Mental health diagnoses have been rising worldwide for over a decade. Depression rates in the US jumped from 8.2% to 13.1% between 2013 and 2023CDC2024. Anxiety disorders in kids and young adults climbed from 12% to 17% between 2017 and 2021Jones2024. Research is now reporting that nearly 50% of college students are living with at least one serious mental illness. Meanwhile, conditions like bipolar disorder and schizophrenia remain as challenging as everSmith2023.

The term "treatment resistance" keeps showing up in research, reflecting a growing frustration with conventional approaches. One 30-year Swiss study even found that long-term antidepressant use was linked to worse depression outcomesHengartner2018.

In this article, we will cover the brain energy theory of mental health, uncover how the keto diet, and exogenous ketone supplements may be able to help, and highlight the available research.

Key Takeaways

• Your brain needs consistent energy to function properly. When that energy supply gets disrupted, mood and mental clarity can suffer.
• Ketones offer a stable alternative fuel source for your brain. You can raise ketone levels through fasting, ketogenic diets, or supplements.
• Early human trials are showing promising results for ketogenic approaches in supporting mood and cognitive function, even in challenging cases like bipolar disorder and depression.
• Ketones work through multiple pathways: more efficient energy production, reduced oxidative stress, better neurotransmitter balance, and stabilized neural networks.

Rethinking Mental Health Through a Metabolic Lens

Conventional psychiatry has long focused on neurotransmitters or the brain chemical theory of mental illness. This theory states that serious mental illnesses are a result of imbalances in key brain chemicals like serotonin, dopamine, GABA, and others.

This understanding of mental illnesses is reflected in the current standard of care treatments for psychiatric illnesses, which largely consist of medications.

Despite billions being poured into pharmaceutical interventions to target mental health, millions of people around the world are failing to find relief.

Your brain is the most metabolically demanding organ in your body, and to properly function, it needs abundant energy. When that fuel supply gets disrupted, everything downstream suffers: neurotransmitter balance, inflammation control, and mood stability.

The Brain Energy Theory

Here's what researchers are finding: people with serious mental illness often show signs of metabolic dysfunction, including brain glucose hypometabolism and insulin resistanceMartin2018.

In plain English? Brain cells aren't converting glucose into usable energy efficiently.

Why not? Multiple factors are at play. Insulin resistance can prevent glucose from entering brain cells effectively in the first place. Then, once inside, the mitochondria (your cells' power plants) can get damaged or dysfunctional. When they're not running smoothly, they produce excess reactive oxygen species (ROS), which leads to oxidative stress and inflammation.

This understanding has paved the way for the Brain Energy Theory of serious mental illness, coined by Harvard’s Christopher Palmer and now supported by neuroimaging research from Dr. Mary Phillips at University of Pittsburgh Medical Center, whose work in bipolar disorder has identified measurable abnormalities in brain energy metabolism and mitochondrial function in mood-regulating regions of the brainPhillips2018.

The Solution: Ketones as Alternative Brain Fuel

This is where ketones can come in. The primary ketone body, beta-hydroxybutyrate (BHB), supports antioxidant pathways and helps modulate inflammationNewman2018, Shimazu2013. It's a cleaner-burning fuel that can be used by an insulin resistant brain and may support brain health without the side effects that come with many pharmaceuticals.

What Are Ketones?

Ketones (also called ketone bodies) are molecules produced naturally by your body when it breaks down fat for energy.

There are three main types of ketone bodies:

• Beta-hydroxybutyrate (BHB) – The primary ketone your body uses for energy
• Acetoacetate (AcAc) – Converts to BHB in the body
• Acetone – Exhaled through breath (creates the "keto breath" some people experience)

When Does Your Body Make Ketones?

Your body naturally produces ketones during:

• Fasting or time-restricted eating – When you go 12+ hours without food
• Low-carb or ketogenic diets – When carbohydrate intake is significantly reduced
• Prolonged exercise – When glycogen stores become depleted

You can also increase blood ketone levels by using exogenous ketone supplements, like Ketone Diol.

Why Ketones Matter for the Brain

Unlike most tissues in your body, your brain cannot use fatty acids for energy. It relies primarily on glucose, but it can also use ketones.

