Ketogenic Diets for ADHD

Can Keto Help ADHD?

Ketogenic diets can help ADHD by treating several areas of underlying pathology identified as causing symptoms. These areas include glucose hypometabolism, neurotransmitter imbalances, low brain-derived neurotrophic factor, inflammation, and oxidative stress. A well-formulated ketogenic diet can also improve the nutrient status and treat cofactor insufficiencies seen in ADHD populations.

Introduction

Attention Deficit Disorder (ADD) and Attention Deficit Hyperactivity Disorder (ADHD) are seen to be primarily influenced by genetics in 80% of cases. However, as with all genes, the environment that turns those genes on and off is a potent factor called epigenetics. And lifestyle, diet, exercise, sun exposure, stressful environments, toxins are all compelling epigenetic factors. Meaning they can make some genes express themselves more and others express themselves less. So something like the ketogenic diet, which is a powerful dietary and lifestyle epigenetic factor, may help alleviate or reduce some of the symptoms of ADHD.

But let me be clear. No RCTs show that the ketogenic diet is helpful in ADHD and ADD. But they may be coming soon. As anecdotal evidence continues to mount, interests and funding in RCTs are more likely. Although we will never see them being done as robustly as we would for pharmaceuticals with high-profit potential. Still, if you search on Reddit for ADHD, ADD, and Keto, you get many people sharing their stories that the ketogenic diet has helped them. You can read some of them here. And as many have asked before, you have likely come to this page asking the question “Can keto help ADHD?”

This blog post will explore some of the mechanisms by which a ketogenic diet may help treat some of the symptoms of ADHD and ADD. In prior posts, we explored how the ketogenic diet treated the following four underlying areas of pathologies, in general. You can read these small but informative posts here, here, and here. In this post, we will explore these same four areas of pathology that are seen in ADHD and ADD and explore whether a ketogenic diet may improve symptoms that may come from these areas of dysfunction:

• Glucose Hypometabolism
• Neurotransmitter Imbalances
• Inflammation
• Oxidative stress

In this blog post, I will expand these potential treatment areas out slightly to include very general information regarding brain-derived neurotrophic factor (BDNF) and the role of the immune system in ADHD/ADD. Both are relevant factors to explore as you try to answer whether the keto diet can help with ADHD and ADD.

I will not be going into the symptoms or diagnostic criteria of ADHD in detail in this blog. It is not meant to be informational in that way, and there are plenty of articles on the internet providing this information. If you have found this blog, it is because you know what ADHD and ADD are, and you may be seeking out ways to treat symptoms for yourself or someone you love.

You may be wondering if you can treat ADHD without stimulant medications. Or you may be exploring whether or not adopting a ketogenic diet may allow you to need less stimulant medication. Less medication can be beneficial, especially since psychiatric drugs deplete nutrients.

Psychiatric medications, like the ones used to treat ADHD and ADD, deplete the following nutrients:

• Magnesium
• Iron
• Folate
• Omega 3s
• B1, B2, B3, B6 and B12
• Zinc
• CoQ10

Micronutrient depletions from medication usage are compounded by appetite suppression found with ADHD and ADD medications. Appetite suppression caused by medication usage can cause you or a loved one not to eat enough to replenish these depletions. You may want to be able to take less stimulant medication for this reason alone. The above list of nutrient depletions is relevant and directly affects how well your brain can work. Whether your brain can fire action potentials to speak between neurons, make neurotransmitters, reduce inflammation, and repair itself are all dependant on adequate amounts of those nutrients listed above.

Ironic, I know.

You may be reading this blog because you have only ADHD or ADD, or you may be reading this blog because you have ADHD and some other comorbid disorder from which you are seeking relief. Many adults with ADHD suffer from comorbid conditions, which include:

• antisocial personality disorder (14-24%)
  • Note: in children this diagnoses is often Oppositional-Defiant Disorder. If it persists past age 18, the diagnoses changes to antisocial PD
• borderline personality disorder (14%)
• affective disorders with depression (20%)
• bipolar disorder (20%)
• anxiety (up to 50%)
• social phobia (32%)
• panic attacks (15%)
• obsessive-compulsive disorder (20%)
• substance abuse (20-30%)

Regardless of why you are reading this blog, I hope that by the end, you will better understand how a ketogenic diet can be a primary or complementary treatment for your ADHD or ADD symptoms.

