Nutrient Deficiencies in Depression

We all know there’s a connection. What we eat directly impacts how we feel. It just makes sense.

Common sense says there’s a connection between what we eat and our mood. If you’re curious about how nutrients from our daily food intake protect against depression, below you’ll discover the specific direct connections between diet (more specifically, micronutrients) and mood.

What exactly is depression?

Each and every one of us has the capacity to become depressed or experience any of the common depressive symptoms. In fact, almost 1 in 5 people will experience an episode of depression in their lifetime (Lee et al., 2023). If you have experienced depressive symptoms or an episode of depression, then you are not alone.

With depression being common, it is also important to highlight that there are multiple pathways leading to depression, including toxins, stress, immune dysregulation, hormonal shifts, and nutrient deficiencies (Alshaya, 2022). This makes the connection between diet/micronutrients and mood essential for all of us to understand.

The full list of depressive signs and symptoms includes sadness, decreased ability to experience joy or pleasure, changes in weight, problems with sleep, low energy or fatigue, excessive guilt, feelings of worthlessness or hopelessness, physical restlessness or feeling slowed down, poor concentration, and thoughts of self-harm. It’s important to note that a clinical diagnosis of depression requires these symptoms to persist for a period of more than two weeks.

Yet, a person does not need to present with all of the nine symptoms listed above to meet the threshold for a depressive episode. The nature and character of a depressive episode is not the same for each person. For some, it feels intensely sad. For others, it feels empty. For others still, there is a heaviness or a sucking out of energy and vitality. How exactly a person develops some of these depressive symptoms, but not others, is not yet fully known.

However, a deeper understanding of brain function can reveal what may be missing or going wrong in the body and brain. Optimal brain function is the best defense against depression. As we will see below, one key defense against suboptimal brain function is adequate nutrition.

What’s happening in the brain normally?

To tell the story of nutrition and mood, we can begin by examining the non-depressed state of being. Specifically, what is going right in the body and brain of a person who feels and functions well?

At the most basic level, humans need to eat to survive. Other tasks are also necessary for survival, but food intake is essential. Food provides energy. Food also provides resources, including the raw materials for humans to rejuvenate the body and brain again and again over a lifetime.

Nutrients (both macronutrients like proteins, fats, and carbohydrates; micronutrients such as vitamins, minerals, and essential fatty acids) provide energy, enzymatic function, and physical structure. If nutrient intake is adequate, we can progress through life with enough optimism, drive, and wherewithal to persist through rough waters.

Yet, if we become undernourished, we’ll encounter problems. Not only our physical health, but our mental and emotional functioning will suffer.

Like many questions of illness, it comes down to function. We have to move. We have to grow and repair. We have to eat. Often we have to cope with a rocky terrain in our lives. Sometimes, the faster you go, the less you feel the bumps in the road. Good nutrition keeps us moving forward.

So how does a healthy and optimally functioning brain keep things moving? Said another way, in a non-depressed person, what functions are keeping depression at bay?

To answer these questions, we will focus on four distinct functions. The four brain functions that must remain active and effective include: energy, wiring, control, and reward. This plain-English framework will help illustrate how we can improve brain health and, in turn, better protect against depressive symptoms.

The Good Delusion

In a depressed state, one or a few of the four functions are not functioning optimally. The brakes are squeaking, the dashboard meters are on the fritz, the power steering is getting sticky, the gas pedal is slow to respond.

For a person in a depressed state, energy can be limited, communication can be impaired by static or dropped signals, the inhibitory systems are not able to shush intense negative emotions, and reward signals are weakened or altogether lacking.

One or more inadequate brain functions can create a different impression of reality. First, we undervalue our own sense of self-worth and prospects in life. Second, we become keenly aware of all of the terrible, horrible, pessimistic, devastating truths about our world.

We overemphasize the risks surrounding us in the world. This impression departs from reality and carries a highly pessimistic, doom-laden flavor. Unfortunately, this combination prompts us to consider giving up, which is devastating for the individual suffering this depressed state, as well as those in their lives who truly care for them.

Here’s the main takeaway: fear is a survival imperative, and emotions help us navigate life successfully. Once we are alerted to the situation, we need to be able to turn down the volume on negative emotions so that we can move forward in a logical, rational, emotionally sober manner. This is one way to describe effective coping.

Conversely, when we feel well, our impression of life and the future may be a bit rosy, and we err on the side of optimism. It’s far better to swim in the delusions that everything will be okay, that it will all work out the way it’s supposed to in the end, even that others find us appealing and worthwhile. When we’re in a good mood, we are either right on target, or we overestimate how great we are, how great things will be in the future, and how enjoyable others find us.

It’s interesting how delusions, or departures from reality, can exist on both sides. Perhaps, at times, feeling well is a sort of good delusion. Well, the water’s warm; jump on in.

How does a non-depressed brain protect against depression?

When we feel well, we exhibit forward momentum. The positive delusions keep us afloat, push us to keep trying, and hold our heads above water when life gets challenging.

The non-depressed brain acts like a dandelion emerging from a crack in a concrete sidewalk. The non-depressed brain has a way of concluding that it’s going to be okay, and sometimes not just okay, but fantastic! What could go wrong?

