The aging process associated with increased life expectancy is not without its problems, a condition that can result in an increased development of acute injuries or chronic diseases, in the frequency of hospital admissions and their complications. Among the numerous conditions associated with aging, we have the loss of generalized muscle tone, the loss of neuromuscular function and skeletal muscle strength, a condition called sarcopenia [1-3], frequently observed in the elderly population, especially in bedridden and hospitalized individuals [1,4-6]. Sarcopenia is considered a multifactorial injury, associated with aging are poor eating habits, inadequate physical exercise, metabolic syndromes, chronic and acute conditions, as well as genetic syndromes [1,4]. It presents itself chronically, however, it may be associated with the presence of other diseases, arise as an acute condition associated with chronic disease, cognitive deterioration and be triggered during a period of hospitalization or as a postoperative complication [6-11]. This review aims to analyze and synthesize consensus regarding the effectiveness of creatine supplementation in the prevention, regression and treatment of sarcopenia, whether isolated or associated with other morbid conditions.

Review of articles published in systematic and meta-analyses, using the Boolean and/or search technique, with the following descriptors: “Sarcopenia”, “Sarcopenia and nutrition”, “Creatine intake”, “Sarcopenia and creatine supplementation”, “Hospitalized patient”; through searches on the Google Scholar, Medline, PubMed and Wiley Online Library platforms. Fifty articles available in the databases between 2012 and 2023 were included in this review.

Sarcopenia is characterized by the progressive loss of skeletal   muscle   mass,   affecting   its   strength   and function [1-3], predominantly affecting the geriatric age group  but  it  has  also  been  diagnosed  in  young  adults (age ≤45 years) [12], hospitalized individuals, bedridden individuals, those undergoing major surgery or those with debilitating chronic diseases. Its onset increases the need for hospitalization, aggravates chronic and/or acute conditions, increases the rate of hospital morbidity and mortality and post-surgical complications, as well as increasing the length of stay and hospital costs [6,13].

With advancing age, sarcopenia is related to loss of muscle mass but also to loss of autonomy, i.e., a worsening of the individual's quality of life, a greater risk of falls and orthopedic injuries, the development of depression [14], cognitive and neuromotor loss and the worsening of chronic and acute conditions [6]. The influence of advancing age on the state of malnutrition is well known, whether due to endocrine-drug interactions, loss of appetite or gastrointestinal dysfunctions [15], the latter being a catalyst for the development of sarcopenia. Similarly to malnutrition, muscle atrophy due to disuse in bedridden hospitalized patients is a factor that exacerbates the loss of muscle mass and muscle capacity, corroborating the development of the sarcopenic state [6]. The pathophysiology of sarcopenia consists of an imbalance between protein synthesis and proteolysis in skeletal muscle tissue [3-4]. Despite the need to implement a high-protein diet to equalize the protein imbalance present in sarcopenia, purely dietary interventions have proven insufficient in combating and preventing this condition, making it necessary to apply dietary supplements, such as protein support formulas or creatine monohydrate [1,2,16], the subject of analysis in this review. Creatine monohydrate is widely studied and its role in the formation and preservation of muscle tissue is well established when consumption is associated with physical activity [3,17-21]. Important in the bioenergy generation process, in the Creatine Kinase-Phosphocreatine System, enabling and making available the energy product to the cellular site where it will be used [17,19-24], with mitochondrial dysfunction as a predictor of the development of sarcopenia [9,25,26]. Elderly and/or hospitalized individuals present a higher inflammatory rate with a high incidence of oxidative stress, which, in association with underlying disease, can potentiate their condition by inducing oxidative stress, influencing the inadequate functioning of mitochondria and consequently, the preservation of cellular energy and skeletal muscle mass [26,27]. Considering the close relationship between mitochondrial function and health and creatine and its possible reflection in the diagnosis and development of sarcopenia [17,25,27], it is necessary to evaluate and understand the possible therapeutic effect of creatine monohydrate supplementation in the prevention or regression of sarcopenia.

Sarcopenia is a condition commonly developed by hospitalized patients, those receiving home care or those in long-term care facilities, as a primary diagnosis and/or subsequent to an underlying disease. Hospital malnutrition is associated with loss of muscle mass and strength, leading to the worsening of sarcopenia and other injuries affecting hospitalized individuals. Erroneously associated with thinness, sarcopenia has also been identified in hospitalized obese individuals, being a condition that is difficult to screen for and diagnose [26]. An association between obesity and old age intensifies the decrease in myofibrillar anabolic resistance, causing a decrease in muscle protein synthesis. A high risk of developing sarcopenia is demonstrated in obese individuals due to the presence of metabolic alterations characteristic of this disease, sedentary lifestyle and also their dietary habits, usually rich in saturated fats and sugars. These conditions, individually or in combination, stimulate the formation of an inflammatory and oxidative stress environment, aggravating the loss of muscle mass and sarcopenia [26,28].

