Drug-induced nutrient depletion

Sodium valproate & Nutrient Depletion

Also searched as Epilim. 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
9Nutrient associations
Insignificant DepletionHighest rating
The bottom line

Sodium valproate has been associated with depletion of INOSITOL, VITAMIN K, ZINC and ACETYL-L-CARNITINE and 5 more. This does not mean a deficiency will occur — it means these are worth knowing about and, if you take Sodium valproate long-term, worth raising with your pharmacist or healthcare provider.

Ask a pharmacist about Sodium valproate Free · usually answered within 24 hours

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

The evidence

Reported nutrient depletions with Sodium valproate

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.

INOSITOL

Insignificant Depletion

VALPROATE

Valproate might modestly reduce inositol levels.

Valproic acid reduces inositol levels in the brain by inhibiting the inositol phosphate synthase enzyme, which is involved in synthesis of inositol. Levels of inositol in the systemic circulation are determined primarily by dietary intake, and are unlikely to be affected significantly by valproic acid. The effect of valproic acid on brain inositol levels might contribute to its therapeutic effect in bipolar disorder. The effect of inositol supplements on the efficacy of valproic acid is unknown.
Taking Sodium valproate? A supplement is not needed for most patients. ⓘ
Dr. Brian Staiger, Pharm.D explains

Inositol is a naturally occurring compound your cells use for signaling, and it plays a role in how the brain regulates mood. Sodium valproate appears to interfere with an enzyme the brain uses to produce inositol locally, which can modestly lower inositol levels in brain tissue. Importantly, the inositol circulating in your bloodstream comes mainly from food and is not meaningfully affected. This is rated as an insignificant depletion, so most people taking valproate do not need to worry about supplementing it, though if you have questions your pharmacist or doctor is the right person to ask.

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

References (3)
  1. Williams RS, Cheng L, Mudge AW, Harwood AJ. A common mechanism of action for three mood-stabilizing drugs. Nature 2002;417:292-5. PubMed
  2. Harwood AJ. Lithium and bipolar mood disorder: the inositol-depletion hypothesis revisited. Mol Psychiatry 2005;10:117-26. PubMed
  3. Shaltiel G, Shamir A, Shapiro J, et al. Valproate decreases inositol biosynthesis. Biol Psychiatry 2004;56:868-74. 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 Sodium valproate? A supplement is not needed for most patients. ⓘ
Dr. Brian Staiger, Pharm.D explains

Vitamin K is the nutrient your blood needs to clot properly and that helps keep bones healthy. Some anticonvulsants are known to speed up the liver's breakdown of vitamin K, but sodium valproate is not a strong enzyme inducer the way drugs like phenytoin or carbamazepine are, so this concern is much less relevant here. The evidence rates this as insignificant for most adults on sodium valproate, meaning routine supplementation is generally not considered necessary. That said, if you are pregnant or have other reasons your vitamin K might already be low, it is worth bringing 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

ZINC

Insignificant Depletion

VALPROATE

Valproic acid might increase zinc excretion and reduce zinc levels.

Valproic acid might bind zinc. Some researchers suggest this contributes to both its mechanism of action and side effects. Whether valproic acid affects zinc balance in humans is unclear. Some studies have reported reduced serum and tissue zinc levels, while others have found no change. However, epilepsy has also been associated with both increases and decreases in zinc levels. There are a few case reports of alopecia and skin problems associated with valproic acid therapy which have responded to zinc supplements. The zinc status of these patients prior to starting valproic acid is not clear. It's unlikely that valproic acid causes clinically significant zinc deficiency in most patients. Consider supplements only if the patient has other risk factors or shows symptoms of deficiency.
Taking Sodium valproate? A supplement is not needed for most patients. ⓘ
Dr. Brian Staiger, Pharm.D explains

Zinc helps your body heal wounds, support immune function, and keep skin healthy. Sodium valproate may actually bind to zinc in the body, and some research suggests it could nudge the kidneys to excrete a little more of it, though studies have gone back and forth on whether this truly lowers zinc levels in people taking the drug. For most patients this is considered an insignificant concern, so there is no reason to worry or reach for a supplement on your own. If you notice unusual hair loss or skin changes while on this medication, that is worth mentioning to your pharmacist or doctor.