This is the question the young concrete sidewalk dandelion asks. Despite the likely fate of being smushed, whacked, violently uprooted, or even casually decapitated by passersby, the concrete dandelion grows without concern for reality. Such is the course of a non-depressed brain in the world; it pursues living life without concern for the risks and problems inherent to its existence on the busy sidewalk.

In the next section, we will link the nutrients needed to support the four functions. But before that, let’s gain a better understanding of the four brain functions that protect us from depressive symptoms and offer us the good delusion.

Meet the Four Functions

Here’s an analogy to help visualize what’s happening (or not happening) in the brain when in a depressed state. These four functions get us to where we need to go in life.

In this frame, the four functions resemble the basic aspects of a car. To head in a certain direction, the car needs fuel (energy), structures like an engine, wheels, frame, interior, computer systems (wiring), control mechanisms (brakes and steering wheel), and the all-important gas pedal (reward).

Without one of these four functions, the others aren’t useful. All gas and no brake leads to crashes. With intact brakes and steering but no gas, you're stuck. Faulty wiring means the car won’t even start. Each of the four functions is needed for us to get where we want to go in life.

Taking this analogy one step further, each of these four functions utilizes a network, or collection of interconnected brain areas. As with a car, the brake pedal, calipers, or brake pads alone would not effectively slow us down. All parts of the braking system must be activated and work in unison to achieve the goal of braking.

Similarly, each of these four brain functions depends upon a collection of brain areas working together. When those brain areas activate together to produce a specific function, it is called a pathway or network.

Now let’s see how each of these four brain functions (and their associated networks) protect against depression.

Energy

Every aspect of moving through life depends upon our brain function. We can’t move unless our brain says so. For the brain to function, it needs an energy supply. Specifically, neurons (the cells in the brain that facilitate communication) need to “fire.” This chemical and electrical activity produces our thoughts, feelings, sensations, perceptions, memories, and behaviors.

Neurons need energy to fire. Neurons also need energy to reset after firing so they can fire again shortly after. The energy available to neurons lets them fire, reset, and fire again in response to the next stimulus. We are creatures gifted with the capacity for reflection, language, future imaginations, and the ability to solve complex problems. Energy is a prerequisite for everything that our human mind can do.

In terms of energy production in the body and brain, macronutrients (carbohydrates, fats, proteins) are foundational. First and foremost, we must consume enough calories to provide our brains with the basic raw material for energy production.

Beyond the basic macronutrients, however, micronutrients (vitamins, minerals, and fatty acids) facilitate energy production, delivery, and use. For mood, cognition, and drive, the outermost, or top, layer of the brain matters most. The top layer of the brain is called the cortex.

For mood, motivation, and thinking, the key part of the brain is the prefrontal cortex, located behind the forehead just above the eyebrows. The prefrontal cortex is a major hub of the central executive network - the circuit that acts as the adult in the room.

The prefrontal cortex supports rational thought, self-aware reflection, and the ability to solve complex problems. Without a well-energized and functioning prefrontal cortex, we would be a puddle of fleeting emotions and erratic behaviors.

With the aid of our prefrontal cortex, we can remain linear in our approach to life. We can take on important problems, solve them, and in turn move forward in life. It’s inescapable. We constantly need to cope in our stressful and complex world. To cope well enough, we need an adequate energy supply to our central executive network.

Wiring

Communication within and across the brain is essential. To maintain a consistent and coherent experience of life, we need efficient, effective communication within our brain.

Communication from one brain area to another and back stabilizes the quality of our thoughts, feelings, perceptions, motivations, and memories. If communication across the brain is clear, uninterrupted, and organized, we can remain calm, stay on track, and find meaning in our experiences.

Each thought, feeling, perception, motivation, or memory is a unique electrical signature from one area of the brain to another. The scientific term for the unique path traveled from one brain area to another is a network (sometimes called a circuit or pathway).

A few common networks have been identified by researchers in the hunt for the elusive location of depression (and other mental illnesses) in the brain. These include the default mode network, the central executive network, the salience network, and the mesocoriticolimbic pathway (also known as the reward pathway).

The main idea is that the thinking brain is on top (the outermost tissue in the brain, close to the skull), and the emotional brain is on the bottom (in the innermost regions of the brain). For our brain to regulate emotions and mood successfully, the top part of the brain needs to be dominant. Essentially, the top of the brain (most notably the prefrontal cortex) can regulate the bottom of the brain (the limbic system, which includes the amygdala).

However, this top-down control depends on healthy neuronal connections between the top and bottom parts. This is the essence of the wiring function. These neuronal connections need to be well-resourced, in good physical shape, and insulated with a fatty covering called myelin.

If neurons are in good shape, they can then effectively deliver messages across the brain - quickly, reliably, and without interruption. Adequate wiring, or connectivity, keeps our thoughts, emotions, and behaviors organized.

The salience network is relevant to this brain function. It monitors emotions and bodily sensations. Once detected, the salience network tags this internal response with importance. In turn, the salience network taps the central executive network on the shoulder. Attention shifts to the emotional processes, and problem solving begins.

