Olive Oil and Nampt on Postprandial Inflammation and Atherosclerosis in the Setting of Metabolic Syndrome

NCT02061267 | Completed

• 1 other identifier: AGL2011-29008
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The metabolic syndrome may be defined as the constellation of cardiovascular disease (CVD) risk factors that comprises obesity, type 2 diabetes, dyslipidemia, and hypertension. Lack of habitual physical activity and certain dietary patterns, including high-saturated fatty acids (SFA) intake, contribute to increase the risk of CVD, whereas the greatest risk reduction is related with monounsaturated fatty acids (MUFA), mainly from olive oil, and omega-3 polyunsaturated fatty acids (PUFA). Vitamin B3, as a major substrate for nicotinamide phosphoribosyltransferase (NAMPT), has also emerged as a nutritional intervention strategy for prevention of CVD. NAMPT has been shown to exert activities of central importance to cellular energetics and innate immunity. Within the cell, NAMPT is the rate-limiting step in a salvage pathway of nicotinamide adenine dinucleotide (NAD+) biosynthesis. By virtue of this role, it can regulate cellular levels of NAD+ and thereby NAD+-consuming enzymes. NAMPT is also released by a variety of cells, and elevated levels can be found in the systemic circulation of subjects with a range of inflammatory disorders. Recent evidences suggest that, primarily due to its high MUFA content, olive oil is useful as an optimal fat for the modulation of CVD risk factors in the postprandial state. In addition, NAMPT has been shown to correlate with triglycerides in the fasting plasma, and a potential regulatory role for fatty acids on NAMPT expression has been proposed. The global aim of the project is to assess whether olive oil (MUFA), compared to other dietary fatty acids (SFA and omega-3 PUFA) and in association with vitamin B3 could have benefits on NAMPT-related inflammation and atherosclerosis. We hope to provide important novel insights on the relationship among dietary fatty acids, NAD+ metabolism, and metabolic syndrome. This aim is expected to be achieved in one principal objective: To elucidate the influence of olive oil (MUFA), butter (SFA) or fish oil (omega-3 PUFA) meals supplemented by vitamin B3 on postprandial NAMPT modulation and its involvement on leukocyte inflammatory response in subjects with metabolic syndrome.

Conditions

Metabolic Syndrome

Keywords

Metabolic Syndrome; Olive Oil; Niacin

Outcome Measures

Primary Outcomes (3)

• Evolution of Metabolic parameters in postprandial state

  Glucose, insulin, C-peptide, triglyceride, and NEFA levels in plasma will be measured at several time-points postprandially (t = 0, 2, 3, 4, and 6 h) using routine biochemical procedures. Different empiric indices of postprandial β-cell function and insulin sensitivity will be determined.

  t = 0, 2, 3, 4 and 6 hours

• Evolution of Inflammatory markers in postprandial state

  Inflammatory markers will be measured in plasma at several time-points postprandially (t = 0, 2, 3, 4, and 6 h) using appropriate methods (EIA, ELISA, and/or Bioplex multiplex system), and will include NAMPT, the acute phase protein (hsCRP), PAI-1, fibrinogen, transferrin, albumin, MPO (myeloperoxidase), and cytokines such as TNFα, IL-1β, IL-6, IL-8, IL-10, ICAM-1, MCP-1, leptin, and adiponectin, among other markers. For NAD+ content in plasma at fasting and postprandially, we will add 0.5 M ice-cold HClO4 to samples; after 2 min, we will collect 100 μL of supernatants by centrifugation at 3,000 g for 5 min, add 20 μL K2HPO4 (1 M) with cooling on ice and adjust pH to 7.2-7.4 with KOH. We will add 50 μL of supernatant to the reaction mixture containing 0.1 M sodiumpyrophosphate-semicarbazid (pH 8.8), absolute ethanol, and dH2O. We will assess NAD+ spectrophotometrically at 339 nm at 25 °C, as a mean difference in absorbance before and 6 min after addition of alcohol dehydrogenase.

  t = 0, 2, 3, 4 and 6 hours

• Pharmacokinetic of Niacin and its metabolites

  Quantitation of nicotinic acid and its metabolites (nicotinamide, nicotinuric acid, and N-methyl-2-pyridone-5-carboxamide) will be assessed in postprandial plasma by LC-MS/MS.

  t = 0, 2, 3, 4 and 6 hours.

Study Arms (4)

Niacin Control

EXPERIMENTAL

The subjects will receive a vitamin B3 supplement (2 g)

Dietary Supplement: Niacin

Niacin + SAT

EXPERIMENTAL

The subjects will receive a vitamin B3 supplement (2 g) and a test meal with high-fat (containing 72% saturated fat, 22% carbohydrate, and 6% protein)

Dietary Supplement: Niacin; Dietary Supplement: Saturated meal

Niacin + ROO

EXPERIMENTAL

The subjects will receive a vitamin B3 supplement (2 g) and a test meal with high-fat (containing 72% monounsaturated fat, 22% carbohydrate, and 6% protein)

Dietary Supplement: Niacin; Dietary Supplement: Monounsaturated meal

Niacin + O3

EXPERIMENTAL

The subjects will receive a vitamin B3 supplement (2 g) and a test meal with high-fat (containing 72% polyunsaturated omega-3 fat, 22% carbohydrate, and 6% protein)

Dietary Supplement: Niacin; Dietary Supplement: Polyunsaturated meal

Interventions

Niacin DIETARY_SUPPLEMENT

The subjects will receive a vitamin B3 supplement (2 g)

Also known as: Vitamine B3, Nicotinic Acid

Niacin + O3; Niacin + ROO; Niacin + SAT; Niacin Control

Saturated meal DIETARY_SUPPLEMENT

Test meal with high-fat (containing 72% saturated fat, 22% carbohydrate, and 6% protein)

Also known as: Butter, Saturated fat

Niacin + SAT

Monounsaturated meal DIETARY_SUPPLEMENT

Test meal with high-fat (containing 72% monounsaturated fat, 22% carbohydrate, and 6% protein)

Also known as: Refined olive oil, olive oil, oleic acid

Niacin + ROO

Polyunsaturated meal DIETARY_SUPPLEMENT

Test meal with high-fat (containing 72% polyunsaturated omega-3 fat, 22% carbohydrate, and 6% protein)

Also known as: Fish oil, Omega-3, DHA, EPA

Niacin + O3

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• clinical diagnosis of metabolic syndrome

Sponsors & Collaborators

• National Research Council, Spain: lead

Study Sites (1)

Instituto de la Grasa, CSIC

Seville, 41012, Spain

Location

MeSH Terms

Conditions

Metabolic Syndrome

Interventions

Niacin; Butter; Fatty Acids; Olive Oil; Oleic Acid; Fish Oils; Docosahexaenoic Acids

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Dietary Fats; Fats; Lipids; Dairy Products; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Dietary Fats, Unsaturated; Fats, Unsaturated; Plant Oils; Oils; Oleic Acids; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Fatty Acids, Omega-3

Study Officials

• Francisco José García Muriana, phD

  National Research Counsil

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Scientific Research Francisco Jose Garcia Muriana

Study Record Dates

• First Submitted: February 5, 2014
• First Posted: February 12, 2014
• Study Start: January 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: June 30, 2015
• Last Updated: March 13, 2019

Record last verified: 2019-03

Locations

ES (1)