Effect of a Multi-ingredient on Visceral Adiposity and Non-alcoholic Fatty Liver Disease in Individuals With Abdominal Obesity (FATHIS)

Effect of a Multi-ingredient on Visceral Adiposity and Non-alcoholic Fatty Liver Disease in Individuals With Abdominal Obesity

Effect of a Multi-ingredient of L-Histidine, L-Serine, L-Carnosine and N-Acetylcysteine on Visceral Adiposity and Non-alcoholic Fatty Liver Disease in Individuals With Abdominal Obesity. Randomized, Parallel, Placebo Controlled, Triple Blind Study.

The aim of this study is to validate the efficacy of specific combination of different natural histidine-related amino acids in the reduction of visceral fat and liver steatosis, as well their associated comorbidities, in individuals with abdominal obesity.

World Health Organization (WHO) defines obesity as an excess of fat accumulation in adipose tissues and in other metabolic organs, leading to serious health implications. Obesity is a rising issue whose prevalence has defined as a global pandemic or globesity (>30% world population) being responsible of millions of deaths annually. Also, obesity is related with several comorbidities such as non-alcoholic fatty liver disease (NAFLD), with a global prevalence of >25%. Thus, strategies to ameliorate obesity and NAFLD are critical to improve life expectancy and quality of life and to reduce the economic burden of both diseases. Current therapies against obesity are mainly focused on weight loss, including lifestyle intervention, to modify eating behaviours and to promote physical activity. However, the compliance of patients with these therapies is small. In addition, there are some drugs to fight against these diseases. In obesity, these medical therapies are focused to decrease fat gastrointestinal absorption using lipase inhibitors with several side effects: faecal incontinence, abdominal cramping and raise in blood pressure. In NAFLD, medical therapies are designed to reduce insulin resistance, using pioglitazone and metformin. However, the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) recommend avoiding pioglitazone use by its relationship with heart failure and cancer, and metformin provides just a modest improvement in NAFLD. Thus, the finding of new and efficient therapeutic agents is highly desirable to combat these global diseases. The main objective of this study is to evaluate the effect of daily intake of a specific combination of L-histidine, L-serine, L-carnosine and N-Acetylcysteine, in combination with dietary recommendations, on the amount of visceral fat in individuals with abdominal obesity. The secondary objectives of this study are to evaluate the effect of daily intake of the multi-ingredient aforementioned in liver fat content and obesity related comorbidities. Participants who fulfilled the inclusion and exclusion criteria will be randomly assigned to the intervention and control group. During the study there will be 4 visits: a preselection visit (V0; day -7) and 3 study visits during the consumption of the treatments, which will take place on the first day of the study (V1; day 1 +/- 3 days; week 1), at 6 weeks of treatment (V2; day 44 +/- 3 day; week 6) and at 12 weeks of treatment (V3; day 90 +/- 3 days; week 12).

Nutraceuticals, Visceral Obesity, NAFLD, Metabolic risk, L-histidine, L-serine, N-Acetylcysteine, L-carnosine, Glucose metabolism, Lipid metabolism, Hepatic steatosis, Hypertension

Participants will daily consume the multi-ingredient (L-Histidine, L-Serine, L-Carnosine and N-Acetylcysteine) for 12 weeks.

The product will be presented in powder format in a single container and with a measuring spoon of the daily dose.

The product will be presented in powder format in a single container and with a measuring spoon of the daily dose.

Change from Baseline Visceral Adiposity at 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline Hepatic Steatosis at 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline Weight at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline Body Mass Index at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline Neck circumference at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline Arm circumference at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline Waist circumference at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline Conicity Index at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline Systolic Blood Pressure at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline Systolic Blood Pressure at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

Metagenomic analysis in fecal samples. The bacteria DNA will be extracted and massive sequenced by the Ion Torrent platform.

Change from Baseline intestinal microbiota composition at 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline biomarkers of oxidative stress at 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline serum glucose levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline serum total cholesterol at 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline serum high-density lipoprotein cholesterol at 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline serum low-density lipoprotein cholesterol at 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline serum triglycerides at 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline serum alanine aminotransferase at 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline serum aspartate aminotransferase at 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline serum gamma glutamyl transferase at 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline serum insulin levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline serum leptin levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline serum adiponectin levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline Adiponectin/Leptin ratio at 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline serum MCP-1 levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline plasma TNF-alpha levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline plasma IL-6 levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline plasma IL-10 levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline plasma ICAM-1 levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline plasma CD14 levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline plasma LDLox levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline serum C-Reactive protein levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

Serum histidine levels will be determined by Liquid Chromatography coupled to tandem Mass Spectrometry

Change from Baseline Histidine levels at 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline HOMA-IR at 12 weeks for each of the two treatments (multi-ingredient and placebo)

FLI will be calculated using BMI, waist circumference, serum triglycerides and gamma glutamyl transferase levels

Change from Baseline Plasma atherogenic index at 12 weeks for each of the two treatments (multi-ingredient and placebo)

Change from Baseline Dietary habits at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

Physical activity will be evaluated through the International Physical Activity Questionnaire (IPAQ)-short for physical activity questionnaire

Change from Baseline Physical activity at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

The consumption of concomitant medication by the volunteers will be controlled by the record of concomitant medication in the case report form

Change from Baseline concomitant medication at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

The consumption of food supplements by the volunteers will be controlled by the record of food supplements in the case report form

Change from Baseline consumption of food supplements at 6 and 12 weeks for each of the two treatments (multi-ingredient and placebo)

Single nucleotide polymorphisms (SNPs) in loci of genetic susceptibility to abdominal adiposity will be studied at 12 weeks after treatment for each of the two treatments (multi-ingredient and placebo)

Change from Baseline Food Intake Biomarkers at 12 weeks for each of the two treatments (multi-ingredient and placebo)

Possible adverse events derived from taking study's products will be recorded in the case report form

After 6 (V2) and 12 weeks (V3) of treatment period for each of the two treatments (multi-ingredient and placebo)

Inclusion Criteria: Men older than 40 years. BMI ≥30.0 kg/m^2 and ≤35.0 kg/m^2 Waist circumference ≥102 cm. Read, write and speak Catalan or Spanish. Sign the informed consent. Exclusion Criteria: Present values of body mass index > 35 kg/m^2 Present values of waist circumference > 150 cm. Present diabetes. Present dyslipidemia (LDL cholesterol ≥ 189 mg/dL and/or triglycerides ≥ 350 mg/dL). Present anemia. Taking supplements, multivitamin supplements or phytotherapeutic products that interfere with the treatment under study. Consume 4 or more Standard Beverage Units (SBU) daily or 28 SBU weekly. Be a smoker. Present any diagnosed liver disease other than NAFLD. Have lost more than 3 kg of weight in the last 3 months. Present food intolerances and/or allergies related to the study products, such as hypersensitivity to maltodextrin or N-Acetylcysteine. Presenting any chronic or autoimmune disease in clinical manifestation such as hepatitis, hyper or hypothyroidism or metabolic diseases. Follow a pharmacological treatment with immunosuppressants, cytotoxic agents, corticosteroids or other drugs that could cause hepatic steatosis or alter the measurements in the liver. Being participating or having participated in a clinical trial or nutritional intervention study in the last 30 days before inclusion in the study. Follow a hypocaloric diet and/or pharmacological treatment for weight loss. Suffering from eating behavior disorders or psychiatric disorders. Being unable to follow study guidelines.