If you are suffering from Androgenetic Alopecia (AGA), you may have learned that using DHT blockers may help.
Currently, the only FDA-approved DHT blocker or 5α-reductase (5α-R) inhibitor is the medication finasteride.
But, new research is showing that there may be some all natural alternatives.
In this article, we’ll look into some of the root causes of overactive 5α-R enzymes and natural 5α-R inhibitors.
Quickly, make sure you take the free hair quiz later in this article.
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What Is 5 Alpha-Reductase?
5α-R is an enzyme responsible for converting testosterone into a more powerful male hormone, DHT.
In AGA, DHT is believed to be a mediator (1). This means that although DHT isn’t fully responsible for hair loss in AGA, it does play a key role.
Androgens are believed to play a role in blood vessel calcification, something seen both in atherosclerosis (artery hardening that puts you at risk of heart attack and stroke) and AGA. In AGA, blood vessel calcification by DHT reduces blood flow to the hair follicle, reducing oxygenation and nutrient supply that hair needs to grow.
DHT also stimulates the proliferation of sebaceous gland cells. As a result, sebaceous glands are enlarged and have more sebum output. This oily, waxy substance is the food for a bacteria strain called P. acnes, the bacteria well-known for its role in acne progression.
When fueled by excess sebum, P. acnes can readily colonize hair follicles. This bacteria strain releases proteins and free radicals that degrade tissues like the skin and stimulate the production of inflammatory molecules.
DHT is also believed to be part of the anti-inflammatory response. In essence, inflammatory molecules, like the ones released in response to P. acnes proteins, signal the production of DHT to keep inflammation in check.
However, this presents an issue. Because DHT is both anti-inflammatory and also a factor in the inflammation in the first place, this can create a very much “catch-22” situation. As a result, the hair loss cycle is exacerbated.
So, the situation presents itself with a few possible solutions:
- Reduce inflammation that stimulates DHT production.
- Downregulate the activity of the 5α-R enzyme that can cause excess DHT and inflammation in the first place.
In the sections below, we’ll go into the possible root cause of overactive 5α-R enzymes as well as some natural herbs known to reduce their activity.
- DHT plays a significant role in AGA by increasing sebum production that leads to inflammation via P. acnes and may calcify blood vessels the nourish hair follicles.
- DHT might also be involved in the anti-inflammatory response.
- The DHT-initiated sebum increase and DHT’s anti-inflammatory response creates a “catch-22” hair loss cycle.
- Possible solutions include reducing inflammation and downregulating the activity of 5α-R enzymes.
What Really Causes Overactive 5 Alpha-Reductase?
Although the cause of excess DHT isn’t fully known, we can gain insight from some conditions.
For women, Polycystic Ovary Syndrome (PCOS) can help us understand excess 5α-R activity. PCOS is characterized by elevated androgen levels and excess 5α-R activity.
Another integral characteristic of PCOS is insulin resistance. Essentially, this is when cells become resistant to the action of insulin.
Insulin is the hormone that binds to glucose and facilitates the entry of glucose, a carbohydrate source of energy, into cells. Then, glucose is metabolized by mitochondria to produce energy for the body.
However, in the case of insulin resistance, insulin can’t bind to insulin receptors (2). Insulin resistance is an interesting condition because it not only causes elevated insulin levels in the blood, called hyperinsulinemia, but is also a result of hyperinsulinemia.
Insulin resistance can also be a result of hyperglycemia, which is elevated blood sugar (3). Eating a diet high in high-glycemic carbohydrates is a common cause of hyperglycemia, which can cause hyperinsulinemia and insulin resistance over time.
Inflammation is also believed to play a part in insulin resistance, possibly because inflammatory signals lead to insulin receptor dysfunction (4). Most research chalks this up to obesity, which can contribute to inflammation, leading to insulin resistance.
Oxidative stress, the stress caused by free radical damage, stimulates chronic inflammation (5). In conditions like PCOS, insulin resistance and oxidative stress are both observed even in non-obese patients (6, 7).
This suggests that there is more to the story than just obesity. The missing piece could be inflammation.
