Alcohol (Ethanol) Related Neuropathy

Updated: Nov 16, 2018
  • Author: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS; Chief Editor: Stephen A Berman, MD, PhD, MBA  more...
  • Print


The clinical symptoms of alcoholic peripheral neuropathy were described more than 200 years ago. The descriptions by Lettsom (1787) [1] and Jackson (1822) [2] have led to the recognition and association of peripheral nerve disease with excessive ethanol use. Several terms connote alcohol neuropathy, including neuritic beriberi, neuropathic beriberi, and alcoholic neuritis. In patients with alcoholic neuropathy, nutritional deficiency goes hand in hand with alcohol abuse.

The similarity between beriberi, which is caused by deficiency of thiamine (vitamin B 1), and alcoholic neuropathy had long been noted, but in 1928, Shattuck was the first to seriously discuss the relationship. [3] He suggested that polyneuritis of chronic alcoholism was caused chiefly by failure to take or assimilate food containing a sufficient quantity of vitamin B complex and might properly be regarded as true beriberi. However, this theory may be only partially true. Independently of thiamine deficiency, ethanol now appears to have a direct toxic effect on peripheral nerves.



The precise pathogenesis of alcohol neuropathy remains unclear. Separating ethanol use from nutritional and vitamin deficiencies, especially thiamine, has always been difficult and a source of long-standing debate. Nutritional deficiency (frequently associated with alcohol neuropathy) and/or the direct toxic effect of alcohol or both have been implicated and studied. [4, 5] In Wernicke-Korsakoff syndrome, a clear association between reduction of thiamine levels or thiamine-mediated enzyme activity (transketolase) has been established, though this has not been conclusively established in the case of peripheral neuropathy.

It is widely assumed that alcohol-related peripheral neuropathy is primarily a consequence of nutritional deficiency. This was largely based on observations made more than eight decades ago demonstrating that thiamine deficiency (beriberi) neuropathy was clinically similar to ALN. In recent studies, failure of thiamine treatment to reverse ALN, together with new information demonstrating clinical and electrophysiological distinctions between ALN and nutritional deficiency neuropathies, suggests that alcohol itself may significantly predispose and enhance development of neuropathy in the appropriate clinical setting. The authors reviewed the evidence on both sides and conclude that ALN should be regarded as a toxic rather than nutritional neuropathy. [6] In their comparison of patients with alcoholism and nonalcoholic control subjects, Behse and Buchthal concluded that nutritional deficiencies alone did not produce the neuropathy. [7]

Monforte et al. concluded that alcohol appears to be toxic to autonomic and peripheral nerves in a dose-dependent manner, based on heart rate, blood pressure, and electrophysiologic examination. [8]

In a study of macaque monkeys, Hallett et al. failed to produce clinical and electrophysiologic signs of neuropathy in monkeys that were given a certain amount of alcohol for 3–5 years. [9]  Studies in rats also failed to demonstrate a direct toxic effect of alcohol on the peripheral nerves.

Most studies of peripheral neuropathy in humans and animals implicate nutritional deficiency as an etiology as opposed to the direct toxic effect of alcohol.

Independent of thiamine deficiency, ethanol now appears to have a direct toxic effect on the peripheral nerves. Dina et al suggest that catecholamines in nociceptors are metabolized to neurotoxic products by monoamine oxidase-A (MAO-A). This can cause neuronal dysfunction, which leads to neuropathic pain. [10]

Painful alcoholic polyneuropathy with predominant small-fiber loss and normal thiamine status is well known. The clinicopathologic features of painful symptoms and small axon loss are distinct from those of beriberi neuropathy. This supports the view of direct neurotoxic effect by alcohol or its metabolites. [11]

Axonal transport and cytoskeletal properties are impaired by ethanol exposure. Protein kinase A and protein kinase C may also play a role in the pathogenesis, especially in association with painful symptoms. [12]

In utero alcohol exposure predisposes to a major risk factor for lifelong aberrant neuroimmune function. Behavioral and physiological sequelae occur throughout life and include cognitive developmental disabilities as well as disease susceptibility related to aberrant immune and neuroimmune actions, in particular significant alterations in the neuroimmune axis occur. [13, 14]




Depending on criteria and patient selection, incidence of peripheral neuropathy ranging from 10% to 50% has been reported. These studies included alcoholics hospitalized for other reasons or for detoxification. Neuropathy is more prevalent in frequent, heavy, and continuous drinkers compared to more episodic drinkers. [8]


Johnson and Robinson studied the mortality rate of individuals with alcoholism who had autonomic neuropathy. [13]

  • Their findings suggested that evidence of vagal neuropathy in long-term alcoholics is associated with a significantly higher mortality rate than in the general population (a reported 88% survival rate at 7 years in alcoholics with autonomic neuropathy as compared to 94% in the general population).

  • Deaths due to cardiovascular disease are a major factor.

  • Many deaths were attributed to strokes, since heavy alcohol consumption is a significant risk factor for stroke.


A high incidence of alcoholic polyneuropathy has been observed in women and men. Women, when compared to men, are more predisposed to alcohol-induced damage, and the susceptibility extends to hepatic, cardiac, cerebral, and muscular changes. Also, there appears to be a greater sensitivity of females to the toxic effects of alcohol on peripheral nerve fibers unrelated to malnutrition.