced the levels of endogenously oxidized DNA bases (from 12.5 ± 5.6 % to 9.6 ± 3.5 %, p ≤ 0.01) and the levels of H2O2-induced DNA damage (from 45.8 ± 7.9 % to 37.2 ± 9.1 %, p ≤ 0.01), while no effect was found after the PL drink. No significant differences were detected for markers of endothelial function and the other variables under study. CONCLUSIONS: In conclusion, the consumption of the WB drink for 6 weeks significantly reduced the levels of oxidized DNA bases and increased the resistance to oxidatively induced DNA damage. Future studies should address in greater detail the role of WB in endothelial function.

Effect of homocysteine lowering by 5-methyltetrahydrofolate on redox status in hyperhomocysteinemia.

The endothelial dysfunction induced by hyperhomocysteinemia can be reversed by 5-methyltetrahydrofolate (5-MTHF) via homocysteine (Hcy) lowering. An additive antioxidant action of 5-MTHF has been suggested to ameliorate endothelial dysfunction through increased nitric oxide production and superoxide radical scavenging, independent of Hcy lowering. The aim of the study was to assess whether 5-MTHF affects the redox state in hyperhomocysteinemia. We examined the effect of 3 months of oral 5-MTHF treatment (15 mg/day) on the redox pattern in 48 hyperhomocysteinemic subjects compared to 24 untreated hyperhomocysteinemic subjects. By analysis of variance with repeated measures in the 72 subjects, 5-MTHF markedly decreased plasma total Hcy (p-tHcy; P = 0.0001) and blood-total glutathione (GSH; b-tGSH; P = 0.002). By multivariate linear regression in the treated subjects, p-tHcy changes from baseline to 3 months (adjusted by baseline p-tHcy levels) correlated only with changes in reduced cysteinylglycine (P = 0.001). The effects of treatment on Hcy lowering and GSH metabolism were greater in medium than in moderate hyperhomocysteinemia. In conclusion, high-dose 5-MTHF treatment for 3 months ensures marked Hcy lowering to normal values even in subjects with high Hcy levels, and should be the treatment of choice in medium hyperhomocysteinemia. Furthermore, 5-MTHF shows a favorable interaction with GSH metabolism.