The salience network reaches down into the bottom part of the brain and brings up to the surface, or top part of the brain, whatever problem has caught our emotional attention so that we can begin to cope. In short, to attend to problems and issues effectively, we need healthy and effective neuronal connections.

Control

So far, we’ve established that the brain needs energy to send signals from one region to another, and those signals need to be fast and reliable. Imagine the chaos of trying to solve every emotion that comes up in a day. Drama and turmoil would predominate our mindscape. At most points in the day, we are better off suppressing, muting, or flat-out ignoring negative emotions. If we can suppress enough, we can get through the day.

Luckily, nature developed a system of checks and balances in our high-powered brains. Our brains are structured to prioritize one signal at a time. In fact, at any given moment, multiple signals are being actively suppressed to allow one priority signal safe, uninterrupted passage.

Think of a white-gloved traffic cop in a busy 5-way intersection. To maintain order and function, the traffic cop has to hold back four lanes of traffic to let one lane of vehicles cruise through the intersection before switching to the next lane of cars. The brain operates in a similar fashion.

Order and temperance are the key features of the function called control. Our brains respond to life by being active. And our brains are always active. But we can move through life with function and a sense of wellness only if we can manage one thought or emotional process at a time. Our mental processes need to get in a line.

Again, fortunately, human brains have a built-in system that can readily shush, or mute, signals emanating from the bottom part of the brain - where intense emotions live. This shushing control dampens intense negative emotional upwellings.

In turn, our rational thinking remains dominant, and we can then get on with our day. It’s a sophisticated control mechanism that keeps us at a safe distance from irrational thought processes and emotional overwhelm.

The default mode network is relevant here. This network is the mind-wandering narrator in our minds. It processes thoughts, reflections, and judgments we have about ourselves. If overactive, or inadequately shushed, the default mode network will whisper, shriek, or mutter on about all sorts of worries, ruminations, self-criticisms, and grievances.

Turning down activity within the default mode network gives the rest of the brain a chance to connect with reality, stay calm, and muster a degree of optimism. If a person experiences frequent or intense negative self-talk, then the default mode network likely needs to be turned down. The brain function of control is the solution here.

Reward

Here’s a question that may have arisen as you’ve read through the above. What’s the point of all this intricate back-and-forth activity and signaling in the brain, if I feel bored and lonely most of the time?

Especially in a depressed state, a person may ask, “Seriously, what’s it all for?” My brain is active, and I’m able to focus and get my stuff done, but I just feel bad. I feel sad. I even feel mad. At times, I feel empty. I think I eat well enough. I exercise. I show up for work every day. What’s missing?

Once we meet the needs for energy, wiring, and a system of control, our brains crave… fun! Fun makes all the work we go through in a day worth it. Without fun, or a sense of reward, there is no forward progress. Anything we put effort into has to seem worth it in the end for our brains to be willing to expend precious resources to get there.

So where is fun located in the brain exactly? Primarily, it’s located in the reward pathway, known as the mesocorticolimbic pathway.

A central component of the reward pathway is the availability and activity of key neurotransmitters. The most common among them are serotonin and dopamine. Serotonin is the neurotransmitter that helps us feel joy and warmth. Dopamine helps us feel confidence and drive.

Without the availability and activity of these two, and other neurotransmitters in the brain, we would not respond to life happening around us. We would feel flat, alone, empty, and possibly hopeless.

Consider what would make us take any action in a particular direction. On some level, there is a goal - meeting a basic need, satisfying a hedonistic desire, or pursuing a longer-term, delayed gratification.

Now think about someone you know who’s encountered a depressive episode. Where did the motivation go? Their values, morals, life demands, cognitive capabilities, and even genuine desires do not vanish. Instead, all of these parts of themselves seem buried under an immovably heavy weight. The spark is absent.

For decades, what psychiatry has believed to be missing in this scenario is the availability and activity of specific neurotransmitters, chief among them serotonin and dopamine. Serotonin and dopamine are behind the sparks we feel from time to time throughout our lives. We try things. They work out. Serotonin and dopamine are released. We feel the sparks of positivity and promise for the future.

The idea that depression comes down to whether or not we have enough serotonin, or another key neurotransmitter like dopamine, has been challenged in recent years (Moncrieff, 2023). However, boosting neurotransmitter presence and activity in the brain still reliably produces effects, at least in the immediate term. We see this effect in our daily lives. Think of caffeine or stimulants or psychedelics. Even our favorite ice cream, a warm embrace from a loved one, or a thrilling roller coaster ride. We take these experiences in, and then we feel something. The feeling is positive, and it makes us want to do it again.

The link between taking it in and feeling it hinges on serotonin and dopamine (and in some instances, other neurotransmitters). Serotonin and/or dopamine release does produce an emotional response, albeit temporarily.

In sum, in order to feel well, we need to respond to life happening around us. We need something to look forward to, a goal to strive toward, and some kind of reward on the horizon. The internal sensations of excitement, confidence, and warm fuzzies are mediated by key neurotransmitters, namely serotonin and dopamine.

We need these neurotransmitter responses to feel like life is worth living. If we can experience adequate neurotransmitter responses, along with the first three brain functions (energy, wiring, and control), we are much more likely to exist in a non-depressed state.

