Ginseng & Hair Loss

The nutraceutical market is fuelled by a growing interest in natural, safe, multi-target and effective solutions and the hair health segment is no exception. Faced with the ineffectiveness and potential associated side effects of existing pharmacological treatments, consumers are demanding innovative clinically proven plant-based alternatives.

Recently revealed as a trending hair growth ingredient in Asia, ginseng has been the subject of encouraging research in the context of androgenic alopecia that may well position it as the next botanical of choice to prevent and treat hair loss.

In this article, we review the scientific data supporting ginseng’s demonstrated efficacy to prevent androgenetic hair loss.

1. HAIR LOSS – INCIDENCE & CAUSES

Hair loss is a common and distressing condition among aging men and women. In Europe alone, it is estimated to affect over 80% of men and up to 40% of women over the age of 70 [1]. Although the causes can be varied and multifactorial – ranging from nutritional deficiencies to high levels of stress and auto-immune disorders (alopecia areata) – hormone-dependent baldness remains the leading cause of hair loss in adults and seniors.

Androgenetic Alopecia (AGA), otherwise known as male-pattern hair loss, is characterized by a gradual patterned baldness with highly variable age onset and makes up for over 95% of hair loss causes in men [2].

Although environmental and lifestyle factors may influence its onset, male-pattern baldness has a significant genetic component which causes high levels of circulating 5α-reductase. This enzyme is involved in androgenic metabolism and is known for its role in converting testosterone into dihydrotestosterone (DHT), a potent androgen metabolite and androgen receptor (AR) antagonist. As a result of this 5α-reductase-mediated increase in DHT, the size and life cycle of hair follicles shortens, and symptoms of hair loss appear.

Among the most common pharmacological solutions to combat hair loss are minoxidil, a hair growth stimulating vasodilator also used in topical applications, and 5α-reductase inhibitors like finasteride and dudasteride. However, these blockbuster drugs require life-long treatments and carry their share of undesirable side effects – all for a limited efficacy. In addition, non-oral solutions (topic, transplants, laser) can be invasive and expensive. The unsatisfactory offer in terms of oral solutions is creating significant traction for new natural, safer and more effective dietary supplements for hair loss prevention and treatment.

2. HAIR LOSS MARKET

In the current context of aging world populations, hair loss is very likely to come to the forefront of the nutraceutical market applications in the next few years.

In 2020 alone, the global hair loss treatment industry – comprising topical and oral solutions only – was estimated at €3,5 billion [3]. The hair supplements market represents 25,3% of that industry, amounting to € 874 million in value last year [4]. The segment is projected to keep growing at a 11,5% annual rate and reach €2,6 billion by 2031.

North America only represents 33% of global hair supplements market shares, making up for half of the market with Europe. In terms of growth, East and South Asia are the main drivers with expected CAGR of 14,6% and 13,8%, respectively [4].

2.1. Market trends

As a result of a boom in the trend of nutricosmetics, feminine hair health supplements are aplenty on the market and have been popularized in recent years by multivitamin gummies brands like Sugarbear. Although an extensive offer is available, it targets adult working women – products promises are therefore more focussed on the improvement of the aesthetic appearance of the hair (shine, volume, strength) rather than the prevention of hair loss.

Meanwhile, equivalent hair health products for men – almost exclusively targeting hair loss – remain relatively rare and tend to address an older target and therefore to be a lot more medicalised.

In both cases, the existing supplement offer mainly comprises multivitamin blends aimed at providing all the necessary nutrients to prevent deficiencies and ensure healthy hair growth, as well as key ingredients such as biotin, keratin, omega fatty acids and antioxidants – all of which have demonstrated benefits in improving hair growth. There are however relatively few plant extracts in this category.

Among the most commonly used botanicals in this category is saw palmetto, recognized for its inhibitory effects on 5α- reductase therefore blocking the synthesis and hair-loss effects of DHT. It could also contribute to hair growth due to its anti-inflammatory potential and strengthen hair follicles. Other natural DHT blockers include pumpkin seeds, pine bark and stinging nettle.