But, what does insulin resistance have to do with hair loss?
Hyperinsulinemia, which is a result of insulin resistance, can increase 5α-R activity in the ovaries, increasing DHT levels (8).
Interestingly, women with AGA also frequently have PCOS or, at the very least, increases in male hormone levels (9). Women with PCOS also experience hair loss.
Consistent with AGA research, studies on PCOS patients show that this increase in androgens might be in an effort to regulate inflammation (10).
But, the role of hyperinsulinemia and insulin resistance in male AGA in less clear.
Men with AGA have a higher prevalence of metabolic syndrome, a condition that involves insulin resistance, obesity, and inflammation (11, 12). However, whether insulin resistance contributes to obesity or obesity causes insulin resistance complicates this observation. Moreover, the question of inflammation being the cart or the horse in this situation is also unclear.
Interestingly, both male and female AGA patients seem to have elevated levels of oxidative stress that contributes to inflammation (13).
Putting the pieces together, we can see that insulin resistance may play a role in excess androgens that contribute significantly to AGA, especially in women. Inflammation seems to play a significant role in insulin resistance.
In most cases, this seems to be a result of obesity-associated inflammation. But, this isn’t always the case, as seen in lean PCOS patients. It’s possible that elevated oxidative stress could be the missing piece here.
Additionally, elevated androgen levels in PCOS could be the body’s attempt in lowering inflammation.
Nonetheless, it’s clear in both sexes that inflammation plays some kind of a role. This warrants including anti-inflammatory and antioxidant nutrients. At the very least, these support overall health.
- PCOS is characterized by high androgen levels and insulin resistance.
- Insulin resistance is a condition where insulin can’t effectively exert its action on cells, leading to hyperinsulinemia.
- Inflammation is believed to contribute to insulin resistance by causing insulin receptor dysfunction.
- Excess insulin stimulates the ovaries to produce excessive amount of DHT through overactive 5α-R enzymes. AGA incidence is associated with PCOS and elevated androgen levels in women.
- This increase in androgens might be an effort of the body to lower inflammation.
- Insulin resistance is observed in PCOS patients independent of excess weight.
- The role of hyperinsulinemia in AGA in men is less clear. AGA is associated with metabolic syndrome which involves insulin resistance, obesity, and inflammation.
- However, whether obesity causes insulin resistance or insulin resistance causes obesity is unclear. Additionally, whether inflammation is the cart or the horse in insulin resistance is unknown.
- One thing we can observe in AGA is elevated levels of oxidative stress, regardless of sex. Oxidative stress and inflammation are inextricably linked. PCOS patients, regardless of obesity, also have elevated markers of oxidative stress.
- While it is not fully known how, inflammation seems to play some sort of a role in insulin resistance and possible androgen dysfunction that contributes to hair loss.
- This could warrant the use of anti-inflammatory and antioxidant nutrients to lower inflammation. At the very least, these support overall health.
Natural 5-Alpha Reductase Inhibitors
Taking the knowledge we have on 5α-R enzyme activity, there are many ways we could possibly balance its activity.
Below, I’ve listed multiple nutrients that could have a beneficial effect on 5α-R enzymes in a variety of ways.
Like I mentioned earlier, oxidative stress is a huge contributor to inflammation (5).
Inflammation could possibly cause insulin resistance and insulin resistance contributes to androgen excess, especially in women. So, mitigating oxidative stress could help prevent inflammation and, thus, insulin resistance. But, this hasn’t been confirmed yet.
Nevertheless, reducing oxidative stress is beneficial for health overall.
Oxidative stress is the cumulative damage of free radicals. Antioxidants can help neutralize free radicals, preventing oxidative stress from happening in the first place.
Some of the most powerful antioxidants are astaxanthin, resveratrol, and vitamin E. Various other antioxidants and nutrients can also support the body’s natural antioxidant systems.
Astaxanthin is a red pigment with powerful antioxidant activity. It can be found in wild caught salmon, shellfish, and krill oil.