The mesocorticolimbic pathway is the relevant network for reward function. This pathway combines our rational thought and true inner emotions and inclinations. The result is motivation or drive toward what truly makes us happy.

What is happening in the brain of someone in a depressive episode?

Energy

It is well known that physical and mental exhaustion accompanies depression. A less recognized feature of depression is cognitive impairment - a decreased ability to think, learn, remember, and make decisions.. Inadequate energy supply in the brain limits how well we can navigate our complex world. Low or inadequate energy availability in the brain also causes decreased cognitive control of emotions.

This relates to top-down control over potential negative emotions welling up from lower structures. Remember, the bottom part of the brain is where fear and intense emotions live. Activity is always percolating in this bottom part of our brains. Emotions are always primed and ready to surge up to the surface of our consciousness. Without inhibitory pressure from the top part of the brain, negative emotions would take over.

In the effort to improve a person’s coping with emotional distress, effective clinicians consider two opposing approaches.

First, clinicians help clients train the top part of the brain to improve inhibitory control and organization. With top-down strategies, the key is to find new and updated ways of thinking through difficult emotions and experiences. Generally, the idea is to place experiences, feelings, and memories in a wider context that makes sense and feels more acceptable - or at least produces some worthwhile meaning.

Second, clinicians help clients attend to the bottom part through soothing activities and practices to lessen fear by providing signals of safety, which also quiets the bottom part of the brain. The bottom-up strategies bypass thinking and narrow in on the body and the felt sense of safety from within. These practices splash cool water on the brain’s fear center. In turn, the body no longer cues the brain to enter self-protection mode. Then the thinking brain can move through life unencumbered by intermittent surges of negativity from below.

Yes, it’s a battle for dominance. If the top-down prefrontal cortex wins, we can move through life in the direction we want. When we aid in our prefrontal cortex’s dominance over the lower emotional centers, we earn more breathing room. We can collect our thoughts long enough to think through our options without emotional static in the background.

Further, with a dominant prefrontal cortex, we can handle complexity, multitask a bit, engage in goal-driven behaviors, edit our speech and behavior appropriately, and even pause for metacognitive ‘thinking about our own thinking,’ which is crucial for navigating life successfully.

Energy fuels the adult part of our brain. When Mom or Dad is driving, we get where we need to go safely and on time. Multiple studies have observed decreased activity in the prefrontal cortex during depressive episodes (Pilmeyer et al., 2022). Adequate energy supply in the prefrontal cortex helps us steer clear of depression.

Wiring

Imagine going through a tough life situation and calling your best friend for support and guidance. You explain the whole story and then mention you’re not sure what to do. A good best friend intuitively knows when to offer supportive listening and when you’re actually seeking some advice.

You’ve explained it all, and now you’re awaiting their response. Exhale, pause, and then… silence. Okay, they must be really taking it all in. It is a lot to digest. The silence continues. Hello? Are you there? I can’t hear you. Can you hear me? Uh oh. The call dropped. How much did they hear? I need to know what to do with all of this!

Now imagine it’s a phone call between the top part and the bottom part of your brain. The part with the story to tell, seeking advice and direction, is the primitive emotional center in the bottom of the brain. On the other line is the trustworthy, rational, and caring adult top part of the brain. Without a good connection between the two, help never arrives. The chaos never gets sorted out.

Without adequate neuronal connections between the rational and emotional parts of our brains, it can feel like a dropped call with your best friend and confidant. The result is an uncomfortable static: scattered thoughts, broken-record negative thought loops, surges of overwhelming emotions, and the dreaded condition of not knowing what to do next.

In those experiencing depressive episodes, researchers have observed reduced connectivity between the prefrontal cortex (the rational part) and the mesocorticolimbic pathway (the emotional part) (Pizzagalli & Roberts, 2021).

This makes sense. The important areas of our brain need to communicate with each other. Much like the calm, steady presence of a caring, composed parent, the prefrontal cortex can quietly but confidently guide our emotional parts through our regularly scheduled after-school meltdown for no reason.

The emotional part needs to consult the rational part so we don’t think, feel, believe, or do anything overly irrational. If the emotional part can’t connect with the rational part, then our emotional self can’t get the help it needs to make sense out of life’s ups and downs.

At the same time, our top part needs our bottom part equally as much. The rational part also needs to consult the emotional part so we can pursue a direction in life aligned with our true feelings and values.

The relevant brain network here is the salience network. This circuit acts as the telephone wire between the prefrontal cortex and the mesocorticolimbic pathway. Without the salience network transferring the call from the emotional center to the rational center, we wouldn’t get the help we need when we need it. Moreover, our emotional responses wouldn’t make sense or allow us a chance to find meaning in our experiences.

Control

Continuing the car analogy, let’s consider a distinct parenting challenge: driving in the car with them. It’s often hard to stay composed when kids are being rambunctious, especially in the car. Dysregulation arises on both sides.

Similarly, in the brain, it’s a perpetual challenge to quell our primal emotional machinery. The emotional center offers us fear, which is actually a gift. Fear has kept humans safe for millennia. Without fear, we’d perpetually take undue risks and likely lose all of our fingers by age 5. In life, we need to be both risk-tolerant and risk-averse.