In terms of galenic forms, capsules remain the largest go-to solution for 44,5% of hair supplements. However, increasingly common trendy food-inspired formats like gummies & soft-gels are achieving the fastest growth (13,1%) [4].

To respond to changing consumer’s needs, the hair health market is evolving towards more natural-based, organic and chemical-free solutions. Holistic lifestyle approaches based on personalized nutrition are also heavily influencing the offer in this segment – including the extension of vegan plant-based alternatives.

2.2. Brands & Product Applications

  •  NUTRAFOL (US)

New-York based brand Nutrafol specializes in hair wellness from within and offers range of patented clinically tested hair growth nutraceuticals for men and women. On top of gender and life-stage specific formulas prescribed through a personalized diagnostic questionnaire, Nutrafol offers a range of add-on boosters and serums, consultations with hair loss professionals and even Hair Mineral Analysis services.

Their Men Hair Growth Nutraceutical Nutrafol Men is a 21-ingredient dietary supplement for hair growth and scalp coverage with a multi-target approach to tackle androgenic alopecia:

  • Nutrition – by covering basic needs in vitamins and minerals needed to promote healthy hair growth.
  • Hormones – through the DHT-inhibiting properties of saw palmetto.
  • Lifestyle – through potent antioxidant / anti-inflammatory bioactives such as curcumin and tocotrienol (vitamin E) complex.
  • Stress – through adaptogenic and stress relieving properties of Ashwagandha.
  • Aging – antioxidants and collagen.

 

  • KRYNEO (LUX)

Kryneo, a Luxembourg-based brand with a small but highly qualitative offer of hair health supplements is also betting on highly concentrated science-backed formulas with 100% natural ingredients. The offer is divided into 2 cures with gender-specific declinations aimed at preventing hair loss and stimulating growth in men and women.

Essential Care cures are a complete keratin, multivitamins and minerals formula designed to prevent deficiency-related hair loss in men and women and promote hair strength & vitality.

Intense Repair on the other hand, brings all the nutrients and benefits of the Essential Care cure to slow hair loss but also highly efficient botanicals to boosts regrowth and density. The 4-capsule day and night cure targets oxidative stress (astaxanthin, grape polyphenols), stress relief (saffron), DHT-inhibition (saw palmetto) and gender-specific botanicals for hormonal regulation (stinging nettle, tribulus terrestris and fenugreek for men, hops, alfalfa, and flax seeds for women).

 

  • ABSOLOGY (FR)

Absology, a young nutricosmetics brand from France, is also in the business of safe, vegan, clean-label natural and high performing hair products – with an additional emphasis on transparency, EU origin and commitment to the environment.

Absology’s two hair health solutions are based on the hair growth potential of KeranatTM, a patented clinically proven natural complex extracted from a French variety of millet. KeranatTM was shown to have direct action on dermal papilla – thus efficiently limiting hair loss and enhancing hair density and volume. Stop and Grow Hair and Healthy & Glowy Hair combine artichoke extract, iron and biotin and vitamins A, E and K respectively – to restore a healthy life cycle and enhance hair beauty.

3. GINSENG & HAIR LOSS

Ginseng is undoubtedly the most famous medicinal plant in traditional Asian medicine, and for a good reason: its virtues as an elixir of longevity have earned it more than 3000 years of use and a place of honour in the Chinese, Korean and Japanese pharmacopoeias. Today, ginseng roots are one of the most well-know and used botanicals in the nutraceutical industry worldwide.

As such, ginseng has long been investigated by modern science, with a significant amount of data supporting its positive effects on age-related discomforts and pathologies like fatigue, cognition and metabolic disbalance, to name a few.

New potential applications for the precious roots keep emerging from the abundant research, inspired by traditional use. One of them is androgenetic alopecia or male hair loss, a popular benefit attributed to ginseng throughout Asia, and especially in China.

