Humans are usually born with approximately 5 million hair follicles, and no new follicles are added after birth [1]. The hair follicle cycle, which begins in utero, comprises 3 stages: the anagen, telogen, and catagen phases. Anagen represents the growth phase associated with extensive mitotic activity, and 90% to 95% of all hair exists in the anagen phase at any given point in time. Hair then involutes during the catagen phase through apoptosis of the follicular keratinocytes and is converted to club hair. Telogen is the resting phase associated with inactivity of the hair follicle. The club hair is shed and new anagen hair growth begins, resuming the cycle [234].

Usually, approximately 50 to 100 hairs are shed per day. Hair loss >100 hairs/d is defined as alopecia. There are different types of alopecia that can cause hair loss on the scalp or on other areas of the body [5]. Hair loss can be attributed to multiple factors, including dandruff, hormonal deficiencies, dietary or nutrient deficiencies, certain diseases, chemotherapy, and/or psychological issues, such as stress and depression [6]. In most men, androgenetic alopecia develops with a distinctive “patterned” hair line recession. In women, the presentation may be less clear; typically women will develop a diffuse thinning over the top ofthe scalp, yielding a “Christmas tree” pattern with more thinning towards the front, although the frontal hairline is maintained [7]. Occasionally, men may develop a female presentation of hair loss and women, primarily those experiencing excess androgen activity, may develop a more men-like hair loss pattern [8]. Five-α reductase inhibitors are used to treat androgenetic alopecia, and are effective for preventing hair loss progression and induction of hair regrowth in androgenetic alopecia in men. However, they are not recommended for women, and side effects, such as erectile dysfunction and decreased libido have been reported [910]. Additionally, alopecia may result from sun exposure, consumption of junk food, use of styling tools, and/or extreme weight loss [11]. Alopecia is associated with significant psychosocial consequences and can affect patients' lives and social behavior, often triggering psychological problems [12]. No robust evidence supports the consistent efficacy of topical treatments, including topical corticosteroids, tacrolimus, cryotherapy, minoxidil, anthralin, or ultraviolet light A combined with oral psoralens in treating alopecia [13], and those options are usually not suitable for patients presenting with extensive alopecia because of their minimal efficacy [1415]. Minoxidil is a topical vasodilator that prolongs the anagen phase and increases the size of smaller hair follicles [1]. Its exact mechanism of action has not yet been determined, although a few research studies have presented data suggesting that an improved nutritional supply to the scalp secondary to vasodilation may play a key role in its demonstrated efficacy [1617]. Despite positive effects on alopecia, several adverse effects of commercial hair restorers have been reported, limiting their use for treatment of patients with alopecia [1819].

Recently, several experimental and clinical studies have reported that probiotic supplementation demonstrated beneficial effects on serum lipid profiles, indicating improvements in peripheral blood flow [2021]. Based on these research data, we hypothesized that dietary supplementation of probiotics could benefit patients presenting with alopecia secondary to improved blood flow to the scalp. We investigated the effect of administration of a kimchi and cheonggukjang probiotic product on patients with hair loss. Kimchi and cheonggukjang (a Korean traditional fermented soybean product) are traditional Korean foods, but ensuring optimal intake of probiotics from kimchi and cheonggukjang is difficult, for two main reasons. First, the amount of probiotics varies depending on the ripening period of kimchi, as different ripening periods lead to differences in pH that could affect personal appetite. Koreans consume cheonggukjang as a boiled hot soup, so it contains no live probiotics. Thus, administration of live probiotics from kimchi and cheonggukjang as a drinkable yogurt would be a more efficient way to obtain the beneficial effects of kimchi and cheonggukjang. The primary ingredients in this product are the probiotic-rich kimchi and cheonggukjang. All patients were administered a kimchi and cheonggukjang probiotic product over the course of 4 months, and hair thickness and count were measured at 1 and 4 months.

