Ephedrine, Phenobarbital, Theophylline & Nutrient Depletion
Also searched as Tedral. What the clinical evidence reports, what it may mean, and what to discuss with your pharmacist.
Ephedrine, Phenobarbital, Theophylline has been associated with depletion of ACETYL-L-CARNITINE, L-CARNITINE, PROPIONYL-L-CARNITINE and VITAMIN K and 8 more. This does not mean a deficiency will occur — it means these are worth knowing about and, if you take Ephedrine, Phenobarbital, Theophylline long-term, worth raising with your pharmacist or healthcare provider.
Take more than one medication? Open the checker with Ephedrine, Phenobarbital, Theophylline pre-loaded and add the rest to see overlapping nutrient signals.
Reported nutrient depletions with Ephedrine, Phenobarbital, Theophylline
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.
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ACETYL-L-CARNITINE
Insignificant DepletionPHENOBARBITAL (Luminal)
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.
Acetyl-L-carnitine is a compound your body uses to help convert fat into energy, particularly for brain and nerve function. Some research has looked at whether phenobarbital might interfere with how the body handles carnitines, possibly affecting how they are processed or stored, but the studies done so far have pointed in different directions with no clear agreement. Because the evidence is conflicting and the overall rating here is insignificant, most people taking this medication are unlikely to need a supplement. That said, if you have any concerns, a quick conversation with your pharmacist or doctor can give you personalized guidance.
Learn more about this nutrient: Acetyl-l-carnitine — uses, safety & interactions
References (5)
- 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
- 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
- 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
- Zelnik N, Fridkis I, Gruener N. Reduced carnitine and antiepileptic drugs: cause relationship or co-existence? Acta Paediatr 1995;84:93-5. PubMed
- 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 DepletionPHENOBARBITAL (Luminal)
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.
Phenobarbital is the focus here, and here is what some research has turned up: a handful of studies found lower levels of L-carnitine, a compound your body uses to turn fat into usable energy, in patients taking it long term. The honest picture is mixed, though, because other studies found no real difference at all. With an insignificant depletion rating, routine supplementation does not appear necessary for most people, but if you have been on phenobarbital for a long time and have questions, your pharmacist or doctor is a good first stop.
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)
- 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
- 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
- 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
- Zelnik N, Fridkis I, Gruener N. Reduced carnitine and antiepileptic drugs: cause relationship or co-existence? Acta Paediatr 1995;84:93-5. PubMed
- 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 DepletionPHENOBARBITAL (Luminal)
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.
Propionyl-L-carnitine is a compound your body uses to help turn fat into usable energy, and some research has looked at whether phenobarbital might nudge levels of it downward, possibly by affecting how the body processes carnitines over time. Honestly, the studies on this are a mixed bag: some found modest reductions in certain patients, while others found no meaningful change at all. Given that this is rated as insignificant depletion, most people taking phenobarbital are not expected to need any supplementation. That said, if you have questions specific to your situation, a quick conversation with your pharmacist or doctor can put your mind at ease.
Learn more about this nutrient: Propionyl-l-carnitine — uses, safety & interactions
References (5)
- 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
- 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
- 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
- Zelnik N, Fridkis I, Gruener N. Reduced carnitine and antiepileptic drugs: cause relationship or co-existence? Acta Paediatr 1995;84:93-5. PubMed
- 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 DepletionANTICONVULSANTS
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.
Vitamin K is the nutrient your blood needs to clot properly and your bones need to stay strong. Of the three drugs listed here, phenobarbital is the one most connected to this: as an anticonvulsant, it revs up liver enzymes that can break down vitamin K faster than usual. That said, this is rated an insignificant depletion for most adults, so for the average person on these medications this is not a practical concern. If you are pregnant and taking phenobarbital, that is worth a specific conversation with your doctor, since the effect on a newborn can be more meaningful.
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.
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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)
- 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
- 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
- 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
- Bleyer WA, Skinner AL. Fatal neonatal hemorrhage after maternal anticonvulsant therapy. JAMA 1976;235:626-7. DOI
- Thorp JA, Gaston L, Caspers DR, Pal ML. Current concepts and controversies in the use of vitamin K. Drugs 1995;49:376-87. PubMed
- 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
- Keith DA, Gundberg CM, Japour A, et al. Vitamin K-dependent proteins and anticonvulsant medication. Clin Pharmacol Ther 1983;34:529-32. PubMed
- 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 DepletionPHENOBARBITAL (Luminal)
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.
Phenobarbital, the anticonvulsant in this combination, has been shown in studies to noticeably reduce biotin levels in the blood, sometimes by as much as half compared to people not taking it. Biotin is a B vitamin your body uses to help enzymes process fats, carbohydrates, and proteins properly. The drug appears to interfere at several points: it may compete with biotin for uptake in the gut, speed up how the body breaks biotin down, and reduce how much the kidneys reclaim before it leaves in urine. Because this is rated moderate depletion and some long-term users do need to supplement, it is worth bringing up with your pharmacist or doctor if you have been on this medication for an extended period.
