Drug & supplement interaction

Ketogenic Diet + Valproic Acid

Valproic Acid brand names: Depakene, Depacon, Valproate.

Moderate Interaction
The bottom line Moderate

Valproic Acid 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 Valproic Acid

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. Valproic Acid 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 Valproic Acid

Valproic Acid 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

Here's the good news if you're using valproic acid (Depakene) and thinking about the keto diet: the interaction we have on file is pretty mild, and it's mostly based on scattered, anecdotal reports rather than strong studies. The theory is that following a very low-carb, ketogenic plan can slightly lower blood levels of some seizure medicines. But the research that looked at this specifically found that valproic acid levels were not significantly reduced, and seizure control held steady.

So for your drug in particular, this looks like a low concern. Still, because valproic acid is a medicine where steady levels matter, and keto itself is sometimes used for epilepsy, I'd loop in your doctor before starting. They may want to check a blood level and watch for any change in seizures or mood.

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

Valproic Acid 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 valproic acid and the keto diet together all the time for tough-to-control epilepsy, and they usually work fine side by side. The concerns on file are uncommon and based mostly on a handful of case reports, so this isn't a reason to panic.

That said, two things are worth knowing. Both valproic acid and ketosis put some extra workload on the liver, and a few children on this combination have had liver trouble, so your doctor will likely keep an eye on liver labs. Also, the diet may slightly lower your valproic acid blood levels (one report saw about a 32% drop), which could weaken seizure or mood control, and valproate can blunt ketosis itself. If you're considering keto while on this medicine, please loop in your doctor or pharmacist first so they can monitor you safely.

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 Valproic Acid one above is among them. If you take anything else, check it against the full list below.

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 Valproic Acid

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 Valproic Acid, 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 Valproic Acid

This page covers Ketogenic Diet only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Valproic Acid page lists 173 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: 9 major · 147 moderate · 17 minor.

From our pharmacist’s overview on the Valproic Acid page

“Anyone taking valproic acid (Depakene, Depacon) for seizures or bipolar disorder should treat this list with genuine care. Of the 173 supplements and herbs on file, nine are rated major.”

Reviewed by 2 · Jul 18, 2026

Open the Valproic Acid interaction page

How much people look this up

Where Ketogenic Diet and Valproic Acid 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 Valproic Acid
Top 25%

#390 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 names: Depakene, Depacon, Valproate

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
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
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

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Pharmacist Counseling Corner

Following Ketogenic Diet While Taking Valproic Acid: Common Questions

Can you follow Ketogenic Diet while taking Valproic Acid?
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 Valproic Acid?
Valproic Acid 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 Valproic Acid 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

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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.