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CLINICAL STUDIES ON THE FOLLOWING INGREDIENTS:

Creatine (Creapure)

Creatine Prevents the Structural and Functional Damage to Mitochondria in Myogenic, Oxidatively Stressed C2C12 Cells and Restores Their Differentiation Capacity

Abstract

Creatine (Cr) is a nutritional supplement promoting a number of health benefits. Indeed Cr has been shown to be beneficial in disease-induced muscle atrophy, improve rehabilitation, and afford mild antioxidant activity. The beneficial effects are likely to derive from pleiotropic interactions. In accord with this notion, we previously demonstrated that multiple pleiotropic effects, including preservation of mitochondrial damage, account for the capacity of Cr to prevent the differentiation arrest caused by oxidative stress in C2C12 myoblasts. Given the importance of mitochondria in supporting the myogenic process, here we further explored the protective effects of Cr on the structure, function, and networking of these organelles in C2C12 cells differentiating under oxidative stressing conditions; the effects on the energy sensor AMPK, on PGC-1α, which is involved in mitochondrial biogenesis and its downstream effector Tfam were also investigated. Our results indicate that damage to mitochondria is crucial in the differentiation imbalance caused by oxidative stress and that the Cr-prevention of these injuries is invariably associated with the recovery of the normal myogenic capacity. We also found that Cr activates AMPK and induces an upregulation of PGC-1α expression, two events which are likely to contribute to the protection of mitochondrial quality and function.

Source: Barbieri E, Guescini M, Calcabrini C, Vallorani L, Diaz AR, Fimognari C, Canonico B, Luchetti F, Papa S, Battistelli M, Falcieri E, Romanello V, Sandri M, Stocchi V, Ciacci C, Sestili P. Creatine Prevents the Structural and Functional Damage to Mitochondria in Myogenic, Oxidatively Stressed C2C12 Cells and Restores Their Differentiation Capacity. Oxid Med Cell Longev. 2016;2016:5152029.

Enhanced mitochondrial biogenesis is associated with the ameliorative action of creatine supplementation in rat soleus and cardiac muscles

Abstract

The current study focused on the effect of creatine supplementation with/without exercise on the expression of genes controlling mitochondrial biogenesis in skeletal and cardiac muscles, as well as its safety profile on the liver and kidney. A total of 40 male Wister rats were included in the present study. Two unexercised groups: The control sedentary group and the sedentary creatine‑treated group (n=10) were treated daily with oral creatine (0.5 g/kg per day). Two exercised groups performed swimming exercise training 5 days/week for a period of 5 weeks; The Exercise training group, and exercise training and creatine (0.5 g/kg per day) treated group. After sacrifice, blood samples, cardiac and soleus muscles were collected for assessment of mtDNA copy number, gene expression analysis and nuclear extraction for the assay of PGC‑1α. The results of the current study demonstrated that, physical activity with short‑term creatine supplementation increased all factors of mitochondrial biogenesis, an effect that is devoid of any kidney or liver adverse effects. Further studies are still required to explore the potential of creatine supplementation in ameliorating mitochondrial diseases, including epilepsy, skeletal and cardiac myopathies, hepatopathies and nephropathies.

Source: Gowayed MA, Mahmoud SA, El-Sayed Y, Abu-Samra N, Kamel MA. Enhanced mitochondrial biogenesis is associated with the ameliorative action of creatine supplementation in rat soleus and cardiac muscles. Exp Ther Med. 2020 Jan;19(1):384-392.

Role of Creatine Supplementation in Conditions Involving Mitochondrial Dysfunction: A Narrative Review

Abstract

Creatine monohydrate (CrM) is one of the most widely used nutritional supplements among active individuals and athletes to improve high-intensity exercise performance and training adaptations. However, research suggests that CrM supplementation may also serve as a therapeutic tool in the management of some chronic and traumatic diseases. Creatine supplementation has been reported to improve high-energy phosphate availability as well as have antioxidative, neuroprotective, anti-lactatic, and calcium-homoeostatic effects. These characteristics may have a direct impact on mitochondrion’s survival and health particularly during stressful conditions such as ischemia and injury. This narrative review discusses current scientific evidence for use or supplemental CrM as a therapeutic agent during conditions associated with mitochondrial dysfunction. Based on this analysis, it appears that CrM supplementation may have a role in improving cellular bioenergetics in several mitochondrial dysfunction-related diseases, ischemic conditions, and injury pathology and thereby could provide therapeutic benefit in the management of these conditions. However, larger clinical trials are needed to explore these potential therapeutic applications before definitive conclusions can be drawn.

