Drug-induced nutrient depletion

Phenobarbital & Nutrient Depletion

Also searched as Solfoton, Luminal. What the clinical evidence reports, what it may mean, and what to discuss with your pharmacist.

Medical content reviewed by Dr. Brian Staiger, PharmD, BCPS · Last reviewed July 2026
11Nutrient associations
Insignificant DepletionHighest rating
The bottom line

Phenobarbital has been associated with depletion of ACETYL-L-CARNITINE, L-CARNITINE, PROPIONYL-L-CARNITINE and VITAMIN K and 7 more. This does not mean a deficiency will occur — it means these are worth knowing about and, if you take Phenobarbital long-term, worth raising with your pharmacist or healthcare provider.

Ask a pharmacist about Phenobarbital Free · usually answered within 24 hours

Take more than one medication? Open the checker with Phenobarbital pre-loaded and add the rest to see overlapping nutrient signals.

The evidence

Reported nutrient depletions with Phenobarbital

Each record below is shown as published in our licensed clinical database, with its evidence rating and citations. Expand a section for food sources and talking points.

ACETYL-L-CARNITINE

Insignificant Depletion

PHENOBARBITAL (Luminal)

Theoretically, acetyl-L-carnitine levels may be reduced in patients taking phenobarbital.

Data on the effect of phenobarbital on blood levels of carnitines are conflicting. Some studies have found reduced L-carnitine levels in some patients taking phenobarbital. However, other studies have found no significant effect. Routine L-carnitine or acetyl-L-carnitine supplementation does not seem to be necessary.
Taking Phenobarbital? A supplement is not needed for most patients. ⓘ
Dr. Brian Staiger, Pharm.D explains

Acetyl-L-carnitine is a compound your body makes naturally that helps cells produce energy, particularly in the brain and muscles. Some early research raised the question of whether phenobarbital might interfere with how the body handles carnitines, possibly by affecting metabolism or how the body uses them over time, but studies on this have gone back and forth with no clear agreement. Given the insignificant rating here, most people taking phenobarbital do not need to worry about this or take a supplement for it. If you have any concerns, it is always fine to bring them up with your pharmacist or doctor.

Learn more about this nutrient: Acetyl-l-carnitine — uses, safety & interactions

References (5)
  1. Hug G, McGraw CA, Bates SR, et al. Reduction of serum carnitine concentrations during anticonvulsant therapy with phenobarbital, valproic acid, phenytoin, and carbamazepine in children. J Pediatr 1991;119:799-802. PubMed
  2. Castro-Gago M, Eiris-Punal J, Novo-Rodriguez MI, et al. Serum carnitine levels in epileptic children before and during treatment with valproic acid, carbamazepine, and phenobarbital. J Child Neurol 1998;13:546-9. PubMed
  3. Thom H, Carter PE, Cole GF, et al. Ammonia and carnitine concentrations in children treated with sodium valproate compared with other anticonvulsant drugs. Dev Med Child Neurol 1991;33:795-802. PubMed
  4. Zelnik N, Fridkis I, Gruener N. Reduced carnitine and antiepileptic drugs: cause relationship or co-existence? Acta Paediatr 1995;84:93-5. PubMed
  5. Opala G, Winter S, Vance C, et al. The effect of valproic acid on plasma carnitine levels. Am J Dis Child 1991;145:999-1001. PubMed

L-CARNITINE

Insignificant Depletion

PHENOBARBITAL (Luminal)

Theoretically, L-carnitine levels may be reduced in patients taking phenobarbital.

Some studies have found reduced levels of L-carnitine in some patients taking phenobarbital. However, other studies have found no significant effect. Routine L-carnitine supplementation does not seem to be necessary.
Taking Phenobarbital? A supplement is not needed for most patients. ⓘ
Dr. Brian Staiger, Pharm.D explains

L-carnitine is a compound your body uses to turn fat into usable energy, particularly in muscle cells. A few studies have spotted lower L-carnitine levels in some people on phenobarbital, possibly because the drug speeds up certain liver enzymes that affect how carnitine is processed and cleared. That said, other studies found no meaningful difference, and the overall evidence rates this as insignificant for most patients. Routine supplementation is not generally recommended, but if you have been on phenobarbital for a long time and have concerns, it is worth a quick conversation with your pharmacist or doctor.

What Carnitine does & food sources

Carnitine shuttles fatty acids into cells' mitochondria so they can be burned for energy.

Common food sources:

  • Red meat (the richest source)
  • Poultry and fish
  • Dairy products

HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.

What to discuss with your clinician

Carnitine questions come up with specific medications (for example, valproic acid) and specific situations — this is a conversation for your prescriber, who can weigh testing or supplementation.

HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.

Supplement considerations

Carnitine supplements are usually reserved for clinician-identified situations rather than general use.

Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.

HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.

