Onion, Cardiovascular Risk Markers and Gene Expression (M197)

The Effects of Onion on Plasma Lipoproteins, Blood Pressure and Gene Expression in Overweight Humans - a Double-blinded, Randomized Cross-over Study

AIMS:

The aims are to investigate whether:

• Increased intake of onion (powder) affects plasma lipid profile, blood pressure, indices of insulin sensitivity and blood coagulation.
• Increased intake of onion (powder) affects the expression/activity of enzymes in the defence against foreign substances, e.g. reactive oxygen species, and whether polymorphisms in some of the involved genes may modulate the effect.
• Polymorphisms involved in the metabolism/effect of bioactive components in onion modulate the excretion of metabolites or modulate some of the outcome variables in the study.

Other aims are to try to identify biomarkers for onion consumption in plasma, urine and feces and to investigate whether onion affects the secretion of fat and bile acids.

HYPOTHESES:

The investigators hypothesize that:

• 2 weeks of increased onion intake will improve the plasma lipid profile
• 2 weeks of increased onion intake will increase the metabolism of potentially harmful substances (such as ROS and free radicals) through a change in the expression or activity of certain enzymes.
• That these effects are modulated by common gene variants (polymorphisms)

Study Overview

• Status: Completed
• Conditions: Blood Pressure; Coagulation Delay
• Intervention / Treatment: Dietary supplement: Onion powder; Dietary supplement: Placebo

Detailed Description

In a randomized controlled crossover design, participants will receive 2 daily meals with or without onion powder for 2 weeks. Between the two 2-week period is a 4-week wash-out period. One week before and during each intervention period, the participants will be instructed to avoid consumption of onion, garlic and all foodstuffs containing the same bioactive components (polyphenols, sulfur-molecules)as in onion. This includes a number of vegetables and fruits, condiments, tea, chocolate, red wine etc.

Fasting blood samples will be drawn before and after (on 2 separate days) each intervention period, where also weight and blood pressure are measured.

Participants will collect 24-hour urine and feces samples twice before and at completion of each intervention period.

After the fasting blood sampling on the first blood sampling day in each period, participants will receive a test meal (with 10 g onion powder or placebo, i.e. 8.5 g sucrose+ 2 g soy protein isolate). The acute effects will be studied by blood sampling and urine sampling 0, 2, 4 and 24 hours after the test meal.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Frederiksberg C, Denmark, 1958
    • Department of Nutrition, Exercise and Sports, University of Copenhagen
  • Frederiksberg C, Denmark, 1958
    • Dep. Human Nutrition, LIFE, University of Copenhagen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy
• BMI 25-40
• No daily medication (except thyroid hormone, stomach acid lowering drugs, mild blood pressure lowering drugs and anti-depressants)
• Not strenuous exercise >10 hours/week
• No blood donation 3 months before or during the study

Exclusion Criteria:

• Diabetes, CVD, hepatitis, HIV/AIDS
• Cancer or cancer treatment within last 6 months
• Smoking
• Simultaneous participation in other research projects

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Onion powder; Initial test meal contained 20g freeze dried onion powder in hot meals (1 potato soup and 1 meatball-meal daily). Subsequent daily meals contained 20g onion powder in the same meal formats.	Dietary supplement: Onion powder; Hot meals with onion powder; 10 g/day onion powder corresponding to 100 g/day fresh onion in meals with potato and beef Intervention period 14 days.
Placebo Comparator: Placebo; Hot meals (1 potato soup and 1 meatball-meal daily)containing 8.5 g sucrose and 2 g soy protein instead of onion powder	Dietary supplement: Placebo; Hot meals without onion powder; Control meal with potato, beef, soy protein, and sucrose to match macronutrient composition of active treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in blood pressure from baseline to two weeks	Measured by a standard arm cuff by a trained bioanalyst	baseline to two weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in waist-to-hip circumference ratio	Measured manually by a trained bioanalyst	Change from baseline to two weeks
Change in fecal microbiota profile	RFLP of 16S cDNA	change from baseline to two weeks
Change in total cholesterol	Total plasma cholesterol in lipoproteins measured by a clinical chemistry kit	change from baseline to 2, 4, and 24 hours and 2 weeks
Change in HDL cholesterol	High density Lipoprotein Cholesterol in plasma measured by an immunokit	change from baseline to 2, 4, and 24 hours and 2 weeks
Change in plasma triacylglycerides	Triacylglycerides in plasma measured by an immunokit	change from baseline to 2, 4, and 24 hours and 2 weeks
Change in blood coagulation parameters	thromboelastography measurements, fibrinogen etc. in plasma	0-4 hours
Change in whole-blood hematocrit	hematocrit by standard clinical chemistry	0-14 days
Change in whole-blood haemoglobin concentration	haemoglobin concentration by standard clinical chemistry	0-14 days
Change in body weight	Measured in triplicate on a calibrated balance	0-14 days
Change in serum VCAM-1	Determined with standard kits	0-14 days
Change in serum IL-6	Determined with standard kit	0-14 days
Change in serum TNF-alpha	Determined with standard kit	0-14 days
Change in faecal metabolic profiles	Untargeted metabolomics by LC-QTOF profiling of polar metabolites	0-14 days
Change in faecal pH	pH by a pH-meter in a 50% aqueous fecal slurry	0-14 days
Change in faecal bile acids	bile acids measured by LC-TQD	0-14 days
Change in urine metabolomic profiles	Untargeted metabolomics by LC-QTOF profiling of polar metabolites	0-14 days
Change in urine pH	pH by a pH-meter	0-14 days
Change in plasma insulin (multivariate ANOVA)	Insulin measured at baseline before meals and at 2, 4 and 24 hours, 2, 7 and 14 days after the start of intervention.	0-14 days
Change in plasma glucose (multivariate ANOVA)	Glucose measured at baseline before meals and at 2, 4 and 24 hours, 2, 7 and 14 days after the start of intervention.	0-14 days
Change in HOMA	Change in HOMA measured at baseline before meals and at 14 days after the start of intervention.	0-14 days
Change in ISI240 (Matsuda insulin sensitivity index 0-240)	Change in ISI240 measured from 0-240 minutes after the first test meal.	0-240 minutes
Change in erythrocyte Glutathione Reductase	Measured by automated colorimetric assays	0-2 weeks
Change in erythrocyte superoxide dismutase	Measured by automated colorimetric assays	0-2 weeks
Change in erythrocyte catalase	Measured by automated colorimetric assays	0-2 weeks
Change in erythrocyte glutathione peroxidase	Measured by automated colorimetric assays	0-2 weeks
Change in plasma untargeted metabolic profile	LC-QTOF profiling of polar metabolites and polar lipids	0-2 weeks
Change from baseline in leucocyte gene expression profile	Selected genes by RT-PCR	0, 2, 4 and 24 hours and 2 weeks

Collaborators and Investigators

• Sponsor: Professor Lars Ove Dragsted
• Collaborators: University of Copenhagen; Instituto De Frio
• Investigators: Principal Investigator: Lars O Dragsted, PhD, Dep Nutrition, Exercise and Sports, University of Copenhagen; Study Director: Susanne G Bügel, PhD, Dep Human Nutrition, LIFE, University of Copenhagen

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: February 8, 2015
• First Submitted That Met QC Criteria: May 19, 2015
• First Posted (Estimate): May 20, 2015

Study Record Updates

• Last Update Posted (Estimate): May 20, 2015
• Last Update Submitted That Met QC Criteria: May 19, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Biomarker; Cardiovascular disease; Onion; Gene expression; metabolomics
• Other Study ID Numbers: M197