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Background: Sarcopenia is an age-related condition characterized by progressive loss of muscle mass, strength, and function. The occurrence of sarcopenia has a huge impact on physical, psychological, and social health. Therefore, the prevention and treatment of sarcopenia is becoming an important public health issue. Method: 35 six-week-old male C57BL/6 mice were randomly divided into five groups, one of which served as a control group, while the rest of the groups were constructed as a model of sarcopenia by intraperitoneal injection of D-galactose. The intervention with lactoferrin, creatine, and their mixtures, respectively, was carried out through gavage for 8 weeks. Muscle function was assessed based on their endurance, hanging time, and grip strength. The muscle tissues were weighed to assess the changes in mass, and the muscle RNA was extracted for myogenic factor expression and transcriptome sequencing to speculate on the potential mechanism of action by GO and KEGG enrichment analysis. Result: The muscle mass (lean mass, GAS index), and muscle function (endurance, hanging time, and grip strength) decreased, and the size and structure of myofiber was smaller in the model group compared to the control group. The intervention with lactoferrin and creatine, either alone or combination, improved muscle mass and function, restored muscle tissue, and increased the expression of myogenic regulators. The combined group demonstrated the most significant improvement in these indexes. The RNA-seq results revealed enrichment in the longevity-regulated pathway, MAPK pathway, focal adhesion, and ECM–receptor interaction pathway in the intervention group. The intervention group may influence muscle function by affecting the proliferation, differentiation, senescence of skeletal muscle cell, and contraction of muscle fiber. The combined group also enriched the mTOR-S6K/4E-BPs signaling pathway, PI3K-Akt signaling pathway, and energy metabolism-related pathways, including Apelin signaling, insulin resistance pathway, and adipocytokine signaling pathway, which affect energy metabolism in muscle. Conclusions: Lactoferrin and creatine, either alone or in combination, were found to inhibit the progression of sarcopenia by influencing the number and cross-sectional area of muscle fibers and muscle protein synthesis. The combined intervention appears to exert a more significant effect on energy metabolism. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is one of the most common cancers in the United States. Advances in detection and treatment have resulted in an increased survival rate, meaning an increasing population experiencing declines in muscle mass and strength. Creatine supplementation has consistently demonstrated improvements in strength and muscle performance in older adults, though these findings have not been extended to cancer populations. PURPOSE: The purpose of this study was to investigate the effects of short-term creatine supplementation on muscular performance in BC survivors. METHODS: Using a double-blind, placebo-controlled, randomized design, 19 female BC survivors (mean ± SD age = 57.63 ± 10.77 years) were assigned to creatine (SUPP) (n = 9) or dextrose placebo (PLA) (n = 10) groups. The participants completed two familiarization sessions, then two test sessions, each separated by 7 days, where the participants supplemented with 5 g of SUPP or PLA 4 times/day between sessions. The testing sessions included sit-to-stand power, isometric/isokinetic peak torque, and upper/lower body strength via 10 repetition maximum (10RM) tests. The interaction between supplement (SUPP vs. PLA) and time (Pre vs. Post) was examined using a group × time ANOVA and effect sizes. RESULTS: No significant effects were observed for sit-to-stand power (p = 0.471; ηp2 = 0.031), peak torque at 60°/second (p = 0.533; ηp2 = 0.023), peak torque at 120°/second (p = 0.944; ηp2 < 0.001), isometric peak torque (p = 0.905; ηp2 < 0.001), 10RM chest press (p = 0.407; ηp2 = 0.041), and 10RM leg extension (p = 0.932; ηp2 < 0.001). However, a large effect size for time occurred for the 10RM chest press (ηp2 = 0.531) and leg extension (ηp2 = 0.422). CONCLUSION: Seven days of creatine supplementation does not influence muscular performance among BC survivors. [ABSTRACT FROM AUTHOR]

Hemodialysis has a detrimental effect on fat-free mass (FFM) and muscle strength over time. Thus, we aimed to evaluate the effect of creatine supplementation on the body composition and Malnutrition-Inflammation Score (MIS) in patients with chronic kidney disease (CKD) undergoing hemodialysis. An exploratory 1-year balanced, placebo-controlled, and double-blind design was conducted with hemodialysis patients (≥18 years). The creatine group (CG) received 5 g of creatine monohydrate and 5 g of maltodextrin per day and the placebo group (PG) received 10 g of maltodextrin per day. MIS and body composition were analyzed at three time points: pre, intermediate (after 6 months), and post (after 12 months). After 6 months, 60% of patients on creatine experienced an increase in FFM compared to a 36.8% increase for those on placebo. Moreover, 65% of patients on creatine increased their skeletal muscle mass index (SMMI) compared to only 15.8% for those on placebo. Creatine increased intracellular water (ICW) in 60% of patients. MIS did not change after the intervention. In the CG, there was an increase in body weight (p = 0.018), FFM (p = 0.010), SMMI (p = 0.022). CG also increased total body water (pre 35.4 L, post 36.1 L; p = 0.008), mainly due to ICW (pre 20.2 L, intermediate 20.7 L, post 21.0 L; p = 0.016). Long-term creatine supplementation in hemodialysis patients did not attenuate the MIS, but enhanced FFM and SMMI, which was likely triggered by an increase in ICW. [ABSTRACT FROM AUTHOR]

(1) Background: The aim of the present paper was to study fetal and infant creatine (Cr) supply to improve nutrition and neuroprotection in term and especially in preterm infants. The primary outcomes were the placental Cr flux at the end of pregnancy and the time course of human milk (HM) Cr. (2) Methods: The estimation of placental Cr flux was based on umbilical arterial and venous cord blood Cr in 10 term infants after elective caesarian section. HM Cr, creatinine (Crn), and macronutrients were measured longitudinally in 10 mothers across the first 6 months of breastfeeding. (3) Results: At the end of pregnancy, the mean fetal Cr flux was negative (−2.07 mmol/min). HM Cr was highest in colostrum, decreased significantly within the first 2 weeks of breastfeeding (p < 0.05), and did not change significantly thereafter. HM Cr was not correlated with HM Crn or macronutrient composition. (4) Conclusions: The present data suggest that fetal endogenous Cr synthesis covers the needs at the end of pregnancy. However, high colostrum Cr and HM Cr levels, independent of macronutrient composition, suggest that there may be a critical Cr demand immediately after birth that needs to be covered by enteral supply. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia is an age-related condition characterized by progressive loss of muscle mass, strength, and function. The occurrence of sarcopenia has a huge impact on physical, psychological, and social health. Therefore, the prevention and treatment of sarcopenia is becoming an important public health issue. Method: 35 six-week-old male C57BL/6 mice were randomly divided into five groups, one of which served as a control group, while the rest of the groups were constructed as a model of sarcopenia by intraperitoneal injection of D-galactose. The intervention with lactoferrin, creatine, and their mixtures, respectively, was carried out through gavage for 8 weeks. Muscle function was assessed based on their endurance, hanging time, and grip strength. The muscle tissues were weighed to assess the changes in mass, and the muscle RNA was extracted for myogenic factor expression and transcriptome sequencing to speculate on the potential mechanism of action by GO and KEGG enrichment analysis. Result: The muscle mass (lean mass, GAS index), and muscle function (endurance, hanging time, and grip strength) decreased, and the size and structure of myofiber was smaller in the model group compared to the control group. The intervention with lactoferrin and creatine, either alone or combination, improved muscle mass and function, restored muscle tissue, and increased the expression of myogenic regulators. The combined group demonstrated the most significant improvement in these indexes. The RNA-seq results revealed enrichment in the longevity-regulated pathway, MAPK pathway, focal adhesion, and ECM–receptor interaction pathway in the intervention group. The intervention group may influence muscle function by affecting the proliferation, differentiation, senescence of skeletal muscle cell, and contraction of muscle fiber. The combined group also enriched the mTOR-S6K/4E-BPs signaling pathway, PI3K-Akt signaling pathway, and energy metabolism-related pathways, including Apelin signaling, insulin resistance pathway, and adipocytokine signaling pathway, which affect energy metabolism in muscle. Conclusions: Lactoferrin and creatine, either alone or in combination, were found to inhibit the progression of sarcopenia by influencing the number and cross-sectional area of muscle fibers and muscle protein synthesis. The combined intervention appears to exert a more significant effect on energy metabolism.

