Creatine HCl

OBJECTIVE: To investigate the effects of an 8-week supplementation with varying doses of creatine hydrochloride, administered alone or in combination with creatine ethyl ester, on cognitive function, clinical outcomes, brain creatine concentrations, and biochemical markers in perimenopausal and postmenopausal women. This study specifically aimed to evaluate the potential of low-dose creatine formulations with enhanced solubility as a targeted intervention for menopause-related neurocognitive and metabolic changes. METHODS: A total of 36 apparently healthy perimenopausal and menopausal women (mean age 50.1 ± 5.7 years) were randomly allocated to one of four groups: low-dose creatine hydrochloride (750 mg/day), medium-dose creatine hydrochloride (1,500 mg/day), creatine hydrochloride plus creatine ethyl ester (800 mg/day), or placebo, in this randomized controlled double-blind trial. Menopausal women were defined as having no menstrual cycle for 12 consecutive months without other causes, while perimenopausal women were still menstruating but reported at least one symptom such as hot flashes, sleep disturbances, mood swings, or concentration difficulties. RESULTS: Supplementation with medium-dose creatine hydrochloride was found to be superior to placebo in enhancing reaction time (1.2 vs. 6.6%; p < 0.01), increasing frontal brain creatine levels (0.9 vs. 16.4%; p < 0.01), and favorably modulating serum lipid profiles (p < 0.05). Moreover, medium-dose creatine hydrochloride demonstrated a potential advantage over other treatments in reducing the severity of mood swings (p = 0.06). All interventions were well tolerated, with no severe adverse effects reported. CONCLUSION: Our findings suggest that this supplementation protocol may be a promising, safe, effective, and practical dietary strategy for improving clinical outcomes and elevating brain creatine concentrations in perimenopausal and menopausal women. The trial was registered at ClinicalTrials.gov (NCT06660004).

The purpose of this study was to determine the effects of resistance training (RT) alongside creatine-hydrochloride (Cr-HCl) or creatine monohydrate (CrM) supplementation on anabolic/catabolic hormones, strength, and body composition. Forty participants with an age range of 18-25 years were randomly divided into four groups (n=10): RT+Cr-HCl (0.03 g.kg-1 of body mass), RT+CrM-loading phase (CrM-LP) (0.3 g.kg-1 of body mass for five days (loading) and 0.03 g.kg-1 body mass for 51 days (maintenance)), RT+CrM-without loading phase (CrM-WLP) (0.03 g.kg-1 body mass), and RT+placebo (PL). The participants consumed supplements and performed RT with an intensity of 70-85 % 1RM for eight weeks. Before and after the training and supplementation period, strength (1RM), body composition (percent body fat (PBF), skeletal muscle mass (SMM), muscular cross-sectional area (MCSA)) and serum levels of testosterone, growth hormone (GH), insulin-like growth factor-1 (IGF-1), cortisol, adrenocorticotropic hormone (ACTH), follistatin and myostatin were measured. The results showed that in the supplementation groups, strength, arm and thigh MCSA, and SMM significantly increased, and PBF significantly decreased (P</=0.05); this change was significant compared to the PL group (P</=0.05). In addition, the results showed a significant increase in GH, IGF-1 levels, the ratio of follistatin/myostatin, testosterone/cortisol (P</=0.05), and a significant decrease in cortisol and ACTH levels (P</=0.05) in the supplementation groups. Hormonal changes in GH, IGF-1, testosterone/cortisol, cortisol, and ACTH levels in the supplementation groups were significant compared to the PL group (P</=0.05). The results showed that CrM and Cr-HCl significantly enhanced the beneficial effects of RT on strength, hypertrophy, and hormonal responses, with Cr-HCl showing no benefit over CrM.

Guanidinoacetic acid (GAA) is the natural biosynthetic precursor of creatine, in a metabolic reaction that requires only a methyl group transfer. The use of GAA as a food additive for restoring creatine load in human tissues is rather unexplored and data on efficacy and safety are limited. In particular, an increase in serum homocysteine after GAA administration can be regarded as critical and should be prevented. The present study evaluated the effects of orally administered GAA with and without methyl group donors on serum and urine creatine concentrations, and the occurrence of adverse events during an intervention in healthy human subjects. A total of twenty male and female volunteers were randomised in a double-blind design to receive either GAA (2.4 g/d) or GAA with methyl donors (2.4 g/d of GAA and 1.6 g/d of betaine HCl, 5 μg/d of vitamin B12, 10 mg/d of vitamin B6 and 600 μg/d of folic acid) by oral administration for 8 weeks. Serum and urine creatine increased significantly from before to after administration in both groups (P< 0.001). The proportion of participants who reported minor adverse events was 33.3 % in the GAA group, and 10.0 % in the GAA with methyl donors group (P= 0.30). Hyperhomocysteinaemia was found in 55.6 % of participants supplemented with GAA, while no participant experienced hyperhomocysteinaemia in the group supplemented with GAA and methyl donors (P= 0.01). In summary, both interventions strongly influenced creatine metabolism, resulting in a significant increase in fasting serum creatine. The concomitant supplementation of methyl donors along with GAA largely precluded the elevation of serum homocysteine caused by GAA administration alone.