Learn more about this nutrient: L-carnitine — uses, safety & interactions

References (5)
  1. Hug G, McGraw CA, Bates SR, et al. Reduction of serum carnitine concentrations during anticonvulsant therapy with phenobarbital, valproic acid, phenytoin, and carbamazepine in children. J Pediatr 1991;119:799-802. PubMed
  2. Castro-Gago M, Eiris-Punal J, Novo-Rodriguez MI, et al. Serum carnitine levels in epileptic children before and during treatment with valproic acid, carbamazepine, and phenobarbital. J Child Neurol 1998;13:546-9. PubMed
  3. Thom H, Carter PE, Cole GF, et al. Ammonia and carnitine concentrations in children treated with sodium valproate compared with other anticonvulsant drugs. Dev Med Child Neurol 1991;33:795-802. PubMed
  4. Zelnik N, Fridkis I, Gruener N. Reduced carnitine and antiepileptic drugs: cause relationship or co-existence? Acta Paediatr 1995;84:93-5. PubMed
  5. Opala G, Winter S, Vance C, et al. The effect of valproic acid on plasma carnitine levels. Am J Dis Child 1991;145:999-1001. PubMed

PROPIONYL-L-CARNITINE

Insignificant Depletion

PHENOBARBITAL (Luminal)

Theoretically, propionyl-L-carnitine levels may be reduced in patients taking phenobarbital.

Data on the effect of phenobarbital on blood levels of carnitines are conflicting. Some studies have found reduced levels in some patients taking phenobarbital. However, other studies have found no significant effect. Routine L-carnitine or propionyl-L-carnitine supplementation does not seem to be necessary.
Taking Phenobarbital? A supplement is not needed for most patients. ⓘ
Dr. Brian Staiger, Pharm.D explains

Propionyl-L-carnitine is a compound your body uses to help convert fat into usable energy, particularly in muscle tissue. Some research has suggested phenobarbital might interfere with how the body handles carnitines, possibly by affecting metabolism in the liver, but other studies found no meaningful difference at all. The evidence here is genuinely mixed and the overall rating is insignificant, meaning most people on phenobarbital do not need to worry about this or take a supplement. If you have been on phenobarbital long-term and have concerns, it is worth a quick conversation with your pharmacist or doctor.

Learn more about this nutrient: Propionyl-l-carnitine — uses, safety & interactions

References (5)
  1. Hug G, McGraw CA, Bates SR, et al. Reduction of serum carnitine concentrations during anticonvulsant therapy with phenobarbital, valproic acid, phenytoin, and carbamazepine in children. J Pediatr 1991;119:799-802. PubMed
  2. Castro-Gago M, Eiris-Punal J, Novo-Rodriguez MI, et al. Serum carnitine levels in epileptic children before and during treatment with valproic acid, carbamazepine, and phenobarbital. J Child Neurol 1998;13:546-9. PubMed
  3. Thom H, Carter PE, Cole GF, et al. Ammonia and carnitine concentrations in children treated with sodium valproate compared with other anticonvulsant drugs. Dev Med Child Neurol 1991;33:795-802. PubMed
  4. Zelnik N, Fridkis I, Gruener N. Reduced carnitine and antiepileptic drugs: cause relationship or co-existence? Acta Paediatr 1995;84:93-5. PubMed
  5. Opala G, Winter S, Vance C, et al. The effect of valproic acid on plasma carnitine levels. Am J Dis Child 1991;145:999-1001. PubMed

VITAMIN K

Insignificant Depletion

ANTICONVULSANTS

Certain anticonvulsants might decrease levels of vitamin K in adults; some anticonvulsants may also decrease vitamin K levels in the fetus when taken during pregnancy.

When taken during pregnancy, anticonvulsants that induce hepatic enzymes (e.g., phenobarbital, phenytoin, carbamazepine) can reduce vitamin K levels in the fetus and increase the risk of intracranial hemorrhage soon after birth. It's thought that liver enzyme induction by these drugs increases vitamin K metabolism. This has a significant effect on vitamin K levels in infants, who haven't built up stores of the vitamin. When anticonvulsants are needed during pregnancy, vitamin K 10-20 mg daily should be taken orally for the last month of pregnancy, and the baby should receive vitamin K immediately after delivery. There is also limited evidence that chronic carbamazepine or phenytoin therapy can cause subclinical reductions in vitamin K activity in adults. There are rare reports of prolonged clotting times and bleeding in people with additional risk factors for vitamin K deficiency, such as poor nutritional intake. These anticonvulsants don't significantly affect vitamin K and clotting parameters in most children and adults. For information on foods that are rich in vitamin K, see our chart.
Taking Phenobarbital? A supplement is not needed for most patients. ⓘ
Dr. Brian Staiger, Pharm.D explains

Vitamin K is something your body needs to form blood clots and keep bones healthy. Phenobarbital is known to rev up liver enzymes, and those enzymes can break down vitamin K faster than normal, nudging levels down over time. For most adults taking phenobarbital, this effect is considered insignificant and a supplement is not typically needed. The one situation where this gets more attention is pregnancy, so if that applies to you, bring it up with your doctor or pharmacist.