Doxorubicin (DOX), a potent chemotherapy agent, useful in the treatment of solid tumors, lymphomas, and leukemias, is limited by its potentially lethal cardiotoxicity. However, exercise has been consistently shown to mitigate the side effects of DOX, including cardiotoxicity. To date, most studies examining the relationship between exercise and DOX-induced cardiotoxicity have focused on aerobic exercise, with very few examining the role of anerobic activity. Therefore, this investigation explored the potential of creatine (CR) and resistance training (RT) in preserving cardiac health during DOX therapy. Male Sprague-Dawley rats were grouped into RT, RT + CR, sedentary (SED), and SED + CR, with each division further branching into saline (SAL) or DOX-treated subsets post-10 weeks of RT or SED activity. RT comprised progressive training utilizing specialized cages for bipedal stance feeding. CR-treated groups ingested water mixed with 1% CR monohydrate and 5% dextrose, while control animals received 5% dextrose. At week 10, DOX was administered (2 mg/kg/week) over 4-weeks to an 8 mg/kg cumulative dose. Cardiac function post-DOX treatment was assessed via transthoracic echocardiography. Left ventricular diameter during diastole was lower in DOX + CR, RT + DOX, and RT + CR + DOX compared to SED + DOX (p < 0.05). Additionally, cardiac mass was significantly greater in RT + CR + DOX SED + DOX animals (p < 0.05). These results suggest RT and CR supplementation, separately and in combination, could attenuate some measures of DOX-induced cardiotoxicity and may offer a cost-effective way to complement cancer treatments and enhance patient outcomes. More investigations are essential to better understand CR's prolonged effects during DOX therapy and its clinical implications. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is one of the most common cancers in the United States. Advances in detection and treatment have resulted in an increased survival rate, meaning an increasing population experiencing declines in muscle mass and strength. Creatine supplementation has consistently demonstrated improvements in strength and muscle performance in older adults, though these findings have not been extended to cancer populations. PURPOSE: The purpose of this study was to investigate the effects of short-term creatine supplementation on muscular performance in BC survivors. METHODS: Using a double-blind, placebo-controlled, randomized design, 19 female BC survivors (mean ± SD age = 57.63 ± 10.77 years) were assigned to creatine (SUPP) (n = 9) or dextrose placebo (PLA) (n = 10) groups. The participants completed two familiarization sessions, then two test sessions, each separated by 7 days, where the participants supplemented with 5 g of SUPP or PLA 4 times/day between sessions. The testing sessions included sit-to-stand power, isometric/isokinetic peak torque, and upper/lower body strength via 10 repetition maximum (10RM) tests. The interaction between supplement (SUPP vs. PLA) and time (Pre vs. Post) was examined using a group × time ANOVA and effect sizes. RESULTS: No significant effects were observed for sit-to-stand power (p = 0.471; ηp2 = 0.031), peak torque at 60°/second (p = 0.533; ηp2 = 0.023), peak torque at 120°/second (p = 0.944; ηp2 < 0.001), isometric peak torque (p = 0.905; ηp2 < 0.001), 10RM chest press (p = 0.407; ηp2 = 0.041), and 10RM leg extension (p = 0.932; ηp2 < 0.001). However, a large effect size for time occurred for the 10RM chest press (ηp2 = 0.531) and leg extension (ηp2 = 0.422). CONCLUSION: Seven days of creatine supplementation does not influence muscular performance among BC survivors.

Red meat and animal-sourced protein are often disparaged as risk factors for developing metabolic syndrome, while emerging research has shown the beneficial effects of dietary taurine, creatine, carnosine, and anserine which are all exclusively abundant in red meat. Thus, it is imperative to highlight the available evidence to help promote red meat as part of a well-balanced diet to optimize human health. In this study, a bibliometric analysis was conducted to investigate the current research status of dietary taurine, creatine, carnosine, and anserine with metabolic syndrome, identify research hotspots, and delineate developmental trends by utilizing the visualization software CiteSpace. A total of 1094 publications were retrieved via the Web of Science Core Collection from 1992 to 2022. There exists a gradual increase in the number of publications on this topic, but there is still much room for research papers to rise. The United States has participated in the most studies, followed by China and Japan. The University of Sao Paulo was the research institute contributing the most; Kyung Ja Chang and Sanya Roysommuti have been identified as the most prolific authors. The analysis of keywords reveals that obesity, lipid profiles, blood pressure, and glucose metabolism, as well as ergogenic aid and growth promoter have been the research hotspots. Inflammation and diabetic nephropathy will likely be frontiers of future research related to dietary taurine, creatine, carnosine, and anserine. Overall, this paper may provide insights for researchers to further delve into this field and enlist the greater community to re-evaluate the health effects of red meat. [ABSTRACT FROM AUTHOR]

A pre-workout supplement's (PWS; 200 mg caffeine, 3.3 g creatine monohydrate, 3.2 g β-alanine, 6 g citrulline malate and 5 g branched chained amino acid (BCAA) per dose) acute effects on the alactic (jumping, sprinting, agility), lactic (Running-Based Anaerobic Sprint Test, RAST) and aerobic performance (Yo-Yo Intermittent Recovery Test Level 1, Yo-Yo IRL1 VO2max) of well-trained basketball players was investigated in this double-blind placebo-controlled study. Thirty players (age 18–31 years, height 166–195 cm, weight 70.2–116.7 kg, body fat 10.6–26.4%) were allocated to pre-workout (PWS, n = 15) or placebo (PL, n = 15) groups. Half of the participants in each group performed the evaluations without PWS or PL, while the rest consumed PWS or PL 30 min before the assessments (1st trial) and vice versa (2nd trial). Significant improvements in counter-movement jump (CMJ) (PWS: 4.3 ± 2.1%; PL: 1.2 ± 1.0%), agility (PWS: −2.9 ± 1.8%; PL: 1.8 ± 1.7%), RAST average (PWS: 18.3 ± 9.1%; PL: −2.2 ± 2.0%), minimum power (PWS: 13.7 ± 8.9%; PL: −7.5 ± 5.9%), and fatigue index (PWS: −25.0 ± 0.9%; PL: −4.6 ± 0.6%) were observed in the PWS group vs. the PL group (p < 0.05). No differences were found regarding sprinting, aerobic performance, and blood lactate concentrations. Thus, although players' alactic and lactic anaerobic performance could be improved, peak power, sprinting and aerobic performance are not. [ABSTRACT FROM AUTHOR]

Creatine has been used to maximize resistance training effects on skeletal muscles, including muscle hypertrophy and fiber type changes. This study aimed to evaluate the impact of creatine supplementation on the myostatin pathway and myosin heavy chain (MyHC) isoforms in the slow- and fast-twitch muscles of resistance-trained rats. Twenty-eight male Wistar rats were divided into four groups: a sedentary control (Cc), sedentary creatine supplementation (Cr), resistance training (Tc), and resistance training combined with creatine supplementation (Tcr). Cc and Tc received standard commercial chow; Cr and Tcr received a 2% creatine-supplemented diet. Tc and Tcr performed a resistance training protocol on a ladder for 12 weeks. Morphology, MyHC isoforms, myostatin, follistatin, and ActRIIB protein expressions were analyzed in soleus and white gastrocnemius portion samples. The results were analyzed using two-way ANOVA and Tukey's test. Tc and Tcr exhibited higher performance than their control counterparts. Resistance training increased the ratio between muscle and body weight, the cross-sectional area, as well as the interstitial collagen fraction. Resistance training alone increased MyHC IIx and follistatin while reducing myostatin (p < 0.001) and ActRIIB (p = 0.040) expressions in the gastrocnemius. Resistance training induced skeletal muscle hypertrophy and interstitial remodeling, which are more evident in the gastrocnemius muscle. The effects were not impacted by creatine supplementation. [ABSTRACT FROM AUTHOR]