In the hospital setting, sarcopenia is frequently found in hospitalized patients, where inadequate nutritional support, muscle atrophy due to disuse in bedridden patients and hypercortisolemia are factors that increase the likelihood of developing sarcopenia [6]. Sarcopenia has also been associated with worsening of chronic heart failure [10,29], aggravating and decompensating chronic and acute respiratory injuries [6,30]. In the postoperative context, the presence of sarcopenia combined with the treatment of tissue trauma increases the risk of complications and mortality, reducing patient survival. Severe sepsis cases have a worsening of recovery and lead to greater readmission of the individual to hospital units [6,30,29,31]. Analysis of biomarkers in elderly individuals as potential indicators of sarcopenia reveals low concentrations of vitamin D, omega-3 fatty acids, muscle and visceral proteins, the amino acid 3-methylhistidine, low concentrations of antioxidant enzymes with higher concentrations of reactive oxygen species [32]. Increased protein catabolism in the muscles of elderly and bedridden individuals results in the degeneration of neural receptor sites responsible for neuromuscular control, exacerbating muscle atrophy, concomitantly with loss of volume and function [33]. These physiological changes cause dysfunction in the balance between mitochondrial synthesis and degradation in muscle cells, impairing the mitophagy process, generating an accumulation of dysfunctional mitochondria, with damaged genetic nuclei and altered membrane permeability. This alteration in mitochondrial membranes generates leakage of cellular contents into the cytosol of muscle cells, generating a signal for apoptosis of the cell, inability to function correctly in the cellular respiratory chain, which results in lower energy production, with damage to the preservation of muscle cells [11,27,34]. These factors combined have indicated mitochondrial dysfunction as an important predictor of sarcopenia in elderly and/or hospitalized patients. In parallel, diets that stimulate the inhibition of proteolysis and protein synthesis, as well as habits and foods favorable to mitochondrial preservation and the consumption of antioxidant foods, have proven to be good measures in preventing and reducing the progression of sarcopenia [1,16,27].

In addition to the biomarkers for sarcopenia already mentioned, there is a massive number of studies indicating the relationship between reduced muscle creatine concentrations and the loss of muscle mass and strength and functions of skeletal muscle [1,4,16]. It is still being evaluated whether the decline in muscle creatine concentration occurs directly due to tissue aging or whether it results from the consequent physiological and habitual changes during aging, such as lower protein intake, greater physical inactivity, lower concentration of antioxidants or whether the drop in creatine is the predictor of these changes [4,17]. The role of creatine supplementation and its ability to preserve and build muscle mass, as well as increase its strength and power, is widely studied [20-22]. However, most studies have obtained positive results in the preservation and recovery of muscle function when creatine supplementation was associated with resistance exercises [12,31,32,35]. Among the studies, it was determined that supplementation of ~20 g/day of creatine for elderly women  and  ~25 g/day  of  creatine  for  elderly  men,  for 7 days, generated an increase in muscle mass, improvement in isotonic and isometric maximum strength tests and improvement in standing performance, as well as improvement in discomfort in the seated position, when compared with a placebo group [12,18]. Although creatine supplementation showed positive effects, adherence to resistance physical activity, musculoskeletal gains in the elderly and hospitalized population did not demonstrate significant changes, as well as in the regression of sarcopenia [18,32], demonstrating the importance of integrated work between nutritionists, physiotherapists and physical educators in the prevention and/or control and regression of sarcopenia. It was also found that creatine was better absorbed when consumed together with a carbohydrate source [31,33], as well as demonstrating greater effectiveness in preserving muscle mass when energy restriction was necessary in elderly, obese and hospitalized patients [20,28].

Based on the analysis of the selected articles and guidelines, it can be concluded that the effect of creatine supplementation in the prevention and regression of sarcopenia in elderly and/or hospitalized individuals is important and fundamental. However, it should not be considered the sole factor; that is, without its association with physical activity and/or another nutritional supplement, it is not possible to consolidate the effectiveness of creatine supplementation in this situation.

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