Free radical scavengers: the bane of PGE2 (read to get your hopes crushed)

[beholder]

So I've been doing my homework regarding the available topical agents and dietary supplements with some potential for hair growth. And guess what, almost no good news.

I have found out that some of the most recommended anti-inflammation compounds and free radical scavengers (=antioxidants) that should be blocking PGD2 also block PGE2. Here is the list:

Melatonin - readily available at all pharmacies. Micromolar or greater concentrations of melatonin decreased significantly the conversion of [3H]-arachidonic acid to prostaglandin (PG) F2 and thromboxane (Tx) B2, and inhibited slightly the conversion to PGE2 and PGD2.
http://www.ncbi.nlm.nih.gov/pubmed/1795220
Furthermore, melatonin counteracts the inhibitory effect of PGE2 on IL-2 production in human lymphocytes via its mt1 membrane receptor.
http://www.ncbi.nlm.nih.gov/pubmed/12594180
This is quite disappointing, especially as melatonin has been shown to grow hair of men in a specialized study.

Resveratrol potently reduces prostaglandin E2 production and free radical formation in lipopolysaccharide-activated primary rat microglia.
http://www.jneuroinflammation.com/content/4/1/25
Very unfortunate. Resveratrol is obtainable as a pure extract online and in some specialized shops.

Quercetin suppresses Cyclooxygenase-2 expression and angiogenesis through inactivation of P300 signaling. It significantly suppressed COX-2 mRNA and protein expression and PGE2 production, as well as COX-2 promoter activation in breast cancer cells. Quercetin also significantly inhibited COX-2-mediated angiogenesis in human endothelial cells in a dose-dependent manner.
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0022934
Very disappointing. Quercetin is obtainable in some pharmacies and as a pure extract online.

Curcumin - inhibition of cell survival and induction of apoptosis by curcumin in colorectal adenocarcinoma cell lines is associated with the inhibition of PGE2 synthesis and down-regulation of COX-2.
http://www.ncbi.nlm.nih.gov/pubmed/16737669
Quite disappointing. Curcumin available as dieatary supplement, possibly also in large amounts somewhere.

Ascorbic acid (vitamin C) dose-dependently inhibited interleukin-1beta (IL-1beta)-mediated PGE2 synthesis in the human neuronal cell line. Furthermore it dose-dependentlyproduced a significant reduction in IL-1beta-mediated production of 8-iso-prostaglandin F2alpha (PGF2a), a reliable indicator of free radical formation, suggesting that the effects of ascorbic acid on COX-2-mediated PGE2 biosynthesis may be the result of the maintenance of the neuronal redox status since COX activity is known to be enhanced by oxidative stress.
http://arxiv.org/abs/0708.0548
This may not be as bad as it looks as the PGE2 synthesis in this particular case was mediated by IL1b and possibly by free radicals. It still is a small warning and a remainder for me to study this particular antioxidant some more. This because few other studies confirmed that L-ascorbic acid 2-phosphate or topical L-ascorbic acid should directly support hair growth:
http://www.ncbi.nlm.nih.gov/pubmed/20701628
http://www.jdsjournal.com/article/S0923-1811(05)00327-0/abstract
http://www.biomedcentral.com/1471-5945/4/13
Verdict - on hold. I am using it topically with MSM, I will know in 5 months. Available and overly expensive as a supplement in pharmacies but also very cheap in large amounts as a food additive.

Vitamin E (tocoferol, tocotrienol) - supplementation with vitamin E succinate resulted in a significant decrease in PGD2 levels, while PGF2alpha levels were significantly decreased. BL6-F10 cells supplemented with 7 and 10 microg/ml vitamin E succinate showed a marked increase in PGE2 levels with a significant increase occurring at 10 microg/ml. PGI2 levels followed a similar trend to PGE2 with a significant increase occurring at 10 microg/ml.
http://www.ncbi.nlm.nih.gov/pubmed/9223656
Verdict - cautious optimism. No real results related to hair loss/growth situation here. Available as supplement.