Hemodialysis has a detrimental effect on fat-free mass (FFM) and muscle strength over time. Thus, we aimed to evaluate the effect of creatine supplementation on the body composition and Malnutrition-Inflammation Score (MIS) in patients with chronic kidney disease (CKD) undergoing hemodialysis. An exploratory 1-year balanced, placebo-controlled, and double-blind design was conducted with hemodialysis patients (≥18 years). The creatine group (CG) received 5 g of creatine monohydrate and 5 g of maltodextrin per day and the placebo group (PG) received 10 g of maltodextrin per day. MIS and body composition were analyzed at three time points: pre, intermediate (after 6 months), and post (after 12 months). After 6 months, 60% of patients on creatine experienced an increase in FFM compared to a 36.8% increase for those on placebo. Moreover, 65% of patients on creatine increased their skeletal muscle mass index (SMMI) compared to only 15.8% for those on placebo. Creatine increased intracellular water (ICW) in 60% of patients. MIS did not change after the intervention. In the CG, there was an increase in body weight (p = 0.018), FFM (p = 0.010), SMMI (p = 0.022). CG also increased total body water (pre 35.4 L, post 36.1 L; p = 0.008), mainly due to ICW (pre 20.2 L, intermediate 20.7 L, post 21.0 L; p = 0.016). Long-term creatine supplementation in hemodialysis patients did not attenuate the MIS, but enhanced FFM and SMMI, which was likely triggered by an increase in ICW.

(1) Background: The aim of the present paper was to study fetal and infant creatine (Cr) supply to improve nutrition and neuroprotection in term and especially in preterm infants. The primary outcomes were the placental Cr flux at the end of pregnancy and the time course of human milk (HM) Cr. (2) Methods: The estimation of placental Cr flux was based on umbilical arterial and venous cord blood Cr in 10 term infants after elective caesarian section. HM Cr, creatinine (Crn), and macronutrients were measured longitudinally in 10 mothers across the first 6 months of breastfeeding. (3) Results: At the end of pregnancy, the mean fetal Cr flux was negative (−2.07 mmol/min). HM Cr was highest in colostrum, decreased significantly within the first 2 weeks of breastfeeding (p < 0.05), and did not change significantly thereafter. HM Cr was not correlated with HM Crn or macronutrient composition. (4) Conclusions: The present data suggest that fetal endogenous Cr synthesis covers the needs at the end of pregnancy. However, high colostrum Cr and HM Cr levels, independent of macronutrient composition, suggest that there may be a critical Cr demand immediately after birth that needs to be covered by enteral supply.

Creatine supplementation has been one of the most studied and useful ergogenic nutritional support for athletes to improve performance, strength, and muscular mass. Over time creatine has shown beneficial effects in several human disease conditions. This review aims to summarise the current evidence for creatine supplementation in advanced chronic liver disease and its complications, primarily in sarcopenic cirrhotic patients, because this condition is known to be associated with poor prognosis and outcomes. Although creatine supplementation in chronic liver disease seems to be barely investigated and not studied in human patients, its potential efficacy on chronic liver disease is indirectly highlighted in animal models of non-alcoholic fatty liver disease, bringing beneficial effects in the fatty liver. Similarly, encephalopathy and fatigue seem to have beneficial effects. Creatine supplementation has demonstrated effects in sarcopenia in the elderly with and without resistance training suggesting a potential role in improving this condition in patients with advanced chronic liver disease. Creatine supplementation could address several critical points of chronic liver disease and its complications. Further studies are needed to support the clinical burden of this hypothesis. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX), a potent chemotherapy agent, useful in the treatment of solid tumors, lymphomas, and leukemias, is limited by its potentially lethal cardiotoxicity. However, exercise has been consistently shown to mitigate the side effects of DOX, including cardiotoxicity. To date, most studies examining the relationship between exercise and DOX-induced cardiotoxicity have focused on aerobic exercise, with very few examining the role of anerobic activity. Therefore, this investigation explored the potential of creatine (CR) and resistance training (RT) in preserving cardiac health during DOX therapy. Male Sprague-Dawley rats were grouped into RT, RT + CR, sedentary (SED), and SED + CR, with each division further branching into saline (SAL) or DOX-treated subsets post-10 weeks of RT or SED activity. RT comprised progressive training utilizing specialized cages for bipedal stance feeding. CR-treated groups ingested water mixed with 1% CR monohydrate and 5% dextrose, while control animals received 5% dextrose. At week 10, DOX was administered (2 mg/kg/week) over 4-weeks to an 8 mg/kg cumulative dose. Cardiac function post-DOX treatment was assessed via transthoracic echocardiography. Left ventricular diameter during diastole was lower in DOX + CR, RT + DOX, and RT + CR + DOX compared to SED + DOX (p < 0.05). Additionally, cardiac mass was significantly greater in RT + CR + DOX SED + DOX animals (p < 0.05). These results suggest RT and CR supplementation, separately and in combination, could attenuate some measures of DOX-induced cardiotoxicity and may offer a cost-effective way to complement cancer treatments and enhance patient outcomes. More investigations are essential to better understand CR’s prolonged effects during DOX therapy and its clinical implications.

The reactive 1,2-dicarbonyl compound methylglyoxal (MGO) is consumed with food and its concentrations decrease during digestion. In the present paper, the reaction of MGO with creatine, arginine, and lysine during simulated digestion, and its reaction with creatine during the digestion in human volunteers, was studied. Therefore, simulated digestion experiments with a gastric and an intestinal phase were performed. Additionally, an intervention study with 12 subjects consuming MGO-containing Manuka honey and creatine simultaneously or separately was conducted. Derivatization with o-phenylenediamine and HPLC–UV was used to measure MGO, while creatine and glycated amino compounds were analyzed via HPLC–MS/MS. We show that MGO quickly reacts with creatine and arginine, but not lysine, during simulated digestion. Creatine reacts with 56% of MGO to form the hydroimidazolone MG-HCr, and arginine reacted with 4% of MGO to form the hydroimidazolone MG-H1. In the intervention study, urinary MG-HCr excretion is higher in subjects who consumed MGO and creatine simultaneously compared to subjects who ingested the substances separately. This demonstrates that the 1,2-dicarbonyl compound MGO reacts with amino compounds during human digestion, and glycated adducts are formed. These contribute to dietary glycation products consumed, and should be considered in studies investigating their physiological consequences. [ABSTRACT FROM AUTHOR]

Red meat and animal-sourced protein are often disparaged as risk factors for developing metabolic syndrome, while emerging research has shown the beneficial effects of dietary taurine, creatine, carnosine, and anserine which are all exclusively abundant in red meat. Thus, it is imperative to highlight the available evidence to help promote red meat as part of a well-balanced diet to optimize human health. In this study, a bibliometric analysis was conducted to investigate the current research status of dietary taurine, creatine, carnosine, and anserine with metabolic syndrome, identify research hotspots, and delineate developmental trends by utilizing the visualization software CiteSpace. A total of 1094 publications were retrieved via the Web of Science Core Collection from 1992 to 2022. There exists a gradual increase in the number of publications on this topic, but there is still much room for research papers to rise. The United States has participated in the most studies, followed by China and Japan. The University of Sao Paulo was the research institute contributing the most; Kyung Ja Chang and Sanya Roysommuti have been identified as the most prolific authors. The analysis of keywords reveals that obesity, lipid profiles, blood pressure, and glucose metabolism, as well as ergogenic aid and growth promoter have been the research hotspots. Inflammation and diabetic nephropathy will likely be frontiers of future research related to dietary taurine, creatine, carnosine, and anserine. Overall, this paper may provide insights for researchers to further delve into this field and enlist the greater community to re-evaluate the health effects of red meat.