ADHD and Hypometabolism

Hypometabolism is a term we use to describe brain areas that do not use energy well (hypo=low; metabolism=use of energy). People with ADHD have areas of the brain that are not active enough and are identified as having brain hypometabolism in certain structures. Hypometabolism in the ADHD brain is seen in the prefrontal cortex (mostly right), caudate nucleus, and anterior cingulate. We can also see a very generalized effect in the uptake of glucose in the ADHD brains of those adults who have symptoms of hyperactivity.

Global cerebral glucose metabolism was 8.1% lower in the adults with hyperactivity than in normal controls. 

Zametkin, A. J., Nordahl, T. E., Gross, M., King, A. C., Semple, W. E., Rumsey, J., … & Cohen, R. M. (1990). Cerebral glucose metabolism in adults with hyperactivity of childhood onset. DOI: http://doi.org/10.15844/pedneurbriefs-4-11-4

In animal studies, one of the mechanisms of methylphenidate (sold as Ritalin and other drug names) is that the medication increases the uptake of glucose in the brain. Problems with glucose hypometabolism in the aforementioned brain regions exist in children, adolescents, and adults. Adults who were diagnosed with ADHD as children have regions of glucose hypometabolism in the brain as adults.

There is even evidence that genetic variations are what cause glucose hypometabolism to occur, specifically in the functioning of certain important receptors like GLUT3. When GLUT3 is working properly, it mediates the uptake of glucose in neurons and is found mainly in axons and dendrites. But in individuals with ADHD, we see that genetic polymorphisms impact the ability of GLUT3 to work properly and that this may be what results in the initial neurocognitive problems thought to contribute to ADHD risk.

How ketogenic diets help brain hypometabolism in ADHD

Hmmm. Wouldn’t it be great if there was an alternative fuel for the ADHD/ADD brain? One that did not rely on glucose or have to deal with faulty GLUT3 transporters? Luckily there is! It happens to be the ketogenic diet.

Ketogenic diets provide an alternative fuel for the brain known as ketones. These ketones go directly into the brain as a fuel source. No fancy GLUT transportation is required. Ketones use monocarboxylate transporters (MCTs), which you get plenty of with a healthy fat intake on a ketogenic diet.

And the crazy thing is, ketones not only help your existing mitochondria work better, but they encourage your brain cells to make more. And there is a lot you can do with that big of upregulation in brain energy. Especially if it occurs in the frontal lobe.

What do mitochondria do?

As if providing an alternative brain fuel for the hypometabolic brain was not enough, ketones also increase energy metabolism by upregulating neuronal cell mitochondria. Mitochondria are the batteries of your cells. Let me make it clear. These little mitochondria are like power reactors. The word “batteries” just does not do them justice.

But wait. There’s more.

Ketones produce MORE energy than glucose. To be exact, about 48 ATP vs. the 36 ATP you get from glucose.

There is a great little blog post about ketosis, mitochondria, and the mechanics of how ketones make ATP here (thank you, Siimland).

Research is completely confused and inconsistent about exactly how much ATP a cell needs, let alone what level of energy a cell needs to flourish as opposed to bare minimum functioning. And the research is even less clear about how much ATP a common neuron, astrocyte, or glial cell may optimally use. Just know that your brain uses 70% of all the ATP you create in your whole body. And you will begin to understand the importance of having access to ketones as an energy source in the ADHD brain.

“But wait a minute!” you may be saying to me as your read this blog. What does this have to do with my symptoms? ADHD/ADD has diagnostic criteria. And a subset of that criteria falls under what is called executive dysfunction.

Executive dysfunction, which is also called executive function deficit or disorder, is when the brain has a hard time with the skills of attention, memory, flexible thinking, and organization/time management.

https://www.verywellmind.com/what-is-executive-dysfunction-in-adhd-5213034

Executive dysfunction comes from broken frontal lobes. Broken frontal lobes can come from a head injury, a stroke, or from not getting enough fuel to run.

And that, my blog reading friend, is how a ketogenic diet can treat the underlying frontal lobe hypometabolism that is part of the disease process underlying your ADHD/ADD symptoms.

ADHD and Neurotransmitter Imbalances

There are several neurotransmitter imbalances in ADHD and ADD. These include serotonin, dopamine, noradrenaline, glutamate, and GABA. Additionally, there is a downregulation seen in an important substance called brain-derived neurotrophic factor (BDNF). While not technically a neurotransmitter, it exerts an influence on the glutamate/GABA system and so will be included.

Serotonin

Differences in gene expression found in those with ADHD alter the functioning of serotonin receptors. This means that how the nerve cell receives and uses the neurotransmitter serotonin is altered. Differences in these receptors and how it affects interconnectivity between brain structures are thought to influence some of the learning and memory impairments we see in ADHD persons. Reduced levels of serotonin are thought to be related to the symptoms of impulsivity seen in some manifestations of the disorder.  