What Zinc does & food sources

Zinc supports immune function, wound healing, taste and smell, and many enzyme systems.

Common food sources:

  • Meat and shellfish (especially oysters)
  • Beans and lentils
  • Nuts and seeds
  • Whole grains

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

What to discuss with your clinician

Ask about zinc status if you take an associated medication long-term and notice slow wound healing, frequent infections, or taste changes — a clinician can decide whether testing or an empiric plan makes sense.

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

Supplement considerations

Zinc competes with copper for absorption — long-term, higher-dose zinc without medical guidance can cause copper deficiency. Zinc also binds some antibiotics in the gut, so dose timing matters.

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: Keep zinc doses moderate and time them away from interacting medications — ask your pharmacist.

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

References (11)
  1. Hurd RW, Van Rinsvelt HA, Wilder BJ, et al. Selenium, zinc, and copper changes with valproic acid: possible relation to drug side effects. Neurology 1984;34:1393-5. PubMed
  2. Altunbasak S, Biatmakoui F, Baytok V, et al. Serum and hair zinc levels in epileptic children taking valproic acid. Biol Trace Element Res 1997;58;117-25. PubMed
  3. Lerman-Sagie T, Statter M, Szabo G, Lerman P. Effect of valproic acid therapy on zinc metabolism in children with primary epilepsy. Clin Neuropharmacol 1987;10:80-6. PubMed
  4. Hurd RW, Wilder BJ, Van Rinsvelt HA. Valproate, birth defects, and zinc (letter). Lancet 1983;1:181. PubMed
  5. Akram M, Sullivan C, Mack G, Buchannan N. What is the clinical significance of reduced manganese and zinc levels in treated epileptic patients? Med J Australia 1989;15:113. PubMed
  6. Verrotti A, Basciani F, Trotta D, et al. Serum copper, zinc, selenium, glutathione peroxidase and superoxide dismutase levels in epileptic children before and after 1 year of sodium valproate and carbamazepine therapy. Epilepsy Res 2002;48:71-5. PubMed
  7. Kaji M, Ito M, Okuno T, et al. Serum copper and zinc levels in epileptic children with valproate treatment. Epilepsia 1992;33:555-7. PubMed
  8. Yuen WC, Whiteoak R, Thompson RP. Zinc concentrations in leucocytes of patients receiving antiepileptic drugs. J Clin Pathol 1998;41:553-5. PubMed
  9. Ilhan A, Uz E, Kali S, et al. Serum and hair trace element levels in patients with epilepsy and healthy subjects: does the antiepileptic therapy affect the element concentrations of hair? Eur J Neurol 1999;6:705-9. PubMed
  10. Fatemi SH, Calabrese JR. Treatment of valproate-induced alopecia (letter). Ann Pharmacother 1995;29;1302. PubMed
  11. Lewis-Jones MS, Evans S, Culshaw MA. Cutaneous manifestations of zinc deficiency during treatment with anticonvulsants. BMJ 1985;290:603-4. PubMed

ACETYL-L-CARNITINE

Moderate Depletion

VALPROATE

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

Valproic acid can reduce blood and tissue carnitine levels. Valproic acid interferes with L-carnitine biosynthesis in the liver and forms a valproylcarnitine ester, which is excreted in the urine, reducing tubular reabsorption of free carnitine. Reduced L-carnitine levels are not clinically significant in most people taking valproic acid. However, some patients may be at increased risk for L-carnitine deficiency with valproic acid, and this may contribute to the development of hyperammonemia and hepatotoxicity associated with the drug. Risk factors for symptomatic L-carnitine deficiency with valproic acid include age less than 2 years, severe neurological problems including mental retardation, taking multiple antiepileptic drugs, poor nutrition, and use of the ketogenic diet. Some experts recommend L-carnitine supplements for people with these risk factors who need to take valproic acid. There is one case report of successful use of acetyl-L-carnitine in a patient with asymptomatic hyperammonemia secondary to valproate. However, carnitine supplements aren't necessary for most people taking valproic acid who are otherwise healthy and consuming a diet adequate in L-carnitine.
Taking Sodium valproate? Monitor for depletion; a supplement is needed for some patients. ⓘ
Dr. Brian Staiger, Pharm.D explains

Carnitine is something your body makes and uses to help cells produce energy, and sodium valproate can pull levels down through two connected pathways: it interferes with the liver's ability to make carnitine, and it binds to carnitine to form a compound that gets flushed out in the urine instead of being recycled by the kidneys. For most adults on valproate, this does not cause a noticeable problem. That said, certain people, including very young children, those on multiple seizure medications, or those with poor nutrition, may be at greater risk, so if any of those apply to you or someone you care for, it is worth bringing up with your doctor or pharmacist.