A pre-workout supplement’s (PWS; 200 mg caffeine, 3.3 g creatine monohydrate, 3.2 g β-alanine, 6 g citrulline malate and 5 g branched chained amino acid (BCAA) per dose) acute effects on the alactic (jumping, sprinting, agility), lactic (Running-Based Anaerobic Sprint Test, RAST) and aerobic performance (Yo-Yo Intermittent Recovery Test Level 1, Yo-Yo IRL1 VO2max) of well-trained basketball players was investigated in this double-blind placebo-controlled study. Thirty players (age 18–31 years, height 166–195 cm, weight 70.2–116.7 kg, body fat 10.6–26.4%) were allocated to pre-workout (PWS, n = 15) or placebo (PL, n = 15) groups. Half of the participants in each group performed the evaluations without PWS or PL, while the rest consumed PWS or PL 30 min before the assessments (1st trial) and vice versa (2nd trial). Significant improvements in counter-movement jump (CMJ) (PWS: 4.3 ± 2.1%; PL: 1.2 ± 1.0%), agility (PWS: −2.9 ± 1.8%; PL: 1.8 ± 1.7%), RAST average (PWS: 18.3 ± 9.1%; PL: −2.2 ± 2.0%), minimum power (PWS: 13.7 ± 8.9%; PL: −7.5 ± 5.9%), and fatigue index (PWS: −25.0 ± 0.9%; PL: −4.6 ± 0.6%) were observed in the PWS group vs. the PL group (p < 0.05). No differences were found regarding sprinting, aerobic performance, and blood lactate concentrations. Thus, although players’ alactic and lactic anaerobic performance could be improved, peak power, sprinting and aerobic performance are not.

Creatine has been used to maximize resistance training effects on skeletal muscles, including muscle hypertrophy and fiber type changes. This study aimed to evaluate the impact of creatine supplementation on the myostatin pathway and myosin heavy chain (MyHC) isoforms in the slow- and fast-twitch muscles of resistance-trained rats. Twenty-eight male Wistar rats were divided into four groups: a sedentary control (Cc), sedentary creatine supplementation (Cr), resistance training (Tc), and resistance training combined with creatine supplementation (Tcr). Cc and Tc received standard commercial chow; Cr and Tcr received a 2% creatine-supplemented diet. Tc and Tcr performed a resistance training protocol on a ladder for 12 weeks. Morphology, MyHC isoforms, myostatin, follistatin, and ActRIIB protein expressions were analyzed in soleus and white gastrocnemius portion samples. The results were analyzed using two-way ANOVA and Tukey’s test. Tc and Tcr exhibited higher performance than their control counterparts. Resistance training increased the ratio between muscle and body weight, the cross-sectional area, as well as the interstitial collagen fraction. Resistance training alone increased MyHC IIx and follistatin while reducing myostatin (p < 0.001) and ActRIIB (p = 0.040) expressions in the gastrocnemius. Resistance training induced skeletal muscle hypertrophy and interstitial remodeling, which are more evident in the gastrocnemius muscle. The effects were not impacted by creatine supplementation.

Low tissue creatine characterizes many conditions, including neurodegenerative, cardiopulmonary, and metabolic diseases, with a magnitude of creatine shortfall often corresponds well to a disorder's severity. A non-invasive monitoring of tissue metabolism with magnetic resonance spectroscopy (MRS) might be a feasible tool to evaluate suboptimal levels of creatine for both predictive, diagnostic, and therapeutic purposes. This mini review paper summarizes disorders with deficient creatine levels and provides arguments for assessing and employing tissue creatine as a relevant target in clinical nutrition. [ABSTRACT FROM AUTHOR]

Traumatic brain injuries (TBIs) constitute a significant public health issue and a major source of disability and death in the United States and worldwide. TBIs are strongly associated with high morbidity and mortality rates, resulting in a host of negative health outcomes and long-term complications and placing a heavy financial burden on healthcare systems. One promising avenue for the prevention and treatment of brain injuries is the design of TBI-specific supplementation and dietary protocols centred around nutraceuticals and biochemical compounds whose mechanisms of action have been shown to interfere with, and potentially alleviate, some of the neurophysiological processes triggered by TBI. For example, evidence suggests that creatine monohydrate and omega-3 fatty acids (DHA and EPA) help decrease inflammation, reduce neural damage and maintain adequate energy supply to the brain following injury. Similarly, melatonin supplementation may improve some of the sleep disturbances often experienced post-TBI. The scope of this narrative review is to summarise the available literature on the neuroprotective effects of selected nutrients in the context of TBI-related outcomes and provide an evidence-based overview of supplementation and dietary protocols that may be considered in individuals affected by-or at high risk for-concussion and more severe head traumas. Prophylactic and/or therapeutic compounds under investigation include creatine monohydrate, omega-3 fatty acids, BCAAs, riboflavin, choline, magnesium, berry anthocyanins, Boswellia serrata, enzogenol, N-Acetylcysteine and melatonin. Results from this analysis are also placed in the context of assessing and addressing important health-related and physiological parameters in the peri-impact period such as premorbid nutrient and metabolic health status, blood glucose regulation and thermoregulation following injury, caffeine consumption and sleep behaviours. As clinical evidence in this research field is rapidly emerging, a comprehensive approach including appropriate nutritional interventions has the potential to mitigate some of the physical, neurological, and emotional damage inflicted by TBIs, promote timely and effective recovery, and inform policymakers in the development of prevention strategies.

Low tissue creatine characterizes many conditions, including neurodegenerative, cardiopulmonary, and metabolic diseases, with a magnitude of creatine shortfall often corresponds well to a disorder’s severity. A non-invasive monitoring of tissue metabolism with magnetic resonance spectroscopy (MRS) might be a feasible tool to evaluate suboptimal levels of creatine for both predictive, diagnostic, and therapeutic purposes. This mini review paper summarizes disorders with deficient creatine levels and provides arguments for assessing and employing tissue creatine as a relevant target in clinical nutrition.

Using nutritional supplements is a widespread strategy among basketball players to ensure the appropriate provision of energy and nutrients to avoid certain complaints. Particularly in basketball, there is no consensus on the type, quantity or form of use in which these supplements should be administered. Therefore, the main aim of this systematic review is to highlight the ergo-nutritional aids that may be effective in basketball. A structured search was carried out following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA®) guidelines in the Medline/PubMed and Web of Science, Cochrane Library, and Scopus databases until 31 December 2021; no year restriction was applied to the search strategy. There were no filters applied to the basketball players’ level, gender, race, or age to increase the power of the analysis. The results of this systematic review have shown that the effective dose of caffeine to enhance anaerobic performance and the feeling of vigorousness and energy ranges from 3 to 6 mg·kg−1, showing more positive effects when is supplemented 60–75 min before exercise in the morning and in test-based task. On the other hand, vitamin E (ranging from 200 to 268 mg), vitamin D (10,000 IU) and EPA (2 g) may have a potential role in recovery and wellness. The primary limitation of this study is the scarcity of studies related to nutritional supplementation in basketball players. However, a major strength is that this is the first systematic review describing what ergo-nutritional aids may be specifically helpful for basketball. Despite the need for future studies, certain nutritional supplements may have promising advantages for basketball (long-term supplementation of nitrates for recovery), whereas others (β-alanine, sodium bicarbonate, and acute nitrate supplementation) might theoretically be regarded as not interesting for basketball, or even not recommended by the World Anti-Doping Agency (WADA) as bovine colostrum.

Creatine is an important energy metabolite that is concentrated in tissues such as the muscles and brain. Creatine is reversibly converted to creatine phosphate through a reaction with ATP or ADP, which is catalyzed by the enzyme creatine kinase. Dietary supplementation with relatively large amounts of creatine monohydrate has been proven as an effective sports supplement that can enhances athletic performance during acute high-energy demand physical activity. Some side effects have been reported with creatine monohydrate supplementation, which have stimulated research into new potential molecules that could be used as supplements to potentially provide bioavailable creatine. Recently, a popular supplement, creatyl-l-leucine, has been proposed as a potential dietary ingredient that may potentially provide bioavailable creatine. This study tests whether creatyl-l-leucine is a bioavailable compound and determines whether it can furnish creatine as a dietary supplement. Rats were deprived of dietary creatine for a period of two weeks and then given one of three treatments: a control AIN-93G creatine-free diet, AIN-93G supplemented with creatine monohydrate or AIN-93G with an equimolar amount of creatyl-l-leucine supplement in the diet for one week. When compared to the control and the creatine monohydrate-supplemented diet, creatyl-l-leucine supplementation resulted in no bioaccumulation of either creatyl-l-leucine or creatine in tissue.

