Creatine supplementation for older adults: Focus on sarcopenia, osteop

Creatine supplementation for older adults: Focus on sarcopenia, osteoporosis, frailty and Cachexia

Highlights

The combination of creatine supplementation and resistance training increases lean mass and muscle strength in aging adults.•
Creatine supplementation decreases measures of bone catabolism which may help explain some of the preliminary increases in bone area and strength.•
Creatine supplementation poses no adverse effect on kidney or liver function.•
Creatine supplementation as the potential to be an effective intervention for treating frailty and cachexia.

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.

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 is multifactorial and includes 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 % in 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], [7], [8], [9], [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) are 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 of aging muscle and bone (including bone turnover markers) and (2) present possible justification and rationale for its utilization in the treatment of frailty and cachexia in older adults.

Section snippets

Creatine supplementation and resistance training

Resistance training is the most effective strategy to attenuate the age-related decrease in strength, muscle mass and function, warranting its ample recommendations to offset characteristics of sarcopenia [16]. Accumulating research over the past few decades shows that the addition of creatine supplementation to a resistance training program has some favorable effects on measures of muscle accretion and performance in older adults compared to resistance training alone (Table 1). However,..........

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...........

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 state of increased vulnerability (particularly to adverse health outcomes) that is associated.........

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 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], [83], [84], [85]. Cachexia............

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.......

CRediT authorship contribution statement

Conceptualization, D.G.C.; writing—original draft preparation: all authors; writing—review and editing: all authors. All authors have read and agreed to the revised version of the manuscript........

Declaration of competing interest

DGC, BG, and HR have conducted industry sponsored research involving creatine supplementation and received creatine donations for scientific studies and travel support for presentations involving creatine supplementation at scientific conferences. DGC serves as an expert witness/consultant in legal cases involving creatine supplementation. In addition, DGC and BG serve on the Scientific Advisory Board for Alzchem (a company that manufactures creatine). SCF has served as a scientific advisor for .......

References

A.J. Cruz-Jentoft et al. Sarcopenia Lancet (2019)

