Table 2.
Characteristics of natural products used by patients with epilepsy in countries with western based type of medical system.
| Product | Main current medical uses | Main adverse events & interactions | Overall estimated extent of use in PWE* | Possible effects in epilepsy | Potential risks for PWE |
|---|---|---|---|---|---|
| Black cohosh (Cimicifuga racemosa) [22,23,26,27,28$] | Ameliorates menopausal symptoms | Possible hepato-toxicity | 4% | NR | NR |
| Black haw (Viburnum prunifolium) [23,26] | Spasmolytic, sedative, anti asthmatic | NR | <1% | NR | NR |
| Bonemeal [27] | Calcium supplementation (not used recently) | Possible prion infection | NR | NR | |
| Seizures secondary to lead poisoning | |||||
| Caffeine [28$] | Stimulant, antinociceptive | Sympathomimetic and GI symptoms | <1% | NR | Associated with seizures. May interact with CBZ. |
| Chondroitin [28$] | Anti arthritis & arthralgia | GI symptoms, hypersensitivity, possible anticoagulation (increased INR with Warfarin) | <1% | NR | NR |
| (Red) clover (Trifolium pretense) [28$] | Ameliorates menopausal symptoms | Possibly inhibits aromatase and extrahepatic CYP1A1, 1B1. May increase INR when taken with Warfarin | <1% | NR | NR |
| Coenzyme Q10 [27,28$] | Antioxidant, ameliorates CHF and neurodegenerative disorders | May increase risk of bleeding in Warfarin users | <1% | May improve seizures in neurological mitochondrial diseases | NR |
| Cranberry [23,26] | Prevents UTI, cardioprotector, anti-cancer, antioxidant | GI intolerance, weight gain, possibly thrombocytopenia and increase in INR in combination with Warfarin | 9% | NR | NR |
| Inhibited P450 system in vitro, but not in vivo. | |||||
| DHEA [28$] | Hormonal replacement therapy in elderly women and men | No adverse events. Induces CYP2B6 | <1% | NR | Possibly associated with seizures |
| No effect in animals | |||||
| Echinacea [23,24,26,27,28$] | Enhances immune system functions | Hypersensitivity, GI disturbance, hepatotoxicity with prolonged use; mild effect on CYP3A4 and CYP1A2 | 11% | NR | NR |
| Ephedra [24,28$] | Induces weight loss, stimulant | HTN, tachycardia, stroke | <1% | NR | Associated with seizures |
| Evening primrose (Oenothera biennis) [23,24,26,27,28$] | Ameliorates menopausal symptoms | NR | 2% | Anti-seizure effects (animals) | Possibly associated with seizures |
| Garlic [22,23,24,26,28$] | Antioxidant, cardiovascular, cancer prevention, immune stimulant | GI disturbance, dizziness. Possible increase in INR, HTN, arrhythmia. Possible influence on CYP3A4 and inhibitor of CYP2C9/19 | 10% | NR | NR |
| Ginger [28$] | Prevents cardiovascular disease and cancer, ameliorates GI symptoms, antioxidant, anti-inflammatory | May increase risk of bleeding in warfarin users. Possible inductor of CYP1A2 and 3A4 | <1% | May have antiepileptic effects | NR |
| Ginseng [21,22,23,24,26,28$] | Anxiety, depression, concentration problems, DM, stimulant, menopausal symptoms, sexual dysfunction in men | Possible hepatotoxicity & increased INR, lethargy | 17% | May have anticonvulsive properties | May exacerbate seizures |
| Ginkgo biloba [21,22,23,24,26,27,28$] | Cognitive enhancer, prevents cardiovascular disease, antioxidant | GI discomfort, anti-coagulant. May inhibit CYP2B6 and induce CYP3A & 1A2, 2C19. | 16% | Leaves and stems may be anticonvulsive | Seeds may be toxic and pro-convulsive. May increase metabolism of AED (PHT, VPA, PB) |
| Glucosamine [28$] | Anti-arthritis & arthralgia | May increase INR in warfarin users. | <1% | NR | NR |
| Glutamine [28$] | Enhances healing after injury, especially GI, promotes muscle building | NR | <1% | NR | NR |
| Goldenseal (Hydrastis Canadensis) [23] | Anti-inflammatory, anti-microbial | Possible hypernatremia, HTN, edema. Strong inhibitor of CYP2D6 & CYP3A4/5, CYP2E1 | 5% | NR | NR |
| Grapefruit juice [28$] | Prevents cardiovascular disease and cancer, antioxidant | Inhibits enteric CYP3A4, possibly increases risk of breast cancer | <1% | NR | Increases bioavailability of CBZ, BDZ |
| Grape seeds [23,26,28$] | Prevents cardiovascular disease and cancer, antioxidant | Hypersensitivity, HA, dizziness, nausea. May inhibit CYP2E1 | 4% | NR | NR |
