This blog is the second part of this blog. The first part explained more about how metabolic health and mental health are connected. If you haven't already seen it please go check it out here.
The Biopsychosocial Model for Mental Wellbeing
I hope that the first part of this blog has helped you to understand how our biology can not be separated from the impact of the world around us and for me this is best explained by the biopsychosocial model for mental wellbeing. This model hypotheses that mental health is shaped by the interplay of biological, psychological, and social factors. Biological aspects like genetics, brain chemistry, and physical health interact with psychological factors such as coping skills, emotions, and personality, while social influences like relationships, community, and cultural contexts also play crucial roles. This holistic approach suggests that mental well-being is most effectively supported by addressing all three domains together.
I like this approach because I think it brings together everything that we know that can help improve mental health. We know that some people benefit from talking therapies, some people from medications, some from social support, others from diet and exercise and also light therapy. What is important is to find what works for you and it may well be a combination of these approaches. Diet is a relatively new aspect in mental health care but one that is becoming increasingly of interest to both patients and clinicians. Light therapy has been around for a while, but I don’t think the concept of it being a metabolic therapy has been fully understood.
Psychosocial Stress & Your Mitochondria
Until recently not much was known about this, but one researcher has been leading some very interesting research in this field. Dr Martin Picard has shown that mitochondria are very sensitive to emotional and social stress, which in turn can accelerate cellular aging and impair mental health. He has also found that more resilient individuals have more adaptable mitochondrial networks that cope better with stress. He discovered that positive social interactions and emotional support can enhance mitochondrial function, while social isolation and chronic stress can have the opposite effect. One of his most recent papers has begun to uncover how the mitochondrial bioenergetics or energy making process is affected. His group found that the proteins making up the super complexes, remember they are part of the electron transport chain in the mitochondria, that strip off the electrons to generate ATP, are less abundant under psychosocial stress. They found that psychosocial stressors could explain an 18% change in the abundance of the first protein complex alone. This suggests that psychosocial stressors play an important role in mitochondrial energy production which is a key component of metabolic health.
Our Circadian Rhythm & Our Mitochondria
Our 24-hour body clock, or circadian rhythm as it is officially known, is an internal timing system that regulates various biological processes in a roughly 24-hour cycle. It aligns our bodies with the day-night and wake-sleep cycles. This body clock is primarily controlled by an area of the brain called the suprachiasmatic nucleus (SCN), it influences our sleep and waking, hormone release, metabolism, and body temperature. The main signal controlling it is light and a lack of light, or darkness.
Scientists have shown that if we disrupt our body clock with irregular sleep times, jet lag, late-night social events, late-evening blue lights from screens and a lack of natural light exposure during the day, it can cause circadian misalignment. This can make it more difficult for us to fall asleep, to sleep soundly without waking, to have good quality sleep and as a consequence it can contribute to fatigue. Chronic disruption of circadian rhythms are strong associated with all mental health conditions including depression, schizophrenia and bipolar disorder. Circadian disruption includes inappropriately timed sleep and waking periods alongside misalignment of sleep/wake with feeding rhythms. It often results in poor sleep, and this adversely affects the mitochondria.
There are other factors that contribute to the control of our circadian rhythm too including the feeding/fasting cycle which is basically when we eat or don’t eat. We know for example, that eating too late at night can push back our 24-hour clock making it harder to get to sleep. Chrono-nutrition is an emerging field in metabolic psychiatry looking at the links between eating patterns, circadian rhythms, and health. We have different genes that are active during the day with he aim of replenishing our energy stores, while overnight we have genes responsible for growth and repair. If we start eating when we should be fasting it can lead to problems. The same meal consumed at different times during the 24-hour period could have a different impact on our energy metabolism. We are not designed to eat when it is dark and our move towards 24/7 lifestyles with a longer eating window and shorter fasting time results in a more constant supply of nutrients which interrupts our circadian rhythm and increases the risk of metabolic disorders.
