Alcoholic myopathy …

Douglas J Lanska MD MS MSPH

Neurotoxicology

Updated 04.29.2024
Released 07.20.1994
Expires For CME 04.29.2027

Alcoholic myopathy

Author: Douglas J Lanska MD MS MSPH

See Contributor Disclosures

Alcoholic myopathy

In This Article

Quick Link

Introduction

Overview

Alcohol can produce several myopathic disorders, including acute alcoholic myopathy with or without myoglobinuria, hypokalemic myopathy, chronic atrophic myopathy, and cardiomyopathy (127; 101; 176; 83; 90). Acute alcoholic myopathy (also termed alcoholic rhabdomyolysis and acute alcoholic necrotizing myopathy) is an uncommon syndrome of abrupt muscle injury that typically occurs in malnourished chronic alcoholics following a binge or in the first days of alcohol withdrawal; experimental studies have demonstrated that both alcohol and nutritional factors are necessary to produce this syndrome (16; 83; 90). Severity ranges from asymptomatic transient elevation of creatine kinase to frank rhabdomyolysis with myoglobinuria. Although, in most instances, full recovery occurs within days to weeks, death may occur in the setting of acute renal failure and hyperkalemia. Chronic alcoholic myopathy is a gradually evolving syndrome of proximal weakness, atrophy, and gait disturbance that frequently complicates years of alcohol abuse. Muscle strength correlates with lifetime consumption of ethanol. Recovery occurs if alcohol is avoided, but the timeframe of improvement is weeks to months, in contrast to the rapid recovery typical of acute alcoholic myopathy. Pathogenic mechanisms include impaired gene expression and protein synthesis as well as increased oxidative damage and apoptosis.

Key points

	• Acute alcoholic myopathy develops suddenly in the context of binge drinking and is characterized by painful muscle weakness and myonecrosis.
	• Chronic alcoholic myopathy develops gradually and is characterized by painless weakness of proximal muscles.
	• Recovery occurs if alcohol is avoided, but the time to recovery varies from rapid (days to weeks) with the acute form to protracted (weeks to months) with the chronic form.

Historical note and terminology

In 1822, American physician James Jackson (1777-1867) concluded that neuropathic lesions could not explain all of the signs in alcoholics and suggested that their muscles were also abnormal (65). Nevertheless, identification of muscular weakness as a complication of alcohol abuse is generally attributed to Swedish physician Magnus Huss (1807-1890) in his treatise Alcoholismus Chronicus published in 1849 (36). Subsequent 19th century reports of "alcoholic paralysis" include instances of reversible weakness that likely represent alcoholic muscle disease (35; 62). Several pathologic reports appeared in the late 19th century, particularly in Germany (120).

James Jackson, American physician (1777-1867)

Courtesy of the U.S. National Library of Medicine. Public domain.
Magnus Huss (1807-1890)

Swedish physician Magnus Huss (1807-1890). (Courtesy of Wikimedia Commons. Public domain.)

Modern recognition of the link between alcohol abuse and myopathy and the differentiation of acute and chronic alcoholic muscle disorders dates to the 1950s and 1960s, particularly by Swedish investigators Ragnar Hed and Karl Ekbom (59; 60; 43; 36). These investigators described two major syndromes: (1) acute alcoholic myopathy in which myonecrosis develops suddenly in the context of binge drinking; and (2) chronic alcoholic myopathy, in which weakness of proximal muscles develops gradually. In addition, alcoholic individuals without muscle-related symptoms were found to have electromyographic and histologic evidence of myopathy (36). In the late 1960s American internist George Thomas Perkoff (1926-2012) and colleagues at Washington University School of Medicine in St. Louis described individuals with chronic alcohol abuse who developed an acute reversible muscular syndrome with dramatic muscle cramps, tender muscles, weakness, variable myoglobinuria, increased creatine kinase blood levels, and a reduced ability to increase serum lactic acid levels in response to ischemic exercise (129; 128). Subsequent studies have linked alcoholic myopathy directly to the injurious effects of ethanol and acetaldehyde (164). The molecular basis of the myopathic effects of alcohol has remained elusive.

Clinical manifestations

Presentation and course

	• Acute alcoholic myopathy (ie, alcoholic rhabdomyolysis and acute necrotizing myopathy) is a syndrome of abrupt muscle injury that typically occurs in malnourished chronic alcoholics following a binge or in the first days of alcohol withdrawal.
	• Hypokalemic alcoholic myopathy develops as a consequence of alcohol-associated loss of potassium from the bowel, which, after several days, produces a vacuolar myopathy associated with myalgia, weakness, and, occasionally, myoglobinuria.
	• Hypokalemic alcoholic myopathy resolves with potassium replacement, cessation of alcohol intake, and resumption of a normal diet.
	• Individuals with chronic alcohol abuse may develop an acute reversible muscular syndrome with dramatic muscle cramps, tender muscles, weakness, variable myoglobinuria, increased creatine kinase blood levels, and a reduced ability to increase serum lactic acid levels in response to ischemic exercise.
	• Chronic alcoholic myopathy is a gradually evolving syndrome of proximal weakness and atrophy that complicates years of alcohol abuse (ie, 100 g to 400 g of ethanol per day for more than 3 years).
	• Alcoholic cardiomyopathy (“alcoholic heart muscle disease”) is a specific disease of heart muscle that occurs in individuals with a history of chronic heavy alcohol ingestion and in the absence of significant coronary artery disease or other cardiac conditions (eg, myocarditis).
	• Alcoholics are prone to develop thiamine deficiency, which itself may produce beriberi cardiomyopathy and in its fulminant form with hemodynamic deterioration is known as Shöshin beriberi.

Acute alcoholic myopathy. Acute alcoholic myopathy (also termed alcoholic rhabdomyolysis and acute necrotizing myopathy) is a syndrome of abrupt muscle injury that typically occurs in malnourished chronic alcoholics following a binge or in the first days of alcohol withdrawal (59; 43; 174; 129; 127; 120; 90; 09; 124; 161; 81). Experimental studies have demonstrated that both alcohol and nutritional factors are necessary to produce this syndrome (16; 83; 90). Severity ranges from asymptomatic transient elevation of creatine kinase to frank rhabdomyolysis with myoglobinuria (119; 175). The clinical presentation is characterized by muscle pain, tenderness, swelling, and proximal or generalized weakness that develop abruptly in association with pigmenturia and a rapid rise in "muscle" enzymes in serum but with preserved reflexes (assuming that they are not otherwise lost due to a peripheral neuropathy) (60; 127). The initial symptoms are often noted on awakening from an alcoholic stupor (43; 60; 129). Acute alcoholic myopathy is a monophasic illness that typically advances over hours to a few days and then recedes over the succeeding week if the affected individual abstains from alcohol (111; 127). Muscle symptoms are often generalized, but focal pain and swelling involving individual muscle groups may predominate. Selective involvement of the calves, mimicking thrombophlebitis, is common (128; 133). Acute alcoholic myopathy is often accompanied by manifestations of alcohol withdrawal ranging from tremulousness to delirium tremens (111), although muscle pain and weakness usually precede the onset of withdrawal symptoms. Coexisting cardiac injury compatible with alcoholic cardiomyopathy may occur (40; 133; 155). Full recovery usually occurs within days to weeks, but death may occur in the setting of acute renal failure and electrolyte disturbances (eg, hyperkalemia) (09; 124; 161).

The major laboratory features of acute alcoholic myopathy are pigmenturia and elevation of muscle enzymes. Serum creatine kinase increases in the first 3 days and then declines to the normal range, usually within 7 to 10 days (111). Muscle biopsy shows scattered muscle-fiber necrosis and regeneration (60; 34; 78; 69; 127; 104). Type I (high oxidative, low glycolytic, slow twitch) muscle fibers are selectively susceptible to injury in acute alcoholic myopathy (104; 53). In autopsied cases, rhabdomyolysis is typically widespread, involving pharyngeal, sternocleidomastoid, pectoral, and diaphragm muscles in addition to limb muscles (59; 69).

Hypokalemic alcoholic myopathy. Alcohol abuse may produce severe hypokalemia due to loss of potassium from the bowel. After several days, severe hypokalemia can produce a vacuolar myopathy associated with myalgia, weakness, and occasionally myoglobinuria (90). Hypokalemic alcoholic myopathy resolves with potassium replacement, cessation of alcohol intake, and resumption of a normal diet (109). Hypokalemic alcoholic vacuolar myopathy and acute necrotizing myopathy can be superimposed, but hypokalemia is not necessary for the development of acute necrotizing myopathy (83).

Alcoholism is one of the most common causes of secondary hypokalemic myopathy, with other common causes being diarrhea and an unbalanced diet (61). Limb weakness may be asymmetric or may involve predominantly the upper limbs (61). About half of such patients develop decreased potassium levels after hospital admission, despite potassium replacement treatment (rebound hypokalemia; two thirds may develop increased CK levels even after 2 to 5 days (delayed hyperCKemia) (61). Rebound hypokalemia is associated with low serum magnesium levels (61). Because rebound hypokalemia and delayed hyperCKemia are common in alcoholic hypokalemic myopathy, despite potassium replacement, careful serial monitoring is needed.

Reversible acute alcoholic muscular syndrome with muscle cramps. Individuals with chronic alcohol abuse may develop an acute reversible muscular syndrome with dramatic muscle cramps, tender muscles, weakness, variable myoglobinuria, increased creatine kinase blood levels, and a reduced ability to increase serum lactic acid levels in response to ischemic exercise (129; 128). Similarities were initially noted between this presentation and the clinical features of hereditary phosphorylase deficiency (McArdle disease), but phosphorylase levels were variable and sometimes entirely normal despite severely depressed lactic acid response to ischemic exercise (129; 128). Affected individuals recover within 2 to 4 weeks if they remain abstinent (129; 128).

Chronic alcoholic myopathy. Chronic alcoholic myopathy is a gradually evolving syndrome of proximal weakness and atrophy that complicates years of alcohol abuse (ie, 100 g to 400 g of ethanol per day for more than 3 years) (36; 128; 120; 90). Muscle strength correlates with lifetime consumption of ethanol (116). Painless weakness and atrophy, affecting predominantly the hip and shoulder girdles, with associated myopathic gait, develops insidiously over weeks or months (101; 109; 172; 90; 161). Muscle atrophy may be striking. Alcoholic peripheral neuropathy is associated in most cases (72% in one study) (101); other complications of alcohol abuse or nutritional deficiency such as confusional states and hepatic cirrhosis may also be present (128). Recovery occurs if alcohol is avoided, but the time frame of improvement is weeks to months, usually on the order of 6 months or more, in contrast to the rapid recovery typical of acute alcoholic myopathy (100; 130). Recovery occurs even without improvement in nutritional status and without clinical recovery from any coexisting neuropathy (100; 130; 90).

Serum creatine kinase levels are often within normal limits and muscle biopsy generally does not reveal muscle-fiber necrosis. The dominant histologic finding is muscle atrophy (36; 78), which affects predominantly type II, especially type IIb (high glycolytic, low oxidative, fast twitch) muscle fibers (74; 101). Despite the frequent coincidence, the muscle atrophy in alcoholic myopathy is independent of neuropathic lesions (134). Electromyography may show myopathic potentials (36), neuropathic features (89), or both (128). Alcoholic type II atrophy is reversible with many months of abstinence from alcohol (101).

In some cases, acute muscle injury, manifested by muscle tenderness and creatine kinase elevation, may be superimposed on chronic alcoholic myopathy (128; 147; 155). Typically, these episodes are related to a period of particularly heavy ethanol abuse (172).

Asymptomatic alcoholic myopathy. Asymptomatic forms of both acute and chronic alcoholic myopathy occur. A transient elevation in creatine kinase, compatible with acute muscle injury, accompanies heavy drinking in a substantial percentage (20% to 50%) of alcoholic individuals (119; 175; 111; 57), the majority of whom do not have overt muscle symptoms. Similarly, histologic features of type II muscle-fiber atrophy, compatible with chronic alcoholic myopathy, were present in approximately 60% of individuals who had consumed an average of 190 g of alcohol daily for an average of 11 years (101). Most of these patients had few, if any, overt muscle symptoms.