Resveratrol is a powerful antioxidant found in blueberries, blackberries, and red grapes. It is also suspected to promote insulin sensitivity, but the studies are still in their early stages (14).
Vitamin E is a fat-soluble vitamin that has antioxidant activity (15). It specifically scavenges lipid peroxides or fatty substances that have been oxidized by free radicals. This is especially beneficial for the skin and the hair because they are sebum-rich environments.
Other nutrients like vitamin C, sulfur compounds found in cruciferous vegetables, the onion family, and organic, pastured animal products, olive oil, and green tea can upregulate the activity of glutathione (16). Glutathione is the body’s natural master antioxidant.
- Oxidative stress causes inflammation which may play a role in insulin resistance. In theory, reducing oxidative stress reduces inflammaton which may improve insulin sensitivity. Because insulin resistance contributes to androgen excess, especially in women, this could be beneficial for AGA.
- Antioxidants reduce oxidative stress by neutralizing free radicals.
- Some of the most powerful antioxidants are astaxanthin, resveratrol, and vitamin E.
- Other nutrients like vitamin C, sulfur compounds, olive oil, and green tea can upregulate glutathione acitivty, the body’s master antioxidant.
Omega-3 Fatty Acids
Omega-3 fatty acids play a key role in keeping inflammation at bay. We know that inflammation could play a role in insulin resistance.
Omega-3s work by incorporating into cell membranes and displacing pro-inflammatory omega-6 fatty acids. Omega-6 fatty acids are converted into arachidonic acid. Then, they interact with enzymes from the COX family to create pro-inflammatory prostaglandins.
When omega-3s are incorporated into cell membranes over arachidonic acid, they secrete anti-inflammatory molecules called resolvins and protectins instead of omega-6s acting as a precursor for prostaglandins (17).
Omega-3s also prevent linoleic acid from over-converting into arachidonic acid. This also reduces the production of inflammatory molecules (18).
The effects of omega-3s on insulin sensitivity have also been directly studied. This could be in part to its anti-inflammatory effects.
In a systematic review of studies on omega-3s and its effects on insulin sensitivity, omega-3-rich fish oil was found to be effective for enhancing insulin sensitivity (19).
Other studies have also mirrored this, confirming that omega-3s enhance insulin sensitivity in PCOS patients (20).
Omega-3s might also help balance androgen levels. Again, this could be due to their anti-inflammatory properties.
Benign Prostatic Hyperplasia (BPH), or benign prostate enlargement, is a condition in males believed to be caused by excess DHT (21). Not surprisingly, AGA and prostate size are associated with each other in some studies (22). This is most likely because they share a similar mediating factor: DHT.
One study showed that patients with BPH have significantly lower levels of omega-3 fatty acids compared to healthy subjects (23). Although, no studies using omega-3 supplementation have observed any benefit for reducing prostate size or how it impacts male hormone levels in men specifically.
In overweight women with PCOS, though, omega-3s reduced androgen levels (24):
Considering the relation of androgen levels to AGA, omega-3s could be a useful tool in preventing insulin resistance-associated androgen excess. This includes 5α-R activity.
However, no studies have looked at omega-3 supplementation or fish consumption alone for treating AGA. But, high omega-3 levels are associated with a lower risk of all-cause mortality and cardiovascular disease-related deaths (25). So, consuming omega-3s may be beneficial for health overall.
- Omega-3s exert anti-inflammatory effects by reducing conversion of linoleic acid to arachidonic acid and increasing the secretion of anti-inflammatory resolvins and protectins.
- Studies suggest omega-3s have a beneficial effect on insulin resistance.
- Omega-3s might also impact androgen levels. Men with BPH, which is mediated by DHT, have lower levels of omega-3s. Omega-3 supplementation reduces androgen levels in overweight women with PCOS.
- However, no studies have observed the effects of omega-3 supplementation on prostate size.
- Because of omega-3s potential effect on androgen levels, it might benefit AGA. But, no studies have looked at the effects of omega-3s alone on AGA.
- High omega-3 levels are associated with alower risk of all-cause mortality and cardiovascular disease-related deaths.
