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Gamma Linolenic Acid (GLA)
GLA is a conditionally essential (may need to be supplemented) Omega-6 (EPA omega-3 -Not DHA- are already known to be anti-inflammatory due to D5D inhibition) prostaglandin E1 (PGE1) and prostaglandin E2 (PGE2) precursor for immune responses. GLA is known to be at elevated levels in human breast milk but not cow's milk. If PGE1 is made, it exerts an anti-inflammatory and anti-cancer effect. If PGE2 is made it exerts a more inflammatory effect. It appears that in normal metabolism of GLA, both are made, and therefore supplementing with GLA will improve PGE1/PGE2 ratio in the body by increasing PGE1 over baseline. Some things like Lignans are known to help improve the PGE1/PGE2 ratio even further upon supplementation of GLA via D5D (Delta-5-desaturase) inhibition.
PGE1 is created from DGLA. DGLA is quickly and easily made from GLA.
PGE2 is created from Arachadonic Acid (AA) and also DGLA. AA is made from DGLA via Delta-5-desaturase (D5D). AA is also made from phospholipids and diacylglycerols via Phospholipase C or Phospholipase A2 or Diacylglycerol lipase.
DGLA and AA compete for COX-2 production of PGE1 and PGE2 respectively and they are about equal. COX-2 is therefore required to make both PGE1 and PGE2. However COX-1 also converts AA to PGE2 so more PGE2 is made almost always.
This explains why COX-2 influencers seem to possibly help in Cancer cases. Depending if they are taken orally (THCA,CBDA) or smoked (THC, CBD) they have opposite effects on COX-1 and COX-2. In general smoked CBD seems to slightly inhibit COX-1 and promote COX-2 (improving PGE1/PGE2 slightly) and smoked THC seems to promote COX-1 strongly and promote COX-2 somewhat, likely worsening PGE1/PGE2 ratio. But taken raw, both CBDA and THCA inhibit COX-1 greater than COX-2 therefore improving PGE1/PGE2 ratio.
Delta 6 Desaturase (D6D)
Delta 6 dehydrogenase creates GLA from Linoleic acid (Linoleic is typical vegetable oil Omega-6). Linoleic acid converts into AA and also prostaglandins (PGE1 and PGE2) and other things. People may be prone to deficiency of D6D which is why GLA seems to be deficient in many people.
DHA actually downregulates D6D supressing GLA manufacture in the body which is bad.
Delta 5 Desaturase (D5D)
D5D is an enzyme that converts DGLA to AA.
D5D also promotes the conversion of DGLA to AA.
EPA inhibits D5D.
Iron Overload and others:
COX-2 elevated in Iron Overload.
Iron overload appears to Induce COX-2 and also enhances AA.
Natural products effects on AA
Heme oxygenase causes cleavage of heme group
bilirubin increased in iron overload, so increased heme oxygenase?
bacteria heme oxygenase:
https://pubmed.ncbi.nlm.nih.gov/15310749/
https://jb.asm.org/content/182/23/6783
https://www.liebertpub.com/doi/abs/10.1089%2Fars.2004.6.825
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4007353/
https://jb.asm.org/content/jb/182/23/6783.full.pdf
Theory: Bacterial infection with pseudomonas/neissaria/mycobacterium or others cause lysis of heme via heme oxygenase, which causes increased bilirubin in iron overload patients and also increased ferritin as ferritin is up-regulated to capture the iron released from heme. The body has to genetically produce more ferritin to compensate for the attack, this is where the Hemochromoatisis gene is selected for.
Histamine stimulates cox-2
https://duckduckgo.com/?q=histamine+cox-2&ia=web&iai=r1-6&page=1&adx=prdsdc&sexp=%7B"v7exp"%3A"a"%2C"prodexp"%3A"b"%2C"prdsdexp"%3A"c"%2C"biaexp"%3A"b"%2C"liapm"%3A"a"%7D
Nk and t cells require histamine
https://www.nature.com/articles/6602768
Histamine needed for il2 efficiency
https://www.nature.com/articles/6602768
Histamine ultimately regulates cox-2
http://europepmc.org/article/MED/18025237
Sesame oil cox-2 inhibitor.