Vitamin D (calcitriol) - inhibiting COX-2 and stimulating 15-PGDH expression, calcitriol decreased the levels of biologically active prostaglandins in prostate cancer cells, thereby reducing the growth stimulation by prostaglandins. Calcitriol also inhibits the expression of the PG receptors EP2 and FP.
http://www.researchgate.net/profile...rostate_Cancer/links/00b4952b8b14f5d7f9000000
http://jn.nutrition.org/content/137/1/205S.full
http://www.ncbi.nlm.nih.gov/pubmed/16886660
Vitamin D available everywhere. And most possibly quite worthless for hairgrowth.

Green tea is also guilty, associated with a reduction in the levels of cyclooxygenase (COX)-2, prostaglandin (PG) E2 and PGE2 receptors (EP2 and EP4). Ingestion of green tea rapidly decreases prostaglandin E2 levels in rectal mucosa in humans.
http://www.ncbi.nlm.nih.gov/pubmed/10744131
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0025224


So how about that, hmm?

I believe that not everything is lost for these compounds. If you just want to stop you hairloss/shedding, you probably could use some kind of combination of a NSAID and some supplement of the above (particularly topical ascorbic acid should complement systemic NSAIDs nicely, perhaps along with topical calcitriol and melatonin). The results you will get from decreased COX-es could be visible on your hairloss/shedding within days, if not hours.

Hair growth is another chapter. Some of these compounds are downright unsuitable for any hair growth situation. I think we should look elsewhere [for hair growth].

 

[bushbush]

that should be blocking PGD2 also block PGE2.

This was also noted in the original Garza et al., paper (Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia.) for aspirin:

"Our results suggest that in mouse and human skin, a balance between PGE2 and PGD2 controls hair growth. This model predicts then that efforts to reverse alopecia should optimally focus on both enhancing PGE2 and inhibiting PGD2 signaling. This model also explains why agents such as aspirin, which inhibit upstream prostaglandin synthesis enzymes (PTGS1 and PTGS2), have minimal effects on hair growth because of likely equally decreased production of PGE2 and PGD2."

 

[beholder]

yep. It's by now a known fact for NSAIDs such as aspirin. This thread is about antioxidants and dietary supplements though.

 

[Iwantmyhairbacknow]

you think that it's the cure?

 

[beholder]

What's the cure? Cure to what? I didn't write about any cure.. I simply wrote about supplements which in combination with NSAIDs may halt hairloss (not necessarily grow hair). You would theoretically not have any PGD2 problem but Wnt signaling pathway would still be off, androgens would still be present and thus probably not all hairloss would be prevented.

This is exactly why no one got much results using the antioxidants or NSAIDs. Even if you turn off COX1 and COX2, there is still so much left to piece together in the great puzzle of Androgenetic Alopecia.

 

[karankaran]

Good post.

 

[abcdefg]

Why would someone that gets lots of these antioxidants in their diet or through supplements still go bald then? I know many men with fantastic diets with severe baldness at early age. They get most of these antioxidants daily in pretty decent amounts

 

[beholder]

exactly what I write here.. no antioxidant is a cure by itself. Not even together when they block COX1 and COX2 they will "cure" baldness. And if you add them to your regime, you can fk it up because they downregulate the PGE2 and thus hair can't grow well. So many guys did fk up their regimen by adding some of these and then wondered why the fk hair doesn't grow. Well that's why.

Diet is IMO not an answer, at least not in traditional sense. However I am not sure how many guys have tried some serious COX blocking via aspirin or other NSAIDs while also taking these other antioxidants/COX-blockers. I've seen some people's messages from 2012. They were trying this route [topical aspirin] and it didn't lead to complete regrowth so I guess they dropped it. I am inclined to believe that this is a good way for pure maintenance: keep COX1 and COX2 down, and keep PGD2 down that way at least to some extent.

