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

Frontiers in Immunology

May 2021

DOI: 10.3389/fimmu.2021.683028

Citations:24

Influential Citations:1

Interventional (Human) Studies

Enhanced Details

Methods

Three-center, randomized, double-blind, placebo-controlled trial (NCT03135873) with 98 adults (BMI ≥30 kg/m2) and NAFLD; men and women, aged 18–67; 87 completed; participants were assigned to Mastiha or placebo for 6 months; NAFLD diagnosed by LiverMultiScan MRI; genetic data collected for nutrigenetic analyses.

Intervention

Mastiha supplementation: 2.1 g/day total, delivered via capsules in 3 equal daily doses for 6 months; placebo capsules contained corn starch and were identical in appearance.

Results

Mastiha supplementation increased total antioxidant status (TAS) in NAFLD patients with severe obesity (BMI > 35 kg/m2) after 6 months vs placebo (P = 0.008; beta = 0.626). No other significant post-treatment changes in measured antioxidant or inflammatory biomarkers were observed in the overall cohort. Genome-wide gene-by-Mastiha interactions identified associations influencing post-treatment levels of Gpx, HB, IL-6, TNF-a, and IL-10, including signals at MLLT3, LSS, GNG5P1, SPOCK3, MIR129-1/LEP, ESR1, TRPC7, CD82, ARHGAP15, and GZMB (genome-wide significance, P ≤ 5×10^-8). These results suggest genetics may modulate responsiveness to Mastiha and warrant replication and functional follow-up. Overall, there is a potential antioxidant benefit in a high-risk subgroup, with no confirmed broad anti-inflammatory effects within the 6-month window.

Limitations

Small sample size with 87 completers; significant TAS improvement confined to BMI >35 kg/m2 subgroup; limited power for genotype-stratified analyses; potential confounding from concomitant medications; biomarker endpoints may not translate to clinical outcomes; limited generalizability beyond severely obese NAFLD.

Abstract

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. show less