Adjunctive Therapies for Canine Epilepsy: CBD, MCT Oil, Omega-3s, and Beyond

When your dog's seizures persist despite medications, the search for additional help becomes urgent. You've tried phenobarbital, potassium bromide, levetiracetam—maybe all of them together—and still, the seizures continue. This is refractory epilepsy, affecting 20-30% of dogs with idiopathic epilepsy.

But here's what many pet owners don't realize: medications address the electrical problem, but seizures also involve metabolic, inflammatory, and oxidative stress issues that drugs alone may not fully resolve. This is where adjunctive therapies enter the picture—not as replacements for medications, but as powerful supplements that work alongside your dog's existing treatment.

Recent clinical trials have identified specific nutritional and botanical supplements that demonstrate statistically significant efficacy in reducing seizure burden. CBD oil, MCT-enriched diets, and omega-3 fatty acids have all shown promise in rigorous studies. However, navigating this landscape requires understanding the evidence, safety considerations, and the critical importance of veterinary oversight.

This comprehensive guide breaks down the science, clinical results, and practical considerations for the most evidence-based adjunctive therapies available for canine epilepsy.

Understanding Refractory Epilepsy: The Therapeutic Gap

Epilepsy affects between 0.5% and 5.7% of dogs, making it one of the most common neurological conditions in veterinary medicine. Despite appropriate therapy with licensed anti-epileptic drugs (AEDs), approximately 20-30% of dogs fail to achieve adequate seizure control and are classified as having refractory epilepsy.

This persistent lack of control creates what researchers call a "therapeutic gap"—a space where traditional medications aren't enough. This gap has driven rigorous investigation into non-pharmacological, adjunctive therapies that address the underlying neurobiological processes associated with epileptogenesis.

Why Adjunctive Therapies Matter

Adjunctive therapies work differently than medications. While drugs like phenobarbital stabilize ion channels and modulate neurotransmitters to suppress electrical activity, nutritional and botanical supplements target:

• Neuroinflammation: Chronic inflammation that lowers seizure thresholds
• Oxidative stress: Free radical damage from repeated seizures
• Metabolic dysfunction: Energy deficits in seizure-prone brains
• Endocannabinoid system: Natural pathways that regulate neuronal excitability

By addressing these underlying mechanisms, adjunctive therapies can complement medications, potentially improving outcomes even in dogs who haven't responded well to drugs alone.

Tier 1: Cannabidiol (CBD) Oil – The Most Studied Supplement

CBD oil has garnered the most substantial scientific attention among veterinary supplements, largely due to multi-year, rigorous clinical trials funded by organizations like the Canine Health Foundation.

Clinical Trial Results: What the Research Shows

A double-blind, crossover trial involving 39 dogs with idiopathic epilepsy provided compelling evidence for CBD's efficacy. Dogs received either CBD oil or placebo for three months, followed by a washout period and a switch to the opposite treatment.

Key Findings at 9 mg/kg/day:

• 24.1% reduction in seizure days compared to baseline
• Placebo group experienced a 5.8% increase in seizure days
• Statistically significant improvement in overall seizure burden

However, there's an important nuance: the study found no significant difference in the number of dogs achieving a 50% or greater reduction in seizures—the gold standard for "well-controlled" epilepsy. This suggests CBD functions primarily as an excellent adjunctive agent that mitigates overall seizure activity, rather than a primary anticonvulsant that eliminates seizures in most patients.

Managing Expectations

When adding CBD to your dog's treatment plan, the clinical goal should be focused on achieving incremental, measurable improvements in seizure frequency and severity—not necessarily eliminating seizures entirely. A 24% reduction in seizure days represents meaningful quality-of-life improvement, even if it doesn't achieve complete seizure freedom.

Safety Profile: Liver Monitoring Is Essential

CBD is generally well-tolerated, with common mild side effects including:

• Gastrointestinal upset
• Vomiting
• Decreased appetite (hyporexia)

However, a critical safety concern involves hepatic function. Liver enzyme activities, notably Alanine Aminotransferase (ALT) and Alkaline Phosphatase (ALP), were found to be significantly increased in dogs receiving CBD, particularly during chronic administration. This enzyme elevation signals that the liver is experiencing metabolic stress, making mandatory monitoring of hepatic health essential.