I have experienced this also, after long-term daily 250mg aspirin use. But it's not enough for a man. I don't want maintenance, I want more growth. People say that if it doesn't fall out - it grows, I think that's bull. It grows VERY slowly. Looks like 3-5x slower than my facial hair.

I was checking out some other thing today: my 6 yo boy's hair. I lifted the hairs that cover his forehead and was surprised to find a dense underfur of smaller hairs, all about the same equal length (1.5-2cm). Looks like this small hair is like that of eyebrows or eye lashes hair: it never grows longer than some length (read: it falls out after a lot shorter time than the normal hair and possibly grows much slower). I am quite baffled by this and still thinking about what could it mean.. is this the hair that is first to be targeted by Androgenetic Alopecia? Are the underfur follicles different from normal hair follicles and do they have more expression for PGD2-related/androgen genes? Could it be possible we're waking them up by PGE2/minoxidil or by elliminating androgens/PGD2 effects? And last perhaps most important question: why doesn't the underfur want to grow beyond certain length?

 

[HairShocka]

Hi beholder. I am content with just maintaining hair or minimize hair loss. What do you suggest I do?

"If you just want to stop you hairloss/shedding, you probably could use some kind of combination of a NSAID and some supplement of the above (particularly topical ascorbic acid should complement systemic NSAIDs nicely, perhaps along with topical calcitriol and melatonin). The results you will get from decreased COX-es could be visible on your hairloss/shedding within days, if not hours."

When you say combination of NSAID and some supplements of the above, are you suggesting taking oral aspirin and a self-made topical consisting of asocorbic acid, calcitriol, melatonin. I know how to read, but just want to be clear.

Also, what do you currently use? I dropped Min and finasteride about 4-5 months ago after 20 months of use and now only on Keto. I'm in search for alternatives that I can continue to use and maintain hair.

Thank you much in advance.

 

[Koga]

Why did you drop finasteride/min ?

 

[HairShocka]

Why did you drop finasteride/min ?

Because the finasteride gave me brain fog, fatigue, crappy sex and the min made my skin's condition noticeably worse. I thought about staying on min but then I also realized that while it artificially kept hair that should be gone alive, in the process it was also making my scalp prone to more balding. I don't have all the scientific evidence to point you towards, but I believe minoxidil puts you in a worse position than if you were never on it after you quit.

 

[beholder]

Hi beholder. I am content with just maintaining hair or minimize hair loss. What do you suggest I do?

Thank you much in advance.

I am no dermatologist to suggest you medical advice however this is what I would do:

First I would immediately counter cyclooxygenases from which PGD2 is made. Using internal NSAID aspirin 125mg 2x daily. That's one quarter of a pill in the morning and in the early evening. Aspirin is pretty safe however a lot of care must be taken to eat it on full stomach as it decreses protective PGE2 functioning in stomach lining exposing you to a possible ulcer. This is what you can do today right after you finish reading this. Take it for at least 1 month to be sure of results. Then you can drop it and note changes in hair loss. Always do tests (pull tests, bath tub hair counting).

At the same time I would try some topical aspirin as well, it's easy to dissolve a pill in distilled water and make any concentration you want. Start with small concentration, like 0,01g / 1g of solvent. Then increase your dosage with subsequent batches to for example 0.05 / 1g of solvent. This is acid so always watch for skin redness or peeling. Topical aspirin should be very safe but still, take care.

Next, you can make a mixture of antioxidants and natural inflammation reducers. Of these most important are: C, D and hormone melatonin. Here is what I wrote in a private message a few days ago:

Ascorbic acid: get 1/2 kg of ascorbic acid food-additive. Not the one from pharmacy. Then solve 5 grams in 50 ml of distilled water, you get something like 10% concentrated solution. Keep the rest in fridge. Then take a few grams of MSM and try to dissolve it in that C solution (will not be easy as it's quite saturated already). Solve as much as you can, as much as it takes. MSM should help with skin penetration. Leave the unsolved crystals in for a day to see if they don't solve by themselves. Keep shaking ocassionally. If they don't solve, carefully take away the top layer of solution leaving crystals with only a little liquid on the bottom. Then you can dump the crystals directly on your head and massage them in. They will dissolve eventually later when you shampoo, doesn't matter. You can do the same thing with an alcohol+water solution (60% alcohol) if you'd like it to dry on head more quickly. But I have a feeling alcohol doesn't dissolve the chemicals as well as distilled water.

