(3) Chart: Eicosanoid Health Effects

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EFAs – Fats of Life!
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“Omega-6 – “How-to”
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EFAs – 5 vital functions:
(1) Cell Membrane integrity
(2) Cellular energy production
(3) Eicosanoids-“First Responders”
• EFA Conversion Chart
• Specific Eicosanoid Effects
(4) Systems Support
(5) Child Development

Chart of significant eicosanoids and their effects

Prostanoids: Prostaglandins & Thromboxanes (produced in most cells via enzymes COX-1 (housekeeping) and COX-2 (mostly induced under stress conditions)
PGE1		Directly derived from: Omega-6 DGLA in breast milk. via COX enzymes.
PGE1		Indirectly derived from: Omega-6 LA in nuts, seeds, vegetable oils, or legumes or GLA in borage, evening primrose or blackcurrant oil, which can all ultimately be converted to Omega-6 AA, and then to more inflammatory /active eicosanoids PG2, TX2, LT4. and EX4. However – this omega-6 AA pathway leading to more inflammatory eicosanoids competes with omega-3 presence for Δ5D, Δ6D and COX enzymes that prefer pathways to the more calming, anti-inflammatory PG1 (incl. PGE1), TX1, PG3, TX3 and LT5 series of eicosanoids.Sufficient omega-3 SDA (in blackcurrant / wild seed oil or derived from omega-3 ALA foods) must be present to ensure COX enzyme conversion of Omega-6 DGLA to anti-inflammatory PG1 series (incl. PGE1) by competing for Δ5D enzymes, instead of COX conversion to Omega-6 AA and then the more active eicosanoids. “EFA Conversion Chart” provides a visual aid to understanding these complicated, interacting conversion pathways.
P G E 1	ALL CELLS	Anti-inflammatory	Reduce Pain
		Sesame lignans promote conversion of omega-6 DGLA to anti-inflammatory PGE1 in favor of pro-inflammatory omega-6 AA
		Inhibit cell proliferation
P G E 1	BLOOD / LYMPH VESSELS	Vasodilator
P G E 1	PLATELETS	Inhibits platelet aggregation (clotting)
P G E 1	IMMUNE SYSTEM CELLS	I.S. Booster
P G E 1	BRONCHIAL AIRWAYS	Dilator
P G E 1	BRONCHIAL AIRWAYS

PGD2		Directly derived from: Omega-6 AA in meat and eggs. If present, Omega-3 EPA competes for COX-1 or COX-2 enzymes reducing their conversion of Omega-6 AA to PGD2 and other inflammatory /active eicosanoids: PG2, TX2,, LT4. and EX4.
PGD2		Indirectly derived from: Omega-6 LA in nuts, seeds, vegetable oils, or legumes, or Omega-6 DGLA in breast milk, or GLA in borage, evening primrose or blackcurrant oil, which can all ultimately be converted to Omega-6 AA, and then to inflammatory /active eicosanoids: PG2 (incl. PGD2), TX2, LT4. and EX4 via COX enzymes.. However – this omega-6 AA pathway leading to more inflammatory eicosanoids competes with omega-3 presence for Δ5D, Δ6D and COX enzymes that prefer pathways to the more calming, anti-inflammatory PG1 (incl. PGE1), TX1, PG3, TX3 and LT5 series of eicosanoids. “EFA Conversion Chart” provides a visual aid to understanding these complicated, interacting conversion pathways.
P G D 2	AIRWAYS;	Potent Contractor
P G D 2	AIRWAYS;	Released by I.S. Mast cells – Involved in allergic rhinitis and allergic bronchial asthma. Attracts neutrophils (WBCs that fight infection and heal injuries). Involved in late phase reactions to allergens (6 hrs after exposure). PGD2 has 10 times higher concentration in asthma patients compared to control patients.
P G D 2	PULMONARY PLACENTAL VESSELS	Potent vasoconstrictor
P G D 2	PULMONARY PLACENTAL VESSELS	Released by I.S. Mast cells – PGD2 is a potent vasoconstrictor via thromboxane/endoperoxide (TX/E) receptor activation in pulmonary vessels, but this mechanism is not responsible for vasoconstriction in systemic vessels or in airway. King, 1991
P G D 2	BLOOD / LYMPH VESSELS	Potent vasoconstrictor	Raise BP
P G D 2	BLOOD / LYMPH VESSELS	PubMed
P G D 2	UTERINE blood vessels	MILD Vasodilator
P G D 2	UTERINE blood vessels	Released by Mast Cells – PGD2 can promote mild vasodilation if TX/E is blocked. King, 1991 PGD2 dilates uterine blood vessels. Together with its ability to constrict placental blood vessels, it may control utero-placental blood flow.
P G D 2	Mast cells in BRAIN
P G D 2	Mast cells in BRAIN	Most abundant prostanoid in mammalian brain; PGD2 promotes sleep [Encyclopedia of Sleep, 2013]
P G D 2	Mast cells in SKIN	Vasodilator
P G D 2	Mast cells in SKIN	PGD2 is the primary mediator of vasodilation after taking niacin (vitamin B3) – the so-called “niacin flush“. Involved in urticuria (hives), and balding- a causal link was found between elevated levels of localized PGD2 and hair growth inhibition (byincreasing Prostaglandin D2 synthase). Garza et al, 2012.