We have to weigh the risks. Sometimes we need to jump. Sometimes we need to sit this one out.

Consider a mind that operates less like a well-calibrated risk calculator, and more like a popcorn maker that fires off random emotional surges, intense memories, and fearful predictions, mixed in with occasional rational thoughts and goal-oriented drives.

There would be a lot going on, but no stable theme. Depression, as well as other mental illnesses, can be experienced this way. It can feel like a chaotic symphony of loud, disjointed, sharp, stabbing popcorn tracers ping-ponging in the mind. Luckily, nature invented a system of checks and balances in the brain to create order out of chaos. The brain imposes order through the neuroanatomical shush.

Now imagine driving through a busy city center. You’re nearing your destination and in need of a parking spot. You are the adult in the driver’s seat. The children are inside the back seat using outside voices, complaining, throwing things at your head, tickling the back of your neck with their outstretched toes, and generally being very “bottom-up” along the way.

You’ve kept it together so far, but now you are getting close to your destination. During this final approach, you have to pay attention and think. You turn down the music. You lean in close to the steering wheel, glancing left and right, ahead and in the rearview. Somehow the kids seem to be getting louder. Emotions are bubbling up in the front and back seats. Finally, you lean to your right, swing your shoulder over the edge of your headrest, and sharply command, “Shush! I’m trying to drive.”

In this analogy, the adult driver is playing the role of the prefrontal cortex. The strongly pointed finger and harsh tone mirror the prefrontal cortex's inhibitory effect on the emotional center below. Similarly, neuronal projections from the prefrontal cortex extend back and down toward the center of the brain and effectively shush the emotional storm welling up from below. The prefrontal cortex tells the mesocorticolimbic pathway to “shush!” Hopefully, the message is received, and things calm down, at least for a moment.

As parents know, in the best-case scenario, it works. In the worst-case scenario, the children laugh and keep it going. In the brain, if our prefrontal cortex cannot inhibit or shush the emotional center, whatever emotional energy (often negative emotion) takes over. Sometimes this emotional energy can grow even stronger and last longer if the prefrontal cortex is ineffective at shushing it.

Being human means we carry an innate potential for emotional reactivity. Emotion is unavoidable and pre-decisional. In the time order of things, emotions strike before we get a chance to decide whether we should feel them.

There is an ever-present underground pool of fears, guilt, shame, and other forms of emotional pain which can erupt under the right conditions. We’re all susceptible. And, without adequate shushing, negative emotions reign over us. To be sure, in depressive episodes, brain scans reveal a simultaneous decrease in prefrontal cortex activity and an increase in emotional centers of the brain (Pan et al., 2024).

Reward

With the first three brain functions, we’ve established how the brain maintains order and puts emotional surges in check. These three functions allow us to feel calm and regulated. Unfortunately, that’s not all that we need to truly feel well. We can’t simply avoid feeling bad too often for too long and call it a victory. We need to feel good, at least every once in a while. To feel good, we need the fourth brain function: reward.

Experiencing a felt sense of reward is vital to living a quality life. Why work hard our whole life, if not to achieve some sort of goal? Whether it's money, success, status, health, the well-being of loved ones, reaching potential, or simply enjoying life’s pleasures, we need a felt sense of reward. Otherwise, why would we want to get out of bed in the morning?

Like it or not, we all need little treats sprinkled throughout the day to keep us going. For some, it’s a hot latte or iced cold brew. For others, it’s loafing on the couch at night, getting sucked into a gripping drama series. For others still, it’s seeing the fruits of your labor - getting to a specific place in life financially, seeing loved ones or children thrive, or sharing memories, good food, and laughter with friends and family.

Bottom line: we have to have our treats. It’s part of being human.

Yet treats only work if our brain has the chemical and electrical setup to feel these rewards. A related concept is the depressive symptom termed anhedonia. Anhedonia translates to the inability to feel pleasure or joy. During periods of anhedonia, the things that used to bring us joy (our favorite food, socializing with friends, playing a sport or musical instrument, etc.) no longer deliver the same positive inner response.

Without joy every so often, our motivation declines, our outlook sours, and life can begin to simply suck. Anhedonia can be truly horrific.

Depressive symptoms and episodes can occur for any of us. Just being human presents a risk. We are all susceptible to a drop in mood, energy, focus, motivation, and the felt experience of joy.

The following section ties together the known connections between nutrition and mood. We will see how nutritional deficiencies can directly contribute to depressive symptoms. Like the framework above, the food-mood connections will track with the four functions: energy, wiring, control, and reward.

So which nutrients contribute to depression?

Energy

The motto for this function is: safety through movement.

If a person stays on track, pursues goals, earns rewards, and makes good decisions along the way, the dark stuff can’t catch up.

Without optimal energy, the top part of our brain (specifically the prefrontal cortex) cannot adequately shush, or put in check, the bottom part (the mesocorticolimbic pathway).

Again, the bottom part of the brain is where intense emotions and irrationality live. Upwellings of intense, often negatively shaded emotions emanate from these lower structures and invade our consciousness.

