ORIGINAL ARTICLE Effects of dietary supplementation with creatine on homocysteinemia and systemic microvascular endothelial function in individuals adhering to vegan diets Diogo Van Bavel a , Roger de Moraes a,b , Eduardo Tibirica a * a National Institute of Cardiology, Ministry of Health, Rua das Laranjeiras 374, Rio de Janeiro 22240-006, Brazil b Research and Productivity Program, Estacio de S a University, Rua do Bispo 83, Rio de Janeiro 20261-064, Brazil Keywords capillary recruitment, intravital video-microscopy, laser speckle contrast imaging, postocclusive reactive hyperemia Received 24 August 2018; revised 15 November 2018; accepted 29 November 2018 *Correspondence and reprints: etibi@uol.com.br ABSTRACT The incidence of cardiovascular diseases in vegetarian individuals is lower than that in the general population. Nevertheless, individuals who adhere to vegan diets have a higher prevalence of hyperhomocysteinemia with eventual adverse effects on vascular reactivity. Creatine supplementation (CrS) reduces plasma homocys- teine levels and enhances vascular reactivity in the microcirculation. Thus, we investigated the effects of CrS on systemic microcirculation and homocysteine blood levels in strict vegan subjects. Forty-nine strict vegan subjects were allocated to the oral CrS (5 g micronized creatine monohydrate daily for three weeks; n = 31) and placebo (n = 18) groups. Laser speckle contrast imaging coupled with acetylcholine skin iontophoresis was used to evaluate cutaneous microvascular reactivity, and intravital video-microscopy was used to evaluate skin capillary den- sity and reactivity before and after CrS. We demonstrated that CrS reduces the plasma levels of homocysteine and increases those of folic acid. After the CrS per- iod, the homocysteine levels of all of the vegan subjects normalized. CrS also induced increases in baseline skin functional capillary density and endothelium- dependent capillary recruitment in both normo- (N-Hcy) and hyperhomocysteine- mic (H-Hcy) individuals. CrS increased endothelium-dependent skin microvascular vasodilation in the H-Hcy vegan subjects but not in the N-Hcy vegan subjects. In conclusion, three weeks of oral CrS was sufficient to increase skin capillary density and recruitment and endothelium-dependent microvascular reactivity. CrS also resulted in plasma increases in folic acid levels and reductions in homocysteine levels among only the H-Hcy individuals. INTRODUCTION Vegan diets, which are defined as a dietary profile characterized by abstention from consuming any ani- mal products, may have positive long-term health impacts, such as reductions in the prevalence of obesity and of cardiovascular disease in the general population [1,2]. Compared with that for omnivores, the incidence of cardiovascular disease and type 2 diabetes is significantly lower in vegetarians and especially in veg- ans, who generally have lower body mass index and total and LDL cholesterol levels and moderately lower blood pressure [1]. For ethical and moral reasons, strict vegans abstain from consuming animal diets. Nevertheless, even though vegans adhere to a diet characterized by a large intake of fruits and vegetables, they present sev- eral micronutrient deficiencies [2]. In fact, eliminating ª 2018 Soci et e Franc ßaise de Pharmacologie et de Th erapeutique 428 Fundamental & Clinical Pharmacology 33 (2019) 428–440 doi: 10.1111/fcp.12442