Dopamine

Another major neurotransmitter dysfunction seen in ADHD is dopamine. Early theories suggested that low levels of dopamine, along with certain other neurotransmitters, were at the root cause of ADHD. This theory has since moved toward the thought that the problem is not because there is not enough dopamine but because there are higher levels of transporters for dopamine. Dopamine transporters allow dopamine to enter the nerve cell through a well-functioning presynaptic membrane.

Pay attention to what I just wrote. For dopamine to be used, you have to have a well-functioning presynaptic membrane. This will be relevant later as we discuss treatment.

Having too many dopamine transporters at work means that dopamine does not hang out long enough in the presynaptic cleft for the right amount of time. It gets vacuumed up into all those receptors. It can’t do its thing!

Because dopamine cannot do its job, the person with ADHD finds it difficult to seek pleasure and feel rewarded by normally pleasurable things throughout their day. They are wired to seek out more dopamine. It’s why ADHD people can develop problems with smartphone use, computer games, and even highly addictive processed foods. All things are carefully designed to provide a high dopamine response in the brain. There is a distinct sensation of being uncomfortable without these extra stimulating activities and foods. This all leads to feeling restless, behaving impulsively, and having problems with attention.

Among the neuro-chemical factors, there is a well-known dysregulation in the production of neurotransmitters; primarily dopamine and nor-adrenaline.

Fayed, N. M., Morales, H., Torres, C., Coca, A. F., & Ríos, L. F. Á. (2021). Brain Magnetic Resonance Imaging in Attention-Deficit/Hyperactivity Disorder (ADHD). https://link.springer.com/chapter/10.1007/978-3-030-61721-9_44

Several different genetic variations contribute to issues of dopamine function seen in those with ADHD and ADD. It is thought that genetic variations to differing degrees contribute to all the many presentations of the disorder we see in individuals. For example, COMT polymorphisms affecting the dopaminergic system are highly correlated with ADHD symptoms and social impairment.

Norepinephrine

Norepinephrine is a neuromodulator that has an important role, along with dopamine, in allowing the prefrontal cortex to function. Remember, we discussed the prefrontal cortex and what it does earlier in this blog post. A dysfunctional prefrontal cortex will lead to executive functioning deficits that are often a sub-class of symptoms seen in the diagnoses of ADHD/ADD.

Although most of the research likes to focus on dopamine, norepinephrine’s influences on the prefrontal cortex are just as powerful and are incredibly relevant to an understanding of ADHD symptomatology. When norepinephrine is working well, it helps with working memory and attention. People with ADHD/ADD report serious issues with working memory and attention.

We know that norepinephrine is involved, in part, because selective noradrenergic medications (e.g., clonidine, guanfacine) can help treat ADHD.

And again, we are dealing with an issue of transporters. It is not necessarily that there is too much or too little of norepinephrine, but that we see genetic variations that influence how what is already there is being moved around and used. And again, we see that certain genetic differences seen in ADHD and ADD are implicated in how the norepinephrine transporter (NET) works.

Glutamate and GABA

We discuss these two neurotransmitters together because they are part of an elegant system that works together. In ADHD, we see an imbalance in this neurotransmitter system. Glutamate levels in the prefrontal cortex, for example, will directly influence levels of dopamine and vice-a-versa.

In certain neurodevelopmental disorders, such as ADHD, we see an imbalance between the excitatory glutamate neurotransmitter and inhibitory GABA. Dopamine receptor (DRD4) dysfunction seen in ADHD creates an environment in which there is more glutamate in the brain. And we don’t want a ton of glutamate just hanging out in the brain, not being balanced by GABA. Because long-term, this causes damage to brain cells and brain structures.

Glutamate is an important neurotoxic brain marker. Excess of glutamate can produce neuronal death through excitotoxic processes. It is also assumed that glutamate in the frontal circuits is an important regulator of dopamine, and through a feedback mechanism the concentration of dopamine can influence the concentration of glutamate

Fayed, N. M., Morales, H., Torres, C., Coca, A. F., & Ríos, L. F. Á. (2021). Brain Magnetic Resonance Imaging in Attention-Deficit/Hyperactivity Disorder (ADHD). In Psychiatry and Neuroscience Update (pp. 623-633). Springer, Cham

Children with ADHD show poorer inhibitory control and significantly reduced GABA in the striatum, which is a brain structure involved both in determining what actions to perform and learning about which of those actions are worth repeating. Poor levels or utilization of GABA are thought to contribute to symptoms of behavioral inhibition seen in ADHD.

