Effect of Oral Caffeine and L-Citrulline Supplementation on Arterial Function in Healthy Males
Condition: Hypertension; Healthy
MeSH terms: Hypertension
Study type: Interventional

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.
    

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.
    

Intervention name(s): Caffeine; Placebo; L-citrulline
Intervention type(s): Drug; Drug; Dietary Supplement
Intervention description(s): A 200 mg caffeine tablet was given to subject to examine the drugs effect on arterial function.; A 750 mg placebo capsule (maltodextrin) was given to subjects to examine the effect of the drug on arterial function.; L-citrulline was used to examine the effect of the supplement on arterial function.
Other intervention name(s): Caffeine tablet (CVS Pharmacy); Placebo from NOW FOODS, USA; L-citrulline (750 mg/capsule)
Intervention MeSH terms: Caffeine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Other
Keywords: Cardiovascular; Caffeine; L-citrulline; Arterial Function; Hemodynamics; Blood Pressure; Pulse Wave Velocity; Pulse Wave Analysis