Although research on ginseng’s potential for hair loss is still at its infancy, an increasing number of data is building, with encouraging results for future applications in this field. Ginseng extract and several its active constituents have been demonstrated beneficial for hair health, several studies even going as far as to claim ginseng and some of its constituents could constitute a natural alternative to minoxidil [5-8] or finasteride [9], two known topical treatments against hair loss.

In this article, we review the scientific data supporting ginseng’s demonstrated efficacy to prevent androgenic hair loss.

3.1. Clinical Studies

Firstly, 2 clinical studies carried out in Korea have demonstrated the positive effects of Korean red ginseng supplementation on androgenetic alopecia in treatment alone [10] as well as on female alopecia in co-treatment with 3% minoxidil [11]. In both cases, the ginseng-treated group demonstrated significant improvement in capillary density and thickness, as well as superior evaluation by patients and dermatologists alike.

Korean ginseng extract was also demonstrated to support hair regrowth in combination with corticosteroid intralesional injections in patients suffering from alopecia areata, an immunogenic hair loss condition [12].

3.2. Animal Studies

A number of animal studies have also been conducted to test ginsengs hair-growth properties in-vivo.

The first consisted in intragastric supplementation of ginsenoside Rb1 to senescent mice with age-related hair loss and grey hair; results showed significant attenuation of age-related hair loss in treated mice [13].

Furthermore, several ginsenosides were tested in topic application. Rb1 and Rd significantly enhanced hair growth in shaved mice rodent strains with a dark, dense coat [14]. Ginsenoside Re demonstrated efficacy in promoting hair growth of nude mice, in a similar manner than that of minoxidil [6]. Finally, a red ginseng extract and Ro even showed an inhibitory effect on hair re-growth suppression in testosterone-treated mice, a model of androgenetic alopecia [15]. In another study, topical application of red ginseng oil also reversed testosterone-induced hair loss in mice [16].

In addition, the hair growth-promoting properties of ginseng in subcutaneous injection were confirmed in-vivo, showing significantly higher hair growth visual score – again, in a similar manner to that of minoxidil treatment – as well as enhanced cellular proliferation within hair follicles [17].

Furthermore, non-saponin compounds may also contribute to ginseng’s effects; application of a gintonin-enriched fraction on synchronized telogen phase (hairless) mice was also shown to stimulate hair growth [18].

3.3. In-vitro Studies

  • Human Hair Follicles (HF) proliferation

 

In-vitro studies – more significant in numbers – show the potential of ginseng extract to induce cells proliferation in keratinocytes from human hair follicles (HFs) [5, 7], particularly with red ginseng [17]. This property may be attributed to the activity of a wide range of specific ginsenosides, namely Rg3 [17], Rd [14], Rb1 [5, 14, 17], F2 [9], Re and Rg1 [5], but also to gintonin [18], a glycoprotein compound found in ginseng.

Ginsenoside Rg3 also showed potential to stimulate the proliferation of dermal papilla through enhanced expression of vascular endothelial growth factor (VEGF) gene, thus promoting hair growth [19]. Studies report that VEGF, a known angiogenic factor, acts as an autocrine growth factor for dermal papilla whose regulation has been correlated to different phases of hair growth. Ginsenoside Rg3 was shown to up-regulate mRNA expression of VEGF in a similar manner to that of minoxidil. Gintonin also stimulated the release of VEGF in papilla dermal cells [18].

Another one of the suggested mechanisms of ginsenosides effects on HFs proliferation could be the induction / up-regulation by Rb1 and Rd of follicular keratinocytes differentiation through p63, a major marker and regulator of keratinocyte progenitors [14].

 

  • Protective effect against hair loss factors

 

As previously mentioned, several ginsenosides have been shown to promote hair growth in several mouse models by preventing apoptosis of HF cells, through effects on various factors of hair loss.