The contribution of this particular type of neurotransmitter imbalance is not insignificant. And the effects of these two neurotransmitters being out of balance are thought to contribute directly to the etiology of ADHD and the neurobiological effects that persist into adulthood.

Brain-derived neurotrophic factor (BDNF)

BDNF is found to be downregulated in ADHD. Some of this may be due to genetic variations found in this population. And people with ADHD/ADD feel this inadequate supply. Because your hippocampus, the brain structure that helps process short-term memories, is very active, and it needs a lot of BDNF to work properly. And this downregulation of this substance may be why we see issues with short-term and working memory in people with ADHD. You also need enough BDNF to just learn in general. You need it for signaling in the glutamatergic and GABAergic (ergic=making) synapses, and it also plays a role in serotonin and dopamine transmission between cells. The bottom line is people with ADHD do not have enough of this good stuff. And we need to find a way to increase it.

How ketogenic diets help neurotransmitter imbalances seen in ADHD

So how could a ketogenic diet improve symptoms of ADHD? After all, it looks like ADHD is mostly genetic. How could a ketogenic diet modify the expression of genes that determine how our neurotransmitters work (or don’t)? How could a dietary therapy change something big like that?

Dopamine, Noradrenaline, and Serotonin

I might have mentioned this earlier, but there are three types of ketones. One of those types is called beta-hydroxybutyrate (βHB). βHB generates more of an enzyme central to metabolism (energy production) called nicotinamide adenine dinucleotide (NADH). It does this through a complicated pathway that you can look at here (see Figure 3) if you are interested at that level.

For our purposes here, it is just important to know that this increases the synthesis of the neurotransmitters dopamine, noradrenaline, serotonin, and melatonin.

And if you remember your reading above, genetic variability in neurotransmitter receptors and transporter expression of serotonin, dopamine, and norepinephrine are issues seen with ADHD brains. Making more of each could be quite beneficial.

• Increased serotinin could improve impulsivity, learning and memory impairments
• Increased dopamine could alleviate restlessness and improve attention
• Increased norepinephrine could improve working memory and attention

There would be more to go neurotransmitter goodness to go around, and it would mean there would likely be more to stay present in synapses where they can work their magic. And this upregulation of key neurotransmitters is done in a balanced way with a ketogenic diet.

Unlike medications in which certain neurotransmitters are increased or made to stay as long as possible in synapses, there will not be medication side effects. We are all well aware, for example, of the side effects people experience when taking SSRIs to increase the time serotonin stays in the synapses to be used. We know that gabapentin, designed to increase GABA levels in the brain can create side effects of drowsiness, for example. This type of thing just does not happen on a ketogenic diet.

But what about glutamate and GABA?

As discussed above, the ADHD brain struggles with too much glutamate and too little GABA. Ketogenic diets can increase glutamic acid decarboxylase activation, which encourages GABA synthesis and also alters enzyme activity that keeps GABA around longer in the synapses. So for the ADHD brain, this means more access to the inhibitory neurotransmitter needed to help balance out higher levels of glutamate.

In animal studies, one of the forms of ketone bodies known as acetoacetate was found to reduce excitatory neurotransmission at hippocampal synapses, which may improve or at least protect memory function. ADHD and ADD individuals often complain of problems with short-term memory and learning. Balancing neurotransmitter function in important memory structures such as the hippocampus could prove helpful for a reduction in symptoms.

Membrane functioning and neurotransmitter balance

You just cannot have a conversation about neurotransmitter balance without discussing neuronal membrane function. βHB helps neuronal membranes repolarize, and that improved ability to repolarize has plenty of benefits for the ADHD/ADD brain.

Repolarization of neuronal membranes, enhanced by βHB allows the cell to accumulate nutrients (often deficient in the ADHD/ADD brain) to make neurotransmitters in the first place. Remember when we discussed issues with neurotransmitter receptors and transporters in the ADHD/ADD brain?

Well, the construction of enzymes that determine how much neurotransmitter gets to hang out in the synaptic cleft, and for how long is something determined by membrane repolarization. The synaptic clefts’ ability to stay sensitive to the neurotransmitters appearing (such as dopamine, serotonin, and norepinephrine) also depends on healthy functioning repolarization.

