The precise cause of male pattern baldness has been discussed and researched for decades. But only in recent years have we started to pinpoint precisely what causes the vast majority of hair loss. And we’re getting close…

there is more PGD2 in the scalps of bald men than in the scalps of men with hair

There have been speculations that reducing scalp DHT may be the key to curing hair loss but recent discoveries show that ‘prostaglandin D2’ might be just as important, or perhaps more so.

A paper from 2012 (Garza et al.) made the connection between prostaglandin D2 (PDG2) and hair loss, concluding that PGD2 might be the real key to curing androgenic alopecia. However, new research shows that increasing PGE2 (another prostaglandin found in the scalp) might be just as important in curing baldness and maintaining healthy hair.

The paper states (Garza et al. 2012) that there is more PGD2 in the scalps of bald men than in the scalps of men with hair. Clearly there is a link, but is it a causal link?

To sum it up in plain English and simplify:

High scalp PGD2 = hair loss
High scalp PGE2 = hair growth

Does decreasing scalp PGD2 and increasing scalp PGE2 cause hair to regrow?

In order to decrease PGD2 researchers tested COX1/COX2 inhibitors that also inhibited the production of PGE2, which shows that inhibiting PGD2 isn’t enough for a complete treatment and a dual approach to increase PGE2 and decrease PGD2 should be more efficacious.

The beneficial effects of PGE2 can be seen in a series of research papers. For example, Malkinson et al. (1993) have shown that prostaglandins, especially topical applications of PGE2 make for good radio-protective agents.

After the administration of topical applications of PGE2 Malkinson’s team saw that the areas were protected from radiation but also that there was an enhanced post-radiation hair regrowth.

Another study has found that elevated PGE2 levels in mice helped with tissue regeneration and it may help with hair regeneration. (Zhang et al.2015)

Anyone up to date with the latest research sees the link between PGE2 and baldness so the logical question is, how do we increase PGE2 in the scalp?

Increasing PGE2

Synthetic PGE2 Powder

You can buy synthetic PGE2 powder that contains the most biologically active prostaglandin and it’s used by scientists in various experiments. There is no standardized medical protocol for applying PGE2 powder to the scalp but there are studies showing topical application of PGE2 for treating vitiligo (a skin condition characterized by patches of pale color) by using a gel with high skin permeation that contains PGE2. (Kapoor et al. 2008; Parsad et al.2002) Synthetic PGE2 has a potency of 0.25-100 ng/mL and can be bought online.

Bimatoprost

Latisse bimatropost

Bimatoprost, also known as Latisse, is an effective treatment for intraocular pressure and glaucoma in adults. Researchers have proposed this drug for hair loss treatment and early stage trials seem promising. The drug thickens and lengthens the eyelashing by increasing PGE2 and PGF2 so in theory, the treatment should have similar effects in the scalp.

the treatment had amazing effects: the hair follicles stayed in anagen significantly longer and in vivo showed one third more hair growth

A huge upside to this treatment is that there are almost no side effects and since it can be applied topically by the patient it is easy to use at home. There was recent clinical trial (late 2016) to develop this into a marketed hair loss treatment. (Allergan 2016)

Previous studies have shown that the drug can grow human hair in vitro and mouse hair in vivo and the treatment had amazing effects: the hair follicles stayed in anagen significantly longer and in vivo showed one third more hair growth with bimatoprost treatment. (Karzan et al. 2013)

The results of the clinical trials on humans have shown that Bimatoprost 1% and Bimatoprost 3% result in superior hair growth when comparing the results with Minoxidil 5% results but further research on more people needs to be completed to provide stronger support for these statements. In any case, this shows that Bimatoprost might be the next big hair loss treatment.

Ginger root

its potential to increase PGE2 has been shown in studies

Ginger is a herbaceous perennial plant, which is a common ingredient in Asian cuisine. Ginger root has been a traditional Asian remedy for hair loss, and even though its effects on the human scalp haven’t been properly researched its potential to increase PGE2 has been shown in studies. Research shows that the plant has an anti-inflammatory effect and increases PGE2 (Shivanad, 2005) (Joland 2004).

