Androgenic alopecia (AGA), also called male-pattern baldness, is the most common form of hair loss and has been associated with other dysfunctions such as coronary heart disease and an enlarged prostate.
It seems that PGD2 prevents the hair follicles from maturing
There have been numerous studies concerning androgenic alopecia but more data is needed to clearly establish a true underlying cause — the key thing(s) that differentiate(s) those with a predisposition from those without.
How to Trigger Rapid Hair Growth
In 2012, the University of Pennsylvania published a breakthrough study concluding that PGD2 was found in higher levels than normal in the scalps of balding men. It seems that PGD2 prevents the hair follicles from maturing. This means that the PGD2 inhibits the follicles from growing hair. In mice studies with explanted hair, when PGD2 was applied topically, it clearly inhibited hair growth. PGD2 causes hair loss when it binds to a receptor called GPR44; when activated by high levels of PGD2 the receptor inhibits hair growth. (Garza et al., 2012)
How does PGD2 cause hair loss?
As far as I know, there’s still no research that has been able to conclusively explain exactly why or how PGD2 causes hair loss. This led some researchers to question whether increased scalp PGD2 actually causes hair loss or whether increased PGD2 is just a side effect of some other cause of hair loss (such as DHT or inflammatory cytokines). However, at least one study has conclusively shown that PGD2 does actually cause hair loss (or at least prevent hair growth) when it binds with the GPR44 receptors in the scalp.
we tested the effect of PGD2 on mouse models with inactivating mutations in each of the receptors for PGD2— PTGDR(DP-1) or GPR44 (DP-2). While PTGDR was not required for PGD2 to inhibit hair growth, GPR44 was required. Recent work from our group has shown that just as PGD2 and GPR44 inhibit hair growth, they also inhibit hair follicle regeneration after wounding
There are, however, supplements that are considered PGD2 blockers
There are many products marketed for hair loss prevention — some contain substances to improve circulation in the scalp, others contain DHT blockers.
Since PGD2’s relation to hair loss is a recent discovery, there haven’t been many products on the market to address this particular issue. There are, however, supplements that are considered PGD2 blockers and could be used by those experiencing hair loss.
A study has analyzed the 289 constituents of 12 selected herbs to see whether they would work as PDG2 inhibitors. The properties were analyzed for skin permeability, sensitization, irritation, corrosion, mutagenicity, tumorigenicity and reproductive effects. Although many were found to have PGD2 inhibition, many caused adverse reaction and also poor skin permeability. Among them, ricinoleic acid, acteorside, amentoflavone, quercetin and hinokiflavone were good inhibitors with minimal adverse skin reactions (Fong et al., 2015) and may be safe and efficient for hair loss treatments. But, without further studies regarding their efficacy in hair loss treatment or at least new research confirming their effect on PGD2, some of the inhibitors presented above remain a mystery.
Fortunately, there are other PGD2 inhibitors that may have the answer to our hair loss problem, at least with more research behind them to support their effect as inhibitors.
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The Most Effective PGD2 Inhibitors
Perhaps the most well-known ‘PGD2 inhibitor’ is the anti-allergy medication Setipiprant. Setipiprant doesn’t actually reduce PGD2, but instead it inhibits PGD2 receptor activity, reducing the action of PGD2 in the scalp.
It seems there are several anti-allergy drugs that have been effective at treating hair loss, either dues to the reduction of PGD2, PGD2 receptors or anti-inflammation. See cetirizine and ramatroban, which work in similar ways.
Eicosapentaenoic acid is an omega-3 fatty acid that has been known to inhibit PGD2. It is a polyunsaturated fatty acid that reduces PGD2 generation in response to IgE-anti-IgE challenge incubation. It is also suggested that endogenous EPA diet supplementation might reduce PGD2 production. (Obata et al., 1999) It is contained in various oily fish and fish oil such as cod liver, herring, mackerel, salmon, menhaden and sardine, as well as seaweed and phytoplankton. (Natural Medicines Database, 2016)
Resveratrol is a naturally occurring phytoalexin that is produced by some spermatophytes such as grapevines, in response to injury. It can be found in small traces in white wine, but it’s more abundant in red wine. There are other fruits and oils that contain minimal traces of resveratrol. It is a known antioxidant and has been shown to modulate the metabolism of lipids and inhibit the oxidation of low-density lipoproteins and aggregation of platelets. (Fremont, 2000)
A study in 2014 and one in 2016 concluded that resveratrol suppresses PGD2-stimulated OPG synthesis through inhibiting p38 MAP kinase and SAPK/JNK in osteoblasts (Kuroyanagi, Gen et al., 2014), as well as the fact that Resveratrol as a therapeutic agent could inhibit PGD2-mediated inflammation. (Devon et al., 2016)
Quercetin is a pigment, also known as a flavonoid, which gives plants their colors. Flavonoids are antioxidants and are known for their neutralizing effects against free radicals. (Boots, Haenen and Bast, 2008) There are several studies showing that Quercetin is effective in reducing PGD2.
