Ginkgo
Effect: Possible Harmful Interaction
The herb ginkgo (Ginkgo biloba) has been used to
treat Alzheimer’s disease and ordinary age-related memory loss, among many other
conditions. Seizures have been reported with the use of ginkgo leaf extract in
people with previously well-controlled epilepsy; in one case, the seizures were
fatal. One possible explanation is contamination of ginkgo leaf products with
ginkgo seeds. It has also been suggested that ginkgo might interfere with the
effectiveness of some antiseizure medications, including phenytoin.
Finally, it has been noted that the drug tacrine (also used to improve memory) has
been associated with seizures, and ginkgo may affect the brain in ways similar to
tacrine.
Glutamine
Effect: Possible Harmful Interaction
The amino acid glutamine is converted to glutamate in the body. Glutamate
is thought to act as a neurotransmitter (a chemical that enables nerve
transmission). Because anticonvulsants work (at least in part) by blocking
glutamate pathways in the brain, high dosages of the amino acid glutamine might
theoretically diminish an anticonvulsant’s effect and increase the risk of
seizures.
Ipriflavone
Effect: Possible Harmful Interaction
Ipriflavone, a synthetic isoflavone
that slows bone breakdown, is used to treat osteoporosis. Test-tube studies
indicate that ipriflavone might increase blood levels of the anticonvulsants
phenytoin and carbamazepine when they are taken therapeutically.
Ipriflavone was found to inhibit a liver enzyme involved in the body’s normal
breakdown of these drugs, thus allowing them to build up in the blood. Higher drug
levels increase the risk of adverse effects.
Because anticonvulsants are known to contribute to the development of osteoporosis, a concern is that the use of ipriflavone for this drug-induced osteoporosis could result in higher blood levels of the drugs, with potentially serious consequences. People taking either of these drugs should use ipriflavone only under medical supervision.
Hops, Kava, Passionflower, Valerian
Effect: Possible Harmful Interaction
The herb kava (Piper methysticum) has a sedative
effect and is used for anxiety and insomnia. Combining kava with anticonvulsants,
which possess similar depressant effects, could result in add-on or excessive
physical depression, sedation, and impairment. In one case report, a
fifty-four-year-old man was hospitalized for lethargy and disorientation, side
effects attributed to his having taken the combination of kava and the antianxiety
agent alprazolam (Xanax) for three days.
Other herbs having a sedative effect that might cause problems when combined with anticonvulsants include ashwagandha, calendula, catnip, hops, lady’s slipper, lemon balm, passionflower, sassafras, skullcap, valerian, and yerba mansa.
Because of the potentially serious consequences, one should avoid combining these herbs with anticonvulsants or other drugs that also have sedative or depressant effects, unless advised by a physician.
White Willow
Effect: Possible Harmful Interaction
The herb white
willow (Salix alba), also known as willow
bark, is used to treat pain and fever. White willow contains a substance that is
converted by the body into a salicylate similar to aspirin. Higher doses of
aspirin may increase phenytoin levels and toxicity during long-term use of both
drugs. This raises the concern that white willow might have similar effects on
phenytoin, though this has not been proven.
Biotin
Effect: Supplementation Possibly Helpful, but Take at a Different Time of Day
Anticonvulsants may deplete biotin, an essential water-soluble B
vitamin, possibly by competing with it for absorption in the intestine. It is not
clear, however, whether this effect is great enough to be harmful. Blood levels of
biotin were found to be substantially lower in 404 people with epilepsy on
long-term treatment with anticonvulsants, compared with 112 untreated people with
epilepsy. The effect occurred with phenytoin, carbamazepine, phenobarbital, and
primidone. Valproic acid appears to affect biotin to a lesser extent than other
anticonvulsants.
A test-tube study suggested that anticonvulsants might lower biotin levels by interfering with the way biotin is transported in the intestine.
Biotin supplementation may be beneficial for persons on long-term anticonvulsant therapy. To avoid a potential interaction, one should take the supplement two to three hours apart from the drug. It has been suggested that the action of anticonvulsant drugs may be at least partly related to their effect of reducing biotin levels. For this reason, it may be desirable to take enough biotin to prevent a deficiency but not an excessive amount.
Folate
Effect: Possible Benefits and Risks
Folate (also known as folic acid) is a B vitamin that plays
an important role in many vital aspects of health, including preventing neural
tube birth defects and possibly reducing the risk of heart disease. Because
inadequate intake of folate is widespread, if one is taking any medication that
depletes or impairs folate even slightly, one may need supplementation.
Most drugs used for preventing seizures can reduce levels of folate in the body. Phenytoin in particular appears to decrease folate levels by interfering with its absorption in the small intestine, as well as by accelerating its normal breakdown by the body. The low blood levels of folate caused by anticonvulsants can raise homocysteine levels, a condition believed to increase the risk of heart disease.
Adequate folate intake is also necessary to prevent neural tube birth
defects, such as spina bifida and anencephaly (absence of a
brain). Because anticonvulsant drugs deplete folate, babies born to women taking
anticonvulsants are at increased risk for such birth defects. Anticonvulsants may
also play a more direct role in the development of birth defects.