What Vitamin K does & food sources

Vitamin K is required for normal blood clotting and contributes to bone health.

Common food sources:

  • Leafy green vegetables (spinach, kale, broccoli)
  • Vegetable oils
  • Fermented foods like natto

HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.

What to discuss with your clinician

If you take warfarin, vitamin K intake is a central part of your therapy — consistency matters more than avoidance. Discuss any planned change in vitamin K intake (diet or supplements) with the clinic that manages your INR.

HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.

Supplement considerations

Never start or stop a vitamin K supplement on your own if you take warfarin — it directly changes how the medication works.

Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.

HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.

Caution: Vitamin K interacts with warfarin: keep intake consistent and involve your anticoagulation clinic in any change.

Learn more about this nutrient: Vitamin K — uses, safety & interactions

References (8)
  1. Cornelissen M, Steegers-Theunissen R, Kollee L, et al. Increased incidence of neonatal vitamin K deficiency resulting from maternal anticonvulsant therapy. Am J Obstet Gynecol 1993;168:923-8. PubMed
  2. Cornelissen M, Steegers-Theunissen R, Kollee L, et al. Supplementation of vitamin K in pregnant women receiving anticonvulsant therapy prevents neonatal vitamin K deficiency. Am J Obstet Gynecol 1993;168:884-8. PubMed
  3. Renzulli P, Tuchschmid P, Eich G, et al. Early vitamin K deficiency bleeding after maternal phenobarbital intake: management of massive intracranial haemorrhage by minimal surgical intervention. Eur J Pediatr 1998;157:663-5. PubMed
  4. Bleyer WA, Skinner AL. Fatal neonatal hemorrhage after maternal anticonvulsant therapy. JAMA 1976;235:626-7. DOI
  5. Thorp JA, Gaston L, Caspers DR, Pal ML. Current concepts and controversies in the use of vitamin K. Drugs 1995;49:376-87. PubMed
  6. Davies VA, Rothberg AD, Argent AC, Atkinson PM, Staub H, Pienaar NL. Precursor prothrombin status in patients receiving anticonvulsant drugs. Lancet 1985;1:126-8. PubMed
  7. Keith DA, Gundberg CM, Japour A, et al. Vitamin K-dependent proteins and anticonvulsant medication. Clin Pharmacol Ther 1983;34:529-32. PubMed
  8. Tam DA Jr, Myer EC. Vitamin K-dependent coagulopathy in a child receiving anticonvulsant therapy. J Child Neurol 1996;11:244-6. PubMed

BIOTIN

Moderate Depletion

PHENOBARBITAL (Luminal)

Phenobarbital might reduce blood levels of biotin.
Reduced plasma biotin levels can occur in people taking phenobarbital. In one study, plasma levels were 50% lower in people taking phenobarbital or various other anticonvulsants than in controls. There may also be increased urinary excretion of organic acids, an indicator of reduced biotin-dependent enzyme activity. Suggested mechanisms include competitive inhibition of biotin transport in the intestine, increased catabolism of biotin, and decreased renal tubular reabsorption of biotin. Phenobarbital contains a carbamide group, which is also present in biotin, and may lead to competition for intestinal and renal tubular absorption sites. The clinical significance of these effects on biotin isn't clear.
Taking Phenobarbital? Monitor for depletion; a supplement is needed for some patients. ⓘ
Dr. Brian Staiger, Pharm.D explains

Biotin is a B vitamin your body uses to convert food into energy and keep your skin, hair, and nervous system working properly. Phenobarbital appears to interfere with biotin in a few ways: it may compete with biotin for the same absorption spots in the gut and kidneys, and it may also speed up how quickly the body breaks biotin down, so less ends up in the bloodstream. Studies have found blood biotin levels noticeably lower in people taking this medication long-term, so this is rated as a moderate concern worth paying attention to. If you have been on phenobarbital for a while, it is worth asking your pharmacist or doctor whether your biotin levels should be checked or whether a supplement makes sense for you.