| Hops (Humulus lupulus) [23] | Ameliorates anxiety, insomnia and menopausal symptoms, anti-inflammatory, antioxidant | Sedation. Possibly inhibits CYP2C9, 1A1/2, 1B1 | <1% | NR | Possibly exacerbates seizure |
| Kava kava (Piper methysticum) [23,28$] | Ameliorates depression, anxiety and insomnia, induces local anesthesia | Possibly psychosis, choreoathetosis, hepatotoxicity, dermopathy, lymphopenia, GI disturbances, potential for addiction. Inhibitor of CYP2E1, 1A2, induction of 1A1. | 4% | May benefit | Possibly exacerbate seizures |
| L-lysine [28$] | Precursor of carnitine, promotes protein building, anti-cancer, anti-viral | NR | <1% | NR | NR |
| Licorice (liquorice or Glycyrrhiza glabra) [23] | Expectorant, anti-viral, anti-spasmodic, ameliorates gastric & duodenal ulcers, and menopausal symptoms | In overdose - hypokalemia and increase in BP, decrease testosterone in men. May increase INR when taken with warfarin. Possibly inhibits CYP3A4, 2B6, 2C9. | 2% | NR | NR |
| Marijuana (Cannabis sativa) [27] | Antinociceptive, ameliorates glaucoma, anti-nausea, muscle relaxant, promotes bone health | Tachycardia, dry mouth, red eyes, euphoria, anxiety, psychosis, memory deficit. Possibly induces CYP2E1 | May benefit | May exacerbate seizures | |
| Melatonin [22,23,26,28$] | Ameliorates insomnia, circadian rhythm abnormalities, depression, and anxiety | HA, nausea, somnolence | 7% | May benefit | Associated with increased seizure frequency |
| Milk thistle [28$] | Ameliorates hepatotoxicity and DM, anticancer | Possible downregulation of CYP3A4, 2C9 | <1% | NR | NR |
| Nettles (Urtica dioica) [28$] | Antinociceptive, anti-arthritis, antioxidant, diuretic, ameliorates BPH | Uterine stimulant | <1% | NR | NR |
| Omega 3/fish oil [27,28$] | Cardioprotective, ameliorates depression, dementia, ADHD | Anti-coagulant | <1% | May be beneficial (SUDEP) | NR |
| Parsley leaf [28$] | Diuretic, ameliorates constipation, promotes bone health | May increase INR when taken with warfarin. Possibly downregulates p450. Possibly stimulates uterine contractions. | <1% | NR | NR |
| Saw palmetto (Serenoa repens) [23] | Ameliorates UTI and BPH | GI disturbance, HA, decreased libido. Inhibition of CYP3A4, 2D6, 2C9. | 2% | NR | NR |
| Skullcap (Scutellaria) [28$] | Sedative, anti-epileptic, hypnotic, anxyolytic, anti-cancer | NR | <1% | May benefit | NR |
| Soy [23,26] | Source of Omega 3 & 6 fatty acids. Ameliorates menopausal symptoms, prevents prostate cancer, and promotes bone health | May increase risk of developing breast cancer. Possibly inhibit CYP2A6, 1A1, 1B1, 3A4. | 8% | NR | NR |
| St. John’s wort (Hypericum perforatum) [21,22,23,24,26,27,28$] | Ameliorates depression, pain, ADHD | Possibly hepatotoxicity, visual disturbances, paresthesia, myalgia, GI disturbances, sedation, photosensitivity. Inducer of CYP3A4, 2E1, 2C19, P-glycoprotein. Possible inhibition of CYP2C9/19, 2D6, 3A4, 1A2. Avoid MAO inhibitors and SSRIs. | 13% | Possible benefit | Possibly associated with seizures |
| Valerian [23,26,28$] | Ameliorates anxiety, insomnia, and epilepsy, nociceptive | GI disturbance, drowsiness, HA. Avoid barbiturates. Possibly inhibits CYP2D6, 3A4 | 5% | May benefit | NR |
* The overall extent of use was calculated by combining data from the publications that provided numerical data for the use of specific products. For Ginseng, Gingko biloba and St. John’s wort, the information was taken from the publications by Gidal, Peebles, Sirven, Liow, and Kaiboriboon (on a total of 1407 PWE) and for all other products from the publications by Peebles, Sirven, Liow, and Kaiboriboon (on a total of 942 PWE) (see last column of Table 1 for enumeration of use of natural products). $This reference reports on neurological conditions in general, including epilepsy. PWE—people with epilepsy; NR—not reported; GI—gastro-intestinal; CHF—congestive heart failure; UTI—urinary tract infection; HTN—hypertension; BHP—benign hypertrophy of prostate; SUDEP—sudden unexplained death in epilepsy patients; HA—headache; AED—anti-epileptic drugs; PHT—phenytoin; VPA—valproic acid; PB—phenobarbital; CBZ—carbamazepine; BDZ—benzodiazepines.