Does Lamotrigine Cause Vitamin Deficiencies?

Lamotrigine stands out among anti-seizure and mood-stabilizing medications as one that does not appear to cause meaningful vitamin deficiencies in most people. Several studies have tested blood levels of folate, vitamin B12, vitamin D, and carnitine in patients taking lamotrigine, and the consistent finding is that their levels remain largely unchanged. That said, the drug’s origins as a folate antagonist and a handful of nuanced findings in pregnancy research and pediatric populations make the story more layered than a flat “no.”

Why This Question Follows Lamotrigine Around

If you take lamotrigine for epilepsy or bipolar disorder, you have probably encountered warnings about vitamin depletion connected to anti-seizure drugs in general. Those warnings are well-earned, but they mostly trace back to older, enzyme-inducing medications like phenytoin, carbamazepine, and phenobarbital. These drugs ramp up liver enzyme activity, which speeds up the breakdown of vitamin D and vitamin B6, among other nutrients. One review noted that the prevalence of vitamin B6 deficiency in patients on enzyme-inducing anti-seizure drugs was roughly half of all patients studied.¹ Similarly, a review of anti-seizure drug effects on bone health identified phenytoin, phenobarbital, carbamazepine, and primidone as the most common offenders, while calling the data on newer drugs like lamotrigine “scanty and controversial.”²

Lamotrigine does not induce the liver enzymes responsible for those depletions. It works through a different mechanism, primarily blocking sodium channels and reducing the release of excitatory neurotransmitters. Because it skips the enzyme-induction pathway, it avoids the downstream nutrient consequences that give older anti-seizure drugs their reputation. The question is whether it causes any nutrient problems through other routes.

Folate and B12 Look Normal in Study After Study

Folate is the nutrient most closely associated with lamotrigine, partly for a reason that surprises many patients: lamotrigine was originally synthesized as a folate antagonist. Researchers in the 1980s were exploring whether folate plays a role in seizure activity, and they designed lamotrigine as one of a series of compounds that could interfere with folate metabolism. The drug ultimately proved useful for seizures through other mechanisms, but its folate-antagonist lineage has kept the question alive.

Despite those origins, human studies have consistently shown that lamotrigine does not lower folate or B12 levels to a clinically significant degree. One study examined serum and red blood cell folate in patients on short-term and chronic lamotrigine therapy and found no meaningful change in either measure. After 12 weeks of lamotrigine, serum folate was slightly higher than at baseline, and red blood cell folate stayed stable. Patients on long-term therapy showed similar results.³ A later study tracked blood homocysteine, folate, and B12 over 32 weeks at a typical dose and again reported no significant effect on any of those markers.⁴ A separate investigation specifically looking for B-vitamin deficiency in anti-seizure drug users found no folate or B12 deficiency in any patient on lamotrigine.⁵

Homocysteine is worth mentioning because it rises when folate or B12 is functionally depleted, even if blood levels of those vitamins look borderline. In the 32-week study, homocysteine did not budge in the lamotrigine group, which is a reassuring secondary signal that folate metabolism was not being disrupted under real-world conditions.⁴

The Pregnancy Exception and the Folic Acid Puzzle

If lamotrigine doesn’t meaningfully deplete folate in adults walking around their daily lives, the question gets more complicated during pregnancy. Folate demands increase dramatically during fetal development, and even small disturbances in folate pathways can have outsized consequences. This is why every pregnant person on anti-seizure medication is advised to take folic acid supplements, regardless of which drug they use.

A mouse study shed some light on what might happen biologically when lamotrigine meets pregnancy. Mice given lamotrigine showed elevated rates of birth defects and growth restriction, alongside measurably lower folate and B12 levels and higher homocysteine. When supplemental folic acid was given alongside lamotrigine, folate and B12 returned to normal, homocysteine dropped, and the birth defects were substantially reduced.⁶ The results in mice were clear enough, though how directly they translate to humans at normal doses is less certain. A review of the clinical evidence in humans concluded that it remains unclear whether folic acid supplementation fully offsets the risk of congenital malformations in women taking anti-seizure medications.⁷

There is another wrinkle. The CEQUEL trial, which studied lamotrigine combined with quetiapine for bipolar depression, stumbled onto an unexpected interaction between folic acid and lamotrigine. The researchers noted that folic acid appeared to reduce the effectiveness of lamotrigine, possibly because both compounds bind to a shared receptor or enzyme site, or because folic acid reduces lamotrigine absorption in the gut.⁸ This finding came as a surprise and has not been fully replicated, but it raises a genuinely tricky clinical tension: folic acid supplementation is considered important during pregnancy, yet it might interfere with the very drug that is keeping seizures or mood episodes under control. If you are pregnant or planning to become pregnant while taking lamotrigine, this is a conversation worth having with your prescriber, because the dosing balance matters.

