Part 2 Of 4: Attacking DHT By Inhibiting 5-Alpha Reductase

Read time: 10 minutes

Note: this is part two of a four-part series — a master guide to reducing DHT levels for the purpose of fighting hair loss. Missed part one? Read it right here.

Part One Summary – Decreasing DHT By Reducing Free Testosterone

In the last article, we uncovered what DHT is, how it’s made, the DHT-hair loss connection, and the four major levers to reduce DHT levels in hopes of stopping hair loss:

1. Decrease free testosterone
2. Inhibit 5-alpha reductase
3. Decrease androgen receptors
4. …and one more we haven’t yet revealed

Then we dove into all the ways we can decrease DHT by using that first lever: reducing free testosterone. Here’s a summary of the mechanisms (but not all the drugs, foods, supplements, and treatments that target these mechanisms):

Unfortunately, most of these approaches are bad ideas. For instance – yes, we can theoretically plummet DHT production via castration. And yes, castration has been shown to significantly slow or stop pattern hair loss. But for most men, the consequences of castration far outweigh the pain of losing our hair.

So when it comes to reducing DHT by decreasing free testosterone, we don’t have many viable options…

The good news? There are still three other levers of attack against DHT.

The one we’ll cover inside this article: inhibiting the enzyme 5-alpha reductase.

Part Two: Decreasing DHT By Inhibiting 5-Alpha Reductase

Review: Three Levers Of DHT Reduction

Remember: in order for dihydrotestosterone (DHT) to form, we need all of the following present:

1. Free testosterone
2. 5-alpha reductase
3. Androgen receptors

As a result, this gives us three major levers to reduce DHT levels: decrease 1) free testosterone, 2) 5-alpha reductase, and / or 3) androgen receptors.

We’ve already covered the major ways to reduce free testosterone (and thereby decrease DHT). Now it’s time to move onto the enzyme 5-alpha reductase.

What Is 5-Alpha Reductase?

5-alpha reductase is the enzyme our bodies use to convert free testosterone into DHT. And without the enzyme 5-alpha reductase, DHT cannot form (at least at relatively high quantities).

There are many types of 5-alpha reductase, but when it comes to hair loss, the one that gets the most attention is type II 5-alpha reductase.

Type II 5-alpha reductase is the enzyme expressed in our scalp skin and prostate. Some men have a rare genetic mutation where their bodies can’t produce any type II 5-alpha reductase. And interestingly enough, these men don’t go bald.

The net: we need type II 5-alpha reductase to make DHT in our scalp skin. And that means if we can reduce the expression of type II 5-alpha reductase, we can also reduce our DHT levels (and possibly prevent or partially reverse pattern hair thinning).

Which brings us to our second angle of attack against DHT…

Angle Of Attack #2: Reducing 5-Alpha Reductase

There seems to be at least two pathways to inhibiting (or reducing the presence of) this enzyme.

1. Directly (competitively inhibit 5-alpha reductase)
2. Indirectly (reduce inflammation)

Let’s take these one-by-one.

#1: Direct 5-Alpha Reductase Inhibition

Competitive Inhibition

5-alpha reductase doesn’t just arrive out of nowhere. In order for this enzyme to form and mediate the whole DHT conversion process, it needs the help of a coenzyme known as nicotinamide adenine dinucleotide phosphate… or in other words, NADPH.

5-alpha reductase needs NADPH to convert free testosterone into DHT. So an effective way to stop the formation of 5-alpha reductase (and reducing DHT) is to…

1. Compete with the coenzyme NADPH, or…
2. Block NADPH

These are two mechanisms of direct 5-alpha reductase inhibition – or for the lay person – reducing 5-alpha reductase by stopping it from forming. The hair loss drugs Finasteride and Dutasteride – two 5-alpha reductase inhibitors – appear to work in this way.

Mechanism 1: Compete With NADPH

Some research shows that Finasteride competes with the coenzyme NADPH. Finasteride’s molecules take the place of NADPH in a cell, and in NADPH’s absence, 5-alpha reductase cannot form. The end-result? Less DHT. And another 5-alpha reductase inhibiting drug – Dutasteride – seems to do the same thing (using a slightly different molecule).

Mechanism 2: Block NADPH (Or Bind To NADPH And Change Its Structure)

There’s also research showing that instead of competing with NADPH, Finasteride may instead bind to NADPH and change NADPH’s structure into a different coenzyme – one that doesn’t support the formation of 5-alpha reductase. The bottom line: free testosterone can no longer convert into DHT.

Interestingly, zinc may also reduce 5-alpha reductase and through a similar manner. Evidence suggests that zinc reduces NADPH production, thereby decreasing 5-alpha reductase activity. The less enzyme activity, the less DHT.

And that’s a (very) brief overview of how to reduce DHT levels by directly inhibiting the enzyme 5-alpha reductase.