This makes ketones particularly valuable for supporting cognitive function, mental clarity, and mood stability when glucose metabolism is compromised or when you need more energy to sustain cognitive performance.

Evidence for Keto in Mental Health

While many people are familiar with keto for weight loss and endurance performance, keto was actually first discovered in 1921 for its impact on the brain, specifically for pediatric epilepsyStafstrom2019.

The first reported scientific investigation into keto for serious mental illness was published in 1965. The pilot study examined 10 women diagnosed with schizophrenia who followed a ketogenic diet and found beneficial effectsPacheco1965.

Over the last couple of decades, there has been a growing scientific interest in the intersection between metabolism and mental health, which has prompted early, but compelling, investigation into ketogenic therapy.

Here are a few of the more recent key findings.

Meta-Analysis: Ketogenic Diets and Depression

A recent meta-analysis published in JAMA reviewed findings related to ketogenic diets and mood-related symptoms, reporting that keto is associated with mild to moderate improvements in depression across different populations and diagnosesFirth2024. The study's classification of “ketogenic” diets included those with up to 26% of calories from carbohydrates, a threshold that may not consistently raise ketone levels into the nutritional ketosis range, possibly underestimating the intervention's impact.

Case Series: Inpatients with Long-Standing Mood Challenges

A case series of 31 inpatient adults with persistent major depressive disorder, bipolar disorder, and schizoaffective disorder were put on a clinically supported ketogenic dietSethi2022.

Key findings:

• Participants showed improvements across multiple psychiatric rating scales
• Metabolic markers (weight, blood sugar, blood pressure, triglycerides) also improved significantly.

Stanford Pilot Study: Bipolar Disorder & Schizophrenia

A 4-month pilot randomized-controlled trial at Stanford University, led by Dr. Shebani Sethi, investigated ketogenic diets for individuals suffering from bipolar disorder and schizophreniaSethi2024.

Key findings:

• 79% of participants had a clinically meaningful psychiatric improvement
• Greater adherence was associated with better improvements. Those who were semi-adherent still improved, but to a lesser extent.
• Metabolic health improvements:
  • 10% average weight loss
  • 100% elimination of metabolic syndrome
  • Improvements in insulin sensitivity

University of Edinburgh: Brain Chemistry Changes

Researchers at the University of Edinburgh examined the relationship between ketone levels, mood, and brain chemistry using magnetic resonance spectroscopy (MRS)McDonald2024.

Key findings:

• 100% of completed participants reached ketosis and ketosis was maintained 91% of the time
• Higher ketone levels were associated with improvements in mood and energy and reductions in anxiety and impulsivity.
• Reductions in brain metabolites such as glutamate and glutamine (associated with bipolar symptoms) in key brain regions.
• Improved markers of metabolic health like weight and blood pressure

Ohio State Pilot Study: Rapid Mood Improvements

A separate pilot study from The Ohio State University involved 16 college students diagnosed with major depressive disorder who maintained nutritional ketosis (R-BHB > 0.5 mM) for most of the study periodDecker2025.

Key findings:

• 100% of study completers experienced clinical improvements in depression scores
• 37% improvements in depression scores in just 2 weeks
• 59% improvements in 6 weeks
• 69-71% improvements by the end of the study
• Improvements in weight, body composition, and metabolic health markers.

Keto Improves Symptoms in Multiple Other Mental Health Diagnoses

In addition to the larger trials mentioned above, emerging research is also highlighting the benefits of ketogenic therapy for:

• PTSDD’Agostino2024
• OCDFrank2025, Frank2025b
• AnorexiaHoke2023, Rusek2022
• Substance abuseTaylor2023
• ADHDArnold2023

How Ketones May Influence Mood

The early evidence on keto for mental health is promising, but researchers are still working to understand if these positive results are from ketones specifically, or from the broader metabolic improvements (weight loss, better blood sugar control, etc.) that often come with ketogenic approaches.

The answer is probably both but there are several unique characteristics about ketones that have many researchers pointing to them as a potential driver of the benefits experienced on the ketogenic diet.

Here are a few of the proposed mechanisms for how ketones may be contributing to the benefits in mental health experienced by those following the ketogenic diet.

Increased Energy

Ketones are an energy source that can be efficiently used by the brain, especially the insulin resistant brain, which is struggling to utilize glucose for energyVeech2016.

