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EGCG: Does This Polyphenol Regrow Hair? | A Scientific Analysis

Epigallocatechin gallate (EGCG), a compound found in green tea, is often included in serums and supplements targeted for hair growth. On the one hand, EGCG has the potential to impact a variety of diseases. As a powerful antioxidant and an antitumor agent, EGCG might have therapeutic benefit for those with diabetes, Parkinson’s disease, Alzheimer’s disease, stroke, and obesity.[1]Singh, B.N., Shankar, S., Srivastava, R.K. (2011). Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications. Biochemical Pharmacology. 82(12). … Continue reading On the other hand, the evidence on EGCG and hair regrowth is incredibly limited – particularly for men and women with pattern hair loss (androgenetic alopecia).

In this article, we will examine the potential for EGCG to impact hair follicle growth and determine whether the evidence supports its use in hair loss products.

Key Takeaways

  • What is it?  EGCG is a naturally occurring chemical found in green tea. There is some data to suggest that EGCG may be able to treat hair loss disorders. However, these studies have mostly been completed in cells (i.e., in vitro research), which often translates poorly to humans. 
  • Evidence Quality: The evidence quality is 11/100 based on our metrics.
  • Clinical Data: The only clinical evidence available is a small study completed in which 3 males applied 10% topical EGCG for 4 days. Unforutnately, the data collected only focused on the mechanism of EGCG, and not on its actual potential to regrow hair. 
  • Safety: Whilst EGCG is considered to be safe to use, oral consumption of 800 mg/day may cause liver toxicity issues. 
  • Who Might Benefit From EGCG? Based on the information about the mechanism of action of EGCG, it may benefit people with androgenetic alopecia. However, there is a distinct lack of clinical data to show that EGCG has any beneficial effect on people with hair loss disorders. 
Molecular Structure
Figure 1: Molecular structure of EGCG. Adapted from:[2]Dhariwala, M, Y., Ravikumar, P. (2019). An overview of herbal alternatives in androgenetic alopecia. Journal of Cosmetic Dermatology. 18. 966-975. Available at: https://doi.org/10.1111/jocd.12930

Green Tea & EGCG

Green tea is one of the oldest and most popular drinks in the world, mainly grown in Japan, China, and Taiwan. Full of several chemicals known as flavonoids (which includes EGCG) green tea is best known for its antioxidant, anti-inflammatory, antimicrobial, and chemoprotective properties.[3]Musial, C., Kuban-Jankowska, A., Gorska, Ponikowska, M. (2020). Beneficial properties of green tea catechins. International Journal of Molecular Science. 21(5). 1744. Available at: … Continue reading It is logical to think that some of these properties may benefit hair growth, however, is there any scientific evidence to show this?

Is There Evidence EGCG can affect Hair Follicles?

There are some studies completed in cells and in hair follicles that elucidate some of the pathways in which EGCG exerts its effects on hair follicles.

5α-Reductase Inhibitory Properties of EGCG

One study determined the effect of EGCG and its derivatives on 5α-reductase activity.[4]Hiipakka, R.A., Zhang, H.Z., Dai, W., Dai, Q., Liao, S. (2002). Structure-activity relationships for inhibition of human 5α-reductases by polyphenols. Biochemical Pharmacology. 63. 1165-1176. … Continue reading In a cell-free enzyme assay, Epicatechin gallate (ECG), and EGCG were both able to effectively inhibit 5α-reductase than Epicatechin and Epigallocatechin. Furthermore, they were more effective inhibitors of Type 1 5α-reductase than Type 2 (Figure 2). However, in a whole-cell assay, none of EGCG or its derivatives has any effect, indicating that it may not be able to cross the cell barrier, and therefore might be limited in its effectiveness in animal or human studies.

EGCG and derivatives on 5-AR inhibitors
Figure 2: Effect of EGCG and its derivatives on 5α-reductase inhibition. Values represent the concentration of each chemical needed to inhibit 50% of 5α-reductase activity. Adapted from:[5]Hiipakka, R.A., Zhang, H.Z., Dai, W., Dai, Q., Liao, S. (2002). Structure-activity relationships for inhibition of human 5α-reductases by polyphenols. Biochemical Pharmacology. 63. 1165-1176. … Continue reading