A research on the effects of powdered ginger on the PGE2 levels in the gastric mucus production, scientists used aspirin to inhibit PGE2 production in the gastric mucus but when ginger was administered, the aspirin failed to inhibit PGE2 production. Also, when only ginger root was administered the mucus showed elevated levels of PGE2. (Wang et al., 2011)

So we have some pretty reasonable evidence that ginger increases PGE2 and may therefore be a useful topical.

Sulfasalazine

their hair had regrown after long term baldness

Sulfasalazine is an anti-inflammatory drug used for rheumatoid arthritis, colitis or Crohn’s disease. The drug is known to increase PGE2 (Wittenberg et al., 1991; Sharon et al., 1978; ) Several case reports of people taking sulfasalazine for one of the illnesses above noticed their hair had regrown after long term baldness.

An uncontrolled study of sulfasalazine in 39 patients with alopecia areata showed that sulfasalazine increased hair regrowth of more than 60% in 25.6% of the patients who participated in the study while 30.7% of the patients had a moderate response to the drug. (Rashidi and Mahd, 2008)

6 of them (6 of 22 patients) achieving complete hair regrowth

Another study that used sulfasalazine as a hair loss treatment was conducted on 26 patients during a period of 3 years and according to the results, the patients were grouped into 3 categories: no hair regrowth <10% terminal hair, partial hair regrowth 10%-90% terminal hair and complete hair regrowth 90-100% hair regrowth. Only 22 of the patients completed the treatment and 68.2% which accounted for 15 of 22 patients responded to therapy with 6 of them (6 of 22 patients) achieving complete hair regrowth and 40.9 of them partial hair regrowth. (Aghaei, 2008)Both studies concluded that sulfasalazine could be considered as an alternative treatment to hair loss and although its mechanism is not completely known it is very likely to be linked to PGE2.

Castor Oil

Organic castor oil

Castor oil is a vegetable oil that is obtained by pressing the seeds of the Ricinus communis plant. It’s used as traditional medicine for a number of ailments including baldness with self-reporting cases all over the internet showing its effects. The mechanism behind hair loss might be its ability to increase PGE2 as research has shown. Studies on pregnant rats have shown that feeding them castor oil increases PGE2 synthesis. (Gao et al., 1999) (Tunaru et al.,2012 ) Although it hasn’t been studied as an actual treatment castor oil has been used topically for years without any side effects so giving it a try wouldn’t do any harm.