Ketones offer a more stable energy source and can provide up to two-thirds of your brain's energy needsCahill1994, and they do it without the crashes.

Brain Network Stabilization

Brain network stabilization refers to how well different regions of your brain stay connected and communicate effectively over time. When your brain networks are stable, you can focus, think clearly, and regulate your emotions. When they become destabilized, it can show up as brain fog, difficulty concentrating, and mood instability.

A groundbreaking 2025 study found that brain networks begin to destabilize in your mid-40s and continue through your 60sZilberter2025. This destabilization was strongly linked to insulin resistance in the brain, suggesting that when brain cells struggle to use glucose for energy, the communication between different brain regions breaks down.

Researchers put individuals on a ketogenic diet and found that it restabilized brain networks, with the most significant benefits occurring in adults aged 40 to 60Zilberter2025.

The study also tested exogenous ketones separately and found that they provided similar benefits, although not to the same extent as the full ketogenic diet. Still, this suggests that ketones play a crucial role, but the full metabolic shift of a ketogenic diet may provide additional stabilizing effects.

Reducing Inflammation

Ketones aren't just fuel. They're also signaling molecules.

BHB (the primary ketone) interacts with receptors like HCAR2 and influences inflammatory pathways, which is key considering the prevalence of inflammation in serious mental illnesses.

When metabolized for energy, ketones also produce fewer reactive oxygen species than glucose, helping to reduce inflammation.

Neurotransmitter Balance

In one human study, supplemental ketones reduced GABA and glutamate activity in specific brain regionsKoutnik2022.

Why does that matter? When these neurotransmitters are elevated in certain areas (like the anterior and posterior cingulate cortex), they're linked to anxiety and depression. Ketones may help bring them back into balance.

The bottom line:

Ketones have a profound impact on the brain through multiple pathways:

• More efficient mitochondrial function
• Less oxidative stress
• Better neurotransmitter balance
• Stabilized neural networks
• Calmer neuronal activity

Who Benefits Most from the Keto for Mental Health?

Ketone supplementation or ketogenic approaches may be particularly beneficial for:

People seeking mental clarity and cognitive support:

• Professionals with demanding cognitive workloads
• Students during intensive study periods
• Anyone experiencing afternoon mental fog or energy crashes

Individuals interested in improving their metabolic brain health

• Those exploring alternatives to high-carbohydrate diets
• People practicing intermittent fasting or time-restricted eating
• Biohackers and performance enthusiasts

People living with serious mental illness

• Individuals looking to reduce mild forms of anxiety or depression
• Those living with serious mental illness and struggling with standard treatment options
• Those who are looking to combat the side effects of psychiatric medications
• People looking for non-pharmaceutical approaches to support mood and focus

How to Use Keto to Support Mental Health

Methods to Elevate Blood Ketone Levels

There are several evidence-based approaches to increasing your blood ketone levels:

1. Ketogenic Diet

A high-fat, moderate-protein, very low-carbohydrate diet (typically 20-50g carbs per day)

Benefits:

• Natural ketone production
• Metabolic health benefits beyond ketones
• No additional supplement costs

Challenges:

• Requires maintaining dietary changes
• May take 2-4 weeks to become "fat-adapted"
• Requires careful planning and commitment

Best for: People willing to make long-term dietary changes and seeking comprehensive metabolic benefits

2. Intermittent Fasting or Time-Restricted Eating

Cycling between periods of eating and fasting (e.g., 16:8, 18:6, or 24-hour fasts)

Benefits:

• Natural ketone production during fasting windows
• Additional autophagy and metabolic benefits
• Free to implement
• Can be combined with any dietary approach

Challenges:

• Ketone elevation is temporary
• May take time to adapt
• Can be challenging socially or for those with certain schedules

Best for: People who can comfortably go 12-18 hours without food and want metabolic benefits beyond ketones

3. Exogenous Ketone Supplements

What it is: Supplements that directly provide ketones or ketone precursors (like BHB salts, ketone esters, or Ketone Diol.)