Food is a Powerful Prescription
It will probably come as no surprise to you that food can both be beneficial but also problematic depending on the kinds on what we feed ourselves. Any diet that is full of foods that cause inflammation or that result in high blood glucose and insulin is going to be detrimental. But the good news is that if you eat a nutrient dense food that keep glucose and insulin low and is also anti-inflammatory will be beneficial.
There have been a lot of small trials in recent years that have sought to improve mental health using food as the prescription and this includes various versions of the Mediterranean Diet. One study called the SMILES trial involved 56 people with 31 in the diet arm and 25 in the social support arm. In the trial participants were encouraged to eat a wide variety of fresh fruits and vegetables, some whole grains like brown rice and quinoa, healthy fats, particularly from sources like olive oil, nuts, and fatty fish, lean proteins, particularly from fish, poultry, legumes, and nuts, while limiting red meat consumption, foods rich in probiotics, like yogurt and kefir, were also included to support gut health and they were also advised to reduce their intake of processed and ultra-processed foods, added sugars, and unhealthy fats. The trial found that participants who adhered to this dietary pattern experienced significant improvements of their depressive symptoms in 12 weeks compared to those receiving usual care. It is likely that this diet reduced inflammation and helped better balance blood glucose and provided more nutrient density than the controls were eating.
Another dietary area of interest is in the use of ketogenic diets, and this is because of their potential to be a metabolic therapy. A ketogenic diet is a diet that is high enough in fat and low enough in carbohydrates and protein to stimulate a process called ketosis or ketogenesis. You might have heard of it also being referred to as a keto diet. I’m now going to explore this in more depth.
The Ketogenic Diet: A Powerful Metabolic Medicine
Ketosis is an evolutionary conserved process which allowed early humans to use alternative fuels and cope with periods of food scarcity. Any time we fast for an extended period our body will start to tap into our stored fat reserves, providing us with energy using a process called ketosis, meaning we are making and running our bodies, and brains, on ketones. This helped us manage as hunters and gatherers when food supplies were limited particularly in winter.
There are three ketone bodies that we can produce beta-hydroxybutyrate, acetoacetate, and acetone. Even on a typical higher-carb western diet, your liver produces tiny amounts of ketones, especially overnight while you sleep. You can initiate a state of ketosis by eating a diet that is high enough in fat and low enough in carbohydrates, when our liver will start to produce ketones. if we get the balance right, we can stay in a state of nutritional ketosis and fuel our body and brain on ketones. When we do this the brain shifts its energy source from glucose to ketones which enhances mitochondrial function and the production of ATP along with some other very beneficial effects.
Once blood ketone (beta-hydroxybutyrate) levels reach 0.5 mmol/L, you are in nutritional ketosis. The range for nutritional ketosis is 0.5 to 5.0 mmol/L.
Here are some of the benefits of being in ketosis:
Efficient Energy Source: Ketones, particularly beta-hydroxybutyrate, provide an efficient and stable energy source for the brain, heart, and muscles. They yield more ATP per molecule of oxygen compared to glucose, making them a more energy-efficient fuel, especially under low-oxygen conditions or metabolic stress. Not only are ketones more efficient but there are fewer steps in the process of burning ketones. Prior to entering the mitochondria glucose must go through 10 enzymatic steps known as glycolysis, compared to only 3 for ketones in ketolysis. Each of these enzymes requires at least one co-factor vitamin or mineral, so there is less potential for ketolysis to go wrong.
Reduction of Oxidative Stress & Inflammation: Ketones reduce oxidative stress by lowering the production of reactive oxygen species (ROS) during energy production. Beta-hydroxybutyrate can act as a signalling molecule to directly dampen inflammation via the NLRP3 inflammasome, a protein complex, which is a senor of internal stress or danger and regulates your bodies inflammatory response. This helps prevent and resolve inflammation resulting in less damage to neurons and other cells.
Neuroprotective Effects: Ketones support brain health by providing an alternative fuel that can bypass problems with the burning of glucose seen in metabolic disorders like T2D, in neurodegenerative diseases like Alzheimer’s and Parkinson’s as well as mental health conditions like depression, schizophrenia and bipolar disorder. Ketones can also help to 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.
