Impact of Creatine Supplementation on Vascular Endothelial Function, Blood Flow and Functional Capacity in Older Adults
Clarke, Holly Elizabeth (author)
Hickner, Robert C., 1962- (professor directing dissertation)
Williams, Diana L. (university representative)
Ormsbee, Michael J. (committee member)
Gordon, Bradley S. (committee member)
Florida State University (degree granting institution)
College of Health and Human Sciences (degree granting college)
Department of Nutrition and Integrative Physiology (degree granting department)
INTRODUCTION: Cardiovascular disease (CVD) remains the leading cause of mortality in United States (US) , and the inevitable process of aging, or one's age, remains the primary unmodifiable risk factor and independent predictor of CVD events across the lifespan . With aging comes a progressive deterioration in vascular health, characterized by arterial stiffening and endothelial dysfunction (ED) [3-5]. Furthermore, oxidative stress, marked by an accumulation of reactive oxygen species (ROS), increases with age and is a prominent feature of vascular disease . These vascular changes, in addition to other age-related declines in strength and cognition, all contribute to reduced functionality in many older adults. While popular dietary interventions have been applauded for their benefits upon cardiovascular health [7, 8], there is emerging evidence that suggests creatine supplementation may also serve as a therapeutic supplement . Although well known for its metabolic properties, recent research has exposed a much broader application for creatine in clinical populations, acting as an antioxidant, energy shuttle and neuroprotective compound [10-12]. Despite these benefits however, there is scarce information on the application of creatine for vascular health and functional capacity in older adults. PURPOSE: Thus, the purpose of this study was to determine the effects of 4 weeks of creatine monohydrate supplementation, as compared to placebo, on vascular endothelial function, blood flow, oxidative stress, and functional capacity in older adults. Methods: Twelve, healthy older adults (M = 6, W = 6, age: 58 ± 3 years, BMI: 26 ± 6) participated in this randomized, double-blind, placebo-controlled crossover study. Eligible participants completed 4 official study visits: Pre-Testing 1, Post-Test 1, Pre-Testing 2, Post-Test 2. At every study visit participants were fasted and completed anthropometric assessments (height, weight, BMI), body composition [dual-energy x-ray absorptiometry (DXA)], and venous blood draw. Participants then completed assessments of vascular function [flow mediated dilation (FMD%), brachial-ankle pulse wave velocity (baPWV), pulse wave analysis (PWA), near-infrared microvascular reperfusion (NIRS MOXY)], cognitive function [forward digit span test (FDS), backward digit span test (BDS), trail making test part A (TMT-A) and B (TMT-B)], and physical function [6-minute walking test (6MWT), BioDex assessment of isometric muscle strength and endurance]. Once all Pre-Testing assessments were complete, participants were randomized to receive one of two blinded supplements: placebo (maltodextrin) or creatine monohydrate. Participants were asked to consume supplements for the following 4 weeks (4 x 5 g/day for 5 days, followed by 1 x 5g for 23 days). Following supplementation, participants returned for Post-Testing. During this visit, all procedures from the Pre-Testing Visit were repeated. Participants were then asked to return to their normal daily lifestyles for a 4-week "wash-out" period. After the washout, participants returned for their second Pre-Testing visit. Following this, participants were given their remaining supplement. Following the final supplementation, participants returned to the lab to complete their final Post-Test visit. Results: After creatine supplementation there was a significant improvement in FMD% (Pre: 7.68 ± 2.25 %, Post: 8.9 ± 1.99 %; p < .005), absolute change in diameter (Pre: 0.33 ± 0.12 mm, Post: 0.38 ± 0.12 mm; p < .05), normalized FMD% (Pre: 2.57E-04 ± 1.03E-04 %/SSAUC, Post: 3.42E-04 ± 1.69E-04 %/SSAUC; p < .05), and microvascular reperfusion (Pre: 2.29 ± 1.42 %/sec, Post: 3.71 ± 1.44 %/sec; p < .05); however, there were no significant changes in baPWV or PWA compared to placebo. There were no significant interactions found for any of the blood biomarkers; however, there was a significant effect of time for oxLDL (p < .05), and a trending toward significant effect of treatment for MDA (p = 0.055). There were significant improvements seen in both FDS (Pre: 7.08 ± 0.99, Post: 7.83 ± 1.27; p < .05) and BDS (Pre: 4.83 ± 1.64, Post: 5.83 ± 1.27; p < .05) following creatine, but no significant changes in TMT-A or TMT-B following either creatine or placebo. There were also no significant changes in 6MWT distance covered or isometric muscle strength; however, isometric muscle endurance, as indicated by total torque produced per set, improved for Set 1 (Pre: 2046.03 ± 823.78 Nm, Post: 2341.92 ± 896.02 Nm, p < .001), Set 2 (Pre: 1753.3 ± 484.26 Nm, Post: 1892.78 ± 583.18 Nm, p < .05), and Set 3 (Pre: 1642.35 ± 463.76 Nm, Post: 1745.7 ± 522.5 Nm, p < .05) following creatine, but not placebo. Conclusion: Our findings indicate that 4 weeks of creatine supplementation, but not placebo, improves endothelial function and microvascular reactivity in older adults; however, there was no benefit for arterial stiffness. Creatine supplementation, in comparison to placebo, can also improve markers of short-term memory and isokinetic muscle endurance, but neither creatine or placebo improved visuospatial awareness or isokinetic muscle strength. However, findings indicate that these improvements were not mediated by any creatine-dependent antioxidant effects. Further research is warranted to determine the mechanism in which creatine elicits these reported vascular benefits in older adults.
Creatine, Endothelial Function, Functional Capacity , Older Adults, Vascular Health
October 22, 2021.
A Dissertation submitted to the Department of Nutrition and Integrative Physiology in partial fulfillment of the requirements for the degree of Doctor of Philosophy.
Includes bibliographical references.
Robert C. Hickner, Professor Directing Dissertation; Diana L. Williams, University Representative; Michael J. Ormsbee, Committee Member; Bradley S. Gordon, Committee Member.
Florida State University