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Preventing hair loss by balancing

the hair cycle, strengthening the hair follicle,


and improving scalp health
By Dr. M. Pflaumbaum*, M. Farwick, M. Mentel, T. Köhler

Sphinganine-based ceramides represent the most abundant cera-


Abstract
mide class present in human hair 3). Based on this and other scien-
The overall impression that people make depends to a significant tific data, sphinganine seems to be a promising active ingredient for
degree on the appearance of their hair. Aging and conditions such as hair-quality promoting cosmetic applications.
androgenic alopecia result in hair follicle miniaturization, which Sphinganine is produced from renewable raw materials such as
shortens the growth phase, resulting in hair loss and the formation sugar in a sustainable biotechnology process.
of fine and lifeless hair. The fermentative production process ensures that Sphinganine
Healthy hair embedded in a healthy scalp is the key to preventing features the same stereochemical configuration as found in nature
hair loss. and in human skin (figure 2). The skin-identical stereochemistry of
Scientifically well-founded claims have been made that substanti- Sphinganine is of key importance for its biological functions.
ate the action of Sphinganine, a skin-identical sphingolipid that tar-
gets hair loss by balancing the hair cycle, strengthening the hair
follicle, and improving scalp health.
Figure 2: The chemical structure of Sphinganine. The absolute stereochemistry on
the asymmetrical carbon atoms is indicated in brackets (in purple)
Hair growth occurs over a cycle consisting of growth (anagen), re-
gression (catagen), resting (telogen), and exogen phases 1, 2) (figure 1). Sphinganine prolongs the anagen phase and improves scalp health
and scalp renewal capacity, making it an ideal active ingredient for
preventing hair loss (figure 3a, 3b)

Figure 3a:
Proposed working
mechanism of
Sphinganine within
the hair life cycle

Figure 1: The hair growth cycle

The hair follicle undergoes a repeated growth cycle and is able to


regenerate a new hair shaft during each cycle. More than 80% of the
hair in young and healthy individuals is actively growing (anagen
phase). Aging and other circumstances such as androgenic alopecia
result in hair follicle miniaturization, which shortens the anagen Figure 3b:
phase, resulting in hair loss and the formation of fine and lifeless Proposed working
hair. mechanism of
Sphinganine within
Healthy hair embedded in a healthy scalp is the key to preventing the hair follicle and
hair loss. on the scalp

* Consumer Specialities Personal Care

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Various in vitro studies have shown that Sphinganine balances The aim of the study was therefore to determine the global effects
the hair cycle by inhibiting 5-␣-reductase, by improving the capacity of Sphinganine treatment in a confluence-induced, in vitro keratino-
of the scalp to renew itself, by stimulating the formation of essential cyte differentiation model, particularly with respect to lipidomic
building blocks such as proteins and ceramides, and by balancing and transcriptomic changes.
microflora to improve scalp health.
Sphinganine treatment strongly promotes ceramide production in
keratinocytes (Figure 5).
Preventing hair loss by inhibiting
5-␣-reductase (in vitro)
The aim of this study was to determine the potential of Sphinga-
nine as an inhibitor of 5-␣-reductase type I, which is the key enzyme
catalyzing irreversible reduction of testosterone (T) to dihydrotes-
tosterone (DHT), the most potent androgen. DHT has been identi-
fied as key factor involved in androgenetic male baldness.

The inhibitory potential towards 5-␣-reductase type I was tested


in a cell-free assay using cell homogenates isolated from stably trans-
fected HEK293 cells, yielding an IC50 of 6.6 µM for Sphinganine
(figure 4). Finasteride, a known 5-␣-reductase inhibitor, was included
as the internal positive control.
Figure 5: Increase in cellular ceramide content after four days [nmol/mg protein]