Learn more about this nutrient: Biotin — uses, safety & interactions

References (7)
  1. Krause KH, Bonjour JP, Berlit P, Kochen W. Biotin status of epileptics. Ann N Y Acad Sci 1985;447:297-313.
  2. Krause KH, Kochen W, Berlit P, Bonjour JP. Excretion of organic acids associated with biotin deficiency in chronic anticonvulsant therapy. Int J Vitam Nutr Res 1984;54:217-22.
  3. Krause KH, Berlit P, Bonjour JP. Vitamin status in patients on chronic anticonvulsant therapy. Int J Vitam Nutr Res 1982;52:375-85.
  4. Mock DM, Dyken ME. Biotin deficiency results from long-term therapy with anticonvulsants (abstract). Gastroenterology 1995;108:A740. DOI
  5. Mock DM, Mock NI, Nelson RP, Lombard KA. Disturbances in biotin metabolism in children undergoing long-term anticonvulsant therapy. J Pediatr Gastroentereol Nutr 1998;26:245-50.
  6. Mock DM, Dyken ME. Biotin catabolism is accelerated in adults receiving long-term therapy with anticonvulsants. Neurology 1997;49:1444-7. PubMed
  7. Rathman SC, Eisenschenk S, McMahon RJ. The abundance and function of biotin-dependent enzymes are reduced in rats chronically administered carbamazepine. J Nutr 2002;132:3405-10. PubMed

CALCIUM

Moderate Depletion

PHENOBARBITAL (Luminal)

Taking phenobarbital decreases calcium absorption and increases calcium requirements.

Phenobarbital decreases calcium absorption by increasing metabolism of vitamin D, which is needed for calcium absorption. Hypocalcemia and osteomalacia have occurred, especially with prolonged therapy or when used in combination with carbamazepine and/or phenytoin. Advise patients taking phenytoin for six months or more that they may also need vitamin D and calcium supplements. For information on foods that are rich in calcium, see our chart.
Taking Phenobarbital? Monitor for depletion; a supplement is needed for some patients. ⓘ
Dr. Brian Staiger, Pharm.D explains

Calcium keeps your bones strong and helps your muscles and nerves work properly, and phenobarbital can gradually chip away at your levels over time. Here is why: the drug speeds up how your liver breaks down vitamin D, and since your gut needs vitamin D to pull calcium out of food, less vitamin D means less calcium gets absorbed. This is rated a moderate concern, so it is not something to ignore, especially if you have been on phenobarbital for six months or longer. It is worth asking your pharmacist or doctor whether checking your levels or adding a vitamin D or calcium supplement makes sense for you.

What Calcium does & food sources

Calcium builds and maintains bone and is essential for muscle contraction and nerve signaling.

Common food sources:

  • Dairy products (milk, yogurt, cheese)
  • Fortified plant milks and juices
  • Canned fish with bones (sardines, salmon)
  • Leafy greens like kale

HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.

What to discuss with your clinician

Ask your provider whether bone health monitoring (and vitamin D testing) makes sense with long-term use of an associated medication — a blood calcium level alone does not capture bone calcium status.

HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.

Supplement considerations

Calcium can interfere with the absorption of several medications (some antibiotics, thyroid medication, iron) — separate the doses and confirm timing with your pharmacist. Total intake from food plus supplements matters more than supplements alone.

Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.

HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.

Caution: Very high calcium intake has its own risks (kidney stones in susceptible people) — more is not better.

Learn more about this nutrient: Calcium — uses, safety & interactions

References (5)
  1. Gough H, Goggin T, Bissessar A, et al. A comparative study of the relative influence of different anticonvulsant drugs, UV exposure and diet on vitamin D and calcium metabolism in out-patients with epilepsy. Quart J Med 1986;59:569-77. DOI
  2. Hoikka V, Alhava EM, Karjalainen P, et al. Carbamazepine and bone mineral metabolism. Acta Neurol Scand 1984;70:77-80. PubMed
  3. Rajantie J, Lamberg-Allardt C, Wilska M. Does carbamazepine treatment lead to a need of extra vitamin D in some mentally retarded children? Acta Paediatr Scand 1984;73:325-8. PubMed
  4. Bell RD, Pak CY, Zerwekh J, et al. Effect of phenytoin on bone and mineral density in ambulatory epileptic children. Brain Dev 1994;16:382-5.
  5. Collins N, Maher J, Cole M, et al. A prospective study to evaluate the dose of vitamin D required to correct low 25-hydroxyvitamin D levels, calcium, and alkaline phosphatase in patients at risk of developing antiepileptic drug-induced osteomalacia. Q J M

FOLIC ACID

Moderate Depletion

PHENOBARBITAL (Luminal)

Phenobarbital can reduce serum folate levels and increase the risk of folate deficiency.