It logically follows that if these upwellings are too strong, too frequent, too long-lasting, or inadequately filtered by the prefrontal cortex, strong negative emotions will take over. All the news channels in the mind will be covering the same disastrous news story. Depressive symptoms may follow.

The prefrontal cortex needs raw materials for energy. The most basic raw materials are the three macronutrients: carbohydrates, fats, and protein. Our brains use these three macronutrients to produce energy.

Micronutrients, on the other hand, help the brain convert these macronutrients into usable energy. Micronutrients relevant to brain energy include B vitamins and minerals such as iron and copper. These micronutrients participate in enzymatic pathways that convert food into energy - energy that neurons in the brain can use to perform and, in turn, protect us from depression (Gao et al., 2025).

Let’s map it out step by step. First, we need to eat foods rich in bioavailable macronutrients and micronutrients. Second, our body and brain process and put to use these energy inputs.

Proteins called enzymes help with this processing, or energy production. Enzymes speed up the conversion of macronutrients into the energy packs in our cells called ATP (adenosine triphosphate). ATP offers cells, including neurons, the energy they need to function.

With adequate energy, the neurons can “fire.” The activation, or firing, of neurons produces some sort of response in the brain. The response is often something we can perceive. The typical response produced by a neuron could be a sensation, a perception, a memory, a thought, or a feeling.

Ironically, one response we tend not to feel is the inhibition, or stopping, of another response. This is the ‘shushing’ described above. Frequently, one neuron (or network) shushes another. If the shushing is successful, we never feel or notice the original sensation, perception, memory, thought, or feeling.

It’s like when we are talking with others and almost say something we would later regret. As the impulse to blurt out rises within us, something strange happens. Suddenly we hold our breath, purse our lips, and nod in agreement instead. The other person will never hear what we wanted to say, and that’s probably a good thing.

Though grateful, we may wonder about what exactly held us back in that moment. But the relationship moves forward. What held us back in the moment was our prefrontal cortex exerting inhibitory control over the rest of the brain, just in time.

Similarly, inhibitory shushing is how the prefrontal cortex can dampen emotions welling up from below. If the shushing is successful, our conscious experience is less chaotic, more linear and rational, and functional enough to keep us moving forward in life.

For inhibitory shushing to unfold effectively, the brain needs specific micronutrients to snuggle into specific enzymes and boost their activity. In this role, B vitamins and minerals support the adult part of the brain so it can shush the kids in the back seat and keep moving toward the destination.

If you experience low drive, disorganized thinking, frequent stops and starts, or even impulsive blurting out, your brain may lack the micronutrients needed to adequately power your prefrontal cortex.

Wiring

The motto for this function is: we all need someone to talk to.

The top part and bottom part of our brain need to communicate with one another. They may not agree, but in order to solve life’s difficult problems, they need to share information and cooperate on possible solutions. We need both parts working together to move forward in a direction that is rational but also meaningful.

The top is logical, smart, reasonable, and effective at problem-solving. However, the top part can become cold and detached from our emotional experiences. Conversely, the bottom is emotional, fearful, irrational, a bit judgmental, but essentially very self-protective.

Despite its emotional reactivity, the bottom also harbors a kind of inner knowledge and wisdom that the top can’t offer. To move toward the life we desire and that is meaningful to us, we have to get them talking to each other. We need these two parts to establish a direct line of communication.

What makes communication effective inside our brain? Generally, the message needs to be clear, uninterrupted, and swift. Nature has accounted for this need. Our brains are designed for fast and effective communication within and across the brain.

Nature’s answer came in the form of myelin, the fatty insulation layer encasing most neurons in the brain - specifically the neurons that connect the top and bottom parts of the brain (Kamali et al., 2026). The myelin sheath enables fast, reliable communication by increasing the speed and accuracy of messages sent across the brain.

Key micronutrients needed for myelin formation and upkeep include omega-3s, B12, folate, and choline. They participate in the construction and maintenance of the myelin sheath, which in turn improves the speed and quality of signals from different parts of the brain - specifically, the wiring between the top and the bottom parts of the brain.

A solid line of communication between these areas allows for better top-down control of intense, negative emotions such as fear, sadness, hopelessness, self-judgment, and grief and loss (Comte et al., 2019).

At the same time, if the thinking part of our brain can receive input from the emotional centers below, we’ll have a better grasp of what we want in life and why we want it. If we listen to this perspective and incorporate it into decision-making, the quality of our lives definitely improves.

We all need someone to talk to. The bottom part of our brain needs a stable friend to help guide the way. Ironically, the top part also needs direction from the bottom part. When these two get together, we remain stable, clear-minded, and unburdened. We also find ourselves more present, driven, and fun.


If you experience brain fog, indecision, frequent dilemmas, or even confusion about how you truly feel about certain things, your brain may lack the micronutrients needed to keep efficient communication between the two key decision-makers in your brain: the prefrontal cortex and limbic system.

Control

The motto for this function is: you can’t outscream a yeller.

When we are upset with someone who’s acting out of order (or if we feel it’s ourselves getting out of hand), with our loudest inside voice, we may scream, “Get control of yourself!” However, in real life, we can’t out-scream a yeller.