Vitamin D and Bone Health

Vitamin D depletion is the other big worry with anti-seizure drugs, because low vitamin D leads to weakened bones over time. Here, lamotrigine again looks better than the older enzyme-inducing drugs, though the picture is not quite as clean as with folate.

A study of bone mineral density in children found that those on lamotrigine monotherapy had z-scores essentially identical to healthy controls and notably higher than children on multi-drug regimens.⁹ An animal study in rats confirmed this finding, showing that lamotrigine treatment had no effect on bone strength, bone mineral density, or bone turnover, while phenytoin in the same experiment significantly worsened all three.¹⁰ And a study comparing levetiracetam and lamotrigine monotherapy over six months found that while levetiracetam users showed harmful bone effects, the lamotrigine monotherapy group did not.¹¹

That said, not every data point is reassuring. One study in children on long-term valproate and lamotrigine found that physically inactive children in the group had lower vitamin D levels, lower bone mineral density, and lower bone growth markers compared to active children. The researchers flagged physical activity level as the more important variable, but the finding serves as a reminder that drug effects, lifestyle, and growing bodies interact in ways that a single variable cannot capture.¹² A small abstract from the American Epilepsy Society noted lamotrigine among drugs that coincided with vitamin D decreases in some children, though the sample was small and the abstract did not isolate lamotrigine from other variables.¹³

A Turkish study comparing vitamin D levels across multiple anti-seizure drugs found that all lamotrigine users had vitamin D below 20, but so did about 70% of the healthy control group. The researchers found no significant connection between vitamin D level and which drug was being used, suggesting that low vitamin D in these populations may reflect lifestyle or geographic factors more than a drug-specific effect.¹⁴ When roughly seven in ten people in your control group are also vitamin D deficient, blaming the medication alone becomes difficult.

Carnitine Stays Put

Valproate, another widely used anti-seizure drug, is well known for depleting carnitine, a compound your body uses to convert fat into energy. This is especially a concern in children. Lamotrigine does not appear to share this problem. A study measuring serum carnitine in children on lamotrigine found that both free and total carnitine levels were normal and similar to children on vigabatrin and topiramate, all of which were within the expected range.¹⁵ If you or your child switched from valproate to lamotrigine partly out of carnitine concerns, the available evidence supports that move.

What Lamotrigine Does to Gut Bacteria

An area of emerging research is how anti-seizure drugs affect the gut microbiome, which in turn influences nutrient absorption. A laboratory study tested multiple anti-seizure medications against panels of gut bacterial strains and found that lamotrigine reduced the growth of more than ten strains. The same study noted that a beneficial strain, Bifidobacterium longum, partially protected cells from the toxic effects of lamotrigine in the lab setting.¹⁶

This does not mean lamotrigine is wrecking your microbiome. Lab experiments with bacterial cultures do not always mirror what happens in a living gut, where bacterial populations are resilient and replenish from food intake and other sources. But the finding is worth noting because gut bacteria play a role in synthesizing certain B vitamins and in making nutrients from food more bioavailable. If future research shows that anti-seizure drugs meaningfully reshape the gut microbiome in patients, that could reveal a secondary pathway for nutrient effects that blood tests might miss. For now, this is early-stage science, not a reason to add a probiotic to your regimen.

Practical Guidance If You Take Lamotrigine

The evidence suggests that lamotrigine is unlikely to drive you into a clinical vitamin deficiency on its own. But “unlikely to cause deficiency” is not the same as “no need to think about nutrition.” Here are some genuinely useful things to keep in mind:

Routine blood work: If you are on lamotrigine long term, periodic checks of vitamin D, folate, and B12 are reasonable, not because lamotrigine is expected to tank them but because many people have suboptimal levels regardless of medication. The Turkish study above found that even healthy controls had widespread vitamin D insufficiency.
Pregnancy planning: Folic acid supplementation before and during pregnancy is standard advice for anyone on anti-seizure medication. With lamotrigine specifically, keep in mind the potential for folic acid to interact with the drug’s effectiveness. Your doctor may need to adjust lamotrigine dosing when adding or changing a folic acid supplement.
Polytherapy matters more than monotherapy: Several of the studies cited here found worse outcomes for patients on multiple anti-seizure drugs. If you take lamotrigine alongside an enzyme-inducing drug like carbamazepine, the nutrient risks of that combination are driven more by the other drug than by lamotrigine.
Children need closer monitoring: The pediatric data showed some mixed signals on vitamin D and bone health. Physical activity level appeared to play a large mediating role, so encouraging exercise in children on anti-seizure medication is not just general wellness advice.

