Muscle toxicity, or toxic myopathy, occurs when ingested drugs, chemicals, or substances disrupt normal muscle cell structure and function. Muscles exhibit high metabolic activity and receive large blood volumes through their tissues, making them particularly vulnerable to toxins. The build-up of such toxins can lead to symptoms ranging from mild cramps to severe, life-threatening muscle breakdown. In this article, we will explore the various causes of muscle toxicity and its aftermath, including how personal trainers might recognize the condition before it causes irreparable damage to a client’s body.
Myopathies Differ Greatly From DOMS
If a client mentions to their trainer that, 2 days following their last session, they found themselves suffering from fatigue, soreness, and muscle weakness, the trainer might immediately think of delayed-onset muscle soreness, or DOMS. In most cases, this guess will prove accurate. However, when do those same symptoms signal a more serious condition?
The term myopathy encompasses a variety of diseases/conditions that affect skeletal muscle. These diseases tend to attack muscle fibers specifically, rendering them weak and often painful. Common symptoms of most myopathies include the following:
- Muscle cramps
- Muscle spasms
- Muscle weakness and/or stiffness
- General lack of energy
- Fatigue/shortness of breath upon exertion
Proximal muscles tend to get affected most often – those closest to the center of the body, such as hips, thighs, shoulders, and upper arms. As a result, some individuals find that over time they begin to struggle with activities of daily living: bathing, getting out of a chair, dressing, brushing/combing hair, and tasks requiring an overhead reach.
Inherited Myopathies
Some individuals inherit abnormal genes from one or both parents, leading to a myopathy evident at birth. Several different types of inherited myopathies have received attention in clinical settings and research:
- Congenital myopathies: often originating at birth or early in childhood, these may not elicit symptoms until an individual reaches their teenage years or early adulthood. Unlike most myopathies, congenital conditions tend to affect all muscles in one’s body, not just proximal muscles.
- Mitochondrial myopathies: caused by defects in the cells’ energy-producing mitochondria, these conditions cause not only muscle weakness but also a variety of other symptoms, as they usually affect the heart, GI tract, and brain. Diseases in this category that arise via gene mutations need not have any familial history.
- Metabolic myopathies: arising from aberrations in the genes coding for enzymes necessary to execute normal muscle function, these conditions appear most often as an intolerance to exercise, pain upon exertion (specifically in the quads and deltoids), and episodes of weakness. Rhabdomyolysis also falls into this category, and we will address this condition later in the article.
Acquired Myopathies
Medications can have a direct or indirect adverse effect on the muscle. Indirect toxic effects may result from the medication creating an electrolyte imbalance or inducing an immunological reaction. Symptoms of toxic acquired myopathies range from muscle pain to more serious muscle damage, again potentially leading to rhabdomyolysis. Although some categories of drugs tend to elicit specific forms of myopathies, a drug can sometimes cause more than one type of myopathy.
A variety of substances, including common pharmaceutical drugs as well as alcohol, can bring about adverse effects in muscle tissue. In recent years, much attention has focused on how cholesterol -lowering medications, particularly the statins, seem to cause myopathies.
We discuss 3 specific types of acquired myopathies: necrotizing, steroid-induced, and alcoholic.
Necrotizing: While many pharmaceutical agents can cause generalized necrotizing myopathy, cholesterol-lowering statins top the list. Other medications include the immunophilins (cyclosporine) and, rarely, the antihypertensive drugs labetalol and propofol. When an individual stops taking the prescribed statin, necrotizing myopathy typically ceases. However, statin drugs also seem capable of triggering autoimmune myopathies; these can progress even several months after discontinuing the medication. Physicians refer to this as statin-associated necrotizing autoimmune myopathy (SANAM).
In laboratory analysis, necrotizing myopathy resulting from statin use typically reveals elevated levels of creatine kinase (CK). In more severe cases, this can lead to myoglobin in the urine. Myoglobin, an oxygen-storing protein found in muscle tissue, is released into the bloodstream when muscle tissue is damaged, filtered by the kidneys, and excreted in the urine, often giving the urine a dark, tea- or cola-like color. In very severe cases, this can lead to renal failure.
Steroid-induced: Prolonged exposure to high doses of oral steroids poses the greatest risk of developing steroid myopathy. Steroid myopathy may occur after just a few weeks of treatment; proximal muscle weakness and atrophy affect the lower limbs to a greater extent than the upper body. Any synthetic glucocorticoid can cause myopathy, but the fluorinated varieties seem more likely to cause muscle weakness than the non-fluorinated compounds. Interestingly, women tend to face a higher risk than men (approximately 2:1) of developing a steroid myopathy.