A better approach is to pause, take a breath, and let time fill the space between our emotional response inside and our outward speech or behavior. We need the pause to sort through emotions, and then choose a better response.

Emotions aren’t all bad, and neither is the person frustrating us. With emotions, it’s best to pause, feel them for a moment, validate what they are trying to call attention to, and then

slide them over to the side while we develop a response. If we can pause and move our emotions aside, we can make good choices. To accomplish this pause, the top part of our brain needs to inhibit the activity from below.

Depression is considered to be the end result of a downward spiral. Negative experiences produce negative emotions and pessimistic or limiting thoughts. In turn, these negative perspectives amplify attention on negative experiences, thoughts, and feelings.

Over time, through a cycle of negative internal and external experiences, we get shoved down an ever-narrowing hallway until we are jammed in so tight we can’t back out.

Effective coping requires the ability to pause, turn down the volume on intense negative emotions, and focus on what is still possible. We have to inhibit some of the negativity to begin developing a plan for how to get unstuck.

Luckily, the brain has an elaborate system of checks and balances that can pause and turn down the volume on negative responses. This system hinges on inhibitory agents, namely the inhibitory neurotransmitter GABA (gamma-aminobutyric acid) and minerals that block excitation on the surface of neurons.

Vitamin B6 plays a number of roles in the inhibitory system. Its main function is to recycle the inhibitory neurotransmitter GABA, so this inhibitory lever is available when needed (Jung et al., 2019).

Relevant minerals that help quiet emotional or excitatory signals in the brain include magnesium, lithium, and zinc (Nechifor, 2023).

Vitamin A, also known as retinoic acid, helps in a very unique way. Additionally, Vitamin A improves synaptic plasticity, which is when the brain learns a new way of doing things and commits it to memory (Otto et al., 2023).

Gathering this crew of vitamins and minerals in the brain not only helps manage emotions, but also allows us to learn new ways of coping with them.

If you experience intense emotional surges, strong bodily sensations, or turmoil in your thoughts, your brain may lack the micronutrients needed to dampen intense, negative responses from within.

Reward

The motto for this function is: what hurts the most is the absence of feeling at all.

Together, the first three functions broker peace in the brain. Calm waters are preferable to rough seas. Yet sailors feared the doldrums, the windless region of the ocean near the equator, for a reason. And there’s a reason why depression has been likened to being in the doldrums.

Beyond tranquility, we need some agitation and challenge in life. If energy, wiring, and control make the cake, the final brain function, reward, is the icing on the cake.

Reward is what makes life worth the effort. Neurotransmitter activity, particularly serotonin and dopamine, underlies our motivation to try for more in life. Neurotransmitter activity at the neuronal receptors produces our felt experience in life.

Serotonin mediates our experience of joy, warmth, and equanimity. Dopamine mediates our experience of excitement, drive, and confidence. These two neurotransmitters are central to the motivation to get up out of bed, take on challenges, and feel like our life is worth the effort. When serotonin and dopamine enter the chat, we feel alive.

As with the first three brain functions, an array of micronutrients is needed to deliver felt rewards.

A collection of B vitamins and minerals is important for processing and amplifying our felt sense of reward (Kennedy, 2016). Vitamin D plays a few key roles in neurotransmitter function as well (Eyles, 2020). These micronutrients act as co-factors for the enzymes that manufacture serotonin, dopamine, and other important neurotransmitters. Further, inositol is a unique sugar, once thought to be a vitamin, that amplifies the effects of serotonin (Concerto et al., 2023).

Once serotonin docks in a receptor on the outside of a neuron, inositol translates this signal into a response within the neuron. Again, neurotransmitter activity allows us to feel life happening around us, often in a positive way.

If you experience episodes of emptiness, listlessness, poor motivation for things you actually like, or a general feeling of “blah”, your brain may lack the micronutrients needed to produce the felt sense of reward that we all need during the day.

Whole Person Approach

The information presented here may help anyone seeking to improve mood and brain function. Yet, it is important to zoom out and look at the big picture.

If a person is deficient in a nutrient, replacing it can quickly and effectively alleviate symptoms. Evidence of this principle appears in the historical records of scurvy (Vitamin C deficiency), beri beri (Vitamin B1 deficiency), pellagra (Vitamin B3 deficiency), and other conditions of specific nutrient deficiencies.

Unfortunately, unlike the success of the pirates of the Caribbean, who quickly cured scurvy with boatloads of limes, it is often not so easy and straightforward. Each of us is a unique mosaic of genetics, stressors, and internal resources. What works for one person may do nothing for another. And the list of contributing factors in depression is long. Nutrition is one known contributing factor, but many other factors play a role.

A more accurate way to think about micronutrients for depression is that increasing intake of (through diet or supplementation) is protective against developing depressive symptoms, helping to limit the severity of symptoms, or adding to the benefits of the primary treatments (therapy, medication, and other lifestyle interventions). Increasing intake of key micronutrients is either helpful or additive, but not curative.

Let’s put it all together. When we give the brain what it needs to function, we tend to feel and function at our best.

