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

OLIVE OIL ON NAMPT AND ITS RELATION WITH POSTPRANDIAL INFLAMMATION AND ATHEROSCLEROSIS IN THE SETTING OF METABOLIC SYNDROME. The OLNAMS Project

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.

Study Overview

• Status: Completed
• Conditions: Metabolic Syndrome
• Intervention / Treatment: Dietary supplement: Niacin; Dietary supplement: Saturated meal; Dietary supplement: Monounsaturated meal; Dietary supplement: Polyunsaturated meal

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Seville, Spain, 41012
    • Instituto de la Grasa, CSIC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• clinical diagnosis of metabolic syndrome

Exclusion Criteria:

• Subjects will be excluded if, allergic to dairy products, allergic to fish oil, vegetarian, tobacco smoker, current or recent (<4 wk) use of fish oil supplements or more than four times fish/week, received innoculations within 2 mo of starting the study or planned to during the study, donated or intended to donate blood from 2 mo before the study till 2 mo after the study, unstable body weight (no weight gain/loss >3 kg), medical condition that can interfere with the study outcome (i.e., biochemical evidence of active heart disease, renal impairment, hypothyroidism, liver dysfunction, etc.), use of medications know to interfere with glucose homeostasis or lipid metabolism, use of anti-inflammatory medication, hormone or cytokine or growth factor therapies, abuse of drugs and/or alcohol, participation in another biomedical study within 1 mo before the first screening visit, or not wanting to be informed about chance-findings during screening. Another exclusion criteria will be severe diabetes, which requires application of insuin and diabetes-related complications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Niacin Control; The subjects will receive a vitamin B3 supplement (2 g)	Dietary supplement: Niacin; The subjects will receive a vitamin B3 supplement (2 g); Other Names: Vitamine B3; Nicotinic Acid
Experimental: Niacin + SAT; 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; The subjects will receive a vitamin B3 supplement (2 g); Other Names: Vitamine B3; Nicotinic Acid; Dietary supplement: Saturated meal; Test meal with high-fat (containing 72% saturated fat, 22% carbohydrate, and 6% protein); Other Names: Butter; Saturated fat
Experimental: Niacin + ROO; 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; The subjects will receive a vitamin B3 supplement (2 g); Other Names: Vitamine B3; Nicotinic Acid; Dietary supplement: Monounsaturated meal; Test meal with high-fat (containing 72% monounsaturated fat, 22% carbohydrate, and 6% protein); Other Names: olive oil; Refined olive oil; oleic acid
Experimental: Niacin + O3; 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; The subjects will receive a vitamin B3 supplement (2 g); Other Names: Vitamine B3; Nicotinic Acid; Dietary supplement: Polyunsaturated meal; Test meal with high-fat (containing 72% polyunsaturated omega-3 fat, 22% carbohydrate, and 6% protein); Other Names: Omega-3; Fish oil; DHA; EPA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.

Collaborators and Investigators

• Sponsor: National Research Council, Spain
• Investigators: Principal Investigator: Francisco José García Muriana, phD, National Research Counsil

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2012
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): June 30, 2015

Study Registration Dates

• First Submitted: February 5, 2014
• First Submitted That Met QC Criteria: February 10, 2014
• First Posted (Estimate): February 12, 2014

Study Record Updates

• Last Update Posted (Actual): March 13, 2019
• Last Update Submitted That Met QC Criteria: March 11, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Metabolic Syndrome; Niacin; Olive Oil
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Disease; Insulin Resistance; Hyperinsulinism; Syndrome; Inflammation; Metabolic Syndrome; Atherosclerosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Nicotinic Acids; Niacin
• Other Study ID Numbers: AGL2011-29008