References and further reading

  1. Malkinson FD, Geng L, Hanson WR. Prostaglandins protect against murine hair injury produced by ionizing radiation or doxorubicin. J Invest Dermatol. 1993 Jul;101(1 Suppl):135S-137S. https://www.ncbi.nlm.nih.gov/pubmed/8326147
  2. Yongyou Zhang, Amar Desai, Sung Yeun Yang, Ki Beom Bae, Monika I. Antczak,Stephen P. Fink, Shruti Tiwari, Joseph E. Willis, Noelle S. Williams, Dawn M. Dawson,David Wald, Wei-Dong Chen, Zhenghe Wang, Lakshmi Kasturi, Gretchen A. Larusch,Lucy He, Fabio Cominelli, Luca Di Martino, Zora Djuric, Ginger L. Milne, Mark Chance, Juan Sanabria, Chris Dealwis, Debra Mikkola, Jacinth Naidoo, Shuguang Wei, Hsin-Hsiung Tai, Stanton L. Gerson, Joseph M. Ready, Bruce Posner, James K. V. Willson,Sanford D. Markowitz. Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration Science 12 Jun 2015: Vol. 348, Issue 6240, DOI: 10.1126/science.aaa2340 http://science.sciencemag.org/content/348/6240/aaa2340
  3. Kapoor, R., Phiske, M.M. and Jerajani, H.R. (2009), Evaluation of safety and efficacy of topical prostaglandin E2 in treatment of vitiligo. British Journal of Dermatology, 160: 861–863. doi:10.1111/j.1365-2133.2008.08923.x http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2133.2008.08923.x/abstract
    http://www.sigmaaldrich.com/catalog/product/sigma/p0409?lang=en&region=RO
    https://clinicaltrials.gov/show/NCT01904721
  4. Khidhir, K. G., Woodward, D. F., Farjo, N. P., Farjo, B. K., Tang, E. S., Wang, J. W., … Randall, V. A. (2013). The prostamide-related glaucoma therapy, bimatoprost, offers a novel approach for treating scalp alopecias. The FASEB Journal, 27(2), 557–567. http://doi.org/10.1096/fj.12-218156 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3545535/
    https://clinicaltrials.gov/ct2/show/NCT02170662
  5. Shivanand D. Jolad, R. Clark Lantz, Guan Jie Chen, Robert B. Bates, Barbara N. Timmermann, Commercially processed dry ginger (Zingiber officinale): Composition and effects on LPS-stimulated PGE2 production, Phytochemistry, Volume 66, Issue 13, July 2005, Pages 1614-1635, ISSN 0031-9422, http://dx.doi.org/10.1016/j.phytochem.2005.05.007.(http://www.sciencedirect.com/science/article/pii/S0031942205002244)
  6. Jolad SD, Lantz RC, Solyom AM, Chen GJ, Bates RB, Timmermann BN. Fresh organically grown ginger (Zingiber officinale): composition and effects on LPS-induced PGE2 production.
    Phytochemistry. 2004 Jul;65(13):1937-54. https://www.ncbi.nlm.nih.gov/pubmed/15280001
  7. Zhongzhi Wang, Junichi Hasegawa, Xinhui Wang, Akiko Matsuda, Takahiro Tokuda, Norimasa Miura and Tatsuo Watanabe Protective Effects of Ginger against Aspirin-Induced Gastric Ulcers in Rats Yonago Acta medica 2011;54:1119 https://www.researchgate.net/publication/256541300_Protective_Effects_of_Ginger_against_Aspirin-Induced_Gastric_Ulcers_in_Rats
  8. Wittenberg HR, Kleemeyer K, Peskar BM, Peskar BA. [Effect of sulfasalazine and its metabolites on prostaglandin and leukotriene liberation from human synovial tissue]. Wien Klin Wochenschr. 1991;103(2):34-9. German. https://www.ncbi.nlm.nih.gov/pubmed/1673814
  9. Sharon P, Ligumsky M, Rachmilewitz D, Zor U. Role of prostaglandins in ulcerative colitis. Enhanced production during active disease and inhibition by sulfasalazine. Gastroenterology. 1978 Oct;75(4):638-40. https://www.ncbi.nlm.nih.gov/pubmed/30669
  10. Ashidi, T. and Mahd, A. A. (2008), Treatment of persistent alopecia areata with sulfasalazine. International Journal of Dermatology, 47: 850–852. doi:10.1111/j.1365-4632.2008.03700.x https://www.ncbi.nlm.nih.gov/pubmed/18717871
  11. Aghaei S. An uncontrolled, open label study of sulfasalazine in severe alopecia areata. Indian J Dermatol Venereol Leprol [serial online] 2008 [cited 2017 Jan 11];74:611-3. Available from: http://www.ijdvl.com/text.asp?2008/74/6/611/45103
  12. Tunaru S, Althoff TF, Nüsing RM, Diener M, Offermanns S.Castor oil induces laxation and uterus contraction via ricinoleic acid activating prostaglandin EP3 receptors Proc Natl Acad Sci U S A. 2012 Jun 5;109(23):9179-84. doi: 10.1073/pnas.1201627109. http://www.pnas.org/content/109/23/9179.full.pdf
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