The first step is to reflect on all the information above, including the descriptions of the four brain functions and the list of signs and symptoms associated with various micronutrient deficiencies.

A next step would be obtaining lab work to verify the presence of any particular deficiency with your provider (note: at this time, accurate blood tests do not exist for all of the relevant vitamins and minerals).

A third step is to consider ways to include some of the foods listed above and/or seek guidance on smart supplementation from a provider well-versed in nutrition.

Thank you for wading through the science, analogies, and comprehensive explanations above. Hopefully the four functions framework adds to your endeavor to improve your mental well-being or possibly recovery from depression.

Where do I go from here?

If you are interested in learning more about your unique biochemistry and nutrient status, start by finding a provider who considers the impact of nutrition, lifestyle, sleep, & exercise, and who is well-versed in the right lab tests.

If you live in Oregon, Washington, or Florida, click the link for your state. The link will take you to the right form you need to get started with treatment with Justin Bethoney, NP.

If you live in a different state, take a look at this directory of integrative mental health providers across the US.

In any case, I encourage you to explore the connections between food and mood further. Hopefully, this article was a good starting place.

FAQ

• Who’s at risk?

  The Standard American or Western Pattern diet, rich in processed foods and limited in the kinds of whole foods that provide micronutrients in ample supply, is a leading risk factor for nutrient deficiencies. This goes beyond simply not consuming enough whole foods that contain the micronutrients listed above. A few unique conditions can contribute to specific nutrient deficiencies.

  Restrictive diets may include healthy whole foods but lack comprehensive nutrition; examples include a strict ketogenic diet, a carnivore diet, and even vegetarian/vegan diets that are not carefully structured.

  In addition, people who chronically experience heightened life or work stress can become deficient in these micronutrients. The general idea is that intense stress uses up our internal resources. Stress responses are geared to help us rise to life’s challenges and demands. However, the stress response itself depends upon, and eventually depletes, micronutrients such as B vitamins, minerals, and omega-3s.

  Adding to chronic stress, intense, frequent, or prolonged exercising produces a similar state of depletion. Any of the above conditions can contribute to the onset of a micronutrient deficiency associated with depression.ion text goes here

• Which lab tests are helpful?

  As noted above, the best first step is to take a mental inventory of physical and mental/emotional symptoms you commonly experience. The next step is to get baseline bloodwork with a primary care or specialist provider. Combining the two can help narrow down any micronutrient deficiencies at play.

  Baseline blood work typically includes: complete blood count, comprehensive metabolic panel, lipid panel, iron panel with ferritin, Vitamin D, Vitamin B12, Folate, and thyroid hormone markers.

  Additional blood work markers that can be helpful, but may not be covered by insurance (unless there is an accepted diagnosis code): RBC Magnesium, Zinc, Copper, Homocysteine, and an Omega-3 index (which measures the percentage of omega-3 fatty acids in red blood cells). This collection of tests offers a great starting point.

• Why do we not hear about this on the nightly news?

  The American healthcare system is at the same time one of the most advanced in the world, and one of the most backward among the developed nations. American/Western healthcare is both innovative and cutting-edge, as well as bureaucratic, bloated, far too siloed, and confusing to navigate.

  At best, the system tends to ‘manage’ long-term chronic illnesses. The American/Western healthcare system, driven by profit and saddled with a mandate to categorize and systematize, places burdensome constraints on both providers and patients.

  Due to a priority on efficiency, categorization, and the algorithmic “pill for every ill” approach, less obvious, more subtle factors go unseen - the impact of sleep, diet, exercise, stress management, and the possibility of micronutrient deficiencies.

  Even medical research is constrained by studying a singular intervention in a group of individuals. For a medication to be considered effective, it has to work better than the placebo for a large group of people. Inside the published conclusion (did it work or not?) is some important nuance. The result averages the individuals who benefited, those who got worse, and those who felt nothing. In real life, healthcare providers treat individuals, not necessarily groups or averages.

  What we tend to see on the nightly news is limited by the mentality of medical research and the healthcare industry. The goal is to find stand-alone home run treatments that work for most people. Unfortunately, this squeezes patients and their conditions into neat little boxes. This is worsened by the outsized impact of advertising from major healthcare corporations. A far better (but also far more labor-intensive) approach is to consider each patient as an individual and to try to figure out what has gone awry in their unique biology.

• How about taking a multivitamin?

  Research on multivitamin supplements for clinical depression reveals mixed results. There have been some positive trials and some negative ones - meaning no benefit from multivitamin use in depression (Young et al., 2019). Again, individual subjects within a study group tested for a single intervention are not all biochemically the same or facing the same situational factors.

  Within the group being studied, some may experience great benefit from the intervention, some mild benefit, and some no benefit and/or adverse effects. Again, research tells us what works on average, not necessarily for an individual.

  Moreover, some multivitamin products/brands exhibit problems, such as poor quality, inaccurate doses of listed micronutrients, and the possibility of overdoing specific nutrients, which could produce negative reactions.

  Yet, if a person eats well some days, but lacks healthy whole foods on other days, a multivitamin could offer some protection against micronutrient deficiencies that contribute to depression.