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PGD2 Enzyme & Hair Loss: Is There a Link?

There are so many solutions for hair loss out there.

But, addressing the root cause of your hair loss is sure to be worth your time and effort.

For some, this may be resolving one tiny issue: elevated levels of Prostaglandin D2 (PGD2).

In this article, you’ll learn what PGD2 is, how it contributes to hair loss, and practical ways to lower it.

Just keep reading!

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What Is PGD2?

PGD2 is a prostaglandin. Prostaglandins are molecules in the body responsible for mediating inflammation.

All prostaglandins are created by two things: arachidonic acid (AA) and cyclooxygenase enzymes (COX).

AA is an omega-6 fatty acid that is converted from dietary linoleic acid. It interacts with COX enzymes to generate prostaglandins for the whole body.

Different prostaglandins contribute a different degree of inflammation. Generally, some are less inflammatory or anti-inflammatory while some are more inflammatory.

PGD2 is one of the more pro-inflammatory prostaglandins. It’s released primarily by mast cells and macrophages which are inflammatory cells responsible for immune reactions like allergies and general inflammation.

Structure of prostaglandin D2
The structure of prostaglandin D2 (PGD2).

Mast cells, when activated, release mediators of allergic reactions like histamine. However, they also secrete PGD2.

These immune cells are unique in that they are activated by immunoglobulin E (IgE), an antibody that is created in response to certain allergens (1). They can also be activated by pathogens like bacteria, viruses, and mold, as well as a peptide that regulates pain called substance P (2, 3).

Key Takeaways:

  • PGD2 is a mediator of inflammation created from AA and COX enzymes. PGD2 is generally a pro-inflammatory prostaglandin.
  • It is primarily released by mast cells, immune cells which are responsible for reactions like allergies and general inflammation.
  • Mast cells can be activated by IgE, bacteria, viruses, mold, and substance P.
  • PGD2 can also be secreted by other immune cells like macrophages.

How Does PGD2 Cause Hair Loss?

Both macrophages and mast cells are known to be present around the hair follicle and believed to play a role in its cycling (4, 5).

This is not surprising considering one of mast cell’s major roles is promoting angiogenesis, a process crucial to enhancing blood circulation the follicle (6). Circulation provides the nutrition that hair follicles need to generate and maintain hair growth.

Macrophages also play a key role in signaling hair growth (5).

But, it’s likely that abnormal overactivity of these immune cells could contribute to hair loss. This is in part due to the excessive release of PGD2.

But, how exactly does PGD2 contribute to hair loss?

Analyses of Androgenetic Alopecia (AGA) scalps, a type of hair loss connected to male hormone (androgen) activity, show us that PGD2 is elevated in this condition (6).

One of PGD2’s effects on the scalp is increasing testosterone activity (7). This prostaglandin produces free radicals which are known to stimulate the activity of androgens through various mechanisms.

Free radicals are also known to be toxic to various components of the hair follicle.

Cells before and after free radicals

For example, dermal papilla cells (DPCs), the cells responsible for signaling hair growth, are sensitive to free radical damage (8). This is demonstrated by a balding scalp’s reduced signaling ability and its association with higher levels of free radical damage.

Free radicals can almost stimulate the cell death of many other hair follicle cells.

Moreover, free radicals can stimulate the production of PGD2 (9).

PGD2 and its degradation products are also activators of a transcription factor called PPAR-γ. This leads to the expression of genes that stimulate the growth of the sebaceous gland (10).

It’s unclear whether or not the sebaceous gland growth and the subsequent increased oil production contributes to AGA. Some researchers believe it’s simply a byproduct of AGA while others suggest it may actually worsen AGA.

Proponents of the latter indicate that sebum production allows a strain of bacteria called P. acnes to colonize the hair follicle. Excess oil not only provides the food for this bacteria but can also deoxygenate the follicle, allowing P. acnes to proliferate further.

P. acnes, in normal physiological concentrations, is not usually an issue. However, when it overgrows, it releases excessive amounts of inflammatory byproducts that may stimulate PGD2-producing immune cells like macrophages (11).

The microbiome might also play a role in PGD2-mediated hair loss.

One study explored this link in psoriasis, an inflammatory skin disease (12). The authors of this study hypothesize that alterations in the microbiome lead to increased intestinal permeability, allowing bacteria to migrate from the gut (where they belong) into systemic circulation.

A woman suffering from scalp psoriasis
A woman suffering from psoriasis on the scalp and neck.

The researchers emphasize that these bacteria are in a “dormant” state that contributes to low-grade systemic inflammation in the body. They also suggest that certain events can trigger the awakening of these microbes and cause them to shed their extremely inflammatory outer casing called lipopolysaccharides (LPS).

Although psoriasis is very different from AGA, this research explains how gut dysbiosis can contribute to inflammatory responses in the skin. AGA could have similar implications, considering the critical involvement of inflammation in its development.

Substance P, a peptide responsible for transmitting pain, may also be involved in hair loss. Substance P release is known to be mediated by psychoemotional stress (13).

Substance P also stimulates mast cell activation, which can lead to the production and secretion of PGD2 (14, 15).

One study emphasizes this connection, stating that telogen effluvium (TE; a type of hair loss characterized by many anagen (growing) hairs transitioning to the telogen (resting) phase at once) is mediated by substance P mast cell activation (16). This is consistent with findings that show elevated levels of mast cells in TE scalps.

Another animal study is in line with this theory. Researchers observed that chronic restraint stress in mice led to substance P mast cell activation, free radical production, and subsequent hair growth inhibition (17).

Mold exposure could also contribute significantly to PGD2-mediated hair loss (18). Mold spores activate receptors on mast cells that induce PGD2 synthesis and secretion.

Considering this research, it is clear that immune cell activation, namely macrophages and mast cells, may contribute to hair loss via PGD2. However, many factors can influence immune cell activation and, thus, resolving excess PGD2 is highly individual.

Key Takeaways:

  • Macrophages and mast cells play a part in hair follicle cycling, although abnormal overactivity of these cells could lead to hair loss due to elevations in PGD2 levels.
  • PGD2 increases testosterone activity via free radical production which has implications in AGA. Free radicals themselves are also toxic to various cells of the hair follicle.
  • PGD2 and its metabolites may stimulate the growth of the sebaceous gland and increase sebum output. Increased sebum production may contribute to inflammation via facilitating P. acnes overgrowth.
  • Changes in the microbiome may lead to gut barrier permeability. Dormant microbes can leak out into systemic circulation via this leaky barrier, contributing to low grade systemic inflammation. Certain events may also trigger these dormant microbes to shed their outer LPS casing, which can activate mast cells to secrete PGD2.
  • Substance P increases in response to psychoemotional stress and is an activator of mast cells. This mast cell activation leads to PGD2 production and free radical damage, which may connect the dot between stress and hair loss.
  •  Mold spores activate receptors on mast cells that induce PGD2 synthesis and secretion.
  • There are various stimulants of mast cell and macrophage activation, so resolving PGD2 excess as a result of overactivity is highly individual.

How to Lower PGD2 Naturally

PGD2 may mediate various forms of hair loss.

Although, the causes of PGD2 excess is highly individual and may require different approaches for each person.

Nonetheless, there are some practical ways you may be able to lower PGD2 naturally.

Omega-3 Fatty Acids

Omega-3 fatty acids are potent anti-inflammatory molecules (19). They work in various ways to lower inflammation.

Omega-3s, specifically DHA and EPA, downregulate the production of pro-inflammatory prostaglandins. They also upregulate the production of less or anti-inflammatory prostaglandins as well as resolvins and protectins that help resolve inflammation.

Overall, they have a beneficial anti-inflammatory effect.

A platter of foods contain Omega 3 fatty acids

In one mast cell culture study, the addition of EPA downregulated PGD2 production in response to mast cell activation (20). Both DHA and EPA may also reduce PGD2 secretion by macrophages (21).

This suggests that omega-3s may reduce mast cell and macrophage-derived PGD2.

Omega-3s can be obtained via consumption of wild-caught fatty fish like salmon and tuna as well as fish oil supplementation.

Key Takeaways:

  • Omega-3s are potent anti-inflammatories that work through various mechanisms.
  • Cell culture studies suggest EPA lowers PGD2 secretion by mast cells and both DHA and EPA may lower PGD2 secretion by macrophages.
  • Omega-3s can be obtained via consumption of wild-caught fatty fish like salmon and tuna as well as fish oil supplementation.

Turmeric

Turmeric is a golden spice that contains concentrated curcuminoids that help fight inflammation.

Sliced turmeric

In one cell culture study, curcumin inhibited mast cell activation and reduced PGD2 production in a dose-dependent manner (22). This means that the more curcumin present, the more PGD2 decreases.

This mast cell-suppressant effect has been confirmed in various other studies (23, 24).

Curcumin also inhibits COX enzyme activity, reducing the bioavailability of the precursors for PGD2 (25).

Curcumin can be consumed through using turmeric in food, however, it can also be consumed as a supplement. When supplementing, look for a liposomal turmeric formulation like Meriva® to enhance absorption (26).

Key Takeaways:

  • Turmeric curcuminoids help fight inflammation.
  • In cell culture studies, curcumin inhibits mast cell activation, reduces PGD2 dose-dependently, and decreases COX enzyme activity.
  • Curcumin can be consumed through using turmeric in food. When supplementing, look for a liposomal turmeric formulation like Meriva® to enhance absorption.

Hemp-Derived CBD

Cannabidiol (CBD) is a cannabinoid found in the industrial hemp plant at high quantities.

CBD, as well as the other minor cannabinoids in hemp, is well-known for its anti-inflammatory action through the endocannabinoid system (ECS) (27).

The ECS is a group of receptors distributed throughout the body that are responsible for influencing various bodily functions. It is mainly comprised of CB1 and CB2 receptors, but the ECS also includes TRPV and PPAR receptors.

All hemp cannabinoids have an affinity for CB1 receptors and can modulate their activity, leading to different downstream effects. One of the actions CB1 receptors may be involved in is mast cell activation (28).

Research suggests activation of CB1 receptors by cannabinoids, like the hemp-derived variety, may suppress mast cell activation.

To garner the most benefit from hemp-derived CBD, you’ll want to invest in a full spectrum hemp extract. This allows a phenomenon called The Entourage Effect to take place (29). The Entourage Effect of cannabinoid synergy produces greater beneficial effects than CBD on its own.

In other words, you get more bang for your buck.

Key Takeaways:

  • CBD and the other minor cannabinoids can modulate CB1 receptors that may result in mast cell suppression.
  • To make the most of the effects of CBD, take advantage of the Entourage Effect by utilizing full spectrum hemp extracts as opposed to CBD isolates.

Probiotics

There is a robust body of evidence that indicates probiotics can help maintain the integrity of the gut barrier (30). These beneficial bacteria release byproducts that help prevent damage to the gut lining while also facilitating barrier repair and maintenance.

Healthy intestinal permeability prevents microbes from translocating to systemic circulation where they have the potential to stimulate inflammation.

Probiotic foods

Probiotics can be consumed through traditional probiotic supplements and fermented foods like sauerkraut, kefir, yogurt, kombucha, and kimchi.

Key Takeaways:

  • Probiotics maintain the integrity of the gut barrier, preventing microbes from translocating to systemic circulation where they have the potential to stimulate inflammation.
  • Sources of probiotics include: sauerkraut, kefir, yogurt, kombucha, and kimchi.

Antioxidants

A lot of the damaging effects of PGD2 are due to downstream free radical generation.

To combat these negative effects, antioxidant-rich foods and foods that bolster natural cellular antioxidant systems can be consumed.

Some foods that provide antioxidant support to the body are:

  • Berries
  • Broccoli sprouts
  • Dark chocolate
  • Green tea
  • Coffee
  • Turmeric
  • Leafy greens
  • Cruciferous vegetables
  • Allium vegetables like garlic and onion
  • Wild-caught salmon and shellfish
  • Vitamin-E rich nuts and seeds

Including these foods help to reduce the oxidative stress load on the body, mitigating the consequences of PGD2 production.

Key Takeaways:

  • Some of the damaging effects of PGD2 production are due to downstream free radical generation.
  • Including antioxidant-rich foods and foods that suppport the natural antioxidant systems of the body help mitigate the consequences of PGD2 production.

Deep Breathing

Emotional stress is a trigger for substance P transmission that activates mast cells and PGD2 production. For this reason, taking action to reduce stress may be beneficial to alleviate PGD2-associated symptoms.

Deep breathing is a technique that you can employ to reduce stress. Slow, deep breathing has been shown to improve heart rate variability, a marker of healthy stress levels (31).

Some holistic experts also suggest that it activates nerves in the base of the stomach that encourage parasympathetic activity. This is the branch of the nervous system activated during restful conditions.

Key Takeaway: Deep breathing helps promote healthy stress levels which may reduce substance P transmission and subsequent mast cell activation and PGD2 production.

Putting the Pieces Together: Can Lowering PGD2 Prevent Hair Loss?

According to research, PGD2 is a definite mediating factor in hair loss.

However, the reasons for elevated PGD2 are highly individual and may be caused by numerous different factors.

So, while lowering PGD2 may reduce hair loss, finding the underlying cause of your elevated PGD2 is a tough undertaking.

Nonetheless, implementing tools to lower PGD2 could be beneficial for hair growth.

Have you determined PGD2 as the root of your hair loss? Leave a comment down below.

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