Brain Fog: A Deeper Dive (Part 1 of 2) |
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Brain Fog: A Deeper Dive (Part 1 of 2)

Brain Fog: A Deeper Dive (Part 1 of 2)

This is a follow up blog to our Brain Fog: An Overview piece (which you should definitely check out). Already read it? Lets get started:


Oxidative Stress

A major participant of oxidative stress is the free radical. A free radical is an oxygen-containing molecule that has one or more free electrons. Thanks to the free electrons, free radicals can interact with elements of the cell, particularly with proteins, DNA, and lipids. These interactions, however, can prove harmful (we’ll explain how in a moment) [1]. In order to prevent these harmful interactions, our body has antioxidants that act as the receptors of the free electrons; this leaves the cells and their components unharmed.

Oxidative stress occurs when there are not enough antioxidants to prevent the free radicals from interacting with the cells. Once the free radicals are free to interact with the cells, the effects may include irreversible changes in the body and contribution to various disorders. The excess of free radicals also causes chronic inflammation [2], thus leading us to the obvious conclusion that oxidative stress itself is a cause of chronic inflammation.

Recall that free radicals tend to interact with lipids. The brain is made up of cells that have high levels of lipids, making the brain highly vulnerable if oxidative stress is present. To make matters even worse, metal ions induce the formation of free radicals. Why do we care? Well, because the brain is host of a considerable amount of metal ions such as Fe3+, Cu2+, and Zn2+, making the brain even more vulnerable [3]. To top it off, the CNS (Central Nervous System) has a lower concentration of antioxidants in contrast to other organs. The cells in the hippocampal CA1 region (Sommer sector), hippocampal CA4 region (Bratz sector), dorsal-lateral striatum, and the neurons of III and V layers of the cortex are considered the most likely to be damaged [4].

The development of neurodegenerative diseases and CNS disorders are closely linked to oxidative stress and chronic inflammation. Examples of neurodegenerative diseases are Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), and stroke [5, 6].

Reactive Free Radical


Orexin is a neuropeptide, a kind of neurotransmitter, responsible for our appetite, wakefulness, and arousal. Lower-than-normal levels of orexin are a sufficient cause for narcolepsy, a neurodegenerative disease characterized by excessive daytime sleepiness and disturbed sleep [7].


Why Should We Increase Orexin?

An increased amount of orexin increases wakefulness. Neurons that produce orexin are particularly active when an individual is engaged in motor activity [8]. Low levels of orexin, on the other hand, happen when an individual is asleep. Although histamine also plays an important role in wakefulness, orexin is thought to regulate the histamine system [9]. The difference between orexin and histamine is that a lack of orexin leads to chronic sleepiness and unwillingness to engage in physical activities, whereas a lack of histamine leads to a decrease in quality of cognitive activities [10].

Deficient levels of orexin are thought to be a sufficient cause for narcolepsy. Low levels of orexin during sleep is normal in healthy subjects, but low levels of orexin during the daytime indicate that the subject has narcolepsy. Low levels of orexin can also lead to depression and anxiety [11].

Orexin also regulates appetite. Increasing the levels of orexin leads to an increased appetite, whereas decreasing the levels of orexin does the opposite. When we are hungry and our glucose levels are low, orexin neurons are excited and produce more orexin [12]. This leads to the somewhat paradoxical sensation of feeling very awake after not having eaten for a prolonged time. When we, on the other hand, have plenty of glucose, orexin neurons are inhibited [8]. However, individuals with a deficit in their levels of orexin do not respond as strongly to hunger [13]. This is indicative of the influence orexin has on our appetite.  

Orexin stimulates oxygen consumption. This in turn increases metabolism and stimulates both energy intake and energy expenditure, as a whole also known as energy homeostasis [14]. Deficiency in orexin leads to obesity, despite regular or even lower amounts of food consumption. This can be attributed to lack of physical activity, lower metabolism, or both.

If you think you are safe from the effects of a deficiency in orexin, think again. As people age, they start losing their appetite, decrease their performance in physical and cognitive activities, and do not have a healthy body weight [15]. These changes can be partially attributed to an alteration in the production of orexin.


Now that we know how brain fog works, we would like to know what causes it. The most common cause of brain fog is a heightened sensitivity to lectin. Lectin is a protein that is present in most foods we consume. Their concentration is particularly high in gluten grains such as wheat, barley, rye, oats and spelt, in nightshade foods such as tomato, tobacco, pepper, potato, eggplant, and curry, and in eggs, chicken, dairy, and all legumes [16].

It is surprising that lectin can be harmful given that it is so ubiquitous in our foods. Let us first understand how the heightened sensitivity to lectin works. Once in our bodies, lectins want to naturally attach themselves to sugar molecules. This makes lectins act like “magnets” that attract sugar. Our bodies perceive this as a threat, and consequently they create an inflammatory response [17].

“...inflammatory response…” that phrase sounds familiar, because it is! Recall that inflammation is a cause for brain fog [link to part 1 of series]. Leptin causes inflammation in different parts of the body, including the brain. This, in turn, leads to brain fog.

If you want to know if you are sensitive to lectin, you should look out for these signs. In case you notice any of them, particularly brain fog, you should consider avoiding all the foods mentioned in the first paragraph and instead eat vegetables and fruits.


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