Effects of dietary creatine supplementation on systemic microvascular density and reactivity in healthy young adults

Abstract

BackgroundDietary creatine supplementation (CrS) is a practice commonly adopted by physically active individuals. However, the effects of CrS on systemic microvascular reactivity and density have never been reported. Additionally, CrS is able to influence blood levels of homocysteine, resulting in presumed effects on vascular endothelial function. Thus, we investigated the effects of CrS on the systemic microcirculation and on homocysteine levels in healthy young individuals.MethodsThis open-label study was performed on a group of 40 healthy male, moderately physically active subjects aged 27.7 ± 13.4 years who received one week of CrS at a dose of 20 g/day of commercially available micronized creatine monohydrate. Laser speckle contrast imaging was used in the evaluation of cutaneous microvascular reactivity, and intra-vital video microscopy was used to evaluate skin capillary density and reactivity, before and after CrS.ResultsCrS did not alter plasma levels of homocysteine, although CrS increased creatinine (p = 0.0001) and decreased uric acid (p = 0.0004) plasma levels. Significant changes in total cholesterol (p = 0.0486) and LDL-cholesterol (p = 0.0027) were also observed along with a reduction in plasma levels of T3 (p = 0.0074) and an increase in T4 levels (p = 0.0003). Skin functional capillary density (p = 0.0496) and capillary recruitment during post-occlusive reactive hyperemia (p = 0.0043) increased after CrS. Increases in cutaneous microvascular vasodilation induced by post-occlusive reactive hyperemia (p = 0.0078) were also observed.ConclusionsOral supplementation with creatine in healthy, moderately physically active young adults improves systemic endothelial-dependent microvascular reactivity and increases skin capillary density and recruitment. These effects are not concurrent with changes in plasma homocysteine levels.

Effects of dietary supplementation with creatine on homocysteinemia and systemic microvascular endothelial function in individuals adhering to vegan diets

“…It is noteworthy that the capillary densities in all of the groups of the present study appeared to be significantly higher than those observed in omnivores of the same age‐group in another study conducted by our group , suggesting that vegans have a higher degree of tissue perfusion than omnivorous subjects.…”

“…Although neither placebo nor CrS was able to alter the vitamin B‐12 levels in normo‐ or hyperhomocysteinemic vegan subjects, these levels were marginally but significantly lower among the hyperhomocysteinemic vegan subjects. Our volunteers did not show any hypothyroidism signs despite this micronutrient deficiency being a risk of vegan diets, and CrS did not change the T3 and T4 serum levels as it did with the omnivorous subjects in our previous study .…”

“…We recently demonstrated that oral supplementation with creatine in healthy, moderately physically active nonvegetarian young adults do not change their plasma homocysteine levels but improves their systemic endothelial‐dependent microvascular reactivity and increases their skin capillary density and recruitment . In this study, creatine supplementation was shown to reduce total cholesterol and LDL cholesterol plasma levels and significantly increase T4 levels .…”

“…Notwithstanding, recent data show that creatine supplementation may be a practical strategy to decrease plasma homocysteine levels and reduce vascular oxidative stress . In fact, our group recently demonstrated that oral supplementation with 20 g per day of creatine for only one week was able to significantly increase skin capillary perfusion at rest and during postocclusive reactive hyperemia in young, healthy, and physically active nonvegetarian individuals . In this study, we hypothesized that the possible increase in the creatine kinase–phosphocreatine ratio (Cr/PCr ratio) induced by CrS in endothelial cells could activate AMPK and increase adenosine levels .…”

“…In this sense, CrS is able to influence metabolic changes, including increases in the adenosine and folic acid levels that could change the DNA‐methyltransferase activity and thereby alter the DNA methylation profile, inducing angiogenesis and anti‐inflammatory effects . In this way, CrS was already suggested to activate AMP‐activated protein kinase (AMPK) and increase the enzyme activity of 5’‐nucleotidase, which catalyzes the AMP deamination in adenosine and phosphate through the PKC pathway .…”