COVID-19: Vaccine | Testing | Self-assessment | Patient & Visitor Safety | Visitor Policy
Emergency Room Wait Times
Home > Living Well > Health Library > Phenobarb-Belladonna Alkaloids
One controlled study showed that long-term use of phenobarbital increases the breakdown of biotin. A test tube study also showed that primidone, a drug that is converted to phenobarbital by the body, prevents the absorption of biotin. Further research is needed to determine whether people taking phenobarbital might be at risk for biotin deficiency.
Individuals on long-term multiple anticonvulsant therapy may develop below-normal blood levels of calcium, which may be related to drug-induced vitamin D deficiency. Two infants born to women taking high doses of phenytoin and phenobarbital while pregnant developed jitteriness and tetany (a syndrome characterized by muscle twitches), cramps, and spasms that can be caused by calcium deficiency during the first two weeks of life. Controlled research is needed to determine whether pregnant women who are taking anticonvulsant medications should supplement with additional amounts of calcium and vitamin D.
Though research results vary, long-term use of anticonvulsant drugs appears to interfere with vitamin D activity, which might lead to softening of bones (osteomalacia). One study showed that blood levels of vitamin D in males taking anticonvulsants were lower than those found in men who were not taking seizure medication. In a controlled study, bone strength improved in children taking anticonvulsant drugs who were supplemented with the activated form of vitamin D and 500 mg per day of calcium for nine months. Some research suggests that differences in exposure to sunlight—which normally increases blood levels of vitamin D—might explain why some studies have failed to find a beneficial effect of vitamin D supplementation. In one controlled study, blood vitamin D levels in children taking anticonvulsants were dramatically lower in winter months than in summer months. Another study of 450 people in Florida taking anticonvulsants found that few had drug-induced bone disease. Consequently, people taking anticonvulsant drugs who do not receive adequate sunlight should supplement with 400 IU of vitamin D each day to help prevent osteomalacia.
In various studies of children treated with valproic acid for epilepsy compared with control groups, serum zinc levels remained normal or decreased, serum copper levels remained normal or decreased, and red blood cell zinc levels were decreased. The importance of these changes and how frequently they occur remain unclear.
Anticonvulsant drugs can occasionally cause birth defects when taken by pregnant women, and their toxicity might be related to low blood levels of vitamin A. One controlled study showed that taking multiple anticonvulsant drugs results in dramatic changes in the way the body utilizes vitamin A. Further controlled research is needed to determine whether supplemental vitamin A might prevent birth defects in children born to women on multiple anticonvulsant therapy. Other research suggests that ingestion of large amounts of vitamin A may promote the development of birth defects, although the studies are conflicting.
Anemia is an uncommon side effect experienced by people taking anticonvulsant drugs. Though the cause may be folic acid deficiency in many cases, a deficiency of vitamin B12 may also be a factor in some instances. Deficiencies of folic acid and vitamin B12 can lead to nerve and mental problems. One study revealed that individuals on long-term anticonvulsant therapy, despite having no laboratory signs of anemia, had dramatically lower levels of vitamin B12 in their cerebrospinal fluid (the fluid that bathes the brain) when compared with people who were not taking seizure medications. Improvement in mental status and nerve function was observed in a majority of symptomatic individuals after taking 30 mcg of vitamin B12 daily for a few days. Another study found that long-term anticonvulsant therapy had no effect on blood levels of vitamin B12. Despite these contradictory findings, people taking anticonvulsant drugs for several months or years might prevent nerve and mental problems by supplementing with vitamin B12.
One controlled study revealed that supplementing with 200 mg of vitamin B6 daily for four weeks resulted in a 45% reduction in phenobarbital blood levels. Therefore, people taking phenobarbital should probably avoid supplementing with large amounts of vitamin B6.
One controlled study revealed that taking anticonvulsant drugs dramatically reduces blood levels of vitamin B6. A nutritional deficiency of vitamin B6 can lead to an increase in homocysteine blood levels, which has been associated with atherosclerosis. Vitamin B6 deficiency is also associated with symptoms such as dizziness, fatigue, mental depression, and seizures. People taking multiple anticonvulsant drugs should discuss with their doctor whether supplementing with vitamin B6 is advisable.
