madman
Super Moderator
Creatine supplementation for older adults: Focus on sarcopenia, osteoporosis, frailty, and Cachexia (2022)
Darren G. Candow, Philip D. Chilibeck, Scott C. Forbes, Ciaran M. Fairman, Bruno Gualano, Hamilton Roschel
ABSTRACT
Sarcopenia refers to the age-related reduction in strength, muscle mass, and functionality which increases the risk for falls, injuries, and fractures. Sarcopenia is associated with other age-related conditions such as osteoporosis, frailty, and cachexia. Identifying treatments to overcome sarcopenia and associated conditions is important from a global health perspective. There is evidence that creatine monohydrate supplementation, primarily when combined with resistance training, has favorable effects on indices of aging muscle and bone. These musculoskeletal benefits provide some rationale for creatine being a potential intervention for treating frailty and cachexia. The purposes of this narrative review are to update the collective body of research pertaining to the effects of creatine supplementation on indices of aging muscle and bone (including bone turnover markers) and present possible justification and rationale for its utilization in the treatment of frailty and cachexia in older adults.
1. Introduction
Sarcopenia, commonly defined as the age-related decrease in strength, muscle mass, and functionality, is associated with osteoporosis, frailty, and cachexia [1]. Furthermore, sarcopenia increases the risk of falls, injuries, fractures, and premature mortality [2]. The etiology and pathophysiology leading to sarcopenia are multifactorial and include alterations in skeletal muscle protein turnover and balance, endocrinological processes, neurophysiology, inflammation, vascularization, and mitochondrial function [3]. Sarcopenia occurs in 5–17 % of community-dwelling aging adults and 14–85 % of those residing in long-term care facilities [4]. With estimates that by the year 2050 there will be 1.5 billion adults ≥65 years of age [5], the prevalence of sarcopenia will continue to rise for the foreseeable future. Therefore, identifying treatments to overcome sarcopenia and associated age-related conditions is critically important from a global health perspective.
We have previously discussed and summarized the small body of research showing some favorable effects of creatine monohydrate supplementation on indices of aging muscle and bone (for reviews see [1,6,7]). Overall, creatine (primarily when combined with resistance training) has been shown to increase measures of muscle accretion, strength, and functionality [6–10]. Creatine has also been shown to increase bone area [11,12] and strength [13], attenuate the rate of bone mineral loss [13], and influence bone turnover by reducing the urinary excretion of cross-linked N-telopeptides (NTx) or C-telopeptides of type I collagen (CTx) in older adults [14]. Assessing bone turnover markers (i. e., NTx, CTx) is clinically relevant as they provide important information regarding the bone remodeling process and predict the risk of osteoporotic fracture in older adults [15]. Based on these musculoskeletal benefits, it is highly plausible that creatine may be an effective intervention to treat frailty (characterized by muscle weakness) and cachexia (characterized by rapid muscle wasting). However, research in these clinical areas is minimal.
The purposes of this narrative review are to (1) expand on our previous publications [1,6,7] and further update the collective body of research pertaining to the effects of creatine supplementation on indices.
2. Aging muscle
2.1. Creatine supplementation and resistance training
2.2. Creatine supplementation combined with other compounds and resistance training
2.3. Creatine supplementation without resistance training
3. Creatine supplementation on aging bone, falls, and fracture risk
Osteoporosis is characterized by the age-related reduction in bone mineral density and microarchitecture which can increase the risk of falls and subsequent fractures [39]. In this section, we review the effects of creatine supplementation on bone, falls, and fracture risk. We have reviewed evidence from cellular studies, animal models, and human interventions.
3.1. Cellular studies
3.2. Animal models
3.3. Human studies
4. Creatine supplementation and frailty
Frailty is overarchingly described as a condition of musculoskeletal weakness and reduced function. Though several definitions and screening criteria exist, frailty has generally been used to broadly define older adults impacted by weight loss, functional deficits, fatigue, cognitive impairment or mood disorders, comorbidities, and poor nutritional status [68]. Ultimately, frailty is considered to be a state of increased vulnerability (particularly to adverse health outcomes) that is associated with an increased risk of falls, disabilities, lack of independent living, and mortality [69,70]. Recognized as an aging condition, recent estimates suggest that approximately 1 in 6 community-dwelling older adults can be characterized as frail [71]. Others have identified the prevalence of frailty as up to ~59 % in older populations [72]. Consequently, the alarming incidence of frailty in older adults underscores the importance of maintaining and/or increasing muscle mass, strength, and physical function in individuals with frailty to preserve the health-related quality of life.
5. Creatine supplementation and Cachexia
Cachexia is used to define a complex, multifactorial, and often aggressive muscle-wasting condition, characterized by progressive weight loss (with or without fat loss), that cannot be reversed with conventional nutritional support [80,81]. Cachexia is strongly associated with a poorer prognosis, worsening of physical function and quality of life (QOL), and reduced survival in a variety of populations, such as cancer, chronic kidney disease, and heart failure [82–85]. Cachexia can arise due to a combination of factors, including systemic inflammation, reduced protein synthesis, and/or an increase in catabolism, along with malnutrition and physical inactivity [86–89].
6. Conclusions
The current body of research indicates that creatine monohydrate supplementation, primarily when combined with resistance training, is a viable lifestyle intervention to improve aging muscle mass, strength, and measures of functionality, which may decrease the risk of falls and fractures in older adults. The combination of creatine and resistance training has some beneficial effects on aging bone. However, these benefits disappear when no exercise intervention is used. Despite having some musculoskeletal benefits, the effects of creatine supplementation in individuals diagnosed with sarcopenia, osteoporosis, frailty, and cachexia are relatively unknown. Long-term, large-scale RCTs are needed to determine the efficacy of creatine supplementation, with and without resistance training, in these clinical populations.