Protection Against the Negative Effects of DHT Through miRNA Regulation

Another study conducted in human dermal papilla cells examined the effects of EGCG on dihydrotestosterone-induced cell death.[6]Shin, S., Kim, K., Lee, M.J., Lee, J., Choi, S., Kim, K.S., Ko, J.M., Han, H., Kim, S.Y., Youn, H.J., Ahn, K.Y., An, I.S., An, S., Cha, H.J. (2016). Epigallocatechin gallate-mediated alteration of … Continue reading Dermal papilla cells are specialized cells involved in cell signaling and hair follicle cycling.[7]Morgan, B.A., (2014). The dermal papilla: an instructive niche for epithelial stem and progenitor cells in development and regeneration of the hair follicle. Cold Spring Harbor Perspectives in … Continue reading

Human dermal papilla cells were treated with dihydrotestosterone (DHT) and EGCG at a range of concentrations. Then the researchers conducted cell viability assays, cell cycle analysis, and intracellular reactive oxygen species assay.

Treatment with 10 µM of EGCG alone showed the highest cell viability, with a subsequent dose-dependent decrease after 20 µM (Figure 3a). Next, the researchers determined whether EGCG treatment was able to protect cells against the negative effects of DHT. The cells treated with only DHT showed a 40% reduction in cell viability, however, the 5 – 15 µM concentrations of EGCG showed a subsequent rescue in cell viability. This rescue however was not able to return cell viability levels to the control level (Figure 3b).

EGCG alone
Figure 3: Effects of (A): EGCG alone, or (B): EGCG and DHT on human dermal papilla cell viability. Adapted from:[8]Shin, S., Kim, K., Lee, M.J., Lee, J., Choi, S., Kim, K.S., Ko, J.M., Han, H., Kim, S.Y., Youn, H.J., Ahn, K.Y., An, I.S., An, S., Cha, H.J. (2016). Epigallocatechin gallate-mediated alteration of … Continue reading

The researchers next determined the percentage of cells that were undergoing cell death (apoptosis), using a technique called flow cytometry. When cells are detected to be in the sub-G1 stage of the cell cycle, this means that they are undergoing apoptosis. Cells were treated with either nothing (- -), DHT alone (- +), EGCG alone (+ -), or EGCG and DHT together (+ +) (Figure 3). DHT treatment alone increased the percentage of dying cells to around 20%. EGCG treatment also increased the number of dying cells, but not to the same extent as DHT treatment. When cells were treated with EGCG and DHT together, there was a notable decrease in cell death indicating that EGCG can rescue cells from DHT-induced cell death. This was not a full rescue, however, as it returned cell death levels to that of EGCG alone, instead of levels after no treatment at all.

EGCG and Cell Death
Figure 4: Effect of EGCG and DHT alone or in combination on intracellular reactive oxygen species. Adapted from:[9]Shin, S., Kim, K., Lee, M.J., Lee, J., Choi, S., Kim, K.S., Ko, J.M., Han, H., Kim, S.Y., Youn, H.J., Ahn, K.Y., An, I.S., An, S., Cha, H.J. (2016). Epigallocatechin gallate-mediated alteration of … Continue reading

The effect of EGCG on levels of reactive oxygen species (ROS) inside the cell was next measured. It was found that DHT drastically increased ROS with around 45% of cells showing a positive signal (Figure 4). EGCG alone reduced the number of cells with ROS to nearly 0%, which was even lower than the no-treatment group. The group treated with EGCG and DHT together showed a reduction in ROS, with around 30% of cells showing a positive signal, however, this was still notably increased compared to the no-treatment group.

Intracellular ROS
Figure 5: Effect of EGCG and DHT alone or in combination on the number of senescent human dermal papilla cells. Adapted from:[10]Shin, S., Kim, K., Lee, M.J., Lee, J., Choi, S., Kim, K.S., Ko, J.M., Han, H., Kim, S.Y., Youn, H.J., Ahn, K.Y., An, I.S., An, S., Cha, H.J. (2016). Epigallocatechin gallate-mediated alteration of … Continue reading

Reactive oxygen species are also one of the factors involved in the induction of senescence.[11]Lai, J.J., Chang, P., Lai, K.P., Chen, L., Chang, C. (2012). The role of androgen and androgen receptors in skin-related disorders. Archives of Dermatological Research. 304(7). 499-510. Available at: … Continue reading Cellular aging leads to a natural process known as senescence, which plays a crucial role in maintaining the balance of cellular function in our body. Senescence is characterized by a decrease in cell division and growth, but it does not necessarily indicate cell death or inactivity. Instead, senescent cells undergo a dynamic transformation in the signaling and secretion of specific markers, ultimately removing them from the body. Although this is beneficial for overall health, the buildup of senescent cells can cause chronic inflammation and lead to various diseases.[12]Hernandez-Segura, A., Nehme, J., Demaria, M. (2018). Hallmarks of cellular senescence. Trends in Cellular Biology. 28(6). 436-453. Available at: https://doi.org/10.1016/j.tcb.2018.02.001

Treatment of dermal papilla cells with DHT alone significantly increased the percentage of cells undergoing senescence to over 20% (Figure 5). Combination treatment with EGCG did lower the percentage of senescent cells to around 15% however this did not reach the same level as the untreated group.

