L-arginine Supplementation and Resistance Exercise
Condition: Healthy Adult
Study type: Interventional

Summary: 
      The purpose of this study was to examine the acute endothelial, cardiovascular, and
      performance responses to L-arginine by assessing flow-mediated dilation (FMD) and heart rate
      variability (HRV) both before and after resistance exercise to fatigue. Thirty (15 male, 15
      female) physically active participants volunteered for a randomized, cross-over,
      double-blind, placebo- controlled clinical trial. Participants completed five sets of elbow
      extension-flexion exercise after consumption of either 3 g of placebo or 3 g L-arginine.
    

Detailed description: 
      Participants Thirty healthy, physically active males (n=15) and females (n=15), 18-25 years
      of age completed the study. Subjects had not participated in another clinical trial or
      consumed another study related investigation product within 30 days of enrollment. If a
      supplement containing L-arginine or other nitrate precursors was being taken, a three-week
      washout period was conducted before participation. All procedures were approved in advance by
      the North Dakota State University Institutional Review Board and written consent was
      obtained.

      Protocol A randomized, double-blind, placebo-controlled research design was implemented for
      this investigation. Prior to the randomized testing sessions, participants completed a
      anthropometric measurements and familiarization session which included:: collection of
      participant age, height (Seca 213, Chino, CA), and body mass data (Detecto, Webb City, MO)
      and familiarization with the Biodex Dynamometer (Biodex Medical Systems, Shirley, NY),
      ultrasound (Philips Ultrasound, Bothell, WA), and electronic sphygmomanometer (Hokanson Rapid
      Cuff Inflation System, Bellevue, WA) procedures. Participants then reported to the laboratory
      for two testing sessions, each separated by at least a 48 hours washout period. Testing
      sessions were conducted at the same time of day to account for circadian variation.
      Participants entered the trial sessions on an 8-our fast, but were encouraged to arrive at
      the session well-hydrated. The participants were instructed not to exercise or consume
      caffeine 24 hours prior to trial time or use toothpaste, chewing gum, or mouthwash the
      morning of the trials, due to the possible effects on nitric oxide absorption. All females
      tested negative for pregnancy based on a urinary pregnancy test (Clinical Guard, Atlanta, GA)
      prior to each trial session. At the start of the trial, participants rested for 5 minutes
      while sitting.

      Endothelial responses were measured by a technique termed flow mediated vasodilation (FMD)
      which assessed the maximal vasodilatory response to shear stress. FMD was measured in
      accordance with recommendations from the International Brachial Artery Reactivity Task Force.
      A Philips HD11XE ultrasound system (Philips, Amsterdam, NL) equipped with 2D imaging, color
      and spectral Doppler, and a high-frequency vascular transducer was used for the protocol. The
      participants laid supine with the right arm inside a pillow for a stabilizer. Probe placement
      was on the brachial artery, above the antecubital fossa in the longitudinal place. Continuous
      2D imaging was used to take an initial brachial artery diameter for 10 seconds to determine
      the resting artery diameter (to cover the full cardiac cycle). Probe placement was outlined
      with a marker. A Hokanson E20 electronic sphygmomanometric cuff and rapid cuff inflation
      system (Bellevue, WA) was placed on the middle of the forearm and inflated to 50 mmHg above
      systolic blood pressure for five mins and cuff placement was marked with a marker. Upon
      release of the cuff, the ultrasound probe was placed in the same area in which the first
      measure was taken. A continuous 2D imaging was used from cuff release to 120 seconds
      post-release. The average of three diameters measured using RadiAnt DICOM software was used
      for determination of FMD (%), which was expressed as the change in post-stimulus diameter as
      a percentage of baseline diameter.

      Measures of the cardiovascular system included heart rate variability (HRV). HRV were
      recorded using a Polar H7 Bluetooth strap (Polar, Bethpage, NY) combined Personal Pro Elite
      HRV smartphone application (elitehrv.com) over 5 min intervals then further analyzed with
      Kubios software using the "very low" artifact correction setting. HRV explored the
      differences in beat-to-beat intervals based on the time (milliseconds) between adjacent R to
      R (RR) peaks within a PQRST waveform. HRV provides a dynamic, sensitive meter of the balance
      or tone between the two branches of the autonomic nervous system, sympathetic (SNS) and
      parasympathetic (PNS), RMSSD and pNN50 are also the most commonly used HRV measures and were
      used in this study.

      After baseline measurements were collected, the participants consumed either 6 capsules (3 g)
      of L-arginine (NOW Foods, Bloomingdale, IL) or 6 capsules of corn starch, placebo (3 g) which
      had an identical appearance (InHealth Specialty Pharmacy, Fargo, ND). Each supplement was
      consumed with 12 oz. of water. The participant then rested for 55 minutes to ensure enough
      time for digestion, absorption and availability. At 55 minutes post-supplementation,
      participants completed a 5 minutes warm up using a cycle ergometer (Monark 828E, Vansbro,
      SV). Sixty minutes post-supplementation, participants completed elbow flexion and extension
      exercise with their right arm on an isokinetic dynamometer to determine the elbow flexor and
      extensor peak torque.The exercise protocol, designed to induce fatigue, consisted of five
      sets of 10 maximal isokinetic extension repetitions of the elbow joint at 90º per second with
      30 seconds of rest in between sets. Participants were instructed and encouraged to use
      full-force for all sets. Isometric peak torque was measured prior to and thirty seconds after
      exercise to determine the fatigue percentage. Dynamometer settings remained constant for each
      testing session as recorded during the anthropometric and familiarization session. At 10
      minutes post-exercise, which was 120 minutes after supplement consumption, FMD and HRV were
      measured for the final time.
    

Intervention name(s): L-arginine; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): NOW Foods, Bloomingdale, IL; InHealth Specialty Pharmacy, Fargo, ND
Other intervention name(s): cornstarch
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: double blind, placebo, controlled -cross over
Masking: Double (Participant, Investigator)
Primary purpose: Other
Keywords: L-arginine; flow mediated dilation; resistance exercise