The intestinal permeability barrier is the protective barrier between the contents of the stomach and the blood. It is selectively permeable, meaning it allows nutrients to get into the blood and keeps harmful compounds out.
However, if the gut barrier becomes too permeable, it can allow inflammatory microbes, toxic bacterial byproducts (called endotoxins), and undigested proteins to leak out into the blood. This pushes the immune system into overdrive, creating a state of low-grade inflammation (26). If the gut barrier isn’t sealed, this inflammation can turn chronic.
Researchers have established a link between circulating endotoxin measurements and insulin resistance (27). Higher circulating endotoxin markers is an indicator that the intestinal barrier might be too permeable and allowing endotoxins to leak into the blood.
This theory has been extrapolated to PCOS (28). In one hypothesis, researchers believe that PCOS could be a result of increased intestinal permeability. By increasing inflammation, microbial byproducts could contribute to insulin resistance and subsequent hyperinsulinemia. In theory, this could lead to excess androgens in PCOS patients, especially lean ones.
So, a healthy gut barrier could translate to healthy insulin signaling. In this way, it might help promote balanced androgen levels that contribute to AGA, especially in women.
In cell culture studies, collagen peptides demonstrate an ability to reinforce the tight junctions of the intestinal barrier (29). This is because collagen peptides have high levels of amino acids important for barrier integrity.
However, whether or not these results translate into real life remains to be proven.
- The gut barrier exists as a protective, selectively permeable barrier that allows nutrients into the blood and keeps harmful compounds out.
- If the barrier becomes too permeable, it can allow inflammatory microbes, toxic bacterial byproducts (called endotoxins), and undigested proteins to leak out into the blood. Low grade systemic inflammation is a result and, if not resolved, can become chronic.
- High levels of circulating endotoxins are correlated with insulin resistance, signaling leaky gut might play a role in the condition.
- In PCOS, researchers have developed a theory that leaky gut causes excess circulating endotoxins, leading to inflammation and insulin resistance. This could explain the excess androgens in PCOS patients, especially lean ones.
- In cell culture studies, collagen peptides have demonstrated an ability to repair the gut barrier. However, whether or not these results translate into real life remains to be proven.
Branching off of the last section, probiotics can also be a useful tool to heal the gut barrier.
The gut microbiota is a diverse colony of bacteria that live in our guts. They have a profound effect on health and research is only beginning to scratch the surface of their impact.
In our modern society, there are various factors that can seriously influence the quality, diversity, and delicate balance between the healthy, beneficial bacteria and pathogenic bacteria. These include excessive antibiotic use, oral contraceptives, and Proton-Pump Inhibitors (PPIs), to name a few (30, 31, 32).
One of the roles of bacteria in the gut is maintaining the integrity of the gut barrier. If the balance is disturbed, it can cause pathogenic bacteria to dominate the gut and increase intestinal permeability.
Supplementing with probiotics and eating probiotic-rich foods like sauerkraut, pickles, yogurt, kefir, and other fermented foods may help to encourage a healthy barrier function.
Each strain of bacteria exerts different effects on the gut. When it comes to protecting the integrity of the gut barrier, Lactobacillus rhamnosus, Lactobacillus plantarum, and Lactobacillus reuteri are strains to consider (33). Saccharomyces and Bifidobacteria strains have also demonstrated an ability to maintain the gut barrier.
- The bacterial microbiota of the gut are important for maintaining the gut barrier.
- Excessive antibiotic use, oral contraceptives, and proton-pump inhibitors, for example, can disrupt the delicate balance and diversity of the gut.
- If the balance is distrubed, it can cause pathogenic bacteria to dominate the gut and increase intestinal permeability.
- Probiotic-rich foods and probiotics with strains like Lactobacillus rhamnosus, Lactobacillus plantarum, Lactobacillus reuteri, Saccharomyces spp., and Bifidobacteria may help protect the integrity of the gut barrier.
L-carnitine is an amino acid that is essential for transporting fatty acids to the mitochondria (34). Once there, the mitochondria metabolize the fatty acids in a process called β-oxidation. In this way, L-carnitine is essential for mitochondrial function.