Cachexia is one of the most common, related factors of malnutrition in cancer patients. Cancer cachexia is a multifactorial syndrome characterized by persistent loss of skeletal muscle mass and fat mass, resulting in irreversible and progressive functional impairment. The skeletal muscle loss cannot be reversed by conventional nutritional support, and a combination of anti-inflammatory agents and other nutrients is recommended. In this review, we reviewed the effects of nutrients that are expected to combat muscle loss caused by cancer cachexia (eicosapentaenoic acid, β-hydroxy-β-methylbutyrate, creatine, and carnitine) to propose nutritional approaches that can be taken at present. Current evidence is based on the intake of nutrients as supplements; however, the long-term and continuous intake of nutrients as food has the potential to be useful for the body. Therefore, in addition to conventional nutritional support, we believe that it is important for the dietitian to work with the clinical team to first fully assess the patient’s condition and then to safely incorporate nutrients that are expected to have specific functions for cancer cachexia from foods and supplements.

Diabetes mellitus (DM) is a worldwide health concern, and projections state that cases will reach 578 million by 2030. Adjuvant therapies that can help the standard treatment and mitigate DM effects are necessary, especially those using nutritional supplements to improve glycemic control. Previous studies suggest creatine supplementation as a possible adjuvant therapy for DM, but they lack the evaluation of potential morphological parameters alterations and tissue injury caused by this compound. The present study aimed to elucidate clinical, histomorphometric, and histopathological consequences and the cellular oxidative alterations of creatine supplementation in streptozotocin (STZ)-induced type 1 DM rats. We could estimate whether the findings are due to DM or the supplementation from a factorial experimental design. Although creatine supplementation attenuated some biochemical parameters, the morphological analyses of pancreatic and renal tissues made clear that the supplementation did not improve the STZ-induced DM1 injuries. Moreover, creatine-supplemented non-diabetic animals were diagnosed with pancreatitis and showed renal tubular necrosis. Therefore, even in the absence of clinical symptoms and unaltered biochemical parameters, creatine supplementation as adjuvant therapy for DM should be carefully evaluated.

Male fertility has been declining globally over the past several decades, advancing from a personal issue to a public health problem. Beyond any doubt, a reduction in fertility (often characterized by low sperm count or motility) can severely threaten reproductive health and lifecourse framework in a long-term fashion. Aside from uncovering the currently unknown etiology of modern-day male infertility, the scientific and medical community faces a double burden: finding an efficient biomarker of impaired fertility and exploring any intervention that can act to enhance fertility. A plethora of nutritional compounds have been recognized as possible modulators of semen quality, and specific dietary patterns and nutrients appear to be accompanied by a lower risk of male infertility. Creatine, a conditionally essential nutrient, has caught attention as a male fertility-promoting candidate due to its role in sperm energy metabolism. This mini-review describes the creatine-related bioenergetics of spermatozoa, explores a connection between creatine levels and sperm quality in men, and critically examines available evidence for interventional studies with creatine to affect sperm viability.

Guanidinoacetic acid (GAA) is a natural amino acid derivative that is well-recognized for its central role in the biosynthesis of creatine, an essential compound involved in cellular energy metabolism. GAA (also known as glycocyamine or betacyamine) has been investigated as an energy-boosting dietary supplement in humans for more than 70 years. GAA is suggested to effectively increase low levels of tissue creatine and improve clinical features of cardiometabolic and neurological diseases, with GAA often outcompeting traditional bioenergetics agents in maintaining ATP status during stress. This perhaps happens due to a favorable delivery of GAA through specific membrane transporters (such as SLC6A6 and SLC6A13), previously dismissed as un-targetable carriers by other therapeutics, including creatine. The promising effects of dietary GAA might be countered by side-effects and possible toxicity. Animal studies reported neurotoxic and pro-oxidant effects of GAA accumulation, with exogenous GAA also appearing to increase methylation demand and circulating homocysteine, implying a possible metabolic burden of GAA intervention. This mini-review summarizes GAA toxicity evidence in human nutrition and outlines functional GAA safety through benefit-risk assessment and multi-criteria decision analysis.

The primary objective of this study was to investigate the potential synergy between low doses of L-carnitine tartrate and creatine monohydrate to induce muscle protein synthesis and anabolic pathway activation in primary human myoblasts. In addition, the effects of Lipid multi-particulates (LMP) formulation on creatine stability and bioavailability were assessed in rodents and healthy human subjects. When used individually, L-carnitine tartrate at 50 µM and creatine monohydrate at 0.5 µM did not affect myoblast protein synthesis and signaling. However, when combined, they led to a significant increase in protein synthesis. Increased AKT and RPS6 phosphorylation were observed with 50 µM L-carnitine tartrate 5 µM creatine in combination in primary human myoblasts. When Wistar rats were administered creatine with LMP formulation at either 21 or 51 mg/kg, bioavailability was increased by 27% based on the increase in the area under the curve (AUC) at a 51 mg/kg dose compared to without LMP formulation. Tmax and Cmax were unchanged. Finally, in human subjects, a combination of LMP formulated L-carnitine at 500 mg (from L-carnitine tartrate) with LMP formulated creatine at 100, 200, or 500 mg revealed a significant and dose-dependent increase in plasma creatine concentrations. Serum total L-carnitine levels rose in a similar manner in the three combinations. These results suggest that a combination of low doses of L-carnitine tartrate and creatine monohydrate may lead to a significant and synergistic enhancement of muscle protein synthesis and activation of anabolic signaling. In addition, the LMP formulation of creatine improved its bioavailability. L-carnitine at 500 mg and LMP-formulated creatine at 200 or 500 mg may be useful for future clinical trials to evaluate the effects on muscle protein synthesis.

There is great need for the identification of new, potentially modifiable risk factors for the poor health-related quality of life (HRQoL) and of the excess risk of mortality in dialysis-dependent chronic kidney disease patients. Creatine is an essential contributor to cellular energy homeostasis, yet, on a daily basis, 1.6–1.7% of the total creatine pool is non-enzymatically degraded to creatinine and subsequently lost via urinary excretion, thereby necessitating a continuous supply of new creatine in order to remain in steady-state. Because of an insufficient ability to synthesize creatine, unopposed losses to the dialysis fluid, and insufficient intake due to dietary recommendations that are increasingly steered towards more plant-based diets, hemodialysis patients are prone to creatine deficiency, and may benefit from creatine supplementation. To avoid problems with compliance and fluid balance, and, furthermore, to prevent intradialytic losses of creatine to the dialysate, we aim to investigate the potential of intradialytic creatine supplementation in improving outcomes. Given the known physiological effects of creatine, intradialytic creatine supplementation may help to maintain creatine homeostasis among dialysis-dependent chronic kidney disease patients, and consequently improve muscle status, nutritional status, neurocognitive status, HRQoL. Additionally, we describe the rationale and design for a block-randomized, double-blind, placebo-controlled pilot study. The aim of the pilot study is to explore the creatine uptake in the circulation and tissues following different creatine supplementation dosages.

Mild cognitive impairment (MCI) designates the boundary area between cognitive function in natural aging and dementia, and this is viewed as a therapeutic window to prevent the occurrence of dementia. The current study investigated the neurocognitive effects of oral creatine (Cr) supplementation in young female Wistar rats that received intracerebroventricular injections of lipopolysaccharide (LPS) to mimic MCI. Neuromolecular changes within the dentate gyrus were analyzed following behavioral testing. We also investigated both neurocognitive and neuromolecular changes following Cr supplementation in the absence of LPS in young female Wistar rats to further investigate mechanisms. Interestingly, based on trial 2 of Barnes maze test, Cr supplementation ameliorated spatial learning and memory deficit induced by LPS, shown by decreased latency time and errors to reach the escape box (p < 0.0001, n = 12). Cr supplementation also attenuated recognition memory deficit induced by LPS, shown by increased amount of time taken to explore the new object (p = 0.002, n = 12) during novel object recognition testing. Within the dentate gyrus, Cr supplementation in LPS injected rats upregulated mTORC1 signaling (p = 0.026 for mTOR phosphorylation, p = 0.002 for p70S6K phosphorylation, n = 8) as well as the synapsin (p = 0.008) and PSD-95 synaptic proteins (p = 0.015), in comparisons to LPS injected rats. However, Cr supplementation failed to further enhance spatial memory and recognition memory in the absence of LPS. In conclusion, Cr ameliorates LPS-induced cognitive impairment in a rodent MCI model. Mechanistically, these phenotypic effects may, in part, be mitigated via an upregulation of mTORC1 signaling, and an enhancement in synaptogenesis in the dentate gyrus. While preliminary, these findings may inform future research investigating neurocognitive effects of Cr for MCI patients.