One of the elucidated mechanisms is through the inhibitory effect of ginseng components on 5α-reductase, a key enzyme in male hair loss as it catalyzes the conversion of testosterone into dihydrotestosterone (DHT) in HFs [15, 17].

DHT is an androgenic hormone believed to be the main intermediary of androgen-dependent hair loss, as it inhibits the up regulation of androgen receptors in hDPCs. It is important to note that the efficacy of finasteride in preventing hair loss is based on an 5α-reductase inhibitory mechanism.

Among the various ginsenosides that show inhibitory action on 5α-reductase are Rg3 [15, 17], which shows de most potent effect, but also Rb1 [17], Rd and Ro [15].

The study showed the positive effects of red ginseng extract and ginsenosides Rg3 and Rb1 against hair growth inhibition by DHT. Both saponins showed significant protective effect against DHT-induced suppression of keratinocyte proliferation in human dermal papilla cells (hDPCs) through upregulation of the mRNA expression of androgen receptor. They also enhanced associated activation of ERK (proliferation factor) and AKT (anti-apoptotic factor) signalling pathways [15]. Red ginseng extract, and its constituents Rg3 and Rb1 in particular, have thus been demonstrated to abrogate DHT-induced suppressive effect and could thus prevent hair loss. A similar DHT protective effect was also shown with ginsenoside F2 [9].

In addition, a 2017 study was conducted to assess the protective effects of ginseng against Dickkopf-1 (DKK-1), a known hair-growth inhibitor, in cultured outer root sheath (ORS) keratinocytes in human hair follicles (HFs) [7]. The tested ginseng was a ginsenoside-enriched extract with Rb1, Rb2, Rc, Rd, Re and Rg1 as major components. When administered in co-treatment with DKK-1, the ginseng extract showed strong antagonistic effects: it protected hair cells against DKK-1-induced apoptosis through down-regulation of apoptotic factor Bax and promotion of anti-apoptotic factor Bcl-2, thus reversing the hair loss resulting from DKK-1 treatment.

An extract of Korean red ginseng showed a similar effect on the regulation of apoptosis factors Bax/Back-2 in human hair follicle organ culture treated with 4-hydroperoxycyclophosphamide (4-HC), a model of chemotherapy-induced alopecia [20].

Other ginsenosides (Re, F) induce decreased expression of apoptosis factors like SCAP [9] and TGF-β2 [6, 9] shown to be involved in HF entry into catagen phase (end of hair growth and early onset of hair loss).

CONCLUSION

Taken together, in-vitro and in-vivo results both point at the high potential of ginseng and its bioactive metabolites to prevent and counteract hair loss, in particular in cases of androgenic alopecia.

Clinical studies on Korean patients with alopecia show promising results for human applications of ginseng hair-loss preventive treatments. However, due to the high variability in tested ginseng extracts, additional clinical data is needed to confirm these effects in humans.

Furthermore, ginseng’s known adaptogenic benefits could play an important part in stress relief  – the latter being an important aggravating lifestyle factor of hair loss.

Ginseng and its bioactive components could very well offer patients a natural and efficient science-backed alternative or adjuvant to current treatments. Based on single molecule results, it seems that rare bioactive ginsenosides like Rg3 are particularly active in this sphere and may contribute substantially to ginseng’s benefits against hair loss. The high content of these noble ginsenosides therefore appears as an important parameter to consider when selecting ginseng root ingredients for the development of efficient hair growth applications.

REFERENCES

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[2] Grand View Research“Alopecia Market Size, Share & Trends Analysis Report”, July 2021.

[3] Ring, C., Heitmiller, K., Correia, E., Gabriel, Z., Saedi, N. (2022) – “Nutraceuticals for Androgenetic Alopecia.” J Clin Aesthet Dermatol. 2022;15(3):26–29.

[4] Transparency Market Research – “Hair Supplements Market, Global Industry Analysis, 2021-2031”, August 2021.