If L-carnitine is low and fatty acids aren’t efficiently transported to the mitochondria, it can lead to impaired fatty acid metabolism. This incomplete metabolism is believed to contribute to insulin resistance by increasing oxidative stress that impairs insulin receptor function (35).
Because of the downstream effects of L-carnitine deficiency, researchers have recently looked into the use of L-carnitine to treat insulin resistance. In one systematic review of the body of literature on L-carnitine for insulin resistance, researchers conclude that L-carnitine is useful for treating insulin resistance (36).
L-carnitine might also be beneficial for women with PCOS. In one study, researchers found that lean PCOS patients had lower blood levels of L-carnitine compared to healthy women (37).
Another study showed that it improved measurements of oxidative stress, which is elevated in both lean and overweight PCOS patients (38). This is consistent with studies that suggest L-carnitine promotes proper fatty acid metabolism, reducing free radical generation by mitochondria. This would lead to reduced oxidative stress.
By promoting insulin sensitivity, L-carnitine could reduce androgen production, in theory.
- L-carnitine is important for proper fatty acid transport and metabolism. L-carnitine deficiency could lead to improper fatty acid metabolism and increased free radical production by mitochondria.
- Oxidative stress impairs insulin receptor function, which could lead to insulin resistance.
- Because of this, researchers have looked into L-carnitine for treating insulin resistance. A systematic review concludes L-carnitine is useful for treating insulin resistance.
- Lean PCOS patients have lower blood levels of L-carnitine compared tohealthy women. Supplementation has been shown to reduce oxidative stress in women with PCOS.
- These results are consistent with the idea that L-carnitine reduces oxidative stress and insulin resistance by promoting full fatty acid metabolism.
Saw palmetto is an herb that contains anti-androgenic sterols (39). It is believed to work by inhibiting the 5α-R enzyme which prevents testosterone from converting to DHT.
However, whether saw palmetto is effective for humans is unclear. Most studies that demonstrate saw palmetto’s anti-androgen activity are cell culture studies. One review notes that the doses used in these studies might be above the normal physiological doses.
Essentially, this means that humans would have to take an incredibly large amount of saw palmetto to mimic the effects seen in cell culture studies. This could potentially be dangerous.
Another review points out that there aren’t a lot of studies showing it is truly effective (40).
One study on the use of saw palmetto in AGA showed improvement in 60 percent of patients (41). However, whether this improvement was clinically relevant when compared to other treatments wasn’t noted. Additionally, there were only 10 subjects that used saw palmetto, so the sample size is too small to tell whether or not it is effective.
Another study suggests topical saw palmetto may reduce sebum production (42). Since DHT is a huge contributor to sebum production, this tells us that saw palmetto may inhibit 5α-R activity when used topically.
Overall, more research is needed to determine the effectiveness of saw palmetto.
- Saw palmetto is an anti-androgenic herb that is believed to inhibit the 5α-R enzyme.
- Most research is inconclusive. Cell culture studies that demonstrate an effective 5α-R enzyme inhibition are at doses possibly too high for human use.
- Small studies show an improvement for AGA, however, the grade of improvement and how it compares to current treatment protocols is unclear.
- Topical saw palmetto may reduce sebum production, suggesting topical saw palmetto may inhibit 5α-R activity.
- More research on saw palmetto both internally and topically is needed to determine its effectiveness.
Pumpkin Seed Oil
Like saw palmetto, pumpkin seed oil (PSO) contains sterols believed to have anti-5α-R properties.
In one randomized, placebo-controlled, double-blind trial, researchers looked into the effects of pumpkin seed oil on 76 male AGA patients (43). Each patient was randomized to receive 400mg of pumpkin seed oil tablets per day or the placebo for 24 weeks.
After the trial period, there was an average 40 percent increase in the number of hairs compared to a 10 percent increase in the placebo group.
It should be noted that the source of the pumpkin seed oil was Octa Sabal Plus®. This is a capsule that contains other ingredients aside from PSO, so it’s difficult to say just how much of an effect the pumpkin seed oil actually had.
