Can topiramate cause B12 deficiency? Understanding the Link

October 7, 2025 •

4 min read

One study found that treatment with the antiepileptic drug (AED) topiramate was associated with lower serum levels of vitamin B12 [1.2.7]. For patients asking, 'Can topiramate cause B12 deficiency?', it is important to understand the potential connection and associated symptoms.

Quick Summary

Research indicates a link between some antiepileptic drugs, including topiramate, and reduced vitamin B12 levels. This can lead to various neurological and physical symptoms, requiring monitoring and possible supplementation.

Key Points

Association, Not Direct Causation: Studies show an association between topiramate use and lower vitamin B12 levels, but a direct causal link is not definitively established in all research [1.2.2, 1.2.7].
Symptoms are Neurological and Physical: B12 deficiency can manifest as fatigue, tingling in extremities, memory problems, and a sore tongue [1.4.1, 1.4.2, 1.4.3].
Part of a Drug Class Effect: Other antiepileptic drugs, such as phenobarbital and pregabalin, have also been linked to reduced B12 levels [1.2.7].
Other Medications Pose a Risk: Drugs like metformin and acid reducers (PPIs, H2 blockers) are well-known to cause B12 deficiency [1.3.4, 1.5.5].
Monitoring is Key: Experts recommend that patients on long-term topiramate therapy have their B12 levels monitored periodically [1.2.2, 1.3.5].
Management is Straightforward: Deficiency can often be managed with dietary changes or oral B12 supplements; injections may be needed in some cases [1.2.7, 1.4.6].
Consult a Healthcare Provider: If you experience symptoms of B12 deficiency while taking topiramate, it is essential to consult your doctor for evaluation [1.3.5].

What is Topiramate?

Topiramate, sold under brand names like Topamax, is a prescription medication primarily used to treat epilepsy and prevent migraines [1.6.3, 1.6.4]. It is approved for treating certain types of seizures (partial-onset, generalized tonic-clonic) in adults and children and for preventing migraine headaches in individuals aged 12 and older [1.6.1, 1.6.2]. Topiramate belongs to a class of drugs known as antiepileptic drugs (AEDs) or anticonvulsants [1.6.3]. Its exact mechanism of action is not fully understood, but it is thought to work by calming overactive nerve cells in the brain [1.6.2]. In 2023, it was the 71st most commonly prescribed medication in the United States, with over 9 million prescriptions [1.6.3].

Common Uses for Topiramate:

Epilepsy: For managing generalized or focal seizures [1.6.3].
Migraine Prevention: To decrease the frequency of migraine attacks [1.6.3].
Lennox-Gastaut Syndrome: A disorder that causes seizures and developmental delay in children [1.6.3].
Off-Label Uses: It has also been used for conditions such as alcohol dependence, essential tremor, and bipolar disorder [1.6.3, 1.6.7].

The Link Between Topiramate and Vitamin B12 Deficiency

Several studies have investigated the impact of antiepileptic drugs on vitamin levels. Research published in Nature and on PubMed indicates that treatment with certain AEDs, including topiramate, is associated with reduced serum levels of vitamin B12 [1.2.2, 1.2.7]. One prospective study involving over 2,700 patients found that those treated with topiramate, phenobarbital, pregabalin, or primidone had lower B12 levels compared to the entire group of patients [1.2.7].

While some sources state there are no direct interactions found between topiramate and vitamin B12, they also caution that this doesn't mean no interactions exist [1.2.5, 1.2.6]. The evidence points towards an association rather than a direct, universally reported depletion. The mechanism isn't entirely clear, but some AEDs are known to interfere with vitamin absorption or metabolism [1.3.5]. This interference can lead to side effects of a B12 deficiency that may not be easily detected by standard blood tests, as one study noted lower B12 levels in the cerebrospinal fluid of long-term anticonvulsant users despite normal blood levels [1.3.1]. Due to this risk, experts recommend that patients on long-term AED therapy have their B12 levels monitored or receive prophylactic vitamin supplementation [1.2.2].

Symptoms of Vitamin B12 Deficiency

A lack of vitamin B12 can affect the body in numerous ways, as this nutrient is crucial for nerve function and the production of healthy red blood cells [1.4.6]. Symptoms often develop gradually and can worsen if left untreated [1.4.2].

Physical Symptoms:

Extreme tiredness and lack of energy (fatigue) [1.4.1, 1.4.2].
Pale or yellowish skin (jaundice) [1.4.2, 1.4.6].
A sore, red, and smooth tongue (glossitis) and mouth ulcers [1.4.2].
Shortness of breath and a fast heart rate [1.4.1, 1.4.6].
Decreased appetite and weight loss [1.4.1, 1.4.4].

