Background: Dietary 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.
Methods: This 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.
Results: CrS 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.
Conclusions: Oral 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.
Alex’s Notes: I’m not one to read creatine research much anymore. Creatine has strongly proven itself to be worthy of a spot on the supplementation table for nearly every regardless of goals, and while it is most well-known for benefiting athletic performance, research continues to shed light on how incredible this simple and dirt-cheap compound is for promoting health in nearly every bodily system. If you are skeptical, then I strongly encourage you to take a look at Examine’s Creatine Monohydrate page (with its monstrous 711 citations). To quote Examine’s lead researcher, Kurtis Frank,
“I honestly see no reason why somebody shouldn't supplement creatine, nor do I see any logical basis for the seeming 'fear' of this compound in society. It's safe, it's healthy, it's cheap, and for most people, it just works. Get some Creatine Monohydrate, take 5g a day, and you're good to go. If humans didn't make any in the body, this thing would be a vitamin. There do exist deficiency symptoms that result in mental retardation. They're rare, but they pretty much establish the importance of this molecule as a vitamin-like compound.”
So with that said; creatine is capable of exerting anti-inflammatory effects on blood vessel walls and lowering arterial stiffness. Some studies have suggested that this is owed to creatine’s ability to reduce homocysteine levels, and thus the current study aimed to investigate the effect of creatine monohydrate on microcirculation and homocysteine in healthy young men.
To approach this problem, the researchers recruited 40 men from among the students at their university who were not athletes, but were all physically active and engaged in aerobic and/or strength training at least three times per week, and had them consume 20g of commercial creatine monohydrate powder per day in four 5g doses. None of the subjects had taken creatine supplementation within the previous three months. To assess vascular function, the researchers used a relatively novel method whereby a laser was beamed on to the forearm skin, creating an image of microvascular flow for analysis.
Keep in mind that the results are after a mere one week of creatine loading. There was a significant increase in body mass (0.5kg) and BMI of the subjects, likely from fluid retention, but a significant reduction in average blood pressure (-2.3mmHg). The laser imaging demonstrated that capillary density of the subjects was significantly increased by about 4%, while capillary recruitment was improved by about 5%. The researchers concluded that the main findings of this study were,
- Oral supplementation with creatine monohydrate in healthy, moderately physically active young adults improves systemic endothelial-dependent microvascular reactivity;
- The supplementation also increased skin capillary density and recruitment, which are dependent on microvascular endothelial function; and
- Blood pressure was also reduced after the supplementation.
As an explanation, the authors suggest that increased intracellular creatine levels in tissues such as blood vessels activate potassium channels that ultimately cause vasodilation. So where does homocysteine come into play? Well, nowhere, as it was not significantly affected from supplementation.
Follow the yellow brick road
An interesting and unexpected finding of the study was a significant reduction in T3 and increase in T4, albeit the changes minor in magnitude. The authors come up with an intriguing series of events to explain this. It has been suggested that creatine supplementation is able to create an “energy deficit” signal by increasing the amount of creatine kinase relative to phosphocreatine. This is in-line with creatine’s ability to stimulate AMPK, glucose oxidation, and mitochondrial respiration.
The conversion of T4 to T3 occurs primarily in the kidneys and skeletal muscle through the type-2 deiodinase enzyme. This process requires energy (ATP), and because creatine signals an energy deficit, it is possible that the supplementation reduced the conversion. This would further explain the other blood work abnormalities. Reductions in T3 increases membrane permeability of skeletal muscle thereby increasing plasma concentrations of creatine kinase (a marker of muscle damage), which was significantly higher after supplementation. Together, the increased creatinine and CK would reduce globulins and mimic conditions of impaired renal function. This has actually led to misdiagnosis.
Anyway, creatine appears to improve endothelial function in a relatively short time. So here is yet another reason to supplement.