Oxidative stress in the central nervous system can cause brain fog. Read on to discover the possible causes & surprising things to avoid. At the end of this post, you can take a quiz to find out your brain fog type.
Origins of My Knowledge of Brain Fog
This post combines knowledge from my research, personal experimentation, experience with clients, and observations. The scientific knowledge is out there, but piecing it all together obviously wasn’t easy.
Understanding brain fog also wouldn’t have been possible without years of personal experimentation.
Almost all doctors aren’t aware of this information and they will think you’re depressed and prescribe antidepressants, which won’t help the problem at all.
The Cause of Brain Fog
In a sentence, brain fog is a condition caused by too much superoxide, which falls under the larger umbrella of “oxidative stress” (OS).
The hypothalamus ‘senses’ this excess superoxide and we experience brain fog.
Immune imbalances, hormonal imbalances, genetics, and changes in the hypothalamus all intersect to cause brain fog.
Inflammation causes oxidative stress [1] and is often the starting point.
The reason inflammation increases OS is because ROS or free radicals (these are the “bad” guys which determine the level of oxidative stress) help the immune system (i.e. your inflammatory response) fight an infection.
So whenever you increase inflammation in the body ROS/oxidative stress also increases [1].
Oxidative stress (OS) causes mitochondrial breakdown, which in turn causes even more OS and inflammation, leading to a vicious cycle [2].
The mitochondria are “the power plants” of the cell and provide energy for the brain and other organs. I noticed through various ways that my mitochondria weren’t up to par after a lifetime of inflammation.
Bottom Line: anything that exacerbates oxidative stress or inflammation will make brain fog worse.
Inflammation in the Hypothalamus
Inflammation, even when not targeted at the hypothalamus, activates the stress response or the HPA axis because cortisol lowers inflammation [3].
Inflammation is a popular term these days, but people forget that inflammation and the immune system are basically the same things.
When people talk about inflammation they are talking about some aspect of the immune system that is hyperactive – or chronically active in the case of chronic inflammation.
The hypothalamus-pituitary-adrenal axis and the thyroid are deeply connected with glucose regulation in the blood and when this system is not functioning properly because of inflammation/OS, people will experience swings in blood glucose levels.
Inflammation also causes brain barrier permeability and that can cause lots of problems on its own. Stuff that isn’t supposed to pass the brain barrier will, resulting in neuroinflammation [4, 5].
Oxidative Stress in the Hypothalamus
For simplicity’s sake, oxidative stress is an umbrella term that refers to an imbalance of molecules that are harmful to us (free radicals like ROS, H2O2, etc.) and other molecules which deactivate these harmful molecules (antioxidants like glutathione).
Harmful molecules are created by normal living – breathing, eating, etc. The body produces “toxins” whenever we make energy to go about our daily life. As mentioned, the body also has a strong mechanism to deactivate these toxins (“detox”), which allows us to function normally.
When the balance of toxins (ROS) exceeds the body’s ability to remove these toxins (antioxidants), a state known as oxidative stress results.
Reactive oxygen species (ie oxidative stress) causes inflammation as well [6].
Taking antioxidants would seem like the logical solution and while that helps a bit, it turns out that turning on our internal detox systems works much better.
When oxidative stress is high, the brain can be the first organ in which you notice issues, especially if your hypothalamus is already weakened by other stressors (like chronic sleep deprivation).
Brain fog is more likely to be felt in the morning for some, because that’s when oxidative stress peaks.
Oxidative stress, like inflammation, causes brain barrier permeability and that can cause lots of problems on its own. Stuff that isn’t supposed to pass the brain barrier will, resulting in neuroinflammation [7, 5].
The symptoms of brain fog are usually transient because the body adjusts to temporary spikes in oxidative stress.
Eventually, various cognitive diseases start to come about. People who experience brain fog will be at an increased risk of just about every chronic disease – cancer, heart disease, Alzheimer’s, cognitive decline, and more.
Oxidative Stress Is Likely the Direct Cause
Inflammation and ROS (oxidative stress) cause each other, so in one sense they can almost be used interchangeably for my intents and purposes.
My guess is, however, that oxidative stress is what is actually causing the brain fog, and since inflammation causes OS, it’s not that relevant.
Since inflammation and OS are so interlinked, it would seem almost impossible to disentangle which one is actually causing the brain fog. I’d be hard pressed coming up with an example of something that causes only one of them.