In people with low dietary folate intake, phenobarbital might reduce serum folate levels leading to megaloblastic anemia, and possibly contributing to neurological side effects, mental changes, and cerebral atrophy. Possible mechanisms include reduced folic acid absorption, increased metabolism, increased demand for folic acid as a coenzyme for induced hepatic enzymes, or competitive interaction between folate coenzymes and phenobarbital. Pregnant patients taking phenobarbital may be especially at risk for reduced folate levels, as low folate levels during pregnancy may contribute to birth defects and pregnancy loss. Folic acid therapy seems to reverse these neurological effects. However, folic acid can worsen seizure control. Advise patients taking phenobarbital to consult their physician before taking folic acid supplements. For information on foods that are rich in folate, see our chart.
Taking Phenobarbital? Monitor for depletion; a supplement is needed for some patients. ⓘ
Dr. Brian Staiger, Pharm.D explains

Folic acid is a B vitamin your body depends on for healthy red blood cells, nerve function, and cell repair. Phenobarbital appears to interfere with folate in several ways: it can reduce how much your gut absorbs, speed up how the liver breaks it down, and even compete with folate at the enzyme level. Because this is rated a moderate depletion, long-term users, especially those with limited folate in their diet or anyone who is pregnant, have a real reason to bring this up with their doctor or pharmacist. One important wrinkle: folic acid supplements can actually affect seizure control, so please do not start one on your own without checking first.

What Folic acid (folate) does & food sources

Folate is needed for cell division, red blood cell formation, and healthy fetal development.

Common food sources:

  • Leafy green vegetables
  • Beans, lentils, and peas
  • Fortified grains and cereals
  • Citrus fruits

HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.

What to discuss with your clinician

Ask your provider whether folate monitoring or supplementation is appropriate for you — this matters most before and during pregnancy, and with long-term use of certain seizure or arthritis medications.

HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.

Supplement considerations

Folate needs are individual. With some medications (for example, methotrexate), folic acid is often prescribed deliberately on a specific schedule — follow your prescriber's instructions rather than adding your own.

Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.

HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.

Caution: High-dose folic acid can mask vitamin B12 deficiency, so the two are often evaluated together.

Learn more about this nutrient: Folic Acid — uses, safety & interactions

References (10)
  1. Froscher W, Maier V, Laage M, et al. Folate deficiency, anticonvulsant drugs, and psychiatric morbidity. Clin Neuropharmacol 1995;18:165-82. PubMed
  2. Taliani U, Camellini A, Bernardi P, et al. A clinical case of severe megaloblastic anemia during treatment with primidone. Acta Biomed Ateneo Parmense 1989;60:245-8.
  3. Lambie DG, Johnson RH. Drugs and folate metabolism. Drugs 1985;30:145-55. PubMed
  4. Botez MI, Peyronnard J, Berube L, Labrecque R. Relapsing neuropathy, cerebral atrophy and folate deficiency. Appl Neurophysiol 1979;42:171-83.. DOI
  5. Reynolds EH. Neurological aspects of folate and vitamin B12 metabolism. Clin Haematol 1976;5:661-96. DOI
  6. Reynolds EH. Folate metabolism and anticonvulsant therapy. Proc R Soc Med 1974;67:68.
  7. Reynolds EH, Trimble MR. Adverse neuropsychiatric effects of anticonvulsant drugs. Drugs 1985;29:570-81. PubMed
  8. Hiilesmaa VK, Teramo K, Granstrom ML, Bardy AH. Serum folate concentrations during pregnancy in women with epilepsy: relation to antiepileptic drug concentrations, number of seizures, and fetal outcome. Br Med J 1983;287:577-9. DOI
  9. Dansky LV, Rosenblatt DS, Andermann E. Mechanisms of teratogenesis: folic acid and antiepileptic therapy. Neurology 1992;42:32-42.
  10. Lewis DP, Van Dyke DC, Stumbo PJ, Berg MJ. Drug and environmental factors associated with adverse pregnancy outcomes. Part I: antiepileptic drugs, contraceptives, smoking, and folate. Ann Pharmacother 1998;32:802-17. PubMed

VITAMIN B12

Moderate Depletion

PHENOBARBITAL (Luminal)

Phenobarbital, especially when taken long-term, might reduce vitamin B12 absorption and increase the risk of deficiency.

In one case report, a 23-year-old male with epilepsy who was taking phenytoin with phenobarbital for two years presented with megaloblastic anemia due to severe decreases in vitamin B12 and folate levels. Theoretically, phenytoin and/or phenobarbital may have interfered with vitamin B12 absorption. Encourage patients to maintain adequate dietary vitamin B12 intake, and check folate and vitamin B12 status if symptoms of anemia develop. If considering alternatives, neither oxcarbazepine (Trileptal), levetiracetam (Keppra), nor valproate have been associated with reduced vitamin B12 levels. For information on foods that are rich in vitamin B12, see our chart.
Taking Phenobarbital? Monitor for depletion; a supplement is needed for some patients. ⓘ
Dr. Brian Staiger, Pharm.D explains

Vitamin B12 is a nutrient your nerves and red blood cells depend on, and taking phenobarbital long-term has been reported to interfere with how well your gut absorbs it. The thinking is that the drug may impair B12 uptake in the digestive tract, though the full picture is still not completely settled by research. Because the evidence here is rated as moderate, this is worth paying attention to rather than dismissing, especially if you have been on phenobarbital for years. Ask your doctor or pharmacist whether checking your B12 and folate levels makes sense for you.

