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Arachidonic acid and other unsaturated FAs as endogenous antimicrobial molecules

Gondwanaland

Senior Member
Messages
5,092
https://www.sciencedirect.com/science/article/pii/S2090123218300018 (open access)
Arachidonic acid and other unsaturated fatty acids and some of their metabolites function as endogenous antimicrobial molecules: A review

Abstract
Our body is endowed with several endogenous anti-microbial compounds such as interferon, cytokines, free radicals, etc. However, little attention has been paid to the possibility that lipids could function as antimicrobial compounds. In this short review, the antimicrobial actions of various polyunsaturated fatty acids (PUFAs, mainly free acids) and their putative mechanisms of action are described. In general, PUFAs kill microbes by their direct action on microbial cell membranes, enhancing generation of free radicals, augmenting the formation of lipid peroxides that are cytotoxic, and by increasing the formation of their bioactive metabolites, such as prostaglandins, lipoxins, resolvins, protectins and maresins that enhance the phagocytic action of leukocytes and macrophages. Higher intakes of α-linolenic and cis-linoleic acids (ALA and LA respectively) and fish (a rich source of eicosapentaenoic acid and docosahexaenoic acid) might reduce the risk pneumonia. Previously, it was suggested that polyunsaturated fatty acids (PUFAs): linoleic, α-linolenic, γ-linolenic (GLA), dihomo-GLA (DGLA), arachidonic (AA), eicosapentaenoic (EPA), and docosahexaenoic acids (DHA) function as endogenous anti-bacterial, anti-fungal, anti-viral, anti-parasitic, and immunomodulating agents. A variety of bacteria are sensitive to the growth inhibitory actions of LA and ALA in vitro. Hydrolyzed linseed oil can kill methicillin-resistant Staphylococcus aureus. Both LA and AA have the ability to inactivate herpes, influenza, Sendai, and Sindbis virus within minutes of contact. AA, EPA, and DHA induce death of Plasmodium falciparum both in vitro and in vivo. Prostaglandin E1 (PGE1) and prostaglandin A (PGA), derived from DGLA, AA, and EPA inhibit viral replication and show anti-viral activity. Oral mucosa, epidermal cells, lymphocytes and macrophages contain and release significant amounts of PUFAs on stimulation. PUFAs stimulate NADPH-dependent superoxide production by macrophages, neutrophils and lymphocytes to kill the invading microorganisms. Cytokines induce the release of PUFAs from cell membrane lipid pool, a potential mechanism for their antimicrobial action. AA, EPA, and DHA give rise to lipoxins (LXs), resolvins, protectins, and maresins that limit and resolve inflammation and have antimicrobial actions. Thus, PUFAs and their metabolites have broad antimicrobial actions.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
I was looking into this twenty five years ago, for about a decade. AA is potentially very inflammatory. It can drive many ME symptoms. There are indeed anti-microbial properties, but I think its far more inflammatory than helpful, and in part that is how it fights microbes. Its also the most likely substance that kills people during alcohol poisoning. Anti-microbial via inflammatory processes is problematic.

Now series 3 eicosanoids, from EPA, have similar actions but are far less inflammatory. Indeed its because EFA results in less inflammatory eicosanoids, and competes with AA for eicosanoid synthesis, that its considered antiinflammatory. It isn't, its much less inflammatory than AA is how that works.

Now there are antiinflammatory eicosanoids that can be produced too, and if we knew how to make them dominate we might have a useful tool. I don't think we do though.

I was using AA and eicosonoid modulation as my main treatment modality through most of the 90s. I got worse in the long run, but it sometimes helps in the short run. Indeed, despite its inflammatory properties, if you have an active infection, not latent or recurring but acute, then evening primrose oil and fish oil might be beneficial in the short run.

Check out this very old paper, from the doc who had his practice about five houses from me at the time - https://preview.ncbi.nlm.nih.gov/pubmed/?term=gray martinovic eicosanoid CFS

PMID:7968718

Med Hypotheses. 1994 Jul;43(1):31-42.
Eicosanoids and essential fatty acid modulation in chronic disease and the chronic fatigue syndrome.
Gray JB, Martinovic AM.
Erratum in
Med Hypotheses 1995 Aug;45(2):219.
  • Med Hypotheses 1995 Aug;45(2):219.
 

ChrisD

Senior Member
Messages
472
Location
East Sussex
https://www.telegraph.co.uk/news/20...-diet-changes-human-dna-raising-risk-of-canc/

''Populations who have had a primarily vegetarian diet for generations were found to be far more likely to carry DNA which makes them susceptible to inflammation.

Scientists in the US believe that the mutation occured to make it easier for vegetarians to absorb essential fatty acids from plants.

But it has the knock-on effect of boosting the production of arachidonic acid, which is linked to inflammatory disease and cancer. When coupled with a diet high in vegetable oils - such as sunflower oil - the mutated gene quickly turns fatty acids into dangerous arachidonic acid.''
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Arachidonic acid is very dangerous. Its usually bound and then released as needed. If released it immediately leads to eicosanoid synthesis, and most of those are inflammatory. Its hormonal regulator is cortisol. Its utilisation is boosted by peroxynitrite, if I recall correctly.

Even a fairly small amount of free arachidonic acid in the blood is lethal. When we release it we release very miniscule amounts. Alcohol causes a release of larger amounts, and blocking arachidonic acid metabolism can save some people from alcohol poisoning.

Amongst other symptoms it causes headaches.

I have not investigated a possible cancer link, but it is long known to be inflammatory.

On the flip side its an essential fatty acid. Its needed to create an entire superfamily of critical hormones. If the quantity of omega-6 polyunsaturated fat in the diet is too low for too long the deficiency can be fatal. The key is in balance, and that is very hard to do.
 

sb4

Senior Member
Messages
1,654
Location
United Kingdom
Whilst this is interesting I would be cautious of implementing it. As many have posted in this thread including alexs very good posts, AA and other polyunsaturated fatty acids (omega 6 in particular) can have very negative effects on the body.

They can increase prostaglandins. This may help kill viruses but its also very inflammatory and a trigger for mitosis.

Oxidize easily. This obviously causes oxidative stress and depending on where it happens it can be big (mitochondria). This can also lead to Lipofuscin which is basically oxidized unsaturated fatty acids cross linked with metals and proteins of which there does seem to be no way for a cell to dispose of without mitosis or apoptosis.

Increase membrane fluidity (useful for cancer). Having a rigid cell membrane full of saturated fats seems to resist mitosis/cancer fairly well, whereas when a cell divides it increases enzymes such as stearoyl coa desaturase which takes stearic/palmitic (saturated) and turns them into monosaturated versions which result in membrane fluidity and thus increase membrane size and allows cell to swell with water.

Cause obesity and diabetes/etc. Peter @ hyperlipid did a great series on this. Basically it has a lower FADH2/NADH ratio, meaning it generates less super oxide through reverse electron flow in mitochondria, this generates less temporary insulin resistance meaning your fat cells pull in more nutrients from your blood than they would with the same amount of calories of SF. This lowers blood glucose geater that it would with SF and makes you more hungry. Do this enough and your fat cells become packed with fat and start to spill into blood, even when insulin is present. This leads to real insulin resistance and diabetes.

I have read quite a few health gurus, forums, etc but the one thing I see most agreement on is the negative effects of polyunsaturated fats, particularly omega 6's.