Source: Marshall RP, Droste JN, Giessing J, Kreider RB. Role of Creatine Supplementation in Conditions Involving Mitochondrial Dysfunction: A Narrative Review. Nutrients. 2022 Jan 26;14(3):529.

Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial

Abstract

Creatine supplementation is in widespread use to enhance sports-fitness performance, and has been trialled successfully in the treatment of neurological, neuromuscular and atherosclerotic disease. Creatine plays a pivotal role in brain energy homeostasis, being a temporal and spatial buffer for cytosolic and mitochondrial pools of the cellular energy currency, adenosine triphosphate and its regulator, adenosine diphosphate. In this work, we tested the hypothesis that oral creatine supplementation (5 g d(-1) for six weeks) would enhance intelligence test scores and working memory performance in 45 young adult, vegetarian subjects in a double-blind, placebo-controlled, cross-over design. Creatine supplementation had a significant positive effect (p < 0.0001) on both working memory (backward digit span) and intelligence (Raven's Advanced Progressive Matrices), both tasks that require speed of processing. These findings underline a dynamic and significant role of brain energy capacity in influencing brain performance.

Source: Rae C, Digney AL, McEwan SR, Bates TC. Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial. Proc Biol Sci. 2003 Oct 22;270(1529):2147-50.

Creatine supplementation and cognitive performance in elderly individuals

Abstract

The purpose of this study was to examine the effect of creatine supplementation on the cognitive performance of elderly people. Participants were divided into two groups, which were tested on random number generation, forward and backward number and spatial recall, and long-term memory tasks to establish a baseline level. Group 1 (n = 15) were given 5 g four times a day of placebo for 1 week, followed by the same dosage of creatine for the second week. Group 2 (n = 17) were given placebo both weeks. Participants were retested at the end of each week. Results showed a significant effect of creatine supplementation on all tasks except backward number recall. It was concluded that creatine supplementation aids cognition in the elderly.

Source: McMorris T, Mielcarz G, Harris RC, Swain JP, Howard A. Creatine supplementation and cognitive performance in elderly individuals. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn. 2007 Sep;14(5):517-28.

Effects of creatine on mental fatigue and cerebral hemoglobin oxygenation

Abstract

While the role of creatine in preventing muscle (peripheral) fatigue for high performance athletes is well understood, its biochemical role in prevention of mental (central) fatigue is not. Creatine is abundant in muscles and the brain and after phosphorylation used as an energy source for adenosine triphosphate synthesis. Using double-blind placebo-controlled paradigm, we demonstrated that dietary supplement of creatine (8 g/day for 5 days) reduces mental fatigue when subjects repeatedly perform a simple mathematical calculation. After taking the creatine supplement, task-evoked increase of cerebral oxygenated hemoglobin in the brains of subjects measured by near infrared spectroscopy was significantly reduced, which is compatible with increased oxygen utilization in the brain.

Source: Watanabe A, Kato N, Kato T. Effects of creatine on mental fatigue and cerebral hemoglobin oxygenation. Neurosci Res. 2002 Apr;42(4):279-85.

Effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol

Abstract

Rationale: Sleep deprivation has a negative effect on cognitive and psychomotor performance and mood state, partially due to decreases in creatine levels in the brain. Therefore, creatine supplementation should lessen the negative effects of sleep deprivation.

Objectives: The objective of this study was to examine the effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol.

