madman
Super Moderator
Abstract
Purpose of Review
Decades of research on nutrition and exercise for athletes and bodybuilders have yielded various strategies to promote anabolism and improve muscle health and growth. We reviewed these interventions in the context of muscle loss in critically ill patients.
Recent Findings
For critically ill patients, ensuring optimum protein intake is important, potentially using a whey-containing source supplemented with vitamin D and leucine. Agents like hydroxyl β-methylbutyrate and creatine can be used to promote muscle synthesis. Polyunsaturated fatty acids stimulate muscle production as well as have anti-inflammatory properties that may be useful in critical illness. Adjuncts like oxandrolone promote anabolism. Resistance training has shown mixed results in the ICU setting but needs to be explored further with specific outcomes.
Summary
Critically ill patients suffer from severe proteolysis during hospitalization as well as persistent inflammation, immunosuppression, and catabolism syndrome after discharge. High protein supplementation, ergogenic aids, anti-inflammatories, and anabolic adjuncts have shown potential in alleviating muscle loss and should be used in intensive care units to optimize patient recovery.
Introduction
Managing nutrition in patients in the critical care setting is imperative to prevent catabolism and muscle loss associated with hospitalization. During hospitalization in the intensive care unit (ICU), patients suffer from acute severe proteolysis and muscle loss as well as disuse atrophy, with loss of nearly 20% of quadriceps femoris muscle mass within 10 days of ICU stay [1]. It is known that muscle loss is associated with a prolonged period of recovery and a decline in metabolic health [2]. ICU patients are also at risk for developing neuromuscular syndromes like critical illness polyneuropathy and myopathy (CIPNM), which is another component of ICU-acquired weakness [3, 4]. Post-hospitalization, patients can also suffer from persistent inflammation, immunosuppression, and catabolism syndrome (PICS), which refers to prolonged low-grade inflammation and catabolism with resultant loss of lean body mass [5••]. Inflammation-induced cachexia develops secondary to an inappropriate interplay between cytokines, neuropeptides, stress hormones, and intermediary substrate metabolism [6]. This is similar to “inflammaging”— chronic low-grade inflammation associated with aging that contributes to the development of sarcopenia [7]. Guidelines by multiple societies recommend that all patients staying for more than 24–48 h in the ICU should be considered at risk for malnutrition, and early enteral nutrition should be encouraged in these patients [8, 9••]. Adequate nutrition in critically ill patients requiring prolonged mechanical ventilation has been shown to improve survival time and physical recovery at 3 months post-hospitalization [10]. However, cachexia and muscle loss from PICS persist despite currently recommended intensive care unit (ICU) nutrition support. The inflammation-induced cachexia in PICS is analogous to that of patients with cancer, major burns, and sarcopenia and may benefit from similar interventions. High protein intake and anti-inflammatories along with anabolic interventions and nutritional rehabilitation are some measures that have been proposed to manage PICS [5••, 11, 12].
Ergogenic supplements are nutritional aids that improve exercise performance capacity or enhance training adaptations. These supplements have been long tested and trialed in athletes and bodybuilders, and retail sales for the same exceeded USD 5 billion in 2016, with a 6.7% growth in sales in 2018 [13]. Ergogenic aids are divided into supplements that improve muscle health and growth and performance enhancers. The International Society of Sports Nutrition (ISSN) has classified these into three categories based on the available evidence, those with strong evidence to support efficacy with apparent safety, limited or mixed evidence to support efficacy, and little to no evidence to support the efficacy and/or safety [14]. There are very few studies involving these supplements to benefit ICU patients to prevent catabolism [15]. We have reviewed ergogenic aids that improve muscle health which have been studied in athletes and bodybuilders and described their significance and possible utility in managing cachexia in the critical care setting.
