Guanidinoacetic Acid and Creatine are Associated with Cardiometabolic Risk Factors in Healthy Men and Women: A Cross-Sectional Study.
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ABSTRACT:
SUBMITTER: Ostojic SM
PROVIDER: S-EPMC5793315 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Guanidinoacetic acid (GAA) is a natural precursor of creatine, yet the potential use of GAA as a nutritional additive for restoring creatine availability in humans has been limited by unclear efficacy and safety after exogenous GAA administration. The present study evaluated the effects of orally administered GAA on serum and urinary GAA, creatine and creatinine concentration, and on the occurrence of adverse events in healthy humans.Twenty-four healthy volunteers were randomized in a double-blind design to receive either GAA (2.4 grams daily) or placebo (PLA) by oral administration for 6 weeks.www.clinicaltrials.gov, identification number NCT01133899. Serum creatine and creatinine increased significantly from before to after administration in GAA-supplemented participants (P < 0.05). The proportion of participants who reported minor side effects was 58.3% in the GAA group and 45.5% in the placebo group (P = 0.68). A few participants experienced serum creatine levels above 70 µmol/L.Exogenous GAA is metabolized to creatine, resulting in a significant increase of fasting serum creatine after intervention. GAA had an acceptable side-effects profile with a low incidence of biochemical abnormalities.
| S-EPMC3547211 | biostudies-literature
Project description:Creatine kinetics were measured in young healthy subjects, eight males and seven females, age 20-30 years, after an overnight fast on creatine-free diet. Whole body turnover of glycine and its appearance in creatine was quantified using [1-(13)C] glycine and the rate of protein turnover was quantified using L-ring [(2)H5] phenylalanine. The creatine pool size was estimated by the dilution of a bolus [C(2)H3] creatine. Studies were repeated following a five days supplement creatine 21 g.day(-1) and following supplement amino acids 14.3 g day(-1). Creatine caused a ten-fold increase in the plasma concentration of creatine and a 50 % decrease in the concentration of guanidinoacetic acid. Plasma amino acids profile showed a significant decrease in glycine, glutamine, and taurine and a significant increase in citrulline, valine, lysine, and cysteine. There was a significant decrease in the rate of appearance of glycine, suggesting a decrease in de-novo synthesis (p = 0.006). The fractional and absolute rate of synthesis of creatine was significantly decreased by supplemental creatine. Amino acid supplement had no impact on any of the parameters. This is the first detailed analysis of creatine kinetics and the effects of creatine supplement in healthy young men and women. These methods can be applied for the analysis of creatine kinetics in different physiological states.
| S-EPMC4754151 | biostudies-literature
Project description:BACKGROUND:Hypertension is a direct cardiovascular disease risk. It causes a heavy burden on the healthcare system globally. We aim to assess hypertension occurrence and its associated factors among women and men in Vietnam. METHODS:A cross-sectional study was conducted from January to February 2019 on 2203 community-dwelling women and men aged 18 years or above. Participants' characteristics, comorbidity, behaviors, and physical measures were evaluated. Hypertension was classified as systolic/diastolic blood pressure ?140/90 mmHg or using antihypertensive medication. We analyzed data using logistic regression models. RESULTS:The prevalence of hypertension was 24.3% (20.9% in women, 29.1% in men). For women, older age (odds ratio, OR, 6.80-12.41; p < 0.001), income above the poverty line (OR, 0.64; p = 0.008), diabetes comorbid (OR, 2.98; p < 0.001), added salts consumption (OR, 1.80; p < 0.001), overweight/obesity (OR, 1.64; p = 0.005), abdominal obesity (OR, 2.07; p < 0.001) were associated with hypertension. For men, older age (OR, 2.67-5.92; p < 0.001), diabetes comorbid (OR, 2.25; p = 0.010), smoking (OR, 1.38; p = 0.046), and overweight/obesity (OR, 2.18; p < 0.001) were associated with hypertension. Conclusions: Hypertension is prevalent in Vietnamese people. The associated factors of hypertension are varied by gender.