A study published in 2012 on contact dermatitis and photosensitivity argued that Quercetin can effectively inhibit secretion of histamine and PGD2. When compared to Cromolyn, Quercetin significantly decreased contact dermatitis and photosensitivity and was argued to be a promising candidate as an effective mast cell inhibitor through sufficient oral absorption. (Weng et al., 2012)
Another study supports these claims as it concluded that Quercetin can eliminate erythema and burning due to niacin in patients with coronary artery disease by inhibiting PGD2. (Kalogeromitros et al., 2008)
There is also a treatment model for alopecia areata with quercetin based on studies in mice. The mice were treated with subcutaneous quercetin and hair regrowth was observed in lesional areas. The study also showed that a systematic delivery of quercetin through intraperitoneal injections prevented and reduced the spontaneous onset of alopecia areata. (Wikramanayake et al., 2012)
Quercetin is found in various foods, from broccoli, berries, apples to tea and red wine. It can also be added as a dietary supplement. (Erdman et al., 2007)
Cromolyn sodium is an anti-inflammatory medication used for asthma. Cromolyn is also a PGD2 inhibitor, however, not as good as Quercetin, according to a study in 2012. (Weng et al., 2012)
Just as other flavonoids in this list, Luteolin has been found to inhibit PGD2 in various studies. A study involving niacin-induced skin temperature shows that the increase in temperature is associated with PGD2 and 5-ht elevations. Rats that received Luteolin had levels of PGD2 and 5-ht inhibited by 100 and 67%, respectively. (Papaliodis et al., 2009)
Another study published in 2000 in Clinical & Experimental Allergy Journal (Kimata et al.,) supports the same findings showing that luteolin and quercetin are potent inhibitors in the release of histamine, leukotrienes, PGD2 and GM-CSF from HCMC in a concentration-dependent manner.
Topical application or dietary supplement
Studies suggest that some flavonoids such as quercetin could be used effectively as topical medication rather than supplements, so that people experiencing hair loss could benefit from an increased effect. When it comes to skin conditions quercetin is efficient in inflammatory skin diseases (Caddeo et al., 2014) as well as to control UVB-mediated oxidative damage of the skin (Casagrande et al.,), so topical application of these flavonoids might be more efficient than using them as dietary supplements. In alopecia areata, subcutaneous injections showed induced hair regrowth in preexisting alopecic lesions (in mice). (Wikramanayake et al., 2012)
Future research and FDA approved medication
Although these PGD2 inhibitors have been shown to work, their full effect is not known since there aren’t many clinical trials on humans regarding their effect on hair loss. Fortunately, for those waiting for approved medication for their conditions, a new drug, called Setipiprant, currently under clinical trial should be released in the next years. The drug was initially researched for the treatment of allergies and inflammatory disorders such as asthmas but was discontinued. In the light of new research concerning PGD2 inhibitor and male pattern baldness, the medication is now in trial. (2016, http://www.kythera.com/products/kyth-105-setipiprant/ )
- Krupa Shankar, D., Chakravarthi, M., & Shilpakar, RMale Androgenetic Alopecia: Population-Based Study in 1,005 Subjects. International Journal of Trichology, 1(2), 131–133. (2009) http://doi.org/10.4103/0974-7753.58556 Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938575/
- Garza LA, Liu Y, Yang Z, et al., Prostaglandin D2 Inhibits Hair Growth and Is Elevated in Bald Scalp of Men with Androgenetic Alopecia. Science Translational Medicine. 2012;4(126):126ra34. doi:10.1126/scitranslmed.3003122. Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319975/