Benefits:

• Rapid ketone elevation (within 30-60 minutes)
• Less dietary restriction required
• More precise dosing and timing control
• Can be used on-demand for specific situations

Challenges:

• Ketone elevation isn’t permanent
• Certain conditions may require high ketone levels

Best for: People seeking on-demand cognitive support without dietary changes, or those wanting to experience ketones before committing to dietary changes

Suggested Protocol for Exogenous Ketones

• Timing: In the morning to kickstart your day or before social or stressful situations
• Dose: Start with 10-15g ketones
• Frequency: Daily/multiple times per day to power through the afternoon.

Pro tips:

• Start with a lower dose to assess tolerance
• Take on an empty stomach for faster absorption
• Stay hydrated
• Test your blood ketone levels (optional but informative) using a ketone blood meter 30-60 minutes after consumption

FAQs about Keto for Mental Health

Is there evidence that ketosis can improve mood or mental health symptoms?

Emerging research points to potential connections between ketosis and cognitive or emotional well-being. Early-stage human studies, including pilot trials at institutions like Stanford and Ohio State, have reported improvements in mood-related outcomes. Animal studies also suggest ketosis may support brain function.

Anecdotally, many individuals report notable changes in their mental clarity and emotional balance when following a ketogenic diet, often sharing supporting data such as lab results or performance tracking. Historically, fasting—a natural state of ketosis—has been associated with periods of heightened focus and clarity.

How is "nutritional ketosis" different from simply reducing sugar or carbs?

Reducing sugar or carbs doesn't always lead to nutritional ketosis. Ketosis generally requires a more specific and sustained carbohydrate restriction, often in the range of 0–50 g per day. In contrast, typical daily intake might range from 200–300 g.

What makes ketogenic diets unique is that they can be measured using a biomarker: blood levels of beta-hydroxybutyrate (BHB). That way, people's adherence can be objectively assessed.

Nutritional ketosis is often defined by BHB levels of approximately 0.5 to 1.0 mmol/L (depending on the convention). It's a threshold measured during fasting or several hours after meals, which is often considered the best time to test ketones. The level of carbohydrate restriction required to reach the conventional thresholds varies.

Are ketones themselves responsible for the mental health effects, or is weight loss the main driver?

The short answer is "both".

Due to the intricate relationship between metabolic health and psychiatric disorder, anyone with mental health issues who also has excess body fat is likely to improve their mental health if they lose the extra weight - whether they do it in nutritional ketosis or not.

However, there are also many weight stable people achieving deep nutritional ketosis and seeing big improvement in their mental health - without weight loss. And experiments using ketone supplements show rapid and meaningful changes in the brain's use of energy and neurotransmission.

How quickly might someone notice mental clarity or mood changes after entering ketosis?

Responses vary by individual and condition.

There's a case-report of a man with early-onset Alzheimer's disease seeing improvements in his memory and conversational ability on the order of hours after ingesting supplemental ketonesNewport2015. Since then, 288 caregiver case reports from people assisting Alzheimer's disease patients have been published, adding to that line of evidenceCunnane2024.

People with depression or anxiety entering nutritional ketosis may see improvements in their mood on the order of days, and deeper benefits on the order of months.

Unsurprisingly, ketones are sometimes positioned as one of several ways to get energy without caffeine.

Is a ketogenic diet safe for people with depression, anxiety, or bipolar disorder?

Available evidence suggests that ketogenic diets are safe for people with depression, anxiety, or bipolar disorder and other mental health issues. In order to implement it as effectively as possible, medical supervision is recommended, particularly for individuals taking psychiatric medications.

Do you need to follow a strict ketogenic diet to see potential brain benefits, or can milder approaches help?

Some individuals report improved mood and focus with moderate carbohydrate restriction, even without reaching deep ketosis. These early changes often motivate further experimentation with stricter ketogenic protocols, which may bring additional effects.

Who should avoid ketogenic diets or ketone supplements without medical supervision?

People with rare metabolic disorders that impair fat metabolism or ketone production should avoid ketogenic interventions, including fasting and ketone supplements, unless guided by medical professionals.

Learn More

Want to dive deeper into the science of ketones and how they can support your performance goals?

Explore these related topics:

• Do Exogenous Ketones Improve Focus and Mental Performance?
• Beta-hydroxybutyrate or BHB –All You Need to Know
• Fueling the Future: How Ketone Supplements Are Redefining Sports Nutrition

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