Neurotransmitters: Ketogenic diets have been shown to help balance the level of GABA and glutamate two important neurotransmitters. GABA is a calming neurotransmitter and puts the brakes on brain activity whereas glutamate is excitatory and ramps it up. Both molecules are made from an amino acid called tryptophan, 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. This 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 which can result in brain structures being harmed. A ketogenic diet helps avoid this by increasing GABA and dampening glutamate.
Mitohormesis: this is when a small amount of stress has a beneficial effect on the mitochondria. The moderate level of free radicals produced by mitochondria when eating a ketogenic diet have been shown to protect against chronic disease by enabling an upregulation of mitochondrial capacity along with the increases in the endogenous (internally produced) antioxidants. This phenomenon is referred to as mitohormesis and occurs when there is an increased reliance on mitochondrial respiration (energy production), which can occur through diet or exercise. A ketogenic diet is reliant on mitochondrial respiration
Photobiomodulation
This sounds a bit of a mouthful, but it is about how light can be used as a tool to support health and of course mental health. We learned already that we have an internal body clock which is regulated by light and darkness as well as by feeding and fasting. It has been understood for some time that light has both positive and negative effects on mental health. We need the right kind of light at the right time of day.
Exposure to bright blue light from LED lamps and screens late in the day can push back your circadian clock and make it harder to get to sleep at night. If you still have to get up for work at 6am the next day this means you will get less than the optimal 7 to 8 hours of sleep, you need for your mitochondria to function well. A lack of exposure to natural light is also a problem, we have become indoor based spending very little time outside and our light exposure is dictated by electrical solutions rather than natural sun’s rays which vary in intensity and wavelength from dawn to dusk.
There are several mental health conditions known to be linked to seasonal changes in light including seasonal affective disorder, which is a specific form of depression, schizophrenia and bipolar disorder. With bipolar hospital admissions related to depression peak in autumn and winter, while admissions for mania, periods of high energy and excited behaviour, are highest in spring and summer. Regarding schizophrenia hospitalisations also follow a seasonal pattern in both men and women with changes in light being linked to worsening symptoms.
Bright Light Therapy, using daylight lamps mimicking bright natural day light is being used as a therapeutic tool in a range of mental health conditions including depression, bipolar and schizophrenia. It can help to resynchronise the biological clock, enhance alertness (energy), increasing sleep pressure (the physiological need for sleep), and act on neurotransmitters to enhance sleep.
There are also other therapies being explored such as exposure to red, near infrared and infrared light therapy. It is hypothesised that we have a lack of exposure to red light which we get from natural sunlight but not from LED lighting. Both red light and infrared light have been shown to enhance mitochondrial function and improve insulin signalling. Red light also increases ATP production and exposure before bed (mimicking sunset) has been shown to increase sleep for insomniacs. Infrared stimulation has been shown to also stabilise mitochondrial energy production and prevent oxidative damage.
Move For Your Mitochondria
Exercise is often claimed to be the most potent therapeutic approach for the improvement of mitochondrial health, not only in muscle, but potentially also in other tissues. In particular it has been shown that exercise upregulates mitochondrial biogenesis, that is the creation of new mitochondria, therefore boosting mitochondria numbers in a cell with all the benefits that brings with it including improving insulin sensitivity (the opposite of insulin resistance). Researchers have also found that inactivity reduces mitochondrial functions including fusion and biogenesis as well as mitophagy. But the good news is that getting active again can retore mitochondrial function quite quickly again.
Heat Therapy
One final suggestion for lifestyle support is the use of heat. Raising body temperature using saunas or even a hot bath maybe beneficial for your mitochondria and metabolic health. Even a single sauna session has been found to reduce blood pressure and improve markers of cardiovascular function. Hot water immersion has also been found to improve blood flow and glucose clearance.
Saunas help improve endothelial function (that's the lining of your blood vessels) by increasing nitric oxide release which dilates the muscles and helps them relax. In addition the heat stimulates several enzymes and proteins including heat shock proteins that help guard against oxidative stress and protein breakdown, improper protein folding and premature apoptosis (cell death). Regular sauna bathing has been shown to improve heat stress tolerance which is linked to a reduction in inflammation as well as improved insulin sensitivity.
