Drug & supplement interaction

Ketogenic Diet + Divalproex Sodium

Divalproex Sodium brand name: Depakote.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Divalproex Sodium falls into 2 drug categories that Ketogenic Diet can interact with; the most serious is rated moderate. Following the ketogenic diet may reduce the levels of certain anticonvulsants, although the clinical significance of this effect is unclear.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Ketogenic Diet and Divalproex Sodium

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Ketogenic Diet interacts with whole categories of medication. Divalproex Sodium falls into 2 of those categories, so it can interact with Ketogenic Diet in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

ANTICONVULSANTS

1 of 2

Why this applies to Divalproex Sodium

Divalproex Sodium falls under ANTICONVULSANTS — the group Ketogenic Diet interacts with.

Following the ketogenic diet may reduce the levels of certain anticonvulsants, although the clinical significance of this effect is unclear.
Pharmacokinetic research in patients chronically taking up to 4 antiepileptic drugs shows that following a modified Atkins diet for 4-12 weeks reduces the average anticonvulsant serum concentrations by 10.5% to 13.5% (range 7% to 19%) without affecting overall seizure control. Antiepileptic agents taken by these patients included carbamazepine, oxcarbazepine, topiramate, valproate, clobazam, nitrazepam, lamotrigine, zonisamide, and others. Levels of oxcarbazepine and levetiracetam did not seem to be significantly affected after the initiation of the ketogenic diet. Additionally, a small clinical study in children with drug-refractory epilepsy taking a variety of anticonvulsant medications shows that following a ketogenic diet for 12 weeks reduces serum concentrations of clobazam and its active metabolite desmethylclobazam, both by 38%, and lamotrigine by 15% without affecting overall seizure control. Levels of levetiracetam, topiramate, and valproic acid were not significantly reduced. Serum levels of anticonvulsants should be monitored in patients following a ketogenic diet.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

If you're managing seizures, migraines, or bipolar mania with divalproex (Depakote), here's the practical takeaway about the keto diet. Some research suggests a very low-carb plan can nudge the blood levels of certain seizure medicines down a little, roughly 10% or so on average. The good news is that in these studies, valproic acid (the active part of divalproex) specifically was not meaningfully lowered, and seizure control held steady.

So this is reassuring, but the evidence is mostly anecdotal and small. Because divalproex has a narrow target range, even modest shifts can matter for some people. If your levels drifted low, you might notice breakthrough seizures or mood changes. Before starting keto, check with your doctor or pharmacist so they can monitor your valproate level if needed.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Kverneland M, Taubøll E, Selmer KK, Iversen PO, Nakken KO. Modified Atkins diet may reduce serum concentrations of antiepileptic drugs. Acta Neurol Scand. 2015;131(3):187-90. PubMed
  2. Kverneland M, Taubøll E, Molteberg E, Veierød MB, Selmer KK, Nakken KO, Iversen PO. Pharmacokinetic interaction between modified Atkins diet and antiepileptic drugs in adults with drug-resistant epilepsy. Epilepsia. 2019;60(11):2235-2244. PubMed
  3. Pedersen S, Kverneland M, Rudi K, et al. Decreased serum concentrations of antiseizure medications in children with drug resistant epilepsy following treatment with ketogenic diet. Epilepsia Open. 2023;8(3):858-866. PubMed
Minor

VALPROATE

2 of 2

Divalproex Sodium also falls under VALPROATE.

There is some concern that the ketogenic diet might have additive hepatotoxic effects when used with valproate.
Valproic acid and the ketogenic diet are commonly combined in patients with epilepsy. However, hepatic dysfunction has been reported in children using the ketogenic diet, with evidence from some cases suggesting that the risk is increased in children also taking valproic acid. Tapering the medication and the diet has allowed for successful re-introduction of the diet in persons affected with liver injury. There is also some concern that combining valproic acid with the ketogenic diet might reduce the effects of both interventions. Valproic acid can inhibit ketosis in children using the ketogenic diet. In at least two cases, valproate levels in the blood were decreased by as much as 32% in adults using the ketogenic diet. However, these risks appear to be rare.
Severity Minor Likelihood Unlikely Evidence D

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the good news first: doctors actually use Depakote (divalproex) and the ketogenic diet together on purpose, especially in kids with tough-to-control epilepsy. So this isn't a combo you need to avoid. The concern on file is rated minor and is based mostly on a handful of case reports, not strong studies.