*High Protein Intake
*Whey
*Branched-Chain Amino Acids (BCAA) Including Leucine
*Hydroxyl β-Methylbutyrate (HMB)
*Creatine
*Vitamin D
*Polyunsaturated Fatty Acids (PUFA)
Anabolic Steroids
Anabolic Steroids Anabolic steroids in supraphysiologic doses have been shown to increase body weight, fat-free mass, and muscle strength in healthy people [105] and hence have been used and abused by bodybuilders and athletes [106]. However, the obvious method to counteract catabolism generated in the ICU is the use of anabolic therapies. Several anabolic adjuncts have been studied, especially in patients with burns who are known to have hypercatabolic responses to injury. One of the most efficacious of these is oxandrolone, a synthetic steroid with enhanced anabolic activity and minimal androgenic activity. In murine models of severe burn injury, oxandrolone-treated animals demonstrate improved organ function, attenuated inflammatory response, and accelerated wound healing [107]. Oxandrolone has been widely studied in burn patients and has been shown to decrease catabolism and weight loss, improve MPS and wound healing, and decrease mortality and length of stay in this cohort both during and post-hospitalization [108–110••]. Long-term supplementation of oxandrolone leads to improved lean body mass, bone mineral content, and muscle strength in burn patients [111]. Other anabolic steroids have also been found to improve lean body mass and muscle strength in various cohorts including patients with HIV, chronic obstructive pulmonary disease patients, and patients on hemodialysis [112]. Oxandrolone is an oral supplement and generally well-tolerated, and although there are recommendations to monitor hepatic function during administration, rises in aminotransferases have been found to be transient [113, 114]. These factors certainly demonstrate the ease in administration. The timing of administration may be a little more controversial; however, initiating treatment after the initial inflammatory phase, in the so-called recovery phase of critical illness, may be most appropriate. This can be signaled by clinical improvement, absent need for organ support, and decreasing inflammatory markers. Small case series have used anabolic steroids with great success in patients with profound critical illness myopathy and weight loss who were already receiving appropriate nutritional support and physiotherapy [115]. Albeit controversial in the world of competitive sports, anabolic steroids may be one of the most promising therapies in post-ICU care.
*Resistance Training
*Phosphatidic Acid (PA)
*Arginine
*Adenosine-5′-Triphosphate (ATP)
Other Considerations
Several anabolic adjuncts are under study for patients with hypercatabolic states and cachexia. These include intensive insulin therapy, propranolol, testosterone, metformin, GLP1, and PPAR agonists. Intensive insulin therapy has been shown to be protective against ICU-acquired weakness, both from achieving euglycemia and insulin-mediated mRNA expression of glucose transporter-4 [145]. Propranolol reduces burn-induced proteolysis and increases muscle anabolism and thus can be used as an anabolic adjunct [146]. Testosterone acts as an anabolic stimulus to skeletal muscle as is evidenced by abuse by bodybuilders, and trials have used them in patients with burns to decrease catabolism with promising results [147]. By inducing adenosine monophosphate-activated protein kinase (AMPK), metformin has been shown to inhibit the production of reactive oxygen species and proinflammatory cytokines and may be protective in critical illness [148]. GLP-1 agonists are also being explored in the ICU, given that GLP-1 has positive actions on the myocardium and vasculature as well as improving glycemic control with a low risk of hypoglycemia [149]. Activation of PPAR-γ may attenuate proinflammatory cytokines and apoptosis and hence be used in catabolic states [150]. These therapies hold some promise in critical illness.
Conclusion
Survivors of critical illness are faced with severe muscle loss and catabolic processes, both during and after their stay in the ICU, which leaves them with a reduced quality of life posthospitalization. Several lessons can be learned from athletes and bodybuilders and extrapolated to improving muscle mass in critically ill patients. High protein intake, with a minimum goal of 2.0 g/kg/day, is key, using a whey-containing protein source early in the acute and immediate post-acute phases, and then adding HMB, creatine, or BCAAs with resistance training in early recovery might be an optimum solution. Anti-inflammatory agents like PUFAs may be used to reduce inflammation in the early phases through to the recovery phase. Other anabolic interventions like steroids may be used as adjuncts in the recovery phase. Many interventions like ATP, PA, PPAR agonists, or GLP-1 are yet in the earlier phases of research and not ready for widespread use in critically ill patients.
Athletes and bodybuilders are afforded the opportunity to focus on a singular issue—building muscle mass, strength, and function—and hence, results obtained in this cohort are dramatic. Intensivists have to manage multiple aspects of critical care (multiorgan failure, sepsis, metabolic derangements, etc.), and their attention and priorities become divided. Consequently, although important, nutrition and prevention of muscle loss too often are assigned a lower priority. This problem is inconclusive studies for many of the supplements and ergogenic aids in the ICU. Trials with these supplements have been designed with outcomes like ICU and hospital length of stay, mortality, and infection but not as part of an aggressive strategy to promote muscle mass and function. Other factors contributing to inconclusive results from these trials include patient heterogeneity and broad patient selection criteria, disparate timing of interventions, imprecise objective parameters and study endpoints, and evaluating complex interventions that are difficult to execute in an ICU setting. Whether aggressive nutritional support and the use of supplements is actually utilized may be more a function of the culture, leadership, and values of the ICU team of physicians, and how much priority they place on these issues. With more research yielding definitive results, and incorporation into guidelines and institutionalized protocols, the lessons learned from athletes and bodybuilders may be incorporated to improve outcomes for survivors of critical illness.