White adipose tissue (WAT) is a dynamic endocrine organ that can play a significant role in thermoregulation. WAT has the capacity to adopt structural and functional characteristics of the more metabolically active brown adipose tissue (BAT) and contribute to non-shivering thermogenesis under specific stimuli. Non-shivering thermogenesis was previously thought to be uncoupling protein 1 (UCP1)-dependent however, recent evidence suggests that UCP1-independent mechanisms of thermogenesis exist. Namely, futile creatine cycling has been identified as a contributor to WAT thermogenesis. The purpose of this study was to examine the efficacy of creatine supplementation to alter mitochondrial markers as well as adipocyte size and multilocularity in inguinal (iWAT), gonadal (gWAT), and BAT. Thirty-two male and female Sprague-Dawley rats were treated with varying doses (0 g/L, 2.5 g/L, 5 g/L, and 10 g/L) of creatine monohydrate for 8 weeks. We demonstrate that mitochondrial markers respond in a sex and depot specific manner. In iWAT, female rats displayed significant increases in COXIV, PDH-E1alpha, and cytochrome C protein content. Male rats exhibited gWAT specific increases in COXIV and PDH-E1alpha protein content. This study supports creatine supplementation as a potential method of UCP1-independant thermogenesis and highlights the importance of taking a sex-specific approach when examining the efficacy of browning therapeutics in future research.

Creatine is classified as a “sports supplement”, but it also has health benefits. The purpose of this study was to assess use of creatine as a dietary supplement in adult non-athletes. Three hundred ninety-nine adults (19–89 years) completed an online survey. Among the respondents, 77% (n = 307) were regularly active, including participation in weightlifting (34%), running (34%), and cycling (21%). Twenty-eight percent (n = 111) reported use of creatine with an average dose of 6.4 ± 4.5 g. Daily creatine use was reported by 45%, and 38% reported using creatine 2–6 times weekly. Primary sources of information about creatine were trainers/coaches (29%), friends/family (32%), and internet (28%). Forty percent (n = 44) of creatine users were female. When compared by age, 46% of young, 32% of midlife, and 6% of old respondents reported creatine use with no differences in dose or frequency. Young and midlife respondents reported primarily trainers/coaches, friends/family, and internet as sources of information about creatine, but old respondents limited their sources to friends/family and fitness magazines. Although creatine is widely used by adult non-athletes who regularly exercise, dietitians and other healthcare providers are not the primary source of information. Fitness trainers can appropriately provide guidance and education regarding safe and effective use of creatine.

The use of dietary supplements is high among athletes and non-athletes alike, as well as able-bodied individuals and those with impairments. However, evidence is lacking in the use of dietary supplements for sport performance in a para-athlete population (e.g., those training for the Paralympics or similar competition). Our objective was to examine the literature regarding evidence for various sport supplements in a para-athlete population. A comprehensive literature search was conducted using PubMed, SPORTDiscus, MedLine, and Rehabilitation and Sports Medicine Source. Fifteen studies met our inclusion criteria and were included in our review. Seven varieties of supplements were investigated in the studies reviewed, including caffeine, creatine, buffering agents, fish oil, leucine, and vitamin D. The evidence for each of these supplements remains inconclusive, with varying results between studies. Limitations of research in this area include the heterogeneity of the subjects within the population regarding functionality and impairment. Very few studies included individuals with impairments other than spinal cord injury. Overall, more research is needed to strengthen the evidence for or against supplement use in para-athletes. Future research is also recommended on performance in para-athlete populations with classifiable impairments other than spinal cord injuries.

(1) Background: Given the physiological characteristics of handball, players may require the use of certain sports supplements (SS). However, very few studies have investigated the consumption of SS in handball. The aims were to determine the number of handball players who consume SS, to analyze their SS consumption pattern according to gender and competitive level, and to assess whether the SS they consume are supported by scientific evidence, and to which group they belong according to the classification of the Australian Institute of Sport (AIS). (2) Methods: A descriptive-correlational study was carried out on the habitual consumption of SS in 360 federated Spanish players by using a self-administered and validated questionnaire. (3) Results: These showed 65.8% of the sample consumed SS. According to the total number of participants, the most consumed supplements were from Group A: sports drinks (30.8%) and whey protein (30.4%). When analyzing the data by gender, the men's consumption was significantly higher for whey protein ( p < 0.001), caffeine ( p = 0.009), and creatine monohydrate ( p < 0.001). When analyzed by competitive level, the provincial category players group showed a significantly lower consumption than the rest of the groups for protein bars ( p = 0.038), whey protein ( p = 0.005) and creatine monohydrate ( p < 0.001), while the honor division group showed a significantly higher intake of creatine monohydrate than the remaining groups ( p < 0.001). (4) Conclusions: The handball players showed a moderate consumption of SS, without using substances that were not supported by scientific evidence and opting in most cases for supplements belonging to group A from the AIS classification. Men tended to consume more SS, and SS consumption increased based on competitive level.

Creatine is a broadly used dietary supplement that has been extensively studied for its benefit on the musculoskeletal system. Yet, there is limited knowledge regarding the metabolic regulation of creatine in cells beyond the muscle. New insights concerning various regulatory functions for creatine in other physiological systems are developing. Here, we highlight the latest advances in understanding creatine regulation of T cell antitumor immunity, a topic that has previously gained little attention in the creatine research field. Creatine has been identified as an important metabolic regulator conserving bioenergy to power CD8 T cell antitumor reactivity in a tumor microenvironment; creatine supplementation has been shown to enhance antitumor T cell immunity in multiple preclinical mouse tumor models and, importantly, to synergize with other cancer immunotherapy modalities, such as the PD-1/PD-L1 blockade therapy, to improve antitumor efficacy. The potential application of creatine supplementation for cancer immunotherapy and the relevant considerations are discussed.

Creatine is an organic compound, consumed exogenously in the diet and synthesized endogenously via an intricate inter-organ process. Functioning in conjunction with creatine kinase, creatine has long been known for its pivotal role in cellular energy provision and energy shuttling. In addition to the abundance of evidence supporting the ergogenic benefits of creatine supplementation, recent evidence suggests a far broader application for creatine within various myopathies, neurodegenerative diseases, and other pathologies. Furthermore, creatine has been found to exhibit non-energy related properties, contributing as a possible direct and in-direct antioxidant and eliciting anti-inflammatory effects. In spite of the new clinical success of supplemental creatine, there is little scientific insight into the potential effects of creatine on cardiovascular disease (CVD), the leading cause of mortality. Taking into consideration the non-energy related actions of creatine, highlighted in this review, it can be speculated that creatine supplementation may serve as an adjuvant therapy for the management of vascular health in at-risk populations. This review, therefore, not only aims to summarize the current literature surrounding creatine and vascular health, but to also shed light onto the potential mechanisms in which creatine may be able to serve as a beneficial supplement capable of imparting vascular-protective properties and promoting vascular health.

A possible role of dietary creatine for ensuring proper growth and development remains unknown. The main aim of this cross-sectional study was to quantify the amount of creatine consumed through regular diet among U.S. children and adolescents aged 2 to 19 years and investigate the relationship between creatine intake and growth indicators, using data from the 2001–2002 National Health and Nutrition Examination Survey (NHANES). We included data for NHANES 2001–2002 respondents (4291 participants, 2133 boys and 2158 girls) aged 2 to 19 years at the time of screening, who provided valid dietary information and examination measures (standing height and weight). Individual values for total grams of creatine consumed per day for each participant were computed using the average amount of creatine (3.88 g/kg) across all sources of meat-based foods. All participants were categorized for height-for-age and BMI-for-age categories. The average daily intake of creatine across the whole sample was 1.07 ± 1.07 g (95% CI, from 1.04 to 1.10). Height, weight, and BMI were significantly different across creatine quartiles (p < 0.001), with all measures significantly higher in the 4th quartile of creatine intake (≥1.5 g/day) than those in other quartiles (p < 0.05). The participants from the 3rd quartile of creatine intake (0.84–1.49 g/day) were significantly different from others with respect to having lower rates of normal stature and higher rates of tall stature (p < 0.05). Each additional 0.1 g of creatine consumed per day increases height by 0.60 cm (simple model) or 0.30 cm (adjusted model). The daily intake of creatine from a regular diet in taller children and adolescents was higher than in shorter peers aged 2–19 years. Future research has to monitor temporal changes in growth and dietary creatine and validate our findings in interventional studies across pediatric populations.

