What supplements should be avoided by patients taking anti-seizure medications?

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Last updated: June 2, 2025View editorial policy

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From the Guidelines

Patients taking anti-seizure medications should avoid St. John's Wort, as it can significantly reduce blood levels of many anticonvulsants, including carbamazepine and phenytoin, by inducing liver enzymes that metabolize these medications 1. When considering supplements that interact with anti-seizure medications, it's crucial to prioritize those that may have the most significant impact on morbidity, mortality, and quality of life.

  • St. John's Wort is a primary concern due to its ability to induce CYP3A4 activity, potentially decreasing the plasma concentrations of various medications, including anti-seizure drugs 1.
  • Other supplements like Ginkgo biloba, evening primrose oil, and borage oil may also be problematic as they could lower the seizure threshold or counteract the benefits of anti-seizure medications.
  • Herbal stimulants such as ephedra, guarana, and excessive caffeine should be avoided due to their potential to increase seizure risk.
  • Additionally, caution is advised with melatonin, as it may interact with anticonvulsants, and high-dose vitamins E and B6 should be avoided, as they might interfere with medication effectiveness. It's essential for patients to consult with their neurologist or pharmacist before starting any supplement to ensure safe and effective management of their condition, considering the potential interactions and the individual's specific medication regimen 1.

From the FDA Drug Label

Agents That Increase Carbamazepine Levels CYP3A4 inhibitors inhibit carbamazepine metabolism and can thus increase plasma carbamazepine levels. Drugs that have been shown, or would be expected, to increase plasma carbamazepine levels include ... grapefruit juice

Concomitant use of carbamazepine with hormonal contraceptive products (e.g., oral, and levonorgestrel subdermal implant contraceptives) may render the contraceptives less effective because the plasma concentrations of the hormones may be decreased.

Phenytoin and other anticonvulsants that have been shown to induce the CYP450 enzyme are thought to affect bone mineral metabolism indirectly by increasing the metabolism of Vitamin D3. This may lead to Vitamin D deficiency

  • Supplements to avoid:
    • Grapefruit juice: may increase plasma carbamazepine levels
    • St. John's Wort: may decrease plasma levels of various medications, including anti-seizure medications, due to CYP3A4 induction
    • Vitamin D supplements may not be sufficient to prevent deficiency due to increased metabolism caused by phenytoin
  • Key considerations:
    • Patients taking anti-seizure medications should consult their physician before taking any supplements
    • Monitoring of plasma levels and dosage adjustments may be necessary when taking supplements with anti-seizure medications 2
    • Alternative or back-up methods of contraception should be considered for patients taking carbamazepine due to decreased effectiveness of hormonal contraceptives 2
    • Patients should be aware of the potential for increased risk of osteomalacia, bone fractures, osteoporosis, hypocalcemia, and hypophosphatemia due to Vitamin D deficiency caused by phenytoin 3

From the Research

Supplements that Interact with Anti-Seizure Medication

  • The following supplements may interact with anti-seizure medications:
    • St John's Wort: Although one study found no significant interaction between St John's Wort and carbamazepine 4, other studies suggest that St John's Wort may induce the metabolism of certain anti-seizure medications, potentially reducing their effectiveness.
    • Magnesium: While magnesium is commonly used as a supplement, high doses may interact with anti-seizure medications such as valproate, increasing the risk of adverse effects 5.
    • Multivitamins: Some multivitamins may contain ingredients that interact with anti-seizure medications, such as folic acid, which may reduce the effectiveness of certain medications 5.

Potential Risks of Supplement Use

  • The use of dietary and herbal supplements is common among patients with epilepsy, with 50.4% of patients in one study reporting supplement use 5.
  • Supplement use may lead to interactions with prescription medications, potentially reducing their effectiveness or increasing the risk of adverse effects 5.
  • Certain supplements, such as those with proconvulsive effects, may worsen seizure control 5.

Importance of Healthcare Provider Awareness

  • Healthcare providers should routinely inquire about supplement use in patients with epilepsy to minimize potential harm 5.
  • Patients should be advised to consult with their healthcare provider before starting any new supplements, especially if they are taking anti-seizure medications 5.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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