Alcoholic cardiomyopathy. Alcoholic cardiomyopathy (“alcoholic heart muscle disease”) is a specific disease of heart muscle that occurs in individuals with a history of chronic heavy alcohol ingestion and in the absence of significant coronary artery disease or other cardiac conditions (eg, myocarditis) (131). Presenting symptoms can include development of an often abrupt, unexplained cough or shortness of breath, fatigue, and weakness, followed by swelling of the legs and abdomen (05). Presenting signs may include jugular venous distention, tachypnea, few if any rales, persistent tachycardia, cold and cyanotic extremities, cardiomegaly, a diastolic gallop, an apical systolic murmur, a mildly enlarged and tender liver (due to cardiac congestion rather than cirrhosis), and evidence of neuropathy (eg, stocking-distribution hypesthesia and hyporeflexia in the legs) (05; 157).

Echocardiographic features of alcoholic cardiomyopathy include left ventricle dilation, normal or reduced left ventricular wall thickness, increased left ventricular mass, and ultimately a reduced left ventricular ejection fraction (< 40%) (131). Alcohol consumption is also a predictor of left atrial enlargement and subsequent incident atrial fibrillation (106). Because there are no pathognomonic markers the diagnosis of alcoholic cardiomyopathy is generally presumptive and is often considered as a diagnosis of exclusion (131).

Although the precise amount and duration of alcohol consumption that is necessary to cause alcoholic cardiomyopathy remain poorly defined, (1) consuming 90 g to 120 g/day of ethanol (approximately 7-15 standard drinks per day) over a 5- to 15-year period is sufficient to produce changes in cardiac structure and function; (2) consuming at least 90 g/day of ethanol on at least 4 days/week over a 5 to 9 year period is associated with left ventricular dilation, and over a 10- to 15-year period is associated with development of diastolic dysfunction and left ventricular enlargement (91; 131).

Beriberi cardiomyopathy (Shöshin beriberi). Alcoholics are prone to develop thiamine deficiency, which itself may produce beriberi cardiomyopathy and in its fulminant form with hemodynamic deterioration is known as Shöshin beriberi (42; 39; 28; 85; 67; 93; 20; 52; 66; 105; 77; 73; 155; 10; 47; 70; 18; 152; 156; 25; 37; 126; 123; 108; 112; 179; 113; 33; 14; 166; 160; 163; 27; 01; 71; 72; 82; 169; 26; 30; 183; 17; 96; 154; 21; 75; 84; 29; 63). Common clinical features include metabolic (lactic) acidosis (typically without hypoxemia), peripheral edema, low peripheral vascular resistance, increased central venous pressure, cardiomegally, T-wave abnormalities, a hyperkinetic (high output) circulatory state (except in Shoshin beriberi, which may be associated with low cardiac output), and increased circulating blood volume (70; 113; 156; 166; 163; 71; 72; 82; 183; 96; 84; 63). It may also be accompanied by signs of Wernicke encephalopathy (30). Improvement is often rapidly achieved following thiamine administration, improved nutrition, and rest (66; 70; 26; 75). Untreated cardiovascular beriberi has a high case fatality (33).

Table 1. Acute and Chronic Alcoholic Myopathy: Clinical and Laboratory Features

	Acute	Chronic
Symptoms and signs	Muscle pain, swelling; weakness may be present	Muscle atrophy; painless, mainly proximal weakness
Evolution	Rapid (hours to few days)	Slower (weeks, months)
Creatine kinase	Elevated	Often normal
Myoglobinuria	Yes	No
EMG	May be normal	Myopathic or denervation potentials
Muscle biopsy	Scattered fiber necrosis; type I fiber susceptibility	Type II fiber atrophy; denervation may be present
Recovery	Rapid (days)	Slower (weeks, months)
Pattern of drinking	Binge	Years of daily alcohol abuse
Affected population	Less than or equal to 4:1 male predominance	More equal sex distribution
Associated disorders	Alcohol withdrawal; seizures; delirium tremens	Peripheral neuropathy
Asymptomatic variety	Binge-related transient elevation in creatine kinase without frank muscle symptoms	Type II muscle fiber atrophy without frank weakness

Prognosis and complications

Acute alcoholic myopathy. Massive muscle injury triggered by acute alcohol abuse may result in multiple organ failure and death. However, alcoholic rhabdomyolysis generally has a good prognosis if renal failure is avoided or is aggressively treated (09). Muscle can regenerate remarkably, and most patients with alcoholic rhabdomyolysis recover full muscle function. Even patients with multiple episodes of myoglobinuria may have no lasting skeletal muscle effects. In patients with chronic alcoholic myopathy, improvement also is usual when ethanol is avoided.

Reversible acute alcoholic muscular syndrome with muscle cramps. Individuals with acute alcoholic muscular syndrome with muscle cramps recover within 2 to 4 weeks if they remain abstinent (129; 128).

Chronic alcoholic myopathy. In contrast to the relatively good prognosis of acute alcoholic myopathies with abstinence, a 5-year study of the natural history of chronic alcoholic myopathy showed that only half of the sober patients recovered to normal strength, indicating that chronic alcoholic myopathy is only partially reversible. In some alcoholics, even a substantial reduction in alcohol consumption may be as effective as complete abstinence in improving muscle strength or preventing its deterioration (41).

Loss of paraspinal muscle mass is a male gender-specific consequence of cirrhosis that predicts complications and death (38). Loss of paraspinal muscle mass was an independent predictor of bacterial infections, spontaneous bacterial peritonitis, hepatic encephalopathy, and hepatorenal syndrome (38).

Alcoholic cardiomyopathy. The prognosis of alcoholic cardiomyopathy is good if the patient stops drinking after the first or second episode of congestive heart failure, but most patients continue to drink (05). Without complete abstinence, the 4-year mortality of alcoholic cardiomyopathy is approximately 50% (91), only modestly improved over what it had been more than 40 years earlier (05; 168; 06).

Clinical vignette

Acute alcoholic myopathy. A 58-year-old woman presented with a 1-day history of pain and numbness in the legs and feet (128). She had been a chronic alcoholic for 38 years. She had one prior hospital admission 10 months earlier for severe intoxication following ethanol and isopropyl alcohol ingestion; at that time, she had diffuse muscle weakness and evidence of peripheral neuropathy but nevertheless recovered uneventfully. She had subsequently been relatively abstinent until she began a binge 2 days before admission.

On the morning of admission, she developed severe sharp pain in her legs and fell. Her feet felt numb, and her legs were extremely tender. She urinated urine of normal color and then returned to bed, but when she urinated again a few hours later, the urine was “brownish-black.” Examination revealed an acutely ill, unkempt woman with gaze-evoked nystagmus, a reddened tongue, a palpable nontender liver, a palpable spleen 3 cm below the costal margin, severe tenderness and swelling of the calves, taut and abnormally warm skin over the swollen legs, severe tenderness of the leg muscles (but only minimal tenderness of the arm muscles), severe calf pain aggravated by motion, severe leg weakness (evaluation of which was confounded by her pain), and decreased proprioception in the legs. Her urine was brown and positive for myoglobin. A creatine kinase level was markedly elevated (using the reference ranges for the lab assay used at that time). The lactic acid response to ischemic exercise was flat. She became anuric after the second day of hospital admission, and this persisted for 8 days. Muscle tenderness continued to be severe for 48 hours and then improved somewhat but, nevertheless, persisted for more than 2 months.

She experienced slow, progressive improvement in strength. After 8 weeks, she could walk with crutches, but not without support, and could rise from a chair with difficulty but could not rise from a squat. When a muscle biopsy was performed on the day after admission, the swollen muscle bulged from the incised fascia and had a pale color with a yellow tinge. A repeat biopsy 6 weeks later showed scattered small fibers, nuclear rows, and endomysial fat. Electron microscopy showed mitochondrial inclusions, degenerating myofilaments, and regenerating muscle fibers.

Reversible acute alcoholic muscular syndrome with muscle cramps. A 47-year-old woman was admitted with alcoholism and severe muscle cramps (78; 128). She drank intermittently until 2.5 years before admission, when she started drinking progressively larger amounts, until 1.5 years previously, when she quit working and began drinking steadily. She lost approximately 50 pounds over the 2 years prior to admission 2 years. For the previous 5 months, she had progressively severe weakness; for the previous 3 months, she had episodic calf cramps, which were initially infrequent and nocturnal but then became frequent, increasingly severe, and no longer confined to one part of the day. She was confined to bed because of weakness and cramps for the previous 2 weeks. There was no change in urine color.

On examination, she was an ill-appearing, thin, disheveled woman. Her liver was palpable 10 cm below the costal margin but was not tender. Painful calf cramps were observed several times during the initial examination. Her neurologic examination demonstrated diffusely tender muscles, weakness, tremor, absent ankle jerks but otherwise normal and symmetric reflexes, and diminished pinprick sensation in the lower legs and feet. A creatine kinase level was markedly elevated (using the reference ranges for the lab assay used at that time), and she also had elevations of aspartate aminotransferase (AST, which was then called serum glutamic oxaloacetic transaminase or SGOT) and lactate dehydrogenase (LDH). Light microscopy of a quadriceps femoris muscle biopsy showed relatively minor and nonspecific abnormalities, including mildly increased nuclear rows, minimal scattered small fibers, and minimal granular cytoplasm. In contrast, electron microscopy showed marked abnormalities of both acute and chronic myopathy, including commonly present separation of myofilaments and myofibrils, and some mitochondrial inclusions and degenerating myofilaments.

She improved steadily over a 3-week period with symptomatic care. Over this interval, her muscle tenderness and cramps resolved, and her strength improved although she still had prominent proximal weakness affecting the shoulder and pelvic girdle muscles.

Chronic alcoholic myopathy (plus Wernicke encephalopathy and peripheral neuropathy). A 54-year-old woman was admitted with severe weakness (78; 128). She had been a heavy drinker for at least 4 years, consuming up to a case of beer daily. She had become increasingly confused and weak over the previous 2 to 3 months, and by 3 weeks before admission, she was so weak that she could not get out of bed. She vomited daily over the 3-week period before admission, usually in the morning.

On examination, she was disheveled, confused, agitated, and actively experiencing both visual and auditory hallucinations. She had a regular tachycardia. The liver and spleen were not palpable. Neurologic examination showed full eye movements, nystagmus, tremor, diffuse muscle atrophy, severe proximal weakness to the point where she was unable to raise her legs off of the bed, absent knee jerks but normal biceps and Achilles reflexes, and stocking-glove hypalgesia. A gastrocnemius muscle biopsy showed moderate scattered small muscle fibers, mild grouping of small fibers, mild nuclear rows, and minimal endomysial fat, consistent with a primary myopathy and a superimposed peripheral neuropathy. EMG showed a scarcity of motor units and fibrillations in the lower extremities and no abnormalities in the upper extremities (despite evident clinical involvement).

She improved steadily with conservative therapy. Four months later, she could walk with a cane and was able to care for herself.

Biological basis

Etiology and pathogenesis

	• Acute alcoholic myopathy is caused by severe alcoholic binges, usually in drinkers of long duration.
	• Acute muscle injury occurs during bouts of high-intensity ethanol abuse and the muscle injury is the consequence of a toxic effect of high ethanol concentrations.
	• Chronic alcoholic myopathy is caused by prolonged, consistent alcohol abuse rather than binge drinking.
	• In alcoholic cardiomyopathy, gross examination of the heart shows dilation of all heart chambers, especially of the left ventricle.

Alcohol misuse, whether as acute intoxication or alcoholism, adversely affects skeletal, cardiac, and smooth muscle contraction (07). Alcohol-mediated disruption of muscle contractility involves various cellular molecules, including contractile proteins, their regulatory factors, membrane ion channels and pumps, and several signaling molecules (07).

