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Muscling in on myopenia and myosteatosis

The relationship between body composition and risk of disease has become more clearly understood in recent years, as the technology available to non-invasively quantify components of body mass has improved. Image based approaches specifically and precisely quantify muscle and fat, while having the capacity to also reveal additional features such as excess inter- and intra-myocellular lipid accumulation within muscle tissue.  Low muscle mass (myopenia) and increased fat content of muscle (myosteatosis) are known to relate to disease risk and outcome.

Muscle mass and strength are critical components for maintaining physical function, mobility and vitality. Loss of muscle mass occurs during aging but is also a feature of many chronic diseases.  Individuals with severe muscle wasting may have difficulty performing daily tasks as well as disability, poor functional capacity and shorter survival contributing to high costs as a result of reduced quality of life, increased caregiver burden and health service utilization.  It has been revealed that low muscle mass is prevalent in every body size, not only in people who appear underweight, but also in those who are overweight or obese.

To quantify different tissues for body composition analysis using computed tomography imaging, a bony landmark is used to consistently measure the same region of the body across patients. The 3rd lumbar vertebrae is an established landmark in body composition analysis that correlates with amount of whole body muscle and fat. Each tissue attenuates radiation in a specific way which is recognized by a software program to enable skeletal muscles and different types of adipose tissues to be identified. Each tissue of interest is then color coded (see legend). When more than one CT image exists in the patient record, tissue changes over the trajectory of the disease can be determined. This image presents 2 scans taken approx 6 months apart at the same region within the same patient. The marked decline in muscle and adipose tissue is evident.
To quantify different tissues for body composition analysis using computed tomography imaging, a bony landmark is used to consistently measure the same region of the body across patients. The 3rd lumbar vertebrae is an established landmark in body composition analysis that correlates with amount of whole body muscle and fat. Each tissue attenuates radiation in a specific way which is recognized by a software program to enable skeletal muscles and different types of adipose tissues to be identified. Each tissue of interest is then color coded (see legend). When more than one CT image exists in the patient record, tissue changes over the trajectory of the disease can be determined. This image presents 2 scans taken approx 6 months apart at the same region within the same patient. The marked decline in muscle and adipose tissue is evident.

Muscle tissue normally contains only small amounts of fat not intended for long-term lipid storage, but rather as a short term energy source for skeletal muscle contraction.   Myosteatosis is characterized by excess deposition of fat in the form of triglycerides into muscle is considered to be a pathological phenomenon. The more fat a muscle contains, the less dense it becomes, and low density muscle is poor quality muscle.   Low muscle density has been described in conditions of aging, detraining, various types of muscle atrophy, insulin resistance, Type 2 diabetes and most recently, cancer.

 

Very little data exists to define the biological, biochemical and physiological features of human muscle that bears the features of myopenia and/or myosteatosis.  What is known reveals that poor prognosis and different types of morbidity are predicted by muscle loss and the presence of fat in muscle.   Resistance exercise appears to combat muscle loss that occurs with aging whereas aerobic exercise modifies the fat content of muscle.  Currently there are no drugs approved for muscle loss or myosteatosis.  Loss of muscle and low density muscle may share common pathways for development.  Many underlying factors contribute to muscle loss including catabolic humoral mediators (i.e. pro-inflammatory cytokines), anabolic failure (i.e. insulin insensitivity) and activation of proteolytic systems.   

This slide shows a CT image from a cancer patient who underwent 16 weeks of first line platinum doublet chemotherapy for lung cancer. Only the intramuscular adipose tissue is shown in color.
This slide shows a CT image from a cancer patient who underwent 16 weeks of first line platinum doublet chemotherapy for lung cancer. Only the intramuscular adipose tissue is shown in color.

 

One nutrient that is showing promise to modify the amount and quality of fatty muscle are the long chain n-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).  N-3 fatty acids are essential nutrients that can only be obtained from the diet from cold water fatty fish and their oils (as well as supplements).  N-3 fatty acids are found ubiquitously in cells and tissues throughout the body.  Several benefits to muscle mass and function have been attributed to EPA and DHA.  N-3 fatty acids are likely to affect more than one pathway, therefore, mechanisms may work collectively to improve muscle health by simultaneously targeting anabolic pathways, inhibiting catabolic pathways and improving energy utilization in a parallel and complimentary way.

My research is currently focussed on  understanding  the underlying pathology contributing to muscle loss and myosteatosis in people with cancer and further, how these pathologies can be modified  from a nutrition vantage point.  In cancer patients, both low muscle mass and muscle density are associated with poor outcomes and risk of death.  Very little is known about these features in the muscle of cancer patients.  Our research program relies on our capacity to collect human tissue during surgical procedures which can be subsequently analyzed  for histological and biological features.  Animal models, first verified for human relevance, are used to study mechanisms related to of n-3 fatty acids and other interventions that have a capacity to modify these pathologies.    

 

The ability to modify muscle wasting and intramuscular fat accumulation has a broad scope of application to aging, diabetes, obesity and various forms of muscle atrophy, which share these common features. While treatment for these conditions remains limited, a number of mechanisms may contribute to the ability of n-3 PUFA to alter body composition, however, a more complete understanding of the features of the muscle characterized by wasting and fat infiltration is required.

Relevant Published Papers

 

  1. Aubrey J, Esfandiari N, Baracos VE, Buteau FA, Frenette J, Putman CT, Mazurak VC.  Measurement of skeletal muscle radiation attenuation and basis of its biological variation.  Acta Physiol (Oxf). 2014 Mar;210(3):489-97. doi: 10.1111/apha.12224
  2. Esfandiari N, Ghosh S, Prado CM, Martin L, Mazurak V, Baracos VE. Age, obesity, sarcopenia, and proximity to death explain reduced mean attenuation in patients with advanced cancer.  J Frailty Aging, 2014 (in press).
  3. Ewaschuk JB, Almasud A, Mazurak VC. Role of n-3 fatty acids in muscle loss and myosteatosis. Appl Physiol Nutr Metab. Lipids.  48:319-32. 2014. doi: 10.1007/s11745-013-3774-6
  4. Murphy RA, Mourtzakis M, Mazurak VC:  n-3 polyunsaturated fatty acids: the potential role for supplementation in cancer.  Current Opinion Clinical Nutrition Metabolic Care. 15:  246-51, 2012. 
  5. Murphy RA, Yeung E, Mazurak VC and Mourtzakis M:  Influence of eicosapentaenoic acid supplementation on lean body mass in cancer cachexia.  British Journal of Cancer 105:  1469-73, 2011
  6. Murphy RA, Mourtzakis M, Reiman T and Chu Q, Mazurak VC:  Nutritional intervention with fish oil provides a benefit over standard of care on weight, and skeletal muscle mass in non-small cell lung cancer patients receiving chemotherapy.  Cancer. 117:1775-82, 2011
  7. Murphy RA, Mourtzakis M, Chu QS, Reiman T, Mazurak VC:  Skeletal muscle depletion is associated with reduced plasma n-3 fatty acids in non-small cell lung cancer patients.  Journal of Nutrition 140:1602-6, 2010