Method: Subjects were divided into a creatine group (n=10) and a placebo group (n=9). They took 5 g of creatine monohydrate or a placebo, dependent on their group, four times a time a day for 7 days, immediately prior to the experiment. The study was double blind. Subjects undertook tests of random movement generation (RMG), verbal and spatial recall, choice reaction time, static balance and mood state pre-test (0 h), after 6, 12 and 24 h of sleep deprivation, with intermittent exercise. They were tested for plasma concentrations of catecholamines and cortisol at 0 and 24 h.

Results: At 24 h, the creatine group demonstrated significantly less change in performance from 0 h (delta) in RMG, choice reaction time, balance and mood state. There were no significant differences between groups in plasma concentrations of catecholamines and cortisol. Norepinephrine and dopamine concentrations were significantly higher at 24 h than 0 h, but cortisol were lower.

Conclusions: Following 24-h sleep deprivation, creatine supplementation had a positive effect on mood state and tasks that place a heavy stress on the prefrontal cortex.

Source: McMorris T, Harris RC, Swain J, Corbett J, Collard K, Dyson RJ, Dye L, Hodgson C, Draper N. Effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol. Psychopharmacology (Berl). 2006 Mar;185(1):93-103.

Role of Creatine in the Heart: Health and Disease

Abstract

Creatine is a key player in heart contraction and energy metabolism. Creatine supplementation (throughout the paper, only supplementation with creatine monohydrate will be reviewed, as this is by far the most used and best-known way of supplementing creatine) increases creatine content even in the normal heart, and it is generally safe. In heart failure, creatine and phosphocreatine decrease because of decreased expression of the creatine transporter, and because phosphocreatine degrades to prevent adenosine triphosphate (ATP) exhaustion. This causes decreased contractility reserve of the myocardium and correlates with left ventricular ejection fraction, and it is a predictor of mortality. Thus, there is a strong rationale to supplement with creatine the failing heart. Pending additional trials, creatine supplementation in heart failure may be useful given data showing its effectiveness (1) against specific parameters of heart failure, and (2) against the decrease in muscle strength and endurance of heart failure patients. In heart ischemia, the majority of trials used phosphocreatine, whose mechanism of action is mostly unrelated to changes in the ergogenic creatine-phosphocreatine system. Nevertheless, preliminary data with creatine supplementation are encouraging, and warrant additional studies. Prevention of cardiac toxicity of the chemotherapy compounds anthracyclines is a novel field where creatine supplementation may also be useful. Creatine effectiveness in this case may be because anthracyclines reduce expression of the creatine transporter, and because of the pleiotropic antioxidant properties of creatine. Moreover, creatine may also reduce concomitant muscle damage by anthracyclines.

Source: Balestrino M. Role of Creatine in the Heart: Health and Disease. Nutrients. 2021 Apr 7;13(4):1215.

Effects of acute creatine supplementation on cardiac and vascular responses in older men; a randomized controlled trial

Abstract

Background and aims: In the recent years creatine has been shown promising results in patients with neurodegenerative diseases, myopathies and dystrophies. Cardiovascular diseases could be another pathology that can benefit from creatine supplementation, considering the influence on the risk factors associated with the development of cardiovascular diseases including reduction in chronic inflammation, and improved control of hyperglycemia and dyslipidemia The aim of the present study was to investigate the impact of short-term creatine supplementation on cardiac and vascular health in older adults.

Methods: Males between the ages of 55–80 were randomly assigned to three groups: creatine, placebo and control. Creatine or placebo was provided for 7-day supplementation, at a dose of 20 g/day. Testing was performed at the same time of the day at baseline and on the eighth day. Vascular responses were assessed using an arterial pulse wave velocity equipment, while cardiac assessment was performed using an impedance cardiography device.

Results: The placebo group was older (71.1 ± 8.2 yr) compared to creatine (61.4 ± 5.2 yr) and control (62.5 ± 7.1 yr). Cardio-ankle vascular index improved just in the creatine group (8.7 ± 0.5 to 8.2 ± 0.5, p = 0.03). While the upstroke time of the placebo and control groups did not change after 7 days, the creatine group had a nonsignificant reduction, 178.9 ± 26.5 ms to 158.4 ± 28.6 ms, p = 0.07. Similar tendency was seen with the systolic blood pressures, while the placebo and control did not change, the creatine group showed nonsignificant improvement, especially on the right, 144.0 ± 12.7 mmHg to 136.1 ± 13.4 mmHg, p = 0.08. All three groups had similar responses in stroke volume (p = 0.61), contractility index (p = 0.64) and ejection fraction (p = 0.72).