Alcohol consumption negatively affects skeletal muscle health through different mechanisms, including an imbalance between anabolic and catabolic pathways, reduced regeneration, increased inflammation and fibrosis, and deficiencies in energetic balance and mitochondrial function (22). These pathological processes occur with various alcohol consumption patterns and are not restricted to chronic alcohol misuse (22).

Acute alcoholic myopathy. Acute alcoholic myopathy is caused by severe alcoholic binges, usually in drinkers of long duration. Clinical and experimental studies support the hypothesis that the muscle injury is the consequence of a toxic effect of high ethanol concentrations. Acute muscle injury occurs during bouts of high-intensity ethanol abuse. Serum creatine kinase elevations in alcoholics are linked to active drinking (119; 111; 57). Serum creatine kinase levels rose in human volunteers receiving 225 g of alcohol daily for 4 weeks, despite a nutritional diet (164). In a retrospective cohort study of 495 Dutch adolescents treated for symptoms of acute alcohol intoxication, elevated creatinine kinase (CK) levels were found in 60%, with a mean CK level of 254 U/I (normal value ≤ 145 U/I) (132). In a rat model of alcoholic rhabdomyolysis, mean serum creatine kinase levels increased with rising levels of blood alcohol (55; 53). The lack of caloric intake apart from ethanol during binge drinking also promotes high blood alcohol levels (118) because fasting retards alcohol clearance (177).

In some cases of acute alcoholic myopathy, additional factors may contribute to muscle injury. For example, muscle crush is a contributing mechanism in some cases, particularly when abuse of alcohol and narcotics are combined (43; 80). In these instances, muscle injury predominates in muscles that are compressed by the weight of the patient's body. Seizures (eg, due to alcohol withdrawal) may sometimes potentiate muscle injury.

Alcoholics are also prone to electrolyte disturbances, particularly depletion of magnesium, inorganic phosphate, and potassium, each of which can injure skeletal muscle (31; 56). Experimental magnesium deficiency causes a myopathy, and hypomagnesemia is common in withdrawing alcoholics. No link between serum magnesium levels and acute alcoholic myopathy has been found (127; 57; 48), but even when serum magnesium levels are normal, muscle magnesium may be low (08). Phosphate depletion and hypophosphatemia have been linked to rhabdomyolysis experimentally and in various clinical settings, including alcoholism (79; 31). However, severe and subclinical forms of acute alcoholic myopathy may occur without hypophosphatemia (57; 48). Potassium depletion may cause a rapidly evolving necrotizing myopathy that mimics alcoholic rhabdomyolysis. Potassium deficiency myopathy has been reported in alcoholic individuals with severe hypokalemia (ie, serum potassium less than 2.2 mM) (103); in such patients, potassium loss is usually due to vomiting or diarrhea. However, in most cases of acute alcoholic myopathy, hypokalemia is less severe, and low serum or muscle potassium levels do not correlate directly with muscle injury (127; 08; 57). In an experimental model of alcoholic rhabdomyolysis, mild hypokalemia coexisted with normal or elevated levels of muscle potassium, suggesting that alcohol promotes potassium redistribution between the intracellular and extracellular space; raising serum potassium by additional dietary supplements did not prevent myopathy in this model (54).

Chronic alcoholic myopathy. Chronic alcoholic myopathy is caused by prolonged, consistent alcohol abuse rather than binge drinking. Muscle strength in alcoholics who abused alcohol for less than 5 years was similar to that in control subjects, whereas progressive weakness was accompanied by longer periods of alcohol use (24). In a study of 50 alcoholic men, deltoid strength and the total lifetime alcohol dose were inversely correlated (172). Chronic alcoholic myopathy is characterized by a reduced cross-sectional area of muscle fibers and impaired anabolic signaling (159).

Duration and level of habitual alcohol consumption are associated with type-II-muscle-fiber atrophy (fast-twitch) and, particularly, with type-IIB-muscle-fiber atrophy (101; 137). Muscle-fiber types are classified by their histochemical, ultrastructural, biochemical, and physiologic properties (Table 2). The speed of muscle fiber contraction depends on myosin ATPase activity, whereas fatigability relates to oxidative capacity. Type IIB fibers (also labeled fast-twitch, fast-fatigable, and fast-glycolytic fibers) generate ATP by anaerobic glycolysis but utilize phosphocreatine as an accessible storage form for ATP to provide a short burst of energy. Type IIB fibers have a myosin heavy chain isoform (IIx) with high ATPase activity that can rapidly utilize the available ATP. The more energy transferred in a certain time, the greater the power. Consequently, type IIB fibers contract rapidly, create forceful contractions, and fatigue quickly. They are a predominant muscle-fiber type in arm muscles, whereas postural muscles of the neck and spine have large quantities of type I fibers, and leg muscles have large quantities of both type I and type IIA fibers.

Table 2. Muscle Fiber Types

Fiber Type	Type I	Type IIA	Type IIB
Also called	Slow twitch	Fast oxidative	Fast glycolytic
Color	Red	Red	White
Activity Used for	Aerobic	Long-term anaerobic	Short-term anaerobic
Contraction speed	Slow	Fast	Very fast
Time to peak power (ms)	100	50	25
Fatigue resistance	High	Intermediate	Low
Force production	Low	High	Very High
Mitochondrial density	High	Medium	Low
Intracellular myoglobin	High	High	Low
Capillary density	High	Medium	Low
Metabolic character	Oxidative	Mixed	Glycolytic
Main metabolic pathway for ATP generation	TCA/OP	TCA/OP/CPK	Glycolysis/CPK
Oxidative enzyme activity	High	High	Low
Glycolytic enzyme activity	Low	High	High
Myosin heavy chain isoform	I	IIa	IIx
Myosin ATPase activity	Low	High	High
Triglyceride content	High	Medium	Low
Glycogen reserves	Low	Medium	High
Phosphocreatine content	Low	High	High
Motor neuron size	Small	Large	Very large
Recruitment frequency	Low	Medium	High
Abbreviations: CPK: creatine phosphokinase; OP: oxidative phosphorylation; TCA: Kreb’s tricarboxylic acid cycle

Although myopathy and neuropathy are frequently both present in chronic alcoholics, the pathogenetic mechanisms involved in each of these forms of tissue damage are presumably not identical, because histologic and clinical evidence of myopathy may occur in the absence of symptoms or electrophysiologic signs of neuropathy or of malnutrition (101; 172).

Nutritional factors may contribute to the pathogenesis of chronic alcoholic myopathy because muscle weakness and histologic myopathy among alcoholics are both more severe in the presence of malnutrition (116), but no clear relationship has been identified for the following micronutrients: thiamine (vitamin B1), riboflavin (vitamin B2), pyridoxine (vitamin B6), folate (vitamin B9), cobalamin (vitamin B12), beta-carotene (provitamin A), retinol (vitamin A), vitamin D, copper, and zinc (178; 139; 143; 137). Deficiencies of alpha-tocopherol (vitamin E) and selenium have also been proposed as candidate risk factors for alcoholic myopathy (178; 137). Animal studies have established that a deficiency of either of these micronutrients can cause neuropathy, and human studies have shown that levels of each of these are lower in alcoholics with myopathy than in normal controls or in nonmyopathic alcoholics (178; 137). Selenium is a cofactor for several enzymes, but especially glutathione peroxidase, the major detoxification enzyme for hydrogen peroxide (H2O2), whereas alpha-tocopherol is critical in preventing the initiation and propagation of lipid peroxidation.

Myotoxic effects of alcohol have been demonstrated in animal models. For example, administration of alcohol with a nutritionally complete diet to rats caused atrophy of type II muscle fibers (170). In addition, chronic binge alcohol consumption in rhesus macaques disrupted myogenic gene expression and myotube formation, which likely impaired skeletal muscle regenerative capacity (162).

The pathogenesis of alcoholic myopathy involves multiple interrelated pathways (144; 143; 137). First, impaired gene expression and protein synthesis, as well as increased oxidative damage, act together to reduce the formation of myofibrillar proteins (139; 137). Second, impaired gene expression, increased oxidative damage, and the pro-apoptotic properties of alcohol act to increase apoptosis. Third, additional muscle damage comes from alterations in ion channels and cell-membrane permeability, impaired energy metabolism, protein adduct formation, and the toxicity of fatty acid ethyl esters. All of these processes contribute to the death and loss of myocytes and, hence, to progressive myopathy (46).

In a study of myoblasts isolated from the vastus lateralis muscle of alcohol-naive adult male and female rhesus macaques, alcohol decreased glycolytic metabolism and impaired myoblast differentiation, which may help explain the decrease in myogenesis with alcohol (94).

Chronic ethanol consumption in mice induces substantial weakness in vivo that is primarily due to muscle atrophy (ie, reduced muscle quantity) and possibly, to a lesser degree, loss of central neural drive (110).

Alcoholic cardiomyopathy. In alcoholic cardiomyopathy, gross examination of the heart shows dilation of all heart chambers, especially the left ventricle (05; 157). The myocardium is pale and flabby with a variable degree of fibrosis (05; 157). Light microscopy of the heart in alcoholic cardiomyopathy shows nonspecific changes, including patchy scarring in the subendocardial layer (05; 157). Histochemical studies demonstrate lipid deposits (mainly triglycerides) and a decrease in myocardial oxidative enzymes (157). Electron microscopy of the myocardium shows much more dramatic abnormalities, including myofibril loss and fragmentation, clusters of giant mitochondria with distorted cristae, cystic dilation of the sarcoplasmic reticulum, increased glycogen and fat deposits, and variable myofiber hypertrophy (05; 157). The dramatic mitochondrial abnormalities indicate a significant disturbance of oxidative metabolism and energy production, resulting in decreased myocardial contractility and congestive heart failure (05).

Several pathogenic mechanisms have been implicated, including oxidative stress, apoptosis, impaired mitochondrial bioenergetics (with consequent loss of energetic efficiency and an increase in the generation of damaging reactive oxygen species), disrupted fatty acid metabolism and transport, including the generation of toxic fatty acid ethyl esters (FAEEs) from the combination of fatty acids with ethanol, decreased protein synthesis that initially manifests as a defect in translational efficiency, and possibly enhanced autophagy and protein catabolism (142; 139; 144; 145; 138; 86; 188; 131). Polymorphic variants of the mitochondrial isoform of aldehyde dehydrogenase (ie, ALDH2) encode enzymes with significantly altered ability to metabolize acetaldehyde and significantly higher associated risk of alcoholism and alcohol-related complications (188). Nevertheless, genetic variations in ALDH2 and other enzymes related to ethanol metabolism have not been clearly shown to influence susceptibility to alcoholic cardiomyopathy (188; 131).

In rats, the combination of periodic fasting in the presence of continuous ethanol intake produces pronounced morphological changes in the myocardium and its organelles (15).

So far, no causal relationships have been established between significant alcohol-related micronutrient deficiencies and the development of alcoholic cardiomyopathy (131). However, thiamine deficiency (beriberi) is known to cause cardiomyopathy (under different labels: eg, “thiamine-deficiency cardiomyopathy,” “beriberi cardiomyopathy,” “beriberi heart disease,” or “Shoshin beriberi”), and certain micronutrient deficiencies, particularly of alpha-tocopherol (vitamin E) and selenium, can cause myopathies, and all of these are common metabolic consequences of alcoholism (180; 167; 12; 11; 137; 02; 01). In a rat model, thiamine supplementation was protective against acetaldehyde-induced cytotoxicity and cardiac contractile dysfunction through protective effects against protein damage and apoptosis in ventricular myocytes (01). In addition, in another rat model of the combined short-term toxic effects of acetaldehyde and nicotine on cardiac contractile function, cotreatment with folate (a vitamin required for DNA synthesis) obviated the toxic effects, possibly through mechanisms related to mitigating DNA damage (02).

