Enhancing Ketamine Therapy: The Role of Nutrition and Supplements
In recent years, ketamine therapy has become a groundbreaking treatment for people with treatment-resistant depression, anxiety disorders, and post-traumatic stress disorder (PTSD). Originally used as an anesthetic in surgical settings, ketamine is now employed in psychiatric treatment due to its rapid-acting antidepressant effects, especially for patients who haven't responded to traditional therapies like oral antidepressants (i.e., SSRIs) or talk therapy.
As promising as ketamine is, its therapeutic benefits are often temporary, and many patients need repeated sessions to sustain relief. This has prompted both clinicians and researchers to look for ways to improve and prolong its effectiveness. Among these, the importance of nutritional support—specifically how diet, micronutrients, and supplements might interact with or support ketamine therapy—is increasingly gaining attention.
Nutrition has long been recognized as a crucial factor in brain health, affecting mood, neurotransmitter production, inflammation, and even neuroplasticity. Now, with ketamine offering another safe method to quickly induce neural changes, the question is: can a targeted nutritional and supplement plan support ketamine therapy to improve outcomes, reduce relapse rates, or extend relief?
This article examines what current research says about combining nutritional support and supplementation with ketamine treatment and offers practical considerations for those interested in a more integrative approach to mental health care.
Understanding Ketamine Therapy
Ketamine was first synthesized in the 1960s and quickly adopted in medical settings for its potent anesthetic properties. Today, ketamine is increasingly used as an off-label treatment for severe depression. In 2019, the FDA approved a derivative of ketamine known as esketamine under the brand name Spravato, which is indicated for individuals with a diagnosis of treatment-resistant depression, defined as not having responded to at least two prior antidepressant medications.
Unlike traditional antidepressants, which mainly target serotonin or norepinephrine pathways and can take weeks to work, ketamine acts quickly—often within hours. It mainly functions as an antagonist of the N-methyl-D-aspartate (NMDA) receptor, a type of glutamate receptor in the brain. By blocking this receptor, ketamine causes a surge in glutamate, the brain’s most common excitatory neurotransmitter. This glutamate increase is thought to stimulate synaptogenesis—the formation of new synaptic connections—and boost brain-derived neurotrophic factor (BDNF), which is crucial for neuroplasticity.
Clinically, ketamine has shown the ability to significantly reduce depressive symptoms and suicidal thoughts. However, its effects are usually short-term. A single infusion can relieve symptoms for a few days to a week, which often requires multiple sessions over time.
Despite these challenges, ketamine represents a paradigm shift in how we approach treatment-resistant mood disorders. And with its mechanisms pointing toward neuroplasticity and inflammation regulation—areas where nutrition also plays a role—the idea of combining ketamine therapy with targeted nutritional interventions is both timely and scientifically grounded.
The Role of Nutrition in Mental Health
What we eat directly affects brain structure and function, influencing mood regulation, cognitive performance, and emotional resilience. Nutrients supply the raw materials for neurotransmitter production, maintain the integrity of neuronal membranes, and help regulate inflammation and oxidative stress, factors all involved in the development of depression and other mood disorders.
Studies have identified dietary patterns linked to better mental health outcomes. The Mediterranean diet, for example, which focuses on whole grains, fruits, vegetables, fish, and healthy fats like olive oil, has consistently been associated with lower rates of depression and anxiety. This contrasts with the Western diet, high in refined carbohydrates, trans fats, and processed foods, which has been linked to increased risk of mood disorders and cognitive decline.
On a biochemical level, certain nutrients are especially important for mental health. Omega-3 fatty acids, present in fatty fish and flaxseed, are vital for maintaining brain cell membrane fluidity and reducing inflammation. B vitamins—particularly B6, B12, and folate—are essential for methylation processes involved in producing neurotransmitters.
Magnesium and zinc act as cofactors in hundreds of enzymatic reactions and have also been shown to affect NMDA receptor function. Vitamin D, which is often missing from many people's diets, is also connected to mental and immune health.
Nutritional deficiencies in any of these areas can impair brain function and may contribute to the onset or persistence of psychiatric symptoms. This understanding has given rise to the field of nutritional psychiatry, which investigates how dietary interventions and targeted supplementation can be used to support mental health.
As the evidence grows, more clinicians are recognizing that nutrition is a modifiable factor with therapeutic potential, particularly when integrated into comprehensive treatment approaches such as ketamine therapy.
Nutritional Synergies with Ketamine Therapy
While ketamine offers a way to boost the brain’s neuroplasticity, nutrition can serve as a complementary tool that supports and potentially enhances these same biological pathways. The overlap between ketamine’s mechanisms of action and the roles certain nutrients play in brain function suggests the potential for synergistic effects that could improve therapeutic outcomes and extend symptom relief.
One of ketamine’s main downstream effects is the production of brain-derived neurotrophic factor (BDNF). BDNF is a protein that encourages the growth and strengthening of synapses—critical processes for mood regulation. Interestingly, several nutrients have also been shown to influence BDNF expression. For example, omega-3 fatty acids, polyphenols (found in berries and green tea), and certain amino acids can help increase BDNF production. In theory, combining ketamine therapy with a diet or supplements that support BDNF could enhance or prolong ketamine’s positive effects on the brain.
Inflammation is another area where ketamine and nutrition may work in tandem. Chronic inflammation has been implicated in treatment-resistant depression, and ketamine has demonstrated anti-inflammatory effects in both animal and human studies. Similarly, anti-inflammatory nutrients such as curcumin, omega-3s, and flavonoids can help lower levels of pro-inflammatory cytokines.