Inflammatory processes have been identified as key mediators of ischemia-reperfusion injury in ST-segment elevation myocardial infarction (STEMI). They add damage to the myocardium and are associated with clinical adverse events (heart failure and cardiovascular death) and poor myocardial recovery. Colchicine is a well-known alkaloid with potent anti-inflammatory properties. In a proof-of-concept phase II trial, colchicine has been associated with a significant 50% reduction of infarct size (assessed by creatine kinase levels) in comparison to placebo in acute STEMI patients referred for primary percutaneous coronary intervention (PPCI). The Colchicine in STEMI Patients Study (COVERT-MI) is an ongoing confirmative prospective, multicenter, randomized, double-blind trial testing whether a short course oral treatment with colchicine versus placebo decreases myocardial injury in patients presenting with STEMI referred for PPCI. Adult patients, with a first STEMI episode and an initial TIMI flow ≤1, referred for PPCI, will be randomized (n = 194) in a 1:1 ratio to receive an oral bolus of colchicine of 2 mg followed by 0.5 mg b.i.d. treatment during 5 days or matching placebo. The primary endpoint will be the reduction in infarct size as assessed by cardiac magnetic resonance at 5 ± 2 days between both groups. The main secondary endpoints will be tested between groups in hierarchical order with left ventricular ejection fraction at 5 days, microvascular obstruction presence at 5 days, and absolute adverse left ventricular remodeling between 5 days and 3 months. This academic study is being financed by a grant from the French Ministry of Health (PHRCN-16-0357). Results from this study will contribute to a better understanding of the complex pathophysiology underlying myocardial injury after STEMI. The present study describes the rationale, design, and methods of the trial. © 2021 S. Karger AG, Basel.

Acetylsalicylic acid (ASA) and pseudoephedrine (PSE) are often administered together for the treatment of symptoms of the common cold, i.e., nasal congestion, runny nose, sore throat and headache. Based on this fact we developed a fixed combination of 500 mg ASA and 30 mg PSE, the recommended doses for both drugs for treating symptoms of the common cold, as granulate to be dissolved in water for administration. The purpose of this open, randomized, three-factorial (three-treatment, three-period, six-sequence) Latin Square clinical study was to investigate the relative bioavailability of ASA and PSE as well as the establishment of bioequivalence after single administration of the fixed combination (final formulation for approval) of 500 mg ASA/30 mg PSE*HCl and the preliminary formulation of this combination. Pharmacokinetic characteristics AUC(norm) and C(max,norm) of ASA, its metabolite SA, and PSE, were determined as measure of rate and extent of absorption of the two formulations. The treatment ratios final/preliminary formulation and their corresponding 90% confidence intervals were calculated to establish bioequivalence. Additionally, descriptive statistics were calculated for the parameters t(max), t((1/2)), and mean residence time (MRT). In total, data from 18 healthy male volunteers were included in the pharmacokinetic evaluation. The primary target parameters were analyzed using an analysis of variance (ANOVA) after logarithmic transformation of the data. Confidence intervals of 90% were calculated for the geometric means of ratios using the mean square error term of the ANOVA. Bioequivalence criteria were fulfilled for AUC(norm) and C(max,norm). Geometric means of individual ratios of AUC(norm) and of C(max,norm) showed equal bioavailability of the new formulation compared with the preliminary. Furthermore, a relative bioavailability of approximately 100% of the preliminary formulation was shown for the newly developed formulation for all parameters. The parameters t(max), t((1/2)), and MRT showed comparable results for ASA, SA, and PSE, respectively, in both formulations. The supplementary evaluation for the non-normalized original parameters AUC and

5. Eur J Clin Pharmacol. 1984;27(2):147-52. doi: 10.1007/BF00544037. Crossover comparison of moxonidine and clonidine in mild to moderate hypertension. Plänitz V. The antihypertensive effect of moxonidine X HCl X H2O (MOX) was compared with that of clonidine X HCl (CLON) in a randomized double-blind crossover study in 20 hypertensive outpatients (BP range 154-178/96-108 mmHg). After 2 weeks without antihypertensive medication, either MOX 0.2 mg daily or CLON 0.2 mg daily was given and the dose was titrated until the diastolic blood pressure fell below 90 mmHg. The first treatment period was continued for 2 weeks and, after crossover without a wash-out period, it was followed by the second treatment for a further 2 weeks. Within the first 4 days of administration 0.2-0.4 mg of either agent caused a significant decrease in BP (p less than 0.001) from a mean of 166/100 mmHg to 149/86 mmHg after CLON (approx. -10/-14%), and 163/99 mmHg to 146/84 mmHg after MOX (approx. -10/-15%). No significant difference in the fall in BP or pulse rate was detected between the two drugs. In the mean daily dose of 0.3 mg both drugs showed the same antihypertensive activity, but on CLON a higher incidence of side effects (p = 0.003) was noted, and after discontinuation of therapy a more rapid rise in BP (systolic BP p less than 0.01, diastolic BP p less than 0.02) was found. 17 patients on CLON complained of side effects, especially tiredness and dry mouth, whilst only 6 patients on MOX were affected (p = 0.003).