Metabolism of ethanol. Ethyl alcohol (ie, ethanol), or commonly just “alcohol,” is metabolized mainly by the liver. As a first step, ethanol is primarily oxidized by the cytosolic enzyme alcohol dehydrogenase to form acetaldehyde. There are additional secondary routes for oxidative metabolism of ethanol to acetaldehyde using either an enzyme in the endoplasmic reticulum, cytochrome P450 IIE 1 (CYP2E1), which operates at high levels of alcohol consumption and is induced by chronic drinking, or a minor pathway utilizing a catalase-mediated reaction in peroxisomes. Acetaldehyde is then oxidized by the mitochondrial enzyme acetaldehyde dehydrogenase (aldehyde dehydrogenase 2) to acetate (187; 186).

Ethanol (3D ball-and-stick model)

(Courtesy of Wikimedia Commons. Public domain.)
Ethanol conversion (skeletal diagrams)

Skeletal diagrams showing the conversion of ethanol via alcohol dehydrogenase (ADH) to acetaldehyde and then via acetaldehyde dehydrogenase to acetate. (Courtesy of Wikimedia Commons. Public domain.)
Acetaldehyde (3D ball-and-stick model)

(Courtesy of Wikimedia Commons. Public domain.)
Alcohol metabolism oxidative pathways

Alcohol is metabolized mainly in the cytosol of hepatocytes by alcohol dehydrogenase (ADH) to produce acetaldehyde. At high levels of alcohol consumption, an enzyme in the endoplasmic reticulum, cytochrome P450 IIE1 (CYP2E1), also...
3D ball-and-stick model of acetate

A resonance form of the molecule is shown. (Courtesy of Wikimedia Commons. Public domain.)

Most of the acetate formed from the metabolism of alcohol in the liver escapes into the blood and is ultimately metabolized by peripheral tissues (68; 187; 186). Skeletal muscle, heart, and brain contain the mitochondrial matrix enzyme acetyl-CoA synthetase (or acetate-CoA ligase), which catalyzes the ligation of acetate with CoA to produce acetyl-CoA:

ATP + Acetate + CoA <=> AMP + Pyrophosphate + Acetyl-CoA

Acetyl-CoA is an essential molecule utilized in various metabolic pathways, including the tricarboxylic acid cycle (an alternate entrée into the TCA cycle, as the more common way is to produce acetyl-CoA from pyruvate through the pyruvate dehydrogenase complex), and also fatty acid and cholesterol synthesis.

Alcohol is not metabolized directly by skeletal muscle, and the injurious effects of alcohol abuse on muscle have been attributed to a toxic effect of ethanol or its metabolite, acetaldehyde (148; 32). Because the rate of acetaldehyde production plateaus at relatively low, nonintoxicating levels of ethanol, any toxic effects linked specifically to a high dose of alcohol are more likely the result of actions of ethanol itself rather than its metabolites.

Alteration of gene expression. Metabolites of alcohol can operate at an epigenetic level, binding to transcription factors or modifying chromatic structure (186). One of the most important epigenetic signals is DNA methylation, which marks or tags selected cytosine moieties in DNA with a methyl group. Chronic alcohol consumption significantly reduces s-adenosyl-methionine (SAM) levels, thereby contributing to DNA hypomethylation. Gene expression is also influenced by alcohol-induced posttranslational modifications of histone proteins (eg, methylation and acetylation) that determine the genome’s accessibility to transcription factors. Ethanol metabolism also alters the ratio of nicotinamide adenine dinucleotide (NAD+) to reduced NAD (NADH) and promotes the formation of reactive oxygen species and acetate, all of which impact epigenetic regulatory mechanisms for gene expression. As a result of such processes, alcohol metabolism can impact several different epigenetic mechanisms, leading to complex alterations in gene expression.

Schematic representation of DNA methylation

DNA methyltransferase (DNMT) catalyzes the conversion of cytosine to 5’methyl-cytosine, typically acting on cytosines that are followed by a guanine (ie, CpG motifs-cytosine and guanine separated by only one phosphate). Source: (Z...
Effect of ethanol on homocysteine/methionine metabolism and DNA methylation

Methionine, which is formed by methylation of homocysteine (using either 5-methyl tetrahydrofolate (5-methyl THF) or betaine as a methyl donor), is essential for the production of s-adenosyl-methionine (SAM), which in turn is used...
Alcohol metabolism and histone acetylation

Acetyl-coenzyme A (acetyl-CoA) synthetase (AceCS), an enzyme that converts acetate to acetyl-CoA, is activated by SIRT1. Acetyl-CoA is used by histone acetyltransferase (HAT) to acetylate the lysine residues in histone proteins. T...
Alcohol metabolism and epigenetic mechanisms interactions

Chronic alcohol consumption leads to lower than normal methylation (ie, hypomethylation) by decreasing the levels of S-adenosyl-methionine (SAM), which is used by DNA methyltransferases (DNMTs) and histone methyl transferases (HMT...

Impaired protein synthesis. Alcohol promotes muscle atrophy by impairing protein synthesis (136; 139; 138; 140). Changes in the regulation of anabolic and catabolic signaling pathways precede the development of skeletal muscle atrophy and clinical symptoms of alcoholic myopathy (158; 22).

Alcohol-induced modulations in transcription and translation are not mediated by the availability of amino acids, the effects of endocrine dysfunction (eg, of cortisol or growth hormone), or the presence of liver impairment or malnutrition (139). Although total messenger RNA falls after ethanol consumption, messenger RNA for specific myofibrillary contractile proteins are unaffected, which implies a role for translational modifications in the initial stages of alcoholic myopathy (139). The reductions in the rate of protein synthesis are related to changes in activation of translation initiation factors (87). For example, alcohol suppresses the insulin-like growth factor (IGF-1)-mediated phosphorylation of ribosomal kinases, thus, limiting the translation of selected mRNAs (139; 88).

Alcohol-induced decreases in protein synthesis are largely governed by impaired activity of a protein kinase, the mechanistic target of rapamycin (or mTOR) (76). mTOR is also known as the mammalian target of rapamycin and FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1). mTOR is a member of the phosphatidylinositol 3-kinase-related kinase family of protein kinases. In humans mTOR is encoded by the MTOR gene. mTOR regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, and transcription (58; 95). mTOR also promotes the activation of insulin receptors and insulin-like growth factor 1 receptors and is involved in the control and maintenance of the actin cytoskeleton (58; 64; 184).

Moreover, numerous studies have implicated the generation of reactive oxygen species and enhanced lipid peroxidation in the pathogenesis of reduced tissue protein synthesis.

Accelerated muscle breakdown. Although accelerated muscle protein breakdown was previously hypothesized to explain the development of chronic alcoholic myopathy, careful studies have not supported this (102).

Reactive oxygen species. The excessive generation of reactive oxygen species leading to enhanced lipid peroxidation is an important feature of alcohol toxicity. Ethanol metabolism causes oxidative stress and lipid peroxidation in liver and extrahepatic tissues, including muscle (03). In mice, oxidative stress due to ethanol metabolism causes extensive degradation and depletion of mitochondrial DNA in liver, brain, heart, and skeletal muscle (97); these effects could be prevented by 4-methylpyrazole, an inhibitor of ethanol metabolism, and attenuated by antioxidants such as vitamin E, melatonin, and coenzyme Q (97). Cholesterol-derived hydroperoxides as a product of lipid peroxidation are significantly elevated after acute ethanol treatment and may contribute to reductions in tissue protein synthesis (03). However, the alcohol-induced reductions in protein synthesis could not be prevented by vitamin E (146). Antioxidant muscle enzyme activities are partially disturbed in chronic alcoholism, although not related to the presence of myopathy, amount of ethanol consumed, or nutritional status of the patients (44). Supplementing the diets of alcohol-fed rats with the antioxidative glutathione precursor, Procysteine, attenuated alcohol-induced oxidant stress, stimulated gene expression of anabolic factors, and reduced the degree of plantaris atrophy. Therefore, antioxidant treatments may benefit individuals with alcoholic myopathy (122).

Lipid peroxidation

Lipid peroxidation is an oxidative degradation of lipids in which free radicals (eg, the hydroxyl radical, OH) "steal" electrons from the lipids in cell membranes in a chain-reaction mechanism, causing cellular damage. This proces...

Apoptosis. Apoptosis has been implicated in the pathogenesis of alcoholic myopathy (45).

Cell membrane and ion channels. Increased muscle sodium and calcium concentrations have been found in alcoholic patients and with experimental alcohol administration (08). These changes in cellular ion composition may be nonspecific indices of cellular injury. However, ethanol directly affects the function of membrane proteins involved in regulating cellular levels of sodium and calcium. Ethanol may promote sodium accumulation in cells by increasing sodium permeability and acutely inhibiting Na⁺-K⁺ adenosine triphosphatase (148). Prolonged ethanol exposure increases membrane Na⁺-K⁺ adenosine triphosphatase activity, possibly in response to increased sodium permeability. Ethanol may also promote cellular calcium accumulation. Ethanol reduces calcium transport by the sarcoplasmic reticulum (164). Ethanol acutely inhibits voltage-sensitive calcium channels, but chronic alcohol administration increases the number of calcium channels (107). A specific role for ethanol-induced changes in calcium permeability in experimental alcoholic cardiomyopathy has been suggested by the finding that verapamil has a protective effect in this model (49).

Impaired cellular metabolism. Acute rhabdomyolysis, similar to that in acute alcoholic myopathy, is a feature of inborn errors of energy metabolism in skeletal muscle. The increase in lactic acid during ischemic exercise is less than normal in patients with alcoholic muscle disease, suggesting that impaired muscle glycogenolysis (akin to that in myophosphorylase deficiency) could contribute to alcohol-related muscle injury. 31P-magnetic resonance spectroscopy in alcoholics has also shown findings consistent with impaired muscular glycolysis or glycogenolysis during aerobic exercise (19). However, impaired lactate production has been found in other acute illnesses, suggesting this may be a nonspecific finding. Several studies have found lower levels of muscle glycolytic enzymes in chronic alcoholics (74; 54; 99; 171). The dominant mechanism is atrophy of type II muscle fibers, which in humans have 2- to 5-fold higher levels of glycolytic enzyme activity than type I fibers (151). In ultrastructural studies, mitochondrial abnormalities are an early feature of acute myopathy (34). However, isolated mitochondria from chronic alcoholics have shown no evidence of impaired oxidative metabolism (23), and oxidative enzyme activity in chronic alcoholic individuals is preserved (74; 171).

Protein adduct formation. Ethanol metabolism by alcohol dehydrogenase and CYP2E1 produces highly reactive molecules, such as acetaldehyde and reactive oxygen species, that can interact with amino acids to form stable and unstable adducts (141; 187; 135). Such adducts may contribute to reductions in protein synthesis, may initiate the formation of autoantibodies and trigger autoimmune damage, and may also interfere with proteins of the contractile system or signaling peptides (142; 144; 138; 182). Acute ethanol administration increased protein adducts with malondialdehyde and acetaldehyde in rats, primarily in type II muscle fibers; this may be associated with the increased susceptibility of anaerobic muscle to alcohol toxicity (117).

Fatty acid ethyl esters (FAEE). FAEE are nonoxidative metabolites of ethanol and are toxic to cells in vitro and in vivo (92). In rats, skeletal muscle contains high levels of FAEE after ethanol exposure, similar to the concentration in the liver (150), so FAEE may contribute to the development of alcoholic myopathy.

Epidemiology

	• Approximately half of chronic alcoholics have loss of lean body mass due to loss of muscle tissue, decreased muscle strength, and associated gait abnormalities.
	• Alcohol is a common cause of nontraumatic myoglobinuria and is implicated as the cause in approximately 20% of such cases.
	• Muscle abnormalities consistent with chronic alcoholic myopathy are common in habitual drinkers, affecting 40% to 60% of patients who chronically abuse alcohol.
	• Alcoholism is responsible for 21% to 36% of all cases of nonischemic dilated cardiomyopathy.