This study warrants larger studies for the use of pumpkin seed oil in AGA.
- Pumpkin seed oil, like saw palmetto, contains sterols believe to block 5α-R activity.
- In one double-blind RCT, men with AGA who took pumpkin seed oil had an average 40 percent increase in hair count compared to 10 percent in the placebo.
- This high-quality study warrants larger studies for the use of pumpkin seed oil in AGA.
Spearmint tea could be an effective anti-androgen, especially in women.
The exact action of spearmint tea is not fully known, however, it has been shown to reduce testosterone and increase estrogen levels in women with PCOS (40). This suggests that it encourages more testosterone to be converted to estrogen rather than DHT. It may also directly lower testosterone production, reducing the chances that testosterone converts to DHT via 5α-R.
More research is needed to understand exactly how spearmint tea works, but animal studies indicate that it could be an effect of one of the oil constituents (44).
It should also be noted that spearmint tea hasn’t been studied in men.
Key Takeaway: Researchers aren’t sure exactly how it works, but spearmint tea lowers testosterone and increases estrogen in women with PCOS. Animal studies suggest it could be an effect of the oil constituents.
Reishi mushroom has been shown to significantly reduce 5α-R expression in animal studies (40).
However, whether these results can be extrapolated to humans warrants further research.
Key Takeaway: Reishi mushroom has been shown to significantly reduce 5α-R expression in animal studies but needs human studies to test its effectiveness.
White peony is a Chinese herb with proposed anti-androgen properties.
One cell culture study showed that the constituents of white peony were able to reduce testosterone production and increase conversion to estrogen in ovarian cells (40).
Additional cell culture studies have shown that it also has anti-inflammatory properties, which could improve insulin sensitivity (46).
But, the use of white peony for lowering DHT hasn’t been tested in humans. It might also not be beneficial for men.
Key Takeaway: Cell culture studies suggest white peony could reduce testosterone production and increase conversion to estrogen in ovarian cells. It also possesses anti-inflammatory activity. But, its effects on DHT hasn’t been tested in humans. It may also not be beneficial for men.
Black cohosh has been traditionally used for menopause symptoms like hot flashes (40). This indicates that it may have some influence on hormone balance.
But, clinical trials on black cohosh have shown that this use might be unfounded.
Currently, there is no data to support the use of black cohosh as a 5α-R inhibitor.
Key Takeaway: Black cohosh has traditionally been used for menopausal symptoms, indicating that it may have some influence on hormone balance. However, studies show these uses might be unfounded. There’s also no data to support the use of black cohosh as a 5α-R inhibitor.
A Word of Caution for Men: 5 Alpha-Reductase Inhibitors Side Effects
DHT, at the right concentrations, is an integral part of hormone balance for both men and women.
Although less important for women, DHT plays a critical role in male physiology. Studies show that DHT deficiency can actually contribute to insulin resistance, sexual dysfunction, increased fat mass, reduced muscle mass, and overall degradation of quality of life (47).
So, while DHT does play a significant role in hair loss, it’s better to target the root causes of excess DHT. Taking this approach promotes balance and hormone synergy rather than attacking and lowering one specific hormone.
As always, you should consult your doctor before trying any alternative therapies or including supplements in your wellness regimen.
Key Takeaway: Targeting and attacking DHT could have serious negative consequences for men. Instead, it’s better to take an approach that targets the root cause of hormone imbalance.
The Verdict: Address the Root Cause and Take Precaution
When it comes to lowering DHT by using natural 5-alpha reductase inhibitors, it’s important to address the root cause of these imbalances. For some, especially women, this could boil down to oxidative stress, inflammation, and insulin resistance.
By using tools that address insulin resistance and natural 5α-R inhibitors, you may be able to reduce excess DHT associated with AGA.
However, it’s important that men take precaution when directly targeting DHT. Lowering DHT levels too far can contribute to insulin resistance, sexual dysfunction, increased fat mass, reduced muscle mass, and overall degradation of quality of life.
Have you used natural 5-alpha reductase inhibitors? Did they work for you in any way? Let me know in the comments.