EGCG and DHT on senescence
Figure 6: Effect of a range of EGCG treatments on protein expression of (LEFT): Akt and (RIGHT): Erk, as well as (BOTTOM): cell growth. Adapted from:[13]Kwon, O.S., Han, J.H., Yoo, H.G., Chung, J.H., Cho, K.H., Eun, H.C., Kim, K.H. (2007). Human hair growth enhancement in vitro by green tea epigallocatechin-3-gallate (EGCG). Phytomedicine. 14. … Continue reading

The researchers also conducted a microarray analysis of over 1000 microRNAs (miRNAs) to determine the mechanism of action of EGCG’s protective effects against DHT. MiRNAs are a class of non-coding RNAs that play important roles in regulating gene expression.[14]O’Brian, J., Hayder, H., Zayed, Y., Peng, C. (2018). Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Frontiers in Endocrinology. 9. 1-12. Available at: … Continue reading It was found that EGCG treatment up-regulated a number of miRNAs involved in cell growth and survival and cell cycle regulation. Some of these included:

  • Hsa-miR-210 (330.95 fold increase) – promotes proliferation and suppresses growth arrest
  • Hsa-miR-590-5p (147.55-fold increase) – promotes cell growth and survival
  • Hsa-miR-370 (2.22-fold increase) – induces proliferation

EGCG treatment also led to the down-regulation of specific miRNAs involved in the suppression of the cell cycle and induction of apoptosis. Some of these include:

  • Hsa-miR-188-5p (147.60-fold decrease) – suppresses the continuation of the cell cycle and subsequent cell growth
  • Hsa-miR-28-5p (49.61-fold decrease) – induces cell death

So, to summarize, EGCG can confer some protective effects against cell death, levels of ROS, and subsequent number of senescent cells in DHT-treated cells, indicating that EGCG treatment might be able to negate some effects of DHT in human dermal papilla cells. These effects however were only partial and did not restore levels to the control. Furthermore, it was found that one way that EGCG exerted its effects was by regulating the expression of specific miRNAs involved in cell growth and survival to offset some of the effects of DHT.

EGCG Promotes Cell and Hair Follicle Growth Through the Upregulation of Cell Growth Pathways and Downregulation of Apoptosis Pathways

Another study was conducted to measure the effect of a range of EGCG concentrations alone on human dermal papilla cells, and a 10% topical treatment on 3 human volunteers (we will go more into this part below).[15]Kwon, O.S., Han, J.H., Yoo, H.G., Chung, J.H., Cho, K.H., Eun, H.C., Kim, K.H. (2007). Human hair growth enhancement in vitro by green tea epigallocatechin-3-gallate (EGCG). Phytomedicine. 14. … Continue reading The effect of EGCG treatment on phosphorylated Erk and Akt expression was then determined using western blot.

The P13-Akt pathway leads to the phosphorylation of the protein P-Akt which promotes keratinocyte survival and growth.[16]Bourguignon, L.Y.W., Matrix hyaluronan-activated CD44 signaling promotes keratinocyte activities and improves abnormal epidermal functions. The American Journal of Pathology. 184(7). 1912-1919. … Continue reading Erk is a protein that when phosphorylates regulates six fundamental processes including cell proliferation, cell survival, cell growth, cell metabolism, cell migration, and cell differentiation.[17]Lavoie, H., Gagnon, J., Therrien, M. (2020). ERK signaling: a master regulator of cell behavior, life, and fate. Nature Reviews Molecular Cell Biology. 21. 607-632. Available at: … Continue reading

Human dermal papilla cells showed a dose-dependent increase in both Erk and Akt protein expression alongside a subsequent increase in cell growth (Figure 6), indicating that EGCG can enhance cell proliferation of human dermal papilla cells.