What Vitamin B12 does & food sources

Vitamin B12 supports red blood cell formation, nerve function, and DNA synthesis.

Common food sources:

  • Meat, poultry, and fish
  • Eggs and dairy products
  • Fortified cereals and nutritional yeast

HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.

What to discuss with your clinician

If you take an associated medication long-term, ask your healthcare provider whether checking a vitamin B12 level (sometimes with methylmalonic acid) is appropriate — especially if you notice fatigue, numbness, tingling, or memory changes.

HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.

Supplement considerations

B12 status is easy to check and low levels are usually straightforward to address, so testing before supplementing is often the sensible order. High-dose folic acid can mask a B12 deficiency, which is one reason B12 and folate questions are best sorted out together with your provider.

Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.

HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.

Caution: B12 deficiency can look like other conditions — do not self-diagnose from symptoms alone.

Learn more about this nutrient: Vitamin B12 — uses, safety & interactions

References (5)
  1. Reynolds EH, Hallpike JF, Phillips BM, et al. Reversible absorptive defects in anticonvulsant megaloblastic anemia. J Clin Pathol 1965;18:593-8.
  2. Rezaei S, Shab-Bidar S, Abdurahman AA, Djafarian K. Oxcarbazepine administration and the serum levels of homocysteine, vitamin B12 and folate in epileptic patients: A systematic review and meta-analysis. Seizure. 2017;45:87-94. PubMed
  3. Sharma TK, Vardey SK, Sitaraman S. Evaluate the Effect of Valproate Monotherapy on the Serum Homocysteine, Folate and Vitamin B12 Levels in Epileptic Children. Clin Lab. 2015;61(8):933-40. PubMed
  4. Mahdavi A, Naeini AA, Najafi M, Ghazvini M, Maracy M. Vitamin B12 and Folate Status in Patients with Epilepsy Under Levetiracetam Monotherapy. Int J Prev Med. 2019;10:32. PubMed
  5. Ozdemir O, Yakut A, Dinleyici EC, Aydogdu SD, Yarar C, Colak O. Serum asymmetric dimethylarginine (ADMA), homocysteine, vitamin B(12), folate levels, and lipid profiles in epileptic children treated with valproic acid. Eur J Pediatr. 2011;170(7):873-7.

VITAMIN D

Moderate Depletion

PHENOBARBITAL (Luminal)

Taking phenobarbital for 6 month or longer might reduce blood levels of vitamin D.
Phenobarbital increases hepatic metabolism of vitamin D to inactive compounds, thereby reducing calcium absorption. Hypocalcemia and osteomalacia have occurred, especially with prolonged therapy, concurrent use of other enzyme-inducing anticonvulsants, or when other risk factors for vitamin D deficiency are present. Patients taking phenobarbital for 6 months or more may need vitamin D and calcium supplements. Doses of vitamin D needed vary from 400-4000 IU daily. For information on foods that are rich in vitamin D, see our chart.
Taking Phenobarbital? Monitor for depletion; a supplement is needed for some patients. ⓘ
Dr. Brian Staiger, Pharm.D explains

Phenobarbital is a liver enzyme inducer, meaning it revs up the liver's processing speed and breaks down vitamin D into inactive forms before your body can use it. Since vitamin D is what helps your gut absorb calcium and keep your bones strong, long-term use can leave both in short supply. This is a well-documented concern, not just a theoretical one, so if you have been taking phenobarbital for six months or more, it is worth asking your doctor or pharmacist whether your vitamin D level should be checked.

What Vitamin D does & food sources

Vitamin D helps the body absorb calcium and supports bone, muscle, and immune health.

Common food sources:

  • Fatty fish (salmon, mackerel)
  • Fortified milk and cereals
  • Egg yolks
  • Sunlight exposure (the main natural source)

HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.

What to discuss with your clinician

A 25-hydroxyvitamin D blood test is the standard way to assess status — ask whether it is appropriate if you take an associated medication long-term, have limited sun exposure, or have bone concerns.

HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.

Supplement considerations

Vitamin D dosing varies a lot between people; some medications change how vitamin D is processed. Your provider can target a dose to your level instead of guessing.

Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.

HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.

Caution: Vitamin D is fat-soluble and can accumulate — very high doses over time can cause harm, so follow a clinician-guided plan.