Approximately half of chronic alcoholics have a loss of lean body mass due to loss of muscle tissue, decreased muscle strength, and associated gait abnormalities (143; 137). Between one third and two thirds of chronic alcoholics have skeletal muscle myopathies, making alcoholic myopathies the most prevalent type of myopathy (137). In addition, up to a third of chronic alcoholics have evidence of cardiomyopathy (137).

Acute alcoholic myopathy. Alcohol is a common cause of nontraumatic myoglobinuria and is implicated as the cause in approximately 20% of such cases (147; 51; 80; 125; 13). Alcoholic rhabdomyolysis predominates in men by a greater than 4-to-1 ratio and usually occurs in the 4th to 6th decades of life. Recurrent episodes are reported in about 30% of cases following an initial episode of rhabdomyolysis. The incidence and prevalence of alcoholic rhabdomyolysis has varied considerably in different studies, probably at least partly due to variations in the intensity and chronicity of drinking, and coexistent nutritional disorders, among the subjects studied. Most studies suggest that alcoholic rhabdomyolysis is infrequent in alcoholics, occurring in less than 5% of chronic alcoholics (139; 143; 137). Nevertheless, the rhabdomyolytic variant of acute alcoholic myopathy represents the most common nontraumatic cause of rhabdomyolysis in hospitalized patients (173; 161). Myerson and Lafair reported 10 cases in 330 patients (3%) with medical complications of alcoholism (111). In 100 autopsies of patients dying with alcoholic liver disease, clinically unsuspected severe rhabdomyolysis was identified in 8% (69). Subclinical muscle injury, as reflected in elevations in serum creatine kinase, has been found in 15% to 80% of patients admitted after active drinking (119; 175; 57; 101). Acute alcoholism or withdrawal accounted for approximately 40% of elevated serum creatine kinase levels in an acute medical ward (115).

Chronic alcoholic myopathy. In a series of patients with chronic alcoholic myopathy, males and females were equally affected (36; 128). Quantitative strength testing and histologic studies indicate that muscle abnormalities consistent with chronic alcoholic myopathy are common in habitual drinkers, affecting 40% to 60% of patients who chronically abuse alcohol (114). In one study, 90 of 151 patients (60%) with chronic alcohol use had type-II-fiber atrophy in needle biopsies of the quadriceps muscle (101). Similarly, 21 of 50 (42%) asymptomatic men with an average alcohol consumption of 240 g/day for 16 years had deltoid weakness on quantitative testing (172).

Alcoholic cardiomyopathy. Alcoholism is responsible for 21% to 36% of all cases of nonischemic dilated cardiomyopathy (91). Beer drinkers seem particularly susceptible to alcoholic cardiomyopathy (05; 157).

Diagnostic workup

	• In acute alcoholic myopathy, creatine kinase is moderately or severely increased in serum, whereas in chronic alcoholic myopathy, creatine kinase is normal.
	• In alcoholics with acute myopathy, the workup should include a careful history and a toxicology screen to identify the possible contribution of other drugs or toxins known to produce myoglobinuria.
	• In alcoholics with acute myopathy, screening for metabolic derangements that can cause myoglobinuria, particularly hypokalemia and hypophosphatemia, should be performed.
	• In acute alcoholic myopathy, EMG shows myopathic potentials and a high frequency of spontaneous discharges attributed to hyperirritability of muscle fibers associated with active muscle fiber necrosis, whereas in chronic alcoholic myopathy, EMG often shows mixed myopathic and neuropathic features with variable spontaneous discharges.

In alcoholics with acute myopathy, the workup should include a careful history and a toxicology screen to identify the possible contribution of other drugs or toxins known to produce myoglobinuria. Serum creatine kinase is moderately or severely increased. Screening for metabolic derangements that can cause myoglobinuria, particularly hypokalemia and hypophosphatemia, should be performed. Other causes of pigmenturia (eg, hematuria, hemoglobinuria, and porphyria) should be excluded. In an individual with recurrent rhabdomyolysis or evidence of muscle injury that has occurred apart from alcohol abuse, perform an evaluation for a possible inborn error of muscle metabolism. EMG shows myopathic potentials (short duration, small-amplitude units with normal recruitment) and a high frequency of spontaneous discharges (fibrillations and positive sharp waves) attributed to hyperirritability of muscle fibers associated with active muscle fiber necrosis (121). Muscle biopsy, if performed, shows muscle fiber necrosis (130).

In patients with symptoms suggesting chronic alcoholic myopathy, a family history should be obtained to exclude familial muscle disease, and laboratory screening should be employed to determine whether an underlying endocrine or electrolyte disorder exists. Serum creatine kinase is normal. Electromyography and muscle biopsy are necessary to exclude other causes of chronic proximal weakness and atrophy. EMG often shows mixed myopathic and neuropathic features with variable spontaneous discharges (121). The most frequent histological findings are myocytolysis, fiber-size variability, and type IIB-fiber atrophy (130). Cardiomyopathy and hepatic cirrhosis are more frequent in patients with chronic alcoholic myopathy and should be checked for in chronic alcoholics with skeletal myopathy (149).

Nerve conduction studies in patients with alcoholic myopathies often show coincident neuropathic abnormalities (ie, borderline or slowed conduction velocities and absent sensory potentials) because distal neuropathies often coexist with myopathy (121).

Management

	• The single most important therapeutic factor in treating alcoholic myopathies in the long term is abstinence from alcohol.
	• An alcohol treatment program is a critical component of treating alcoholic myopathies.
	• Acute rhabdomyolysis with myoglobinuria requires urgent inpatient interventions to monitor and maintain renal function and to avoid or correct hyperkalemia.
	• In chronic alcoholic myopathy, associated nutritional deficiencies need to be corrected and a diet with adequate protein and carbohydrates ensured.

The single most important therapeutic factor in treating alcoholic myopathies in the long term is abstinence from alcohol. Therefore, an alcohol treatment program is a critical component of the treatment of alcoholic myopathies.

Acute rhabdomyolysis with myoglobinuria requires urgent inpatient interventions to monitor and maintain renal function and to avoid or correct hyperkalemia. Aggressive intravenous fluid resuscitation may decrease the likelihood of acute renal failure and lessen the need for dialysis (153). Hemodialysis may, nevertheless, be needed (09; 124). Blood levels of potassium, phosphate, and magnesium should be determined, and deficiencies should be corrected, although some practice guidelines have conditionally recommended against treatment with bicarbonate or mannitol in patients with rhabdomyolysis (153).

In chronic alcoholic myopathy, associated nutritional deficiencies need to be corrected and a diet with adequate protein and carbohydrates ensured.

Vitamin D deficiency is found in a large proportion of alcoholics (55% of alcoholics had vitamin D deficiency in one study), and there are clinical and morphological similarities between hypovitaminosis D myopathy and chronic alcoholic myopathy (181). Moreover, alcoholics are prone to low bone mineral density and have a multifactorial increased risk of falls and falls with injury. Taken together, these data suggest that individuals with alcoholic myopathy may benefit from vitamin D supplementation, with target 25-hydroxy vitamin D levels above 30 ng/ml, preferably above 40 to 50 ng/ml. Although there are no human-controlled clinical trials to establish the effectiveness of vitamin D supplementation in subjects with alcoholic myopathy, in Sprague-Dawley rats with experimental alcoholic myopathy, low vitamin D levels correlated with muscle fiber atrophy (50).

Although there are no human randomized clinical trials of drugs or supplements that may impact the myopathy pathogenesis of alcoholic myopathy, antioxidant treatments may be considered in individuals with alcoholic myopathy based on the results from animal studies. In rodent models, ethanol-induced degradation and depletion of mitochondrial DNA were attenuated by the antioxidants vitamin E, melatonin, or coenzyme Q (97). Similarly, supplementing the diets of alcohol-fed rats with the antioxidative glutathione precursor, Procysteine, attenuated alcohol-induced oxidant stress, stimulated gene expression of anabolic factors, and reduced the degree of plantaris atrophy (122).