Muscle biopsies in cases of steroid myopathy reveal atrophy of type 2 muscle fibers, specifically the fast-twitch, glycolytic type 2B fibers, with a lesser degree of atrophy in type 1 muscle fibers. The precise pathogenesis of corticosteroid myopathy is not well understood, but it may arise as a result of decreased protein synthesis, increased protein degradation, alterations in carbohydrate metabolism, and/or mitochondrial aberrations.
Alcoholic: While regular abuse of alcohol tends to cause neuropathy more often than true myopathy, several forms of toxic myopathy may also align with binge drinking, such as acute hypokalemic myopathy and alcoholic cardiomyopathy. Once again, laboratory analysis shows elevated CK levels, along with the aforementioned typical muscular symptoms. Renal failure has occurred in some individuals with severe cases of alcoholic myopathy. Low potassium levels may also occur, but they can usually resolve with appropriate potassium supplementation.
Rhabdomyolysis
This frightening condition leads to the disintegration of muscle tissue, causing muscle death. When this occurs, toxic components of muscle fibers enter the circulatory system as well as the kidneys, leading almost always to severe kidney damage/renal failure. Symptoms of rhabdomyolysis include the following:
- Muscle weakness
- Muscle stiffness
- Muscle pain
- Change in urine color from pale yellow to dark brown
This dangerous condition can result from extreme overexertion/high-intensity exercise, particularly if an individual plunges headlong into a vigorous exercise program too quickly. When muscles are chronically given insufficient time to heal between workouts, rhabdomyolysis can easily take hold of the body.
Injury or trauma to the body can also elicit this condition. A severe burn that covers a large amount of surface area, a severe injury, or even electrocution can cause muscle fibers to break down rapidly. Crushing injuries rank as the primary cause of trauma-induced rhabdomyolysis.
Coupled with overheating from extreme exercise, severe dehydration can also bring about rhabdomyolysis. Heat causes muscle tissue/fibers to break down more rapidly. In addition, the kidneys cannot properly dispose of the body’s waste materials in the absence of sufficient liquid.
Why Muscles?
As we have seen, skeletal muscles seem to bear the brunt of toxicity from drug use and alcohol abuse. In most adults, muscle mass accounts for close to 50% of body weight; as a result, muscles receive proportionately large drug doses. Muscle tissue boasts high metabolic activity and contains neurotransmitters, receptors, enzymes, and many other critical molecules for binding and interaction. By having different fiber compositions, muscles can be classified as fast-, slow-, and mixed-fiber; each type of muscle may respond differently to toxicants of various classes.
A New Culprit on the Playing Field
A previously unknown autoimmune muscle disease, presenting with sudden onset of debilitating muscle pain and weakness, was identified recently by researchers at the Washington University School of Medicine in St. Louis. The syndrome could easily be mistaken and therefore misdiagnosed as any one of many other muscle diseases that require different treatment, so these findings will help physicians treat patients appropriately.
“We observed only 4 patients in more than 20 years of research work, so it’s very rare,” said senior author Alan Pestronk, MD, a Professor of Neurology, Pathology and Immunology. “It has never been described before, and it seems to be treatable, so it will be helpful for physicians to be aware of it. People don’t need to be afraid this is going to happen to them, but in the extremely rare event that it does, physicians should now have the tools to respond.” Dr. Pestronk’s findings appeared in the April 6 issue of the journal Neurology.
Dr. Pestronk noticed something unusual while reviewing microscope slides of muscle tissue from a patient who presented with muscle pain and weakness: scavenger cells, which normally feed on dead material, were crowded around injured muscle fibers.
Over the next 22 years, he encountered 3 more patients hospitalized for muscle pain and weakness whose biopsies showed muscle breakdown coupled with scavenger cells. By carefully analyzing the biopsies, Pestronk and colleagues discovered that the patients’ own muscles had come under attack by immune scavenger cells known as histiocytes. They named the newfound syndrome large-histiocyte-related immune myopathy.
The disease also reflects a new way in which the immune system can damage muscle cells. Understanding how muscle fiber damage occurs through immune cells could lead to ways to prevent it. “There are several immune muscle diseases where the primary damage you see under the microscope is muscle fiber breakdown. Each of those diseases has a different prognosis and requires a different treatment,” Pestronk said. “Physicians need to recognize the immune nature of this condition in order to treat it appropriately.”