Silymarin is a collection of complex flavonoids found in milk thistle (Silybum marianum) that has been shown to elevate liver glutathione levels in rats.Acetaminophen can cause liver damage, which is believed to involve glutathione depletion. In one study involving rats, silymarin protected against acetaminophen-induced glutathione depletion. While studies to confirm this action in humans have not been conducted, some doctors recommend silymarin supplementation with 200 mg milk thistle extract, containing 70–80% silymarin, three times per day for people taking acetaminophen in large amounts for more than one year and/or with other risk factors for liver problems.
Long-term treatment with phenobarbital results in dramatic reductions in folic acid blood levels, though the clinical significance of this effect is unclear. Nevertheless, some healthcare practitioners might recommend supplemental folic acid to individuals taking phenobarbital.
One preliminary study showed that pregnant women who use anticonvulsant drugs without folic acid supplementation have an increased risk of having a child with birth defects, such as heart defects, cleft lip and palate, neural tube defects, and skeletal abnormalities. However, supplementation with folic acid greatly reduces the risk. Consequently, some healthcare practitioners recommend that women taking multiple anticonvulsant drugs supplement with 5 mg of folic acid daily, for three months prior to conception and during the first trimester, to prevent folic acid deficiency-induced birth defects. Other practitioners suggest that 1 mg or less of folic acid each day is sufficient to prevent deficiency during pregnancy.
One well-controlled study showed that adding folic acid to multiple anticonvulsant therapy resulted in reduced seizure frequency. In addition, three infants with seizures who were unresponsive to medication experienced immediate relief following supplementation with the active form of folic acid.
Despite the apparent beneficial effects, some studies have indicated that as little as 0.8 mg of folic acid taken daily can increase the frequency and/or severity of seizures. However, a recent controlled study showed that both healthy and epileptic women taking less than 1 mg of folic acid per day had no increased risk for seizures. Until more is known about the risks and benefits of folic acid, individuals taking multiple anticonvulsant drugs should consult with their healthcare practitioner before supplementing with folic acid. In addition, pregnant women or women who might become pregnant while taking anticonvulsant drugs should discuss folic acid supplementation with their practitioner.
Taking 3 grams vitamin C with acetaminophen has been shown to prolong the amount of time acetaminophen stays in the body. This theoretically might allow people to use less acetaminophen, thereby reducing the risk of side effects. Consult with a doctor about this potential before reducing the amount of acetaminophen. However, increasing the time acetaminophen is in the body might also theoretically increase its toxicity. Consult with a doctor before taking vitamin C along with acetaminophen.
Some studies have shown that babies born to women taking anticonvulsant drugs have low blood levels of vitamin K, which might cause bleeding in the infant. Though some researchers recommend vitamin K supplementation prior to delivery, not all agree that supplementation for women taking anticonvulsant drugs is necessary. Until more information is available, pregnant women or women who might become pregnant while taking anticonvulsant drugs should discuss vitamin K supplementation with their healthcare practitioner.
Last Review: 03-24-2015
Copyright © 2022 TraceGains, Inc. All rights reserved.
Please read the disclaimer about the limitations of the information provided here. Do NOT rely solely on the information in this article. The TraceGains knowledgebase does not contain every possible interaction.
Learn more about TraceGains, the company.
The information presented by TraceGains is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over-the-counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires December 2022.
Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.
Disclaimer: The information contained in this website, and its associated websites, is provided as a benefit to the local community, and the Internet community in general; it does not constitute medical advice. We try to provide quality information, but we make no claims, promises or guarantees about the accuracy, completeness, or adequacy of the information contained in or linked to this website and its associated sites. As medical advice must be tailored to the specific circumstances of each patient and healthcare is constantly changing, nothing provided herein should be used as a substitute for the advice of a competent physician. Furthermore, in providing this service, Adventist HealthCare does not condone or support all of the content covered in this site. As an Adventist health care organization, Adventist HealthCare acts in accordance with the ethical and religious directives for Adventist health care services.
Find an Adventist HealthCare affiliated doctor by calling our FREE physician referral service at 800-642-0101 or by searching our online physician directory.
Set Your Location
Setting your location helps us to show you nearby providers and locations based on your healthcare needs.