Learn more about this nutrient: Biotin — uses, safety & interactions
References (7)
- Krause KH, Bonjour JP, Berlit P, Kochen W. Biotin status of epileptics. Ann N Y Acad Sci 1985;447:297-313.
- 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.
- Krause KH, Berlit P, Bonjour JP. Vitamin status in patients on chronic anticonvulsant therapy. Int J Vitam Nutr Res 1982;52:375-85.
- Mock DM, Dyken ME. Biotin deficiency results from long-term therapy with anticonvulsants (abstract). Gastroenterology 1995;108:A740. DOI
- 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.
- Mock DM, Dyken ME. Biotin catabolism is accelerated in adults receiving long-term therapy with anticonvulsants. Neurology 1997;49:1444-7. PubMed
- 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 DepletionPHENOBARBITAL (Luminal)
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.
Phenobarbital can interfere with how your body processes vitamin D, and since vitamin D is what helps your gut actually absorb calcium (the mineral that keeps your bones strong and your muscles working), less vitamin D in the picture means less calcium gets in. 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 calcium 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)
- 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
- Hoikka V, Alhava EM, Karjalainen P, et al. Carbamazepine and bone mineral metabolism. Acta Neurol Scand 1984;70:77-80. PubMed
- 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
- 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.
- 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 DepletionPHENOBARBITAL (Luminal)
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.
Phenobarbital, one of the medications in this combination, has a well-documented connection to lower folate levels in the body. Folate is a B vitamin your body relies on to make healthy red blood cells and support normal nerve and brain function. Phenobarbital appears to work against folate in several ways at once: it may reduce how much folate your gut absorbs, speed up how quickly your liver breaks it down, and increase the body's overall demand for it as a coenzyme. Because this is rated as moderate depletion, long-term users and anyone with a diet low in folate-rich foods (like leafy greens and beans) may be at greater risk, and this is especially important to flag if you are pregnant. That said, folate supplements are not straightforward here because folic acid can sometimes affect seizure control, so please talk with your doctor or pharmacist before making any changes.
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)
- Froscher W, Maier V, Laage M, et al. Folate deficiency, anticonvulsant drugs, and psychiatric morbidity. Clin Neuropharmacol 1995;18:165-82. PubMed
- 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.
- Lambie DG, Johnson RH. Drugs and folate metabolism. Drugs 1985;30:145-55. PubMed
- Botez MI, Peyronnard J, Berube L, Labrecque R. Relapsing neuropathy, cerebral atrophy and folate deficiency. Appl Neurophysiol 1979;42:171-83.. DOI
- Reynolds EH. Neurological aspects of folate and vitamin B12 metabolism. Clin Haematol 1976;5:661-96. DOI
- Reynolds EH. Folate metabolism and anticonvulsant therapy. Proc R Soc Med 1974;67:68.
- Reynolds EH, Trimble MR. Adverse neuropsychiatric effects of anticonvulsant drugs. Drugs 1985;29:570-81. PubMed
- 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
- Dansky LV, Rosenblatt DS, Andermann E. Mechanisms of teratogenesis: folic acid and antiepileptic therapy. Neurology 1992;42:32-42.
- 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
POTASSIUM
Moderate DepletionMETHYLXANTHINES
Methylxanthines like theophylline can reduce serum potassium levels, possibly by increasing intracellular uptake of potassium. Hypokalemia is most likely to occur after acute overdose of these drugs. However, reduced potassium levels can occur with therapeutic doses, and the incidence and degree of hypokalemia increases with increasing serum theophylline levels. Monitor potassium levels in people with other risk factors for hypokalemia. For information on foods that are rich in potassium, see our chart.
Potassium is a mineral your heart, muscles, and nerves depend on to work properly. Theophylline appears to push potassium out of the bloodstream and into cells, which can lower the amount your body has available to use. This is a moderate concern, meaning low potassium does not happen to everyone, but the risk goes up as theophylline levels in the blood rise. If you take theophylline long-term, it is worth asking your doctor or pharmacist whether your potassium levels should be checked.
What Potassium does & food sources
Potassium keeps nerve signals, muscle contractions, and heart rhythm working normally.
Common food sources:
- Bananas and citrus fruits
- Potatoes and sweet potatoes
- Beans and lentils
- Tomatoes and leafy greens
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
What to discuss with your clinician
Potassium is routinely checked with basic blood work. If you take a medication associated with potassium loss (like some diuretics), ask your provider how often your electrolytes should be monitored.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Supplement considerations
Do not start potassium supplements on your own. Both low and high potassium can affect heart rhythm, and several common medications (ACE inhibitors, ARBs, potassium-sparing diuretics) raise potassium.
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: Potassium supplementation can be dangerous in kidney disease or alongside potassium-raising medications — this is a decision for your prescriber, guided by lab results.