Forty-six patients were enrolled in this study. All patients completed the study. The patients' characteristics are shown in Table 1. The hair parameters measured after 1 and 4 months of administration of a kimchi and cheonggukjang probiotic product were compared with the baseline (0-month) values. At baseline, in all patients (n=46), the hair count was 85.98±20.54 hairs/cm² and thickness was 0.062±0.011 mm. As shown in Table 2, hair count and thickness had significantly increased at 1 month (90.28±16.13 hairs/cm² and 0.068±0.008 mm, respectively) and at 4 months (91.54±16.29 hairs/cm² and 0.066±0.009 mm, respectively) compared to the baseline value (p<0.001). We observed that after 1 month of administration of the kimchi and cheonggukjang probiotic product, 63.0% of the total patients (n=29) showed improvements in the measured hair parameters (thickness and count), and 21.8% (n=10) and 4.3% (n=2) of all patients showed improvements in only hair thickness and count, respectively. In 10.9% (n=5) of the total patients, no improvement was observed in either hair parameter that was assessed (Fig. 1). After 4 months, 54.3% (n=25) of all patients showed improvement in both assessed parameters, while 21.8% (n=10) and 17.4% (n=8) of the total patients showed improved hair thickness and count, respectively, and 6.5% (n=3) of the total patients showed no improvement in either assessed parameter (Fig. 2).

We analyzed data based on sex (23 male and 23 female) to determine whether the efficacy of the kimchi and cheonggukjang probiotic product differed by sex. In male patients, hair count increased steadily from baseline to 4 months (86.91±22.21 hairs/cm² at the initial visit, 88.17±17.50 hairs/cm² at 1 month, and 90.78±17.65 hairs/cm² at 4 months; p<0.001). Thickness had also increased at 1 month (0.064±0.007 mm) and 4 months (0.063±0.006 mm) compared to baseline (0.058±0.009 mm, p=0.002) (Table 3). In female patients, hair count had increased at 1 month (92.39±14.72 hairs/cm²) and 4 months (92.30±15.17 hairs/cm²) compared to the initial visit (85.04±19.18 hairs/cm²) (p<0.001). After 1 and 4 months, hair thickness in female patients was observed to have increased (0.072±0.006 mm and 0.072±0.010 mm, respectively) compared to baseline (0.066±0.011 mm, p=0.001) (Table 4). We observed that 52.2% (n=12) of male and 73.9% (n=17) of female patients showed improvement in both parameters (hair thickness and count) after 1 month of administration of the kimchi and cheonggukjang probiotic product. In 39.1% (n=9) of male patients, we observed an improvement in only hair thickness, without any change in hair count during the same period. In 8.7% (n=2) of men, the hair parameters were unaffected following administration of the kimchi and cheonggukjang probiotic product over 1 month. After 1 month of probiotic administration, 4.3% (n=1) and 8.7% (n=2) of female patients showed improved hair thickness and hair count, respectively. We observed that in 13.1% (n=3) of female patients, both hair parameters were unaffected after 1 month of kimchi and cheonggukjang probiotic product administration (Fig. 3). An improvement in both hair parameters was noted after 4 months of probiotic product administration in 39.1% (n=9) of male and 69.6% (n=16) of female patients. Hair thickness had improved in 30.5% (n=7) of male and 13.0% (n=3) of female patients after 4 months of administration of the kimchi and cheonggukjang probiotic product. We observed that 26.1% (n=6) of male and 8.7% (n=2) of female patients showed an improved hair count during the same period. No improvement in either hair parameter was observed in 4.3% (n=1) of male and 8.7% (n=2) of female patients after 4 months of probiotic administration (Fig. 4). Fig. 5 presents a vertex view of female and male patients with alopecia showing that administration of the kimchi and cheonggukjang probiotic could increase hair density and number after 4 months when compared with baseline (0 month).

As their health benefits have become known, probiotics are being widely used globally. Probiotics primarily include bacteria from the genera Streptococcus, Enterococcus, Pediococcus, Weissella, and Lactobacillus, although the most commonly used probiotics belong to Lactobacillus and Bifidobacterium spp. [24]. Probiotics are live organisms that are primarily used to improve the signs and symptoms of gastrointestinal disorders such as diarrhea, irritable bowel syndrome, constipation, and lactose intolerance, as well as to inhibit the excessive proliferation of pathogenic intestinal bacteria. However, recent studies have suggested that probiotics could have beneficial effects that extend beyond gastrointestinal health, as they have demonstrated efficacy in improving certain metabolic disorders such as hypertension [25], hypercholesterolemia [21], and atherosclerosis [26]. The suggested mechanisms of probiotic action in metabolic disorders include inhibition of pathogen adhesion to the gut mucosa, stabilization of microbial flora, and/or improvement of mucosal integrity and barrier function, which can improve energy metabolism and insulin sensitivity [27]. Metabolic diseases such as hypercholesterolemia negatively affect microvascular function, which can be reversed with use of cholestyramine lipid-lowering therapy [28]. Based on these data, intake of appropriate quantities of probiotics could lead to a beneficial effect on peripheral vascular blood flow and hair growth.