Creatine metabolism is an important component of cellular energy homeostasis. Via the creatine kinase circuit, creatine derived from our diet or synthesized endogenously provides spatial and temporal maintenance of intracellular adenosine triphosphate (ATP) production; this is particularly important for cells with high or fluctuating energy demands. The use of this circuit by tissues within the female reproductive system, as well as the placenta and the developing fetus during pregnancy is apparent throughout the literature, with some studies linking perturbations in creatine metabolism to reduced fertility and poor pregnancy outcomes. Maternal dietary creatine supplementation during pregnancy as a safeguard against hypoxia-induced perinatal injury, particularly that of the brain, has also been widely studied in pre-clinical in vitro and small animal models. However, there is still no consensus on whether creatine is essential for successful reproduction. This review consolidates the available literature on creatine metabolism in female reproduction, pregnancy and the early neonatal period. Creatine metabolism is discussed in relation to cellular bioenergetics and de novo synthesis, as well as the potential to use dietary creatine in a reproductive setting. We highlight the apparent knowledge gaps and the research “road forward” to understand, and then utilize, creatine to improve reproductive health and perinatal outcomes.

Post-viral fatigue syndrome (PVFS) is a widespread chronic neurological disease with no definite etiological factor(s), no actual diagnostic test, and no approved pharmacological treatment, therapy, or cure. Among other features, PVFS could be accompanied by various irregularities in creatine metabolism, perturbing either tissue levels of creatine in the brain, the rates of phosphocreatine resynthesis in the skeletal muscle, or the concentrations of the enzyme creatine kinase in the blood. Furthermore, supplemental creatine and related guanidino compounds appear to impact both patient- and clinician-reported outcomes in syndromes and maladies with chronic fatigue. This paper critically overviews the most common disturbances in creatine metabolism in various PVFS populations, summarizes human trials on dietary creatine and creatine analogs in the syndrome, and discusses new frontiers and open questions for using creatine in a post-COVID-19 world.

Background: Treatment with the chemotherapy drug doxorubicin (DOX) may lead to toxicities that affect non-cancer cells including the liver. Supplementing the diet with creatine (Cr) has been suggested as a potential intervention to minimize DOX-induced side effects, but its effect in alleviating DOX-induced hepatoxicity is currently unknown. Therefore, we aimed to examine the effects of Cr supplementation on DOX-induced liver damage. Methods: Male Sprague-Dawley rats were fed a diet supplemented with 2% Cr for four weeks, 4% Cr for one week followed by 2% Cr for three more weeks, or control diet for four weeks. Animals then received either a bolus i.p. injection of DOX (15 mg/kg) or saline as a placebo. Animals were then sacrificed five days-post injection and markers of hepatoxicity were analyzed using the liver-to-body weight ratio, aspartate transaminase (AST)-to- alanine aminotransferase (ALT) ratio, alkaline phosphatase (ALP), lipemia, and T-Bilirubin. In addition, hematoxylin and eosin (H&E) staining, Picro-Sirius Red staining, and immunofluorescence staining for CD45, 8-OHdG, and β-galactosidase were performed to evaluate liver morphology, fibrosis, inflammation, oxidative stress, and cellular senescence, respectively. The mRNA levels for biomarkers of liver fibrosis, inflammation, oxidative stress, and senescence-related genes were measured in liver tissues. Chromosomal stability was evaluated using global DNA methylation ELISA. Results: The ALT/AST ratio and liver to body weight ratio tended to increase in the DOX group, and Cr supplementation tended to attenuate this increase. Furthermore, elevated levels of liver fibrosis, inflammation, oxidative stress, and senescence were observed with DOX treatment, and Cr supplementation prior to DOX treatment ameliorated this hepatoxicity. Moreover, DOX treatment resulted in chromosomal instability (i.e., altered DNA methylation profile), and Cr supplementation showed a tendency to restore chromosomal stability with DOX treatment. Conclusion: The data suggest that Cr protected against DOX-induced hepatotoxicity by attenuating fibrosis, inflammation, oxidative stress, and senescence.

The creatine (Cr) energy system has been implicated in Alzheimer’s disease (AD), including reductions in brain phosphoCr and Cr kinase, yet no studies have examined the neurobehavioral effects of Cr supplementation in AD, including the 3xTg mouse model. This studied investigated the effects of Cr supplementation on spatial cognition, plasticity- and disease-related protein levels, and mitochondrial function in the 3xTg hippocampus. Here, 3xTg mice were fed a control or Cr-supplemented (3% Cr (w/w)) diet for 8–9 weeks and tested in the Morris water maze. Mitochondrial oxygen consumption (Seahorse) and protein levels (Western blots) were measured in the hippocampus in subsets of mice. Overall, 3xTg females exhibited impaired memory as compared to males. In females, Cr supplementation decreased escape latency and was associated with increased spatial search strategy use. In males, Cr supplementation decreased the use of spatial search strategies. Pilot data indicated mitochondrial enhancements with Cr supplementation in both sexes. In females, Cr supplementation increased CREB phosphorylation and levels of IκB (NF-κB suppressor), CaMKII, PSD-95, and high-molecular-weight amyloid β (Aβ) species, whereas Aβ trimers were reduced. These data suggest a beneficial preventative effect of Cr supplementation in females and warrant caution against Cr supplementation in males in the AD-like brain.

Creatine is a naturally occurring compound, functioning in conjunction with creatine kinase to play a quintessential role in both cellular energy provision and intracellular energy shuttling. An extensive body of literature solidifies the plethora of ergogenic benefits gained following dietary creatine supplementation; however, recent findings have further indicated a potential therapeutic role for creatine in several pathologies such as myopathies, neurodegenerative disorders, metabolic disturbances, chronic kidney disease and inflammatory diseases. Furthermore, creatine has been found to exhibit non-energy-related properties, such as serving as a potential antioxidant and anti-inflammatory. Despite the therapeutic success of creatine supplementation in varying clinical populations, there is scarce information regarding the potential application of creatine for combatting the current leading cause of mortality, cardiovascular disease (CVD). Taking into consideration the broad ergogenic and non-energy-related actions of creatine, we hypothesize that creatine supplementation may be a potential therapeutic strategy for improving vascular health in at-risk populations such as older adults or those with CVD. With an extensive literature search, we have found only four clinical studies that have investigated the direct effect of creatine on vascular health and function. In this review, we aim to give a short background on the pleiotropic applications of creatine, and to then summarize the current literature surrounding creatine and vascular health. Furthermore, we discuss the varying mechanisms by which creatine could benefit vascular health and function, such as the impact of creatine supplementation upon inflammation and oxidative stress.