Media

References

01: Aberle NS 2nd, Burd L, Zhao BH, Ren J. Acetaldehyde-induced cardiac contractile dysfunction may be alleviated by vitamin B1 but not by vitamins B6 or B12. Alcohol Alcohol 2004;39(5):450-4. PMID 15304379
02: Aberle NS 2nd, Privratsky JR, Burd L, Ren J. Combined acetaldehyde and nicotine exposure depresses cardiac contraction in ventricular myocytes: prevention by folic acid. Neurotoxicol Teratol 2003;25(6):731-6. PMID 14624973
03: Adachi J, Asano M, Ueno Y, et al. 7alpha- and 7beta-hydroperoxycholest-5-en-3beta-ol in muscle as indices of oxidative stress: response to ethanol dosage in rats. Alcohol Clin Exp Res 2000;24:675-81. PMID 10832909
04: Adickes ED, Shuman RM. Fetal alcohol myopathy. Pediatr Pathol 1983;1:369-84. PMID 6687287
05: Alexander CS. Alcohol and the heart. Ann Intern Med 1967;67(3):670-4. PMID 6042653
06: Alexander CS. The concept of alcoholic myocardiopathy. Med Clin North Am 1968;52(5):1183-91. PMID 4876833
07: Alleyne J, Dopico AM. Alcohol use disorders and their harmful effects on the contractility of skeletal, cardiac and smooth muscles. Adv Drug Alcohol Res 2021;1:10011. PMID 35169771
08: Anderson R, Cohen M, Haller RG, Elms J, Carter NW, Knochel JP. Skeletal muscle phosphorus and magnesium deficiency in alcoholic myopathy. Minee Electrolyte Metab 1980;4:106-12.
09: Asokan N, Binesh VG, Andrews AM, Jayalakshmi PS. Bullous lesions, sweat gland necrosis and rhabdomyolysis in alcoholic coma. Indian J Dermatol 2014;59(6):632. PMID 25484420
10: Attas M, Hanley HG, Stultz D, Jones MR, McAllister RG. Fulminant beriberi heart disease with lactic acidosis: presentation of a case with evaluation of left ventricular function and review of pathophysiologic mechanisms. Circulation 1978;58(3 Pt 1):566-72. PMID 679449
11: Ba A, Seri BV, Aka KJ, Glin L, Tako A. Comparative effects of developmental thiamine deficiencies and ethanol exposure on the morphometry of the CA3 pyramidal cells. Neurotoxicol Teratol 1999;21(5):579-86. PMID 10492392
12: Ba A, Seri BV, Han SH. Thiamine administration during chronic alcohol intake in pregnant and lactating rats: effects on the offspring neurobehavioural development. Alcohol Alcohol 1996;31(1):27-40. PMID 8672172
13: Baeza-Trinidad R. Rhabdomyolysis: A syndrome to be considered. Med Clin (Barc) 2022;158(6):277-83. PMID 34872769
14: Bakker SJ, Leunissen KM. Hypothesis on cellular ATP depletion and adenosine release as causes of heart failure and vasodilatation in cardiovascular beriberi. Med Hypotheses 1995;45(3):265-7. PMID 8569549
15: Baruah JK, Kinder D. Ethanol induced cardiomyopathy--role of periodic fasting. Exp Pathol 1988;33(4):201-6. PMID 3229455
16: Baruah JK, Washington M, Kinder D. Ethanol induced skeletal muscle degeneration--role of calcium. Exp Pathol 1988;33(4):207-12. PMID 3229456
17: Bello S, Neri M, Riezzo I, Othman MS, Turillazzi E, Fineschi V. Cardiac beriberi: morphological findings in two fatal cases. Diagn Pathol 2011;6:8. PMID 21244717
18: Blacket RB. Shoshin or acute pernicious beri beri. Aust N Z J Med 1981;11(5):566-7. PMID 6948555
19: Bollaert PE, Robin-Lherbier B, Escanye JM, et al. Phosphorus nuclear magnetic resonance evidence of abnormal skeletal muscle metabolism in chronic alcoholics. Neurology 1989;39:821-4. PMID 2725876
20: Brink AJ, Lochner A, Lewis CM. Thiamine deficiency and beriberi heart disease. S Afr Med J 1966;40(25):581-90. PMID 5943852
21: Brown TM. A case of Shoshin Beriberi: lessons old and new for the psychiatrist. Psychosomatics 2013;54(2):175-80. PMID 22658327
22: Caceres-Ayala C, Pautassi RM, Acuña MJ, Cerpa W, Rebolledo DL. The functional and molecular effects of problematic alcohol consumption on skeletal muscle: a focus on athletic performance. Am J Drug Alcohol Abuse 2022;48(2):133-47. PMID 35389308
23: Cardellach F, Galofre J, Grau JM, et al. Oxidative metabolism in muscle mitochondria from patients with chronic alcoholism. Ann Neurol 1992;31:515-8. PMID 1596087
24: Carlsson C, Dencker SJ, Grimby G, Tichy J. Muscle weakness and neurological disorders in alcoholics. Q J Stud Alcohol 1969;30:585-91. PMID 5809949
25: Carson P. Alcoholic cardiac beriberi. Br Med J (Clin Res Ed) 1982;284(6332):1817. PMID 6805710
26: Coelho LS, Hueb JC, Minicucci MF, Azevedo PS, Paiva SA, Zornoff LA. Thiamin deficiency as a cause of reversible cor pulmonale. Arq Bras Cardiol 2008;91(1):e7-9. PMID 18660937
27: Corcoran TB, O'Hare B, Phelan D. Shoshin beri-beri precipitated by intravenous glucose. Crit Care Resusc 2002;4(1):31-4. PMID 16573401
28: Crawford JS. A case of beriberi with organic changes in the heart. Can Med Assoc J 1952;67(4):356-9. PMID 13009563
29: Dabar G, Harmouche C, Habr B, Riachi M, Jaber B. Shoshin beriberi in critically-ill patients: case series. Nutr J 2015;14:51. PMID 25982313
30: Daly MJ, Dixon LJ. A case of ST-elevation and nystagmus--when coronary thrombosis is not to blame. QJM 2009;102(10):737-9. PMID 19622676
31: Daras M, Singh BM, Fass AE, Morris LJ, Spiro AJ. Acute hypokalemic, hypophosphatemic myopathy in chronic alcoholism. Muscle Nerve 1981;4(3):258. PMID 7242565
32: Diamond I. Alcoholic myopathy and cardiomyopathy. N Engl J Med 1989;320:458-60. PMID 2913510
33: Djoenaidi W, Notermans SL, Dunda G. Beriberi cardiomyopathy. Eur J Clin Nutr 1992;46(3):227-34. PMID 1313764
34: Douglas RM, Fewings JD, Casley-Smith JR, West RF. Recurrent rhabdomyolysis precipitated by alcohol. A case report with physiological and electron microscopic studies of skeletal muscle. Aust Ann Med 1966;15:251-61. PMID 5986704
35: Dreschfield J. On alcoholic paralysis. Brain 1885;7:200-11.
36: Ekbom K, Hed R, Kirstein L, Astrom KE. Muscular affections in chronic alcoholism. Arch Neurol 1964;10:449-58. PMID 14120636
37: Engbers JG, Molhoek GP, Arntzenius AC. Shoshin beriberi: a rare diagnostic problem. Br Heart J 1984;51(5):581-2. PMID 6721953
38: Engelmann C, Schob S, Nonnenmacher I, et al. Loss of paraspinal muscle mass is a gender-specific consequence of cirrhosis that predicts complications and death. Aliment Pharmacol Ther 2018;48(11-12):1271-81. PMID 30417398
39: Epstein S. Observations on beriberi heart disease. Am Heart J 1947;34(3):432-40.
40: Erlenborn JW, Pilz CG. Paroxysmal myoglobinuria. JAMA 1962;181:95-8. PMID 13890604
41: Estruch R, Sacanella E, Fernandez-Sola J, Nicolas JM, Rubin E, Urbano-Marquez A. Natural history of alcoholic myopathy: a 5-year study. Alcohol Clin Exp Res 1998;22:2023-8. PMID 9884146
42: Evans JA, Elliott FD. Multiple vitamin deficiencies including beriberi heart with congestive failure. Lahey Clin Bull 1945;4:173-81. PMID 21016382
43: Fahlgren H, Hed R, Lundmark C. Myonecrosis and myoglobinuria in alcohol and barbiturate intoxication. Acta Med Scand 1957;158:405-12. PMID 13469262
44: Fernandez-Sola J, Garcia G, Elena M, et al. Muscle antioxidant status in chronic alcoholism. Alcohol Clin Exp Res 2002;26:1858-62. PMID 12500110
45: Fernandez-Sola J, Nicolas JM, Fatjo F, et al. Evidence of apoptosis in chronic alcoholic skeletal myopathy. Hum Pathol 2003;34:1247-52. PMID 14691909
46: Fernandez-Sola J, Preedy VR, Lang CH, et al. Molecular and cellular events in alcohol-induced muscle disease. Alcohol Clin Exp Res 2007;31(12):1953-62. PMID 18034690
47: Fond B, Richard C, Comoy E, Tillement JP, Auzépy P. Two cases of shoshin beri beri with hemodynamic and plasma catecholamine data. Intensive Care Med 1980;6(3):193-8. PMID 7391348
48: Gabow PA, Daehny WD, Kelleher SP. The spectrum of rhabdomyolysis. Medicine 1982;61:141-52. PMID 7078398
49: Garrett JS, Wikman-Coffelt J, Sievers R, Finkbeiner WE, Parmley WW. Verapamil prevents the development of alcoholic dysfunction in hamster myocardium. J Am Coll Cardiol 1987;9:1326-31. PMID 3584721
50: Gonzalez-Reimers E, Durán-Castellón MC, López-Lirola A, et al. Alcoholic myopathy: vitamin D deficiency is related to muscle fibre atrophy in a murine model. Alcohol Alcohol 2010;45(3):223-30. PMID 20190231
51: Grossman RA, Hamilton RW, Morse BM, Penn AS, Goldberg M. Nontraumatic rhabdomyolysis and acute renal failure. N Engl J Med 1974;291:807-11. PMID 4423658
52: Gubbay ER. Beri-beri heart disease. Can Med Assoc J 1966;95(1):21-7. PMID 5940785
53: Haller RG. Experimental acute alcoholic myopathy--a histochemical study. Muscle Nerve 1985;8:195-203. PMID 4058464
54: Haller RG, Carter NW, Ferguson E, Knochel JP. Serum and muscle potassium in experimental alcoholic myopathy. Neurology 1984a;34:529-32. PMID 6538310
55: Haller RG, Drachman DB. Alcoholic rhabdomyolysis: an experimental model in the rat. Science 1980;208:412-5. PMID 7189294
56: Haller RG, Knochel JP. Skeletal muscle disease in alcoholism. Med Clin North Am 1984b;68:91-103. PMID 6361420
57: Hallgren R, Lundin L, Toxin LE, Venge P. Serum and urinary myoglobin in alcoholics. Acta Med Scand 1980;208:33-9. PMID 7001859
58: Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev 2004;18(16):1926-45. PMID 15314020
59: Hed R. Acute myoglobinuria; report of a case with fatal outcome. Acta Med Scand 1955;152:459-63. PMID 13292165
60: Hed R, Lundmark C, Fahlgren H, Orell S. Acute muscular syndrome in chronic alcoholism. Acta Med Scand 1962;171:585-99. PMID 13905857
61: Hiraga A, Kojima K, Kuwabara S. Clinical features and recovery pattern of secondary hypokalaemic paralysis. J Neurol 2023;270(11):5571-7. PMID 37542171
62: Hun H. Alcoholic paralysis. Am J Med Sci 1885;89:372-88.
63: Imamura T, Kinugawa K. Shoshin beriberi with low cardiac output and hemodynamic deterioration treated dramatically by thiamine administration. Int Heart J 2015;56(5):568-70. PMID 26346515
64: Jacinto E, Loewith R, Schmidt A, Lin S, Rüegg MA, Hall A, Hall MN. Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol 2004;6(11):1122-8. PMID 15467718
65: Jackson J. On a pecular disease resulting from the use of ardent spirits. N Engl J Med 1822;2:351-3.
66: Jeffrey FE, Abelmann WH. Recovery from proved Shoshin beriberi. Am J Med 1971;50(1):123-8. PMID 5539573
67: Jones RH Jr. Beriberi heart disease. Circulation 1959;19(2):275-83. PMID 13629790
68: Jorfeldt L, Juhlin-Dannfelt A. The influence of ethanol on human splanchnic and skeletal muscle metabolism during exercise. Scand J Clin Lab Invest 1977;37:609-18. PMID 594641
69: Kahn LB, Meyer JS. Acute myopathy in chronic alcoholism. Am J Clin Pathol 1970;53:516-30. PMID 5444726
70: Kawai C, Wakabayashi A, Matsumura T, Yui Y. Reappearance of beriberi heart disease in Japan. A study of 23 cases. Am J Med 1980;69(3):383-6. PMID 7416185
71: Kawano H, Koide Y, Toda G, Yano K. ST-segment elevation of electrocardiogram in a patient with Shoshin beriberi. Intern Med 2005a;44(6):578-85. PMID 16020883
72: Kawano H, Hayashi T, Koide Y, Toda G, Yano K. Histopathological changes of biopsied myocardium in Shoshin beriberi. Int Heart J 2005b;46(4):751-9. PMID 16157967
73: Keefer CS. Nutrition classics from The Archives of Internal Medicine 45:1-22, 1930. The beriberi heart. Chester S. Keefer. Nutr Rev 1974;32(10):304-7. PMID 4606854
74: Kiessling KH, Pilstrm L, Bylund AC, Piehl K, Saltin B. Effects of chronic ethanol abuse on structure and enzyme activities of skeletal muscle in man. Scand J Clin Lab Invest 1975;35:601-7. PMID 173013
75: Kim J, Park S, Kim JH, Kim SW, Kang WC, Kim SJ. A case of shoshin beriberi presenting as cardiogenic shock with diffuse ST-segment elevation, which dramatically improved after a single dose of thiamine. Cardiovasc J Afr 2014;25(6):e1-5. PMID 25625639
76: Kimball SR, Lang CH. Mechanisms underlying muscle protein imbalance induced by alcohol. Annu Rev Nutr 2018;38:197-217. PMID 30130465
77: King JF, Easton R, Dunn M. Acute pernicious beriberi heart disease. Chest 1972;61(5):512-4. PMID 5046854
78: Klinkerfuss G, Bleisch V, Dioso MM, Perkoff GT. A spectrum of myopathy associated with alcoholism, II. Light and electron microscopic observations. Ann Int Med 1967;67:493-510. PMID 6042640
79: Knochel JP, Barcenas C, Cotton JR, Fuller TJ, Haller RG, Carter NC. Hypophosphatemia and rhabdomyolysis. J Clin Invest 1978;62:1240-6. PMID 748377
80: Koffler A, Feirdler RM, Massry SG. Acute renal failure due to nontraumatic rhabdomyolysis. Ann Int Med 1976;85:23-8. PMID 937919
81: Kolovou G, Cokkinos P, Bilianou H, Kolovou V, Katsiki N, Mavrogeni S. Non-traumatic and non-drug-induced rhabdomyolysis. Arch Med Sci Atheroscler Dis 2019;4:e252-63. PMID 32368681
82: Kountchev J, Bijuklic K, Bellmann R, Joannidis M. A patient with severe lactic acidosis and rapidly evolving multiple organ failure: a case of shoshin beri-beri. Intensive Care Med 2005;31(7):1004. PMID 15875157
83: Kuncl RW, Wiggins WW. Toxic myopathies. Neurol Clin 1988;6(3):593-619. PMID 3065603
84: Kuno T, Nakamura H, Endo Y, et al. Clinical history and colliquative myocytolysis are keys to the diagnosis of shoshin beriberi. Case Rep Pathol 2014;2014:506072. PMID 24891966
85: Lahey WJ, Arst DB, Silver M, Kleeman CR, Kunkel P. Physiologic observations on a case of beriberi heart disease, with a note on the acute effects of thiamine. Am J Med. 1953;14(2):248-55. PMID 13016605
86: Lang CH, Frost RA, Summer AD, Vary TC. Molecular mechanisms responsible for alcohol-induced myopathy in skeletal muscle and heart. Int J Biochem Cell Biol 2005;37(10):2180-95. PMID 15982919
87: Lang CH, Kimball SR, Frost RA, Vary TC. Alcohol myopathy: impairment of protein synthesis and translation initiation. Int J Biochem Cell Biol 2001;33:457-73. PMID 11331201
88: Lang CH, Pruznak AM, Deshpande N, Palopoli MM, Frost RA, Vary TC. Alcohol intoxication impairs phosphorylation of S6K1 and S6 in skeletal muscle independently of ethanol metabolism. Alcohol Clin Exp Res 2004;28:1758-67. PMID 15547464
89: Langohr H, Wietholter H, Peiffer F. Muscle wasting in chronic alcoholics: comparative histochemical and biochemical studies. J Neurol Neurosurg Psychiatry 1983;46:248-54. PMID 6221080
90: Lanska DJ, Ruff RL. Myopathies and myalgias in the aged. In: Barclay L, editor. Clinical geriatric neurology. Philadelphia: Lea & Febinger Publishing Co., 1993:294-309.**
91: Laonigro I, Correale M, Di Biase M, Altomare E. Alcohol abuse and heart failure. Eur J Heart Fail 2009;11(5):453-62. PMID 19336433
92: Laposata M, Hasaba A, Best CA, et al. Fatty acid ethyl esters: recent observations. Prostaglandins Leukot Essent Fatty Acids 2002;67(2-3):193-6. PMID 12324241
93: Lessard R, Bernier JP, Morin Y. Physiological studies on beriberi heart disease by injection of radioactive material. Can Med Assoc J 1959;80(2):112-4. PMID 13618804
94: Levitt DE, Chalapati N, Prendergast MJ, Simon L, Molina PE. Ethanol-impaired myogenic differentiation is associated with decreased myoblast glycolytic function. Alcohol Clin Exp Res 2020;44(11):2166-76. PMID 32945016
95: Lipton JO, Sahin M. The neurology of mTOR. Neuron 2014;84(2):275-91. PMID 25374355
96: Loma-Osorio P, Peñafiel P, Doltra A, Sionis A, Bosch X. Shoshin beriberi mimicking a high-risk non-ST-segment elevation acute coronary syndrome with cardiogenic shock: when the arteries are not guilty. J Emerg Med 2011;41(4):e73-7. PMID 18930369
97: Mansouri A, Demeilliers C, Amsellem S, Pessayre D, Fromenty B. Acute ethanol administration oxidatively damages and depletes mitochondrial DNA in mouse liver, brain, heart, and skeletal muscles: protective effects of antioxidants. J Pharmacol Exp Ther 2001;298:737-43 PMID 11454938
