Applying fats to your head to stop hair loss?

You may think I’m crazy, but I wanted to do a post on fats - specifically, long-chain unsaturated fatty acids that may actually have some promise as an adjunct in your ‘Big 3’ hair loss protocol.

I know, I know, there is so much random stuff online about new supplements or methods, and I get it - I’m skeptical too of like 95% of these so called ‘breakthrough’ supps.

This post isn’t going to revolutionise your protocol - in my opinion, hitting the 3 vectors of DHT (Finasteride, Dutasteride), blood-flow and cell cycle timeline manipulation (minoxidil) and wound healing response (micro-needling) are still your best bet.

However, I do think looking at alternative vectors is always interesting. Even if it just helps you understand a little bit more about your own body.

This study looked at the constituents of Saw Palmetto and whether they have any efficacy at inhibiting the enzyme that converts Testosterone to DHT, 5-alpha reductase (5AR). The key function of this enzyme and why it’s so important in hair loss is that 5AR catalyses the reduction of the double bond in testosterone to convert DHT. As you can see in the diagram below, DHT is the exact same molecule as Testosterone except one less double bond in the area highlighted. As such, in terms of clinical outcomes for hair loss, stopping 5AR from doing this job will lead to less DHT being produced and therefore less follicle miniaturization.

And in using a model of 5AR, this study found that molecules that can bind to the 5AR enzyme can assume 2 different orientations:

1. The productive position: i.e. the molecule bound in such a way that it CAN carry out the double bond reduction of T to DHT.
2. The unproductive position: i.e. the molecule bound in such a way that it CANNOT carry out the double bond reduction of T to DHT.

Testosterone in the productive position is what we are trying to stop for hair loss - when it is in the productive position, the 5AR enzyme can then remove the double bond to create the DHT molecule. This makes sense when you read what the researchers discussed:

“According to PyRosetta-computed binding energies, testosterone and finasteride have the same affinity for the unproductive position, whereas finasteride is a better candidate for binding the productive position, thus confirming the effectiveness of finasteride as a 5AR-inhibitor already known from clinical experience.”

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Tell us something we don’t know, right?

But it was what they found after, that was the most interesting. Keeping in mind that the best inhibitors have more negative values in the table for ‘Productive Position’, the researchers found that components of Saw Palmetto such as Oleic Acid and Linoleic Acid had even higher binding affinities/inhibition of 5AR than Finasteride, especially in the unproductive position (the one we want). This led the researchers to conclude:

“On the basis of our computational results, long chain and unsaturated fatty acids, like oleic and linoleic acid, are the best candidates from SRE (Saw Palmetto) to act as competitive inhibitors of 5AR with respect to saturated and short/middle chain fatty acids.”

So this got me thinking, would these long-chain fatty acids be suitable as a topical adjunct to something like minoxidil? I was slightly concerned about the length of these long chain fatty acids and their molecular weight - longer molecules are generally heavier, and there is the concept of the ‘500 Dalton rule’ - that is, molecules with a molecular weight >500g/mol have a rapidly decreasing bioavailability of skin permeation in line with the graph below. So something that has a MW of say 750g/mol is simply too large to penetrate normal human skin (NS):

But upon checking, this doesn’t seem to be an issue:

Molecular Weight of Oleic Acid: 282.46 g/mol

Molecular Weight of Linoleic Acid: 280.45 g/mol

Both well and truly under 500 g/mol. So in terms of the 500 rule, these both seem to be small enough molecules to permeate the skin.

And it isn’t just their interactions with 5AR that is interesting about these long-chain fatty acids. They also contribute positively to the hair cycle in a few other, nuanced ways as seen in this study:

When DHT binds to hair cells, the expression of DKK-1 induces apoptosis (programmed cell death). Linoleic acid reduced the expression of DKK-1 and also increased the activation of Wnt/β-catenin signaling, which basically regulates the cell cycle and in this study promoted the cell cycle such that growth factors were secreted. Basically, linoleic acid induced proliferation of dermal papilla cells, increased hair growth and blunted the DKK-1 death pathway of hair follicles. As you can see in the images below, for increasing concentrations of linoleic acid, cell proliferation is increased and DKK-1 expression was decreased once concentration hit 30 micrograms/mL. Now, I’m not entirely sure what oral or topical dosage would be required to achieve that sort of cellular concentration of LA, but perhaps that’s a question for another time (and one definitely worth checking as telling people to go and drink long-chain unsaturated fatty acids probably isn’t the healthiest of ideas).

But hey, I find it really interesting that certain signalling factors can be turned on/off by linoleic and oleic acid that may have some promise in a 4th ‘vector’ for hair loss prevention.

Thanks so much for reading as always and please reach out if you have any questions.