Atropine, Hyoscyamine, Phenobarbital & Nutrient Depletion
Also searched as Hypnaldyne. What the clinical evidence reports, what it may mean, and what to discuss with your pharmacist.
Atropine, Hyoscyamine, Phenobarbital has been associated with depletion of ACETYL-L-CARNITINE, L-CARNITINE, PROPIONYL-L-CARNITINE and BIOTIN and 3 more. This does not mean a deficiency will occur — it means these are worth knowing about and, if you take Atropine, Hyoscyamine, Phenobarbital long-term, worth raising with your pharmacist or healthcare provider.
Take more than one medication? Open the checker with Atropine, Hyoscyamine, Phenobarbital pre-loaded and add the rest to see overlapping nutrient signals.
Reported nutrient depletions with Atropine, Hyoscyamine, 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.
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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 turn fat into energy, and it also supports nerve cell function. The phenobarbital component of this combination has been studied in relation to carnitine levels, though the research is genuinely mixed, with some studies finding a modest reduction and others finding no meaningful change at all. Given that this is rated as an insignificant depletion, most people taking this medication do not need to worry about supplementing. That said, if you have questions or any concerns about long-term use, it is always worth a quick conversation with your pharmacist or doctor.
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, one of the ingredients in this combination, has shown up in some research as possibly affecting L-carnitine levels, a nutrient your muscles and cells use to turn fat into energy. The evidence is genuinely mixed though: some studies found lower levels in people taking phenobarbital, while others found no real difference. Given that this is rated as an insignificant depletion, most people taking this medication do not need to worry about it or add a supplement. If you have questions or take phenobarbital long-term, it is always fine to bring it up with your pharmacist.
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 convert fats into energy, particularly in muscle tissue. The phenobarbital component of this combination has shown up in some studies as possibly affecting carnitine levels in the blood, though other studies found no real change at all. Because the evidence is genuinely mixed and the overall rating here is insignificant, most people taking this medication are not expected to need any supplementation. That said, if you have questions about your nutritional status, your pharmacist or doctor is a good person to check in with.
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
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.
Biotin is a B vitamin your body uses to convert food into energy and keep your skin, hair, and nervous system healthy. In this combination product, phenobarbital appears to be the ingredient most likely to affect biotin levels, possibly by competing with biotin for absorption in the gut and by causing the kidneys to hold onto less of it, so more gets lost in urine. Studies have found meaningfully lower biotin levels in people taking phenobarbital long-term, so this is rated a moderate concern worth paying attention to. If you have been on this medication for a while, it is worth asking your pharmacist or doctor whether your biotin level should be checked or whether a supplement makes sense for you.
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, the seizure-preventing component in this combination, can quietly work against your calcium levels over time. It does this indirectly: phenobarbital speeds up the liver's breakdown of vitamin D, and without enough vitamin D your gut simply cannot absorb calcium properly. Because this is rated a moderate depletion concern, long-term users have a real reason to bring it up. If you have been taking this medication for six months or more, it is worth asking your pharmacist or doctor whether checking your calcium and vitamin D levels 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 active ingredients in this combination, is the reason folate shows up on your radar here. Folate is a B vitamin your body needs to build healthy red blood cells and support your nervous system. Phenobarbital appears to interfere with folate in several ways at once: it can reduce how much your gut absorbs, speed up how quickly your liver breaks it down, and compete with folate at the enzyme level. Because the evidence is rated moderate, long-term users, especially those with a modest diet or who are pregnant, may want to bring this up with their doctor or pharmacist before considering any supplement, since folic acid can actually affect seizure control in some people.
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
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 (vitamin B2) helps your body turn food into energy and keeps your skin, nerves, and eyes healthy. The phenobarbital component of this combination may cause the liver to process riboflavin faster than usual, potentially lowering active levels in the body. That said, the research on this is early, partly from animal studies, and the results are mixed, so its real-world significance in people is simply not known yet. If you have been on this medication long-term and have concerns, it is worth bringing up 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 Atropine, Hyoscyamine, Phenobarbital
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.
Atropine, Hyoscyamine, Phenobarbital & nutrients: FAQs
Does Atropine, Hyoscyamine, Phenobarbital deplete ACETYL-L-CARNITINE?
Should I take a supplement because I take Atropine, Hyoscyamine, Phenobarbital?
Should I stop taking Atropine, Hyoscyamine, Phenobarbital?
Where does this information come from?
Questions about Atropine, Hyoscyamine, Phenobarbital and your nutrition?
Ask a licensed pharmacist — free, no appointment needed.
Sources & How We Checked
Nutrient depletion records for Atropine, Hyoscyamine, Phenobarbital 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.