#2: Indirect 5-Alpha Reductase Inhibition

Reduce Inflammation

Studies show there’s an association with DHT and inflammation. The net: DHT might regulate the inflammatory process. And in some tissues, increased DHT might even be a response to increased inflammation.

Hypothetically, if we can reduce inflammation, we might also reduce 5-alpha reductase activity (and thereby DHT levels).

Interestingly, reducing chronic inflammation may be an indirect way of reducing 5-alpha reductase. This is because reducing inflammation doesn’t directly inhibit 5-alpha reductase, but rather, inhibits the inflammation that signals 5-alpha reductase to arrive in certain tissues (like our scalp skin and prostates).

There are hundreds of ways to reduce chronic inflammation. But most boil down to two methods: we can either 1) take away whatever’s causing the inflammation in the first place, or 2) stop the signaling proteins that tell our bodies to send inflammatory cells to injury sites.

In the case of pattern hair loss, we don’t really know what causes chronic inflammation in our scalps. It could be scalp muscular tension, protruded bone growth, skin tightening, the arrival of DHT to genetically sensitive hair follicles, an inflammatory marker induced by DHT… the list goes on. But since we don’t know the cause, we’re more or less stuck with that second inflammation-reducing option: muting signaling proteins that channel inflammatory cells to injured tissues.

Fortunately, there are hundreds of substances that can do this. Covering each is out-of-scope for this article, so we’ll instead highlight just two.

Again, the list here is not a suggestion that you should use these methods. They’re just examples of substances that might hit these pathways.

1. #1: Pumpkin Seed Oil
   1. Antioxidants: decrease oxidation, decrease transforming growth factor beta
   2. Linoleic acid: decreases COX-2 enzyme
2. #2: Rosemary Oil
   1. Polyphenols: decreases COX-2 enzyme
   2. Volatile oils: decreases COX-2 enzyme, interleukins, and tumor necrosis factor

Recap: Direct Vs. Indirect 5-Alpha Reductase Inhibition

We can decrease DHT by inhibiting 5-alpha reductase through two major pathways: direct versus indirect 5-AR inhibition. Direct 5-AR inhibition is how steroid-derived hair loss drugs like Finasteride and Dutasteride work.

Conversely, we may be able to indirectly inhibit 5-alpha reductase by reducing inflammation in tissues. Inflammation and hair loss are closely linked, but since we don’t yet know what causes the inflammation that triggers hair loss, we’re more or less limited to reducing scalp inflammation by simply inhibiting the signaling proteins that send more inflammatory cells to those tissues. Rosemary oil and pumpkin seed oil have these anti-inflammatory properties. Unfortunately, they’re less studied in terms of hair loss, and probably aren’t as effective at stopping hair loss versus Finasteride (Propecia) or Dutasteride (Avodart).

Any Other Ways To Reduce 5-Alpha Reductase – Directly Or Indirectly?

Absolutely.

There’s evidence that polyunsaturated fatty acids like linoleic acid may act directly and indirectly on 5-alpha reductase by 1) reducing inflammation, and 2) altering lipid bilayers in cell membranes to decrease 5-alpha reductase formation.

There’s also evidence that vitamin B2- also known as riboflavin – may decrease 5-alpha reductase activity, though the mechanisms aren’t completely understood.

Even the polyphenols inside green tea may inhibit 5-alpha reductase.

The pathways these substances take to reduce 5-alpha reductase are complex, and they’re still being explored. As a result, I’ve omitted these from the flowchart until studies can confirm their exact mechanisms.

Finally – we can also reduce 5-alpha reductase activity by decreasing total androgen production. The less androgens our bodies produce, the less 5-alpha reductase is activated. This was covered in the first article about reducing free testosterone, and as a result, we won’t cover it again here.

Again, there’s very limited research on the effects of these non-drug strategies on hair loss outcomes. Nonetheless, I figured I’d mention them.

Summary Of Series (So Far)

When it comes to fighting hair loss by reducing DHT, there are four main levers of attack:

1. Reducing free testosterone
2. Inhibiting 5-alpha reductase
3. Blocking androgen receptors
4. A mystery lever (we’ll get to that soon)

In the last article, we covered the major ways of reducing DHT by reducing free testosterone, and provided some examples of the drugs and supplements which achieve this (inadvertently or not).

In this article, we uncovered how we can reduce DHT by inhibiting 5-alpha reductase – and through a variety of mechanisms.

So let’s combine what we know so far into one major flowchart. So far, we’re 2/4’s of the way to a complete DHT Reduction Master Flowchart:

Remember, the drugs and supplements listed above are just examples. These are by no means the most effective drugs and supplements within their respective categories, nor are they the only drugs or supplements that can achieve these effects. This flowchart is educational and not endorsing of any specific treatment.

What’s To Come…

The third installment of a Master Guide To The Mechanisms Behind DHT Reduction uncovers how to decrease DHT by decreasing androgen receptors.

Anyone researching or experimenting with additional ways to reduce 5-alpha reductase? Leave a comment! I respond to everyone.