Niacin Induces Pgd2 Flush Through Dp2 Receptor. Thoughts?

[ZenHead]

Hey everyone, long time lurker here. I've been following this forum for a few months now, and would like to thank some of you for all the information you've gathered. I've been scouring the internet and educating myself on the science of hair loss for the past few months, and would like to revisit the famous (or infamous) study done by Dr. George Cotsarelis "Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319975/

As I'm sure many of you are aware, PGD2 and PGE2 play a significant role in androgenic alopecia. People with this disease have highly elevated PGD2 levels and significantly lower PGE2 levels. Interestingly enough, one mechanism in which minoxidil works is to increase PGE2 (Nieves, 2014). Just like minoxidil, niacin is also a vasodilator (widens blood vessels and improves circulation).
When taking niacin, you will most likely experience a "flush". This is the itchy, hot sensation in your skin caused by a release of PGD2 from mast cells. Now in the human body, there are 2 types of PGD2 receptors - DP1 and DP2. Cotsarelis showed that the DP2 receptor (and not DP1) is involved in hair growth downregulation. DP1 is not shown to be involved with hair loss. Now this is where niacin comes into play - it flushes PGD2 through the DP1 receptor, the one that has nothing to do with hair loss. This action makes PGD2 less available for the "bad" receptor (DP2) to use, theoretically having a positive affect on hair loss.

I have not tested this theory personally. All I have done is read scientific studies to try to understand the process of prostaglandins in hair loss. I'm posting this to have a mature, scientific conversation about how niacin flushing may or may not help our situation. I am aware that this has been discussed on other forums, but in light of new information on the link between PGD2 and hair loss I figured this could be a worthy discussion. Sorry about this lengthy post but I believe this might be a piece of the puzzle. Please let me know your thoughts!

 

[whatevr]

Now this is where niacin comes into play - it flushes PGD2 through the DP1 receptor, the one that has nothing to do with hair loss.

I want to know the source for this. Is this just your speculation or did you find any evidence for that ?

 

[ZenHead]

I got this information through this article, at
The bottom of the “Prostaglandins involved in flushing” section: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2779993/#!po=24.6667
“These experiments indicate that PGD2 and PGE2, signalling through the DP1, EP2 and EP4receptors, are likely responsible for the flushing side effects of niacin.”

I understand that we don’t want to “flush” PGE2, but this quote is also interesting:
“The production of PGI2 and PGD2 decreases after repetitive administration of niacin in parallel with the development of flushing tolerance”
Maybe this could be a natural way to reduce PGD2 with repetitive use?

 

[IdealForehead]

I don't know. Niacin is complicated in part because there are so many forms and derivatives.

I have always focused on niacinamide as it is the best overall form in my opinion. Overall there is more evidence in favor of hair benefit for topical use than against.

It is anti-wrinkle, anti-aging. It improves blood supply. There are studies on niacin derivatives showing growth stimulation of hair. It reduces sebum production. It is anti-acne which is a partially androgen driven process. It helps repair damaged DNA.

Here's a summary here of some of the hair research:

http://www.regrowth.com/hair-loss-forums/topic/david-sinclair-defends-niacinamide/

I've read so much on niacinamide and you won't find a concrete answer on much with this stuff, but it's dirt cheap, easily soluble in water/alcohol, commonly used in many major brand shampoos, and generally good for skin. Probably overall good for hair too.

Probably be careful not to reduce everything to basic prostaglandins. Some compounds have complex effects through multiple pathways and this is one of them.

I use 5% topically in my solutions both for my face skin and my hair.

 

[ZenHead]

Never thought about putting niacinamide in topical solutions, but it makes a lot of sense since it increases circulation via vasodilation. Maybe this could increase the effectiveness / absorption.

 

[HairCook]

Niacinamide topical is nothing really new. It is apparently supposed to thicken your hair.
There was supposed to be a taiwanese study even which never happed to take place.

Orally, the flush effect is an entire different topic, maybe stick to that here.
I wouldnt do the flush daily cause it can lead to insulin resistance.

It seems also that it activates to some extent a PGE2 cascade, however not as far as PGD2 which increases even in Langerhans cells.
I wonder what this mean for hair loss. maybe we flush PGD2 into outer (irrelevant?) cells and replace it with a touch of PGE2? Not sure :/

I think swiss and his forum were against niacin however I still wonder. I do it like once or twice a week since like a month already.

For ppl who didnt know about the flush, see this video:

 

[ZenHead]

Wouldn’t this be exactly what we want though? Flushing the PGD2 from the langherhans cells into the bloodstream through the DP1 receptor? That means that the langherhans cells would be depleted of PGD2 and would need to synthesize more. This is all speculation but maybe combined with a DP2 receptor antagonist like Setipiprant / ramatroban, this could improve results. Either way, I’ll continue to flush regularly as part of my regimen. I think Swiss was incorrect about avoiding the flush. It makes too much sense to me to not be beneficial

 

[HairCook]

Wouldn’t this be exactly what we want though? Flushing the PGD2 from the langherhans cells into the bloodstream through the DP1 receptor? That means that the langherhans cells would be depleted of PGD2 and would need to synthesize more. This is all speculation but maybe combined with a DP2 receptor antagonist like Setipiprant / ramatroban, this could improve results. Either way, I’ll continue to flush regularly as part of my regimen. I think Swiss was incorrect about avoiding the flush. It makes too much sense to me to not be beneficial

People who dislike the flush take aspirin, it blocks Cox1 and 2, with that also PGD2 and PGE, hence you wont flush. In other words, once we get a real CRTH2 inhibitor niacin would be history I assume.

