great info here on pdg2 its not as simple as simply lowering pdg2 and raising pge2
As has been stated before its the ratio between the two as stated many times before but worth a revisit for the newbies. who may go NUTS as they think seti is not working!!!!
http://www.life-enhancement.com/mag...may-be-surprisingly-beneficial-to-your-health
taken from the above link
THE KEY TO UNDERSTANDING THE EFFECTS OF THE PGD2-CAUSED NIACIN FLUSH IS TO REALIZE THAT IN ITS ACUTE RELEASE, PGD2 ACTS IN MANY MODEL SYSTEMS AS AN ANTI-INFLAMMATORY. IN ITS CHRONIC RELEASE, PGD2 APPEARS TO BE USUALLY PRO-INFLAMMATORY, but depending on the rate at which PGD2 is released, the amount released, and the state of inflammation in the tissue where it is released, you can get a pro-inflammatory or an anti-inflammatory effect. As the old saying goes, the devil is in the details and it is the rush to avoid considering the details so as to rapidly develop a non-flushing niacin that is leading to the rash abandonment by some drug companies and health practitioners of flushing (immediate-release or plain) niacin.
It has long been known that the prostaglandins PGD2 and PGE2 are responsible for inflammation induction (Haworth, 2007). Later in the biosynthetic pathways of these prostaglandins, anti-inflammatory circuits are induced (Haworth, 2007). Here is where we believe is the source of a major misunderstanding concerning the pro-inflammatory or anti-inflammatory effects of PGD2, the prostaglandin that causes the niacin flush: A CHRONICALLY HIGH LEVEL OF A SIGNALING MOLECULE, SUCH AS PGD2 (generally pro-inflammatory when at a chronically high level) CAN INTERFERE WITH SIGNALS BY ACUTELY RELEASED (PULSATILE) AMOUNTS OF THAT SIGNALING MOLECULE (generally anti-inflammatory) BY THE ACUTE SIGNAL SIMPLY BEING “LOST” IN THE NOISE OF THE CHRONICALLY HIGH LEVEL OF THAT MOLECULE. Hence, we think that chronically high levels of PGD2 are likely to prevent or reduce the effect of acute signals of PGD2 that would otherwise be anti-inflammatory. See sections on Alzheimer’s disease (AD) below, where chronically high PGD2 signaling is thought to be a major cause of the neurodegenerative features characteristic of AD (Maesaka, 2013).
now as it relates to scalp
MALE PATTERN BALDNESS (Nieves, 2014)
The hair follicle in male pattern baldness balding areas (but not in normal hair of balding men) have chronically high levels of prostaglandin D2 accompanied by lower levels of prostaglandin E2. One way that minoxidil has been found to work is by *increasing prostaglandin E2, which in this model “normalizes” the PGD2/PGE2 ratio. However, PGE2 is an inflammatory molecule, so you wouldn’t want to increase it very much, and that is undoubtedly the “secret” of minoxidil, to NORMALIZE the ratio of PGD2/PGE2 so as to eliminate a chronically high PGD2 level.
* can someone confirm this is true? PGE2 has an upper limit that shouldn't be raised too much?
One of the signals of the catagen phase of hair growth, where hair growth ceases for a time and some hair follicles die, is the release of very large amounts (7 fold higher than baseline) of PGD2 (Nieves, 2014). For that reason, there is interest in blocking PGD2 as a “treatment” for balding. But once again, there is a risk that blocking PGD2’s unwanted effects will also block important beneficial effects of PGD2. This, not surprisingly, is a major problem in medicine, that the change you want in a certain tissue at a certain time and by a certain amount may cause harm elsewhere where you do not want that change.
Nieves and Garza. Does prostaglandin D2 hold the cure to male pattern baldness? Exp Dermatol. 23(4):224-7 (2014).
and this
and a bit more here....