Two small things can happen. First, both the diet and divalproex can stress the liver, and rare cases (mostly in children) suggest the combination might add to that risk, so your doctor may want to check liver labs. Second, they can slightly blunt each other: the diet may lower your valproate blood level a bit, and the drug can make it harder to stay in ketosis. If you're considering keto while on Depakote, loop in your doctor or pharmacist so they can monitor you.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Cai QY, Zhou ZJ, Luo R, et al. Safety and tolerability of the ketogenic diet used for the treatment of refractory childhood epilepsy: a systematic review of published prospective studies. World J Pediatr. 2017;13(6):528-536. PubMed
  2. Kverneland M, Taubøll E, Selmer KK, Iversen PO, Nakken KO. Modified Atkins diet may reduce serum concentrations of antiepileptic drugs. Acta Neurol Scand. 2015;131(3):187-90. PubMed
  3. Kossoff EH, Zupec-Kania BA, Auvin S, et al. Optimal clinical management of children receiving dietary therapies for epilepsy: Updated recommendations of the International Ketogenic Diet Study Group. Epilepsia Open. 2018;3(2):175-192. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Ketogenic Diet Also Interacts With Other Medications

Ketogenic Diet has 136 moderate, 122 minor known drug interactions in our database — the Divalproex Sodium one above is among them. If you take anything else, check it against the full list below.

Moderate 136 Minor 122 No known interaction 2,572 (incl. Divalproex Sodium)
Taking anything else?

Check Another of Your Medications Against Ketogenic Diet

Covers the 2,830 medications we’ve checked against Ketogenic Diet. Pick one to open its full report.

From our Q&A

Questions About Ketogenic Diet or Divalproex Sodium

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Ketogenic Diet or Divalproex Sodium, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Divalproex Sodium

This page covers Ketogenic Diet only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Divalproex Sodium page lists 134 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Kava (major).

By severity: 7 major · 110 moderate · 17 minor.

Open the Divalproex Sodium interaction page

How much people look this up

Where Ketogenic Diet and Divalproex Sodium Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Ketogenic Diet
Steady interest

#1,206 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Divalproex Sodium
Top 25%

#446 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Eating pattern

About Ketogenic Diet

What is Ketogenic Diet?

  • Weight loss
  • Type 2 diabetes and blood sugar control
  • Drug-resistant epilepsy (especially in children)
  • Reducing appetite
  • Athletic and metabolic interest

The ketogenic diet is a very low-carbohydrate, high-fat eating plan that shifts the body to burn fat for fuel. It has the strongest evidence as a medical therapy for hard-to-treat epilepsy and may help short-term weight loss and blood sugar, but it can be hard to sustain and is not right for everyone. Talk with a doctor or pharmacist before starting, especially if you have a medical condition or take medication.

Read the full Ketogenic Diet monograph & all interactions
Medication

About Valproic Acid

What Is Valproic Acid Used For?

Brand name: Depakote

Valproic acid capsules (brands Valproic and Valproic Acid) and valproic acid oral solution (brand Valproic Acid) are both used to treat epilepsy. Specifically, they are approved for complex partial seizures (either alone or with other seizure types) as monotherapy or add-on therapy, and for simple and complex absence seizures as sole therapy or add-on therapy.

Both forms are intended for adults and pediatric patients. Always follow your prescriber's guidance on which product and regimen is right for you.

See full Valproic Acid drug information
Keep checking

Other Drugs & Ketogenic Diet

Browse every other medication we’ve checked against Ketogenic Diet — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
136Moderate
122Minor
2,571No known interaction
136 Moderate 122 Minor 2,571 No interaction
Moderate

136 interactions

Showing 60 of 136 moderate interactions — see all 136 on the Ketogenic Diet page.

Minor

122 interactions

Showing 60 of 122 minor interactions — see all 122 on the Ketogenic Diet page.

No interaction 2,571 drugs checked — show the list

We also checked Ketogenic Diet against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,571 medications checked with no known interaction — see the full Ketogenic Diet list.

See the full Ketogenic Diet interactions page
See every supplement checked against Divalproex Sodium, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

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

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Ketogenic Diet monograph › Uses, safety, and every drug interaction in one place Divalproex Sodium supplement interactions › Every supplement checked against Divalproex Sodium, ranked by severity Valproic Acid drug information › The full plain-English guide to this medication Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Following Ketogenic Diet While Taking Divalproex Sodium: Common Questions

Can you follow Ketogenic Diet while taking Divalproex Sodium?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for Ketogenic Diet and Divalproex Sodium?
Divalproex Sodium belongs to more than one drug category, and Ketogenic Diet interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Ketogenic Diet and Divalproex Sodium interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Divalproex Sodium and Ketogenic Diet?

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.