madman
Super Moderator
Purpose
Androgenetic alopecia (AGA) is the most common type of hair loss in humans, affecting self-esteem and emotional well-being. This study aimed to assess the safety and efficacy of VISPOTM, a standardized saw palmetto oil (2–3% β-sitosterol), in subjects with mild-to-moderate AGA.
Methods
In a double-blind, placebo-controlled, four-arm clinical study, 80 healthy male and female subjects aged 18–50 years were randomly allocated (1:1:1:1) to receive either 400 mg capsules of VISPO or 5 mL of a topical formulation containing 20% VISPO or the respective placebo once daily for 16 weeks. The primary endpoints included hair count (hair comb and hair pull tests) and the self-assessment of perceived efficacy. The objective evaluation was performed using the global photographic assessment score. Hair density, thickness, and anagen/telogen ratio were evaluated using phototrichogram analysis.
Results
At the end of the study, oral and topical formulations of VISPO reduced hair fall by up to 29% (p<0.001) and 22.19%(p<0.01) from the baseline, respectively. Hair density increased by 5.17% and 7.61% in the oral and topical VISPO groups, respectively (p<0.001). In addition, oral ingestion of VISPO resulted in a marked reduction in serum dihydrotestosterone (DHT)levels in the subjects compared to placebo (p<0.001). However, the effect of the VISPO formulations on the anagen/telogen ratio was significant. No serious adverse effects were observed during the study.
Conclusion
VISPO formulations reduced hair fall and promoted hair regrowth and scalp appearance in AGA patients.
Introduction
Androgenetic alopecia (AGA) is a progressive hair loss condition, with a characteristic pattern in both men and women. In men, AGA, also known as male pattern hair loss (MPHL), is caused by a greater sensitivity of the hair follicles to the androgens;1 however, the cause of female pattern hair loss (FPHL) and its association with androgen remain unclear.2The incidence of progressive hair loss by AGA has become more prevalent in recent years. AGA is common in nearly 80% of aging men.3 Hair loss negatively impacts the psychological and social well-being of an individual.4 Presently, minoxidil and finasteride are the only FDA (Food and Drug Administration) approved medications for AGA. Minoxidil is used for topical applications and works by stimulating hair follicles via anagen phase induction. Several clinical studies have reported the efficacy of minoxidil against alopecia, including AGA, Alopecia areata, and scarring alopecia.5–7Minoxidil is associated with non-serious side effects such as scalp irritation, facial hypertrichosis, and allergic contact dermatitis.8 Finasteride, another well-known medication for AGA, functions by inhibiting the conversion of testosterone to dihydrotestosterone (DHT) via regulation of 5α-reductase enzyme activity.9 Despite its efficacy against hair loss, the associated side effects cannot be ignored. Long-term treatment with finasteride has been reported to have sexual side effects such as erectile dysfunction and decreased libido.10
Serenoa repens (Fam.) Arecaceae) dwarf trees, commonly known as saw palmetto (SP), are grown largely in parts of North America. Saw palmetto oil extracted from plant berries contains 85–90% fatty acids and other constituents such asβ-sitosterol, capric acid, caprylic acid, and caproic acid.11,12 SP competitively inhibits 5α-reductase activity and restricts the conversion of testosterone to DHT.13 Due to its anti-androgenic properties SP has gained potential as a dietary supplement and medication for conditions such as benign prostate hyperplasia and hair loss.14 Previously, SP in food supplements has been clinically evaluated for the prevention of hair loss in AGA subjects.15–17 However, most clinical studies have been conducted on formulations of SP with vitamins and minerals, making it difficult to understand the magnitude of efficacy of SP alone. Hence, it is important to study the hair care potential of SP individually, using randomized clinical trials.
VISPOTM is a proprietary extract containing standardized β-sitosterol and total fatty acid contents. Previously, the efficacy of VISPO was studied in a preclinical model of benign prostate hyperplasia (BPH).18 Further in a comparative clinical study with conventional SP extract, the efficacy and safety of VISPO were confirmed in BPH subjects.19 Here, the protective effect of VISPO as an oral and topical supplement against hair fall was observed in subjects with AGA.