Conclusions: In older adults, acute creatine supplementation can positively affect vascular parameters of arterial stiffness and atherosclerosis. Creatine supplementation has the potential to serve as a potent adjuvant in the management of CVD for older adults.

Source: Aron A, Landrum EJ, Schneider AD, Via M, Evans L, Rawson ES. Effects of acute creatine supplementation on cardiac and vascular responses in older men; a randomized controlled trial. Clin Nutr ESPEN. 2024 Oct;63:557-563.

Effect of oral creatine supplementation on human muscle GLUT4 protein content after immobilization

Abstract

The purpose of this study was to investigate the effect of oral creatine supplementation on muscle GLUT4 protein content and total creatine and glycogen content during muscle disuse and subsequent training. A double-blind placebo-controlled trial was performed with 22 young healthy volunteers. The right leg of each subject was immobilized using a cast for 2 weeks, after which subjects participated in a 10-week heavy resistance training program involving the knee-extensor muscles (three sessions per week). Half of the subjects received creatine monohydrate supplements (20 g daily during the immobilization period and 15 and 5 g daily during the first 3 and the last 7 weeks of rehabilitation training, respectively), whereas the other 11 subjects ingested placebo (maltodextrine). Muscle GLUT4 protein content and glycogen and total creatine concentrations were assayed in needle biopsy samples from the vastus lateralis muscle before and after immobilization and after 3 and 10 weeks of training. Immobilization decreased GLUT4 in the placebo group (-20%, P < 0.05), but not in the creatine group (+9% NS). Glycogen and total creatine were unchanged in both groups during the immobilization period. In the placebo group, during training, GLUT4 was normalized, and glycogen and total creatine were stable. Conversely, in the creatine group, GLUT4 increased by approximately 40% (P < 0.05) during rehabilitation. Muscle glycogen and total creatine levels were higher in the creatine group after 3 weeks of rehabilitation (P < 0.05), but not after 10 weeks of rehabilitation. We concluded that 1) oral creatine supplementation offsets the decline in muscle GLUT4 protein content that occurs during immobilization, and 2) oral creatine supplementation increases GLUT4 protein content during subsequent rehabilitation training in healthy subjects.

Source: Op 't Eijnde B, Ursø B, Richter EA, Greenhaff PL, Hespel P. Effect of oral creatine supplementation on human muscle GLUT4 protein content after immobilization. Diabetes. 2001 Jan;50(1):18-23.

Creatine in type 2 diabetes: a randomized, double-blind, placebo-controlled trial

Abstract

Creatine supplementation improves glucose tolerance in healthy subjects.

Purposes: The aim was to investigate whether creatine supplementation has a beneficial effect on glycemic control of type 2 diabetic patients undergoing exercise training.

Methods: A 12-wk randomized, double-blind, placebo-controlled trial was performed. The patients were allocated to receive either creatine (CR) (5 g·d) or placebo (PL) and were enrolled in an exercise training program. The primary outcome was glycosylated hemoglobin (HbA1c). Secondary outcomes included the area under the curve of glucose, insulin, and C-peptide and insulin sensitivity indexes. Physical capacity, lipid profile, and GLUT-4 protein expression and translocation were also assessed.

Results: Twenty-five subjects were analyzed (CR: n=13; PL: n=12). HbA1c was significantly reduced in the creatine group when compared with the placebo group (CR: PRE=7.4 ± 0.7, POST=6.4 ± 0.4; PL: PRE=7.5 ± 0.6, POST=7.6 ± 0.7; P=0.004; difference=-1.1%, 95% confidence interval=-1.9% to -0.4%). The delta area under the curve of glucose concentration was significantly lower in the CR group than in the PL group (CR=-7790 ± 4600, PL=2008 ± 7614; P=0.05). The CR group also presented decreased glycemia at times 0, 30, and 60 min during a meal tolerance test and increased GLUT-4 translocation. Insulin and C-peptide concentrations, surrogates of insulin sensitivity, physical capacity, lipid profile, and adverse effects were comparable between the groups.