However, I believe that oxidative stress is what’s actually causing it because of the following:
1) When I get inflammation I first get tired (see my post about this) and only later a bit foggy. Since we know that inflammation causes OS, this would make sense that fogginess would follow an acute bout of inflammation.
2) I’ve experimented with almost every over the counter supplement. A few of these, especially a nootropic drug called piracetam, gave me brain fog. In this case, there was no fatigue or inflammation preceding the brain fog; rather, it came on suddenly.
I noticed that brain fog was a common complaint about people taking this drug (Piracetam Supplement Dangers and Risks read my post on it).
Since I already suspected OS was the direct culprit, I decided to do some digging and see if I could unearth anything that spoke about oxidative stress in the hypothalamus.
And then I found it:
MDA [a marker for oxidative stress] increased in cortex and hippocampus and in the cortex, hypothalamus, and striatum by the higher dose of vinpocetine or piracetam, respectively along with decreased TAC (total antioxidant capacity), at their high concentration, these drugs exhibit pro-oxidant properties and increase free radical production or act as a free radical [8].
Since OS causes inflammation, I still can’t be sure, but I have a strong hunch it’s the OS that is the direct cause. I haven’t seen any studies mentioning piracetam causing inflammation.
There are other lines of evidence for my OS theory, but I won’t get into it here.
Either way, this is just an intellectual curiosity and the treatment wouldn’t change.
How to Know If Something Is Worsening or Helping with Your Brain Fog
I find that most of my brain fog clients have trouble telling if something is somewhat helpful with their brain fog. They would be able to tell if a supplement or device completely takes away the brain fog, but not if it partially improves their brain function. Brain fog is a complex problem and most people will need multiple interventions to completely fix it. Therefore, I recommend using Brain Gauge to quantify if any supplements, devices, or lifestyle changes help with your brain function to any degree, so that you can create your own brain fog protocol that works.
Causes of Oxidative Stress
Oxidative stress and inflammation are caused by all sorts of things previously mentioned, but the most common causes are all too familiar – chronic sleep deprivation, circadian rhythm disruption, stress, infections, food sensitivities, depression, poor diet, toxins, and being inactive.
When oxidative stress is chronic and reaches a level the body can no longer handle, the system breaks down and the brain can be the first organ that experiences issues.
I discussed how OS is a key player in the pathogenesis of brain fog, but I didn’t describe what causes oxidative stress.
Here’s a list:
- Circadian disruption
- Excess cortisol
- Sleep deprivation
- Hypoglycemia
- Nutrient deficiencies or excess
- Dysthyroid
- Sleep apnea
- Endocrine abnormalities
- External toxins
- Endotoxins
- Heavy metals
- Hypoxia
- Hyperoxia
- Infections
- Food sensitivities (gluten and casein)
- Excess iron
- Excess copper
- Excess salt
- Exercise
- Heat
- Cold
- Alcohol
- IGF-1 excess
- UV
- High-fat diet [9, 10]
- Cell phones [11]
- Superoxide, Nitric oxide, H2O2
Conditions That Contribute to Brain Fog
Insulin Resistance and Hypoglycemia
Stopping the hypothalamic insults is important because it controls glucose homeostasis and the rest of the endocrine system.
This accords with my experience, since I’ve noticed that people with brain fog also have hampered glycemic balance.
The hypothalamus is the organ that senses blood glucose levels.
When the hypothalamus is hypersensitive to glucose because of oxidative stress and mitochondrial dysfunction, it leads to hyperinsulinism and hypoglycemia [12].
Another condition that most of the population has and contributes to hypoglycemia is insulin resistance. Insulin resistance is when insulin doesn’t do a good job of bringing glucose into cells.
When you are insulin resistant, your body will produce more insulin and more significant blood glucose fluctuations, which is even worse than sustained high levels of glucose [13]. (Read my post on how to fix insulin resistance and what causes insulin resistance to occur in the first place.)
These swings in blood glucose levels result in oxidative stress and inflammation and, therefore, even more brain fog [14].
Perhaps most important, hypoglycemia drives psychiatric conditions by causing neurons to get over excited (glutamate excitotoxicity). This excitation causes increased levels of free radicals and mitochondrial breakdown [15]. This is the most damaging aspect of hypoglycemia.
Mitochondrial breakdown leads to even more oxidative stress and even more hypersensitivity to glucose.
Positive feedback is a b*tch. These feedback loops, in part, is what makes chronic diseases so hard to cure.
The pituitary and adrenal glands are particularly involved in glucose regulation, but since these are controlled by the hypothalamus, hypothalamic inflammation will disrupt these systems.