Materials and Methods
VISPOTM
The investigational product VISPOTM used in this study was manufactured by Vidya Herbs Pvt. Ltd. (Bangalore, India) via supercritical fluid extraction. VISPO is a standardized saw palmetto extract containing 2–3% β-sitosterol and ≥ 85% total fatty acids. The extract was formulated for ingestion and topical application. Each 400 mg capsule contained 100 mg of VISPO. The placebo capsules contained maltodextrin and had a similar appearance and color to VISPO capsules. VISPO was formulated into a lotion form for topical application, such that each 100 g lotion contained 20g VISPO. The composition details of the oral and topical formulations are provided in Supplementary Tables 1 and 2.
Secondary Outcomes
In the present study, serum samples from the subjects at baseline and at the end of the study were quantified for 5αreductase levels using ELISA. As shown in Figure 5A, the VISPO oral and topical groups showed no significant change in the enzyme level from baseline to the end of the study compared to the respective placebo groups. Interestingly, the serum DHT level was significantly reduced in the VISPO oral treatment group by 1.29-fold at the end of the study compared to that at baseline (p<0.001). This change in the DHT level was significant compared to that in the placebo (p<0.001). However, the VISPO topical treatment group showed no significant change in DHT from baseline to the end of the study compared to the placebo group (Figure 5B). These data clearly suggest that oral administration of VISPO could markedly inhibit 5α-reductase activity, and thus, the accumulation of DHT in the subjects.
Discussion
*One of the limitations of the present study is that the duration of treatment was restricted to 16 weeks. Our results clearly demonstrated that VISPO formulations were effective in reducing hair loss at the end of treatment. However, the formulation did not significantly change the anagen/telogen ratio from the baseline to the end of the study. Previously, SP extracts were used for longer durations to observe a significant change with respect to perceived efficacy and anagen induction.15,26 Overall, these observations clearly suggest that prolonged treatment with VISPO formulations could stimulate hair growth in subjects. Although no adverse effects were recorded during the study, it should be noted that the study duration was short and the sample size was small. Another limitation of this study was that we did not use any standard medications for efficacy comparisons.
*Experimental studies of SP extracts have demonstrated their anti-androgenic effects as a function of 5α-reductase inhibition. SP extracts are rich in saturated fatty acids, such as lauric acid, myristic acid, linoleic acid, oleic acid, and sterols (β-sitosterol), which contribute significantly to 5α-reductase inhibition.27,28 These attributes could be responsible for the observed reduction in DHT levels in subjects after oral intake of VISPO. Interestingly, in the topical VISPO group, there was no significant reduction in the serum DHT level from baseline compared to the placebo group. One possible explanation for this observation is that the topical application of the actives generally results in a higher DHT reduction in the scalp than in systemic circulation.29 In a recent double-blind study by Piraccini et al, the topical administration of finasteride showed similar efficacy to that of oral treatment in improving the hair count of subjects, but with less impact on serum DHT levels.30 Given that there is a clear DHT inhibition by VISPO oral treatment, it would seem there may also be sexual side effects, menstrual effects, and mood changes in women, as in the case of finasteride.31,32However, none of the subjects reported such side effects during the study. The adverse effects reported with oral SP are mostly limited to mild gastrointestinal issues like nausea, diarrhea, and constipation.33
In addition to its anti-androgenic action, SP extracts have been demonstrated to mediate hair regrowth in murine models via transforming growth factor-β (TGF-β) signaling.34 Further, SP formulations have been reported to exert anti-inflammatory effects in human keratinocytes.35 There are reports that β-sitosterol, the key constituent of SP, can instigate vascularization through its angiogenic ability.36 Based on these reports, it can be presumed that VISPO potentiates hair loss arrest by its anti-androgenic effect and further supports hair regrowth via stimulation of growth factors and neovascularization in the scalp.
Conclusion
A 16-week treatment of AGA patients with oral and topical formulations of VISPO was effective for hair fall arrest. Furthermore, oral ingestion of VISPO significantly inhibited 5α-reductase activity and hence reduced DHT accumulation in the subjects. Though the data from this study provide limited evidence on the topical application of VISPO, long-term treatment with these formulations may be required to establish the complete efficacy of VISPO for hair regrowth in patients with AGA. Overall, VISPO can be effectively used as an active ingredient in functional and cosmetic formulations.
