11/8/24 Inhibiting Myostatin To Promote Muscle Mass in Men
By Chris D. Meletis, N.D.
("Educational Only" - This article written for medical professional healthcare providers.)
With age, the sails of our sailboat become deflated unless we take a proactive approach to fight the statistical trends. This is never more true than with the loss of muscle mass. After age 30, people lose about 3% to 5% of their muscle mass each decade, with the most significant losses occurring in inactive people.1 At around age 60, muscle loss accelerates. After age 80, research indicates that 11% to 50% of people have sarcopenia,1 the significant loss of skeletal muscle mass, muscle strength, and function that occurs during advancing age.
Reduced skeletal muscle mass and function in adults are associated with chronic diseases, poor quality of life, physical disability, increased risk of fractures, and risk for frailty.2 Muscle loss becomes a vicious cycle since it promotes injury, contributing to a more sedentary phase of life, leading to more muscle loss.
Aging is the primary cause of muscle loss. However, it can also be caused by other factors. For example, the pharmaceutical GLP-1 weight loss protocols can lead to excess loss on metabolically active muscle (more on this later). Inactivity after surgery or injury also can result in muscle loss. In addition, certain diseases such as chronic obstructive pulmonary disease (COPD), muscular dystrophies, acquired immune deficiency syndrome (AIDS), immune disorders, and congestive heart failure can be accompanied by muscle atrophy.3
Men have more muscle mass in general compared with women, and males have a notably higher reference range for total red blood cell count, hemoglobin, and hematocrit to help perfuse this greater muscle mass. Although both males and females experience a steady decline of muscle mass with aging, men lose muscle mass at a faster rate than women,4, which may explain why one study found that sarcopenia prevalence in nursing homes was greater in men than in women (51% vs. 31%).5 For this reason, this article on reducing the loss of muscle mass is particularly relevant to males.
Standard Way to Build Muscle Mass
Protein consumption and resistance exercises are the two conventional non-pharmaceutical ways to increase or maintain skeletal muscle mass. This can be in combination with anabolic medications. This article proposes another way to build and maintain muscle mass: inhibiting myostatin through an all-natural molecule derived from fertilized chicken yolk. However, before we discuss that solution, let’s talk about anabolic resistance as a cause of muscle atrophy, why testosterone is vital in preserving muscle mass in men, why myostatin is involved in losing muscle mass, and what male patients can do about it.
Anabolic Resistance as a Driver of Muscle Atrophy
In younger patients, muscle protein synthesis is stimulated by the ingestion of protein and amino acids as well as exercise. However, with age, this response is blunted due to anabolic resistance.6 Obesity and leading a sedentary lifestyle can promote anabolic resistance due to insulin resistance and inflammation.6
Due to the decrease in response to protein ingestion with age, older men need more protein in order to trigger muscle protein synthesis compared with younger men.7 Resistance exercise is another means to stimulate muscle protein synthesis, although the response to exercise is less in older muscle.8
Testosterone’s Role in Muscle Mass Loss in Males
Testosterone is an anabolic hormone that plays a critical part in protein synthesis and regeneration of skeletal muscles. Beginning in the fourth decade of life, testosterone concentrations fall by 1% - 3% per year.9 In older men, reduced testosterone levels are linked to an increased risk of falls, lower muscle mass, and reduced physical performance.10,11 Exercise training has been shown to enhance free testosterone levels in sedentary aging men.12 Interestingly, increasing testosterone levels leads to a reduction in myostatin, indicating that the beneficial effects of raising testosterone in men are partly due to a simultaneous reduction in myostatin levels.13
Muscle Atrophy During Weight Loss
The GLP-1 receptor agonist medications (Ozempic® and Wegovy®, also known as semaglutide) have become wildly popular as a way to lose weight. These medications control appetite and glucose metabolism by mimicking the action of glucagon-like peptide-1 hormone. Their mechanism of action includes gastric emptying, suppressing appetite, and increasing insulin sensitivity. These actions lead to notable weight loss in obese patients or type 2 diabetes.
The drawback? Evidence suggests that accelerated loss of muscle mass occurs alongside fat loss in people taking GLP-1 agonists. The same can be said for those who have also undergone bariatric surgery.
In fact, there’s even an indication that a significant amount of the weight loss that occurs with these drugs arises disproportionately from the loss of lean tissue. This loss of muscle mass in people taking GLP-1 agonists was demonstrated in a study that showed these medications led to both fat and muscle loss during long-term treatment.14 A systematic review of the medical literature also found that semaglutide was associated with a reduction in muscle mass, particularly in trials with a larger number of participants.15
The mechanism by which GLP-1 agonists could reduce muscle mass is because by suppressing appetite and reducing food intake including critical micro and macronutrients, the body may start to not only break down fat for energy, but also muscle. Unless steps such as increased protein intake or resistance training are put into practice, less food intake could lead to more muscle and fat break down.
