What are the risks of alpha-lipoic acid (ALA) toxicity?

Toxicity of Alpha Lipoic Acid (ALA)

Alpha lipoic acid can cause severe toxicity including multi-organ failure and death in overdose cases, with reported fatalities at doses as low as 6g. While ALA is generally considered safe at therapeutic doses, clinicians should be aware of its potential toxicity profile, especially in overdose situations.

Therapeutic Use and Safety at Standard Doses

• ALA is commonly used as an antioxidant supplement for various conditions including diabetic neuropathy, with typical therapeutic doses ranging from 400-1200 mg/day 1
• At standard therapeutic doses (600 mg/day), ALA is generally well-tolerated with minimal side effects in most patients 2
• Long-term use (up to 4 years) of ALA at doses of 400-1200 mg/day appears to be safe with no significant difference in adverse events between lower and higher dosages 1

Common Side Effects at Therapeutic Doses

• Mild gastrointestinal disturbances are the most commonly reported adverse effects 1, 3
• Other potential side effects include:
  • Nausea and vomiting 1
  • Dizziness 1
  • Cutaneous rash 1
  • Hypoglycemia 1
  • Hypotension 1

Severe Toxicity in Overdose

• ALA overdose can lead to life-threatening complications and death 4, 5
• There have been nine reported cases of ALA toxicity in the literature, with two documented fatalities 4
• Fatal doses have been reported at 6g (approximately 92.3 mg/kg in adults), though some patients have survived similar or higher doses (18g) 4, 5

Clinical Manifestations of ALA Toxicity

• Refractory seizures that may be difficult to control with standard anticonvulsant therapy 4, 5
• Severe metabolic acidosis 4, 5
• Thrombocytopenia 4
• Rhabdomyolysis 4
• Cardiac complications:
  • Depressed cardiac contractility 4
  • Supraventricular tachycardia 4
  • T-wave inversions on ECG 5
• Altered mental status and confusion 5
• Multi-organ failure in severe cases 4

Management of ALA Toxicity

• Aggressive supportive care is the cornerstone of management 4, 5
• Consider the following interventions for severe toxicity:
  • Airway protection and ventilatory support as needed 4
  • Vasopressor support for hypotension 4
  • Anti-epileptic medications for seizure control 4
  • High-dose insulin and euglycemia protocol for cardiac toxicity 4
  • Methylene blue (1 mg/kg) has been used in severe cases 4
• Early recognition and intensive care management are critical 4, 5

Special Considerations

• The toxic dose range is not well established, with significant individual variation in response 4
• Patients with pre-existing conditions such as diabetes may be more susceptible to certain effects like hypoglycemia 1
• Clinicians should maintain a high index of suspicion for ALA toxicity in patients presenting with unexplained seizures, metabolic acidosis, and multi-organ dysfunction 4, 5