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[6] Li Z, Ryu SW, Lee J, Choi K, Kim S, Choi C (2016) – “Protopanaxatirol type ginsenoside Re promotes cyclic growth of hair follicles via inhibiting transforming growth factor beta signaling cascades.” Biochem Biophys Res Commun. 2016 Feb 19;470(4):924-9.

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[8] Park, S., Shin, W. S., & Ho, J. (2011) – Fructus panax ginseng extract promotes hair regeneration in C57BL/6 mice.” Journal of ethnopharmacology, 138(2), 340–344.

[9] Shin, H. S., Park, S. Y., Hwang, E. S., Lee, D. G., Mavlonov, G. T., & Yi, T. H. (2014)“Ginsenoside F2 reduces hair loss by controlling apoptosis through the sterol regulatory element-binding protein cleavage activating protein and transforming growth factor-β pathways in a dihydrotestosterone-induced mouse model.” Biological & pharmaceutical bulletin, 37(5), 755–763.

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[11] Ryu HJ, Yoo MG, Son SW – “The efficacy of 3% minoxidil vs. combined 3% minoxidil and Korean red ginseng in treating female pattern alopecia.” Int J Dermatol 2014;53(June (6)):e340–2.

[12] Oh, G. N., & Son, S. W. (2012) – “Efficacy of korean red ginseng in the treatment of alopecia areata.” Journal of ginseng research36(4), 391–395.

[13] Yu S, Xia H, Guo Y, Qian X, Zou X, Yang H, Yin M, Liu H (2020) – “Ginsenoside Rb1 retards aging process by regulating cell cycle, apoptotic pathway and metabolism of aging mice.” J Ethnopharmacol. 2020 Jun 12;255:112746.

[14] Li Z, Li JJ, Gu LJ, Zhang DL, Wang YB, Sung CK (2013) – “Ginsenosides Rb1 and Rd regulate proliferation of mature keratinocytes through induction of p63 expression in hair follicles.” Phytother Res. 2013 Jul;27(7):1095-101.

[15] Murata K, Takeshita F, Samukawa K, Tani T, Matsuda H (2012) – “Effects of ginseng rhizome and ginsenoside Ro on testosterone 5α-reductase and hair re-growth in testosterone-treated mice.” Phytother Res. 2012 Jan;26(1):48-53.

[16] Truong, V. L., & Jeong, W. S. (2021) – “Hair Growth-Promoting Mechanisms of Red Ginseng Extract through Stimulating Dermal Papilla Cell Proliferation and Enhancing Skin Health.” Preventive nutrition and food science26(3), 275–284.

[17] Park GH, Park KY, Cho HI, Lee SM, Han JS, Won CH, Chang SE, Lee MW, Choi JH, Moon KC, Shin H, Kang YJ, Lee DH (2015) – “Red ginseng extract promotes the hair growth in cultured human hair follicles.” J Med Food. 2015 Mar;18(3):354-62.

[18] Lee, N. E., Park, S. D., Hwang, H., Choi, S. H., Lee, R. M., Nam, S. M., Choi, J. H., Rhim, H., Cho, I. H., Kim, H. C., Hwang, S. H., & Nah, S. Y. (2020) – Effects of a gintonin-enriched fraction on hair growth: an in vitro and in vivo study.” Journal of ginseng research44(1), 168–177.

[19] Shin DH, Cha YJ, Yang KE, Jang IS, Son CG, Kim BH, Kim JM (2014) – “Ginsenoside Rg3 up-regulates the expression of vascular endothelial growth factor in human dermal papilla cells and mouse hair follicles.” Phytother Res. 2014 Jul;28(7):1088-95.

[20] Keum, D. I., Pi, L. Q., Hwang, S. T., & Lee, W. S. (2016) – Protective effect of Korean Red Ginseng against chemotherapeutic drug-induced premature catagen development assessed with human hair follicle organ culture model.” Journal of ginseng research40(2), 169–175.