title: Acute and chronic safety and efficacy of dose dependent creatine nitrate supplementation and exercise performance.
abstract: BACKGROUND
  Creatine monohydrate (CrM) and nitrate are popular supplements for improving exercise performance; yet have not been investigated in combination. We performed two studies to determine the safety and exercise performance-characteristics of creatine nitrate (CrN) supplementation.
  
  
  METHODS
  Study 1 participants (N = 13) ingested 1.5 g CrN (CrN-Low), 3 g CrN (CrN-High), 5 g CrM or a placebo in a randomized, crossover study (7d washout) to determine supplement safety (hepatorenal and muscle enzymes, heart rate, blood pressure and side effects) measured at time-0 (unsupplemented), 30-min, and then hourly for 5-h post-ingestion. Study 2 participants (N = 48) received the same CrN treatments vs. 3 g CrM in a randomized, double-blind, 28d trial inclusive of a 7-d interim testing period and loading sequence (4 servings/d). Day-7 and d-28 measured Tendo™ bench press performance, Wingate testing and a 6x6-s bicycle ergometer sprint. Data were analyzed using a GLM and results are reported as mean ± SD or mean change ± 95 % CI.
  
  
  RESULTS
  In both studies we observed several significant, yet stochastic changes in blood markers that were not indicative of potential harm or consistent for any treatment group. Equally, all treatment groups reported a similar number of minimal side effects. In Study 2, there was a significant increase in plasma nitrates for both CrN groups by d-7, subsequently abating by d-28. Muscle creatine increased significantly by d-7 in the CrM and CrN-High groups, but then decreased by d-28 for CrN-High. By d-28, there were significant increases in bench press lifting volume (kg) for all groups (PLA, 126.6, 95 % CI 26.3, 226.8; CrM, 194.1, 95 % CI 89.0, 299.2; CrN-Low, 118.3, 95 % CI 26.1, 210.5; CrN-High, 267.2, 95 % CI 175.0, 359.4, kg). Only the CrN-High group was significantly greater than PLA (p < 0.05). Similar findings were observed for bench press peak power (PLA, 59.0, 95 % CI 4.5, 113.4; CrM, 68.6, 95 % CI 11.4, 125.8; CrN-Low, 40.9, 95 % CI -9.2, 91.0; CrN-High, 60.9, 95 % CI 10.8, 111.1, W) and average power.
  
  
  CONCLUSIONS
  Creatine nitrate delivered at 3 g was well-tolerated, demonstrated similar performance benefits to 3 g CrM, in addition, within the confines of this study, there were no safety concerns.
authors.affiliation: Department of Health and Kinesiology, Exercise and Sport Nutrition Laboratory, Texas A&M University, College Station, TX 77843-4243 USA.
authors.forename: Elfego
authors.initials: E
authors.lastname: Galvan
authors.affiliation: Department of Health and Kinesiology, Center for Translational Research in Aging and Longevity, Texas A&M University, College Station, TX 77843-4243 USA.
authors.forename: Dillon K
authors.initials: DK
authors.lastname: Walker
authors.affiliation: Department of Health and Kinesiology, Center for Translational Research in Aging and Longevity, Texas A&M University, College Station, TX 77843-4243 USA.
authors.forename: Sunday Y
authors.initials: SY
authors.lastname: Simbo
authors.affiliation: Department of Health and Kinesiology, Exercise and Sport Nutrition Laboratory, Texas A&M University, College Station, TX 77843-4243 USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Dalton
authors.affiliation: Department of Health and Kinesiology, Exercise and Sport Nutrition Laboratory, Texas A&M University, College Station, TX 77843-4243 USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Levers
authors.affiliation: Department of Health and Kinesiology, Exercise and Sport Nutrition Laboratory, Texas A&M University, College Station, TX 77843-4243 USA.
authors.forename: Abigail
authors.initials: A
authors.lastname: O'Connor
authors.affiliation: Department of Health and Kinesiology, Exercise and Sport Nutrition Laboratory, Texas A&M University, College Station, TX 77843-4243 USA.
authors.forename: Chelsea
authors.initials: C
authors.lastname: Goodenough
authors.affiliation: United States Military-Baylor University Graduate Program in Nutrition, Joint Base, San Antonio, TX 78234 USA.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Barringer
authors.affiliation: Department of Health and Kinesiology, Exercise and Sport Nutrition Laboratory, Texas A&M University, College Station, TX 77843-4243 USA.
authors.forename: Mike
authors.initials: M
authors.lastname: Greenwood
authors.affiliation: Department of Health and Kinesiology, Exercise and Sport Nutrition Laboratory, Texas A&M University, College Station, TX 77843-4243 USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Rasmussen
authors.affiliation: Department of Animal Science, Texas A&M University, College Station, TX 77843-4243 USA.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Smith
authors.affiliation: Department of Health and Kinesiology, Human Countermeasures Laboratory, Texas A&M University, College Station, TX 77843-4243 USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Riechman
authors.affiliation: Department of Health and Kinesiology, Muscle Biology Laboratory, Texas A&M University, College Station, TX 77843-4243 USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Fluckey
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843-4243 USA.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Murano
authors.affiliation: Nutrabolt, Bryan, TX 77807 USA.
authors.forename: Conrad P
authors.initials: CP
authors.lastname: Earnest
authors.affiliation: Department of Health and Kinesiology, Exercise and Sport Nutrition Laboratory, Texas A&M University, College Station, TX 77843-4243 USA.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Kreider
mesh_terms: D000328:Adult; D015308:Anaerobic Threshold / Q000187:drug effects* / Q000502:physiology; D054874:Athletic Performance; D001794:Blood Pressure / Q000187:drug effects; D003401:Creatine; D018592:Cross-Over Studies; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D053580:Muscle Strength / Q000187:drug effects* / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects; D009566:Nitrates / Q000008:administration & dosage*; D010807:Physical Endurance / Q000187:drug effects*; D010809:Physical Fitness / Q000502:physiology*; D014891:Weight Lifting / Q000502:physiology*
chemical_list: D009566:Nitrates; D003401:Creatine
keywords: Creatine; Creatine nitrate; Exercise performance; Nitrate; Nutrition; Supplementation