 

[ZenHead]

True. Real CRTH2 (aka DP2) receptor antagonists are the future. I actually think they are the best treatment “available” at the moment, although incredibly expensive. High dose Setipiprant seems to completely stop shedding and even reverse it a little bit. Exciting to see more updates on that stuff. In the mean time I’ll be messing around with niacin and seeing if it does any good. @HairCook do you use niacin in topical ssolutions? Thinking about adding it to my zix which I just stared

 

[HairCook]

Not yet. I am going to get it soon mixed in with l-threonate(for dkk1) and some other stuff. Not sure when I get that topical though it is some private testing. However I doubt that topical has works the same way as the flush.

 

[ZenHead]

Not yet. I am going to get it soon mixed in with l-threonate(for dkk1) and some other stuff. Not sure when I get that topical though it is some private testing. However I doubt that topical has works the same way as the flush.

This is off topic but what is dkk1?

 

[HairCook]

This is off topic but what is dkk1?

https://www.ncbi.nlm.nih.gov/pubmed/22358062

 

[badhabiz]

People who dislike the flush take aspirin, it blocks Cox1 and 2, with that also PGD2 and PGE, hence you wont flush. In other words, once we get a real CRTH2 inhibitor niacin would be history I assume.

https://www.ncbi.nlm.nih.gov/pubmed/27554763

unf "We show that low-dose aspirin inhibits systemic PGE2 biosynthesis by 45% in healthy volunteers "

have you found a topical niacin high % topical? or someone did?

 

[Capone]

https://www.ncbi.nlm.nih.gov/pubmed/27554763

unf "We show that low-dose aspirin inhibits systemic PGE2 biosynthesis by 45% in healthy volunteers "

have you found a topical niacin high % topical? or someone did?

Would topical aspirin work and how to make it?

 

[badhabiz]

Would topical aspirin work and how to make it?

i don't know.
from what we know now, you would want to raise pge2 and lower pgd2, talking about PG and hair. so aspirin seems to be great friend of your penis rather than your hair, beacause of its cox inhibition.
niacin seems to be beneficial to both, since its action well explained above.

 

[Chronic Tronic]

What i find interesting is that Luteolin and Quercetin, both powerful pgd2 inhibitors, are shown to prevent the "niacin flush". But they block pgd2 significantly, i wonder how that works

https://www.ncbi.nlm.nih.gov/m/pubmed/18831918/


Hmm...

 

[HairCook]

What i find interesting is that Luteolin and Quercetin, both powerful pgd2 inhibitors, are shown to prevent the "niacin flush". But they block pgd2 significantly, i wonder how that works

https://www.ncbi.nlm.nih.gov/m/pubmed/18831918/


Hmm...

Actually it works as stated. COX produces prostaglandins. Cox gets inhibited by them hence the flush doesnt occur. you can do the same with anti-histamines from what I know. Dunno if you still get the same benefits without flush for cholesterol control etc though.

Flush is still a mystery to me if its hair beneficial or negative. I actually stumbled the other day about a paper showing that PGE2 actually might be responsible for the flush and not as long believed pgd2. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2912194/)

In the end, niacin is probably too cheap to further research and recently there seems to be some wind against it (as use for high cholesterol) as it seems to also have negative effects on insulin sensitivity someone might better go keto when you take dutasteride at the same time.

 

[HairCook]

i don't know.
from what we know now, you would want to raise pge2 and lower pgd2, talking about PG and hair. so aspirin seems to be great friend of your penis rather than your hair, beacause of its cox inhibition.
niacin seems to be beneficial to both, since its action well explained above.

If you want a friend for penis and hair, tadalafil should be your friend. Nitric oxide is great for both

 

[Chronic Tronic]

Actually it works as stated. COX produces prostaglandins. Cox gets inhibited by them hence the flush doesnt occur. you can do the same with anti-histamines from what I know. Dunno if you still get the same benefits without flush for cholesterol control etc though.

Flush is still a mystery to me if its hair beneficial or negative. I actually stumbled the other day about a paper showing that PGE2 actually might be responsible for the flush and not as long believed pgd2. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2912194/)

In the end, niacin is probably too cheap to further research and recently there seems to be some wind against it (as use for high cholesterol) as it seems to also have negative effects on insulin sensitivity someone might better go keto when you take dutasteride at the same time.

A lot of people have lost hair doing keto. It's good to cut carbs but i wouldnt want to force my body into ketosis. It's very stressful to the body

 

[balda]

Niacin works, niacinamide seems doesn't. And it supposed to be taken orally. Seen a research of topical application with no positive results.

Be happy having a flush ) That's how it works, removing PGD2. Previously was thought it generates PGD2, what is bad. But later researches have shown that Niacin "flush" it out. As a result there is less inflammation in dermal adipose tissue. And less new fibrosis. Final effect could be compared to finasteride, only without hormonal tricks.

Daily regimen (niacin, not niacinamide!):
- 1gm
- on empty stomach
- don't eat right after
- better before sleep, as it can cause sedative effects.

Here is a hypothesis, why and how it works:

https://www.hairlosstalk.com/interact/threads/dwat-dermal-white-adipose-tissue-hypothesis.130609