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

References (17)
  1. 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
  2. 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
  3. Riva R, Albani F, Gobbi G, et al. Carnitine disposition before and during valproate therapy in patients with epilepsy. Epilepsia 1993;34:184-7. 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
  6. De Vivo DC, Bohan TP, Coulter DL, et al. L-carnitine supplementation in childhood epilepsy: Current perspectives. Epilepsia 1998;39:1216-25.
  7. 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
  8. Shapira Y, Gutman A. Muscle carnitine deficiency in patients using valproic acid. J Pediatrics 1991;118:646-9. PubMed
  9. Winter SC, Szabo-Aczel S, Curry CJR, et al. Plasma carnitine deficiency: Clinical observations in 51 pediatric patients. Am J Dis Child 1987;141:660-5. PubMed
  10. Coulter DL. Carnitine, valproate, and toxicity. J Child Neurol 1991;6:7-14.
  11. Raskind JY, El-Chaar GM. The role of carnitine supplementation during valproic acid therapy. Ann Pharmacother 2000;34:630-8. PubMed
  12. Coulter DL. Prevention of hepatotoxicity recurrence with valproate monotherapy and carnitine. Ann Neurol 1988;24:301.
  13. Vance CK, Vance H, Winter SC, et al. Control of valproate-induced hepatotoxicity with carnitine. Ann Neurol 1989;26:456.
  14. Hirose S, Mitsudome A, Yasumoto S, et al. Valproate therapy does not deplete carnitine levels in otherwise healthy children. Pediatrics 1998;101:E9 (abstract). PubMed
  15. Van Wouwe JP. Carnitine deficiency during valproic acid treatment. Int J Vitam Nutr Res 1995;65:211-4.
  16. Suzuki H, Hibino H, Inoue Y, Mikami A, Matsumoto H, Mikami K. Effect of acetyl-l-carnitine in elderly patient who presented with hyperammonemia associated with administration of sodium valproate. Asian J Psychiatr. 2017;30:179. PubMed
  17. Freeman JM, Vining EPG, Cost S, Singhi P. Does carnitine administration improve the symptoms attributed to anticonvulsant medications? A double-blinded, crossover study. Pediatrics 1994;93:893-5. DOI

FOLIC ACID

Moderate Depletion

VALPROATE

Valproate might reduce serum folate levels and increase the risk of folate deficiency.

Valproate may reduce folate levels in some people, but symptomatic deficiency has not been reported. Pregnant patients taking valproate may be especially at risk from reduced folate levels, as low folate levels during pregnancy may contribute to birth defects and pregnancy loss. However, most research suggests that taking folic acid 1-5 mg daily perinatally with valproate does not reduce the rate of fetal malformations. Furthermore, folic acid supplements have worsened seizure control in some people with epilepsy. Advise patients taking valproate chronically to consult their physician before taking folic acid supplements. For information on foods that are rich in folate, see our chart.
Taking Sodium valproate? Monitor for depletion; a supplement is needed for some patients. ⓘ
Dr. Brian Staiger, Pharm.D explains

Folic acid is a B vitamin your body needs to build healthy cells and, during pregnancy, to support normal fetal development. Sodium valproate appears to interfere with how the body processes and uses folate, which over time can nudge blood folate levels lower in some people. This is rated a moderate concern, so it is worth keeping on your radar, especially if you are pregnant or planning to become pregnant. Because folic acid supplements can actually affect seizure control in some people, please talk with your doctor or pharmacist before adding one on your own.