The Phenobarbital Interaction: Why Monitoring Matters

CBD is a known inhibitor of the cytochrome P450 (CYP450) enzyme system—the primary metabolic pathway for many drugs, including phenobarbital. Theoretically, this could slow the breakdown of phenobarbital, causing blood levels to remain elevated and potentially increasing side effects or toxicity.

While some pharmacokinetic studies have found conflicting results regarding this interaction, the established clinical risk and documented liver enzyme elevation are sufficient grounds for mandatory monitoring. Your veterinarian should perform therapeutic drug monitoring (TDM) for phenobarbital levels when initiating CBD therapy, and you should watch for signs of liver distress such as:

• Jaundice (yellowing of gums or skin)
• Increased thirst and urination
• Unusual lethargy

Critical Rule: Never start CBD without veterinary supervision, and never adjust your dog's medications based on CBD supplementation without your veterinarian's guidance.

Tier 1/2: Medium Chain Triglycerides (MCTs) and Metabolic Therapy

Dietary modulation represents another robust adjunctive approach for canine epilepsy, capitalizing on the anti-seizure properties of ketogenic metabolism.

How MCTs Work

Medium Chain Triglycerides (MCTs) are unique fatty acids that bypass standard digestive processes and are readily metabolized by the liver into ketone bodies. This shifts the brain's energy source from glucose to ketones, stabilizing neuronal membrane excitability and reducing seizure propensity.

Think of it this way: if your dog's brain struggles to use glucose effectively (a common problem in epilepsy), ketones provide an alternative fuel source that can bypass the compromised pathways.

Clinical Efficacy: Strong Evidence for MCT-Enriched Diets

Field trials have demonstrated compelling efficacy for MCT-enriched diets. A study involving dogs with idiopathic epilepsy utilized a commercially available diet enriched with 6.5% MCT oil. Over an 84-day period, results showed:

• 32% decrease in mean seizure frequency per month
• 42% reduction in seizure days
• High quality of life maintained throughout the trial

The dietary intervention was well-tolerated, indicating this method is a valuable and highly acceptable therapeutic addition for owners.

Important Distinction: Specialized Diet vs. Isolated Supplement

The strong evidence base for MCTs currently rests on the performance of a complete, commercially available diet enriched with a specific concentration of MCTs (6.5% total). This format ensures the entire macronutrient profile is balanced to facilitate ketogenesis and neuronal stability.

Simply adding raw MCT oil supplements to a conventional, high-carbohydrate kibble diet may not induce the necessary metabolic switch and could result in severe caloric imbalance and gastrointestinal side effects. While research is ongoing regarding standalone MCT supplements, the strongest clinical recommendation currently focuses on specialized, complete MCT-enriched commercial diets.

For more detailed information about one such diet, see our guide to Purina NC NeuroCare, which uses this MCT-enriched approach.

Tier 2/3: Long-Chain Omega-3 Fatty Acids (EPA and DHA)

Omega-3 fatty acids, specifically Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA), are frequently recommended for their potential neuroprotective benefits, despite a less consistent clinical evidence base compared to CBD or MCT diets.

Neuroprotective Mechanisms

Omega-3 FAs are integral components of neuronal membranes, where DHA is the main polyunsaturated fatty acid. These compounds participate in:

• Synaptic plasticity and neuron preservation
• Ion channel modulation
• Eicosanoid metabolism regulation
• Neuroimmune-modulation, reducing pro-inflammatory mediators

This dual action—direct neuronal stabilization and inflammation dampening—provides a sound mechanistic rationale for their use in refractory patients.

The Clinical Data: Mixed Results

Translating the mechanistic potential into consistent clinical efficacy has proven challenging:

Positive findings:

• A case study involving a dog supplemented with 2 g/day of omega-3 fatty acids for over 18 months reported a reduction in seizure incidence from three per month to one per three months.

