Vitamin C to Reduce Morning Cardiovascular Risk

Study Overview
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Brief Summary
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This study will test the efficacy of Vitamin C to counteract morning cardiovascular (CV) risk markers in a randomized, double blind, placebo controlled crossover pilot study. The participants will also perform morning typical behaviors such as arousal from sleep, change in posture (getting out of bed) and mild intensity physical activity; identical to the stressors encountered in everyday life. Primary dependent variables are markers of cardiovascular risk including vascular endothelial function and oxidative stress.

Detailed Description
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The investigators plan to test the efficacy of Vitamin C to counteract morning cardiovascular (CV) risk markers in a randomized, double blind, placebo controlled crossover pilot study. The participants will also perform morning typical behaviors such as arousal from sleep, change in posture (getting out of bed) and mild intensity physical activity; identical to the stressors encountered in everyday life. This pilot study is in healthy middle aged adults without a history of CV disease. Participants will spend two nights in an inpatient hospital suite at Hatfield Research Center. Upon awakening in the morning, they will either ingest Vitamin C or placebo in a randomized order. This will be followed by moderate intensity exercise, recovery, and discharge.

Official Title
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Chronotherapeutic Use of Vitamin C to Reduce Morning Cardiovascular Risk

Conditions
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Cardiovascular Risk Factor

Intervention / Treatment
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* Dietary Supplement: Vitamin C
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy participants Normal weight or overweight but not obese (18.5<BMI<33 kg/m2) Exclusion Criteria: History of smoking/tobacco use Current prescription/non-prescription medications or drugs of abuse Acute, chronic, or debilitating medical conditions History of working irregular day and night hours, regular night work, or rotating shift work for the six months prior to the study.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin C then Placebo<br>Participants will receive a 1.5g dose of Ascorbic Acid upon wake for the first visit, and a placebo tablet on the second visit. | Dietary Supplement: Vitamin C<br>* 1.5g Ascorbic Acid<br>* Other names: Ascorbic Acid;Other: Placebo<br>* Inactive placebo to mimic 1.5g ascorbic acid.<br>|
| Experimental: Placebo then Vitamin C<br>Participants will receive a placebo tablet upon wake for the first visit, and a 1.5g dose of Ascorbic Acid on the second visit. | Dietary Supplement: Vitamin C<br>* 1.5g Ascorbic Acid<br>* Other names: Ascorbic Acid;Other: Placebo<br>* Inactive placebo to mimic 1.5g ascorbic acid.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vascular Endothelial Function | Vascular endothelial function will be measured as flow-mediated dilation (FMD). We will measure brachial artery FMD immediately upon awakening in a constant posture following an overnight fast using the standard guidelines and protocol. | Approximately three months | 
| Oxidative stress | Oxidative stress will be measured as malondialdehyde (MDA) adducts from Ethylenediaminetetraacetic acid (EDTA) plasma. Higher values may indicate increased oxidative stress. | Approximately three months | 
| Plasma Vitamin C and Tetrahydrobiopterin | We will measure Vitamin C levels in the plasma to ensure that the levels are increased after supplementation, and to control for baseline levels. We will measure tetrahydrobiopterin (BH4) from plasma to test if levels are increased upon administration of Vitamin C. | Approximately three months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet aggregation | Platelet aggregation will be measured using Chronolog 560 VS Platelet aggregometer as an indicator of how well blood clots or clumps together. Higher values may indicate increased cardiovascular risk. | Approximately three months | 
| Plasminogen activator inhibitor -1 | Plasminogen activator inhibitor-1 (PAI-1) will be measured from plasma as a blood inflammatory marker. Higher values may indicate increased cardiovascular risk. | Approximately three months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sleep, Vitamin C