Can statins (HMG-CoA reductase inhibitors) cause peripheral neuropathy?

Statin Therapy and Peripheral Neuropathy

Yes, statins can cause peripheral neuropathy, although it is a relatively uncommon adverse effect that should be monitored in patients on long-term statin therapy.

Evidence for Statin-Associated Peripheral Neuropathy

• The FDA drug label for rosuvastatin specifically lists peripheral neuropathy as a reported adverse reaction during postmarketing surveillance, noting "rare postmarketing reports" of this condition 1
• A 2019 study found that 66% of patients on long-term statin therapy (atorvastatin or rosuvastatin) showed evidence of polyneuropathy on neurological examination and electroneuromyography (ENMG), while none was detected in the control group 2
• Early case reports from 1999 documented seven cases of reversible peripheral neuropathy associated with long-term statin therapy, where other causes were thoroughly excluded 3

Risk Factors and Characteristics

• The risk of peripheral neuropathy appears to increase with:

  • Longer duration of statin therapy (>1 year) 2
  • Higher statin doses 4
  • Lipophilic statins (particularly atorvastatin and fluvastatin) may have a stronger association with neuropathy than hydrophilic statins 5

• The neuropathy is typically:

  • Axonal in nature, affecting both thick and thin nerve fibers 3
  • May present with symptoms such as tingling, numbness, pain, tremor in extremities, and unsteadiness while walking 2

Monitoring and Management

• While routine monitoring for peripheral neuropathy is not explicitly recommended in guidelines, clinicians should:

  • Be vigilant for neurological symptoms in patients on long-term statin therapy 2
  • Consider early detection of peripheral neuropathy to prevent permanent nerve damage 2
  • Evaluate for other common causes of peripheral neuropathy, particularly in patients with diabetes 4

• For patients who develop symptoms of peripheral neuropathy while on statins:

  • Consider dose reduction or temporary discontinuation of the statin 4
  • Evaluate whether to reinstitute therapy based on symptom resolution and risk-benefit assessment 4

Conflicting Evidence

• A 2021 meta-analysis found a non-significant increase in peripheral neuropathy with statin exposure (RR 1.26,95% CI 0.92-1.74), concluding that statins do not significantly influence the risk of developing peripheral neuropathy 6
• However, a 2013 study using NHANES data found that statin use was significantly associated with peripheral neuropathy (adjusted OR 1.3; 95% CI 1.1-1.6), controlling for multiple factors including diabetes status 7

Potential Mitigation Strategies

• Some research suggests that combining statins with niacin (vitamin B3) may reduce the risk of peripheral neuropathy attributed to statins 5
• The 2025 diabetes care guidelines note that conventional lipid-lowering therapy (including statins) does not appear effective in treating or preventing diabetic peripheral neuropathy development, despite the relationship between dyslipidemia and neuropathy 4

Clinical Implications

• The benefits of statin therapy in reducing cardiovascular events generally outweigh the risk of peripheral neuropathy for most patients 4
• Patients at higher risk for statin-associated myopathy (advanced age, frailty, multisystem disease, multiple medications) may also warrant closer monitoring for peripheral neuropathy 4
• Early detection of peripheral neuropathy symptoms and appropriate management may prevent permanent nerve damage 2