- Fong P, Tong HH, Ng KH, Lao CK, Chong CI, Chao CM, In silico prediction of prostaglandin D2 synthase inhibitors from herbal constituents for the treatment of hair loss. Journal of Ethnopharmacology, 2015, Dec 4;175:470-80. doi: 10.1016/j.jep.2015.10.005 Link: http://www.ncbi.nlm.nih.gov/pubmed/26456343
- Obata T., Nagakura T., Masaki T., Maekawa K., Yamashita K. Eicosapentaenoic acid inhibits prostaglandin D2 generation by inhibiting cyclo-oxygenase-2 in cultured human mast cells. Clin. Exp. Allergy. 1999;29:1129–1135. doi: 10.1046/j.1365-2222.1999.00604.x. Link: http://www.ncbi.nlm.nih.gov/pubmed/10457118
- Eicosapentaenoic acid – Natural Medicines Comprehensive Database Link: http://naturaldatabase.therapeuticresearch.com/nd/Search.aspx?cs=&s=ND&pt=100&id=994&fs=ND&searchid=57146335
- Fremont Lucie, Biological effects of resveratrol, Life Sciences Volume 66, Issue 8, 14 January 2000, Pages 663-673 Link: http://www.sciencedirect.com/science/article/pii/S0024320599004105
- Gen Kuroyanagi, Jun Mizutani, Akira Kondo, Naohiro Yamamoto, Rie Matsushima-Nishiwaki, Takanobu Otsuka, Osamu Kozawa, Haruhiko Tokuda, Suppression by resveratrol of prostaglandin D2-stimulated osteoprotegerin synthesis in osteoblasts Prostaglandins, Leukotrienes and Essential Fatty Acids ,2014 Volume 91 , Issue 3 , 73 – 80 Link: http://www.plefa.com/article/S0952-3278(14)00072-6/abstract
- Devon Shirley, Cody McHale, Gregorio Gomez, Resveratrol preferentially inhibits IgE-dependent PGD2 biosynthesis but enhances TNF production from human skin mast cells, Biochimica et Biophysica Acta (BBA) – General Subjects, Volume 1860, Issue 4, April 2016, Pages 678-685, ISSN 0304-4165, http://dx.doi.org/10.1016/j.bbagen.2016.01.006. Link: http://www.sciencedirect.com/science/article/pii/S0304416516000155
- Agnes W. Boots, Guido R.M.M. Haenen, Aalt Bast, Health effects of quercetin: From antioxidant to nutraceutical., European Journal of Pharmacology, Volume 585, Issues 2–3, 13 May 2008, Pages 325-337, ISSN 0014-2999, http://dx.doi.org/10.1016/j.ejphar.2008.03.008.Link: http://www.sciencedirect.com/science/article/pii/S0014299908002884
- Weng Z, Zhang B, Asadi S, Sismanopoulos N, Butcher A, Fu X, et al., (2012) Quercetin Is More Effective than Cromolyn in Blocking Human Mast Cell Cytokine Release and Inhibits Contact Dermatitis and Photosensitivity in Humans. PLoS ONE 7(3): e33805. doi:10.1371/journal.pone.0033805 Link: http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0033805
- D. Kalogeromitros, M. Makris, C. Chliva, X. Aggelides, D. Kempuraj, T. C. Theoharides, A quercetin containing supplement reduces niacin-induced flush in humans, Int J Immunopathol Pharmacol. 2008 Jul-Sep; 21(3): 509–514. Link: http://www.ncbi.nlm.nih.gov/pubmed/18831918
- Erdman JW, Jr, Balentine D, Arab L, Beecher G, Dwyer JT, Folts J, Harnly J, Hollman P, Keen CL, Mazza G, Messina M, Scalbert A, Vita J, Williamson G, Burrowes J. Flavonoids and heart health: proceedings of the ILSI North America Flavonoids Workshop. J Nutr. 2007;137:718S–737S. Link: http://www.ncbi.nlm.nih.gov/pubmed/17311968
- Wikramanayake, T. C., Villasante, A. C., Mauro, L. M., Perez, C. I., Schachner, L. A., & Jimenez, J. J. (2012). Prevention and treatment of alopecia areata with quercetin in the C3H/HeJ mouse model. Cell Stress & Chaperones, 17(2), 267–274. http://doi.org/10.1007/s12192-011-0305-3
- Papaliodis, D., Boucher, W., Kempuraj, D. and Theoharides, T. C. (2008), The flavonoid luteolin inhibits niacin-induced flush. British Journal of Pharmacology, 153: 1382–1387. doi: 10.1038/sj.bjp.0707668 Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2437911/
- Kimata, Shichijo, Miura, Serizawa, Inagaki and Nagai (2000), Effects of luteolin, quercetin and baicalein on immunoglobulin E-mediated mediator release from human cultured mast cells. Clinical & Experimental Allergy, 30: 501–508. doi:10.1046/j.1365-2222.2000.00768.x http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2222.2000.00768.x/abstract