PGE2		Directly derived from: Omega-6 AA in meat and eggs. If present, Omega-3 EPA competes for COX-1 or COX-2 enzymes reducing their conversion of Omega-6 AA to PGD2 and other inflammatory /active eicosanoids: PG2, TX2,, LT4. and EX4.
PGE2		Indirectly derived from: Omega-6 LA in nuts, seeds, vegetable oils, or legumes, or Omega-6 DGLA in breast milk, or GLA in borage, evening primrose or blackcurrant oil, which can all ultimately be converted to Omega-6 AA, and then to inflammatory /active eicosanoids: PG2 (incl. PGE2), TX2, LT4. and EX4 via COX enzymes.. However – this omega-6 AA pathway leading to more inflammatory eicosanoids competes with omega-3 presence for Δ5D, Δ6D and COX enzymes that prefer pathways to the more calming, anti-inflammatory PG1 (incl. PGE1), TX1, PG3, TX3 and LT5 series of eicosanoids. “EFA Conversion Chart” provides a visual aid to understanding these complicated, interacting conversion pathways.
P G E 2	BRAIN; JOINTS	Inflammatory /Increase Pain Via Cox-2 – Promotes all signs of classic inflammation: i.e. redness, swelling and pain. Redness and edema result from increased blood flow into the inflamed tissue through PGE2-mediated increase in arterial dilation and microvascular permeability. Pain results from the action of PGE2 on peripheral sensory neurons and on central sites within the spinal cord and the brain Quercetin reduces PGE2 in RA joints Link
P G E 2	AIRWAYS	Dilator
P G E 2	AIRWAYS
P G E 2	Walls of: BLOOD / LYMPH VESSELS. STOMACH, INTESTINE, BLADDER, UTERUS	Vasodilator Normalize BP	Smooth muscle relaxer
P G E 2		Dilates blood vessels in kidneys PubMed Relaxes Vascular SMCs which form the supporting tissue of arteries, veins, capillaries & lymphatic vessels) and SMCs in walls of other hollow organs: stomach, intestine, bladder, uterus, others
P G E 2	PLATELETS
P G E 2	PLATELETS
	STOMACH /INTESTINAL MUCOSA	Image gastric mucosa
P G E 2	STOMACH /INTESTINAL MUCOSA	Via Cox1 – Protects stomach and intestinal lining; Gastric mucosa: ↑ mucous /bicarbonate secretion; ↑ mucosa blood flow; ↓ gastric acid /PEPSIN secretion; Intestinal mucosa: ↑ duodenal mucus secretion Provides gastrointestinal integrity (via Cox-2?)
	TUMORS Cell proliferation	Image cell proliferation
P G E 2	TUMORS Cell proliferation	Promotes tumor growth: PGE2 is the most abundant prostaglandin found in various human malignancies, including colon, lung, breast, and head and neck cancer, also often associated with a poor prognosis. In contrast, the enzyme that catalyzes the degradation of PGE2 (15-PGDH, an antagonist /suppressor of Cox-2) is highly expressed in normal tissues but is ubiquitously lacking in human colon, gastric, lung and breast cancer resulting in increased endogenous PGE2 levels in these tumors. Furthermore, there may be a negative feedback loop, since a product of the Cox-2 enzymatic pathway, upregulates the expression of 15-PGDH in breast cancer MDA-MD-231 cells. 15-PGDH is being investigated as a potential avenue for tissue regeneration. PubMed. Prostaglandin E Synthase (PGES) converts PGH to PGE
	FERTILITY
	FERTILITY	Regulates immune responses; Involved in fertility
	UTERUS
	UTERUS	Dinoprostone (PGE2) is an FDA approved drug for evacuating the uterus (i.e. promoting abortion or inducing labor; helps dilate cervix)