Learn more about this nutrient: Potassium — uses, safety & interactions
References (5)
- Ellenhorn MJ, et al. Ellenhorn's Medical Toxicology: Diagnoses and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams & Wilkins, 1997.
- Crane J, Burgess CD, Graham AN, Maling TJB. Hypokalemic and electrocardiographic effects of aminophylline and salbutamol in obstructive airways disease. NZ Med J 1987;100:309-11. DOI
- Zantvoort FA, Derkx FHM, Boomsma F, et al. Theophylline and serum electrolytes (letter). Ann Int Med 1986;104:134-5. PubMed
- Braat MCP, Jonkers RE, Bel EH, Van Boxtel CJ. Quantification of theophylline-induced eosinopenia and hypokalamia in healthy volunteers. Clin Pharmacokinet 1992;22:231-7..
- Flack JM, Ryder KW, Strickland D, Whang R. Metabolic correlates of theophylline therapy: a concentration-related phenomenon. Ann Pharmacother 1994;28:175-9.. PubMed
VITAMIN B12
Moderate DepletionPHENOBARBITAL (Luminal)
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.
Vitamin B12 is something your nerves and red blood cells genuinely depend on, and long-term phenobarbital use has been linked to lower levels of it, possibly because the drug interferes with how well your gut takes it in. This is rated as a moderate concern, meaning it does not affect everyone but is worth paying attention to over time, particularly if you notice symptoms like unusual fatigue or weakness. Keeping vitamin B12-rich foods in your diet is a reasonable step, and if you have been on phenobarbital for a while, it is worth asking your pharmacist or doctor whether checking your 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)
- Reynolds EH, Hallpike JF, Phillips BM, et al. Reversible absorptive defects in anticonvulsant megaloblastic anemia. J Clin Pathol 1965;18:593-8.
- 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
- 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
- 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
- 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 DepletionPHENOBARBITAL (Luminal)
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.
Phenobarbital is the key concern here: it revs up the liver's enzyme activity, which causes vitamin D to get broken down faster than normal, leaving less of it available to help your body absorb calcium and keep bones strong. With long-term use (six months or more), this can be enough of a drop to matter, which is why this is rated as a moderate depletion. If you have been on phenobarbital for a while, it is worth having a conversation with your doctor or pharmacist about whether checking your vitamin D level makes sense for you.
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)
- 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
- Hoikka V, Alhava EM, Karjalainen P, et al. Carbamazepine and bone mineral metabolism. Acta Neurol Scand 1984;70:77-80. PubMed
- 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
- 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.
- 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 DepletionPHENOBARBITAL (Luminal)
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).
Phenobarbital, a seizure medication, has been linked to lower blood levels of vitamin E, a nutrient your body uses to protect cells from damage and support immune function. Researchers think phenobarbital may speed up how the liver processes and clears vitamin E, leaving less of it circulating in the bloodstream. Studies in children taking phenobarbital have found their vitamin E levels noticeably lower than in untreated peers, so this is worth paying attention to rather than brushing aside. If you or your child is on phenobarbital long-term, it is reasonable to ask your doctor or pharmacist whether checking vitamin E levels or adjusting dietary intake makes sense for your situation.
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)
- Ogunmekan AO. Relationship between age and vitamin E level in epileptic children and normal children. Am J Clin Nutr 1979;32:2269-71.
- 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
- 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.
- 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
- 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.
- 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 EvidencePHENOBARBITAL (Luminal)
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.
Riboflavin is a B vitamin your body uses to convert food into energy and keep cells working properly. Animal studies have suggested that phenobarbital may prompt the liver to process riboflavin more quickly, potentially shifting its active form around, but other animal research found no meaningful change at all. Because the evidence comes only from animal studies and points in different directions, we simply do not know whether this matters in people. If you have been on phenobarbital long-term and have questions about your nutritional status, 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)
- 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
- 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..
- 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
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.
More about Ephedrine, Phenobarbital, Theophylline
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.
Ephedrine, Phenobarbital, Theophylline & nutrients: FAQs
Does Ephedrine, Phenobarbital, Theophylline deplete ACETYL-L-CARNITINE?
Should I take a supplement because I take Ephedrine, Phenobarbital, Theophylline?
Should I stop taking Ephedrine, Phenobarbital, Theophylline?
Where does this information come from?
Questions about Ephedrine, Phenobarbital, Theophylline and your nutrition?
Ask a licensed pharmacist — free, no appointment needed.
Sources & How We Checked
Nutrient depletion records for Ephedrine, Phenobarbital, Theophylline are evidence-graded and sourced from the Natural Medicines database, and are displayed as published with their citations.
- Natural Medicines (Therapeutic Research Center) — Evidence-graded clinical reference for drug-induced nutrient depletions, supplements, and interactions — the basis for this page.
- MedlinePlus, U.S. National Library of Medicine — NIH consumer drug information, used for medication overviews across the site.
Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.