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Steroids are commonly used to treat chronic conditions and muscular dystrophy. However, long-term use of steroids can lead to muscle wasting and weakness. A recent study conducted on mice revealed that weekly doses of steroids promote muscle repair and recovery from injury better than daily doses. The study found that weekly doses of steroids, such as prednisone, help to stimulate the production of annexins, proteins that aid in muscle healing. This suggests that the way steroids are administered can be modified to maximize their benefits and minimize their harmful side effects. While the study provides valuable insights, further research is needed to confirm the effects of weekly steroid doses on human muscle repair and recovery.
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What You'll Learn
Weekly steroids doses repair muscle damage
A 2017 study conducted by Northwestern University found that weekly doses of glucocorticoid steroids, such as prednisone, help speed recovery in muscle injuries and repair muscles damaged by muscular dystrophy. The study was conducted on mice, with broad implications for humans.
In the study, normal mice with a muscle injury received steroids just before injury and for two weeks after the injury. Mice receiving two weekly doses of steroids after the injury performed better on treadmill testing and had stronger muscles than mice receiving a placebo. Mice that received daily steroids for two weeks after the muscle injury performed poorly on the treadmill and in muscle strength studies, compared to placebo-treated mice.
The study also showed that prednisone directs the production of annexins, proteins that stimulate muscle healing. Giving weekly doses of prednisone also stimulated a molecule called KLF15, which is associated with improved muscle performance. Daily doses of prednisone, on the other hand, reduced KLF15, leading to muscle wasting.
Dr. Elizabeth McNally, the lead investigator of the study, said, "We don't have human data yet, but these findings strongly suggest some alternative ways of giving a very commonly used drug in a manner that doesn't harm but, in fact, helps muscle."
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Steroids help treat muscular dystrophy
Steroids are used to treat many different conditions, and in the case of muscular dystrophy, they can be beneficial. Muscular dystrophy (MD) is a group of inherited muscle disorders that cause progressive muscle degeneration without nerve abnormalities. Duchenne Muscular Dystrophy (DMD) is a specific type of MD that is treated with steroids, specifically corticosteroids. Corticosteroids are used to maintain muscle strength and slow down skeletal muscle damage caused by Duchenne. They can also help the heart and lungs and reduce the chance of scoliosis.
While steroids can be beneficial in treating DMD, they also come with side effects and risks. For example, adrenal suppression, or adrenal crisis, is a potentially life-threatening complication of steroid use. It can occur when the body is under extreme stress or when doses are missed. Long-term steroid use is also associated with adverse effects, which has led to the development of novel dissociative steroids, such as vamorolone, that may provide a better alternative with reduced side effects.
The timing of steroid treatment initiation is crucial in DMD. Steroids should be started before significant weakness occurs and before the "plateau phase," generally around ages 4-5. This early intervention helps to optimize upper body strength and function and support the heart and lungs. It is important to discuss the use of steroids with a neuromuscular specialist and carefully consider the different steroid options and regimens available.
Research has shown that weekly doses of steroids, rather than daily doses, promote muscle repair and strength. A study on mice with muscular dystrophy found that those receiving weekly doses of prednisone, a type of glucocorticoid steroid, were stronger and performed better on treadmill tests than those receiving a placebo or daily doses. The study also showed that prednisone directs the production of annexins, proteins that stimulate muscle healing, and increases the molecule KLF15, which is associated with improved muscle performance.
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Steroids direct the production of annexins
Steroids, specifically glucocorticoid steroids, have been found to direct the production of annexins, a family of proteins with calcium-regulated membrane binding capabilities. These proteins have a wide array of cellular activities, including acting as sensors and regulators of cellular and organismal stress, controlling inflammatory reactions in mammals, and responding to environmental stress in plants.
Annexin A1, also known as lipocortin I, is encoded by the ANXA1 gene in humans. It is a protein that belongs to the annexin family of Ca2+-dependent phospholipid-binding proteins. These proteins have a molecular weight of approximately 35,000 to 40,000 Daltons and are typically located on the cytosolic face of the plasma membrane.
Glucocorticoids, such as budesonide, cortisol, and beclomethasone, are a class of endogenous or synthetic anti-inflammatory steroid hormones that bind to the glucocorticoid receptor (GR). These receptors are present in almost every vertebrate animal cell. Glucocorticoids are used in medicine to treat diseases caused by an overactive immune system, including allergies, asthma, autoimmune diseases, and sepsis. They work by suppressing inflammatory pathways.