Neurological Symptoms:

Numbness or a tingling "pins and needles" sensation (paresthesia), especially in the hands and feet [1.4.1, 1.4.2].
Difficulty walking and problems with physical coordination (ataxia) [1.4.1, 1.4.2].
Disturbed vision [1.4.2].
Muscle weakness [1.4.2].

Psychological Symptoms:

Problems with memory, understanding, and judgment (cognitive decline) [1.4.2, 1.4.3].
Confusion [1.4.2].
Depression, irritability, and changes in feelings or behavior [1.4.2, 1.4.4].

Comparison of Medications That May Cause B12 Deficiency

Topiramate is not the only medication that can affect vitamin B12 levels. Several other common drugs are known to interfere with its absorption.


Medication Class	Examples	Mechanism of B12 Depletion
Antiepileptics	Topiramate, Phenobarbital, Pregabalin, Carbamazepine	May interfere with vitamin absorption or metabolism, though the exact mechanism is not fully defined [1.2.7, 1.5.4].
Proton Pump Inhibitors (PPIs)	Omeprazole (Prilosec), Lansoprazole (Prevacid)	Reduce stomach acid, which is needed to release vitamin B12 from ingested proteins [1.3.4, 1.5.5].
H2 Receptor Antagonists	Famotidine, Cimetidine	Also reduce stomach acid, leading to malabsorption of B12 from food [1.5.1, 1.5.7].
Metformin	Glumetza, Fortamet	An oral diabetes medication known to decrease B12 absorption, possibly by interfering with the B12-intrinsic factor complex [1.3.4, 1.5.4].
Colchicine	Colcrys, Mitigare	An anti-inflammatory drug used for gout that can lower the body's ability to absorb vitamin B12 [1.5.4].

Managing and Preventing B12 Deficiency on Topiramate

For patients taking topiramate, especially long-term, proactive management is key. It's advisable to periodically monitor vitamin B12 levels through blood tests [1.3.5]. If symptoms like fatigue, numbness, or cognitive changes appear, consulting a healthcare provider for evaluation is crucial [1.3.5].

Management strategies include:

Dietary Adjustments: Increasing the intake of B12-rich foods can help. Vitamin B12 is naturally found in animal products like meat, fish, poultry, eggs, and dairy [1.4.6]. For those on vegetarian or vegan diets, fortified foods like cereals, plant milks, and nutritional yeast are good sources [1.4.6].
Supplementation: Oral vitamin B12 supplements can effectively restore normal levels [1.2.7]. In cases of severe deficiency or absorption issues, a doctor might prescribe B12 injections [1.4.6].
Regular Monitoring: Healthcare providers may recommend closely monitoring B12 serum levels for patients on long-term AED therapy [1.2.2].

Conclusion

The evidence suggests that while not a universally reported side effect, there is an association where topiramate can cause B12 deficiency as part of a broader effect seen with several antiepileptic drugs [1.2.7]. The risk appears to increase with long-term use. Given the importance of vitamin B12 for neurological and overall health, patients taking topiramate should be aware of the potential symptoms of deficiency, such as fatigue, tingling sensations, and cognitive changes [1.4.1, 1.4.2]. Regular communication with a healthcare provider, periodic monitoring of B12 levels, and potential dietary changes or supplementation are effective strategies to mitigate this risk and ensure continued well-being during treatment.

For more information on the effects of antiepileptic drugs on vitamin levels, you can refer to research published on the National Institutes of Health website: https://pubmed.ncbi.nlm.nih.gov/21246600/

Frequently Asked Questions

Topiramate is a prescription medication used to treat epilepsy (specifically partial-onset and generalized tonic-clonic seizures) and to prevent migraine headaches in adults and children [1.6.3, 1.6.4].

Yes, some studies have found an association between treatment with topiramate and lower serum levels of vitamin B12, similar to other antiepileptic drugs [1.2.2, 1.2.7].

Common symptoms include extreme fatigue, a pins-and-needles sensation in the hands and feet, a sore and red tongue, muscle weakness, memory problems, and psychological changes like depression or confusion [1.4.2, 1.4.4].

You should consult your healthcare provider. They may recommend monitoring your B12 levels, especially with long-term use. If a deficiency is detected, they may suggest dietary changes or supplementation [1.2.2, 1.3.5].

Yes, several medications are known to cause B12 deficiency, including metformin (for diabetes), proton pump inhibitors like omeprazole, and H2 blockers like famotidine [1.3.4, 1.5.5].

Treatment typically involves oral vitamin B12 supplements or, in more severe cases, B12 injections. Studies show that oral supplementation is effective at restoring normal vitamin levels [1.2.7, 1.4.6].

Common side effects of topiramate include tingling sensations, fatigue, loss of appetite, weight loss, difficulty with memory or speech, and dizziness [1.6.1, 1.6.2].