EGCG treatment and protein expression
Figure 7: Effect of a range of EGCG treatments on protein expression of (LEFT): Akt and (RIGHT): Erk, as well as (BOTTOM): cell growth. Adapted from:[18]Kwon, O.S., Han, J.H., Yoo, H.G., Chung, J.H., Cho, K.H., Eun, H.C., Kim, K.H. (2007). Human hair growth enhancement in vitro by green tea epigallocatechin-3-gallate (EGCG). Phytomedicine. 14. … Continue reading

The researchers also examined the effect of EGCG on key proteins involved in the induction and suppression of apoptosis. Bax is an apoptosis promotor and Bcl-2 is an apoptosis inhibitor.[19]Muller-Rover, S., Rossiter, H., Lindner, G., Peters, E.M.J., Kupper, T.S., Paus, R. (1999). Hair follicle apoptosis and Bcl-2. Journal of Investigative Dermatology. 4. 272-277. Available at: … Continue reading Compared to the control group, EGCG treatment increased protein expression of Bcl-2 – the apoptosis inhibitor – and decreased expression of Bax – the apoptosis promoter – in a dose-dependent manner (Figure 7).

EGCG treatments
Figure 8: Effect of a range of EGCG treatments on the percentage of Bcl-2 (apoptosis inhibitor) and Bax (apoptosis promotor) protein expression. Adapted from:[20]Muller-Rover, S., Rossiter, H., Lindner, G., Peters, E.M.J., Kupper, T.S., Paus, R. (1999). Hair follicle apoptosis and Bcl-2. Journal of Investigative Dermatology. 4. 272-277. Available at: … Continue reading

So the in vitro (in cells) data suggests that EGCG can promote hair follicle growth through inhibition of proteins involved in cell death, and the enhancement of expression of proteins involved in cell survival and proliferation. Furthermore, there is also some evidence that EGCG can inhibit 5α-reductase and protect against the effects of DHT.

We can see how EGCG might affect hair follicles, but is there any clinical evidence to show that it works?

EGCG: Is there Human Data showing Hair Regrowth?

The only clinical data that we could find that used EGCG alone – in humans – was a small study conducted on three healthy volunteers who did not have any hair loss disorders.[21]Kwon, O.S., Han, J.H., Yoo, H.G., Chung, J.H., Cho, K.H., Eun, H.C., Kim, K.H. (2007). Human hair growth enhancement in vitro by green tea epigallocatechin-3-gallate (EGCG). Phytomedicine. 14. … Continue reading Ten percent EGCG in ethanol or ethanol vehicle (control) was applied once daily to two areas of the scalp for 4 successive days. The treated areas were then excised and dissected to separate the dermal papillae. These were then lysed and used in a technique called western blotting to determine the protein expression of key markers involved in cell growth Akt and Erk, as well as markers involved in the induction or suppression of apoptosis.

When analyzing the effects of topical EGCG on the expression of the above proteins, it was found that phosphorylated ERK and phosphorylated Akt were both increased, indicating that EGCG confers a positive effect on cell growth (Figure 9). Furthermore, EGCG treatment increased the expression of Bcl-2, a suppressor of apoptosis, and reduced the expression of Bax, a key inducer of apoptosis.

Once daily topical EGCG
Figure 9: Effect of once daily 10% topical EGCG on the protein expression of Erk, Akt, BCl-2, and Bax in 3 healthy subjects after 4 days. Adapted from:[22]Muller-Rover, S., Rossiter, H., Lindner, G., Peters, E.M.J., Kupper, T.S., Paus, R. (1999). Hair follicle apoptosis and Bcl-2. Journal of Investigative Dermatology. 4. 272-277. Available at: … Continue reading

So, these findings indicate that topical EGCG can suppress cell death whilst simultaneously enhancing cell growth in humans. However, this study was not completed in people with any type of hair loss disorder, therefore we cannot say whether it will actually work to stimulate hair growth in those with hair loss.

Is EGCG Supplementation Safe?

The European Food Safety Authority has assessed the safety of green tea catechins. They have determined that catechins from green tea infusions and similar drinks are generally safe. However, when taken as a food supplement, catechin doses at or above 800 mg/day may pose health concerns due to liver damage.[23]Younes, M., Aggett, P., Aguilar, F., Crebelli, R., Dusemund, B., Filipic, M., Frutos, M.J., Galtier, P., Gott, D., Gundert-Remy, U., Lambre, C., Leblanc, J.C., Lillegaard, I.T., Moldeus, P., … Continue reading

Who might benefit from EGCG Supplementation?

Based on the limited available data, people with androgenetic alopecia may benefit from EGCG treatment. However, there are no clinical studies undertaken using EGCG alone in patients with hair loss disorders, so we cannot recommend using it alone.