Annexin A1 has been found to play a critical role in mediating the anti-inflammatory actions of glucocorticoids. It was first identified in rat peritoneal macrophages as a potential mediator of the anti-inflammatory actions of these steroid hormones. Subsequent studies have confirmed that annexin A1 contributes to the regulation of various processes, including cell migration, cell growth, differentiation, apoptosis, vesicle fusion, lipid metabolism, and cytokine expression.
In addition to its role in inflammation, annexin A1 has been studied for its potential use as an anticancer drug. It has been shown to inhibit the NF-κB signal transduction pathway, which is often exploited by cancerous cells to proliferate and avoid apoptosis.
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Steroids stimulate the molecule KLF15
Steroids, such as glucocorticoid steroids, have been found to stimulate the molecule KLF15. This molecule is a protein that, in humans, is encoded by the KLF15 gene in the Krüppel-like factor family. The molecule is associated with improved muscle performance.
KLF15 is a transcriptional regulator of amino acid metabolism that is induced by glucocorticoids and fasting. It is one of several Kruppel-like, zinc finger transcription factors (KLFs) whose expression is directly induced by the glucocorticoid receptor (GR). KLF15 has been shown to exert transcriptional control over amino acid, lipid, and glucose metabolism and is also implicated in the induction of proatrophic targets in skeletal muscle in response to GCs.
The glucocorticoid receptor regulates adaptive transcriptional programs that alter metabolism in response to stress. KLF15 forms coherent and incoherent feed-forward circuits with GR that correlate with the expression dynamics of the glucocorticoid response. Coherent feed-forward gene regulation by GR and KLF15 is characterized by the combinatorial activation of linked GR-KLF15 regulatory elements by both factors and increased GR occupancy.
KLF15 levels in both humans and mice increase two to three times in response to exercise and control the ability of muscle tissue to burn fat and generate force. A deficiency of the KLF15 gene in mice was shown to prevent the efficient burning of fat and prevent mice from sustaining aerobic exercise.
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Steroids can cause muscle wasting
While steroids are commonly used to treat muscle injuries, they can also cause muscle wasting and other health complications. Steroid-induced myopathy is a condition that develops due to an excess of endogenous or exogenous corticosteroids in the body. Endogenous corticosteroid excess can arise from adrenal tumours, while exogenous corticosteroid excess is often a result of steroid treatments for asthma, chronic obstructive pulmonary disease, and inflammatory processes such as rheumatoid arthritis.
The use of steroids can lead to muscle wasting through catabolic and anti-anabolic mechanisms. Glucocorticoids, a type of steroid, have a direct catabolic effect on muscles, decreasing protein synthesis and increasing protein breakdown, leading to muscle atrophy. This was evident in a study where mice that received daily steroids for two weeks after a muscle injury performed poorly in treadmill and muscle strength studies compared to those given a placebo. The muscles of the mice that received daily steroids atrophied and wasted.
Additionally, steroids can cause acute and chronic steroid myopathy, which results in muscle weakness, especially in the proximal muscles of the upper and lower limbs and the neck flexors. This condition typically occurs with doses higher than 10 mg prednisone equivalents per day for four weeks or longer. Higher doses, such as 40 to 60 mg per day, can lead to more acute presentations of the condition. Steroid myopathy can cause severe muscle damage, including atrophy, lipid deposits, necrotic areas, and increased connective tissue between muscle fibres.
The risk factors for developing steroid-induced myopathy include older age, male gender, and obesity. Women, however, are twice as likely to develop muscle weakness from a given dose of steroids. Steroid-induced myopathy is usually reversible, and symptoms typically improve within 3 to 4 weeks of reducing or discontinuing steroid use. In some cases, switching to different types of steroids or altering the dosage may be necessary to manage the condition. Physical therapy, including resistance and aerobic exercises, is also effective in treating and preventing muscle wasting in patients with steroid-induced myopathy.
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Frequently asked questions
Yes, steroids do repair muscles. A study conducted on mice showed that weekly doses of steroids promote muscle repair and speedy recovery from muscle injuries.
Taking steroids on a weekly basis, as opposed to daily, promotes muscle repair. Mice that received steroids weekly showed stronger muscle performance on treadmill testing compared to those that received a placebo.
Daily doses of steroids, such as prednisone, can lead to muscle wasting and weakness. Long-term use of steroids is also associated with uncommon risks like clots, fracture, and sepsis.
Weekly doses of steroids stimulate the production of a molecule called KLF15, which is associated with improved muscle performance.
