Clinical trial NCT04810572: Nutraceutical Composition Containing Natural Products Derivatives on the Modulation of the Endocrine Neuroimmune Axis
Official title: Evaluation of the Effects of a Nutraceutical Composition Containing Derivatives From Natural Products on the Modulation of the Endocrine Neuroimmune Axis - Translational Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Insulin Resistance
Inflammatory Bowel Diseases
Overweight and Obesity
Healthy
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
Collaborators: name: University of Sao Paulo
First posted: 2021-03-23
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The use of natural products in the prevention or treatment of chronic diseases is an emerging field in current medicine. And studying the mechanisms of actions by which natural products act in our bodies contributes to the rational use of these products. And the combination of different natural products such as prebiotics (FOS- fructooligosaccharides, GOS-Galactooligosaccharides and beta-glucans derived from yeast), herbal medicine (Silybum marianum), and minerals (Se-selenium, Zn-Zinc, and Mg-Magnesium), o which would result in a synergistic association between them can contribute to achieving not only preventive effects but treatment for chronic diseases such as diabetes and obesity. The present study aims to study the effects of a composition containing natural products on factors and markers that are part of mitochondrial biogenesis and the neuroimmune-endocrine system in healthy volunteers and that present grade 1 overweight/obesity.

Detailed description: Obesity and diabetes are chronic diseases characterized by increased visceral adipose tissue and sub-acute inflammation. These conditions can lead to insulin resistance, hyperglycemia, oxidative stress\], and lipotoxicity, and lead to the development of metabolic syndrome. Previous work has shown that these comorbidities, as well as high levels of glucocorticoids, can modulate the hypothalamic-pituitary-adrenal (HPA) axis and inflammatory response. In some cases, these conditions and responses perturb neuroimmune endocrine system homeostasis.

Another potential outcome arising from inflammation, insulin resistance, hyperglycemia, and lipotoxicity is a nonalcoholic fatty liver disease (NAFLD), a chronic liver disease that often coexists with obesity-related type 2 diabetes. Previous studies have demonstrated that NAFLD compromises glycemic and lipid homeostasis. The hyperglycemia and the lipotoxicity drive the metabolic pathways of the cell towards gluconeogenesis, glycolysis, and de novo lipogenesis, and the subsequent increase in free fatty acid (FFA) production can cause oxidative stress.

Previous studies have shown that non-pharmacological interventions can be used as strategies for treating and/or preventing inflammatory and metabolic diseases. Furthermore, exploiting specific proteins and transcription factors that target the mitochondria represents potential mechanisms for these interventions.

Along these lines, natural products and derivatives thereof, often referred to as natural medicines, have been gaining notoriety as sources of effective therapeutics. For example, polyphenols present in plants can be metabolized to form propionic acid, which is later transformed into another metabolite, butyrate. As reviewed by Juárez-Hernández et al., Na-butyrate and synthetic derivatives thereof increase prebiotic lactobacilli and bifidobacteria growth in the colon, consequently improving thermogenesis and energy expenditure, ultimately reducing hepatic lipid deposition, improving triacylglycerol content and insulin resistance and protecting against metabolic impairment, as well as liver inflammation and/or damage. Furthermore, butyrate can induce the expression of fibroblast growth factor 21 (FGF-21), which plays a vital role in stimulating hepatic fatty acid β-oxidation. In this sense, prebiotics may be a promising treatment for chronic inflammatory and metabolic diseases in humans.

The efficacy of prebiotic compounds, such as fructooligosaccharides (FOS), galacto-oligosaccharides (GOS) and yeast β-glucans, minerals including magnesium, zinc, selenium, and plants like Silybum marianum (L.) Gaerth. (Silymarin), have been evaluated for the treatment of specific diseases. However, most of these studies only describe the effects of the supplements being administered alone. Thus, the present study monitored the synergic effects of a novel supplement formulation containing prebiotics, yeast β-glucans, minerals, and silymarin on lipid metabolism, inflammatory and mitochondrial proteins in eutrophic, and overweight/obesity I volunteer.

Eligibility criteria: Inclusion Criteria:

* Healthy (healthy) and sedentary volunteers: people without chronic use of drugs for chronic inflammatory diseases that require the use of corticosteroids or NSAIDs (Non-Steroidal Anti-inflammatories) for a period of more than 15 days. BMI (Body Mass Index) of 24.9 Kg / m2.
* Sedentary overweight/obesity grade 1 volunteer: overweight people, with a BMI of 25.0 to 29.9 kg / m2; and grade 1 obesity with a BMI of 30.0 and 34.9 kg / m2, with or without dyslipidemia and/or non-insulin-dependent type 2 diabetics.

Exclusion Criteria:

* Volunteers who are allergic to some of the components of the nutraceutical formulation, who use insulin, corticosteroids, and NSAIDs for more than 15 days, AIDS, hepatitis, patients undergoing chemotherapy.

Primary outcomes:
measure: Change Lipid Profile Baseline after 4, 12 and 24 weeks of intervention.
timeFrame: Baseline and 4, 12 and 24 weeks.
measure: Change Lymphocyte Phenotype at 4, 12 and 24 weeks after intervention.
timeFrame: Baseline and 4, 12 and 24 weeks.
measure: Change Serum Cortisol Level Baseline after 4, 12 and 24 weeks of intervention.
timeFrame: Baseline and 4, 12 and 24 weeks.
measure: Change Gut Microbiota Baseline after 4, 12 and 24 weeks of intervention.
timeFrame: Baseline and 4, 12 and 24 weeks.
measure: Change Haemogram Parameters Baseline after 4, 12 and 24 weeks of intervention.
timeFrame: Baseline and 4, 12 and 24 weeks.
measure: Change Leucogram Parameters Baseline after 4, 12 and 24 weeks of intervention.
timeFrame: Baseline and 4, 12 and 24 weeks.
measure: Change Circadian Rhythms Over time of Intervention.
timeFrame: Baseline and 4, 12 and 24 weeks.
measure: Change Quality of Life Assessments Over time of Intervention.
timeFrame: Baseline and 4, 12 and 24 weeks.
measure: Change Sleep Patterns Over time of Intervention.
timeFrame: Baseline and 4, 12 and 24 weeks.
measure: Change Sleep Quality Over Time of Intervention.
timeFrame: Baseline and 4, 12 and 24 weeks.
measure: Change Sleepiness Patterns Over time of Intervention.
timeFrame: Baseline and 4, 12 and 24 weeks.
Secondary outcomes:
measure: Change Body Mass Index (BMI) Over time of Intervention.
timeFrame: Baseline and 4, 12 and 24 weeks.
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: USP Medical School
Study officials:
affiliation: University of São Paulo - Medical School - FMUSP
name: Ana Flavia M Pessoa, Ph.D
role: PRINCIPAL_INVESTIGATOR
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