If you are someone who has suffered with mental health issues you have probably tried various therapies to try and help yourself. This might have included counselling or CBT, medication, mindfulness, meditation, breathing and getting more exercise. However, emerging research suggests that there's another player in this game and recent trials are showing that it can be a powerful medicine - your diet. Specifically, the ketogenic diet has been receiving attention not only for its weight loss benefits but also for its potential to enhance mental well-being through positive effects on your body’s metabolism. So, in this blog I aim to unveil to you the secrets of the ketogenic diet and why it can help improve your mental health.
The ketogenic diet is a high-fat, moderate-protein, and very low carbohydrate eating style that shifts your body's primary fuel source from carbohydrates (glucose) to fat (ketones). Ketones are molecules that are produced by the liver from fat when carbohydrate intake is restricted, they circulate in the blood stream and are used by your cells as an alternative energy source. And yes, the brain can use them too, in fact there is some evidence that the brain prefers them! Studies have shown that the brain will use ketones in preference to glucose when they are available and reduce glucose consumption accordingly. If you want to learn about how to try a ketogenic diet you can download my guide here.
How Does a Ketogenic Diet Work?
One of the key mechanisms through which the ketogenic diet influences mental health is by optimising mitochondrial function and cellular energy production. Mitochondria, are often referred to as the powerhouse of the cell, they are tiny organelles in our cells which play a crucial role in generating ATP (adenosine triphosphate) which is the primary energy molecule our cells use for all their activity. In the brain, where energy demands are exceptionally high, efficient ATP production is essential for various functions, including making your neurotransmitter molecules, sending signals through your neurons, and maintaining a healthy neuronal structure. You can read my blog: Fatigue: The Miracle of Making Energy for more detail.
Research indicates that ketones, particularly beta-hydroxybutyrate (BHB), the main ketone body produced during ketosis, have a unique ability to enhance ATP output in the brain. Ketones can freely cross the blood-brain barrier and enter neurons, where they are efficiently metabolised to produce ATP. There are fewer steps requiring enzymes and cofactor micronutrients to convert them compared to glucose, they don’t require the production of the hormone insulin in order to be used, and they have a higher rate of combustion due to their chemical structure which results in more ATP being produced compared to glucose (you can read more about this here). Studies have shown that ketone bodies help protect brain health, in particular the health of neurons and glial cells (these are the brains immune cells) by improving mitochondrial activity and increasing mitochondrial ATP production. The way that energy is produced using ketones results in fewer reactive oxygen species (ROS) being created, these are highly reactive molecules that can contribute to tissue damage resulting in inflammation.
Restricting carbohydrates as happens with a ketogenic diet results in lower blood glucose levels along with lower insulin levels, improved insulin sensitivity and reduced insulin resistance (which you can read about here). Whereas high blood glucose and insulin levels are linked to several features common to many psychiatric disorders including: a range of neurotransmitter imbalances; excess inflammation and oxidative stress; cerebral glucose hypometabolism; mitochondrial damage; unstable neural networks; impaired neuroplasticity; low brain derived neurotrophic factor (BDNF) activity; sensory gating deficits; NMDA (glutamate) receptor dysfunction and glutamate excitotoxicity.
A ketogenic diet also has a significant impact on inflammation. Studies have shown that beta-hydroxybutyrate inhibits the NLRP3 inflammasome, which is a sensor of internal stress or danger and regulates your bodies inflammatory response. This helps prevent and resolve inflammation, helping to protect neurons from damage. In addition, beta-hydroxybutyrate can help promote the ability of neurons to grow and reorganise or rewire connections, and support the production of neurotrophic factors (such as brain derived neurotrophic factor). These are a small group of proteins that are important for the growth, survival, and differentiation of both developing and mature neurons in the brain.
Ketogenic diets have been found to help prevent neurons from self-destructing, something called apoptosis. This happens because of an impact on the sirtuin (SIRT)-1 pathway which is a process in the body involved in the maintenance of cell health, increasing energy efficiency and reducing inflammation.