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 (6)
  1. Hendel J, Dam M, Gram L, et al. The effects of carbamazepine and valproate on folate metabolism in man. Acta Neurol Scan 1984;69:226-31. PubMed
  2. 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
  3. Reynolds EH, Trimble MR. Adverse neuropsychiatric effects of anticonvulsant drugs. Drugs 1985;29:570-81. PubMed
  4. Dansky LV, Rosenblatt DS, Andermann E. Mechanisms of teratogenesis: folic acid and antiepileptic therapy. Neurology 1992;42:32-42.
  5. Vajda FJE, O'Brien TJ, Graham JE, Hitchcock AA, Perucca P, Lander CM, Eadie MJ. Folic acid dose, valproate, and fetal malformations. Epilepsy Behav. 2021;114(Pt A):107569. PubMed
  6. Froscher W, Maier V, Laage M, et al. Folate deficiency, anticonvulsant drugs, and psychiatric morbidity. Clin Neuropharmacol 1995;18:165-82. PubMed

L-CARNITINE

Moderate Depletion

VALPROATE

L-carnitine levels may be reduced in patients taking valproate.

Valproic acid can reduce blood and tissue carnitine levels. Valproic acid interferes with L-carnitine biosynthesis in the liver, and formation of a valproylcarnitine ester which is excreted in the urine, reducing tubular reabsorption of free carnitine. Reduced L-carnitine levels are not clinically significant in most people taking valproic acid. However, some patients may be at increased risk for L-carnitine deficiency with valproic acid, and this may contribute to the development of hyperammonemia and hepatotoxicity associated with the drug. Risk factors for symptomatic L-carnitine deficiency with valproic acid include age less than 2 years, severe neurological problems including mental retardation, taking multiple antiepileptic drugs, poor nutrition, and use of the ketogenic diet. Some experts recommend L-carnitine supplements for people with these risk factors who need to take valproic acid. However, carnitine supplements aren't necessary for most people taking valproic acid who are otherwise healthy and consuming a diet adequate in L-carnitine.
Taking Sodium valproate? Monitor for depletion; a supplement is needed for some patients. ⓘ
Dr. Brian Staiger, Pharm.D explains

L-carnitine is a compound your body uses to move fatty acids into cells for energy production, and sodium valproate can lower your levels through two routes: it partially blocks the liver from making carnitine on its own, and it bonds to carnitine to form a byproduct that gets flushed out in the urine instead of being recycled by the kidneys. For most adults on valproate, this drop is not clinically significant and no action is needed. That said, certain people face a higher risk, including young children, those on multiple seizure medications, or anyone with poor nutrition, and for them a carnitine supplement may genuinely be warranted. If any of those risk factors apply to you, it is worth bringing up 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 (17)
  1. 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
  2. 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
  3. Riva R, Albani F, Gobbi G, et al. Carnitine disposition before and during valproate therapy in patients with epilepsy. Epilepsia 1993;34:184-7. 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
  6. De Vivo DC, Bohan TP, Coulter DL, et al. L-carnitine supplementation in childhood epilepsy: Current perspectives. Epilepsia 1998;39:1216-25.
  7. 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
  8. Shapira Y, Gutman A. Muscle carnitine deficiency in patients using valproic acid. J Pediatrics 1991;118:646-9. PubMed
  9. Winter SC, Szabo-Aczel S, Curry CJR, et al. Plasma carnitine deficiency: Clinical observations in 51 pediatric patients. Am J Dis Child 1987;141:660-5. PubMed
  10. Cattaneo CI, Ressico F, Valsesia R, D'Innella P, Ballabio M, Fornaro M. Sudden valproate-induced hyperammonemia managed with L-carnitine in a medically healthy bipolar patient: Essential review of the literature and case report. Medicine (Baltimore). 2017 PubMed
  11. Coulter DL. Carnitine, valproate, and toxicity. J Child Neurol 1991;6:7-14.
  12. Raskind JY, El-Chaar GM. The role of carnitine supplementation during valproic acid therapy. Ann Pharmacother 2000;34:630-8. PubMed
  13. Coulter DL. Prevention of hepatotoxicity recurrence with valproate monotherapy and carnitine. Ann Neurol 1988;24:301.
  14. Vance CK, Vance H, Winter SC, et al. Control of valproate-induced hepatotoxicity with carnitine. Ann Neurol 1989;26:456.
  15. Hirose S, Mitsudome A, Yasumoto S, et al. Valproate therapy does not deplete carnitine levels in otherwise healthy children. Pediatrics 1998;101:E9 (abstract). PubMed
  16. Van Wouwe JP. Carnitine deficiency during valproic acid treatment. Int J Vitam Nutr Res 1995;65:211-4.
  17. Freeman JM, Vining EPG, Cost S, Singhi P. Does carnitine administration improve the symptoms attributed to anticonvulsant medications? A double-blinded, crossover study. Pediatrics 1994;93:893-5. DOI

NIACIN

Moderate Depletion

VALPROATE

Valproate might reduce levels of niacin.