The Complication of Myositis
Myositis, an autoimmune disease characterized by inflammation of the muscles, can present in a variety of forms. Individuals dealing with lupus, scleroderma, or vasculitis may also suffer to some degree from muscle inflammation. In contrast to DOMS, myositis can affect the whole body, not only one or two muscle groups.
The muscle inflammation in myositis reflects a broader issue involving white blood cells of the immune system, the very cells which, under normal conditions, protect the body from infections. In individuals with myositis, however, these cells mistakenly attack their own healthy muscle fibers, injuring or even destroying them. This, in turn, has a powerful effect on total muscle function, leading to fatigue and weakness.
Blood Markers and Myositis Autoantibodies
Damaged muscle cells leak certain proteins into the bloodstream. Different parts of the body have different proteins; an infection/injury to a particular type of cell elicits a spike in the proteins of that cell.
Muscle proteins most commonly leaked into the blood, easily detected upon laboratory analysis, include the following:
- creatine kinase or creatine phosphokinase (CK or CPK)
- aldolase
- lactate dehydrogenase (LDH)
- myoglobin
Anything from muscle injury to vigorous exercise can cause a spike in the blood levels of these proteins. In most patients with myositis, elevated levels occur in cases where the disease has inadvertently spun out of control. Once the patient receives treatment, these levels soon return to baseline. However, some patients with severe disease present with normal or only slightly elevated blood markers; in such cases, a medical professional must make a diagnosis based on the totality of the person’s signs and symptoms.
The recent identification of markers for specific abnormal immune responses, called autoantibodies, is frequent in many, but not all, myositis patients. Some autoantibodies have clear clinical associations, such as an increased risk of lung disease, arthritis, or cancer, in which case they can help guide the use of additional testing to monitor patients. The tests have been used to identify subgroups of patients with distinct symptom profiles.
Including the Exercise and/or Physical Therapy Prescription for Myositis
It may seem counterintuitive when medical professionals or personal trainers recommend exercise to patients living with myositis, whose immune systems have already injured their muscles. However, recent research indicates that physical therapy can help maintain and improve muscle function in patients with myositis, without a significant risk of additional harm. Physical therapy plays a key role specifically in inclusion body myositis, since patients with this form of myositis do not generally respond to the same medications that work so well for other forms. Upon successful completion of a course of physical therapy, patients often reach out to personal trainers to continue their progress. Fitness professionals can continue to help these individuals on their exercise journeys as long as they understand and respect the clients’ potential limitations.
Muscles and Environmental/Dietary Toxins
Research has demonstrated that exposure to heavy metals, certain snake/insect venoms, and specific plant/mushroom toxins can directly damage muscle tissue. The good news? Our muscles do not store systemic toxins like heavy metals or environmental pollutants. Instead, those substances get processed by the liver and kidneys and tend to accumulate in fat tissue and bones.
However, muscles do temporarily trap metabolic waste products produced during daily cellular activity and intense exercise. The distinction between true toxins and metabolic waste reflects the manner in which the muscles function and interact with the body’s natural detoxification systems:
- Metabolic Waste: Working muscles generate byproducts such as lactic acid and urea. These can cause temporary soreness/stiffness if they accumulate in tight muscle knots.
- True Toxins: Environmental poisons, heavy metals, and chemicals do not get stored in muscle tissue.
The human body relies on highly specialized organs and systems to neutralize and remove waste. The liver and kidneys, as noted above, serve as the body’s ultimate filtration system, neutralizing true toxins and eliminating them through either bile or urine. The lymphatic system, a complex bio-highway of nodes and vessels, does an excellent job of collecting excess waste and fluids from the body’s tissues, filtering them and returning the cleaned fluids to the bloodstream. To that end, activities such as stretching and massage improve lymphatic circulation and blood flow. Deep-tissue massages, in particular, increase localized circulation, helping clear cellular waste and foster muscle recovery.
Much of what this article covers may transcend the usual scope of practice for most personal trainers. We can acknowledge the condition(s), but typically lack the training and specific medical knowledge to diagnose them. However, now that we have an understanding of what causes muscle maladies beyond simple DOMS, we can suggest that clients reach out to their physicians, outline their symptoms, and obtain a proper diagnosis and exercise prescription. From that point on, we truly can make a difference in these clients’ quality of life.
References
journals.physiology.org/doi/full/10.1152/physrev.00002.2019
hss.edu/health-library/conditions-and-treatments/list/myositis
medicine.washu.edu/news/newfound-autoimmune-syndrome-causes-muscle-pain-weakness/
sciencedirect.com/science/chapter/edited-volume/abs/pii/B9780124046306000178
my.clevelandclinic.org/health/diseases/21184-rhabdomyolysis