A signaling system is reported here (Woodling, 2014) that the authors found to regulate an important protective anti-inflammatory mechanism in the early stages of Alzheimer pathology that decreases significantly (along with its protective effect) as the disease progresses. This is a signal from the prostaglandin PGE2 to its EP4 receptor. See section below on the PGE2 receptor system (EP1, 2, 3, and 4) and new findings suggesting that it is a key to some of the antiinflammatory properties of DHA (docosahexaenoic acid, an omega 3 fatty acid found in fish oils) and possibly that of curcumin.
As reported in a 2012 paper (Ruan, 2012), the EP1 receptor for PGE2 appears to be the key target for DHA and fish oils. There they showed that, in cultured stromal cells, the IC50 for fish oil (that is, the amount that inhibited 50% of the PGE2 activity) was 18 mg/L or 54 μM. The authors calculated that, for a 150 pound human containing 4-5 liters of blood, “consuming 100 mg. fish oil should yield IC50 results.” (This depends, of course, on how the DHA partitions in the blood and tissues, but the calculation provides a crude estimate.) The authors then indicate that they would recommend taking 500-1000 mg fish oil daily on the basis of their findings.
It is interesting to note the opposing effects of PGD2 (the prostaglandin that induces the niacin flush) and PGE2 in the balding model (above), where chronically high PGD2 resulted in suppression of PGE2. A pulsatile release of PGD2 (an ACUTE release) as in the niacin flush would be anti-inflammatory, not pro-inflammatory as with chronically high PGD2. *Hence, you could see an INCREASE in PGE2 by suppressing chronically high PGD2. The balding model, in fact, shows hair growth and the cessation of hair follicle death resulting from slight modulation in the ratio of PGD2/PGE2, in which PGE2 is increased, while chronically high PGD2 levels are reduced to “normalize” the ratio. The niacin flush causes pulsatile, not chronic, release of PGD2. It is relevant to note that another paper (see just below) describes CHRONICALLY high PGD2 signalling in full-blown Alzheimer’s.
* what is the normal RATIO though??????
As has been stated before its the ratio between the two as stated many times before but worth a revisit for the newbies. who may go NUTS as they think seti is not working!!!!
http://www.life-enhancement.com/mag...may-be-surprisingly-beneficial-to-your-health
taken from the above link
THE KEY TO UNDERSTANDING THE EFFECTS OF THE PGD2-CAUSED NIACIN FLUSH IS TO REALIZE THAT IN ITS ACUTE RELEASE, PGD2 ACTS IN MANY MODEL SYSTEMS AS AN ANTI-INFLAMMATORY. IN ITS CHRONIC RELEASE, PGD2 APPEARS TO BE USUALLY PRO-INFLAMMATORY, but depending on the rate at which PGD2 is released, the amount released, and the state of inflammation in the tissue where it is released, you can get a pro-inflammatory or an anti-inflammatory effect. As the old saying goes, the devil is in the details and it is the rush to avoid considering the details so as to rapidly develop a non-flushing niacin that is leading to the rash abandonment by some drug companies and health practitioners of flushing (immediate-release or plain) niacin.
It has long been known that the prostaglandins PGD2 and PGE2 are responsible for inflammation induction (Haworth, 2007). Later in the biosynthetic pathways of these prostaglandins, anti-inflammatory circuits are induced (Haworth, 2007). Here is where we believe is the source of a major misunderstanding concerning the pro-inflammatory or anti-inflammatory effects of PGD2, the prostaglandin that causes the niacin flush: A CHRONICALLY HIGH LEVEL OF A SIGNALING MOLECULE, SUCH AS PGD2 (generally pro-inflammatory when at a chronically high level) CAN INTERFERE WITH SIGNALS BY ACUTELY RELEASED (PULSATILE) AMOUNTS OF THAT SIGNALING MOLECULE (generally anti-inflammatory) BY THE ACUTE SIGNAL SIMPLY BEING “LOST” IN THE NOISE OF THE CHRONICALLY HIGH LEVEL OF THAT MOLECULE. Hence, we think that chronically high levels of PGD2 are likely to prevent or reduce the effect of acute signals of PGD2 that would otherwise be anti-inflammatory. See sections on Alzheimer’s disease (AD) below, where chronically high PGD2 signaling is thought to be a major cause of the neurodegenerative features characteristic of AD (Maesaka, 2013).