Case reports describe symptomatic niacin deficiency in people taking valproic acid alone or in combination with other anticonvulsants; however, the mechanism is not known.
Taking Sodium valproate? Monitor for depletion; a supplement is needed for some patients. ⓘ
Dr. Brian Staiger, Pharm.D explains

Niacin is a B vitamin your body uses for energy production and keeping your skin, nerves, and digestion working properly. Real-world case reports have shown that some people taking sodium valproate developed signs of niacin deficiency, though researchers have not yet pinned down exactly why this happens. Because the evidence is rated moderate, this is not something to ignore if you have been on this medication long-term. It is worth bringing up with your pharmacist or doctor, especially if you notice symptoms like skin changes, fatigue, or digestive upset.

What Vitamin B3 (niacin) does & food sources

Niacin supports energy metabolism, skin health, and nervous system function.

Common food sources:

  • Poultry, beef, and fish
  • Peanuts and legumes
  • Fortified grains

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

What to discuss with your clinician

Deficiency is rare in a typical diet. Discuss with your provider before using niacin as a supplement — at pharmacologic doses it behaves like a medication.

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

Supplement considerations

High-dose niacin causes flushing and can affect the liver, blood sugar, and uric acid — it is not a casual supplement.

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: Treat high-dose niacin as a medication decision, not a nutrition one.

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

References (2)
  1. Gillman MA, Sandyk R. Nicotinic acid deficiency induced by sodium valproate (letter). S Afr Med J 1984;65:986.
  2. Lyon VB, Fairley JA. Anticonvulsant-induced pellagra. J Am Acad Dermatol 2002;46:597-9. PubMed

PROPIONYL-L-CARNITINE

Moderate Depletion

VALPROATE

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

Valproic acid can reduce blood and tissue carnitine levels. Valproic acid interferes with L-carnitine biosynthesis in the liver and forms a valproylcarnitine ester, which is excreted in the urine, reducing tubular reabsorption of free carnitine. Reduced L-carnitine levels are not clinically significant in most people taking valproic acid. However, some patients may be at increased risk for L-carnitine deficiency with valproic acid, and this may contribute to the development of hyperammonemia and hepatotoxicity associated with the drug. Risk factors for symptomatic L-carnitine deficiency with valproic acid include age less than 2 years, severe neurological problems including mental retardation, taking multiple antiepileptic drugs, poor nutrition, and use of the ketogenic diet. Some experts recommend L-carnitine supplements for people with these risk factors who need to take valproic acid. There is no data on the use of propionyl-L-carnitine supplements in people taking valproic acid. Supplements of carnitines aren't necessary for most people taking valproic acid who are otherwise healthy and consuming a diet adequate in L-carnitine.
Taking Sodium valproate? Monitor for depletion; a supplement is needed for some patients. ⓘ
Dr. Brian Staiger, Pharm.D explains

Propionyl-L-carnitine is a form of carnitine, a compound your body uses to move fatty acids into cells for energy production. Sodium valproate can gradually pull down carnitine levels in two ways: it interferes with the liver's ability to make carnitine, and it binds to carnitine to form a byproduct that gets flushed out through the kidneys rather than recycled. For most adults on valproate, this does not cause a meaningful problem, but certain patients, including very young children, those on multiple seizure medications, or those with poor nutrition, may be at higher risk. If any of those situations apply to you or someone you care for, it is worth bringing up with your pharmacist or doctor.