Learn more about this nutrient: Vitamin D — uses, safety & interactions

References (5)
  1. Gough H, Goggin T, Bissessar A, et al. A comparative study of the relative influence of different anticonvulsant drugs, UV exposure and diet on vitamin D and calcium metabolism in out-patients with epilepsy. Quart J Med 1986;59:569-77. DOI
  2. Hoikka V, Alhava EM, Karjalainen P, et al. Carbamazepine and bone mineral metabolism. Acta Neurol Scand 1984;70:77-80. PubMed
  3. Rajantie J, Lamberg-Allardt C, Wilska M. Does carbamazepine treatment lead to a need of extra vitamin D in some mentally retarded children? Acta Paediatr Scand 1984;73:325-8. PubMed
  4. Bell RD, Pak CY, Zerwekh J, et al. Effect of phenytoin on bone and mineral density in ambulatory epileptic children. Brain Dev 1994;16:382-5.
  5. Collins N, Maher J, Cole M, et al. A prospective study to evaluate the dose of vitamin D required to correct low 25-hydroxyvitamin D levels, calcium, and alkaline phosphatase in patients at risk of developing antiepileptic drug-induced osteomalacia. Q J M

VITAMIN E

Moderate Depletion

PHENOBARBITAL (Luminal)

Phenobarbital might reduce vitamin E levels.

There is some evidence that children taking phenobarbital have serum vitamin E levels 9% to 26% lower than children with untreated epilepsy. The clinical significance of this effect isn't clear. Vitamin E supplements don't seem to be harmful in children with epilepsy. They've been associated with either no effect on seizure control, or improved seizure control. Advise patients to maintain the recommended dietary intake of vitamin E. Consider supplements if plasma vitamin E levels are low (below 5 micrograms/mL).
Taking Phenobarbital? Monitor for depletion; a supplement is needed for some patients. ⓘ
Dr. Brian Staiger, Pharm.D explains

Vitamin E is an antioxidant your body uses to protect cells from damage, and children taking phenobarbital long-term have been found to have noticeably lower blood levels of it, possibly because the drug speeds up the liver enzymes that break vitamin E down. This is rated a moderate depletion, so it is worth paying attention to, especially for kids on this medication for seizure control. Eating vitamin E-rich foods (nuts, seeds, leafy greens) is a reasonable everyday step, and if levels look low on a blood test, a supplement may be worth discussing. Talk with your doctor or pharmacist about whether checking vitamin E levels makes sense for you or your child.

What Vitamin E does & food sources

Vitamin E is a fat-soluble antioxidant that protects cell membranes.

Common food sources:

  • Vegetable oils
  • Nuts and seeds
  • Wheat germ
  • Leafy greens

HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.

What to discuss with your clinician

Deficiency is rare; ask your provider before supplementing, particularly if you take blood thinners.

HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.

Supplement considerations

Higher-dose vitamin E can increase bleeding tendency, especially with warfarin or antiplatelet medications.

Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.

HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.

Caution: Discuss vitamin E supplements with your provider if you take any blood thinner.

Learn more about this nutrient: Vitamin E — uses, safety & interactions

References (6)
  1. Ogunmekan AO. Relationship between age and vitamin E level in epileptic children and normal children. Am J Clin Nutr 1979;32:2269-71.
  2. Kataoka K, Kanamori N, Oishi M, et al. Vitamin E status in pediatric patients receiving antiepileptic drugs. Devel Pharmacol Ther 1989;14:96-101. DOI
  3. Ogunmekan AO. Plasma vitamin E (alpha-tocopherol) levels in normal children and in epileptic children with and without anticonvulsant drug therapy. Trop Geog Med 1985;37:175-7.
  4. Higashi A, Ikeda T, Matsukura M, Matsuda I. Serum zinc and vitamin E concentrations in handicapped children treated with anticonvulsants. Devel Pharmacol Ther 1982;5:109-13. DOI
  5. Higashi A, Tamari H, Ikeda T, et al. Serum vitamin E concentration in patients with severe multiple handicaps treated with anticonvulsants. Pediatr Pharmacol 1980;1:129-34.
  6. Ogunmekan AO, Hwang PA. A randomized, double-blind, placebo-controlled, clinical trial of D-alpha-tocopheryl acetate (vitamin E), as add-on therapy, for epilepsy in children. Epilepsia 1989;30:84-9.

RIBOFLAVIN

Insufficient Evidence

PHENOBARBITAL (Luminal)

Phenobarbital might reduce active riboflavin levels; however, the clinical significance of this is unclear.
Some evidence in animals suggests that phenobarbital induces metabolism of riboflavin in the liver. Levels of the active form of riboflavin, flavin adenine dinucleotide (FAD), are increased in the liver and levels of a hydroxylated metabolite are increased in the urine. Also, some animal research suggests that phenobarbital does not significantly affect the content of flavin in the liver.
Taking Phenobarbital? Insufficient evidence to rate; clinical significance is not known. ⓘ
Dr. Brian Staiger, Pharm.D explains

Riboflavin is a B vitamin your body uses to convert food into energy and keep cells working properly. There is some animal research suggesting phenobarbital may speed up how the liver processes riboflavin, potentially affecting its active form, but this has not been clearly shown to matter in people. Given the insufficient evidence rating, this is more of an open question than a proven concern, so most patients taking phenobarbital do not need to act on this right now. If you are curious or have been on this medication long-term, it is worth a quick conversation with your pharmacist or doctor.