Brain-derived neurotrophic factor (BDNF)

Ketogenic diets are known to upregulate the production of BDNF. It is thought that this may be an important mechanism that allows them to improve various neurological disorders, such as traumatic brain injury (TBIs) and dementias. Ketones upregulate BDNF in their role as a signaling molecule, turning genes on and off in such a way that more of this substance is created. So producing ketones, on a ketogenic diet, would create more BDNF in the ADHD/ADD brain.

Genes are not destiny

ADHD is considered highly influenced by genes. And anytime a disease is discussed in that way, people can get the wrong idea about whether they would be able to “fix” or modulate underlying pathologies associated with a condition.

We don’t know how much of the problems with these things in ADHD come from impaired neuronal membrane functioning due to epigenetic factors (e.g., hypometabolism due to diet, micronutrient deficiencies, chronic neuroinflammation, oxidative stress).

Even though problems with receptors and transporters are said to occur on a genetic level in those with ADHD brains, I want to go on record as communicating that I think it is quite possible that changing the environment in which those genes are expressed could mean symptom improvement. How genetic expression unfolds for serotonin, dopamine, and norepinephrine transporters and receptors may be amenable to epigenetic influences.

And epigenetic interventions, like a ketogenic diet, are quite powerful in influencing gene expression. Ketones are signaling molecules, meaning they have the power to turn genes on and off. Just because you have been told something is hereditary does not mean you are powerless in making changes to modify how that expression happens.

ADHD and Neuroinflammation

People with ADHD have significant levels of neuroinflammation coming at them from many different directions. Inflammation can be caused for a variety of reasons. A diet high in fructose (those sweet beverages at the convenience store) can increase inflammation. Pollution can increase inflammation. A leaky blood-brain barrier that lets toxins into the brain can cause inflammation. Acute stressors, like taking an exam or blowing a tire on the freeway, can increase inflammation. And immune system dysfunction can increase inflammation. Pay attention to that last one because the inflammation caused by immune system dysfunction appears to be highly relevant in ADHD.

So what does that mean? When our immune system becomes activated, something called cytokines is then produced. These are little signaling molecules that tell the immune system what to do to keep the “bad guy” they were just told is there in line. But cytokines are not subtle when they fight different intruders off. They do a lot of damage. Imagine a very chaotic police chase scene and all the damage that happens as they go after the bad guy with great intensity and high speeds.

That is how cytokines roll. They may or may not catch the bad guy, and there is a big inflammatory mess to clean up. And it takes a lot of labor, equipment, and resources to do that clean-up. For the brain, that means tons of spent energy (labor), other cells that are healthy and can pick up the slack (equipment), and a lot more micronutrients (resources) than you are probably getting in your diet.

Now imagine a lot of car chases all the time, like nonstop (chronic). Eventually, clean-up and repair would fall behind. The city and road would start to look like a hot mess. That’s your brain dealing with chronic neuroinflammation.

Here is a great article that expands this analogy in a way that helps you understand neuroinflammation and oxidative stress, and how they interrelate with one another!

If Your Brain Were a City: Understanding Oxidative Stress and Neuroinflammation

The best way I can illustrate how significant inflammation is in ADHD is to provide a quote from a research article I pulled to write this post.

While still limited, this evidence includes 1) the above-chance comorbidity of ADHD with inflammatory and autoimmune disorders, 2) initial studies indicating an association with ADHD and increased serum cytokines, 3) preliminary evidence from genetic studies demonstrating associations between polymorphisms in genes associated with inflammatory pathways and ADHD, 4) emerging evidence that early life exposure to a number of environmental risk factors may increase risk for ADHD via an inflammatory mechanism, and 5) mechanistic evidence from animal models of maternal immune activation documenting behavioral and neural outcomes consistent with ADHD.

Dunn, G. A., Nigg, J. T., & Sullivan, E. L. (2019). Neuroinflammation as a risk factor for attention deficit hyperactivity disorder. https://doi.org/10.1016/j.pbb.2019.05.005

So let’s review the significance of what we just read. People with ADHD are more likely to have inflammatory and autoimmune disorder comorbidities. In other words, something is wrong with the immune system, and it causes inflammation as a result. So not surprisingly, when they test people with ADHD for blood markers of inflammation, they find they have many more inflammatory cytokines than controls.

When we look at developmental factors for ADHD, we see early life exposure to environmental risks that cause inflammation. In animal models, they have identified the mechanisms between immune system activation during pregnancy and subsequent brain and behavior changes in the offspring similar to those seen in people with ADHD.

If all that is not enough to convince you that neuroinflammation is highly relevant in ADHD, allow me to tell you about the genetic polymorphisms they have found associated with the pathways that create that inflammation.