98: Maramattom BV. Acute ptotic myelopathy: cervical compressive myelopathy resulting from prolonged head ptosis after alcohol intoxication. Clin Med (Lond) 2023;23(5):515-7. PMID 37775176
99: Martin F, Levi AJ, Slavin G, Peters TJ. Glycogen content and activities of key glycolytic enzymes in muscle biopsies from control subjects and patients with chronic alcoholic skeletal myopathy. Clin Sci 1984;66:69-78. PMID 6317276
100: Martin F, Peters TJ. Alcoholic muscle disease. Alcohol Alcohol 1985a;20(2):125-36. PMID 2932118
101: Martin F, Ward K, Slavin G, Levi J, Peters TJ. Alcoholic skeletal myopathy, a clinical and pathological study. Q J Med 1985;55:233-55. PMID 2991970
102: Martin FC, Peters TJ. Assessment in vitro and in vivo of muscle degradation in chronic skeletal muscle myopathy of alcoholism. Clin Sci (Lond) 1985b;68(6):693-700. PMID 2485272
103: Martin JB, Craig JW, Eckel RE. Hypokalemic myopathy in chronic alcoholism. Neurology 1971;21:1160-8. PMID 5166222
104: Martinez AJ, Hooshmand H, Faris AA. Acute alcoholic myopathy, enzyme histochemistry and electron microscopic findings. J Neurol Sci 1973;20:245-52. PMID 4357768
105: McIntyre N, Stanley NN. Cardiac beriberi: two modes of presentation. Br Med J 1971;3(5774):567-9. PMID 5571454
106: McManus DD, Yin X, Gladstone R, et al. Alcohol consumption, left atrial diameter, and atrial fibrillation. J Am Heart Assoc 2016;5(9). PMID 27628571
107: Messing RO, Carpenter CL, Diamond I, Greenberg DA. Ethanol regulates calcium channels in clonal neural cells. Proc Natl Acad Sci USA 1986;83:6213-5. PMID 2426713
108: Meulders Q, Laterre PF, Sergant M, Corbeel L. Shoshin beriberi: a fulminant beriberi heart disease. Acta Clin Belg 1988;43(2):115-9. PMID 3400376
109: Mills KR, Ward K, Martin F, Peters TJ. Peripheral neuropathy and myopathy in chronic alcoholism. Alcohol Alcohol 1986;21(4):357-62. PMID 3028439
110: Moser SE, Brown AM, Clark BC, Arnold WD, Baumann CW. Neuromuscular mechanisms of weakness in a mouse model of chronic alcoholic myopathy. Alcohol Clin Exp Res 2022;46(9):1636-47. PMID 35869821
111: Myerson RM, Lafair JS. Alcoholic muscle disease. Med Clin North Am 1970;54:723-30. PMID 5423141
112: Naidoo DP. Beriberi heart disease in Durban. A retrospective study. S Afr Med J 1987;72(4):241-4. PMID 3616806
113: Naidoo DP, Gathiram V, Sadhabiriss A, Hassen F. Clinical diagnosis of cardiac beriberi. S Afr Med J. 1990;77(3):125-7. PMID 2305319
114: Nemirovskaya TL, Shenkman BS, Zinovyeva oE, Kazantseva IuV, Samkhaeva ND. The development of clinical and morphological manifestations of chronic alcoholic myopathy in men with prolonged alcohol intoxication [Article in Russian]. Fiziol Cheloveka 2015;41(6):65-9. PMID 26859989
115: Nevins MA, Saran M, Bright M, Lyon LJ. Pitfalls in interpreting serum creatine phosphokinase activity. JAMA 1973;224:1382-7. PMID 4739986
116: Nicolas JM, Garcia G, Fatjo F, et al. Influence of nutritional status on alcoholic myopathy. Am J Clin Nutr 2003;78:326-33. PMID 12885717
117: Niemela O, Parkkila S, Koll M, Preedy VR. Generation of protein adducts with malondialdehyde and acetaldehyde in muscles with predominantly type I or type II fibers in rats exposed to ethanol and the acetaldehyde dehydrogenase inhibitor cyanamide. Am J Clin Nutr 2002;76:668-74. PMID 12198016
118: Nygren A. Serum creatine phosphokinase in chronic alcoholism. Acta Med Scand 1967;182:383-7. PMID 6058366
119: Nygren A. Serum creatine phosphokinase in chronic alcoholism, in connection with acute alcohol intoxication. Acta Med Scand 1966;179:623-30. PMID 5936184
120: Oh SJ. Alcoholic myopathy, a critical review. Alabama J Med Sci 1972;9(1):79-95. PMID 4556487
121: Oh SJ. Alcoholic myopathy, electrophysiological study. Electromyogr Clin Neurophysiol 1976;16(2-3):205-18. PMID 964199
122: Otis JS, Guidot DM. Procysteine stimulates expression of key anabolic factors and reduces plantaris atrophy in alcohol-fed rats. Alcohol Clin Exp Res 2009;33(8):1450-9. PMID 19426167
123: Pang JA, Yardumian A, Davies R, Patterson DL. Shoshin beriberi: an underdiagnosed condition? Intensive Care Med 1986;12(5):380-2. PMID 3771918
124: Papadatos SS, Deligiannis G, Bazoukis G, et al. Nontraumatic rhabdomyolysis with short-term alcohol intoxication - a case report. Clin Case Rep 2015;3(10):769-72. PMID 26509002
125: Paternostro C, Gopp L, Tomschik M, et al. Incidence and clinical spectrum of rhabdomyolysis in general neurology: a retrospective cohort study. Neuromuscul Disord 2021;31(12):1227-34. PMID 34711480
126: Pereira VG, Masuda Z, Katz A, Tronchini V Jr. Shoshin beriberi: report of two successfully treated patients with hemodynamic documentation. Am J Cardiol 1984;53(10):1467. PMID 6720597
127: Perkoff GT. Alcoholic myopathy. Ann Rev Med 1971;22:125-32. PMID 4944411
128: Perkoff GT, Dioso MM, Bleisch V, et al. A spectrum of myopathy associated with alcoholism. Ann Intern Med 1967;67:481-92. PMID 6042640
129: Perkoff GT, Hardy P, Valez-Garcia E. Reversible acute muscular syndrome in chronic alcoholism. N Engl J Med 1966;274:1277-85. PMID 5936410
130: Peters TJ, Martin F, Ward K. Chronic alcoholic skeletal myopathy--common and reversible. Alcohol 1985;2(3):485-9. PMID 3161521
131: Piano MR, Phillips SA. Alcoholic cardiomyopathy: pathophysiologic insights. Cardiovasc Toxicol 2014;14(4):291-308. PMID 24671642
132: Pigeaud L, de Veld L, van der Lely N. Elevated creatinine kinase levels amongst Dutch adolescents with acute alcohol intoxication. Eur J Pediatr 2023;182(3):1371-5. PMID 36662269
133: Prasad P, Tabatznik B, Kotler MN. Recurrent acute alcoholic myopathy simulating deep vein thrombosis in association with cardiomyopathy and parasystolic ventricular tachycardia. Johns Hopkins Med J 1974;134:226-32. PMID 4821135
134: Preedy VR, Adachi J, Ueno Y, et al. Alcoholic skeletal muscle myopathy: definitions, features, contribution of neuropathy, impact and diagnosis. Eur J Neurol 2001;8:677-87. PMID 11784353
135: Preedy VR, Crabb DW, Farrés J, Emery PW. Alcoholic myopathy and acetaldehyde. Novartis Found Symp 2007;285:158-77; discussion 177-82, 198-9. PMID 17590994
136: Preedy VR, Marway JS, Macpherson AJ, Peters TJ. Ethanol-induced smooth and skeletal muscle myopathy: use of animal studies. Drug Alcohol Depend 1990;26:1-8. PMID 1698602
137: Preedy VR, Patel VB, Reilly ME, Richardson PJ, Falkous G, Mantle D. Oxidants, antioxidants and alcohol: implications for skeletal and cardiac muscle. Front Biosci 1999b;4:e58-66. PMID 10430553
138: Preedy VR, Patel VB, Why HJ, Corbett JM, Dunn MJ, Richardon PJ. Alcohol and the heart: biochemical alterations. Cardiovasc Res 1996;31(1):139-47. PMID 8849598
139: Preedy VR, Peters TJ, Patel VB, Miell JP. Chronic alcoholic myopathy: transcription and translational alterations. FASEB J 1994a;8(14):1146-51. PMID 7958620
140: Preedy VR, Reilly ME, Patel VB, Richardson PJ, Peters TJ. Protein metabolism in alcoholism: effects on specific tissues and the whole body. Nutrition 1999a;15(7-8):604-8. PMID 10422097
141: Preedy VR, Richardson PJ. Alcoholic cardiomyopathy: clinical and experimental pathological changes. Herz 1996;21(4):241-7. PMID 8805004
142: Preedy VR, Richardson PJ. Ethanol induced cardiovascular disease. Br Med Bull 1994;50(1):152-63. PMID 8149190
143: Preedy VR, Salisbury JR, Peters TJ. Alcoholic muscle disease: features and mechanisms. J Pathol 1994d;173(4):309-15. PMID 7965390
144: Preedy VR, Siddiq T, Why HJ, Richardson PJ. Ethanol toxicity and cardiac protein synthesis in vivo. Am Heart J 1994b;127(5):1432-9. PMID 8172081
145: Preedy VR, Siddiq T, Why H, Richardson PJ. The deleterious effects of alcohol on the heart: involvement of protein turnover. Alcohol Alcohol 1994c;29(2):141-7. PMID 8080594
146: Reilly ME, Patel VB, Peters TJ, Preedy VR. In vivo rates of skeletal muscle protein synthesis in rats are decreased by acute ethanol treatment but are not ameliorated by supplemental alpha-tocopherol. J Nutr 2000;130:3045-9. PMID 11110866
147: Rowland LP, Penn AS. Myoglobinuria. Med Clin North Am 1972;50:1233-56. PMID 5085857
148: Rubin E. Alcoholic myopathy in heart and skeletal muscle. N Engl J Med 1979;301:28-33. PMID 377072
149: Sacanella E, Fernandez-Sola J, Cofan M, et al. Chronic alcoholic myopathy: diagnostic clues and relationship with other ethanol-related diseases. QJM 1995;88:811-7. PMID 8542266
150: Salem RO, Laposata M, Rajendram R, Cluette-Brown JE, Preedy VR. The total body mass of fatty acid ethyl esters in skeletal muscles following ethanol exposure greatly exceeds that found in the liver and the heart. Alcohol Alcohol 2006;41:598-603. PMID 16980711
151: Saltin B, Gollnick PD. Skeletal muscle adaptability: significance for metabolism and performance. In: Handbook of physiology. Skeletal muscle. Bethesda, Maryland: Am Physiol Soc, 1983:555-631.
152: Sambrook PN, Dalton WR. Shoshin Beriberi. Aust N Z J Med 1981;11(2):190-2. PMID 6944046
153: Sawhney JS, Kasotakis G, Goldenberg A, et al. Management of rhabdomyolysis: A practice management guideline from the Eastern Association for the Surgery of Trauma. Am J Surg 2022;224(1 Pt A):196-204. PMID 34836603
154: Saya RP, Baikunje S, Prakash PS, Subramanyam K, Patil V. Clinical correlates and outcome of shoshin beriberi. N Am J Med Sci. 2012;4(10):503-6. PMID 23112976
155: Seneviratne BI. Acute cardiomyopathy with rhabdomyolysis in chronic alcoholism. Brit Med J 1975;4:378-80. PMID 1192080
156: Seta T, Okuda K, Toyama T, Himeno Y, Ohta M, Hamada M. Shoshin beriberi with severe metabolic acidosis. South Med J 1981;74(9):1127-30. PMID 7280764
157: Shanoff HM. Alcoholic cardiomyopathy: an introductory review. Can Med Assoc J 1972;106(1):55-62. PMID 4550483
158: Shenkman BS, Belova SP, Zinovyeva OE, et al. Effect of chronic alcohol abuse on anabolic and catabolic signaling pathways in human skeletal muscle. Alcohol Clin Exp Res 2018;42(1):41-52. PMID 29044624
159: Shenkman BS, Zinovyeva OE, Belova SP, et al. Cellular and molecular signatures of alcohol-induced myopathy in women. Am J Physiol Endocrinol Metab 2019;316(5):E967-76. PMID 30912963
160: Shivalkar B, Engelmann I, Carp L, De Raedt H, Daelemans R. Shoshin syndrome: two case reports representing opposite ends of the same disease spectrum. Acta Cardiol 1998;53(4):195-9. PMID 9842404
161: Simon L, Jolley SE, Molina PE. Alcoholic myopathy: pathophysiologic mechanisms and clinical implications. Alcohol Res 2017;38(2):207-17. PMID 28988574
162: Simon L, LeCapitaine N, Berner P, et al. Chronic binge alcohol consumption alters myogenic gene expression and reduces in vitro myogenic differentiation potential of myoblasts from rhesus macaques. Am J Physiol Regul Integr Comp Physiol 2014;306(11):R837-44. PMID 24671243
163: Smith SW. Severe acidosis and hyperdynamic circulation in a 39-year-old alcoholic. J Emerg Med 1998;16(4):587-91. PMID 9696175
164: Song SK, Rubin E. Ethanol produces muscle damage in human volunteers. Science 1972;175:327-8. PMID 5008161
165: Su F, Meng XX, Su CZ, Zhang JL. A case of drug-induced myopathy in alcoholic cirrhosis caused by voriconazole. Eur Rev Med Pharmacol Sci 2023;27(9):3833-6. PMID 37203807
166: ter Maaten JC, Hoorntje SJ, Hillen HF. Acute pernicious or fulminating beriberi heart disease. A report of 6 patients. Neth J Med 1995;46(5):217-24. PMID 7783822
167: Tobias SL, van der Westhuyzen J, Davis RE, Icke GC, Atkinson PM. Alcohol intakes and deficiencies in thiamine and vitamin B6 in black patients with cardiac failure. S Afr Med J 1989;76(7):299-302. PMID 2799573
168: Tobin JR Jr, Driscoll JF, Lim MT, Sutton GC, Szanto PB, Gunnar RM. Primary myocardial disease and alcoholism. The clinical manifestations and course of the disease in a selected population of patients observed for three or more years. Circulation 1967;35(4):754-64. PMID 4225807
169: Tran HA. A 74-year-old woman with increasing dyspnea. Wet berberi with fulminant (Shoshin) cardiac failure and elevated troponin I. Arch Pathol Lab Med 2006;130(1):e8-10. PMID 16390253
170: Trounce I, Byrne E, Dennet X. Biochemical and morphological studies of skeletal muscle in experimental chronic alcoholic myopathy. Acta Neurol Scand 1990;82:386-91. PMID 2291400
171: Trounce I, Byrne E, Dennet X. Chronic alcoholic proximal wasting: physiological, morphological and biochemical studies in skeletal muscle. Aust N Z J Med 1987;17:413-9. PMID 3435319
172: Urbano-Marquez A, Estruch R, Navarro-Lopex F, Grau JM, Mont L, Rubin E. The effects of alcoholism on skeletal and cardiac muscle. N Engl J Med 1989;320:409-15. PMID 2913506
173: Urbano-Márquez A, Fernández-Solà J. Effects of alcohol on skeletal and cardiac muscle. Muscle Nerve 2004;30(6):689-707. PMID 15490485
174: Valaitis J, Pilz CG, Oliner H, Chomet B. Myoglobinuria, myoglobinuric nephrosis, and alcoholism. Arch Pathol 1960;70:195-202. PMID 13840755
175: Velez-Garcia E, Hardy P, Diosos M, Perkoff GT. Cysteine-stimulated serum creatine phosphokinase: unexpected results. J Lab Clin Med 1966;68:636-45. PMID 4958833
176: Victor M. Toxic and nutritional myopathies. In: Engel AG, Banker BQ, editors. Myology. New York: McGraw-Hill, 1986:1807-42.
177: Wallgren H, Barry H. Actions of alcohol. Vol. I. Biochemical, physiological and psychological effects. New York: Elsevier, 1970.
178: Ward RJ, Peters TJ. The antioxidant status of patients with either alcohol-induced liver damage or myopathy. Alcohol Alcohol 1992;27(4):359-65. PMID 1418110
179: Webster MW, Ikram H. Myocardial function in alcoholic cardiac beriberi. Int J Cardiol 1987;17(2):213-5. PMID 3679603
180: Whyte KF, Dunnigan MG, McIntosh WB. Excessive beer consumption and beri-beri. Scott Med J 1982;27(4):288-91. PMID 7146877
181: Wijnia JW, Wielders JP, Lips P, van de Wiel A, Mulder CL, Nieuwenhuis KG. Is vitamin D deficiency a confounder in alcoholic skeletal muscle myopathy. Alcohol Clin Exp Res 2013;37 Suppl 1:E209-15. PMID 23240627
182: Worrall S, Niemela O, Parkkila S, Peters TJ, Preedy VR. Protein adducts in type I and type II fibre predominant muscles of the ethanol-fed rat: preferential localisation in the sarcolemmal and subsarcolemmal region. Eur J Clin Invest 2001;31(8):723-30. PMID 11473574
183: Yamasaki H, Tada H, Kawano S, Aonuma K. Reversible pulmonary hypertension, lactic acidosis, and rapidly evolving multiple organ failure as manifestations of shoshin beriberi. Circ J 2010;74(9):1983-5. PMID 20622473
184: Yin Y, Hua H, Li M, et al. mTORC2 promotes type I insulin-like growth factor receptor and insulin receptor activation through the tyrosine kinase activity of mTOR. Cell Res 2016;26(1):46-65. PMID 26584640
185: Young IS, McEneny J. Lipoprotein oxidation and atherosclerosis. Biochem Soc Trans 2001;29 (Pt 2):358-62. PMID 11356183
186: Zakhari S. Alcohol metabolism and epigenetics changes. Alcohol Res 2013;35(1):6-16.** PMID 24313160
187: Zakhari S. Overview: how is alcohol metabolized by the body? Alcohol Res Health 2006;29(4):245-54.** PMID 17718403
188: Zhang Y, Ren J. ALDH2 in alcoholic heart diseases: molecular mechanism and clinical implications. Pharmacol Ther 2011;132(1):86-95. PMID 21664374