The kimchi and cheonggukjang probiotic product analyzed in this study included various kinds of probiotics and prebiotics obtained from kimchi, cheonggukjang, and natural herbs. Choi et al [5] reported that ultra-high molecular weight poly-γ-glutamic acid (UHMW γ-PGA) isolated from Bacillus subtilis (used to ferment cheonggukjang) could improve hair growth in vivo. The authors showed that UHMW γ-PGA inhibited activity of 5-α reductase, an enzyme produced in the prostate, adrenal glands, and scalp, which metabolizes the male hormone testosterone into dihydrotestosterone [29], resulting in an improvement of alopecia in men. Thus, in that study, we concluded that the difference in the pattern of improvement observed between men and women was secondary to the difference in its effect on the 5-α reductase present in the scalp.

In our present study, all enrolled patients were administered a kimchi and cheonggukjang probiotic product over a maximum period of 4 months. Overall, 93% of all patients demonstrated beneficial effects in terms of the hair parameters that were assessed (thickness and hair count); furthermore, the proportion of those who experienced no effects decreased over time (10.9% vs. 6.5%) (Fig. 1, 2). These effects were evident within a month of intake of the kimchi and cheonggukjang probiotic product. The effectiveness of the kimchi and cheonggukjang probiotic product varied between men and women. Men were more likely to experience an effect on only hair thickness (30.4%) or only hair count (26.1%) than an effect on both parameters (39.1%). In contrast, most women showed a positive effect on both hair parameters that were assessed (65.2%), and only 13.0% and 8.7% of women showed improvements in only hair thickness or only hair count, respectively. We observed that administration of the kimchi and cheonggukjang probiotic product was ineffective in 4.3% of men and 8.7% of women (Fig. 4). Cheonggukjang is a known source of thrombolytic enzymes. Jeong et al [30] studied the characterization of a fibrinolytic enzyme from Bacillus subtilis CH3-5 that was isolated from cheonggukjang. This thrombolytic enzyme could increase the peripheral blood flow, including to the scalp, and increase the amount of nutrition provided to hair follicles.

In this study, the efficacy of the kimchi and cheonggukjang probiotic product was different between male and female patients, as improvements in both criteria (thickness and count) at 1 month (73.9% vs. 52.2%) and 4 months (65.2% and 39.1%) were more common than in male patients in the same period. However, male patients were more likely to experience improvements in only hair thickness at 1 month (39.1% vs. 4.3%) and 4 months (30.4% vs. 13.0%) than female patients in the same period. The prevalence of androgenetic alopecia in Korean shows a sex bias, as 10.8% of Korean men and 3.8% of Korean women in their 40s are diagnosed with androgenetic alopecia [31]. According to our data, we suggest that kimchi and cheonggukjang probiotics exert limited effects on androgenetic alopecia, and further study is therefore needed to verify the different effects of kimchi and cheonggukjang probiotics on men and women.

The use of drugs associated with hair regrowth such as finasteride and minoxidil is limited and temporary, due to adverse effects associated with their use, such as irregular heartbeat and weight gain [32]. In this study, we found that a kimchi and cheonggukjang probiotic product could promote hair growth and reverse hair loss without associated adverse effects such as diarrhea. Thus, we conclude that the use of natural probiotic products is a safer treatment strategy for patients presenting with alopecia.

This study has some limitations. First, we did not measure changes in the blood flow of the scalp and or blood lipid profiles of all patients enrolled this study. Second, we did not use a placebo group as a negative control. However, we did compare the effects of probiotics before and after administration. Third, the observation period was relatively short, and the number of patients was relatively small; therefore, we were not able to establish whether the probiotic effects on alopecia would be reversed or maintained during a longer period.

To summarize, we suggest that the observed improvements in hair count and thickness resulted from initiation of the anagen phase in hair follicles secondary to the improved blood flow and modulation of androgenetic effects by probiotics. However, ours is a clinical study. Therefore, further studies investigating the mechanism of action of probiotics and their role in hair growth are warranted.