Depression:
riboflavin decreases cox-2 and therefore can lower pgd2 and cause depression.
depression caused by low PGD2. This can be because AA is converted preferably to PGE2 instead of D2. Or because COX-2 is low.
hair loss caused by PGD2 excess. So unlikely you have hair loss and depression at the same time.
Pgd2 also elevated in asthma and acts opposite pge2
https://en.m.wikipedia.org/wiki/Prostaglandin_D2
Calcium lowers pge2
https://www.sciencedirect.com/science/article/pii/S0022202X86908547
Mg increases responsiveness to prostaglandins
/https://pubmed.ncbi.nlm.nih.gov/7394065/
Pgd2 induces chloride excretion
https://www.ncbi.nlm.nih.gov/pubmed/25534438
Calcium might support cox-2 inhibiton
https://pubmed.ncbi.nlm.nih.gov/27162170/
Vitamin d reduces pge2 synthesis, likely promoting pgd2
https://www.atsjournals.org/doi/full/10.1165/rcmb.2013-0211OC
COVID PGD2 increase. While PGE1 helps COVID patients.
Cytokines boost cox 2 and modulate CAMP.
Prostaglandins reduce cytokines by increasing CAMP.
PGE1 increases camp.
P Acnes stimulates likely PGE2 (PGD2?)
Quercetin PGD2 inhibitor, good for covid.
PGD2 high in salicylate sensitivity.
bacteria involved (TB included) with cytokines and mast cell activation (PGD2).
staph aureus superantigen B promotes PGD2?
Staph seems to fight off p acnes.
pge2 might be uprefulated in Mycobacterium tubercluosis infection. Vitamin D and garlic kill MTB so may help reduce bodies production of PGE2 and therefore boost PGD2 to treat depression.
Adhd gla helps and epa so likely pge1 deficiency possibly a pge2 or pgd2 over expression
https://pubmed.ncbi.nlm.nih.gov/24560325/
PGD2 increases serotonin.
0ge1 blocks Aa
https://www.sciencedirect.com/science/article/abs/pii/030698778190044X
Pge1 absent in schizophrenics upon adp, de0ressed, manic, normal ppl about the same with depressed responding a little less to adp and mani responding a little more
https://pdfs.semanticscholar.org/999e/27b902490eb201ba0e552d918c7fa71f5eba.pdf
Sleep deprivation reduces pge2 and increases pgd2.
REM deprivation increase pge2 and decreases pgd2.
Personal experience: taking riboflavin caused depression lowering PGD2. Taking Evening Primrose oil boosted REM sleep increasing PGE2.
PGE2 increase boosts hair growth emu oil, evening primrose oil.
Hairloss cure: Evening primrose oil, riboflavin, staph and p acnes killeng eo since staph feeds on p acnes.
Evening primrose oil, castor oil, cinnamon eo, oregano eo, lemongrass eo, riboflavin. maybe glycerol to lower temp and improve riboflavin dissolution? probably lecithin to dissolve riboflavin.
Hair/Scalp Tonic:
15ml castor oil mixed with 100mg riboflavin. 700mg beta-carotene?
Add 15 mL Evening primrose oil (GLA).
12 drops german chamomile,
4 drops cinnamon bark,
4 drops oregano,
4 drops lemongrass,
3 drops eucalyptus,
3 drops lavender,
3 drops mastic,
3 drops fresh ginger
glycerol does reduce body temperature.
glycerine does not form a solution with oil, but lecithin does.
cinnamon staph.
some natural pgd2 inhibitors.
pgd2 receptors in sleep.
Chamomile blocks cox-2 pge2 and seems to help hair loss.
pge2 stops biotin pantothenic acid uptake to brain.
vit e omega 3 lower pge2.
pge2 might cause photosensitivity.
beta carotene for photosensitivity.
beta carotene does not reduce pge2.
PGE2 reduced by vitamin E.
retinoic acid effects prostaglandins.
tnfa and pge2 elevated from retinol. Lutien?