| S-EPMC6926662 | biostudies-literature
Project description:Background:An average adult American consumes sulfur amino acids (SAA) at levels far above the Estimated Average Requirement (EAR) and recent preclinical data suggest that higher levels of SAA intake may be associated with a variety of aging-related chronic diseases. However, there are little data regarding the relationship between SAA intake and chronic disease risk in humans. The aim of this study was to examine the associations between consumption of SAA and risk factors for cardiometabolic diseases. Methods:The sample included 11,576 adult participants of the Third National Examination and Nutritional Health Survey (NHANES III) Study (1988-1994). The primary outcome was cardiometabolic disease risk score (composite risk factor based on blood cholesterol, triglycerides, HDL, C-reactive protein (CRP), uric acid, glucose, blood urea nitrogen (BUN), glycated hemoglobin, insulin, and eGFR). Group differences in risk score by quintiles of energy-adjusted total SAA, methionine (Met), and cysteine (Cys) intake were determined by multiple linear regression after adjusting for age, sex, BMI, smoking, alcohol intake, and dietary factors. We further examined for associations between SAA intake and individual risk factors. Findings:Mean SAA consumption was > 2.5-fold higher than the EAR. After multivariable adjustment, higher intake of SAA, Met, and Cys were associated with significant increases in composite cardiometabolic disease risk scores, independent of protein intake, and with several individual risk factors including serum cholesterol, glucose, uric acid, BUN, and insulin and glycated hemoglobin (p < 0.01). Interpretation:Overall, our findings suggest that diets lower in SAA (close to the EAR) are associated with reduced risk for cardiometabolic diseases. Low SAA dietary patterns rely on plant-derived protein sources over meat derived foods. Given the high intake of SAA among most adults, our findings may have important public health implications for chronic disease prevention. Funding:This study does not have any funding.
| S-EPMC7046517 | biostudies-literature
Project description:Diet regulates gene expression profiles by several mechanisms. The objective of this study was to examine gene expression in relation with dietary patterns.Two hundred and fifty four participants from the greater Quebec City metropolitan area were recruited. Two hundred and ten participants completed the study protocol. Dietary patterns were derived from a food frequency questionnaire (FFQ) by factor analysis. For 30 participants (in fasting state), RNA was extracted from peripheral blood mononuclear cells (PBMCs) and expression levels of 47,231 mRNA transcripts were assessed using the Illumina Human-6 v3 Expression BeadChips®. Microarray data was pre-processed with Flexarray software and analysed with Ingenuity Pathway Analysis (IPA).Two dietary patterns were identified. The Prudent dietary pattern was characterised by high intakes of vegetables, fruits, whole grain products and low intakes of refined grain products and the Western dietary pattern, by high intakes of refined grain products, desserts, sweets and processed meats. When individuals with high scores for the Prudent dietary pattern where compared to individuals with low scores, 2,083 transcripts were differentially expressed in men, 1,136 transcripts in women and 59 transcripts were overlapping in men and women. For the Western dietary pattern, 1,021 transcripts were differentially expressed in men with high versus low scores, 1,163 transcripts in women and 23 transcripts were overlapping in men and women. IPA reveals that genes differentially expressed for both patterns were present in networks related to the immune and/or inflammatory response, cancer and cardiovascular diseases.Gene expression profiles were different according to dietary patterns, which probably modulate the risk of chronic diseases.NCT: NCT01343342.
| S-EPMC3598224 | biostudies-literature
Project description:The creatine precursor guanidinoacetate (GAA) was used as a dietary supplement in humans with no adverse events. Nevertheless, it has been suggested that GAA is epileptogenic or toxic to the nervous system. However, increased GAA content in rodents affected by guanidinoacetate methyltransferase (GAMT) deficiency might be responsible for their spared muscle function. Given these conflicting data, and lacking experimental evidence, we investigated whether GAA affected synaptic transmission in brain hippocampal slices. Incubation with 11.5 μM GAA (the highest concentration in the cerebrospinal fluid of GAMT-deficient patients) did not change the postsynaptic compound action potential. Even 1 or 2 mM had no effect, while 4 mM caused a reversible decrease in the potential. Guanidinoacetate increased creatine and phosphocreatine, but not after blocking the creatine transporter (also used by GAA). In an attempt to allow the brain delivery of GAA when there was a creatine transporter deficiency, we synthesized diacetyl guanidinoacetic acid ethyl ester (diacetyl-GAAE), a lipophilic derivative. In brain slices, 0.1 mM did not cause electrophysiological changes and improved tissue viability after blockage of the creatine transporter. However, diacetyl-GAAE did not increase creatine nor phosphocreatine in brain slices after blockage of the creatine transporter. We conclude that: (1) upon acute administration, GAA is neither epileptogenic nor neurotoxic; (2) Diacetyl-GAAE improves tissue viability after blockage of the creatine transporter but not through an increase in creatine or phosphocreatine. Diacetyl-GAAE might give rise to a GAA-phosphoGAA system that vicariates the missing creatine-phosphocreatine system. Our in vitro data show that GAA supplementation may be safe in the short term, and that a lipophilic GAA prodrug may be useful in creatine transporter deficiency.
