Several controlled studies have shown that long-term anticonvulsant treatment decreases blood levels of biotin.^{1 , 2 , 3 , 4} In children, a deficiency of biotin can lead to withdrawn behavior and a delay in mental development. Adults with low biotin levels might experience a loss of appetite, feelings of discomfort or uneasiness, mental Reference depression, or hallucinations. To avoid side effects, individuals taking anticonvulsants should supplement with biotin either alone or as part of a Reference multivitamin.

Several controlled and preliminary studies showed that multiple drug therapy for Reference seizures results in dramatic reductions in blood carnitine levels.^{5 , 6 , 7} Further controlled research is needed to determine whether children taking anticonvulsants might benefit by supplementing with L-carnitine, since current studies yield conflicting results. For example, one controlled study indicated that children taking Reference valproic acid and carbamazepine received no benefit from supplementing with L-carnitine.⁸ However, another small study revealed that children taking valproic acid experienced less fatigue and excessive sleepiness following L-carnitine supplementation.⁹ Despite the lack of well-controlled studies, individuals who are taking anticonvulsants and experiencing side effects might benefit from supplementing with L-carnitine.

Anticonvulsant drugs can occasionally cause Reference birth defects when taken by Reference 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.¹⁰ 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 many researches believe that low blood levels of Reference folic acid are involved, the effects might be caused by a vitamin B12 deficiency. 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.¹¹ Another study found that long-term anticonvulsant therapy had no effect on blood levels of vitamin B12.¹² The results of these two studies indicate that people taking anticonvulsant drugs might experience side effects of vitamin B12 deficiency, and that the deficiency is not easily detected by the usual blood tests. Therefore, individuals taking anticonvulsant drugs for several months or years might prevent nerve and mental problems by supplementing with vitamin B12.

One controlled study revealed that taking anticonvulsant drugs dramatically reduces blood levels of vitamin B6.¹³ A nutritional deficiency of vitamin B6 can lead to an increase in Reference homocysteine blood levels, which has been associated with Reference atherosclerosis. Vitamin B6 deficiency is also associated with symptoms such as dizziness, fatigue, mental Reference depression, and seizures. On the other hand, supplementation with large amounts of vitamin B6 (80–200 mg per day) has been reported to reduce blood levels of some anticonvulsant drugs, which could theoretically trigger seizures. People taking multiple anticonvulsant drugs should discuss with their doctor whether supplementing with vitamin B6 is advisable.

Though research results vary, long-term use of anticonvulsant drugs appears to interfere with vitamin D activity,¹⁴ which might lead to softening of bones (Reference 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.¹⁵ 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 Reference calcium for nine months.¹⁶ 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.¹⁷ Another study of 450 people in Florida taking anticonvulsants found that few had drug-induced bone disease.¹⁸ 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.

Two studies showed that individuals taking phenytoin and Reference phenobarbital had lower blood vitamin E levels than those who received no treatment for seizures.^{19 , 20} Though the consequences of lower blood levels of vitamin E are unknown, people taking multiple anticonvulsant drugs might supplement with 100 to 200 IU of vitamin E daily to help prevent a deficiency.

Though research results vary, long-term use of anticonvulsant drugs appears to interfere with vitamin D activity,²¹ which might lead to softening of bones (Reference 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.²² 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 Reference calcium for nine months.²³ 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.²⁴ Another study of 450 people in Florida taking anticonvulsants found that few had drug-induced bone disease.²⁵ 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.

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.²⁶ Though some researchers recommend vitamin K supplementation prior to delivery,^{27 , 28} not all agree that supplementation for women taking anticonvulsant drugs is necessary.²⁹ Until more information is available, Reference pregnant women or women who might become pregnant while taking anticonvulsant drugs should discuss vitamin K supplementation with their healthcare practitioner.