PGF2α		Directly derived from: Omega-6 AA in meat and eggs. If present, *Omega-3 EPA competes for COX-1 or COX-2 enzymes* reducing their conversion of Omega-6 AA to PGF2α and other inflammatory /active eicosanoids: PG2, TX2,, LT4. and EX4.
PGF2α		Indirectly derived from: Omega-6 LA in nuts, seeds, vegetable oils, or legumes, or Omega-6 DGLA in breast milk, or GLA in borage, evening primrose or blackcurrant oil, which can all ultimately be converted to Omega-6 AA, and then to inflammatory /active eicosanoids: PG2 (incl. PGF2α), TX2, LT4. and EX4 via COX enzymes.. However – this omega-6 AA pathway leading to more inflammatory eicosanoids competes with omega-3 presence for Δ5D, Δ6D and COX enzymes that prefer pathways to the more calming, anti-inflammatory PG1 (incl. PGE1), TX1, PG3, TX3 and LT5 series of eicosanoids. “EFA Conversion Chart” provides a visual aid to understanding these complicated, interacting conversion pathways.
P G F 2 α	AIRWAYS
P G F 2 α	AIRWAYS	Constricting; Anomaly: Promoted by Cox1 inhibitors (aspirin, traditional NSAIDs) Harrington, 2008
P G F 2 α	Walls of: BLOOD / LYMPH VESSELS. STOMACH, INTESTINE, BLADDER, UTERUS	Vaso- Constricting	Image contracting SMC
P G F 2 α		Via Cox2 –CONSTRICTS Vascular SMCs which form the supporting tissue of blood vessels in arteries, veins, lymphatic vessels; uterus CONTRACTS SMCs in other hollow organs: stomach walls, intestine, bladder, uterus
P G F 2 α	EYES
P G F 2 α	EYES
P G F 2 α	STOMACH Gastric mucosa
P G F 2 α	STOMACH Gastric mucosa

PGI2 Prostacyclin		Directly derived from: Omega-6 AA in meat and eggs. If present, *Omega-3 EPA competes for COX-1 or COX-2 enzymes* reducing their conversion of Omega-6 AA to PGI2 (Prostacyclin) and ALSO reducing conversion to inflammatory /active eicosanoids: PG2, TX2,, LT4. and EX4.
PGI2 Prostacyclin		Indirectly derived from: Omega-6 LA in nuts, seeds, vegetable oils, or legumes, or Omega-6 DGLA in breast milk, or GLA in borage, evening primrose or blackcurrant oil, which can all ultimately be converted to Omega-6 AA, and then to mostly inflammatory /active eicosanoids: PG2 (includes calming PGI2), TX2, LT4. and EX4 series via COX enzymes.. However – this omega-6 AA pathway leading to more inflammatory eicosanoids competes with omega-3 presence for Δ5D, Δ6D and COX enzymes that prefer pathways to the more calming, anti-inflammatory PG1 (incl. PGE1), TX1, PG3, TX3 and LT5 series of eicosanoids. “EFA Conversion Chart” provides a visual aid to understanding these complicated, interacting conversion pathways.
P G I 2	BLOOD / LYMPH VESSELS:	Vasodilator	Potent inhibitor of platelet aggregation ³
P G I 2	BLOOD / LYMPH VESSELS:	PGI2 released by endothelial cells(ECs) lining blood and lymphatic vessels; (Via Cox-1 and Cox-2). Potent inhibitor of platelet aggregation (clot formation), also inhibits fibroblast proliferation, and leukocyte adhesion.
P G I 2	SMOOTH MUSCLE CELLS (SMCs)	SMC Relaxer
P G I 2	SMOOTH MUSCLE CELLS (SMCs)	PGI2 regulates smooth muscle cells; counteracts Thromboxane A2 (TXA2)
P G I 2	BRONCHIAL AIRWAYS	Bronchial dilator
P G I 2	BRONCHIAL AIRWAYS	Released by epithelial cells (EPCs) lining airways, Prostacyclin (PGI2) has a beneficial effect on allergic airway responses and pulmonary hypertension. e.g. in asthma. Zhou, 2016
P G I 2	PLATELETS	image for deaggregation Potent Inhibitor
P G I 2	PLATELETS	Via Cox2 – PGI2 is a potent inhibitor of clot formation
P G I 2	KIDNEY, LIVER, LIVER, LUNG, HEART	Anti-inflammatory
P G I 2	KIDNEY, LIVER, LIVER, LUNG, HEART
P G I 2	STOMACH Gastric mucosa	Vasodilator Via Cox1. Protects stomach (gastrointestinal) lining / epithelial cells