Magnesium is another nutrient of interest for individuals undergoing ketamine therapy. It acts as a natural NMDA receptor modulator and has been linked to fewer symptoms of depression and anxiety. Low magnesium levels have also been associated with poor responses to antidepressant treatment. Since ketamine also targets NMDA receptors, maintaining adequate magnesium levels might not only improve mood on its own but could also enhance ketamine’s effectiveness and reduce its side effects.
Mitochondrial function and energy metabolism, which are often impaired in mood disorders, also influence how well treatments work—nutrients like B-complex vitamins, CoQ10, and alpha-lipoic acid support cellular energy production and lower oxidative stress.
Taken together, the biochemical environment in which ketamine functions can be directly affected by nutritional factors. While ketamine provides an immediate and potent intervention, nutritional support may offer a stable and lasting foundation. This biological synergy deserves further investigation, but the theoretical and initial clinical evidence is encouraging.
What the Research Shows
To date, most studies examining ketamine's effects have focused on its pharmacological profile and clinical efficacy as a stand-alone treatment. Pilot research has found that individuals with higher levels of omega-3 fatty acids or B vitamins tend to show improved mood outcomes and more sustained response to antidepressant treatments in general, which could reasonably extend to ketamine-based therapies.
Some studies suggest that taking magnesium as a dietary supplement may enhance the antidepressant-like effects of ketamine. Research also indicates that agmatine sulfate could have antidepressant effects akin to ketamine, potentially with a biological synergistic interaction.
There is also a growing interest in the concept of “biological terrain,” or the internal environment where psychiatric treatments work. Just as chemotherapy results can be affected by a patient’s nutritional and metabolic status, it’s reasonable to think that brain-based interventions like ketamine might also be influenced by fundamental biological factors such as nutrient levels, gut health, and inflammation.
Practical Nutritional Strategies for Patients Undergoing Ketamine Therapy
Although no single diet or supplement guarantees improvement, certain nutrients and dietary patterns have demonstrated potential in supporting brain function, mood regulation, and addressing some of the biological mechanisms that ketamine influences.
The foundation starts with a nutrient-rich, anti-inflammatory diet. A whole-foods approach that emphasizes vegetables, fruits, healthy fats, lean proteins, and fiber-rich carbs can help stabilize blood sugar, reduce systemic inflammation, and provide the essential building blocks for neurotransmitter production.
Diets inspired by the Mediterranean or anti-inflammatory eating styles are particularly advantageous. These emphasize omega-3-packed fish like salmon, monounsaturated fats from olive oil, leafy greens, berries, nuts, legumes, and fermented foods that promote gut health.
Beyond general dietary habits, specific nutrients may play a more active role in supporting ketamine’s effects. For a more in-depth discussion on this topic, be sure to read "10 Best Supplements to Take During Ketamine Therapy for Depression and Anxiety."
For those considering supplements, it's essential to seek guidance. More isn’t always better, and some supplements might interact with medications or cause side effects if used improperly. Functional medicine practitioners, integrative psychiatrists, or registered dietitians with mental health expertise can help develop a safe and effective plan tailored to individual needs, lab results, and treatment objectives.
Ultimately, nutritional strategies should complement, not replace, ketamine therapy or other medical treatments. By providing the body with what it needs for optimal functioning, patients may find that the relief from ketamine becomes more consistent, sustainable, and better integrated into their long-term recovery.
Risks, Gaps, and Limitations in the Research
Although combining nutritional strategies with ketamine therapy shows promise, current research is still in early development. Few clinical trials directly investigate this combination, and most supporting evidence is indirect—coming from animal studies, observational data, or broader nutritional psychiatry research.
A key limitation is the lack of standardization. Ketamine is administered in different doses and forms, while nutritional interventions also vary in type, timing, and quality. This variation makes it difficult to develop clear clinical guidelines. Additionally, individual factors—such as genetics, gut health, and baseline nutrient levels—can significantly influence outcomes, making a one-size-fits-all approach unlikely.
Safety considerations are also important. While nutrients like magnesium and omega-3s are usually safe, taking high doses or mixing them improperly can cause side effects or interact with medications.
Conclusion
While ketamine offers rapid relief for individuals with treatment-resistant depression and other mental health conditions, its effects can be short-lived without ongoing support. Nutrition, on the other hand, provides a foundation for brain health by influencing neurotransmitter production, inflammation, and neuroplasticity—many of the same systems ketamine targets.
Although research on this combined approach remains limited, the biological rationale is compelling, and early evidence indicates that addressing nutritional factors can improve and extend the benefits of ketamine therapy. Diets rich in whole foods, healthy fats, and essential micronutrients—along with carefully selected supplements—may help optimize results when incorporated into a thoughtful, personalized plan.
For patients, the takeaway is clear: mental health care doesn’t have to be limited to medication or therapy alone. Working with professionals who understand both psychiatric treatment and nutritional science can offer a more comprehensive, sustainable path to healing.
About the Author:
Dr. Ray Rivas is a medical doctor, former trauma surgeon, and the founder of Innerbloom Ketamine Therapy, a clinic dedicated to advancing mental health care through innovative treatments. With a deep passion for holistic wellness, he also leads Newy, a nootropic supplement company designed to support brain health. Drawing on decades of clinical expertise, a career focused on mental health, and personal experiences with growth and healing, Dr. Rivas is devoted to empowering individuals with the tools they need to achieve lasting mental and physical health.
Disclaimer:
The content provided on this blog and website is for educational and informational purposes only and should not be considered medical advice. Newy supplements are not intended to diagnose, treat, cure, or prevent any disease. Always consult a qualified healthcare professional before starting any new supplement, especially if you are pregnant, nursing, have a medical condition, or are taking other medications.
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