And finally ketogenic diets have been shown to help balance the level of GABA and glutamate two important neurotransmitters. GABA is a calming neurotransmitter and put the brakes on brain activity whereas glutamate is excitatory and ramps it up. Both of these molecules are made from an amino acid called tryptophan, but when there is excess stress, oxidation or inflammation more of the tryptophan which usually goes to make serotonin (sometimes referred to as your happy hormone) and melatonin (your sleep hormone) is diverted to make more dopamine (your reward hormone), less GABA and far more glutamate (up to 100x more) in the kynurenine pathway. When this happens it can result in glutamate excitotoxicity which can lead to reduced levels of BDNF and as a result less neuroplasticity or rewiring of the brain with an adverse impact on learning and memory. Excess glutamate also damages proteins, lipids, nucleic acids, and mitochondria and many brain structures can be harmed.
How Does This Help Your Mental Health?
So how does more brain energy, better insulin sensitivity and glucose control along with less inflammation make a difference to your mental health?
Scientists have known for quite a while that chronic inflammation has been implicated in various psychiatric disorders, including depression, anxiety, and cognitive decline. Here is a direct quote from a research article exploring this. “Neuropsychiatric disorders (i.e., mood disorders and schizophrenia) and inflammation are closely intertwined, and possibly powering each other in a bidirectional loop. Depression facilitates inflammatory reactions and inflammation promotes depression and other neuropsychiatric disorders” Bauer & Teixeira 2019. And another one “Severe mental illnesses (SMI), including major depressive disorder, bipolar disorder, and schizophrenia, are associated with increased inflammation…. Importantly, our approach suggests that (SMI) Severe Mental Illness individuals with lower cognitive functioning and higher immune/inflammatory dysregulation may experience more symptoms, worse functioning and have higher DDD (defined daily dose) of antipsychotics” Sæther et al. 2023. You can see that there is evidence not only of a link between mental illness and inflammation but the worse the inflammation the greater the symptoms.
Let’s look at brain energy next. We have already explored how mitochondria, the tiny cellular organelles in our cells are involved in energy production. The brain has among the highest energy needs in the human body and ATP production by mitochondria is thus essential to maintain the brain’s activity. Several studies have found a relationship between mitochondrial dysfunction and mood disorders, such as major depressive disorder, bipolar disorder and schizophrenia. Problems with energy production are found in these disorders together with higher levels of oxidative stress. Oxidative stress is when there are too many unstable molecules (called free radicals or ROS) in the body and not enough antioxidants to get rid of them.
Mitochondria also help to control the cell membrane potential (the electrical charge across our cell membranes), which involves keeping the right balance of sodium and potassium ions in and outside of the cell, something that is constantly changing as neurons fire electrical impulses in our brain and nervous system. Calcium levels also must be tightly controlled during this process and again it is the job of the mitochondria to do this. Any problems with mitochondria are going to lead to problems with the health of neurons and the nervous system overall therefore impacting on mental health.
The third factor is glucose metabolism and insulin sensitivity. This has been found to be disturbed in the brain of patients with mood disorders. Impaired glucose control has been found at the onset of serious mental illnesses which basically means higher blood glucose levels. High glucose levels are very toxic to cells so your body works hard to tell with it quickly by releasing insulin which helps to escort glucose out of the bloodstream and into cells to be used for energy or stored as fat. If you become insulin resistant your cells are not able to accept all the glucose and it remains in the blood stream leading to higher blood glucose levels. The extreme form of this is diabetes. Patients with a serious mental illness are at a much greater risk of developing diabetes, for example, if you have with bipolar disorder you at 1.7–3.2x greater risk of having diabetes. And the same is true the other way around that people with diabetes have a 50 to 100% greater risk of having depression than people without diabetes. Problems with glucose metabolism are also seen in neurological conditions like Parkinson’s disease and epilepsy as well as with traumatic brain injury.
The third area was about better insulin sensitivity to lets delve into that. There is a blood-brain barrier which is like a membrane separating the brain from the rest of the body. This barrier controls the flow of glucose from the bloodstream into the brain, there is always around 40% less glucose in the brain than in the body. This does not change even if you have insulin resistance or Type2 Diabetes. The higher the blood sugar in your body the higher will be the sugar in your brain. The problem is with insulin. If you have insulin resistance which by definition is a state of high insulin because the body is producing more to try and get your cells to accept the glucose and move it out of the bloodstream, in this situation high insulin leads to insulin resistance at the blood-brain barrier making it difficult for insulin to get into the brain. So although insulin maybe high in the body it is lower in the brain and this means that brain cells cannot access the glucose and use it for energy. In this scenario of insulin resistance the brain can be swimming in a sea of glucose and still be starving to death, something known as cerebral glucose hypometabolism. Of course the answer is to fuel the brain on fat and ketones instead of glucose.