TXA2 Thromboxane (TXA2 ==>TXB2)		Directly derived from: Omega-6 AA in meat and eggs. If present, Omega-3 EPA competes for COX-1 or COX-2 enzymes reducing their conversion of Omega-6 AA to PGF2α and other inflammatory /active eicosanoids: PG2, TX2,, LT4. and EX4.
TXA2 Thromboxane (TXA2 ==>TXB2)		Indirectly derived from: Omega-6 LA in nuts, seeds, vegetable oils, or legumes, or Omega-6 DGLA in breast milk, or GLA in borage, evening primrose or blackcurrant oil, which can all ultimately be converted to Omega-6 AA, and then to inflammatory /active eicosanoids: PG2, TX2 (incl. TXA2),, LT4. and EX4 via COX enzymes. However – this omega-6 AA pathway leading to more inflammatory eicosanoids competes with omega-3 presence for Δ5D, Δ6D and COX enzymes that prefer pathways to the more calming, anti-inflammatory PG1 (incl. PGE1), TX1, PG3, TX3 and LT5 series of eicosanoids. “EFA Conversion Chart” provides a visual aid to understanding these complicated, interacting conversion pathways.
T X A 2	BLOOD / LYMPH VESSELS	Vaso -constricting ECs via Cox2
T X A 2	PLATELETS	Blood clotting¹ Via Cox1 Involved in thrombosis
T X A 2	PLATELETS
T X A 2	VSMC proliferation	Cell proliferation aids damage repair. Involved in development of atherosclerosis;
T X A 2	VSMC proliferation
T X A 2	AIRWAYS
T X A 2	AIRWAYS	An anomaly is that bronchoconstriction is promoted by Cox-1 inhibitors (aspirin, traditional NSAIDs), but not selective Cox-2 inhibitors. Harrington, 2008
T X A 2	PLACENTA
T X A 2	PLACENTA
T X A 2	KIDNEY
T X A 2	KIDNEY
T X A 2	Macrophages
T X A 2	Macrophages