Aim: The aim of the study was to evaluate the effects of 16 weeks of a low dose of magnesium creatine chelate supplementation on repeated sprint ability test (RAST) results in elite soccer players. Materials: Twenty well-trained soccer players participated in the study. The players were divided randomly into two groups: the supplemented group (SG = 10) and placebo group (PG = 10). Out of the 20 subjects selected for the study, 16 (SG = 8, PG = 8) completed the entire experiment. The SG ingested a single dose of 5500 mg of magnesium creatine chelate (MgCr-C), in 4 capsules per day, which was 0.07 g/kg/d. The PG received an identical 4 capsules containing corn starch. Before and after the study, the RAST was performed. In the RAST, total time (TT), first and sixth 35 m sprint length (s), average power (AP) and max power (MP) were measured. Additionally, before and after the test, lactate LA (mmol/L) and acid–base equilibrium pH (-log(H+)), bicarbonates HCO3− (mmol/L) were evaluated. Also, in serum at rest, creatinine (mg/dL) concentration was measured. Results: After the study, significantly better results in TT, AP and MP were observed in the SG. No significant changes in the RAST results were observed in the PG. After the study, significant changes in the first 35 m sprint, as well as the sixth 35 m sprint results were registered in the SG, while insignificant changes occurred in the PG. A significantly higher creatinine concentration was observed. Also, a higher post-RAST concentration of LA, HCO3− and lower values of pH were observed in April, May and June compared with baseline values. Conclusions: The long timeframe, i.e., 16 weeks, of the low dose of magnesium creatine chelate supplementation improved the RAST results in the SG. Despite the long period of MgCr-C supplementation, in the end of the study, the creatinine level in the SG reached higher but still reference values.

Ischemia-reperfusion injury (IRI) is one of the factors limiting the success of lung transplantation (LTx). IRI increases death risk after transplantation through innate immune system activation and inflammation induction. Some studies have shown that creatine (Cr) protects tissues from ischemic damage by its antioxidant action. We evaluated the effects of Cr supplementation on IRI after unilateral LTx in rats. Sixty-four rats were divided into four groups: water + 90 min of ischemia; Cr + 90 min of ischemia; water + 180 min of ischemia; and Cr + 180 min of ischemia. Donor animals received oral Cr supplementation (0.5 g/kg/day) or vehicle (water) for five days prior to LTx. The left lung was exposed to cold ischemia for 90 or 180 min, followed by reperfusion for 2 h. We evaluated the ventilatory mechanics and inflammatory responses of the graft. Cr-treated animals showed a significant decrease in exhaled nitric oxide levels and inflammatory cells in blood, bronchoalveolar lavage fluid and lung tissue. Moreover, edema, cell proliferation and apoptosis in lung parenchyma were reduced in Cr groups. Finally, TLR-4, IL-6 and CINC-1 levels were lower in Cr-treated animals. We concluded that Cr caused a significant decrease in the majority of inflammation parameters evaluated and had a protective effect on the IRI after LTx in rats.

Old age is associated with lower physical activity levels, suboptimal protein intake, and desensitization to anabolic stimuli, predisposing for age-related muscle loss (sarcopenia). Although resistance exercise (RE) and protein supplementation partially protect against sarcopenia under controlled conditions, the efficacy of home-based, unsupervised RE (HBRE) and multi-ingredient supplementation (MIS) is largely unknown. In this randomized, placebo-controlled and double-blind trial, we examined the effects of HBRE/MIS on muscle mass, strength, and function in free-living, older men. Thirty-two sedentary men underwent twelve weeks of home-based resistance band training (3 d/week), in combination with daily intake of a novel five-nutrient supplement (‘Muscle5’; M5, n = 16, 77.4 ± 2.8 y) containing whey, micellar casein, creatine, vitamin D, and omega-3 fatty acids, or an isocaloric/isonitrogenous placebo (PLA; n = 16, 74.4 ± 1.3 y), containing collagen and sunflower oil. Appendicular and total lean mass (ASM; +3%, TLM; +2%), lean mass to fat ratios (ASM/% body fat; +6%, TLM/% body fat; +5%), maximal strength (grip; +8%, leg press; +17%), and function (5-Times Sit-to-Stand time; −9%) were significantly improved in the M5 group following HBRE/MIS therapy (pre vs. post tests; p < 0.05). Fast-twitch muscle fiber cross-sectional areas of the quadriceps muscle were also significantly increased in the M5 group post intervention (Type IIa; +30.9%, Type IIx, +28.5%, p < 0.05). Sub-group analysis indicated even greater gains in total lean mass in sarcopenic individuals following HBRE/MIS therapy (TLM; +1.65 kg/+3.4%, p < 0.05). We conclude that the Muscle5 supplement is a safe, well-tolerated, and effective complement to low-intensity, home-based resistance exercise and improves lean mass, strength, and overall muscle quality in old age.

The aim of the present study was to analyze the effect of creatine (Cr) supplementation on peak torque (PT) and fatigue rate in Paralympic weightlifting athletes. Eight Paralympic powerlifting athletes participated in the study, with 25.40 ± 3.30 years and 70.30 ± 12.15 kg. The measurements of muscle strength, fatigue index (FI), peak torque (PT), force (kgf), force (N), rate of force development (RFD), and time to maximum isometric force (time) were determined by a Musclelab load cell. The study was performed in a single-blind manner, with subjects conducting the experiments first with placebo supplementation and then, following a 7-day washout period, beginning the same protocol with creatine supplementation for 7 days. This sequence was chosen because of the lengthy washout of creatine. Regarding the comparison between conditions, Cr supplementation did not show effects on the variables of muscle force, peak torque, RFD, and time to maximum isometric force (p > 0.05). However, when comparing the results of the moments with the use of Cr and placebo, a difference was observed for the FI after seven days (U3: 1.12; 95% CI: (0.03, 2.27); p = 0.02); therefore, the FI was higher for placebo. Creatine supplementation has a positive effect on the performance of Paralympic powerlifting athletes, reducing fatigue index, and keeping the force levels as well as PT.

High-intensity interval training (HIIT) involves short bursts of intense activity interspersed by periods of low-intensity exercise or rest. HIIT is a viable alternative to traditional continuous moderate-intensity endurance training to enhance maximal oxygen uptake and endurance performance. Combining nutritional strategies with HIIT may result in more favorable outcomes. The purpose of this narrative review is to highlight key dietary interventions that may augment adaptations to HIIT, including creatine monohydrate, caffeine, nitrate, sodium bicarbonate, beta-alanine, protein, and essential amino acids, as well as manipulating carbohydrate availability. Nutrient timing and potential sex differences are also discussed. Overall, sodium bicarbonate and nitrates show promise for enhancing HIIT adaptations and performance. Beta-alanine has the potential to increase training volume and intensity and improve HIIT adaptations. Caffeine and creatine have potential benefits, however, longer-term studies are lacking. Presently, there is a lack of evidence supporting high protein diets to augment HIIT. Low carbohydrate training enhances the upregulation of mitochondrial enzymes, however, there does not seem to be a performance advantage, and a periodized approach may be warranted. Lastly, potential sex differences suggest the need for future research to examine sex-specific nutritional strategies in response to HIIT.

The combination of resistance exercise and creatine supplementation has been shown to decrease body fat percentage in adults ≥ 50 years of age. However, the effect on adults < 50 years of age is currently unknown. To address this limitation, we systematically reviewed the literature and performed several meta-analyses comparing studies that included resistance exercise and creatine supplementation to resistance exercise and placebo on fat mass and body fat percentage Twelve studies were included, involving 266 participants. Adults (<50 years of age) who supplemented with creatine and performed resistance exercise experienced a very small, yet significant reduction in body fat percentage (-1.19%, p = 0.006); however, no difference was found in absolute fat mass (-0.18 kg, p = 0.76). Collectively, in adults < 50 years of age, the combination of resistance exercise and creatine supplementation produces a very small reduction in body fat percentage without a corresponding decrease in absolute fat mass.

Guanidinoacetic acid (GAA) conversion to creatine is thought to be involved in cardiometabolic disturbances through its role in biological methylation and insulin secretion. We evaluated the association of serum GAA and creatine with cardiometabolic risk factors in a cohort of 151 apparently healthy adults (82 women and 69 men) aged 18-63 years. Serum levels of GAA and creatine were measured with liquid chromatography-tandem mass spectrometry. A multiple linear regression model adjusted for age and sex was employed to examine the relationship of serum GAA and creatine with cardiometabolic risk factors. Higher GAA levels were associated with an unfavorable cardiometabolic risk profile (higher insulin, higher total homocysteine, and higher body fat percentage), while having elevated serum creatine levels (≥31.1 µmol/L) was associated with being overweight (body mass index ≥ 25.0 kg/m). The results from our study suggest a possible role of the GAA-creatine axis in the pathogenesis of cardiovascular and metabolic diseases. [ABSTRACT FROM AUTHOR]