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Musclechemistry Member
by Monica Mollica

For most people, the mere word “muscles” brings to mind huge muscular bodybuilders…

The importance of muscle mass, strength, and power for physical performance in exercise and sports is obvious.

However, muscles aren’t just for show. Here I will explain why….

Role of Muscle in the Body’s Metabolism

Muscle (or more precisely skeletal muscle) comprises around 45% and 35% of an average young man’s and woman’s body weight, respectively.[1] An adequate muscle mass is essential to ensure basic physiological functions such as movements, strength and respiration.[2] In order for us to survive, certain organs and tissues and, like the brain, heart, liver and skin, rely on a steady supply of amino acids via the blood to serve as precursors for the synthesis of new proteins to balance the continuous rate of protein breakdown that normally occurs as part of protein metabolism.

In the absence of nutrient intake (for example in between meals and during sleep) muscle protein serves as the principal reservoir to replace blood amino acid taken up by other tissues.[3-5] In the fasting state, blood amino acids serve not only as precursors for the synthesis of proteins but also as precursors for hepatic gluconeogenesis.[6] This is how the body is able to keep the protein mass of essential tissues and organs, as well as blood glucose levels, relatively constant despite intermittent food intake.

The primary fate of ingested amino acids is incorporation into muscle protein to replete the reserves of amino acids lost in the fasting state. Under typical conditions, gains in muscle protein mass in the fed state balance the loss of muscle protein mass in the fasted state. When combined with proper nutrition and resistance training, muscle protein gains will exceed muscle protein losses, which results in a net positive muscle protein balance. Over time, this leads to muscle growth.

Muscle, together with the liver, is also the main place for storage of glucose as glycogen after meals, and therefore plays an important role in glucose disposal and glucose metabolism.[7-13] In line with this, a lower muscle mass is associated with higher fasting and after-meal blood glucose levels, as well as elevated insulin levels.[14] Higher levels of glucose and/or insulin reflect some degree of insulin resistance. This suggests that the association of higher glucose and insulin levels with reduced muscle strength [15-17] is mediated, at least in part, by reduced muscle mass.

Muscle and Insulin Resistance – how do your muscles protect you?

A larger muscle mass is associated with better insulin sensitivity (less insulin resistance), lower levels of HbA1c (glycosylated hemoglobin, a marker of long-term blood glucose levels) as well as a reduced risk for both pre-diabetes and overt type-2 diabetes, in both men and women, old and young.[14, 18] It has been suggested that insulin resistance it what drives the association between elevated blood glucose levels (hyperglycemia) and cardiovascular disease risk; in other words, insulin resistance is largely responsible for the relationship between blood glucose levels and cardiovascular disease risk.[19]

And here comes the kicker; increases in muscle mass above average levels are associated with additional protection against insulin resistance and elevated blood glucose levels (i.e. pre-diabetes).[14] After adjusting for age, ethnicity, sex, and obesity and waist circumference, each 10% increase in muscle mass index (calculated as muscle mass divided by height squared) is associated with a 14% reduction in insulin resistance and a 23% reduction in prediabetes risk.[14] Needless to say, this only applies to increases in muscle mass that are achieved by resistance training and proper nutrition. Use of anabolic steroids causes insulin resistance despite marked increases in muscle mass.[20]

Muscle also protects against the metabolic syndrome; a greater muscle mass is associated with a lower prevalence of the metabolic syndrome [21], as well as a reduced risk of developing the metabolic syndrome in the future.[22] Notably, muscle mass and strength are strong protective factors against the metabolic syndrome, independent of insulin resistance and abdominal fat accumulation.[21]

Insulin Resistance – things you didn’t know

The protection conferred by muscle mass against development of insulin resistance and metabolic syndrome should be highlighted. Insulin resistance is very common in the general population. The prevalence of insulin resistance has been estimated to be as high as 88% in people with blood lipid (cholesterol, fat and lipoprotein) abnormalities, such as elevated trigycerides (blood fats) and low HDL (the “good” cholesterol).[23] This, coupled with the fact that the majority of U.S. adults are affected by some form of lipid abnormality [24], shows that insulin resistance is not a problem confined to diabetes, but a mass problem afflicting the large majority of people. It may come as a surprise to many that in people with elevated triglycerides (blood fats) and low HDL (the “good” cholesterol), insulin resistance is as common as in type 2 diabetics.[23]