Conclusions: Creatine supplementation combined with an exercise program improves glycemic control in type 2 diabetic patients. The underlying mechanism seems to be related to an increase in GLUT-4 recruitment to the sarcolemma.

Source: Gualano B, DE Salles Painneli V, Roschel H, Artioli GG, Neves M Jr, De Sá Pinto AL, Da Silva ME, Cunha MR, Otaduy MC, Leite Cda C, Ferreira JC, Pereira RM, Brum PC, Bonfá E, Lancha AH Jr. Creatine in type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Med Sci Sports Exerc. 2011 May;43(5):770-8.

Does creatine supplementation improve functional capacity in elderly women?

Abstract

The purpose of this study was to determine the effects of short-term (7 days) oral creatine supplementation (0.3 g.kg(-1)) in elderly women during exercise tests that reflect functional capacity during daily living tasks. We assessed several indices of endurance capacity (1-mile walk test, gross mechanical efficiency, ventilatory threshold, and peak oxygen intake determined during cycle-ergometry) and lower-extremity functional performance (time to complete sit-stand test). Subjects were assigned to a creatine (n = 10; age 67 +/- 6 years) or placebo (n = 6; age 68 +/- 4 years) group. We found a significant improvement only after creatine loading in the sit-stand test (placebo: 9.7 +/- 0.9 seconds for pretest and 9.3 +/- 0.7 seconds for posttest, p > 0.05; creatine: 10.0 +/- 0.7 seconds for pretest and 8.8 +/- 1.1 seconds for posttest). Significance was recorded at p < 0.05 for the interaction effect (group [creatine, placebo] x time [pretest, posttest]). In elderly women, short-term oral creatine supplementation does not improve endurance capacity but increases the ability to perform lower-body functional living tasks involving rapid movements.

Source: Cañete S, San Juan AF, Pérez M, Gómez-Gallego F, López-Mojares LM, Earnest CP, Fleck SJ, Lucia A. Does creatine supplementation improve functional capacity in elderly women? J Strength Cond Res. 2006 Feb;20(1):22-8.

Use of creatine in the elderly and evidence for effects on cognitive function in young and old

Abstract

The ingestion of the dietary supplement creatine (about 20 g/day for 5 days or about 2 g/day for 30 days) results in increased skeletal muscle creatine and phosphocreatine. Subsequently, the performance of high-intensity exercise tasks, which rely heavily on the creatine-phosphocreatine energy system, is enhanced. The well documented benefits of creatine supplementation in young adults, including increased lean body mass, increased strength, and enhanced fatigue resistance are particularly important to older adults. With aging and reduced physical activity, there are decreases in muscle creatine, muscle mass, bone density, and strength. However, there is evidence that creatine ingestion may reverse these changes, and subsequently improve activities of daily living. Several groups have demonstrated that in older adults, short-term high-dose creatine supplementation, independent of exercise training, increases body mass, enhances fatigue resistance, increases muscle strength, and improves the performance of activities of daily living. Similarly, in older adults, concurrent creatine supplementation and resistance training increase lean body mass, enhance fatigue resistance, increase muscle strength, and improve performance of activities of daily living to a greater extent than resistance training alone. Additionally, creatine supplementation plus resistance training results in a greater increase in bone mineral density than resistance training alone. Higher brain creatine is associated with improved neuropsychological performance, and recently, creatine supplementation has been shown to increase brain creatine and phosphocreatine. Subsequent studies have demonstrated that cognitive processing, that is either experimentally (following sleep deprivation) or naturally (due to aging) impaired, can be improved with creatine supplementation. Creatine is an inexpensive and safe dietary supplement that has both peripheral and central effects. The benefits afforded to older adults through creatine ingestion are substantial, can improve quality of life, and ultimately may reduce the disease burden associated with sarcopenia and cognitive dysfunction.