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

References (16)
  1. 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
  2. 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
  3. Riva R, Albani F, Gobbi G, et al. Carnitine disposition before and during valproate therapy in patients with epilepsy. Epilepsia 1993;34:184-7. 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
  6. De Vivo DC, Bohan TP, Coulter DL, et al. L-carnitine supplementation in childhood epilepsy: Current perspectives. Epilepsia 1998;39:1216-25.
  7. 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
  8. Shapira Y, Gutman A. Muscle carnitine deficiency in patients using valproic acid. J Pediatrics 1991;118:646-9. PubMed
  9. Winter SC, Szabo-Aczel S, Curry CJR, et al. Plasma carnitine deficiency: Clinical observations in 51 pediatric patients. Am J Dis Child 1987;141:660-5. PubMed
  10. Coulter DL. Carnitine, valproate, and toxicity. J Child Neurol 1991;6:7-14.
  11. Raskind JY, El-Chaar GM. The role of carnitine supplementation during valproic acid therapy. Ann Pharmacother 2000;34:630-8. PubMed
  12. Coulter DL. Prevention of hepatotoxicity recurrence with valproate monotherapy and carnitine. Ann Neurol 1988;24:301.
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  14. Hirose S, Mitsudome A, Yasumoto S, et al. Valproate therapy does not deplete carnitine levels in otherwise healthy children. Pediatrics 1998;101:E9 (abstract). PubMed
  15. Van Wouwe JP. Carnitine deficiency during valproic acid treatment. Int J Vitam Nutr Res 1995;65:211-4.
  16. Freeman JM, Vining EPG, Cost S, Singhi P. Does carnitine administration improve the symptoms attributed to anticonvulsant medications? A double-blinded, crossover study. Pediatrics 1994;93:893-5. DOI

SELENIUM

Insufficient Evidence

VALPROATE

Valproate might reduce selenium levels; however, evidence is conflicting.

Animal model research and anecdotal reports suggest that valproate reduces plasma selenium levels, possibly by chelation and increased excretion. Theoretically, this might contribute to valproate side effects. However, other studies have found no effect. There isn't enough data to recommend routine selenium supplements with valproate therapy.
Taking Sodium valproate? Insufficient evidence to rate; clinical significance is not known. ⓘ
Dr. Brian Staiger, Pharm.D explains

Selenium is a trace mineral your body uses for antioxidant protection and thyroid function, and there are some animal studies and scattered reports suggesting valproate might lower selenium levels, possibly by binding to it in the body and nudging the kidneys to excrete more. That said, other studies have found no effect at all, and right now the evidence is simply too mixed to draw a clear conclusion. For most people taking valproate, this is more of an open question than a proven concern. Still, if you have been on valproate long-term and are curious whether this applies to you, it is worth a conversation with your pharmacist or doctor.

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

References (5)
  1. Hurd RW, Van Rinsvelt HA, Wilder BJ, et al. Selenium, zinc, and copper changes with valproic acid: possible relation to drug side effects. Neurology 1984;34:1393-5. PubMed
  2. Fatemi SH, Calabrese JR. Treatment of valproate-induced alopecia (letter). Ann Pharmacother 1995;29;1302. PubMed
  3. Linday LA, Pippenger CE, Howard A, Lieberman JA. Free radical scavenging enzyme activity and related trace metals in clozapine-induced agranulocytosis: a pilot study. J Clin Psychopharmacol 1995;15:353-60. PubMed
  4. Verrotti A, Basciani F, Trotta D, et al. Serum copper, zinc, selenium, glutathione peroxidase and superoxide dismutase levels in epileptic children before and after 1 year of sodium valproate and carbamazepine therapy. Epilepsy Res 2002;48:71-5. PubMed
  5. Kurekci AE, Alpay F, Tanindi S, et al. Plasma trace element, plasma glutathione peroxidase, and superoxide dismutase levels in epileptic children receiving antiepileptic drug therapy. Epilepsia 1995;36:600-4. 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 Sodium valproate

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

Sodium valproate & nutrients: FAQs

Does Sodium valproate deplete INOSITOL?
Sodium valproate has been associated with lower INOSITOL 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 Sodium valproate long-term, ask your healthcare provider whether checking your INOSITOL status is appropriate.
Should I take a supplement because I take Sodium valproate?
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 Sodium valproate?
No — never stop a prescribed medication because of a nutrient association. Sodium valproate 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 Sodium valproate and your nutrition?

Ask a licensed pharmacist — free, no appointment needed.

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Sources

Sources & How We Checked

Nutrient depletion records for Sodium valproate 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.