Whether or not all these associations are found to be causal or not, I would argue, does not matter. We don’t perfectly underly the causal mechanism of most things, and we slap a pharmaceutical on top to modify what we think is going on, and we do it all the time. So why wouldn’t we consider inflammation as a potential target to help alleviate symptoms of ADHD?

Luckily, a lot of really smart researchers already agree with me. I wouldn’t want you to think this is just something I came up with by myself.

Based on our hypothesis, targeting neuroinflammation may serve as a potential new therapeutic intervention to treat ADHD

Kerekes, N., Sanchéz-Pérez, A. M., & Landry, M. (2021). Neuroinflammation as a possible link between attention-deficit/hyperactivity disorder (ADHD) and pain. https://doi.org/10.1016/j.mehy.2021.110717

This neuroinflammation is also relevant to what we read in the last section regarding neurotransmitter imbalances. Inflammation creates more excitatory neurotransmitters and promotes the upset we see between glutamate and GABA. Inflammation creates an environment in the brain where it cannot make the appropriate ratios of GABA to glutamate. It is probably because it is under duress (from all those nonstop car chases).

It is unreasonable to think that you would be making neurotransmitters telling you to be chill and that everything is alright when you have chronic neuroinflammation. This is why it is important to pay attention to your symptoms. It is your brain’s way of telling you something is seriously wrong. It needs you not to ignore the nonstop car chases going on and doing damage. It requires you to pay attention. It’s probably not a fan of you trying to find prescriptions that help you pretend that the damage is not occurring.

Let’s make inflammation one of the core targets of intervention that we see contributing to symptoms in ADHD/ADD brains.

How ketogenic diets are a treatment for neuroinflammation seen in ADHD

As we discussed above, neuroinflammation seen in ADHD comes in part from dysfunctional immune responses. I do not usually discuss the effects of ketogenic diets on the immune system, but it appears to be highly relevant to etiology and symptom presentation with this population.

However, I am not well studied in immune systems, so I will be very general here and do further research if you feel the need.

Ketogenic diets upregulate and balance immune function. We use them to help treat some forms of cancer, in part, because of favorable immune response in T-cell activation. Researchers found enough positive effects of a ketogenic diet on immune system function that an RCT was initiated to see if it could be used to provide a protective factor against COVID.

Some people think that this upregulation of the immune system happens because of a ketogenic diet’s changes to the gut microbiome. One of the guts’ favorite fuels is butyrate, a component of certain ketone bodies and can be found in the highest amounts in butter. I always find this to be super ironic, given the focus so far seems to be all about prebiotic fiber as the superhero of gut health and wellness. I also have to point out that some healing happens in the blood-brain barrier when you go on a ketogenic diet.

Thus, beneficial effects of the ketogenic diet may depend on increased brain uptake of KBs to match metabolic demand and repair of a disrupted BBB. As the effects of KBs on the BBB and their transport mechanisms across the BBB are better understood, it will be possible to develop alternative strategies to optimize the therapeutic benefits of KBs for brain disorders where the BBB is compromised.

(KBs=ketone bodies; BBB=blood brain barrier)
Banjara, M., & Janigro, D. (2016). Effects of the ketogenic diet on the blood-brain barrier. 
DOI: 10.1093/med/9780190497996.001.0001

A healthy blood-brain barrier means fewer things floating up into your brain that quite frankly do not belong. And when you have toxins or substances that get through that blood-brain barrier that does not belong, it leads to a triggering of the cytokines and contributes to neuroinflammation.

So consider the effects a ketogenic diet has on immune function as a bonus that plays an important role in helping you alleviate your ADHD/ADD symptoms help alleviate your symptoms.

Another mechanism by which ketogenic diets reduce inflammation is by inhibiting inflammatory pathways. Ketones, which are made in abundance on a ketogenic diet, are signaling molecules, and being a signaling molecule means that they serve as a messenger, telling some genes to turn off and other genes to turn on. And ketogenic diets reduce inflammation in this very cool way. Like, directly.

In the next section, we will learn about how inflammation plays a role in oxidative stress and how decreasing this pathological mechanism might influence symptoms we see in ADHD.

ADHD and Oxidative Stresss

Oxidative stress occurs when there is an imbalance of the body’s ability to deal with byproducts that happen just by being alive. Lots of things can cause oxidative stress. Just breathing creates something called reactive oxygen species (ROS). So your body expects a certain amount of ROS, just from being alive. And it isn’t a problem when your damage/antioxidant systems are in balance. As we will talk about later in this blog post, we were made to deal with ROS, at least to some extent. But the levels at which we are exposed today are unprecedented in your evolutionary history.