Source: Rawson ES, Venezia AC. Use of creatine in the elderly and evidence for effects on cognitive function in young and old. Amino Acids. 2011 May;40(5):1349-62.

Prevention of traumatic headache, dizziness and fatigue with creatine administration. A pilot study

Abstract

Aim: The complex pathobiology of traumatic brain injury (TBI) offers numerous targets for potential neuroprotective agents. We evaluate the clinical benefit after creatine (Cr) administration in children and adolescents.

Methods: A prospective, randomized, comparative, open- labelled pilot study of the possible neuroprotective effect of Cr was carried out on 39 children and adolescents, aged between 1 and 18 years of age, with TBI. The Cr was administered for 6 months, at a dose of 0.4 g/kg in an oral suspension form every day. For categorical variables, we used the Chi-square test to identify differences between controls and cases. Statistical significance was defined as a p-value <0.05 and not statistically significant if p-value >0.1.

Results: The administration of Cr to children and adolescents with TBI improved results in several parameters, including duration of post traumatic amnesia (PTA), duration of intubation, intensive care unit stay. Significant improvement was recorded in the categories of headache (p<0.001), dizziness (p=0.005) and fatigue (p<0.001), aspects in all patients. No side effects were seen due to Cr administration.

Conclusion: More specific examinations including brain spectroscopy for in vivo evaluation of Cr can be done, in order to draw conclusions for the optimal duration and manner of Cr supply, as well as its possible role for the prevention of TBI complications, in double blind studies.

Source: Sakellaris G, Nasis G, Kotsiou M, Tamiolaki M, Charissis G, Evangeliou A. Prevention of traumatic headache, dizziness and fatigue with creatine administration. A pilot study. Acta Paediatr. 2008 Jan;97(1):31-4.

Effects of six‐month creatine supplementation on patient‐ and clinician‐reported outcomes, and tissue creatine levels in patients with post‐COVID‐19 fatigue syndrome

Abstract

Dietary creatine has been recently put forward as a possible intervention strategy to reduce post‐COVID‐19 fatigue syndrome yet no clinical study so far evaluated its efficacy and safety for this perplexing condition. In this parallel‐group, randomized placebo‐controlled double‐blind trial, we analyzed the effects of 6‐month creatine supplementation (4 g of creatine monohydrate per day) on various patient‐ and clinician‐reported outcomes, and tissue creatine levels in 12 patients with post‐COVID‐19 fatigue syndrome. Creatine intake induced a significant increase in tissue creatine levels in vastus medialis muscle and right parietal white matter compared to the baseline values at both 3‐month and 6‐month follow‐ups (p < .05). Two‐way analysis of variance with repeated measures revealed a significant difference (treatment vs. time interaction) between interventions in tissue creatine levels (p < .05), with the creatine group was superior to placebo to augment creatine levels at vastus medialis muscle, left frontal white matter, and right parietal white matter. Creatine supplementation induced a significant reduction in general fatigue after 3 months of intake compared to baseline values (p = .04), and significantly improved scores for several post‐COVID‐19 fatigue syndrome‐related symptoms (e.g., ageusia, breathing difficulties, body aches, headache, and difficulties concentrating) at 6‐month follow‐up (p < .05). Taking creatine for 6 months appears to improve tissue bioenergetics and attenuate clinical features of post‐COVID‐19 fatigue syndrome; additional studies are warranted to confirm our findings in various post‐COVID‐19 cohorts.

Source: Slankamenac J, Ranisavljev M, Todorovic N, Ostojic J, Stajer V, Ostojic SM. Effects of six-month creatine supplementation on patient- and clinician-reported outcomes, and tissue creatine levels in patients with post-COVID-19 fatigue syndrome. Food Sci Nutr. 2023 Sep 20;11(11):6899-6906.