Conflicting findings:

• A double-blind randomized control study involving 15 dogs found no overall effect of supplementation (using 40 mg/kg EPA and 25 mg/kg DHA for 12 weeks), with the exception of one German Shepherd that showed a tenfold reduction in seizure frequency.

A systematic review acknowledged that omega-3 FA supplementation may be beneficial but emphasized the necessity for further research to determine optimal dosing and confirm widespread efficacy.

Dosing Challenges

One significant factor contributing to ambiguous clinical outcomes is the inconsistency in dosing across studies. Veterinary research has utilized a wide range of dosages:

• EPA: 1 to 43 mg/kg
• DHA: 0.6 to 30 mg/kg

This widespread variation compromises the ability to recommend a singular, globally effective dose for epilepsy management. Your veterinarian will need to determine dosing based on your dog's specific situation, potentially drawing from protocols established for other inflammatory or neurological conditions.

Safety Profile

Long-chain omega-3 fatty acids are generally considered safe, with no known drug-drug interactions reported when administered concurrently with primary AEDs such as levetiracetam or phenobarbital. This favorable safety profile makes omega-3s a low-risk addition to complex, multi-drug regimens.

Conditional Support: Vitamins, Minerals, and Antioxidants

While CBD, MCTs, and Omega-3s possess the most evidence for direct anti-seizure benefits, other micronutrients are sometimes considered. Their use, however, is highly conditional, usually reserved for confirmed deficiencies or mechanistic support against neuronal damage.

Vitamin B6: Proceed with Extreme Caution

The only vitamin deficiency definitively known to cause or worsen seizures is a severe deficiency of Vitamin B6 (pyridoxine), primarily seen in rare, genetic conditions. For a dog consuming a nutritionally complete diet, routine B-vitamin supplementation is unlikely to improve seizure control.

Critical safety warning: Extreme chronic excess of Vitamin B6 is severely neurotoxic. Over-supplementation can induce sensory neuropathy (nerve injury) and result in ataxia (alterations in balance). Given the risk of inducing severe neurological deficit versus the rarity of the specific deficiency it treats, Vitamin B6 should never be utilized as a general anticonvulsant adjunct. Supplementation is warranted only when specific clinical diagnostics confirm a pyridoxine deficiency.

Vitamin E: Antioxidant Support

Epileptic activity generates significant oxidative stress and free radicals, which contribute to neuronal damage. Vitamin E, known for its potent antioxidant and free radical scavenging properties, plays a crucial role in mitigating this oxidative damage.

In human epileptic patients receiving anti-epileptic therapy, add-on Vitamin E administration was shown to reduce seizure frequency and improve electroencephalogram (EEG) findings. While canine-specific controlled trials are needed to determine optimal dosing, the strong mechanistic rationale positions Vitamin E as a reasonable, low-risk antioxidant adjunct when used under veterinary guidance.

The Critical Importance of Veterinary Oversight

This cannot be emphasized enough: all adjunctive therapies must be implemented under direct veterinary supervision.

Why Veterinary Oversight Is Non-Negotiable

1. Drug-Drug Interactions: Supplements can interact with medications in dangerous ways. CBD's effect on cytochrome P450 enzymes, for example, requires careful monitoring of phenobarbital levels.

2. Liver Function: Many supplements, particularly CBD, can cause liver enzyme elevation. Baseline blood work and frequent monitoring are essential.

3. Dosing Accuracy: Optimal dosing varies significantly between dogs and conditions. Your veterinarian will determine appropriate dosing based on your dog's weight, condition, and concurrent medications.

4. Safety Monitoring: Regular blood work, therapeutic drug monitoring, and clinical assessment ensure your dog remains safe while receiving adjunctive therapy.

Never Stop Medications Abruptly

Critical rule: Adjunctive therapies are designed to supplement, not replace, primary anti-seizure medications. Never unilaterally reduce or stop existing medications, regardless of how significantly seizure frequency may decline after starting supplements. Abrupt withdrawal of AEDs can be extremely dangerous, potentially leading to status epilepticus or severe rebound cluster seizures.