| S-EPMC8773658 | biostudies-literature
Project description:The aim of this study was to investigate the effects of dietary supplementation with guanidinoacetic acid (GAA) on the growth performance, creatine and energy metabolism, and carcass characteristics in growing-finishing pigs. In Exp. 1, Duroc × Landrace × Yorkshire pigs (n = 180, 33.61 ± 3.91 kg average BW) were blocked by weight and sex, and allotted to 5 treatments with 6 replicates (3 gilts and 3 barrows per replicate pen). Diets were corn-soybean meal-basal diets supplemented with 0, 300, 600, 900, and 1,200 mg/kg of GAA and fed to the pigs for 98 d. From days 1 to 98, G:F increased (linear, P < 0.05) with increasing addition of dietary GAA. Using a broken-line model, the optimum level of dietary GAA was 300 mg/kg during the overall experimental period (days 1 to 98) to maximize G:F. Hot carcass weight, carcass length, and lean percentage showed a tendency to increase (quadratic, 0.05 < P < 0.10) with increasing addition of dietary GAA. On day 98, serum GAA and liver creatine tended to increase (linear, P = 0.10, 0.07) as dietary GAA increased. In addition, serum ATP on day 98 increased linearly (linear, P < 0.01), and muscle ATP and adenosine monophosphate increased quadratically (quadratic, P = 0.05) with incremental GAA supplementation. In Exp. 2, Duroc × Landrace × Yorkshire pigs (n = 180, 53.19 ± 5.63 kg average BW) were blocked by weight and sex, and allotted to 5 treatments with 6 replicates (3 gilts and 3 barrows per replicate pen). Diets were corn-soybean meal-basal diets supplemented with 0, 150, 300, 600, and 1,200 mg/kg of GAA for 35 d. As dietary GAA increased, final BW, ADG, and G:F increased quadratically (quadratic, P < 0.01), and 300 mg/kg of GAA maximized ADG and final BW (P < 0.05).The results indicate that dietary GAA could increase the creatine and ATP load in the tissues of pigs and accordingly improve growth performance. Dietary supplementation with 300 mg/kg of GAA was suitable to maximize the growth performance of growing-finishing pigs.
| S-EPMC6095271 | biostudies-literature
Project description:The emergence of creatine as a potential cognitive enhancement supplement for humans prompted an investigation as to whether supplemental creatine could enhance spatial memory in young swine. We assessed memory performance and brain concentrations of creatine and its precursor guanidinoacetic acid (GAA) in 14-16-week-old male Yucatan miniature pigs supplemented for 2 weeks with either 200 mg/kg∙d creatine (+Cr; n = 7) or equimolar GAA (157 mg/kg∙d) (+GAA; n = 8) compared to controls (n = 14). Spatial memory tests had pigs explore distinct sets of objects for 5 min. Objects were spatially controlled, and we assessed exploration times of previously viewed objects relative to novel objects in familiar or novel locations. There was no effect of either supplementation on memory performance, but pigs successfully identified novel objects after 10 (p < 0.01) and 20 min (p < 0.01) retention intervals. Moreover, pigs recognized spatial transfers after 65 min (p < 0.05). Regression analyses identified associations between the ability to identify novel objects in memory tests and concentrations of creatine and GAA in cerebellum, and GAA in prefrontal cortex (p < 0.05). The concentration of creatine in brain regions was not influenced by creatine supplementation, but GAA supplementation increased GAA concentration in cerebellum (p < 0.05), and the prefrontal cortex of +GAA pigs had more creatine/g and less GAA/g compared to +Cr pigs (p < 0.05). Creatine kinase activity and maximal reaction velocity were also higher with GAA supplementation in prefrontal cortex (p < 0.05). In conclusion, there appears to be a relationship between memory performance and guanidino compounds in the cerebellum and prefrontal cortex, but the effects were unrelated to dietary supplementation. The cerebellum is identified as a target site for GAA accretion.