Creatine ameliorates high-fat diet-induced obesity by regulation of lipolysis and lipophagy in brown adipose tissue and liver

Abstract

Diet-induced obesity in mice and humans is commonly associated with an imbalance between energy intake and expenditure. Reportedly, creatine can enhance energy expenditure in brown adipose tissue and reduce hepatic triglycerides accumulation; however, the molecular mechanism underlying the role of exogenous creatine supplementation in regulating lipid droplet mobilization remains elusive. Herein, we employed a high-fat diet (HFD)- induced mouse model to investigate the role of creatine in regulating lipolysis and lipophagy in brown adipose tissue and the liver. Exogenous creatine supplementation ameliorated HFD-induced obesity, increased insulin sensitivity and improved glucose homeostasis. Creatine supplementation enhanced the expression of uncoupling protein 1 (UCP1), cell death-inducing DNA fragmentation factor alpha-like effector A (CIDEA), and other brown adipose tissue-specific thermogenic genes Cpt1a, Gyk, and Pgc1β in brown adipose tissue. Furthermore, creatine inhibited the expression of CIDEA, which promotes hepatic lipid accumulation. Creatine stimulated the expression of triglyceride lipase adipose triglyceride lipase, and phospho-hormone-sensitive lipase (HSL) induced increased lipolysis in brown adipose tissue and the liver. Meanwhile, reduced LC3B expression was accompanied by an increased level of p62 in HFD-fed mice, indicating diminished basal autophagy in brown adipose tissue and the liver; however, creatine enhanced P62/LC3B induced lipophagy in brown adipose tissue and the liver. Collectively, our results suggest that creatine may function as a brown adipose tissue activator to increase whole-body energy metabolism via coordinated lipolysis and lipophagy in brown adipose tissue and the liver.

Source: Chen Y, Jiang Y, Cui T, Hou L, Zhao R, Bo S, Zou L, Yin C. Creatine ameliorates high-fat diet-induced obesity by regulation of lipolysis and lipophagy in brown adipose tissue and liver. Biochimie. 2023 Jun;209:85-94.

A review of creatine supplementation in age-related diseases: more than a supplement for athletes

Abstract

Creatine is an endogenous compound synthesized from arginine, glycine and methionine. This dietary supplement can be acquired from food sources such as meat and fish, along with athlete supplement powders. Since the majority of creatine is stored in skeletal muscle, dietary creatine supplementation has traditionally been important for athletes and bodybuilders to increase the power, strength, and mass of the skeletal muscle. However, new uses for creatine have emerged suggesting that it may be important in preventing or delaying the onset of neurodegenerative diseases associated with aging. On average, 30% of muscle mass is lost by age 80, while muscular weakness remains a vital cause for loss of independence in the elderly population. In light of these new roles of creatine, the dietary supplement’s usage has been studied to determine its efficacy in treating congestive heart failure, gyrate atrophy, insulin insensitivity, cancer, and high cholesterol. In relation to the brain, creatine has been shown to have antioxidant properties, reduce mental fatigue, protect the brain from neurotoxicity, and improve facets/components of neurological disorders like depression and bipolar disorder. The combination of these benefits has made creatine a leading candidate in the fight against age-related diseases, such as Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, long-term memory impairments associated with the progression of Alzheimer’s disease, and stroke. In this review, we explore the normal mechanisms by which creatine is produced and its necessary physiology, while paying special attention to the importance of creatine supplementation in improving diseases and disorders associated with brain aging and outlining the clinical trials involving creatine to treat these diseases.

Source: Smith RN, Agharkar AS, Gonzales EB. A review of creatine supplementation in age-related diseases: more than a supplement for athletes. F1000Res. 2014 Sep 15;3:222.

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  36. https://www.bodybuilding.com/content/5-reasons-your-creatine-may-not-be-working.html#:~:text=Sure%2C%20you%20could%20rely%20on,%2C%20don't%20sweat%20it.
  37. https://www.healthline.com/nutrition/types-of-creatine
  38. https://www.creapure.com/en/creapure/what-creapure
  39. https://www.amazon.com/Nutricost-Creapure%C2%AE-Creatine-Monohydrate-1KG/dp/B06W5J8KGQ