This increased level of OS will, in turn, cause more inflammation and make the hypothalamus more dysfunctional.
Bottom Line: if the hypothalamus is dysregulated because of inflammation and oxidative stress, it will cause the thyroid, pituitary, and adrenal glands to be dysregulated as well and affect glucose homeostasis.
Every time you get hypoglycemic you damage your brain
Thyroiditis
A balanced level of thyroid hormones is crucial for our bodies to function normally. Concerning brain fog, the hypothalamus and thyroid depend on each other and are critical for maintaining homeostasis (balance) in the body.
The pituitary and adrenal glands are also dependent on the hypothalamus and thyroid and vice versa.
If brain fog occurs in the morning, then it’s more likely that the thyroid is an issue as well because a hypo- or hyperthyroid can cause oxidative stress and therefore brain fog [16].
Before I knew how to control it, I constantly swung from a hyper to hypothyroid state. I’d become hyperthyroid pretty easily from something as simple as taking a long walk, and this would result in increased immunity/inflammation [17, 18].
If I then ate something that I’m sensitive to (which causes inflammation), the effect would be amplified 3-fold and the resulting fatigue would be worse.
Be careful if you do a full thyroid panel and it shows you have hypothyroidism because that’s what my results were even though I had hyperthyroidism throughout the day. Hypothyroidism may be most pronounced in the morning (at least it was for me).
Bottom Line: Inflammation of the hypothalamus leads to a thyroid imbalance. A thyroid imbalance can also contribute to brain fog both directly and indirectly.
Leaky Gut and Dysbiosis
With regard to gut health, intestinal permeability or “leaky gut” and/or an imbalance of your gut microbiota (“gut dysbiosis”) can increase autoimmunity and inflammation, thereby contributing to brain fog.
With regard to leaky gut, I think the human body is incredible at healing itself as long as it’s not under constant attack. This is why I feel that as long as your gut isn’t experiencing inflammation from food/toxins you’re ingesting, it will heal itself.
To prevent microbial imbalance or dysbiosis, the gut needs the right ingredients to work well (like prebiotics), which is also why the right foods matter.
Probiotics can also help to modify inflammation.
I’ve noticed that most people with brain fog also have IBS (including my former self).
Research also shows that people with chronic fatigue syndrome (caused by OS and inflammation) are also more likely to have IBS. This is because inflammation of the gut contributes to IBS [19].
Hypothalamic inflammation dysregulates the endocrine system, causing changes in motility, which also leads to IBS.
Sleep Apnea
Sleep apnea can be associated with brain fog in two ways.
First, sleep apnea is probably caused by Th17-related inflammation [20], and therefore someone with this type of inflammation will be more likely to experience brain fog.
Second, sleep apnea causes hypoxia (lack of oxygen) which increases ROS/oxidative stress [21].
People with morning brain fog should particularly watch out for this.
Hypoxia drives psychiatric conditions by causing neurons to get over excited (glutamate excitotoxicity). Glutamate excitotoxicity commonly comes from hypoglycemia as well. This excitation causes increased levels of free radicals and mitochondrial breakdown [15].
Histamine
People with excessive Th2 dominance commonly report brain fog, which seems to be from the production and consumption of histamine.
Histamine can be produced from lectins or allergic reactions as a result of an elevated Th2 immune system.
People can also consume foods with histamine -mainly fermented and cured foods and beverages.
The mechanism by which histamine cause brain fog may be as a result of oxidative stress [22].
Alternatively, histamine is quite active in the hypothalamus. It interacts with other transmitter systems and influences homeostasis, higher brain functions, sleep-wake regulation, circadian and feeding rhythms, immunity, learning, and memory in health and disease [23].
Read my post on reducing histamine.
Heavy Metals and Minerals
Heavy metals increase oxidative stress in the body. Since heavy metals bioaccumulate, they may cause increased levels of oxidative stress in the body.
However, while heavy metals may be a contributing factor, I don’t think it’s the main cause. Unless you have a specific reason to believe that you’ve been exposed to excess heavy metals, it’s probably best not to assume that this is a significant factor.
ALL beneficial minerals can also accumulate in the body and cause problems, but these usually occur later in life.
So unless you’re over 60-70 years old or have reason to believe you’ve been exposed to heavy metals, I wouldn’t focus on this.
The recommendations for this type of brain fog are in part 2.