References

References
1 Singh, B.N., Shankar, S., Srivastava, R.K. (2011). Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications. Biochemical Pharmacology. 82(12). 1807-1821. Available at: https://doi.org/10.1016/j.bcp.2011.07.093
2 Dhariwala, M, Y., Ravikumar, P. (2019). An overview of herbal alternatives in androgenetic alopecia. Journal of Cosmetic Dermatology. 18. 966-975. Available at: https://doi.org/10.1111/jocd.12930
3 Musial, C., Kuban-Jankowska, A., Gorska, Ponikowska, M. (2020). Beneficial properties of green tea catechins. International Journal of Molecular Science. 21(5). 1744. Available at: https://doi.org/10.3390/ijms21051744
4, 5 Hiipakka, R.A., Zhang, H.Z., Dai, W., Dai, Q., Liao, S. (2002). Structure-activity relationships for inhibition of human 5α-reductases by polyphenols. Biochemical Pharmacology. 63. 1165-1176. Available at: https://10.1016/s006-2952(02)00848-1
6, 8, 9, 10 Shin, S., Kim, K., Lee, M.J., Lee, J., Choi, S., Kim, K.S., Ko, J.M., Han, H., Kim, S.Y., Youn, H.J., Ahn, K.Y., An, I.S., An, S., Cha, H.J. (2016). Epigallocatechin gallate-mediated alteration of the microRNA expression profile in 5α-Dihydrotestosterone-treated human dermal papilla cells. Annals of Dermatology. 28(3). 327-334. Available at: https://10.5021/ad.2016.28.3.327
7 Morgan, B.A., (2014). The dermal papilla: an instructive niche for epithelial stem and progenitor cells in development and regeneration of the hair follicle. Cold Spring Harbor Perspectives in Medicine. 4(7). a015180. Available at: https://doi/org/10.1101/cshperspect.a015180
11 Lai, J.J., Chang, P., Lai, K.P., Chen, L., Chang, C. (2012). The role of androgen and androgen receptors in skin-related disorders. Archives of Dermatological Research. 304(7). 499-510. Available at: https://doi.org/10.1007/s00403-012-1265-x
12 Hernandez-Segura, A., Nehme, J., Demaria, M. (2018). Hallmarks of cellular senescence. Trends in Cellular Biology. 28(6). 436-453. Available at: https://doi.org/10.1016/j.tcb.2018.02.001
13, 15, 18, 21 Kwon, O.S., Han, J.H., Yoo, H.G., Chung, J.H., Cho, K.H., Eun, H.C., Kim, K.H. (2007). Human hair growth enhancement in vitro by green tea epigallocatechin-3-gallate (EGCG). Phytomedicine. 14. 551-555. Available at: https://doi.org/10.1016/j.phymed.2006.09.009
14 O’Brian, J., Hayder, H., Zayed, Y., Peng, C. (2018). Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Frontiers in Endocrinology. 9. 1-12. Available at: https://doi.org/10.3389/fendo.2018.00402
16 Bourguignon, L.Y.W., Matrix hyaluronan-activated CD44 signaling promotes keratinocyte activities and improves abnormal epidermal functions. The American Journal of Pathology. 184(7). 1912-1919. Available at: https://dx.doi.org/10.1016/j.ajpath.2014.03.010
17 Lavoie, H., Gagnon, J., Therrien, M. (2020). ERK signaling: a master regulator of cell behavior, life, and fate. Nature Reviews Molecular Cell Biology. 21. 607-632. Available at: https://doi.org/10.1038/s41580-020-0255-7
19, 20, 22 Muller-Rover, S., Rossiter, H., Lindner, G., Peters, E.M.J., Kupper, T.S., Paus, R. (1999). Hair follicle apoptosis and Bcl-2. Journal of Investigative Dermatology. 4. 272-277. Available at: https://doi.org/10.1038/sj.jidsp.5640228
23 Younes, M., Aggett, P., Aguilar, F., Crebelli, R., Dusemund, B., Filipic, M., Frutos, M.J., Galtier, P., Gott, D., Gundert-Remy, U., Lambre, C., Leblanc, J.C., Lillegaard, I.T., Moldeus, P., Mortenson, A., Oskarsson, A., Stankovic, I., Waalkens-Berendsen, I., Wouterson, R.A., Andrade, R.J., Fortes, C., Mosesso, P., Restani, P., Arcella, D., Pizzo, F., Smeraldi, C., Wright. (2018). Scientific opinion on the safety of green tea catechins. EFSA Journal. Available at: https://doi.org/10.2903/j.efsa.2018.5239

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