How Lamotrigine Compares to Other Anti-Seizure Medications

If you are choosing between medications or considering a switch, the nutrient profile of lamotrigine is one of its relative strengths. Phenytoin and carbamazepine are notorious for vitamin D depletion and bone loss through their enzyme-inducing effects. Valproate carries carnitine depletion risk and its own set of metabolic concerns. Even some newer drugs appear to cause problems: the levetiracetam-lamotrigine comparison study found that levetiracetam monotherapy showed harmful effects on bone while lamotrigine monotherapy did not.¹¹

The consistent pattern across the literature is that lamotrigine’s non-enzyme-inducing profile spares it from most of the nutrient-depleting mechanisms that affect older drugs. Researchers have described it as a safe option for bone health.¹⁰ That does not make it nutritionally inert. It was designed to interact with folate pathways, and there are signals in pregnancy research and gut microbiome studies that deserve continued investigation. But for the typical adult taking lamotrigine as monotherapy, vitamin deficiency is not among the side effects you need to lose sleep over.

When Generic Advice Gets It Wrong

Many drug information websites and pharmacy printouts lump all anti-seizure medications together when listing nutritional risks. You will frequently see blanket warnings about folate depletion, vitamin D loss, and bone thinning attributed to “anti-epileptic drugs” as a class. For phenytoin and carbamazepine, those warnings are justified. For lamotrigine, they are largely inherited guilt by association. The mechanism that causes those problems in older drugs, hepatic enzyme induction, is not part of how lamotrigine works.

This matters practically because patients sometimes start unnecessary supplement regimens, or worse, avoid a medication that would work well for them because of nutrient fears that apply to a different drug. If your pharmacist hands you a sheet warning about vitamin D depletion with your lamotrigine prescription, the warning is not wrong in a generic sense (some anti-seizure drugs do this), but the specific evidence for lamotrigine is reassuring. Ask your prescriber which concerns apply to your particular medication rather than treating class-wide warnings as equally relevant to every drug in the class.

1
Annals of Clinical Nutrition and Metabolism. Drug-Induced Vitamin Deficiency – Section: VITAMIN B6 (PYRIDOXINE) DEPLETION
2
PubMed Central. Impact of antiepileptic drugs on bone health: Need for monitoring, treatment, and prevention strategies
3
Epilepsy Research. An assessment of serum and red blood cell folate concentrations in patients with epilepsy on lamotrigine therapy – Section: Abstract
4
PubMed. Blood homocysteine, folate and vitamin B-12 concentrations in patients with epilepsy receiving lamotrigine or sodium valproate for initial monotherapy
5
Epilepsy & Behavior. B-Vitamin deficiency in patients treated with antiepileptic drugs – Section: Abstract
6
PubMed. Ameliorative effects of supplemental folinic acid on Lamotrigine-induced fetal malformations in the mouse
7
Clinical Epileptology. Pregnancy, folic acid, and antiseizure medication
8
The Lancet. Lamotrigine plus quetiapine combination therapy versus quetiapine monotherapy in bipolar depression (CEQUEL) – Section: Discussion
9
PubMed. Bone mineral density with lamotrigine monotherapy for epilepsy
10
PubMed. Effects of the antiepileptic drugs topiramate and lamotrigine on bone metabolism in rats
11
Arquivos de Neuro-Psiquiatria. Levetiracetam and lamotrigine effects as mono- and polytherapy on bone mineral density in epileptic patients
12
Epilepsia. Long‐Term Valproate and Lamotrigine Treatment May Be a Marker for Reduced Growth and Bone Mass in Children with Epilepsy
13
American Epilepsy Society. EFFECT OF ANTIEPILEPTIC DRUGS ON VITAMIN D LEVELS IN CHILDREN – Section: Results
14
Acta Medica Alanya. Investigation of the Antiepileptics on Levels of Vitamin D and Calcium – Section: Results
15
PubMed. Vigabatrin, lamotrigine, topiramate and serum carnitine levels
16
PubMed Central. Exposure to anti-seizure medications impact growth of gut bacterial species and subsequent host response