PUFA Dangers Part 3: The brain

Medical institutions, as well as common research, will teach you that PUFAs are highly essential for brain function, mainly because they are found in such high concentrations within the brain. To assume that PUFAs are essential because they are found in such high concentrations in the brain, is like assuming that because tics are so abundant on dirty dogs, they must be essential for them.
However, after reading this article you can decide for yourself whether or not PUFAs are essential for brain function.

So let’s have a look at the side effects that PUFAs have on the brain…

As already mentioned, PUFAs are majorly incorporated into the brain. Of all the fatty acid phospholipids within the brain, arachidonic acid (which is a PUFA) is present at 8 – 11% , which is several fold higher than any other ω-6 (omega 6). Whereas linoleic acid is only present at 1% compared to arachidonic acid (s).

PUFAs are shown to be chaotropic and increase the membrane fluidity of cells, which makes the cells less orderly. SFAs however, are shown to have the exact opposite effect on cell membranes. (s)

This increase in fluidity (caused by both ω3 and ω6), increases the water content of the cells by increasing calcium, sodium and chloride entry and loss of potassium and magnesium. This causing swelling, resulting in brain edema, (especially in the glial cells), ischemia, hypoxia (PUFAs impair oxygen transmission into the cell. Whereas a COX inhibitor protects against hypoxia) and vascular permeability. (sss, s, s)

The increase in fluidity also increases the permeability of not only the cells, but also the blood brain barrier, allowing more toxins, such as heavy metals, pathogens, bacteria, viruses, serotonin, estrogen, etc., to get access to the brain and damage it. (s)

PUFAs are also shown to inhibit normal glucose metabolism of cells, create lactate, reduce CO2 production, cause insulin resistance, increase serotonin, cortisol and estrogen, reduce ATP production, promote oxidative stress and inflammation (TNFα, NFκB, IL1β, IL6, etc.), etc.

Mitochondrial dysfunction (improper usage of glucose) and oxidative damage, peroxidation of membrane lipids and circulating PUFAs (including omega 3) by ROS (reactive oxygen species), are found amongst the earliest events in pathological aging, as exemplified in the initiation and progression of AD (Alzheimer disease). Studies show that ω3 (omega 3) is protective in the brain, but this is only because ω3 antagonizes arachidonic acid and creates less harmful prostaglandins than ω6. As mentioned above, ω3 is also chaotropic and increases serotonin, and it’s actually cholesterol that is shown to be protective and rather than ω3 (s).

The more PUFAs you have in the brain, the more it’s susceptible to oxidative stress and inflammation, and as a bonus, PUFAs also deplete vitamin E, leaving you with no anti-oxidant do inhibit the toxic effect of PUFAs. SFAs however, such as coconut oil, has been shown to be protective, even in the absence of vitamin E (s).

It has been found that inhibiting leukotriene (thus the LOX enzyme) and the thromboxane receptors, restores brain function, memory, working memory and learning, back to youthful levels in old rats (s, s). This study also shows that inhibiting
12-LOX made neurons resistant to glutamate-induced death (s).

 

Serotonin

Not only are PUFAs substrates for prostaglandins, thromboxanes, lipotrienes, and lipid peroxidation etc., but they also increase serotonin. Serotonin causes fibrosis of tissue, lesions, depression, anxiety, jumpiness (easily frightened), migraines, traumatic memory formation, emotional response to pain, and vision and auditory hyper-sensitivity. It is also anti-metabolic, increases cortisol and prolactin, is an estrogen receptor agonist, and much more (ss) (more on serotonin here). So as you can see, serotonin is really not a hormone that you want elevated at all, especially not chronically.

PUFAs are direct agonists to serotonin receptors, they increase tryptophan hydroxylase (which increases serotonin synthesis), and inhibit serotonin transporters, thus increasing the potency of serotonin (s).

Cortisol, increased by PUFAs, decreases 5-HT1A, (the autoreceptor which will lower serotonin synthesis when activated) and inhibits serotonin downregulation, leading to chronic high serotonin. Also, the hyperinsulinemia caused by cortisol increases tryptophan entry into the brain, and increases serotonin synthesis.

Serotonin will then increase its own synthesis by stimulating phospholipase A2, via 5-HT2 agonism and cortisol, and release arachidonic acid from cell membranes.
SFAs however, are shown to inhibit this effect. (s)

PUFAs increase serotonin, which are harmful and is high in many brain disorders.

 

Dopamine

Prostaglandin H synthase can lead to the oxidation of dopamine, to form dopamine-quinone (neuromelanin), which in turn is highly reactive (s), and uses catecholamines and serotonin as endogenous cofactors. Dopamine-quinone can react with cysteinyl residues in proteins, leading to protein transformation and subsequently to the alteration of protein function. This in turn can lead to the cell death, as seen in Parkinson’s disease (s). EP1 receptor activation, by prostaglandins, leads to increased dopamine turnover. (s)

PUFAs lower dopamine, which further increases serotonin, and amplifies the negative effect of serotonin.