Androgenetic alopecia (AGA) is the most common type of hair loss in humans, affecting self-esteem and emotional well-being. This study aimed to assess the safety and efficacy of VISPOTM, a standardized saw palmetto oil (2–3% β-sitosterol), in subjects with mild-to-moderate AGA.
Methods
In a double-blind, placebo-controlled, four-arm clinical study, 80 healthy male and female subjects aged 18–50 years were randomly allocated (1:1:1:1) to receive either 400 mg capsules of VISPO or 5 mL of a topical formulation containing 20% VISPO or the respective placebo once daily for 16 weeks. The primary endpoints included hair count (hair comb and hair pull tests) and the self-assessment of perceived efficacy. The objective evaluation was performed using the global photographic assessment score. Hair density, thickness, and anagen/telogen ratio were evaluated using phototrichogram analysis.
Results
At the end of the study, oral and topical formulations of VISPO reduced hair fall by up to 29% (p<0.001) and 22.19%(p<0.01) from the baseline, respectively. Hair density increased by 5.17% and 7.61% in the oral and topical VISPO groups, respectively (p<0.001). In addition, oral ingestion of VISPO resulted in a marked reduction in serum dihydrotestosterone (DHT)levels in the subjects compared to placebo (p<0.001). However, the effect of the VISPO formulations on the anagen/telogen ratio was significant. No serious adverse effects were observed during the study.
Conclusion
VISPO formulations reduced hair fall and promoted hair regrowth and scalp appearance in AGA patients.
Introduction
Androgenetic alopecia (AGA) is a progressive hair loss condition, with a characteristic pattern in both men and women. In men, AGA, also known as male pattern hair loss (MPHL), is caused by a greater sensitivity of the hair follicles to the androgens;1 however, the cause of female pattern hair loss (FPHL) and its association with androgen remain unclear.2The incidence of progressive hair loss by AGA has become more prevalent in recent years. AGA is common in nearly 80% of aging men.3 Hair loss negatively impacts the psychological and social well-being of an individual.4 Presently, minoxidil and finasteride are the only FDA (Food and Drug Administration) approved medications for AGA. Minoxidil is used for topical applications and works by stimulating hair follicles via anagen phase induction. Several clinical studies have reported the efficacy of minoxidil against alopecia, including AGA, Alopecia areata, and scarring alopecia.5–7Minoxidil is associated with non-serious side effects such as scalp irritation, facial hypertrichosis, and allergic contact dermatitis.8 Finasteride, another well-known medication for AGA, functions by inhibiting the conversion of testosterone to dihydrotestosterone (DHT) via regulation of 5α-reductase enzyme activity.9 Despite its efficacy against hair loss, the associated side effects cannot be ignored. Long-term treatment with finasteride has been reported to have sexual side effects such as erectile dysfunction and decreased libido.10
Serenoa repens (Fam.) Arecaceae) dwarf trees, commonly known as saw palmetto (SP), are grown largely in parts of North America. Saw palmetto oil extracted from plant berries contains 85–90% fatty acids and other constituents such asβ-sitosterol, capric acid, caprylic acid, and caproic acid.11,12 SP competitively inhibits 5α-reductase activity and restricts the conversion of testosterone to DHT.13 Due to its anti-androgenic properties SP has gained potential as a dietary supplement and medication for conditions such as benign prostate hyperplasia and hair loss.14 Previously, SP in food supplements has been clinically evaluated for the prevention of hair loss in AGA subjects.15–17 However, most clinical studies have been conducted on formulations of SP with vitamins and minerals, making it difficult to understand the magnitude of efficacy of SP alone. Hence, it is important to study the hair care potential of SP individually, using randomized clinical trials.
VISPOTM is a proprietary extract containing standardized β-sitosterol and total fatty acid contents. Previously, the efficacy of VISPO was studied in a preclinical model of benign prostate hyperplasia (BPH).18 Further in a comparative clinical study with conventional SP extract, the efficacy and safety of VISPO were confirmed in BPH subjects.19 Here, the protective effect of VISPO as an oral and topical supplement against hair fall was observed in subjects with AGA.