It is also relatively unknown that in the general population, insulin resistance can be found even in the absence of any major metabolic disorders [23], and 25% of apparently healthy people are severely insulin resistant.[25] This can be detected by elevated fasting insulin and glucose levels, and/or after-meal blood sugar spikes above 140 mg/dL [26, 27], and may be an indicator of “silent” atherosclerosis.[28]

Among apparently healthy people, insulin-stimulated glucose uptake can vary threefold between the most insulin-sensitive and most insulin-resistant individuals.[27] Furthermore, the absolute amount of glucose uptake in the subjects who are the most insulin resistant is comparable with that of people with pre-diabetes (impaired glucose tolerance) and frank type 2 diabetes.[29]

Insulin resistance is a predictor of future aging-related diseases such as cardiovascular disease and diabetes [30-42], and causes impairments in physiological processes that contribute to premature aging.[43-46] For example, mechanistic experiments show that insulin resistance accelerates atherosclerosis.[47, 48] In apparently healthy people, 1 out of 3 who are insulin resistant at baseline develop either heart disease or diabetes 6 years later, while insulin sensitive people don’t.[30] Insulin resistance seems to be the common metabolic defect underlying both type 2 diabetes, dyslipidemia (abnormal amount of lipids [cholesterol and/or fat] and lipoproteins in the blood), cardiovascular disease (including high blood pressure) and obesity.[49, 50]

Insulin – a vascular hormone

In addition to mediating metabolic effects in muscle, liver and adipose tissue, insulin is a vascular hormone.[51-53] In physiological doses and in lean healthy insulin sensitive people, insulin is a vasodilator due to its stimulation of nitric oxide production.[53] However, insulin’s beneficial vascular actions are impaired in insulin-resistant conditions such as obesity, type 2 diabetes and high blood pressure, in whom it contributes to development of cardiovascular disease.[53] In people who are insulin resistant, insulin actually causes vasoconstriction.[53]

Insulin resistance – even in the absence of overt diabetes or the metabolic syndrome – reduces nitric oxide production [47, 53, 54] and causes endothelial (i.e. blood vessel) dysfunction [47, 48, 53-56], which in turn may cause erectile dysfunction.[57, 58] This is why erectile function can be seen as a “window” on cardiovascular health.[59] Thus, gaining muscle to prevent insulin resistance comes with both immediate and long-term benefits.

Negative effect of Insulin Resistance on Muscle – vicious circle

The relation between muscle and insulin resistance is bi-directional. As stated above, a low muscle mass increases the risk for developing insulin resistance and its consequences. However, insulin resistance – once developed – also negatively impacts muscle in several ways that speed up age-related muscle mass loss.[60, 61] For example, insulin resistance results in decreased stimulation of muscle protein synthesis to anabolic stimuli like protein intake and resistance exercise, and also increases muscle protein breakdown.[62-65]

This explains the finding that high fasting and after-meal levels of glucose and insulin independently are associated with muscle loss, even in individuals without diabetes.[16] This suggests that insulin resistance may be a risk factors for accelerated muscle loss.

It has also been demonstrated that insulin resistance is not only associated with impaired nitric oxide production but also with a reduced muscle capillarization, independently of age, body mass, adiposity, and resting energy metabolism.[66] This in turn impairs oxygen and nutrient delivery to muscle and reduces performance, as well as interferes with adaptations to any exercise program.

Role of Muscle in Chronic Disease

Both low muscle mass and poor muscle strength are highly prevalent and important risk factors for disability, morbidity and mortality in individuals as they age.[61] Chronic diseases related to poor lifestyle behaviors account for more than two-thirds of deaths in the United States [67], and detrimental alterations in muscle metabolism and loss of muscle mass (muscle wasting) play an important role in disease outcomes.[68] Heart disease and cancer are the major chronic diseases suffered in the Western world [67], and both cardiac failure and cancer are often associated with rapid and extensive loss of muscle mass and strength, and marked deterioration in metabolic function.[2, 69, 70] During critical illness, excessive loss of muscle mass caused by alterations in muscle metabolism [2] – for example an increased expression of muscle catabolic pathways and myostatin (which inhibits muscle growth) [71] – negatively impacts survival.