What Vitamin B2 (riboflavin) does & food sources

Riboflavin helps the body produce energy and process other B vitamins.

Common food sources:

  • Dairy products and eggs
  • Lean meats
  • Fortified grains
  • Green vegetables

HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.

What to discuss with your clinician

Deficiency is uncommon with a varied diet; ask your provider if you have persistent mouth-corner cracking, sore tongue, or unexplained fatigue on a long-term associated medication.

HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.

Supplement considerations

Riboflavin is water-soluble and excess is excreted (it turns urine bright yellow — harmless).

Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.

HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.

Learn more about this nutrient: Riboflavin — uses, safety & interactions

References (3)
  1. Ohkawa H, Ohishi N, Yagi K. Hydroxylation of the 7- and 8-methyl groups of riboflavin by the microsomal electron transfer system of rat liver. J Biol Chem 1983;258:5629-33.. DOI
  2. Hamajima S, Ono S, Hirano H, Obara K. Induction of the FAD synthetase system in rat liver by phenobarbital administration. Int J Vit Nutr Res 1979;49:59-63..
  3. Shargel L, Mazel P. Effect of riboflavin deficiency on phenobarbital and 3-methylcholanthrene induction of microsomal drug-metabolizing enzymes of the rat. Biochem Pharmacol. 1973;22(19):2365-73. PubMed
Important

This tool is educational and is not a substitute for professional medical advice. An association is not a diagnosis and does not mean a deficiency will occur. Always talk to your pharmacist or healthcare provider before starting, stopping, or changing any medication or supplement.

Disclaimer: This checker finds which nutrients might be depleted by prescription or over-the-counter medications. Each nutrient depletion issue is rated based on clinical significance. Use your own professional judgment prior to making clinical decisions.

© 2026 Therapeutic Research Center Licensed records refresh weekly · last updated July 3, 2026.
Keep exploring

More about Phenobarbital

Understand the basics

What drug-induced nutrient depletion means

Some medications can, over time, lower the levels of certain vitamins, minerals, or other nutrients — through reduced absorption, increased loss, or changes in how the body uses them.

Association is not deficiency

An entry here means a depletion has been reported or studied — not that it happens to everyone, or that you are deficient. Dose, duration, diet, and your own health all matter.

Evidence varies by pair

Some drug–nutrient links (like metformin and vitamin B12) are well studied; others rest on limited or preliminary research. Each entry shows the evidence rating from our licensed clinical database.

When to ask about labs

If you take an associated medication long-term, ask your healthcare provider whether monitoring is appropriate for you. Not everyone needs testing — your provider can weigh your dose, duration, and symptoms.

Don't self-supplement blindly

Supplements are not risk-free: some can interact with medications, and some (like potassium or magnesium) can be risky with kidney disease. Talk to your pharmacist before adding anything.

Never stop a medication over this

These medications are prescribed for good reasons, and the benefit usually far outweighs a manageable nutrient consideration. Any change belongs in a conversation with your prescriber.

Food first, usually

For many nutrients, a varied diet covers the gap. Each entry lists common food sources; a supplement is a decision to make with your pharmacist or provider, not a default.

Common questions

Phenobarbital & nutrients: FAQs

Does Phenobarbital deplete ACETYL-L-CARNITINE?
Phenobarbital has been associated with lower ACETYL-L-CARNITINE levels in the clinical literature — see the evidence rating and details above. An association is not a guarantee: dose, duration, diet, and your own health all matter. If you take Phenobarbital long-term, ask your healthcare provider whether checking your ACETYL-L-CARNITINE status is appropriate.
Should I take a supplement because I take Phenobarbital?
Not automatically. The right first step is usually a conversation with your pharmacist or provider — they can weigh your dose and duration, decide whether testing makes sense, and recommend food-first strategies or a supplement if genuinely needed. Some supplements can interact with medications, so do not add one without checking.
Should I stop taking Phenobarbital?
No — never stop a prescribed medication because of a nutrient association. Phenobarbital is prescribed for good reasons, and nutrient considerations are usually manageable with monitoring or diet. Any change to your medication belongs in a conversation with your prescriber.
Where does this information come from?
The depletion records come from the Natural Medicines (Therapeutic Research Center) database — an evidence-graded clinical reference — and are displayed as published, with their citations. The plain-English context is written and reviewed by licensed HelloPharmacist pharmacists.

Questions about Phenobarbital and your nutrition?

Ask a licensed pharmacist — free, no appointment needed.

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Sources

Sources & How We Checked

Nutrient depletion records for Phenobarbital are evidence-graded and sourced from the Natural Medicines database, and are displayed as published with their citations.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.