now as it relates to scalp
MALE PATTERN BALDNESS (Nieves, 2014)
The hair follicle in male pattern baldness balding areas (but not in normal hair of balding men) have chronically high levels of prostaglandin D2 accompanied by lower levels of prostaglandin E2. One way that minoxidil has been found to work is by *increasing prostaglandin E2, which in this model “normalizes” the PGD2/PGE2 ratio. However, PGE2 is an inflammatory molecule, so you wouldn’t want to increase it very much, and that is undoubtedly the “secret” of minoxidil, to NORMALIZE the ratio of PGD2/PGE2 so as to eliminate a chronically high PGD2 level.
* can someone confirm this is true? PGE2 has an upper limit that shouldn't be raised too much?
One of the signals of the catagen phase of hair growth, where hair growth ceases for a time and some hair follicles die, is the release of very large amounts (7 fold higher than baseline) of PGD2 (Nieves, 2014). For that reason, there is interest in blocking PGD2 as a “treatment” for balding. But once again, there is a risk that blocking PGD2’s unwanted effects will also block important beneficial effects of PGD2. This, not surprisingly, is a major problem in medicine, that the change you want in a certain tissue at a certain time and by a certain amount may cause harm elsewhere where you do not want that change.
Nieves and Garza. Does prostaglandin D2 hold the cure to male pattern baldness? Exp Dermatol. 23(4):224-7 (2014).
and this
and a bit more here....
A signaling system is reported here (Woodling, 2014) that the authors found to regulate an important protective anti-inflammatory mechanism in the early stages of Alzheimer pathology that decreases significantly (along with its protective effect) as the disease progresses. This is a signal from the prostaglandin PGE2 to its EP4 receptor. See section below on the PGE2 receptor system (EP1, 2, 3, and 4) and new findings suggesting that it is a key to some of the antiinflammatory properties of DHA (docosahexaenoic acid, an omega 3 fatty acid found in fish oils) and possibly that of curcumin.
As reported in a 2012 paper (Ruan, 2012), the EP1 receptor for PGE2 appears to be the key target for DHA and fish oils. There they showed that, in cultured stromal cells, the IC50 for fish oil (that is, the amount that inhibited 50% of the PGE2 activity) was 18 mg/L or 54 μM. The authors calculated that, for a 150 pound human containing 4-5 liters of blood, “consuming 100 mg. fish oil should yield IC50 results.” (This depends, of course, on how the DHA partitions in the blood and tissues, but the calculation provides a crude estimate.) The authors then indicate that they would recommend taking 500-1000 mg fish oil daily on the basis of their findings.
It is interesting to note the opposing effects of PGD2 (the prostaglandin that induces the niacin flush) and PGE2 in the balding model (above), where chronically high PGD2 resulted in suppression of PGE2. A pulsatile release of PGD2 (an ACUTE release) as in the niacin flush would be anti-inflammatory, not pro-inflammatory as with chronically high PGD2. *Hence, you could see an INCREASE in PGE2 by suppressing chronically high PGD2. The balding model, in fact, shows hair growth and the cessation of hair follicle death resulting from slight modulation in the ratio of PGD2/PGE2, in which PGE2 is increased, while chronically high PGD2 levels are reduced to “normalize” the ratio. The niacin flush causes pulsatile, not chronic, release of PGD2. It is relevant to note that another paper (see just below) describes CHRONICALLY high PGD2 signalling in full-blown Alzheimer’s.
* what is the normal RATIO though??????
