Friday, June 28, 2013

How "Anabolic Resistance" can Derail Your Fight Against Age-related Muscle and Bone Loss

A recent article by Bouillanne et al. in Clinical Nutrition explains why optimal protein intake can help limit muscle loss during aging and why this is vital for maintaining health.

"Aging per se is responsible for a gradual loss of skeletal muscle mass (40% from 20 to 80 years of age) and muscle function, termed sarcopenia.  Sarcopenia is a major cause of the increased prevalence of disability, falls, morbidity and mortality in elderly people.  Malnutrition greatly accelerates sarcopenia in elderly subjects, in whom it preferentially induces a loss of lean muscle mass, unlike younger, similarly malnourished patients, in whom a loss of fat mass is preferentially induced.  The prevalence of malnutrition in the elderly is between 30% and 78% on hospital admission.  It is the most common cause of decreased skeletal muscle mass and strength and secondary immune dysfunction."

Preventing sarcopenia is more complex than simply engaging in an exercise program and eating a healthy, protein rich diet. Although these two factors are vital to successfully limiting muscle loss, to ensure an anabolic response we must also make sure that our body can metabolically respond to exercise and nutritional intake. If we are laden with inflammatory mediators from chronic systemic inflammation (which I have talked about numerous times in past blogs), then our body will not be able to utilize/metabolize this muscle stimulus/nourishment for anabolic rebuilding of muscle and bone.

This inability to respond to anabolic input has been referred to as "anabolic resistance" by Dardevet et al. in an article published in The Scientific World Journal. Here, the authors talk about the "anabolic threshold concept".

"These signaling alterations lead to an 'anabolic resistance' of muscle even if the anabolic factor requirements (amino acids e.g.) are theoretically covered, that is, with a normal nutrient availability fitting the recommended dietary protein allowances in healthy subjects."

 "This anabolic resistance may be in part explained by an increase of the muscle 'anabolic threshold' required to promote maximal anabolism and protein retention.  Because the muscle 'anabolic threshold' is higher, the anabolic stimuli (including aminoacidemia) cannot reach anabolic threshold anymore and by consequence, muscle anabolism is reduced with the usual nutrient intake."

"A possible nutritional therapy is then to increase the intake of anabolic factors (especially amino acids) to reach the new 'anabolic threshold.'  There are several ways to increase amino acid availability to skeletal muscle: increase protein intake, to supplement the diet with one or several free amino acids or to select the protein source on its amino acid composition and physicochemical properties when digested in the digestive tract."

The authors further explain that the amino acid leucine is key for stimulating protein synthesis for muscle growth. But they also caution that simply adding leucine supplements to a daily nutrient regime probably won't help to increase muscle mass.

"Studies with a synchronized leucine signal and amino acid availability have been performed by using leucine rich proteins that are rapidly digested (whey proteins).  With such proteins, leucine availability is increased simultaneously with the other amino acids to reach the increased muscle anabolic threshold.  However, as observed for free leucine supplementation, when such dietary proteins were given on the long term in elderly rodents, muscle anabolism was acutely improved but muscle mass remained unchanged." 

"...a strategy to reverse the increase in the 'anabolic threshold' would restore the anabolic stimulation during the postprandial period with lower intake of dietary proteins or amino acid supplementation.  This requires the knowledge of the factors involved and responsible in the 'anabolic threshold' elevation.  The causes can be multiple and specific for each catabolic state.  However, most of these muscle loss situations have in common an increase of the inflammatory status.  Regarding aging, levels of inflammatory markers, such as interleukin-6 (IL6) and C reactive protein (CRP), increase slightly, and these higher levels are correlated with disability and mortality in humans.  Even if the increase is moderate, higher levels of cytokines and CRP increase the risk of muscle strength loss and are correlated with lower muscle mass in healthy older persons.  We have recently shown that the development of a low grade inflammation challenged negatively the anabolic effects of food intake on muscle protein metabolisms and that the pharmacologic prevention of this inflammatory state was able to preserve muscle mass in old rodents. A resensitization of muscle protein synthesis to amino acids could also be achieved with other nutrients such as antioxidants." 

The take home message from all of this is that if your body is inflamed--if it harbors chronic systemic inflammation--simply eating a "good" diet will not suffice. Muscle loss will continue as you age due to this increased anabolic threshold. The key to preventing muscle loss (which is directly connected to bone loss) is to ensure a diet that includes rich sources of quality protein with an emphasis on leucine intake, and address/eliminate factors that promote inflammation. I give lots of tips on how you can reduce inflammation and promote an anabolic body in my book The Whole-Body Approach to Osteoporosis. Check out Chapter 9 (starting on page 171), it's all about "How to Create an Anabolic Body."

Bouillanne O et al. Impact of protein pulse feeding on lean mass in malnourished and at-risk hospitalized elderly patients: A randomized controlled trial. Clin Nutr. 2013;32:186-92.

Dardevet D et al. Muscle wasting and resistance of muscle metabolism: The 'anabolic threshold concept' for adapted nutritional strategies during sarcopenia. The Scientific World Journal. 2012;2012(ID 269531).
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