Saunas also increase the expression of 5′-AMP-activated protein kinase (AMPK) which is a cellular energy sensor capable of sensing ATP and AMP (a precursor to ATP) production. When ATP levels decrease, AMPK activity increases, which helps regulate energy production. PGC-1α is a transcription factor (meaning it control the transcription of DNA into RNA) which can help to activate several different antioxidant genes which help to eliminate free radicals and hence reduce oxidative stress. PGC-1α also controls the density or number of mitochondria in a cell and is therefore thought to be one reason why saunas are so beneficial for health.
How does this translate to brain health? Well one study has shown that men who took 4–7 sauna sessions per week had a 78% reduced risk of developing psychosis compared to those who had one a week. Another study found that whole-body heat treatment was a safe, rapid-acting therapy which significantly reduced depressive symptoms and had prolonged benefit.
A Holistic Approach With Metabolic Health At Its Heart
In this last section of the blog, I want to bring this altogether by acknowledging both the traditional practice of psychiatry using medications and talking therapies and other types of treatment and the new paradigm of metabolic psychiatry.
The biological aspect clearly involves mitochondria and their role regulating metabolism. It involves the processes of oxidative stress and inflammation. It incorporates the timing of when we eat and what we eat. It also includes light exposure and how we can optimise it to support our body clock and our mitochondria. Also important is making sure we move our bodies and avoid a sedentary lifestyle. Some of these I have only explored very briefly such as exercise but that’s not to say there are not an important part of the biological element of this model.
The psychological aspects have been alluded to including the different kinds of psychological stress, our emotional resilience, and our coping mechanisms which all have a knock on effect with our biological and in particular our mitochondrial function. Chronic stress can damage mitochondria, but psychological interventions (e.g., mindfulness, talking therapies, yoga, CBT, EFT) can improve mental health by reducing stress and improving mitochondrial resilience.
Then there is the social aspect which is another major topic which I have only skirted around in this blog. Things like relationships, family networks, community, housing situations, education, work and socio-economic factors, social isolation, cultural issues and access to services can potentially all impact mental health via mitochondrial function too. Positive social environments which are supportive and of course can enable us to practice some of the biological and psychological strategies can enhance mitochondrial performance and, by extension, mental health. There is even evidence that some types of music can enhance mitochondrial function and ATP output!
My view is that the time is right to integrate metabolic and psychosocial Interventions by taking a more holistic approach that addresses the biological, psychological, and social factors influencing mental health. This includes potentially a ketogenic diet, eating during daylight hours and fasting at night, using bright light and red light therapies, implementing strategies for stress reduction and management, creating supportive environments and strong social bonds. It is my hope that a combination of metabolic approaches is the key to rewire our brains, unlock and maintain brain energy and support mental well-being. A health coach like myself can help you make a simple and sustainable plan to help you implement a holistic approach to give yourself the best chance of optimising your mental wellbeing. I hope you enjoyed reading this blog and you are inspired to take some action to improve your own mental wellbeing.
There are some more suggested reading links below as well as all of the references.
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Book A Call To Start Your Health Journey With Me
If you would like to book a call with me to discuss how best to start using nutrition to help you improve, and perhaps even reverse, your symptoms then please use the link below to book a free 30 minute chat. I can help you work out the best place to begin based on your own individual circumstances.
You can also download my quick start keto guide.
If you would like to know more about some of the studies looking at metabolic mental health and trials of ketogenic diets, please read this blog: https://www.moiranewiss.co.uk/post/metabolic-mental-health-the-link-between-brain-energy-ketogenic-diets
If you would like to understand more about insulin resistance please read this blog: https://www.moiranewiss.co.uk/post/unpacking-insulin-resistance-fatigue-sugar-crashes-to-chronic-diseases
If you would like to know more about ketones then read this blog. https://www.moiranewiss.co.uk/post/how-to-get-30-more-energy-understanding-how-ketones-work
To understand more about how mitochondria make your energy then this is the one to read. https://www.moiranewiss.co.uk/post/fatigue-the-miracle-of-making-energy
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. 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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