Nutrient depletion·Folate (Vitamin B9)·Reviewed June 9, 2026
What depletes folate?
23 medications in the NutriStack database are documented to lower Folate with ongoing use, most notably Carbamazepine, Methotrexate, Phenytoin, and Sulfasalazine. The pattern spans 16 drug classes. Depletion builds slowly and is easy to miss; the table below shows how each medication drives it and which biomarker to check. Never start a replacement supplement without your prescriber's input.
Folate (Vitamin B9) depletion at a glance.
A quick, data-grounded summary. The per-medication table is below.
23 medications in the NutriStack database are documented to lower Folate with ongoing use, most notably Carbamazepine, Methotrexate, Phenytoin, and Sulfasalazine. The pattern spans 16 drug classes. Depletion builds slowly and is easy to miss; the table below shows how each medication drives it and which biomarker to check. Never start a replacement supplement without your prescriber's input.
What is documented to lower folate.
Worst documented severity first. Open any medication for its full interaction and depletion guide. Absence from this table means no documented record, not proven safety.
| Medication | Severity | How it lowers folate | Monitor |
|---|---|---|---|
| Carbamazepine Antiepileptic | Significant | Carbamazepine lowers folate through enzyme induction and altered intestinal handling during chronic therapy. | Serum folate or RBC folate |
| Methotrexate Disease-Modifying Antirheumatic Drug (DMARD) | Significant | Methotrexate directly inhibits dihydrofolate reductase, lowering reduced folate pools and increasing mucosal and hematologic toxicity risk. | CBC trend + liver enzymes; folate rescue should follow the prescriber's protocol |
| Phenytoin Antiepileptic | Significant | Phenytoin impairs intestinal folate absorption and increases folate catabolism during chronic use. | Serum folate or RBC folate |
| Sulfasalazine Aminosalicylate (IBD/DMARD) | Significant | Sulfasalazine impairs folate absorption in the small intestine and can lower folate status during chronic therapy. | Serum folate or RBC folate |
| Combined Oral Contraceptive Hormonal Contraceptive | Moderate | Estrogen-progestin contraceptives can lower folate status through altered metabolism and increased requirement in some users. | Serum folate or RBC folate |
| Metformin Biguanide | Moderate | Long-term metformin use is associated with lower folate status, likely through impaired intestinal absorption and altered enterohepatic handling. | Serum folate or RBC folate |
| Phenobarbital Barbiturate anticonvulsant | Moderate | Chronic enzyme-inducing anticonvulsant therapy can lower folate status through altered metabolism and absorption, increasing risk of megaloblastic... | CBC, serum folate, red blood cell folate, and homocysteine |
| Primidone Anticonvulsant metabolized to phenobarbital | Moderate | Chronic older anticonvulsant therapy can lower folate status and contribute to megaloblastic anemia. | CBC, serum folate, red blood cell folate, and homocysteine |
| Trimethoprim-Sulfamethoxazole Sulfonamide/Diaminopyrimidine Combination | Moderate | Trimethoprim inhibits dihydrofolate reductase and sulfamethoxazole adds antifolate pressure, which can lower functional folate status in susceptible... | CBC + serum folate or RBC folate |
| Valproic Acid Mood Stabilizer / Anticonvulsant | Moderate | Valproate is associated with lower folate status and altered one-carbon metabolism during chronic therapy. | Serum folate or RBC folate |
| Aluminum/Magnesium Hydroxide Antacid | Mild | Antacid-related pH changes can modestly reduce folate absorption during chronic use. | Serum folate or RBC folate |
| Calcium Carbonate Antacid | Mild | Chronic acid buffering can modestly reduce folate absorption in some users. | Serum folate or RBC folate |
| Cholestyramine Bile acid sequestrant | Mild | Cholestyramine can bind folate in the gut and lower its absorption; reduced serum and red-cell folate has been reported with prolonged therapy, with... | Serum folate and red-blood-cell folate |
| Citalopram SSRI | Mild | Lower folate status is associated with poorer SSRI response and may be reduced in some chronic users through altered one-carbon metabolism. | Serum folate or RBC folate |
| Escitalopram SSRI | Mild | Lower folate status is associated with poorer SSRI response and may be reduced in some chronic users through altered one-carbon metabolism. | Serum folate or RBC folate |
| Fluoxetine SSRI | Mild | Lower folate status is associated with poorer SSRI response and may be reduced in some chronic users through altered one-carbon metabolism. | Serum folate or RBC folate |
| Fluvoxamine SSRI | Mild | Lower folate status is associated with poorer SSRI response and may be reduced in some chronic users through altered one-carbon metabolism. | Serum folate or RBC folate |
| Gemfibrozil Fibrate (fibric acid derivative) | Mild | Fibrate therapy is associated with an increase in plasma total homocysteine, an effect attributed largely to altered renal handling/creatinine and... | Plasma total homocysteine; serum/red blood cell folate |
| Levodopa/Carbidopa Dopaminergic / Antiparkinson | Mild | Levodopa methylation can increase methyl-donor demand, making folate status clinically relevant when homocysteine rises on chronic therapy. | Serum folate or RBC folate + homocysteine |
| Paroxetine SSRI | Mild | Lower folate status is associated with poorer SSRI response and may be reduced in some chronic users through altered one-carbon metabolism. | Serum folate or RBC folate |
| Sertraline SSRI | Mild | Lower folate status is associated with poorer SSRI response and may be reduced in some chronic users through altered one-carbon metabolism. | Serum folate or RBC folate |
| Valganciclovir Antiviral (nucleoside analogue prodrug) | Mild | Ganciclovir (the active moiety of valganciclovir) is a guanosine nucleoside analog that inhibits DNA synthesis and is markedly myelosuppressive,... | Complete blood count (CBC) with neutrophil count; serum or red-cell folate if megaloblastic features are present |
| Zonisamide Sulfonamide anticonvulsant and carbonic anhydrase inhibitor | Mild | Long-term antiseizure therapy has been associated with reduced folate status in some patients; the evidence is stronger for older enzyme-inducing... | CBC, serum folate, red blood cell folate, and homocysteine |
If you need to restore folate.
Repletion is not automatic: dose, form, and timing depend on the medication involved, and some pairings need separation from the very drug causing the depletion. Confirm with your prescriber before adding folate.
Common folate depletion questions.
Quick answers drawn from the table above.
Which medications deplete folate?
23 medications in the NutriStack database are documented to lower folate, including Carbamazepine, Methotrexate, Phenytoin, Sulfasalazine, and Combined Oral Contraceptive. Severity differs by drug; the full table with mechanisms and monitoring biomarkers is on this page.
How do I know if my folate is low?
The biomarkers used to track folate status in this context include Serum folate or RBC folate, CBC trend + liver enzymes; folate rescue should follow the prescriber's protocol, and CBC, serum folate, red blood cell folate, and homocysteine. If you take one of the medications above long term, ask your prescriber whether checking is worthwhile; depletion develops gradually.
Should I take a folate supplement with these medications?
Not automatically. Documented depletion makes repletion worth discussing, but the right answer depends on your labs, dose, and the specific drug. Bring it up with your prescriber or pharmacist.
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