Neuropathy, or damage to the peripheral nerves, has dozens of possible causes, but a handful account for the vast majority of cases. Diabetes is the single most common cause, followed by alcohol use, chemotherapy, vitamin deficiencies, infections, autoimmune conditions, inherited disorders, and toxic exposures. In roughly 25 to 30 percent of cases, no cause is ever identified, a condition called idiopathic neuropathy.
Diabetes and High Blood Sugar
Persistently elevated blood sugar is the leading cause of peripheral neuropathy worldwide. The damage isn’t simply from sugar “coating” nerves. Instead, excess glucose triggers a chain of metabolic problems inside nerve cells. One major pathway works like this: an enzyme converts surplus glucose into a sugar alcohol called sorbitol, which builds up and disrupts the water balance inside cells. The cell tries to compensate by pushing out other protective molecules, and the resulting stress damages the nerve’s internal structure. Sorbitol is then converted into fructose, and both of these byproducts promote oxidative damage to nerve tissue.
A second pathway involves glucose being shunted into a chemical route that ramps up production of certain proteins. One of these proteins promotes tiny blood clots in the small vessels that feed nerves, starving them of oxygen. Another triggers the production of damaging free radicals that cause nerve cells to self-destruct. These processes are slow and cumulative, which is why diabetic neuropathy typically appears after years of poorly controlled blood sugar and usually starts in the feet before progressing upward.
Alcohol Use
Heavy, long-term alcohol consumption damages peripheral nerves through two overlapping mechanisms. The first is direct toxicity: when your body breaks down ethanol, it produces acetaldehyde, a compound that is directly poisonous to nerve tissue. Alcohol also disrupts the internal transport system that nerve cells rely on to shuttle nutrients and structural materials along their length.
The second mechanism is nutritional. People who drink heavily often eat poorly and absorb nutrients less efficiently. Thiamine (vitamin B1) is especially vulnerable. It plays a critical role in nerve metabolism, and alcohol both depletes the liver’s stores and impairs the gut’s ability to absorb it. The combination of direct nerve poisoning and thiamine deficiency is likely additive, meaning each one makes the other worse. Alcoholic neuropathy can be distinguished from pure thiamine deficiency (beriberi), but in practice both factors are usually at work together. Oxidative stress from chronic alcohol exposure adds a third layer of damage by generating free radicals that injure nerve fibers.
Chemotherapy
Certain cancer drugs are notorious for causing neuropathy, sometimes severely enough to force a dose reduction or treatment change. The agents most likely to cause nerve damage are platinum-based drugs (cisplatin, oxaliplatin), taxanes, vinca alkaloids, and bortezomib. The risk depends on the specific drug, the cumulative dose, and how long treatment continues. Symptoms often begin in the fingers and toes during treatment and can persist for months or even years after chemotherapy ends. In some people, symptoms actually worsen for a period after the last dose before stabilizing, a pattern sometimes called “coasting.”
Vitamin Deficiencies
B vitamins are essential for maintaining the insulating sheath (myelin) that wraps around nerve fibers and allows signals to travel quickly. Vitamin B12 deficiency is the most clinically significant. Without enough B12, the body cannot properly maintain myelin, and nerve signals slow down or misfire. This causes numbness, tingling, and balance problems that typically start in the feet. B12 deficiency can develop from poor dietary intake (especially in strict vegans), from conditions that impair absorption like pernicious anemia or celiac disease, or from long-term use of acid-reducing medications.
Thiamine (B1), B6, and folate deficiencies can also contribute to neuropathy. Notably, excessive B6 intake from supplements can itself cause nerve damage, making it one of the few vitamins where both too little and too much are harmful.
Autoimmune Conditions
Sometimes the immune system mistakenly attacks the peripheral nerves. Guillain-Barré syndrome (GBS) is the most dramatic example: an acute autoimmune attack that causes rapidly progressive weakness, often starting in the legs and moving upward over days to weeks. Most people recover, though it can be life-threatening if it affects the muscles used for breathing.
Chronic inflammatory demyelinating polyneuropathy (CIDP) is essentially the long-term version of GBS. Instead of a single acute episode, the immune system wages a sustained campaign against the nerve’s myelin coating, causing progressive or relapsing weakness and sensory loss over months. CIDP can be difficult to diagnose because its variants present differently. Other autoimmune diseases that can cause neuropathy include lupus, rheumatoid arthritis, Sjögren’s syndrome, and vasculitis, which damages the small blood vessels supplying nerves.