Myostatin’s Role in Muscle Breakdown and Synthesis
One of the biggest culprits behind muscle loss is myostatin, a component of skeletal muscle that serves as a negative regulator of muscle growth. Myostatin blocks the Akt/mammalian target of the rapamycin (mTOR) pathway, which leads to a reduction in protein synthesis.16 Myostatin has been studied for its suspected role in sarcopenia, while its inhibition is thought to have therapeutic benefit.
Writing in the journal Gerontology, researchers stated, “Myostatin inhibition provides a promising means to attenuate or reverse skeletal muscle loss in the context of sarcopenia as well as cachexia (disease-associated muscle loss), and to enhance skeletal muscle regeneration in the context of congenital disease (i.e., muscular dystrophies) and injury.”1
Aging is associated with an increase in myostatin levels. A study of younger, middle-aged, and older men and women found that serum myostatin levels increased with age.17 The study also found that higher skeletal muscle mass correlated with lower myostatin levels.
Rodents with a mutated or deleted myostatin gene demonstrate other beneficial effects of lower myostatin, such as a reduced risk of obesity, hepatic steatosis, atherogenesis, and macrophage infiltration/activation in skeletal muscle and adipose tissue.1 Mice with depleted levels of myostatin also had increased bone mineral density.1
Myostatin may also be why obesity is linked to poor skeletal muscle health.18 In patients who are obese and extremely obese, myostatin expression and secretion are increased in skeletal muscle and adipose tissue samples, and higher myostatin levels were associated with insulin resistance.19 Additionally, after weight loss in obese patients, myostatin expression in skeletal muscle is substantially lower and correlates with enhanced insulin action.20 The key during rapid weight loss is to maintain sufficient active mitochondrially rich lean muscle mass.
Inhibiting Myostatin to Preserve Muscle Mass
Due to anabolic resistance reducing the effect of strategies like protein supplementation and exercise, a complementary method is needed to build muscle mass in men. Some men also are reluctant to embark on testosterone replacement therapy. Furthermore, due to the risk of muscle mass loss during weight loss, patients on regimens to manage their weight need a way to preserve muscle mass.
A promising new strategy for counteracting muscle atrophy involves inhibiting myostatin through the use of a bioactive complex derived from a raw, fertile egg yolk powder (Fortetropin). Store-bought eggs are non-fertilized, which do offer certain benefits, hence the long history of use by athletes and body builders. However, cooking eggs will denature the bioactivity and reduce their efficacy. On the other hand, the eggs yolks in this bioactive complex are fertilized and pasteurized without being exposed to high heat, so the yolk remains uncooked throughout the process.
Supplementation with this fertile egg yolk complex increases lean body mass, reduces markers of protein breakdown consistent with inhibition of myostatin, and increases mTOR signaling, which is associated with muscle growth. These results were evident in human and animal studies.
One human study of 37 resistance-trained college-age males found a substantial increase in lean body mass in patients given Fortetropin compared with placebo.21 A more significant effect on lean body mass occurred in subjects given 19.8 grams compared with those given 6.6 grams. Both groups demonstrated pronounced increases in muscle thickness, and Fortetropin also lowered protein breakdown markers.
In another human study of 20 older subjects, scientists determined the effects of 21 days of Fortetropin supplementation on muscle protein synthesis.22 The randomized, placebo-controlled, double-blind trial showed no change in myostatin. Furthermore, there was an 18% higher rate of average muscle protein synthesis in the Fortetropin group than in the placebo group. The study suggests this fertile egg yolk-derived complex may manage age-related muscle loss (sarcopenia) in older adults. The lead researcher wrote, “Stimulating muscle protein synthesis in elderly patients could potentially result in increased muscle mass and better outcomes for those with sarcopenia.”
Another study investigated the effects of Fortetropin on 24 healthy young men who underwent single-leg immobilization for two weeks.23 The fertile egg yolk complex suppressed the rise in circulating myostatin that would have normally occurred in these subjects.
Dogs suffering from disuse muscle atrophy after undergoing tibial plateau leveling osteotomy (TPLO) surgery experienced no change in myostatin levels when given Fortetropin. By contrast, myostatin increased in dogs treated with a placebo over eight weeks.24 Dogs administered the fertile egg yolk complex also experienced no change in thigh circumference. On the other hand, over eight weeks, thigh circumference was reduced in dogs treated with a placebo.
Conclusion
Due to men’s greater prevalence of sarcopenia and the fact they lose muscle mass at a greater rate than women, it’s of critical importance to help male patients build their muscle mass as they age or during other risk factors for skeletal muscle mass loss, such as when taking GLP-1 receptor agonist medications. In addition to resistance exercise and protein supplementation, an emerging strategy to build muscle mass is by inhibiting myostatin with a bioactive complex derived from a raw, fertile egg yolk powder. This well-researched method can yield excellent results for our male patients and keep them healthy and active throughout life. There are comparable applications for female patients as well.
References
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(The information shared here is "Educational Only." These articles are written for medical professional healthcare providers. Always consult with your medical provider before taking any supplement. The content of the articles is not intended as diagnosis or treatment.)