However, there can be problems with using folate supplements. High folate levels may speed up the normal breakdown of phenytoin. This can lead to breakthrough seizures. For this reason, folate supplementation during phenytoin therapy should be supervised by a physician.
Calcium
Effect: Supplementation Probably Helpful, but Take at a Different Time of Day
Anticonvulsant drugs may impair calcium absorption and, in this way, increase the risk of osteoporosis and other bone disorders. Calcium absorption was compared in twelve people on anticonvulsant therapy (all taking phenytoin and some also taking phenobarbital, primidone, and/or carbamazepine) and twelve people receiving no treatment. Calcium absorption was found to be 27 percent lower in the treated participants.
An observational study found low blood calcium levels in 48 percent of 109 people taking anticonvulsants. Other findings in this study suggested that anticonvulsants might also reduce calcium levels by directly interfering with parathyroid hormone, a substance that helps keep calcium levels in proper balance.
A low level of blood calcium can itself trigger seizures, and this might reduce
the effectiveness of anticonvulsants. Calcium supplementation may be beneficial
for people taking anticonvulsant drugs. However, some studies indicate that
antacids containing calcium carbonate may interfere with the absorption of
phenytoin and perhaps other anticonvulsants. For this reason, one should take
calcium supplements and anticonvulsant drugs several hours
apart if possible.
Carnitine
Effect: Supplementation Possibly Helpful
Carnitine is an amino acid that has been used for heart
conditions, Alzheimer’s disease, and intermittent claudication. Long-term therapy
with anticonvulsant agents, particularly valproic acid, is associated with low
levels of carnitine. However, it is not clear whether the anticonvulsants cause
the carnitine deficiency or whether it occurs for other reasons. It has been
hypothesized that low carnitine levels may contribute to valproic acid’s damaging
effects on the liver. The risk of this liver damage increases in children younger
than twenty-four months, and carnitine supplementation does seem to be protective.
However, in one double-blind crossover study, carnitine supplementation produced
no real improvement in “well-being” as assessed by parents of children receiving
either valproic acid or carbamazepine.
L-carnitine supplementation may be advisable in certain cases, such as in infants and young children (especially those younger than two years) who have neurologic disorders and are receiving valproic acid and multiple anticonvulsants.
Vitamin D
Effect: Supplementation Possibly Helpful
Anticonvulsant drugs may interfere with the activity of vitamin D. As
proper handling of calcium by the body depends on vitamin D, this may be another
way that these drugs increase the risk of osteoporosis and related bone disorders.
Anticonvulsants appear to speed up the body’s normal breakdown of vitamin D,
decreasing the amount of the vitamin in the blood. A survey of forty-eight people
taking both phenytoin and phenobarbital found significantly lower levels of
calcium and vitamin D in many of them, compared with thirty-eight untreated
people. Similar but lesser changes were seen in thirteen people taking phenytoin
or phenobarbital alone. This effect may be apparent only after several weeks of
treatment.
Another study found decreased blood levels of one form of vitamin D but normal levels of another. Because there are two primary forms of vitamin D circulating in the blood, the body might be able to adjust in some cases to keep vitamin D in balance, at least for a time, despite the influence of anticonvulsants. Adequate sunlight exposure may help overcome the effects of anticonvulsants on vitamin D by stimulating the skin to manufacture the vitamin. Of 450 people on anticonvulsants residing in a Florida facility, none was found to have low blood levels of vitamin D or evidence of bone disease. This suggests that environments providing regular sun exposure may be protective. People regularly taking anticonvulsants, especially those taking combination therapy and those with limited exposure to sunlight, may benefit from vitamin D supplementation.
Vitamin K
Effect: Supplementation Possibly Helpful for Pregnant Women
Phenytoin, carbamazepine, phenobarbital, and primidone speed up the normal
breakdown of vitamin K into inactive byproducts, thus depriving the body
of active vitamin K. This can lead to bone problems, such as osteoporosis. In
addition, use of these anticonvulsants can lead to a vitamin K deficiency in
babies born to pregnant women taking the drugs, resulting in bleeding disorders or
facial bone abnormalities in the newborns. Women who take these anticonvulsants
may need vitamin K supplementation during pregnancy to prevent these conditions in
their newborns.
Bibliography
De Vivo, D. C., et al. “L-carnitine Supplementation in Childhood Epilepsy: Current Perspectives.” Epilepsia 30 (1998): 1216-1225.
Granger, A. S. “Ginkgo biloba Precipitating Epileptic Seizures.” Age and Ageing 30 (2001): 523-525.
Gregory, P. J. “Seizure Associated with Ginkgo biloba?” Annals of Internal Medicine 134 (2001): 344.
Kupiec, T., and V. Raj. “Fatal Seizures Due to Potential Herb-Drug Interactions with Ginkgo biloba.” Journal of Analytical Toxicology 29 (2006): 755-758.
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