Infections That Damage Nerves
A range of infections can injure peripheral nerves through direct invasion, inflammation, or immune-mediated damage.
- Shingles (herpes zoster): The reactivated chickenpox virus travels along a nerve root, causing a painful, blistering rash in a band-like pattern. Nerve pain and tingling typically persist for four to six weeks, though some people develop postherpetic neuralgia, pain lasting months or years. Muscle weakness in the same limb can appear within a few days of the rash.
- Lyme disease: Nerve involvement occurs in 10 to 40 percent of infections. Facial nerve paralysis is the most common pattern, and it affects both sides of the face in about 75 percent of those cases. In the chronic stage, a distal sensory-motor neuropathy can develop anywhere from six months to eight years after the initial infection.
- HIV: Neuropathy is the most common peripheral nerve complication of HIV, affecting roughly 35 percent of people with advanced disease. It typically causes painful burning and tingling in the feet, with sensory loss that can become severe.
- Leprosy: Still a significant cause of neuropathy globally, leprosy bacteria directly invade skin nerves. About 20 to 30 percent of people with leprosy develop nerve damage, most commonly affecting the ulnar nerve in the forearm. Sensory loss appears in 95 percent of cases.
- Syphilis: Untreated syphilis can cause a form of neuropathy called tabes dorsalis 10 to 30 years after the initial infection, with characteristic “lightning pains” in the legs, loss of position sense, and an unsteady gait.
Toxic Exposures
Heavy metals and industrial chemicals can poison peripheral nerves. The pattern and severity depend on the substance involved.
Lead neuropathy is now rare but still occurs in industries like smelting and battery manufacturing. Unusually for a toxic neuropathy, lead preferentially attacks motor nerves, causing weakness in the wrist and finger extensors (resulting in wrist drop) rather than the typical numbness-first pattern. Mercury causes a sensory neuropathy with balance problems, often accompanied by tremor and behavioral changes. Arsenic poisoning can mimic Guillain-Barré syndrome, with rapid-onset weakness appearing weeks after an acute exposure. Chronic low-level arsenic exposure causes a milder neuropathy along with characteristic skin changes and nail lines. Thallium, historically used as a rat poison, causes painful neuropathy followed by hair loss weeks later.
Industrial chemicals are another category. Acrylamide, used in dye and paper manufacturing, causes a slowly progressive neuropathy with prominent balance problems. n-Hexane, found in industrial solvents and inhaled recreationally as “glue-sniffing,” damages sensory and motor nerves. Organophosphate pesticides can cause numbness and foot drop about three weeks after exposure.
Inherited Neuropathy
Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy, affecting about 1 in 3,300 people worldwide and an estimated 150,000 people in the United States. CMT is not a single disease but a group of genetic conditions that damage peripheral nerves.
The most common form, CMT1, is caused by mutations in a gene called PMP22 in 70 to 80 percent of cases. This gene provides instructions for making a protein critical to the myelin sheath. Another 10 to 12 percent of CMT1 cases involve mutations in the MPZ gene. CMT2, which damages the nerve fiber itself rather than its insulation, is most commonly linked to mutations in the MFN2 gene (about 20 percent of cases). The X-linked form, CMTX, traces to GJB1 gene mutations in roughly 90 percent of affected individuals. CMT typically begins in childhood or young adulthood with foot deformities, ankle weakness, and gradual loss of sensation in the hands and feet.
Other Common Causes
Kidney disease allows toxins to accumulate in the blood that damage nerves. Hypothyroidism causes fluid retention that can compress nerves and also impairs nerve metabolism directly. Physical compression or entrapment of a nerve, as in carpal tunnel syndrome, is technically a form of neuropathy, though most people think of it as a separate condition. Certain medications beyond chemotherapy, including some antibiotics, anticonvulsants, and heart medications, can cause neuropathy as a side effect. And in a substantial number of cases, no underlying cause is found despite thorough testing, leaving the diagnosis as idiopathic neuropathy, which tends to progress slowly and primarily affects sensory nerves in the feet.