Another chronic condition – sarcopenia – is caused by muscle loss. Sarcopenia is the progressive age-related loss of muscle mass and function, and contributes to development of frailty.[72-75] Sarcopenia is a widespread syndrome that has a devastating effect on quality of life, activities of daily living, independence, and ultimately, survival.[72-75] A sub-optimal muscle mass isn’t just an issue for the elderly, it can also occur in younger people (in whom it is called myopenia) and has detrimental consequences regardless of age.[76]

Another chronic disease where muscle mass (and exercise) is of importance is osteoporosis. Mechanical force on bone is essential for increasing and maintaining bone strength and mass [77]. Whereas body weight and weight-bearing exercises provide a direct mechanical force on bones, the largest loads on bone originate from muscle contractions [77]. Correlations between grip strength and bone area, bone mineral content, and bone mineral density in both healthy athletes [78] and stroke patients [79] support the notion that muscle contractions play a significant role in bone strength and mass. In addition, the positive correlation between body weight and bone mass can be explained on the basis of the force exerted on bone by muscle contractions, in that it takes more force per unit area to move heavier bodies. Furthermore, changes in bone mass and muscle strength move in the same direction over the life span [77]. Although it is debatable whether it is muscle strength or simply muscle mass that is important in determining bone strength and bone mass, is has been shown that muscle mass correlates positively with bone mineral content and bone mineral density [80]. Thus, maintenance of adequate bone strength and density with aging is highly dependent on the maintenance of adequate muscle mass and function.

Resistance Exercise Training – building muscle is for everyone!

Exercise, both aerobic and resistance, dose-dependently increase insulin sensitivity.[81, 82] Resistance exercise in particular has been shown to reverse aging in human muscle tissue [83] and attenuates major hallmarks of aging.[84] Resistance exercise training effectively elicits muscle gains even in aging adults, but provides superior effectiveness if started early in life.[85]

Resistance exercise training is well documented to be beneficial in chronic diseases and conditions that are associated with a low muscle mass [2, 69, 70, 72, 74, 75]. Studies show that resistance exercise training may serve as an effective countermeasure to some of the adverse consequences of the metabolic syndrome, fibromyalgia and rheumatoid arthritis.[86] Evidence showing that resistance exercise reduces insulin resistance or improves insulin action comes both from indirect biomarkers, such as glycosylated haemoglobin (HbA1c), and insulin responses to oral glucose tolerance tests, as well as from more direct procedures such as hyperglycemic and hyperinsulinemic-euglycaemic clamp techniques.[86] it is notable that the improvement in insulin sensitivity and glucose tolerance with resistance exercise training is not a mere consequence of the increase in muscle mass associated but also likely a result of qualitative changes in resistance-trained muscle.[87]

There is also consistent evidence for the effectiveness of resistance exercise in reducing triglyceride levels.[86] Studies also show that cognitive function may improve with resistance exercise, and the prevalence of Alzheimer’s disease is inversely associated with muscle mass and strength, i.e. stronger people with a larger muscle mass tend to be less affected by Alzheimer’s.[86, 88] One study measured muscle strength in several muscle groups in the arms, legs and trunk, and summarized into a composite index of muscle strength, in apparently healthy older persons without dementia.[88] After a follow-up of 3.6 years is was found that each 1-unit increase in muscle strength at baseline was associated with a 43% decrease in the risk of Alzheimer’s, independently of physical activity, BMI, cardiovascular risk factors, heart disease and lung function.[88] Increased muscle strength was associated with a slower rate of decline in global cognitive function, as well as a decreased risk of mild cognitive impairment (the precursor to Alzheimer’s.[88]

Muscle also prevents body fat gain, and thus improves both physical/esthetic appearance as well as obesity associated risk factors. The role of muscle in fat gain prevention is a topic I will cover in more depth in an upcoming article.

Muscle and Longevity – is there a relation?

With all the beneficial health effects of an increased muscle mass, one may guess it beneficially impacts longevity. And rightly so. A larger muscle mass is associated with a greatly reduced mortality risk, independently of fat mass and cardiovascular and metabolic risk factors.[89-92] Greater muscle strength also reduces mortality risk.[93] Thus, anabolic metabolic pathways that promote muscle growth (which is correlated with muscle strength) seem to be associated with longevity.

Bottom Line

Now you have some legit and scientifically supported arguments to present when you encounter opposition to your passion for training, nutrition and muscle building.

The research presented here underscores the importance of muscle for health and longevity, and clearly shows that gaining muscle is not just about getting in shape and looking good. Muscle deserves getting more attention than it has been, and interventions to increase muscle mass – such as resistance training combined with proper nutrition – should be encouraged for everybody.

Simply put, muscles aren’t just for show!
 
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