Any medication adjustments must be medically supervised decisions based on objective clinical data, including therapeutic drug monitoring.

Tracking Your Dog's Response to Adjunctive Therapies

When implementing any adjunctive therapy, detailed tracking becomes invaluable for assessing efficacy and safety. Keep comprehensive records of:

• Seizure frequency and severity: Track every seizure, noting duration, type, and any triggers
• Medication timing and dosages: Ensure consistent administration
• Supplement administration: Document when and how much you're giving
• Behavioral changes: Note any improvements or concerns
• Side effects: Report any gastrointestinal issues, changes in appetite, or other concerns
• Blood work results: Track liver enzymes and medication levels over time

PupPal's comprehensive tracking system makes this easier by allowing you to log seizures, medications, supplements, and behavioral observations in one place. You can generate detailed reports to share with your veterinarian, helping them make data-driven decisions about your dog's treatment plan.

The more detailed your tracking, the better your veterinarian can assess whether adjunctive therapies are working and whether any medication adjustments are appropriate.

Evidence Summary: What Works and What Doesn't

Based on rigorous clinical data, here's a quick reference guide:

Highest Evidence (Tier 1):

• CBD Oil: 24.1% reduction in seizure days at 9 mg/kg/day. Requires liver monitoring and therapeutic drug monitoring for phenobarbital.
• MCT-Enriched Diets: 32% reduction in seizure frequency, 42% reduction in seizure days. Well-tolerated, requires specialized commercial diet.

Moderate/Conflicting Evidence (Tier 2/3):

• Omega-3 Fatty Acids: Strong theoretical basis, mixed clinical results. Generally safe, but optimal dosing unclear. May benefit some individual dogs.

Conditional Use:

• Vitamin E: Reasonable antioxidant adjunct with strong mechanistic rationale. Low risk when used appropriately.
• Vitamin B6: Only for confirmed deficiency. High risk of neurotoxicity with over-supplementation.

Making Decisions: Working with Your Veterinarian

If your dog has refractory epilepsy, discuss adjunctive therapies with your veterinarian. Come prepared with:

• Detailed seizure logs showing frequency, severity, and patterns
• Complete medication history and current dosages
• Recent blood work results
• Your dog's complete medical history

PupPal can help you organize this information into clear reports that make it easier for your vet to assess your dog's situation and determine which adjunctive therapies might be appropriate.

Your veterinarian will consider:

• Your dog's specific seizure pattern and frequency
• Current medications and potential interactions
• Baseline liver and kidney function
• Overall health status
• Your ability to monitor and administer supplements consistently

Together, you can develop a comprehensive treatment plan that combines medications with evidence-based adjunctive therapies, maximizing your dog's chances for improved seizure control and quality of life.

Conclusion: A Multi-Faceted Approach to Refractory Epilepsy

Managing refractory epilepsy requires a comprehensive approach that addresses both the electrical and metabolic components of seizures. Adjunctive therapies like CBD oil, MCT-enriched diets, and omega-3 fatty acids offer evidence-based options that can complement traditional medications.

The key to success lies in:

• Understanding the evidence for each therapy
• Working closely with your veterinarian
• Maintaining detailed tracking of your dog's response
• Never stopping medications without veterinary guidance
• Regular monitoring for safety and efficacy

Remember: these therapies are adjuncts, not replacements. They work best when integrated thoughtfully into a comprehensive treatment plan managed by your veterinary team.

The journey with refractory epilepsy is challenging, but you have more tools available than ever before. With proper veterinary oversight, evidence-based adjunctive therapies, and careful monitoring, many dogs achieve meaningful improvements in seizure control and quality of life.

Ready to track your dog's response to adjunctive therapies? Start tracking seizures, medications, supplements, and behavioral changes with PupPal. Our comprehensive system helps you monitor your dog's progress and share detailed reports with your veterinarian, making it easier to optimize treatment plans and assess the effectiveness of adjunctive therapies.