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

  • 2021-05-07
  • Frontiers in immunology 12
    • Stavroula Kanoni
    • Satish Kumar
    • Charalampia Amerikanou
    • Mary Jo Kurth
    • Maria G Stathopoulou
    • Stephane Bourgeois
    • Christine Masson
    • Aimo Kannt
    • Lucia Cesarini
    • Maria-Spyridoula Kontoe
    • Maja Milanović
    • Francisco J Roig
    • Mirjana Beribaka
    • Jonica Campolo
    • Nuria Jiménez-Hernández
    • Nataša Milošević
    • Carlos Llorens
    • Ilias Smyrnioudis
    • M Pilar Francino
    • Nataša Milić
    • Andriana C Kaliora
    • Maria Giovanna Trivella
    • Mark W Ruddock
    • Milica Medić-Stojanoska
    • Amalia Gastaldelli
    • John Lamont
    • Panos Deloukas
    • George V Dedoussis
    • Sophie Visvikis-Siest

Study Design

Type
Randomized Controlled Trial (RCT)
Sample size
n = 98
Population
98 patients with obesity (BMI ≥ 30 kg/m2) and NAFLD
Methods
Randomized, placebo-controlled trial; 6-month Mastiha supplementation (2.1 g/day) vs placebo; genome-wide genetic data obtained
Blinding
Double-blind
Duration
6 months
Funding
Unclear
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.

Research Insights

  • Mastic→Increased Antioxidant Enzyme Levels

    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).

    Effect
    Beneficial
    Effect size
    Moderate
    Dose
    2.1 g/day
  • Mastic→Increased Hemoglobin Levels

    the mitochondrial pyruvate carrier-1 gene (MPC1) and the sphingolipid transporter-1 gene (SPNS1) associated with hemoglobin levels

    Effect
    Neutral
    Effect size
    Small
    Dose
    2.1 g/day
  • Mastic→Reduced Glutathione Peroxidase Level

    We identified several novel gene-by-Mastiha interaction associations with levels of cytokines and antioxidant biomarkers. Some of the identified genetic loci are implicated...including the lanosterol synthase gene (LSS) associated with glutathione peroxidase activity (Gpx) levels

    Effect
    Neutral
    Effect size
    Small
    Dose
    2.1 g/day
  • Mastic→Reduced Interleukin-10 Levels

    the granzyme B gene (GZMB) associated with IL-10 levels

    Effect
    Neutral
    Effect size
    Small
    Dose
    2.1 g/day
  • Mastic→Reduced Interleukin-6 Levels

    the transforming growth factor-beta-induced gene (TGFBI) and the micro-RNA 129-1 (MIR129-1) associated with IL-6

    Effect
    Neutral
    Effect size
    Small
    Dose
    2.1 g/day
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