Increase Scalp PGE2 (and Decrease PGD2): The Cure for Hair Loss?

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

How does PGE2 increase hair growth?

PGE2 activates the Wnt signalling pathway in the hair follicles.

Activating the Wnt pathway is critical for hair growth. I’ll be publishing a write up explaining how to do this in the next week. Check back soon.

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 PGD2, which shows that inhibiting PGD2 isn’t enough for a complete treatment and a dual approach that increases PGE2 and decreases 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.

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Bimatoprost

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

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.

What are prostaglandins?

Prostaglandins are a group of naturally occurring lipid compounds that play a crucial role in various physiological processes in the body. They are derived from fatty acids and are involved in regulating inflammation, blood flow, and a wide range of cellular activities. Prostaglandins are produced and released by cells throughout the body in response to various stimuli and act as signaling molecules to mediate a variety of responses.

Here are some key characteristics and functions of prostaglandins:

Inflammatory Response: Prostaglandins are known for their involvement in the inflammatory response. They are produced at sites of tissue injury or infection and contribute to the redness, heat, swelling, and pain associated with inflammation. They also help recruit immune cells to the site of injury.

Vasodilation and Vasoconstriction: Prostaglandins can influence blood vessel dilation (vasodilation) and constriction (vasoconstriction). They help regulate blood flow and blood pressure in different tissues and organs.

Fever and Pain: Prostaglandins are involved in the regulation of body temperature (fever) and the perception of pain. Some pain-relief medications, such as non-steroidal anti-inflammatory drugs (NSAIDs), work by inhibiting the production of prostaglandins.

Gastrointestinal Protection: Certain prostaglandins help maintain the integrity of the stomach lining by promoting mucus production and reducing acid secretion, protecting the stomach from damage.

Reproductive Function: Prostaglandins are involved in several aspects of reproductive function, including uterine contractions during childbirth and the regulation of the menstrual cycle.

Immune Response: Prostaglandins play a role in modulating immune responses and inflammation, which are important for the body’s defense against infections.

Respiratory Function: Prostaglandins can influence the contraction of smooth muscles in the respiratory tract, affecting airway size and airflow.

Wound Healing: Prostaglandins are involved in various stages of the wound healing process, including inflammation, tissue repair, and blood vessel formation.

Prostaglandins are classified into different types (e.g., PGD, PGE, PGF) based on their chemical structures, and each type can have distinct effects on the body. The regulation of prostaglandin production is tightly controlled, and imbalances can lead to various health issues. As a result, medications that target prostaglandin pathways are used to manage conditions such as inflammation, pain, and fever.