We just discussed inflammation. Does inflammation make more oxidative stress? Yes. Yes, it most certainly does.

Inflammatory process induces oxidative stress and reduces cellular antioxidant capacity.

Khansari, N., Shakiba, Y., & Mahmoudi, M. (2009). Chronic inflammation and oxidative stress as a major cause of age-related diseases and cancer. https://doi.org/10.2174/187221309787158371

These ROS have to be detoxed or neutralized. And for your body to do that, you need a lot of micronutrients (cofactors) and a good level of both endogenous (made inside your body) antioxidants. People also consume antioxidants (e.g., turmeric, quercetin, vitamins C and E), attempting to reduce oxidative stress.

Oxidative stress is no joke. Allowed to run unchecked over time, you get damage to your DNA. Let’s go back to our car chase analogy. It is as if the car chase has gotten so out of hand that buildings are falling and roads are crumbling. But now, the knowledge for fixing all these things has been lost in all the chaos. And now the people trying to rebuild the city, after all those car chases, can’t do it quite right or in a stable way. This is an analogy for the DNA damage that occurs with unchecked oxidative stress. As you can imagine, chronic diseases will develop as a result of this.

There are a lot of different ways that more ROS is created than what our body can handle. Besides just breathing and metabolizing energy, some of the things that can increase the burden of oxidative stress that are environmental include:

• UV and ionizing radiations
• pollutants
• heavy metals
• plant constituents
• drugs
• pesticides
• cosmetics
• flavorings
• fragrances
• food additives
• industrial chemicals
• environmental pollutants

These all significantly increase ROS and cause this imbalance that we refer to as oxidative stress. Oxidative stress leads to cell and tissue damage, and brains, in general, are particularly sensitive to it.

But ADHD/ADD brains are even more so. No, really, and it’s in the research literature. But before we discuss that, let’s talk about medications used to treat ADHD.

On top of all those environmental sources of oxidative stress outlined above, people’s very medications to treat ADHD symptoms can exacerbate the problem. The use of ADHD medications like Methylphenidate (MPH), sold as Ritalin and other names, increases levels of oxidative stress.

In MPH there is evidence for increased OS, altered AO defense and neuro inflammation in ADHD children

Kovacic, P., & Weston, W. Attention-deficit/hyperactivity disorder–unifying mechanism involving antioxidant therapy: Phenolics, reactive oxygen species, and oxidative stress. https://www.biochemjournal.com/articles/23/1-2-10-853.pdf

In the research literature, we see high levels of oxidative stress in the ADHD brain, and this may come from a particular genetic vulnerability to ROS.

One example of this is Organophosphates, such as dimethyl phosphate (DMP; a pesticide). Genetic studies have shown that being exposed to higher levels of this substance in the environment created a significantly higher risk for developing some of the exact mutations we see in ADHD with dopamine receptors.

59% of ADHD cases in DMP-exposed children with the DRD4 GG genotype were due to the gene-environment interaction. After adjustment for other covariates, children who carried the DRD4 GG genotype, had been exposed to high DMP levels (more than the median), and had … a significantly increased risk for developing ADHD

Chang, C. H., et al., (2018). The interactions among organophosphate pesticide exposure, oxidative stress, and genetic polymorphisms of dopamine receptor D4 increase the risk of attention deficit/hyperactivity disorder in children. https://doi.org/10.1016/j.envres.2017.10.011

So oxidative stress may very well be part of the etiology (how it begins) of ADHD. But does it play a role in its maintenance? I would say yes. There are polymorphisms in inflammatory-related genes seen in those with ADHD. Reduced antioxidant levels are seen in children, adolescents, and adults compared to control groups.

Oxidative stress is such an issue in the ADHD/ADD brain that one very popular and reportedly fantastic treatment is the use of OPCs. OPCs are particularly powerful antioxidants. I first learned about them in a free webinar at Psychiatry Redefined, which you can watch here. I don’t want to get off-topic, so I will not go into OPCs in this blog post. You can learn more about them here:

Are OPCs an option for treating depression without medication?

But I did want to point out that oxidative stress is a target of treatment in functional psychiatry. You may not have the benefit of a prescriber trained in functional medicine. So I leave this info here if you want to explore more for your wellness journey.

But as we are going to learn, there are many ways that a ketogenic diet helps treat oxidative stress, thereby potentially (and likely) improving your symptoms. One more way in which keto can help ADHD.