You can even experiment, one day make for example 15% or 20% water solution. It stings the head a little, but it's actually very nice feeling. I never peeled but I knew this is the percentage that is maximum effective for penetration (from one study on skin of pigs).

L-ascorbic acid must be formulated at pH levels less than 3.5 to enter the skin. Maximal concentration for optimal percutaneous absorption was 20%. Tissue levels were saturated after three daily applications; the half-life of tissue disappearance was about 4 days.

Add melatonin right into the C solution as well, in concentration of 0.005g of melatonin / 1g of solvent. You can up the dosage later if you want, to 0.010g / 1g of solvent later. Think like one 5mg pill for whole body, so 0.01 g / 1 g of solvent is A LOT -- 2 tablets per one milliliter of water. Hope I got the numbers down correctly. I am not even sure about the dosage and if it all dissolves but melatonin should be quite safe anyway. Filter out the tablets filler like described above, don't forget to put it on your head 1-2 hours before regular shampooing. Use melatonin internaly or externally only at night, before sleep.

Vitamin D will be a problem since it's usually distributed in capsules with oil (it's dissolved in the oil). I would open 1-3 capsules and simply dump them on head, massage them in. I would do this at home, a few hours before washing head with shampoo. Eat the used capsules. This kind of use would really nicely go with other anti-inflammatory extracts with resveratrol, quercetin and even perhaps silymarin. You can really add anything from the above to the goo which you then put on your head. With enough skill the application of 2-3 compounds takes you just 5 minutes. That is acceptable I think.

Don't forget to add from the rest of the ascorbic acid into every possible drink you drink (water, teas, softdrinks, etc.), i.e. never drink just plain tea or water, always fortify. It's very difficult to overdose on this antioxidant and it will be good for your health if you fortify your drinks all the time. That's why you bought it so cheaply!
http://www.profikoreni.cz/Kyselina-askorbova-500g-d940.htm

Keep up the keto.

 

[HairShocka]

Thank you for all the info beholder!

I have a few more questions:

How often do you use this solution?

Also, is topical aspirin a form a PGD2 blocker? I think you mentioned that aspirin also reduces production of PGE2 so why even bother with it?

I know the Cet craze has died down a while ago, but the guys that were trying it out seemed to have good vellus growth and claimed it maintained the hair they had. http://www.hairlosstalk.com/interac...r-Hair-Loss-instead-of-Finasteride-(Propecia)

Do you think this would work better than topical aspirin used in conjunction with the C solution you told me in your reply?

Thanks again.

 

[beholder]

well, if you try it you will find your hair so glued together that it's quite difficult to use it more than 2x a day (unless you wash your hair every day). However the correct answer would take in account the half-lives of the compounds. Aspirin has 3-30 hours (dose dependent), C is quite degradable but it's an immense amount you're putting on head. Melatonin has half life only in minutes [this might be information of half-life in body, not external or in skin] but I do believe at such a high dose we may be talking about hours. Don't worry about the rest of the compounds, they will be fine when taken topically.

The thing is you're using strong C potion which is an antioxidant by itself so it may keep others "alive" for a bit longer, especially in dead skin cells layer. Remember the skin saturation study, others saturate skin as well.

I put on my C solution twice or thrice a day, but I can afford it as I am working mostly from home. My hair looks completely ****ty whole day except the time I wash it and it's beautiful for just a few minutes.

Please don't use one solution for starters. You need to distinguish the sides so you need to keep them separate (they will mix in the skin anyway but that's not the point). The point is that if you get ANY sides, first stop using the aspirin potion and see what happens using only C+friends.