E. Dent et al. International clinical practice guidelines for sarcopenia (ICFSR): screening, diagnosis and management J. Nutr. Health Aging (2018)
M. Bemben et al. The effects of supplementation with creatine and protein on muscle strength following a traditional resistance training program in middle-aged and older men J. Nutr. Health Aging (2010)
K.A. Eliot et al. The effects of creatine and whey protein supplementation on body composition in men aged 48 to 72 years during resistance training J. Nutr. Health Aging (2008)
J. Chami et al. Effect of creatine supplementation dosing strategies on aging muscle performance J. Nutr. Health Aging (2019)
D.M. Lobo et al. Effects of long-term low-dose dietary creatine supplementation in older women Exp. Gerontol. (2015)
J. Ch’ng et al. Transcriptional and posttranscriptional mechanisms modulate creatine kinase expression during differentiation of osteoblastic cells J. Biol. Chem. (1994)
B. Gualano et al. Creatine supplementation and resistance training in vulnerable older women: a randomized double-blind placebo-controlled clinical trial Exp. Gerontol. (2014)
D. Candow et al. Effect of pre-exercise and post-exercise creatine supplementation on bone mineral content and density in healthy aging adults Exp. Gerontol. (2019)
H. Roschel et al. Supplement-based nutritional strategies to tackle frailty: a multifactorial, double-blind, randomized placebo-controlled trial Clin. Nutr. (2021)
A. Bender et al. Long-term creatine supplementation is safe in aged patients with Parkinson's disease Nutr. Res. (2008)
M. Huisingh-Scheetz et al. How should older adults with cancer be evaluated for frailty? J. Geriatr. Oncol. (2017)
J.E. Morley et al. A simple frailty questionnaire (FRAIL) predicts outcomes in middle-aged African Americans J. Nutr. Health Aging (2012)
C.K. Liu et al. Exercise as an intervention for frailty Clin. Geriatr. Med. (2011)
L.A. Riesberg et al. Beyond muscles: the untapped potential of creatine Int. Immunopharmacol. (2016)
J.E. Morley et al. Cachexia: pathophysiology and clinical relevance Am. J. Clin. Nutr. (2006)
K. Fearon et al. Definition and classification of cancer cachexia: an international consensus Lancet Oncology (2011)
D. Blum et al. Validation of the consensus-definition for cancer cachexia and evaluation of a classification model--a study based on data from an international multicentre project (EPCRC-CSA) Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. (2014)
A. Jatoi et al. A double-blind, placebo-controlled randomized trial of creatine for the cancer anorexia/weight loss syndrome (N02C4): an alliance trial Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. (2017)
K. Norman et al. Effects of creatine supplementation on nutritional status, muscle function and quality of life in patients with colorectal cancer–a double blind randomized controlled trial Clin. Nutr. (2006)
J.M.M. Antunes et al. Exercise training as therapy for cancer-induced cardiac cachexia Trends Mol. Med. (2018)
D.G. Candow et al. Current evidence and possible future applications of creatine supplementation for older adults Nutrients (2021)
L. Larsson et al. Sarcopenia: aging-related loss of muscle mass and function Physiol. Rev. (2019)
A. Okayama et al. Prevalence of sarcopenia and its association with quality of life, postural stability, and past incidence of falls in postmenopausal women with osteoporosis: a cross-sectional study Healthc. (Basel, Switzerland) (2022)
World Population Ageing 2020 Highlights
D.G. Candow et al. Effectiveness of creatine supplementation on aging muscle and bone: focus on falls prevention and inflammation J. Clin. Med. (2019)
P.D. Chilibeck et al. Effect of creatine supplementation during resistance training on lean tissue mass and muscular strength in older adults: a meta-analysis Open Access J. Sport. Med. (2017)
M. Devries et al. Creatine supplementation during resistance training in older adults-a meta-analysis Med. Sci. Sports Exerc. (2014)
S.C. Forbes et al. Meta-analysis Examining the Importance of Creatine Ingestion Strategies on Lean Tissue Mass and Strength in Older Adults (2021)
E.E.P. Dos Santos et al. Efficacy of creatine supplementation combined with resistance training on muscle strength and muscle mass in older females: a systematic review and meta-analysis Nutrients (2021)
D. Candow et al. Effect of 12 months of creatine supplementation and whole-body resistance training on measures of bone, muscle and strength in older males Nutr. Health (2021)
D.G. Candow et al. Efficacy of creatine supplementation and resistance training on area and density of bone and muscle in older adults Med. Sci. Sports Exerc. (2021)
P. Chilibeck et al. Effects of creatine and resistance training on bone health in postmenopausal women Med. Sci. Sports Exerc. (2015)
D.G. Candow et al. Low-dose creatine combined with protein during resistance training in older men Med. Sci. Sports Exerc. (2008)
S. Shetty et al. Bone turnover markers: emerging tool in the management of osteoporosis Indian J. Endocrinol. Metab. (2016)
D.G. Candow et al. Creatine supplementation and aging musculoskeletal health Endocrine (2014)
B. Gualano et al. Creatine supplementation in the aging population: effects on skeletal muscle, bone and brain Amino Acids (2016)
M.S. Fragala et al. Resistance training for older adults: position statement from the National Strength and conditioning association J. Strength Cond. Res. (2019)
T.A. Churchward-Venne et al. Supplementation of a suboptimal protein dose with leucine or essential amino acids: effects on myofibrillar protein synthesis at rest and following resistance exercise in men J. Physiol. (2012)
M.G. Villanueva et al. Periodized resistance training with and without supplementation improve body composition and performance in older men Eur. J. Appl. Physiol. (2014)
J. Collins et al. Resistance training and co-supplementation with creatine and protein in older subjects with frailty J. Frailty Aging. (2016)
C. Pinkoski et al. The effects of conjugated linoleic acid supplementation during resistance training Med. Sci. Sports Exerc. (2006)
M. Tarnopolsky et al. Creatine monohydrate and conjugated linoleic acid improve strength and body composition following resistance exercise in older adults PLoS One (2007)
L.A. Gotshalk et al. Creatine supplementation improves muscular performance in older women Eur. J. Appl. Physiol. (2007)
L. Gotshalk et al. Creatine supplementation improves muscular performance in older men Med. Sci. Sports Exerc. (2002)
J. Stout et al. Effects of creatine supplementation on the onset of neuromuscular fatigue threshold and muscle strength in elderly men and women (64 - 86 years) J. Nutr. Health Aging (2007)
E. Rawson et al. Effects of 30 days of creatine ingestion in older men Eur. J. Appl. Physiol. Occup. Physiol. (1999)
S. Cañete et al. Does creatine supplementation improve functional capacity in elderly women? J. Strength Cond. Res. (2006)
S. Forbes et al. Effects of creatine supplementation on properties of muscle, bone, and brain function in older adults: a narrative review J. Diet. Suppl. (2021)
R. Harris et al. Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation Clin. Sci. (1992)

December 31 2024 Mike Hutta

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