Purpose of Review
Decades of research on nutrition and exercise for athletes and bodybuilders have yielded various strategies to promote anabolism and improve muscle health and growth. We reviewed these interventions in the context of muscle loss in critically ill patients.
Recent Findings
For critically ill patients, ensuring optimum protein intake is important, potentially using a whey-containing source supplemented with vitamin D and leucine. Agents like hydroxyl β-methylbutyrate and creatine can be used to promote muscle synthesis. Polyunsaturated fatty acids stimulate muscle production as well as have anti-inflammatory properties that may be useful in critical illness. Adjuncts like oxandrolone promote anabolism. Resistance training has shown mixed results in the ICU setting but needs to be explored further with specific outcomes.
Summary
Critically ill patients suffer from severe proteolysis during hospitalization as well as persistent inflammation, immunosuppression, and catabolism syndrome after discharge. High protein supplementation, ergogenic aids, anti-inflammatories, and anabolic adjuncts have shown potential in alleviating muscle loss and should be used in intensive care units to optimize patient recovery.
Introduction
Managing nutrition in patients in the critical care setting is imperative to prevent catabolism and muscle loss associated with hospitalization. During hospitalization in the intensive care unit (ICU), patients suffer from acute severe proteolysis and muscle loss as well as disuse atrophy, with loss of nearly 20% of quadriceps femoris muscle mass within 10 days of ICU stay [1]. It is known that muscle loss is associated with a prolonged period of recovery and a decline in metabolic health [2]. ICU patients are also at risk for developing neuromuscular syndromes like critical illness polyneuropathy and myopathy (CIPNM), which is another component of ICU-acquired weakness [3, 4]. Post-hospitalization, patients can also suffer from persistent inflammation, immunosuppression, and catabolism syndrome (PICS), which refers to prolonged low-grade inflammation and catabolism with resultant loss of lean body mass [5••]. Inflammation-induced cachexia develops secondary to an inappropriate interplay between cytokines, neuropeptides, stress hormones, and intermediary substrate metabolism [6]. This is similar to “inflammaging”— chronic low-grade inflammation associated with aging that contributes to the development of sarcopenia [7]. Guidelines by multiple societies recommend that all patients staying for more than 24–48 h in the ICU should be considered at risk for malnutrition, and early enteral nutrition should be encouraged in these patients [8, 9••]. Adequate nutrition in critically ill patients requiring prolonged mechanical ventilation has been shown to improve survival time and physical recovery at 3 months post-hospitalization [10]. However, cachexia and muscle loss from PICS persist despite currently recommended intensive care unit (ICU) nutrition support. The inflammation-induced cachexia in PICS is analogous to that of patients with cancer, major burns, and sarcopenia and may benefit from similar interventions. High protein intake and anti-inflammatories along with anabolic interventions and nutritional rehabilitation are some measures that have been proposed to manage PICS [5••, 11, 12].
Ergogenic supplements are nutritional aids that improve exercise performance capacity or enhance training adaptations. These supplements have been long tested and trialed in athletes and bodybuilders, and retail sales for the same exceeded USD 5 billion in 2016, with a 6.7% growth in sales in 2018 [13]. Ergogenic aids are divided into supplements that improve muscle health and growth and performance enhancers. The International Society of Sports Nutrition (ISSN) has classified these into three categories based on the available evidence, those with strong evidence to support efficacy with apparent safety, limited or mixed evidence to support efficacy, and little to no evidence to support the efficacy and/or safety [14]. There are very few studies involving these supplements to benefit ICU patients to prevent catabolism [15]. We have reviewed ergogenic aids that improve muscle health which have been studied in athletes and bodybuilders and described their significance and possible utility in managing cachexia in the critical care setting.