Materials and Methods
VISPOTM
The investigational product VISPOTM used in this study was manufactured by Vidya Herbs Pvt. Ltd. (Bangalore, India) via supercritical fluid extraction. VISPO is a standardized saw palmetto extract containing 2–3% β-sitosterol and ≥ 85% total fatty acids. The extract was formulated for ingestion and topical application. Each 400 mg capsule contained 100 mg of VISPO. The placebo capsules contained maltodextrin and had a similar appearance and color to VISPO capsules. VISPO was formulated into a lotion form for topical application, such that each 100 g lotion contained 20g VISPO. The composition details of the oral and topical formulations are provided in Supplementary Tables 1 and 2.
Secondary Outcomes
In the present study, serum samples from the subjects at baseline and at the end of the study were quantified for 5αreductase levels using ELISA. As shown in Figure 5A, the VISPO oral and topical groups showed no significant change in the enzyme level from baseline to the end of the study compared to the respective placebo groups. Interestingly, the serum DHT level was significantly reduced in the VISPO oral treatment group by 1.29-fold at the end of the study compared to that at baseline (p<0.001). This change in the DHT level was significant compared to that in the placebo (p<0.001). However, the VISPO topical treatment group showed no significant change in DHT from baseline to the end of the study compared to the placebo group (Figure 5B). These data clearly suggest that oral administration of VISPO could markedly inhibit 5α-reductase activity, and thus, the accumulation of DHT in the subjects.
Discussion
*One of the limitations of the present study is that the duration of treatment was restricted to 16 weeks. Our results clearly demonstrated that VISPO formulations were effective in reducing hair loss at the end of treatment. However, the formulation did not significantly change the anagen/telogen ratio from the baseline to the end of the study. Previously, SP extracts were used for longer durations to observe a significant change with respect to perceived efficacy and anagen induction.15,26 Overall, these observations clearly suggest that prolonged treatment with VISPO formulations could stimulate hair growth in subjects. Although no adverse effects were recorded during the study, it should be noted that the study duration was short and the sample size was small. Another limitation of this study was that we did not use any standard medications for efficacy comparisons.
*Experimental studies of SP extracts have demonstrated their anti-androgenic effects as a function of 5α-reductase inhibition. SP extracts are rich in saturated fatty acids, such as lauric acid, myristic acid, linoleic acid, oleic acid, and sterols (β-sitosterol), which contribute significantly to 5α-reductase inhibition.27,28 These attributes could be responsible for the observed reduction in DHT levels in subjects after oral intake of VISPO. Interestingly, in the topical VISPO group, there was no significant reduction in the serum DHT level from baseline compared to the placebo group. One possible explanation for this observation is that the topical application of the actives generally results in a higher DHT reduction in the scalp than in systemic circulation.29 In a recent double-blind study by Piraccini et al, the topical administration of finasteride showed similar efficacy to that of oral treatment in improving the hair count of subjects, but with less impact on serum DHT levels.30 Given that there is a clear DHT inhibition by VISPO oral treatment, it would seem there may also be sexual side effects, menstrual effects, and mood changes in women, as in the case of finasteride.31,32However, none of the subjects reported such side effects during the study. The adverse effects reported with oral SP are mostly limited to mild gastrointestinal issues like nausea, diarrhea, and constipation.33
In addition to its anti-androgenic action, SP extracts have been demonstrated to mediate hair regrowth in murine models via transforming growth factor-β (TGF-β) signaling.34 Further, SP formulations have been reported to exert anti-inflammatory effects in human keratinocytes.35 There are reports that β-sitosterol, the key constituent of SP, can instigate vascularization through its angiogenic ability.36 Based on these reports, it can be presumed that VISPO potentiates hair loss arrest by its anti-androgenic effect and further supports hair regrowth via stimulation of growth factors and neovascularization in the scalp.
Conclusion
A 16-week treatment of AGA patients with oral and topical formulations of VISPO was effective for hair fall arrest. Furthermore, oral ingestion of VISPO significantly inhibited 5α-reductase activity and hence reduced DHT accumulation in the subjects. Though the data from this study provide limited evidence on the topical application of VISPO, long-term treatment with these formulations may be required to establish the complete efficacy of VISPO for hair regrowth in patients with AGA. Overall, VISPO can be effectively used as an active ingredient in functional and cosmetic formulations.