I love cetirizine and I am using it as well. But I thought you want only maintenance not regrowth. Cet might be good if you don't use aspirin etc, otherwise you may just get the same old maintenance. Remember, with PGD2 you're also negating PGE2 using NSAIDs and inflammation calmers. I don't use NSAIDs anymore, this weekend was an exception since I got fever, chills, sore throat for 3 days and feel like **** all the time. It's a laryngitis virus that makes you afraid of swallowing, that's how bad/painful it is. Almost like the damn rabies man. 3 days of this already, I am so fked. I used both NSAIDs I have here as well as paracetamol/acetaminophen. Hope internal melatonin helps with sleep otherwise tomorrow I will feel like sh!t again.

 

[Swoop]

Why do you focus so much on PGE2 and PGD2 though? Do you think that it will do much for hair if you get a perfect pgd2/pge2 ratio and why? Nonetheless good post about compounds affecting these pathways!

 

[beholder]

Thank you for all the info beholder!

Also, is topical aspirin a form a PGD2 blocker? I think you mentioned that aspirin also reduces production of PGE2 so why even bother with it?

Nope, aspirin is a COX1 and COX2 blocker. COX-es make the PGs. So you downturn both good and bad PG. My self-verified theory is that aspirin may just keep PGD2 from harming (while C helping aspirin at it according to one study). So you get maintenance, just not hair growth. Don't be mistaken, your hair will still look bad. But you may stop the shedding, if I am right. Perhaps also in combination with anti-androgenic effects of C. I am too tired to post studies links today but they are easy to find on the web. I also posted them in other threads.

FYI, I had no minoxidil shedding pre- or post-minoxidil. Thanks to internal aspirin and others I think (mainly internal silymarin). NONE I think. I may just be a non-responder, but then why the hairs don't fall out anymore? I look forward to the day I resume minoxidil + sildenafil experiment, as sildenafil proved to be a blessing as well. Check out my other thread for it, I have some more to write about soon but not right now, as I am too fked up.

 

[Quantum Cat]

wasn't somebody developing a med that suppressed PGD2? what happened to that? still in trials?

 

[beholder]

BTW, I am also thinking about the theory that PGD2 and PGE2 are both young birds which try to get as much food from parent (you, duh) while stealing it from each other. So if you upregulate PGE2, PGD2 goes down AUTOMATICALLY, as it is made from the same precursor [PGH2] but via different enzyme. This would also explain why frequent inflammation marker PGE2 serves for hair growth. And vice versa, perhaps.

But THE HYDRA (=Androgenetic Alopecia) is not so simple I guess. Wish it would be. Haha, PGD2 as a cuckoo brood parasite, I bet no one thought about that analogy before!

- - - Updated - - -

wasn't somebody developing a med that suppressed PGD2? what happened to that? still in trials?

Yep, PGD2 [GPR44/DP2] receptor antagonist exists and not just one. But all are expensive and unavailable. Blame FDA I guess. This whole PGD2 blocker business looks like a fcking conspiracy against mankind.

We also have PTGDS antibodies as well, all expensive as hell.

All no-go, in my opinion.

The aliens in US government don't want us to have them.

 

[bushbush]

Why do you focus so much on PGE2 and PGD2 though? Do you think that it will do much for hair if you get a perfect pgd2/pge2 ratio and why? Nonetheless good post about compounds affecting these pathways!

http://www.ncbi.nlm.nih.gov/pubmed/22440736 This paper explains why.

 

[beholder]

Why do you focus so much on PGE2 and PGD2 though? Do you think that it will do much for hair if you get a perfect pgd2/pge2 ratio and why? Nonetheless good post about compounds affecting these pathways!

This thread talks about compounds that inhibit both. As for the "golden PGE/PGD ration", well, that sounds like cut off from some advertisement on the new hairloss cure. Your body is more messy than that. Each follicle may be different, there may be classes of follicles we have no idea yet they exist. I do believe there are alopecia zones on our skulls.

Thanks for kind words thought. This puzzle is consuming me, literally. I almost sign every post with blood today. :x