Trials of a Ketogenic Diet for Mental Illness
So what evidence do we have from clinical trials of the effectiveness of a ketogenic diet as a metabolic therapy to improve mental illness?
Depression
Adams et al. (2022) studied changes in depressive symptoms in 262 patients with Type2 Diabetes with sub clinical depression using therapeutic carbohydrate restriction. Subclinical depressive symptoms decreased over the first 10 weeks and reductions were maintained out to 2 years. Blood ketone levels indicated adherence to a ketogenic diet.
Bipolar & Schizophrenia
A very recent 4-month pilot study by Sethi et al (2014) investigated the effects of a ketogenic diet on 23 individuals with schizophrenia or bipolar disorder. Results showing improvements in metabolic health, including a significant reduction in weight, BMI, waist circumference and fat tissue. Blood biomarkers improved including a measure of insulin resistance and triglyceride levels. Participants with schizophrenia had a 32 % reduction in Brief Psychiatric Rating Scale scores. Overall Clinical Global Impression (CGI) severity improved by an average of 31 %, and the proportion of participants that started with elevated symptomatology improved at least 1-point on CGI (79 %). Psychiatric outcomes across the cohort encompassed increased life satisfaction (17 %) and enhanced sleep quality (19 %).
In another study by Needham et al. (2023) at Edinburgh University 27 euthymic individuals with bipolar disorder were recruited to a 6-8 week trial of a modified ketogenic diet. 26 commenced and 20 completed the trial. Mean daily blood ketone readings were 1.3 mmol/L and 91% of all readings indicated ketosis, suggesting a high degree of adherence to the diet. Over 91% of daily blood glucose readings were within normal range. Over the 8 week period it was found that the ratio of blood glucose to ketones related to mood, energy and anxiety with mood and energy increasing as GKI falls (indicating an increasing ratio of ketones to glucose) an conversely, in the same period, anxiety falls as GKI decreases. One third of the group experienced improvements in mood stability as measured by Affective Lability Scale, sufficient that they opted to remain on a ketogenic diet at the end of the study. This subgroup was characterised by elevated HOMA-IR, fasting insulin, glucose and HbA1c markers at the start of the study.
Alzheimer’s Disease
A ketogenic trial alongside MCT oil supplementation was done by Taylor et al. (2017) for one month with 10 patients with clinical dementia rating. They all achieved ketosis and had a mean Alzheimer's Disease Assessment Scale-cognitive subscale score improvement of 4.1 points.
Phillips et al. (2021) completed a cross over trial of 12 people with mild Alzheimer’s using a modified ketogenic diet vs. a low-fat diet. Ketone levels averaged 0.95 mM. No significant improvement was found in cognition but there was a significant improvement on tests of daily function and on quality of life.
A 12-week trial of a ketogenic diet by Buchholz et al. (2024) of 20 assigned to a modified Atkins diet and 18 to a control diet. Despite low rates of adherence, there was significant changes in circulating lipids and other metabolites with the ketogenic diet group showing greater, albeit nonsignificant, improvement in memory.
Autistic Spectrum Disorders
A pilot prospective follow-up study by Evangeliou et al. (2003) looked at the impact of a ketogenic diet on 30 children with autistic behaviour over a 6 month period. 18 of 30 children (60%) remained on the diet and improvement was recorded in several parameters and in accordance with the Childhood Autism Rating Scale.
El-Rashidy et al. (2017) studied 45 children with autism spectrum disorders over 6months who were divided into 3 groups, first group received ketogenic diet as a modified Atkins diet (MAD), second group received a gluten free casein free (GFCF) diet and the third group received a control diet. Both diet groups showed significant improvement in ATEC and CARS scores compare to the control group, the ketogenic scored better results in cognition and sociability compared to the GFCF diet group.