| S-EPMC6944358 | biostudies-literature
Project description:BackgroundAssociations between diet and cardiometabolic disease (CMD) risk may vary in men and women owing to sex differences in eating habits and physiology. The current secondary analysis sought to determine the ability of sex differences in dietary patterns to discriminate groups with or without CMD risk factors (CMDrf) in the adult population and if this was influenced by age.MethodsDiet patterns and quality were evaluated using 24 h recall-based Healthy Eating Index (HEI-2015) in free-living apparently healthy men (n = 184) and women (n = 209) 18-65 y of age with BMIs of 18-44 kg/m2. Participants were stratified into low- and high-CMDrf groups based on the presence/absence of at least one CMDrf: BMI > 25 kg/m2; fasting triglycerides > 150 mg/dL; HDL cholesterol < 50 mg/dL-women or < 40 mg/dL-men; HOMA > 2; HbA1c > 5.7. Sex by age dietary patterns were stratified by multivariate analyses, with metabolic variable associations established by stepwise discriminant analysis.ResultsDiet quality increased with age in both sexes (P < 0.01), while women showed higher fruit, vegetable and saturated fat intake as a percentage of total energy (P < 0.05). The total-HEI score (i.e. diet quality) was lower in the high-CMDrf group (P = 0.01), however, diet quality parameters predicted CMDrf presence more accurately when separated by sex. Lower 'total vegetable' intake in the high-CMDrf group in both sexes, while high-CMDrf men also had lower 'total vegetables', 'greens and beans' intake, and high-CMDrf women had lower 'total fruits', 'whole-fruits', 'total vegetables', 'seafood and plant-proteins', 'fatty acids', and 'saturated fats' intakes (P < 0.05). Moreover, 'dairy' intake was higher in high-CMDrf women but not in men (sex by 'dairy' interaction P = 0.01). Sex by age diet pattern models predicted CMDrf with a 93 and 89% sensitivity and 84 and 92% specificity in women and men, respectively.ConclusionsSex and age differences in dietary patterns classified participants with and without accepted CMDrfs, supporting an association between specific diet components and CMD risk that differs by sex. Including sex specific dietary patterns into health assessments may provide targeted nutritional guidance to reduce the burden of cardiovascular disease.Trial registrationClinicalTrials.gov : NCT02367287 . ClinicalTrials.gov : NCT02298725 .
| S-EPMC8218401 | biostudies-literature
Project description:Contradictory data exist on the impact of occupational physical activity (OPA) on cardiovascular health. We aimed to evaluate the association between OPA and cardiometabolic risk factors. A cross-sectional study was performed in an environmental services company in 2017 (Spain). OPA was classified by work categories as being low (≤3 METs) or moderate-high (>3 METs). Multiple linear and logistic binary regression models were used to assess the associations between OPA and cardiometabolic risk factors related to obesity, blood pressure, blood lipids, and associated medical conditions, adjusted by age, sex, alcohol consumption, and global physical activity. In total, 751 employees were included (547 males and 204 females), and 55.5% (n = 417) had moderate-high OPA. Significant inverse associations were observed between OPA and weight, body mass index, waist circumference, waist-hip ratio, and total cholesterol both overall and in males. OPA was significantly inversely related to dyslipidemia overall and in both sexes, while the overweight plus obesity rate was inversely related only in the total and male populations. OPA was associated with a better cardiometabolic risk factor profile, particularly in males. The fact that our models were also adjusted by global physical activity highlights the associations obtained as being independent of leisure time physical activity effects.
| S-EPMC10055795 | biostudies-literature