Darren G. Candow, Philip D. Chilibeck, Scott C. Forbes, Ciaran M. Fairman, Bruno Gualano, Hamilton Roschel
ABSTRACT
Sarcopenia refers to the age-related reduction in strength, muscle mass, and functionality which increases the risk for falls, injuries, and fractures. Sarcopenia is associated with other age-related conditions such as osteoporosis, frailty, and cachexia. Identifying treatments to overcome sarcopenia and associated conditions is important from a global health perspective. There is evidence that creatine monohydrate supplementation, primarily when combined with resistance training, has favorable effects on indices of aging muscle and bone. These musculoskeletal benefits provide some rationale for creatine being a potential intervention for treating frailty and cachexia. The purposes of this narrative review are to update the collective body of research pertaining to the effects of creatine supplementation on indices of aging muscle and bone (including bone turnover markers) and present possible justification and rationale for its utilization in the treatment of frailty and cachexia in older adults.
1. Introduction
Sarcopenia, commonly defined as the age-related decrease in strength, muscle mass, and functionality, is associated with osteoporosis, frailty, and cachexia [1]. Furthermore, sarcopenia increases the risk of falls, injuries, fractures, and premature mortality [2]. The etiology and pathophysiology leading to sarcopenia are multifactorial and include alterations in skeletal muscle protein turnover and balance, endocrinological processes, neurophysiology, inflammation, vascularization, and mitochondrial function [3]. Sarcopenia occurs in 5–17 % of community-dwelling aging adults and 14–85 % of those residing in long-term care facilities [4]. With estimates that by the year 2050 there will be 1.5 billion adults ≥65 years of age [5], the prevalence of sarcopenia will continue to rise for the foreseeable future. Therefore, identifying treatments to overcome sarcopenia and associated age-related conditions is critically important from a global health perspective.
We have previously discussed and summarized the small body of research showing some favorable effects of creatine monohydrate supplementation on indices of aging muscle and bone (for reviews see [1,6,7]). Overall, creatine (primarily when combined with resistance training) has been shown to increase measures of muscle accretion, strength, and functionality [6–10]. Creatine has also been shown to increase bone area [11,12] and strength [13], attenuate the rate of bone mineral loss [13], and influence bone turnover by reducing the urinary excretion of cross-linked N-telopeptides (NTx) or C-telopeptides of type I collagen (CTx) in older adults [14]. Assessing bone turnover markers (i. e., NTx, CTx) is clinically relevant as they provide important information regarding the bone remodeling process and predict the risk of osteoporotic fracture in older adults [15]. Based on these musculoskeletal benefits, it is highly plausible that creatine may be an effective intervention to treat frailty (characterized by muscle weakness) and cachexia (characterized by rapid muscle wasting). However, research in these clinical areas is minimal.
The purposes of this narrative review are to (1) expand on our previous publications [1,6,7] and further update the collective body of research pertaining to the effects of creatine supplementation on indices.
2. Aging muscle
2.1. Creatine supplementation and resistance training
2.2. Creatine supplementation combined with other compounds and resistance training
2.3. Creatine supplementation without resistance training
3. Creatine supplementation on aging bone, falls, and fracture risk
Osteoporosis is characterized by the age-related reduction in bone mineral density and microarchitecture which can increase the risk of falls and subsequent fractures [39]. In this section, we review the effects of creatine supplementation on bone, falls, and fracture risk. We have reviewed evidence from cellular studies, animal models, and human interventions.
3.1. Cellular studies
3.2. Animal models
3.3. Human studies
4. Creatine supplementation and frailty
Frailty is overarchingly described as a condition of musculoskeletal weakness and reduced function. Though several definitions and screening criteria exist, frailty has generally been used to broadly define older adults impacted by weight loss, functional deficits, fatigue, cognitive impairment or mood disorders, comorbidities, and poor nutritional status [68]. Ultimately, frailty is considered to be a state of increased vulnerability (particularly to adverse health outcomes) that is associated with an increased risk of falls, disabilities, lack of independent living, and mortality [69,70]. Recognized as an aging condition, recent estimates suggest that approximately 1 in 6 community-dwelling older adults can be characterized as frail [71]. Others have identified the prevalence of frailty as up to ~59 % in older populations [72]. Consequently, the alarming incidence of frailty in older adults underscores the importance of maintaining and/or increasing muscle mass, strength, and physical function in individuals with frailty to preserve the health-related quality of life.
5. Creatine supplementation and Cachexia
Cachexia is used to define a complex, multifactorial, and often aggressive muscle-wasting condition, characterized by progressive weight loss (with or without fat loss), that cannot be reversed with conventional nutritional support [80,81]. Cachexia is strongly associated with a poorer prognosis, worsening of physical function and quality of life (QOL), and reduced survival in a variety of populations, such as cancer, chronic kidney disease, and heart failure [82–85]. Cachexia can arise due to a combination of factors, including systemic inflammation, reduced protein synthesis, and/or an increase in catabolism, along with malnutrition and physical inactivity [86–89].
6. Conclusions
The current body of research indicates that creatine monohydrate supplementation, primarily when combined with resistance training, is a viable lifestyle intervention to improve aging muscle mass, strength, and measures of functionality, which may decrease the risk of falls and fractures in older adults. The combination of creatine and resistance training has some beneficial effects on aging bone. However, these benefits disappear when no exercise intervention is used. Despite having some musculoskeletal benefits, the effects of creatine supplementation in individuals diagnosed with sarcopenia, osteoporosis, frailty, and cachexia are relatively unknown. Long-term, large-scale RCTs are needed to determine the efficacy of creatine supplementation, with and without resistance training, in these clinical populations.