How ketogenic diets reduce oxidative stress levels in people with ADHD

There are many pathways by which are influenced by ketogenic diets. One example is that there is an increase in agmatine, a less popular neurotransmitter made from the amino acid L-arginine. This increase of agmatine in the brain that happens on a ketogenic diet has well-documented neuroprotective properties that help protect the ADHD brain from increased levels of oxidative stress.

Another thing to know about ketogenic diets, concerning their effects on oxidative stress, is that ketones are a very clean-burning energy source. Less ROS has created burning ketones for fuel than other primary fuel sources. Because of this, βHB (a type of ketone body) decreases ROS production and increases antioxidant defenses.

The other way that a ketogenic diet helps directly treat oxidative stress is that βHB alleviates oxidative damage due to excitotoxic insults (e.g., remember glutamate?) at the site where damage occurs. Somehow βHB helps dampen or repair the damage done by oxidative stress. And researchers think this may be due to the improved mitochondrial function or influencing gene expression.

But wait, there is even more that a ketogenic diet does to help reduce oxidative stress.

Ketogenic diets help us make more of an important antioxidant that we make in our own bodies. Remember, we talked about how your body knows that ROS will be a thing. Because you breathe and eat and move and stuff. So obviously, it has a way to deal with that. And it deals with that normal level of ROS with something called Glutathione. But as we learned, there are a lot of factors in our environment that push our ROS way past expected levels.

Glutathione is a vital antioxidant that can protect the cell from DNA damage. Ketogenic diets help you make more glutathione by increasing GCL, an enzyme needed to synthesize Glutathione. GCL is considered a “rate-limiting enzyme,” meaning that you only get as much glutathione as you have that enzyme. And so, the ketogenic diet making more GCL is what gives you more glutathione and is a very powerful ally in reducing oxidative stress in the ADHD brain.

Conclusion

So there you have it. Those are some of the many ways that a ketogenic diet can help reduce symptoms of ADHD and ADD. As you can see, a ketogenic diet is a multi-layered intervention.

It improves neuronal cell membrane health, improving communication between cells. Ketogenic diets upregulate GABA, helping to improve the glutamate/GABA imbalance seen in this population.

Ketones upregulate (make more of) brain-derived neurotrophic factor (BDNF) to make neuronal cell repairs. Remember, those dopamine receptors don’t fix themselves. But perhaps more relevant is how the upregulation in BDNF can potentially improve working memory and learning in those with ADHD.

Ketogenic diets don’t stop there.

They reduce neuroinflammation and are neuroprotective, which will reduce oxidative stress in the ADHD brain.

Ketogenic diets improve mitochondrial function and create an excellent energy source for parts of the brain that are hypometabolic. This improved energy production stabilizes neuronal membranes (remember hyperpolarization?) and allows cells to function better. Possibly quite beneficial for the variability of expression in serotonin and dopamine receptors and transporters seen in those with ADHD and ADD.

These are all areas of potential healing involved in ADHD symptoms.

But wait, you may say. I don’t just have ADHD or ADD. I have comorbid issues, like mood disorders and substance abuse problems. This would not surprise me. When executive functioning is impaired, for any reason, people have trouble regulating moods. You need a fully functioning frontal lobe and neurotransmitter balance to control your emotions. And because ketogenic diets help with just that sort of thing, it should not surprise you that I have a variety of posts discussing how ketogenic diets also help treat anxiety, depression, and substance use disorder.

How do ketogenic diets help anxiety disorders?

Ketogenic Diet Treats Alcoholism

Can keto treat my depression without medication?

While the standard of care should always be offered to you, it is also important for you to know other options that are also evidence-based. So you can make informed decisions regarding their care.

Because you have the right to know all of the ways that you can feel better.

The ketogenic diet is one of them. And it is important to me that someone communicates that to you so you can make informed decisions about your treatment.

I want to encourage you to learn more about your treatment options from any of my blog posts. I write about different mechanisms in varying degrees of detail that you may find helpful to learn on your wellness journey.

Share this blog post or others with friends and family suffering from symptoms. Let people know there is hope.

You can learn more about me here. If you would like to work with me to assist in your transition to a ketogenic diet, you can do so through the online program I offer.

Brain Fog Recovery Program

I am, as always, very excited at the prospect that you could feel better.

Like what you are reading on the blog? Want to learn about upcoming webinars, courses, and even offers around support and working with me towards your wellness goals? Sign up below and download your free Brain Nutrition Guide.

Free Brain Nutrition Guide

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