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Effect of Oral Caffeine and L-Citrulline Supplementation on Arterial Function in Healthy Males

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02214290
Recruitment Status : Completed
First Posted : August 12, 2014
Last Update Posted : August 12, 2016
Information provided by (Responsible Party):
Arturo Figueroa, Florida State University

Brief Summary:
Caffeine is an exceedingly popular and consumed pharmacological agent. Although caffeine is primarily consumed from coffee and tea beverages, it is also available in other forms such as sodas, energy drinks, tablets and capsules. Nevertheless, caffeine acutely increases brachial and aortic systolic blood pressure (BP) and arterial stiffness. Arterial stiffness is an independent predictor of cardiovascular disease (CVD) and assessed through pulse wave velocity (PWV). Interestingly, previous studies have proposed that caffeine may increase aortic BP through increases in aortic PWV and augmentation index (AIx), a measurement of wave reflection. Yet, these effects were seen in middle-aged adults with treated hypertension and a wide age range. Therefore, it is imperative to consider that caffeine may cause different effects in young normotensive individuals than in older adults independently of BP levels. Importantly, oral supplementation of the amino-acid, L-citrulline has been shown to enhance the bioavailability of L-arginine levels and nitric oxide (NO) production and, therefore, improve arterial function. L-citrulline supplementation for 7 days given at 6 g/day has shown to increase NO levels while improving PWV. Previous studies by our group also demonstrated that L-citrulline supplementation reduces the BP response to cold exposure; a condition with an increased vasoconstriction. Therefore, the acute effects of caffeine on central and peripheral PWV and BP in healthy young men are yet to be fully evaluated. We hypothesized that acute caffeine intake would increase peripheral and aortic BP and PWV and that L-citrulline supplementation would attenuate the effects induced by acute caffeine ingestion.

Condition or disease Intervention/treatment Phase
Hypertension Healthy Drug: Caffeine Drug: Placebo Dietary Supplement: L-citrulline Not Applicable

Detailed Description:

The specific aims of this study are:

AIM 1: To examine the effects of the acute ingestion of 200mg caffeine (tablets) on arterial function in young adults. The working hypothesis is that acute caffeine intake would increase brachial, ankle and aortic BP, PWV (aortic and leg), and wave reflection. In order to test this hypothesis, the investigators will perform non-invasive measurements of arterial stiffness (aortic and leg PWV) and pulse wave analysis (aortic BP and AIx) using applanation tonometry of the radial artery 30, 45, and 60 minutes following caffeine ingestion.

AIM 2: To determine the effectiveness of L-citrulline supplementation to attenuate the acute cardiovascular effects of caffeine ingestion. The working hypothesis is that 7 days of L-citrulline supplementation will attenuate the unfavorable arterial responses (increases in BP, PWV, and wave reflection) to acute caffeine ingestion. In order to test this hypothesis, the investigators will perform the same procedures previously specified in AIM 1.

Description of the study:

Sixteen healthy young men 18-40 years of age will be enrolled in this study. Participants with CVD history, resting BP (> 160/100 mmHg), recent history of smoking, or considered competitive athlete will be excluded from the study. All subjects will refrain from food and caffeine for > 8 hours and from exercise for > 24 hours before testing.

Study design:

Following an initial screening, arterial function measurements will be collected. Measurements will be assessed at baseline following 10 minutes of rest in the supine position and then again at 30, 45, and 60 minutes after 200 mg caffeine or placebo ingestion. Participants will receive caffeine or placebo supplementation on two separate visits with a minimum of 48 hours in between sessions. Following the acute phase of the study, subjects will be randomized to consume L-citrulline or placebo for 7 days given at 6 grams/day. Following the same protocol as the acute phase with 200 mg caffeine, measurements will be collected before and after the 7 day supplementation period.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Official Title: Effect of Oral Caffeine and L-Citrulline Supplementation on Arterial Function in Healthy Males
Study Start Date : September 2012
Actual Primary Completion Date : March 2014
Actual Study Completion Date : March 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Caffeine

Arm Intervention/treatment
Active Comparator: Caffeine
200 mg caffeine tablet produced by CVS Pharmacy, USA
Drug: Caffeine
A 200 mg caffeine tablet was given to subject to examine the drugs effect on arterial function.
Other Name: Caffeine tablet (CVS Pharmacy)

Placebo Comparator: Placebo
Placebo pill produced by NOW FOODS, USA
Drug: Placebo
A 750 gram placebo capsule (maltodextrin) was given to subjects to examine the effect of the drug on arterial function.
Other Name: Placebo from NOW FOODS, USA

Experimental: L-citrulline
L-citrulline capsule (750 g) provided by NOW FOODS
Dietary Supplement: L-citrulline
L-citrulline was used to examine the effect of the supplement on arterial function.
Other Name: L-citrulline (750 grams/capsule)

Primary Outcome Measures :
  1. Blood Pressures [ Time Frame: One week ]
    Measuring brachial, ankle, and central blood pressures acutely following caffeine tablet versus placebo and following L-citrulline supplementation.

Secondary Outcome Measures :
  1. Arterial Function [ Time Frame: One week ]
    Measuring arterial stiffness (PWV) and wave reflection at rest, acutely after caffeine or placebo, and following L-citrulline supplementation.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Young healthy males
  • Non smoker
  • Non endurance trained athlete
  • No previous history of cardiovascular disease

Exclusion Criteria:

  • Female
  • Blood pressure greater than 160/100
  • Smoker

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02214290

Sponsors and Collaborators
Florida State University
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Principal Investigator: Arturo Figueroa, M.D. Ph.D Florida State University

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Responsible Party: Arturo Figueroa, Associate Professor, Florida State University Identifier: NCT02214290    
Other Study ID Numbers: HSC2013.10514
First Posted: August 12, 2014    Key Record Dates
Last Update Posted: August 12, 2016
Last Verified: August 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Arturo Figueroa, Florida State University:
Arterial Function
Blood Pressure
Pulse Wave Velocity
Pulse Wave Analysis
Additional relevant MeSH terms:
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Vascular Diseases
Cardiovascular Diseases
Central Nervous System Stimulants
Physiological Effects of Drugs
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents