Category Archives: Vascular Endothelial Growth Factor (VEGF)

How Does Minoxidil Work for a Receding Hairline?

This post on how does Minoxidil work was originally written in 2014. It has now been updated with newer studies discussing Minoxidil’s mechanism of action in stimulating hair growth.

Minoxidil Chemical Structure

Minoxidil (brand name Rogaine) is known to be one of only two medications officially approved for hair loss treatment (the other being Finasteride).

Minoxidil was first approved by the US FDA to treat hair loss in men in 1988. In 1991 the product was also made available for women with hair loss. Make sure to read my post on whether Minoxidil can grow a beard.

Also see some before and after results of patients on Minoxidil and/or Finasteride.

How does Minoxidil Work?

Scientists do not know the exact mechanism via which Minoxidil® has a positive effect on hair growth. However, there are a number of proven mechanisms of action that suggests how Minoxidil stimulates hair growth.

The original use of Minoxidil was as an oral medication for high blood pressure. The side effect of hypertrichosis (excessive body hair) led to its becoming a popular treatment option for hair loss.

To date, the main hypothesis about how Minoxidil works relates to its vasodilatory, potassium channel opening and increased blood flow effects. There are also other theories about how Minoxidil helps grow scalp hair, and further below I have outlined all of the main ones.

It should be noted that Minoxidil, besides prolonging the growth phase of the hair cycle, has also been shows to increase the diameter of existing hair follicles. According to a study from 1988, seven subjects who received a 5 percent dose of minoxidil had a mean hair shaft diameter of 0.029 mm before treatment, which then increased to 0.043 mm at 12 weeks.

Minoxidil and Hair Growth Studies

The current findings provide evidence that minoxidil could be used to treat both cancer and age-related disease, and open a new avenue for applications of minoxidil in treating androgen-AR pathway-related diseases.

Minoxidil enhances hair keratinocyte proliferation and activates hDP cells to induce growth factors. IGF-1 is among these growth factors, and has been shown to exhibit a potent hair elongation effect.

Minoxidil Side Effects

In general, topical Minoxidil is well tolerated in most people at the typical 5% dosage. Most people even tolerate higher concentration levels of the drug. However, some people will get side effects.

The most common entail adverse skin reactions such as burning, itching, redness and stinging in the areas of application. Another common complaint is an increase in body hair growth after taking Minoxidil, especially in the forehead, eyebrow and beard regions.

In rare instances, people complain about dizziness or breathing difficulties after taking Minoxidil. Allergic reactions, including rashes, are also possible in some cases. Please see a doctor immediately if you get such serious side effects. Also make sure to stop using this medication right away.

Minoxidil Shedding

Some people will shed a lot of hair after changing their Minoxidil® dosage. For those who quit Minoxidil entirely, a major shed of scalp hair is almost always guaranteed. Sometimes this can take weeks or even months after drug use cessation. In many instances, sheds are temporary and just the regular part of the hair cycle.

Minoxidil Toxicity in Cats

If you own pets, note that Minoxidil® is very poisonous to some animals, especially cats. If your cat is exposed to Minoxidil via a spill or accident, some side effects to look out for include:

  • Fatigue and lethargy.
  • Changes in heart rate due to cardiac damage.
  • Dehydration.
  • A drop blood pressure (hypotension).
  • Coughing.
  • Changes in appetite.

Prompt action and treatment by a veterinarian will prevent your cat from dying. If the medication was applied topically, make sure to wash the cat’s paws and fur promptly and thoroughly.

Key Growth Factors in Platelet-Rich Plasma

I have mentioned platelet-rich plasma (PRP) in a dozen or so posts on this blog over the past three years. Although the positive effect of PRP on hair growth is somewhat controversial, there is no controversy when it comes to the fact that PRP contains numerous concentrated growth factors. And many of these growth factors are known to at least modestly benefit hair quality as well as hair quantity.

While in the past I have briefly discussed some of the key growth factors that are highly concentrated in PRP, I think that it is worth having a separate post here that discusses all of them in a bit more detail. It took me a while to research and write this post, and there is a good chance that I am still missing things so any corrections and suggestions in the comments are most welcome.

It should be noted that even many non-PRP related hair loss hair loss products have targeted one or more of the below listed growth factors in order to stimulate hair growth. There is a good chance that both PRP as well as hair loss products that contain some or all of the below growth factors make existing hair stronger, but it is highly unlikely that they ever bring back hair that has been lost for a long time. They could bring back recently lost hair, but that is also a controversial subject.

Growth Factors in Platelet-Rich Plasma

The key growth factors in PRP that are supposedly beneficial to hair growth are:

  • Insulin-Like Growth Factor 1 (IGF-1).
  • Fibroblast Growth Factor (FGF).
  • Platelet-Derived Growth Factor (PDGF).
  • Vascular Endothelial Growth Factor (VEGF).
  • Epidermal Growth Factor (EGF).
  • Transforming Growth Factor Beta (TGF-β).
  • Nerve Growth Factor (NGF).

IGF-1

I start with the growth hormone insulin-like growth factor 1 (IGF-1) because I have already covered it a few times on this blog before.

  • Promotion of IGF-1 expression is one of the main considerations behind Shiseido’s bestselling adenosine based products.
  • US-based Follicept is also targeting IGF-1 delivery in its hair loss product.
  • Adipose-derived stem cells (ADSCs — one of the more exciting recent developments in the hair loss world) are rich in various growth factors including IGF-1.
  • Last year, an important and widely publicized study found that topical application of oleuropein (derived from the leaves of olive drupes) induces hair growth in mice. According to the study findings, oleuropein-treated mouse skin showed substantial upregulation of IGF-1.

FGF

I list fibroblast growth factor (FGF) next because I have also covered it many times on this blog before. There are 22 types of FGFs numbered FGF-1 through FGF-22. A significant number of these influence hair growth and I may write an entire detailed post on FGFs at some point in the future. I have covered some of the key ones on this blog before, in particular FGF-5, which discourages hair growth and has to be inhibited. Australian company Cellmid’s Evolis line of products claims to inhibit FGF-5.

Note that PRP does not inhibit growth factors, so it is more relevant for the purposes of this post to discuss some of the FGFs that promote hair growth. It seems like the main ones are FGF-1, FGF-2, FGF-7, FGF-9 and FGF-10.  Evidence for three of those (FGF-1, FGF-2 and FGF-10) positive effects on hair is found in an important 2014 study from China. Note that “hair cell regeneration” or variations of that term are mentioned a number of times in this study, even if in mice.  PRP is said to increase FGF-2 concentration levels. Interestingly, when I interviewed Dr. Malcolm Xing last year, he mentioned that FGF-2 is the preferred growth factor used at this clinic for his work purposes.

FGF-9 has become an especially important growth factor in large part due to the work of the renowned Dr. George Cotsarelis, who holds a patent titled “Fibroblast growth factor-9 promotes hair follicle regeneration after wounding“. Dr. Cotsarelis is also a co-author of a 2013 paper that concludes: “The importance of FGF-9 in hair follicle regeneration suggests that it could be used therapeutically in humans“.

Finally, FGF-7 (also called keratinocyte growth factor, or KGF) is required for hair growth. The well known researcher Dr. Elaine Fuchs co-authored an important study on FGF-7, hair development and wound healing all the way back in 1995. Moreover, Histogen’s Hair Stimulating Complex product is focusing on KGF as one of the key growth factors to be injected in human scalps.

PDGF

Platelet-derived growth factor (PDGF) is a key growth factor involved in blood vessel formation. A 2006 study from Japan found that “PDGF isoforms induce and maintain anagen phase of murine hair follicles“. Adipose-derived stem cells (ADSCs) are rich in various growth factors including  PDGF, and are becoming increasingly utilized in the hair loss world.

VEGF

Besides hair growth, vascular endothelial growth factor (VEGF) is also involved in blood vessel formation. A 2001 study concluded that “normal hair growth and size are dependent on VEGF-induced perifollicular angiogenesis”. Note that Shiseido’s adenosine based shampoo also promotes the expression of VEGF. The previously discussed adipose-derived stem cells are also rich in various growth factors including  VEGF.

Also, one of the ways in which Minoxidil works is via the upregulation of VEGF. Moreover, Histogen’s Hair Stimulating Complex product is focusing on VEGF as one of the key growth factors to be injected in human scalps.

A number of studies have examined natural and synthetic products that increase VEGF and their impact on scalp hair. For example, in 2018, Japanese researchers found that water-soluble chicken egg yolk peptides stimulate hair growth through induction of VEGF production.

EGF

Epidermal growth factor (EGF) promotes cell growth, proliferation and differentiation. A 2003 study from Hong Kong concluded that EGF functions as a biological switch that is “turned on and off in hair follicles at the beginning and end of the anagen phase of the hair cycle“.

TGF-β

Transforming growth factor beta (TGF-β) is a cytokine protein growth factor. From the brief research I did, it seems like TGF-β actually adversely impacts hair growth!  e.g., see here, here and here. So I am not sure if this growth factor in PRP benefits hair.  Will update this if I find out more.

NGF

There seem to be mixed opinions on the impact of nerve growth factor (NGF) on the hair cycle in any significant manner. A 2006 study suggests both anagen-promoting and catagen-promoting effects of NGF on the hair cycle. Another study, also from 2006, seems to also find different effects of NGF on the hair cycle.