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.

Vitamin D supplementation in patients with alcoholic liver cirrhosis: a prospective study.

BACKGROUND: The liver is involved in the metabolism of vitamin D. The prevalence of osteopenia in alcoholic liver disease (ALD) patients is 34-48%, and the prevalence of osteoporosis is 11-36%. Advanced liver disease is considered a risk factor for the development of osteoporosis. The aim of this study was to establish the relationship between vitamin D level and Child-Pugh score in patients with alcoholic liver cirrhosis (ALC), and to evaluate the effects of oral vitamin D supplementation. METHODS: Seventy male ALC patients in the absence of active alcohol intake were enrolled and their clinical and laboratory data were recorded. A supplementation of cholecalciferol 1000 IU/day was administered. The vitamin D status was analyzed during the study, in patients stratified by Child-Pugh score. RESULTS: The study was completed by fifty patients. At the enrollment, the mean level of vitamin D was 60.73±28.02, 50.53±39.52 and 26.71±12.81 nmol/L, respectively for Child-Pugh score class A, B and C. During vitamin D supplementation it was found in all the patients a significant increase of its levels during the first six months (P<0.05). However, in class C the improvement was consistent also after year (P<0.05). At the end of the study, two of seven patients initially in class C changed in class A, four from class C to B, and one remained in class C (P=0.012). Out of seventeen patients initially in class B, eleven changed to class A, and six remained in class B. CONCLUSIONS: In patients with ALC, higher level of vitamin D level is related with lower Child-Pugh score. The supplementation of 1000 IU/day of vitamin D in these patients was optimal for a period of at least six months. A decrease in the Child-Pugh score was also found, with a redistribution of the patients in different classes.

May Patients with Alcohol Liver Disease Benefit from Herbal Medicines?

Alcoholism is currently listed as the third leading cause of death. Chronic alcohol consumption brings serious medical complications like gastrointestinal, cardiovascular, musculoskeletal, respiratory system disorders. Liver can be seriously damage by alcohol misuse. Alcoholic Liver Disease (ALD) is the first important warning sign of alcohol abuse. Since effective therapies for ALD are still limited, natural products in the treatment of ALD become very important. In this regard, there have been done very few clinical trials with poor results. Silymarin, glycyrrhizin, garlic show some promising results in ALD patients while the in vivo and in vitro studies with green tee, quercetin and curcumin indicate positive effect on patients with ALD.

Osteoporosis reversibility in a patient with celiac disease and primary autoimmune hypothyroidism on gluten free diet--a case report.

INTRODUCTION: Secondary osteoporosis occurs in many diseases. Celiac disease-induced osteoporosis is the consequence of secondary hyperparathyroidism. Biochemical bone markers show predominance of bone resorption, thus making the bisphosphonates the first line therapy option. Intestinal mucosal changes are reversible on gluten-free diet. Osteoporosis reversibility is also possible, provided postmenopausal osteoporosis risk factors independent from celiac disease are not present. CASE REPORT: We presented a postmenopausal woman with at least a 10-year history of celiac disease prior to diagnosis, which had overt secondary hyperparathyroidism with insufficient status of vitamin D and a significant bone mass reduction. At the time of diagnosis of celiac disease the patient was receiving 250 µg of levothyroxine daily without achieving optimal substitution. Three years after the initiation of gluten-free diet the patient was without any signs and symptoms of the disease. All laboratory findings were within normal range. It was decided to treat the underlying disease and to supplement calcium and vitamin D without the initiation of bisphosponate therapy. CONCLUSION: Osteoporosis regression justified this therapeutic approach. The presence of primary autoimmune hypothyroidism makes this case specific, since the inability for optimal substitution therapy with a high daily dose of levothyroxine provoked the suspicion of celiac disease.