Pathogens, Infections, and Candida
Science is increasingly becoming aware of the link between various autoimmune conditions and infections – usually earlier in life.
Infections can cause chronic inflammation and oxidative stress, leading to brain fog.
Sometimes, infections – usually viruses – can be latent and then be reactivated by some stressor (lack of sleep, poor diet, etc.)
While infections play an important role in autoimmunity and OS, the question is whether you are capable of getting rid of your infection and if getting rid of your infection will even make a difference.
Sometimes, trying to get rid of an infection is like chasing rainbows and nothing will come of it.
Most people who attempt to get rid of an infection usually take various herbal products that may make them feel better, but likely because they reduce inflammation and OS instead of actually killing any pathogen.
When someone was healthy their whole life and suddenly comes down with brain fog after an infection, effort should be made to identify and get rid of the infection.
If you can identify the infection, then targeted drugs would be a better option than herbs. My recommendations for killing an infection is in part 2.
Out of the cases of brain fog caused by infections, candida is sometimes the cause and this infection is usually curable.
Candida comes from an immune deficiency. Environmental triggers include refined carbs, stress, low stomach acidity (could be from antacids,) and antibiotics. Anybody with brain fog after antibiotic treatment and/or a particularly stressful period should look into candida as being the cause, although it isn’t certain that candida is the cause.
People with candida or bacterial infections will often have a chronic type of brain fog. The mechanism fits in with the mechanism for almost all other types of brain fog: inflammation and oxidative stress. Candida increases TNF-alpha, IL-1, and IL-6 [24], which are inflammatory cytokines and this leads to OS.
Gram-negative bacteria are also known to cause overproduction of TNF-α, IL-1, and IL-6 [25]. Only gram-negative bacteria have LPS, which is why they cause inflammation.
Candida and bacterial infections can usually be cured through conventional and alternative means. See my post on curing candida. The latent viral infections are the tricky ones.
Possible Infections:
- Epstein Barr – Decreases VDR by a factor of about five [26] EBV also blocks the ability of VDR to produce products [27]
- E. coli (feces, animal products)
- Salmonella (feces, animal products) – harms VDR
- Shigella (causes diarrhea) – harms VDR
- Helicobacter Pylori (ulcers, gastritis) – 50% of the global population has this. Produces “Sulfolipid ligand capnine” [28]
- Mycoplasma pneumoniae – increases H2O2, superoxide, resistant to antibiotics [29]
- Stenotrophomonas macrophilia (hospital-acquired, breathing tubes, catheters, prosthetics, cystic fibrosis, latent lung infections)
- Spirochaetes (lyme) – Live Borrelia reduces VDR by 50 times (in monocytes) and “dead” Borrelia reduces it by 8 times [30] – This could explain why people develop autoimmune conditions after Lyme infection
- Neisseria gonorrhea (gonorrhea)
- Neisseria meningitides (meningitis)
- Moraxella catarrhalis (respiratory symptoms)
- Hemophilus influenzae (flu, primarily respiratory problems)
- Klebsiella pneumoniae (pneumonia, primarily respiratory problems)
- Legionella pneumophila (primarily respiratory problems)
- Pseudomonas aeruginosa (hospital acquired, primarily respiratory problems) – Produces “Sulfonolipid ligand capnine” [28] Antibiotics don’t work well [31]
- Proteus mirabilis (primarily urinary problems)
- Enterobacter cloacae (primarily urinary problems)
- Serratia marcescens (primarily urinary problems)
- Helicobacter pylori (primarily GI problems)
- Salmonella enteritidis (primarily GI problems)
- Salmonella typhi (primarily GI problems)
- Acinetobacter baumannii (associated with hospital-acquired infections, causes bacteremia)
- Legionella (found in fluids, Legionnaires’ disease)
- Mycobacterium leprase – produces mir-21 to target multiple genes associated with the VDR [32]
- Tuberculosis – Reduces VDR 3.3-fold [32]
- Chlamydia (trachomatis) – disrupts VDR
- HIV – binds to the VDR [33] and inhibits conversion to active D [34]
- Aspergillus fumigatus – In cystic fibrosis patients, the fungus A. fumigatus has been shown to secrete gliotoxin, a toxin which dose-dependently decreases VDR
- Cytomegalovirus – CMV decreases VDR 2.2 fold [35]
- Hepatitis C virus – Inhibits CYP24A1, the enzyme responsible for breaking down excess 1,25-D [36]
My recommendations for killing an infection is in part 2.
How Oxidative Stress Causes Inflammation