 

Excitatory neurotransmitters

PUFAs are also shown to increase glutamate synthesis. PUFAs redirect the synthesis of niacin from tryoptophan, to kynurenine (KYN), via indoleamine 2,3-dioxygenase (IDO) (s). Elevated KYN is associated with cognitive deficits in schizophrenia, Alzheimer’s disease, cardiovascular disease, depression, inflammation, HIV induced dementia, Tourette syndrome, anxiety disorders, Multiple sclerosis, Huntington’s disease, Encephalopathies, Lupus, etc (w). Furthermore, PGE2 (prostaglandin E2) enhances the release of glutamate, and excitatory amino acid-induced synaptic depolarization. (s) Not only is PUFAs excitatory, but it also inhibits the uptake of the protective GABA in the brain. (s)

PUFAs increase excitatory neurotransmitters, which leads to over-excitation, brain damage and related disorders.

 

Endocannabinoid

PUFAs increase endocannabinoid receptors (CB1 & CB2) angonists, namely, anandamide and 2 arachidonoyl glycerol (2AG).
Anandamide and 2 arachidonoyl glycerol are both substrates for COX, but don’t have as high affinity for COX as arachidonic acid does.

An increase in endocannabinoids levels induces hyperphagia (munchies), lipogenesis, fatty liver and liver damage. It also increases nitric oxide synthesis, free radical formation, neural damage and could have an impact on glycemia (s, s, s).
2AG are potentially anti-androgenic, because progesterone increases sperm motility by displacing 2AG (We know that PUFAs lower androgens, but I just wanted to show that even endocannabinoids can have a negative effect as well) (s).

Arachidonic acid is a precursor to endocannabinoids, which have direct actions on brain function.

 

Estrogen

The increase in cell swelling, caused by increased membrane fluidity and permeability, increases the synthesis of estrogen. Estrogen is directly associated with autoimmune diseases, which is also why women are 4 times more likely to suffer from an autoimmune disease than men. Estrogen in the brain causes demyelination, which leads to conditions such as ALS, multiple sclerosis etc. However, lowering estrogen, blocking free fatty acid release, inhibiting COX, and stimulating normal glucose metabolism, have been shown to put autoimmune patients in remission.

PUFAs are estrogenic, and estrogen is highly toxic and damaging to the brain.

 

Cortisol

PUFAs increase cortisol production in the absence of ACTH, and potentiates the effect of ACTH (the hormone that signals the adrenals to release cortisol), whereas SFAs are inhibitory. (sss) PUFAs also increase liver mRNA level for the enzyme HSD11B1 (the enzyme which converts cortisone to cortisol; the active form) (s).

Chronic high cortisol levels cause demyelination and brain damage, which leads to memory impairment, depressions, anxiety, loss of executive functions (including decision-making), visuoconstructive skills, verbal ability, motor functions and a reduction in information processing speed. (s)

PUFAs increase cortisol, are catabolic to brain tissue and reduce brain function.

 

Here are a few studies showing the disease side effects which PUFAs have on the brain:

  • Alzheimers. (s) There are studies which speculate that Alzheimers might just be diabetes of the brain. Reducing fatty acid β-oxidation decreases oxidative stress in the brain, and β-oxidation inhibitors may be a novel therapeutic approach for brain disorders associated with oxidative stress (s). Inhibiting LOX induces autophagy, which breaks down tau and defective proteins (s). Pharmacological inhibition of 12/15-lipoxygenase reverses learning and memory impairments and reduces Aβ and tau neuropathology.
  • Bipolar disease. Drugs that are approved for bipolar disease, such as lithium, inhibits arachidonic turnover and COX, thus reducing inflammation and improving the condition (s).
  • Multiple sclerosis. (s) Aspirin is protective as it inhibits COX, LOX, free fatty acids, and lowers estrogen and cortisol. (s) Prostaglandin receptor antagonists are also used to treat this disease. (s)
  • Parkinson’s disease (s). COX is mainly expressed on the dopamineric neurons, and its activation will lead to neurodegeneration. (s) COX also increases formation of neuromelanin, which is involved in the development of Parkinson’s disease. (s)
  • Depression and suicide risk. PUFAs increase nuclear factor-κB (NF-κB) (s), lower CREB, increase MDA (lipid peroxide) and lower glucose metabolism, which all contribute to depression. (s)
  • Amyotrophic lateral sclerosis (ALS). (s) Reducing prostaglandin formation significantly suppresses of astrogliosis and demyelination (s).
  • ADHD. (s, s) PGE2 blocks inhibitory glycine receptors.
  • Epilepsy (s). PUFAs increase glutamate signalling and increase the permeability of the blood brain barrier, allowing inappropriate proteins, such as albumin and IgG, to enter the brain. This leads to increased excitation and seizures, and then cell death and inflammation. (s)
  • Schizophrenia (s). PGE is found in high concentrations in the cerebrospinal fluid of schizophrenics compared to that of healthy controls. (s)

The above mentioned “diseases” are just a few conditions initiated and exacerbated by PUFAs.
PUFAs always synergize with stress hormones such as cortisol, serotonin, estrogen and prolactin and increase the risk of many diseases. PUFAs are not the single cause of these conditions, but do play a significantly large role. Eliminating PUFAs should be the first step to take when wanting to prevent or recover from such conditions. In the meanwhile, SFAs, such as coconut oil, are protective as it “dilutes” the PUFAs. Vitamin E inhibits lipid peroxidation and inflammation, but is unable to stop all of it when PUFAs are too much. Aspirin is the best natural COX inhibitor with almost no side effects. If you get GI upset from it, take it with glycine to protect the stomach.

 

Be sure to read more on PUFA Dangers in Part 4 where we’ll be discussing the side effects it has on hormones.

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