Series 3 PGs		Derived from: Omega-3 EPA e.g. in salmon, fish or krill oil, Brown / red algae. Grass-fed animals and poultry, land animals’ brains testes, adrenals, eyeballs. Mm Mmm Mmmmm! Compete for COX enzymes in prostanoid (prostaglandin and thromboxane) PG1, TX1, PG2/PG2, TX2 pathways to eicosanoids,
Series 3 PGs
		Fish oil capsules⁴
	MOST CELLS	Anti-inflammatory via Cox1 and Cox 2 COUNTER PG-2s / LT-4s. Compete for COX and 5-LO enzymes
	Leukotrienes
Series 4 LTs		Directly derived from: Omega-6 AA in meat and eggs. If present, Omega-3 EPA competes for 5-LO enzymes reducing their conversion of Omega-6 AA to inflammatory /active LT4 and also EX4 series eicosanoids.
Series 4 LTs		Indirectly derived from: Omega-6 LA in nuts, seeds, vegetable oils, or legumes, or Omega-6 DGLA in breast milk, or GLA in borage, evening primrose or blackcurrant oil, which can all ultimately be converted to Omega-6 AA, and then to inflammatory /active eicosanoids: series PG2 and TX2, via COX enzymes, or LT4 and EX4 via 5-LO enzymes. However – this omega-6 AA pathway leading to more inflammatory eicosanoids competes with omega-3 presence for Δ5D, Δ6D and COX and 5-LO enzymes that prefer pathways to the more calming, anti-inflammatory PG1 (incl. PGE1), TX1, PG3, TX3 and LT5 series of eicosanoids. “EFA Conversion Chart” provides a visual aid to understanding these complicated, interacting conversion pathways.
	AIRWAYS	Constricting
	AIRWAYS	Mast cells via 5-LO (concurrent release with histamine). Part of the inflammation response, especially in asthma and allergic rhinitis. Attract white blood cells to sites of tissue damage and cause smooth muscles to contract. LTC4 and LTD4 increase respiratory mucous secretion. PubMed

Series 5 LTs		Directly derived from: Omega-3 EPA e.g. in salmon, fish or krill oil, Brown / red algae. Grass-fed animals and poultry, land animals’ brains testes, adrenals, eyeballs. Mm Mmm Mmmmm! Compete for 5-LO enzymes in LT4, EX4 pathways to eicosanoids,
Series 5 LTs
	Mast cells via 5-LO Counters inflammation

	Specialized Pro-resolving Mediators (SPMs) Deal with reducing excessive tissue injury and resolving inflammation.
Lipoxins		Derived from: Omega-6 AA in meat and eggs
Lipoxins		With sufficient presence of omega-3 EPA : Indirectly derived from: Omega-6 LA in nuts, seeds, vegetable oils, or legumes or Omega-6 DGLA in breast milk or GLA in borage /evening primrose oil. Low dose aspirin can also trigger LIPOXIN synthesis
	Neutrophils	Via 15-LO From AA
	Erythrocytes, Reticulocytes	Via 12-LO From AA
	Platelets	Via 12-LO From LTA5

Resolvins (RVs)		Derived from:< Omega-3 EPA or DHA e.g. in salmon, fish or krill oil
		Newly discovered. Resolve inflammation, Clear away inflammation debris. Modulates immune system (IS). Serhan et al, 2000 Block prostanoid effects

Protectins (PDs)		Derived from:< Omega-3 EPA or DHA e.g. in salmon, fish or krill oil
	Tissue protective	Protectin D1 (derived from DHA) protects tissue including neuronal tissue from excessive damage Serhan et al. 2002
Eoxins (EXs)		Derived from: Omega-6 AA in meat and eggs (competing for
Eoxins (EXs)		With sufficient presence of omega-3 EPA: Indirectly derived from: Omega-6 LA in nuts, seeds, vegetable oils, or legumes or Omega-6 DGLA in breast milk or GLA in borage /evening primrose oil.
	Eosinophils (WBCs), Mast cells	Via 15-LO-1 Involved in asthma, lymphoma of Hodgkins disease, prostate cancer, colon cancer, and other cancers

References

Garza, Luis A.; et al. (2012, Mar 12). “Prostaglandin D Inhibits Hair Growth and Is Elevated in Bald Scalp of Men with Androgenetic Alopecia”. Science Translational Medicine. 4 (126): 126ra34.PubMed

Green, P., Gispan-Herman, I., & Yadid, G. (2005). Increased arachidonic acid concentration in the brain of Flinders Sensitive Line rats, an animal model of depression. Journal of lipid research, 46(6), 1093-1096. PubMed

Multiple functions of endothelial cells

¹Medical gallery of Blausen Medical 2014 CC BY 3.0

²Version 8.25 from the Textbook OpenStax Anatomy and Physiology (Altered) CC BY 4.0

³Guy Waterval, Apache License 2.0

⁴Fish oil capsules by SemtrioLicensed CC BY 2.0