*High Protein Intake
*Whey
*Branched-Chain Amino Acids (BCAA) Including Leucine
*Hydroxyl β-Methylbutyrate (HMB)
*Creatine
*Vitamin D
*Polyunsaturated Fatty Acids (PUFA)
Anabolic Steroids
Anabolic Steroids Anabolic steroids in supraphysiologic doses have been shown to increase body weight, fat-free mass, and muscle strength in healthy people [105] and hence have been used and abused by bodybuilders and athletes [106]. However, the obvious method to counteract catabolism generated in the ICU is the use of anabolic therapies. Several anabolic adjuncts have been studied, especially in patients with burns who are known to have hypercatabolic responses to injury. One of the most efficacious of these is oxandrolone, a synthetic steroid with enhanced anabolic activity and minimal androgenic activity. In murine models of severe burn injury, oxandrolone-treated animals demonstrate improved organ function, attenuated inflammatory response, and accelerated wound healing [107]. Oxandrolone has been widely studied in burn patients and has been shown to decrease catabolism and weight loss, improve MPS and wound healing, and decrease mortality and length of stay in this cohort both during and post-hospitalization [108–110••]. Long-term supplementation of oxandrolone leads to improved lean body mass, bone mineral content, and muscle strength in burn patients [111]. Other anabolic steroids have also been found to improve lean body mass and muscle strength in various cohorts including patients with HIV, chronic obstructive pulmonary disease patients, and patients on hemodialysis [112]. Oxandrolone is an oral supplement and generally well-tolerated, and although there are recommendations to monitor hepatic function during administration, rises in aminotransferases have been found to be transient [113, 114]. These factors certainly demonstrate the ease in administration. The timing of administration may be a little more controversial; however, initiating treatment after the initial inflammatory phase, in the so-called recovery phase of critical illness, may be most appropriate. This can be signaled by clinical improvement, absent need for organ support, and decreasing inflammatory markers. Small case series have used anabolic steroids with great success in patients with profound critical illness myopathy and weight loss who were already receiving appropriate nutritional support and physiotherapy [115]. Albeit controversial in the world of competitive sports, anabolic steroids may be one of the most promising therapies in post-ICU care.
*Resistance Training
*Phosphatidic Acid (PA)
*Arginine
*Adenosine-5′-Triphosphate (ATP)
Other Considerations
Several anabolic adjuncts are under study for patients with hypercatabolic states and cachexia. These include intensive insulin therapy, propranolol, testosterone, metformin, GLP1, and PPAR agonists. Intensive insulin therapy has been shown to be protective against ICU-acquired weakness, both from achieving euglycemia and insulin-mediated mRNA expression of glucose transporter-4 [145]. Propranolol reduces burn-induced proteolysis and increases muscle anabolism and thus can be used as an anabolic adjunct [146]. Testosterone acts as an anabolic stimulus to skeletal muscle as is evidenced by abuse by bodybuilders, and trials have used them in patients with burns to decrease catabolism with promising results [147]. By inducing adenosine monophosphate-activated protein kinase (AMPK), metformin has been shown to inhibit the production of reactive oxygen species and proinflammatory cytokines and may be protective in critical illness [148]. GLP-1 agonists are also being explored in the ICU, given that GLP-1 has positive actions on the myocardium and vasculature as well as improving glycemic control with a low risk of hypoglycemia [149]. Activation of PPAR-γ may attenuate proinflammatory cytokines and apoptosis and hence be used in catabolic states [150]. These therapies hold some promise in critical illness.
Conclusion
Survivors of critical illness are faced with severe muscle loss and catabolic processes, both during and after their stay in the ICU, which leaves them with a reduced quality of life posthospitalization. Several lessons can be learned from athletes and bodybuilders and extrapolated to improving muscle mass in critically ill patients. High protein intake, with a minimum goal of 2.0 g/kg/day, is key, using a whey-containing protein source early in the acute and immediate post-acute phases, and then adding HMB, creatine, or BCAAs with resistance training in early recovery might be an optimum solution. Anti-inflammatory agents like PUFAs may be used to reduce inflammation in the early phases through to the recovery phase. Other anabolic interventions like steroids may be used as adjuncts in the recovery phase. Many interventions like ATP, PA, PPAR agonists, or GLP-1 are yet in the earlier phases of research and not ready for widespread use in critically ill patients.
Athletes and bodybuilders are afforded the opportunity to focus on a singular issue—building muscle mass, strength, and function—and hence, results obtained in this cohort are dramatic. Intensivists have to manage multiple aspects of critical care (multiorgan failure, sepsis, metabolic derangements, etc.), and their attention and priorities become divided. Consequently, although important, nutrition and prevention of muscle loss too often are assigned a lower priority. This problem is inconclusive studies for many of the supplements and ergogenic aids in the ICU. Trials with these supplements have been designed with outcomes like ICU and hospital length of stay, mortality, and infection but not as part of an aggressive strategy to promote muscle mass and function. Other factors contributing to inconclusive results from these trials include patient heterogeneity and broad patient selection criteria, disparate timing of interventions, imprecise objective parameters and study endpoints, and evaluating complex interventions that are difficult to execute in an ICU setting. Whether aggressive nutritional support and the use of supplements is actually utilized may be more a function of the culture, leadership, and values of the ICU team of physicians, and how much priority they place on these issues. With more research yielding definitive results, and incorporation into guidelines and institutionalized protocols, the lessons learned from athletes and bodybuilders may be incorporated to improve outcomes for survivors of critical illness.