Lee et al. (2018) used a ketogenic gluten-free diet supplemental MCT oil with 15 children for 3 months. Core autism features were significantly improved but no significant difference was observed in restricted and repetitive behaviour score. 8 out of 15 children experienced significant improvement in their core autism features with AODS-2 scores improving for 6 out of 8 by >30%. All had adhered to the protocol proven by testing ketosis via urine testing.
Binge Eating
There is currently only one small study done by Rostanzo et al. (2021) with five women including those with food addiction and binge eating (2 or them). They used a ketogenic diet for 5-7 weeks followed by a low energy diet. All the women experienced weight loss and no case of food addiction and/or binge eating symptoms was recorded. Muscle mass was preserved.
Serious Mood & Psychotic Illnesses
A study by Danan et al (2022)of 31 adults with severe, persistent mental illness (major depressive disorder, bipolar disorder, and schizoaffective disorder) whose symptoms were poorly controlled despite intensive psychiatric management were admitted to a psychiatric hospital and placed on a ketogenic diet. Among the patients that remained on the diet for more than 14 days they had an improvement for the Hamilton Depression Rating Scale scores from 25.4 (6.3) to 7.7 (4.2), P < 0.001 and the Montgomery-Åsberg Depression Rating Scale from 29.6 (7.8) to 10.1 (6.5), P < 0.001. Among the 10 patients with schizoaffective illness, mean (SD) of the Positive and Negative Syndrome Scale (PANSS) scores improved from 91.4 (15.3) to 49.3 (6.9), P < 0.001. Significant improvements were also observed in metabolic health measures including weight, blood pressure, blood glucose, and triglycerides. The diet was deemed to be feasible, well-tolerated, and was associated with significant and substantial improvements in depression and psychosis symptoms as well as multiple markers of metabolic health.
Is It Safe?
Is it safe? This is a question often asked about ketogenic diet. Some of the trials have noted side effects most of which are usually due to medication which needs adjusting on a ketogenic diet. If CT oil is use there are sometimes gastric problems including diarrhoea. There are also on occasion some temporary side effects of transitioning into ketosis as the body adapts which can result in fatigue, nausea and palpitations which mostly disappear especially is good hydrated and adequate electrolytes are consumed. Some people find their anxiety or panic attacks may increase, there is some limited evidence that this perhaps happens at higher levels of nutritional ketosis and that there is a sweet spot to be found that everyone needs to experiment with individually.
But perhaps we should go back and think about how we evolved. Paleoanthropologists think that as humans we perhaps evolved spending periods of time in a ketogenic state. And of course, as babies we may remain in a state of mild ketosis throughout the breastfeeding period as human breastmilk is high in MCT oils which are ketogenic fats. It is likely that our modern high carbohydrate processed diets simply don’t allow us to enter ketosis for any significant length of time if at all, that does not mean that we are not designed to do it.
Conclusion
There is a growing body of research, with more needed, that is beginning to demonstrate the effectiveness of a ketogenic diet in helping manage and treat mental health conditions. This research provides us with a fascinating insight into the key relationship between nutrition and mental health and how the right dietary approach can help to tackle and reverse some of the underlying biological processes such as mitochondrial function, oxidative stress inflammation and insulin resistance. Ketogenic diets are beginning to show real promise, providing us with a new string to our bow for how we might support ourselves and others with mental health conditions. I hope that in ten years time we will see nutrition being incorporated into the standard of care for people with a wide range of mental health needs. For now I hope this has inspired you to think about how food affects your mood and indeed your brain energy! I will leave you with this question - could food be the most powerful medicine for mental health?
Need Help?
If this blog has inspired you to make changes to your diet I would love to help you! You can read more about my work with metabolic mental health here. I have personally suffered with severe brain fog and depersonalisation and use a ketogenic diet to help keep it in remission.
You can book a free 30 minute energy review with me to help you work out where to get started.
Disclaimer: Before changing your diet or lifestyle and taking any supplements always seek the advice of your doctor or another suitably qualified professional such as a nutritional therapist. This is particularly important if you are on medication for which you must seek medical advice. The content of this blog is for informational purposes only and is not a substitute for professional medical advice. Always seek the advice of your doctor with regards to any questions you have about a medical condition.
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