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

Douglas J Lanska MD MS MSPH

Dr. Lanska of the University of Wisconsin School of Medicine and Public Health and the Medical College of Wisconsin has no relevant financial relationships to disclose.
See Profile

Former Authors

Linda Chang MD, Ronald G Haller MD, and Thomas Klopstock MD

Patient Profile

Age range of presentation: 19 to 65+ years
Sex preponderance: male>female, >2:1
Heredity: none
Population groups selectively affected: none selectively affected
Occupation groups selectively affected: none selectively affected

This is an article preview.
Start a Free Account
to access the full version.

Nearly 3,000 illustrations, including video clips of neurologic disorders.
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
Full spectrum of neurology in 1,200 comprehensive articles.
Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink®, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660

Support: service@medlink.com

Editor: editor@medlink.com

ISSN: 2831-9125

Alcoholic myopathy

Associated Disorders

Acute alcohol withdrawal
Acute renal failure
Alcoholic cardiomyopathy
Alcoholic peripheral neuropathy
Crush syndrome
- Delirium tremens
- Fetal alcohol myopathy
- Hepatic cirrhosis
- Hyperkalemia
- Nutritional deficiency

Differential Diagnosis

acquired rhabdomyolysis
heroin abuse
cocaine abuse
amphetamine abuse
trauma/crush injury
- phosphate depletion
- potassium depletion
- underlying metabolic defect in carbohydrate or lipid metabolism
- chronic myopathic weakness
- inflammatory myopathies
- acquired metabolic myopathies
- limb girdle dystrophy
- steroid myopathy
- hypophosphatemia
- muscle disuse

Also Relevant

Alcohol abuse and its neurologic complications
Alcohol withdrawal seizures
Drug-induced myopathies
Myoglobinuria
Nutrition-related peripheral neuropathies
- Sleep and alcohol use and abuse

Alcoholic myopathy

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Table 1. Acute and Chronic Alcoholic Myopathy: Clinical and Laboratory Features

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Table 2. Muscle Fiber Types

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Diagnostic workup

Management

Special considerations

Pregnancy

Anesthesia

Media

References

Contributors

Author

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

ALS-like disorders of the Western Pacific

Paraspinal neuromuscular syndromes

Dementia associated with amyotrophic lateral sclerosis

Collagen VI-related dystrophies: Ullrich congenital muscular dystrophy, Bethlem muscular dystrophy, and intermediate COL6-RD

Sleep and neuromuscular and spinal cord disorders

Periodic paralysis and the nondystrophic myotonias (skeletal muscle channelopathies)

Malignant hyperthermia

Thallium neuropathy

This is an article preview.
Start a Free Account
to access the full version.