Overall ceramide pools were stimulated in a balanced way,


leading to concomitant upregulation of all major ceramide classes
containing sphinganine, phytosphingosine, or sphingosine in
their backbones. In particular, very long-chain fatty acid cera-
mides, which are deemed critical for intact barrier function, were
upregulated. Moreover, microarray analysis (data not shown) in-
dicates significant induction of overall sphingolipid metabolism
Figure 4: and keratinocyte differentiation caused by the Sphinganine treat-
Inhibition of ment.
5-␣-reductase I by
Sphinganine in vitro
In addition to applying Sphinganine on differentiating epidermal
The test results show that Sphinganine is a potent inhibitor of keratinocytes, a complementary experiment was conducted on a
5-␣-reductase type I. Consequently, Sphinganine is a suitable cos- non-differentiating keratinocyte model in order to explore effects on
metic ingredient for inhibiting the conversion of testosterone to di- the transcriptome of proliferating epidermal keratinocytes. The
hydrotestosterone. This will positively influence the hair growth purpose of this experiment was to explore the effects of Sphinga-
cycle by preventing the transition to the catagen phase and follicle nine once it had penetrated deeper layers of the viable epidermis,
miniaturization, particularly among men. the follicle shaft, and the hair root. Because the hair shaft arises from
rapidly proliferating keratinocytes in the bulb (one of the highest
Moreover, reduction of scalp sebum production will lead to a less rates of proliferation in the body), special attention was paid to
greasy scalp and an overall improvement in scalp health. genes known for their roles in cell proliferation. This class of genes
includes growth factors, as well as genes controlling synthesis and
turnover of the intracellular messenger molecule sphingosine-
Improvement of the scalp barrier 1-phosphate. Another class of genes relevant in the context of proper
function and renewal capacity (in vitro) hair structure is one that mediates cell-cell interaction and includes
integrin and cadherin genes.
A functional skin barrier is a prerequisite for a healthy scalp. By
contrast, compromised barrier function can lead to a dry, itchy In summary, the gene expression data obtained for undifferenti-
scalp. Improving the barrier formation should therefore lead to an ated, proliferating keratinocytes suggest that Sphinganine maintains
improvement in overall scalp health, with the additional, indirect the proliferative state of keratinocytes and favors epidermal renewal
benefit of combatting hair loss. (figure 6).

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Sphinganine improves scalp health directly via antimicrobial ac-
tivity and indirectly by stimulating HBD2 formation.

An in vitro germ count reduction test revealed profound direct


anti-microbial activity against Malassezia furfur (figure 7), which
is known to cause dandruff. Moreover, Sphinganine treatment
stimulates HBD2 gene expression in an in vitro keratinocyte model
(figure 8).

Figure 6: Stimulation of proliferation markers (gene expression after 24h)

In particular, the stimulation of basic fibroblast growth factor ex-


pression, as well as the stimulation of gene expression related to
sphingosine-1-phosphate and sphinganine-1-phosphate synthesis,
indicates that treating keratinocytes with Sphinganine triggers sign- Figure 7:
aling cascades that ultimately promote cell proliferation and coun- Malassezia furfur
germ count
teract apoptosis. Assuming that these signaling cascades are reduction.
conserved, it seems likely that the positive effects of Sphinganine 1% Sphinganine
treatment also apply to hair matrix keratinocytes, which represent efficiently reduces
M. furfur germ
one of the fastest proliferating cell populations in the body. As such, counts by three
Sphinganine will likely keep hair follicles in an active, growing state, orders of magnitude
and prevent follicles from prematurely undergoing apoptosis and within 20 minutes.
entering the catagen phase. Moreover, developing hair follicles ben-
efit from inducing genes for cadherin and integrin, two classes of
proteins that mediate cell-cell and cell-matrix adhesion processes,
and that are critically important for proper hair follicle and hair shaft
architecture.

Figure 8:
Improvement in scalp health Effect of Sphinganine
on human ␤-defensin
by equalizing micro flora (in vitro) 2 (HBD2) gene
expression in
Overall scalp health is always the outcome of multiple influencing primary human
factors. One important factor is scalp microflora. While the natural keratinocytes after
72h of incubation
scalp microflora comprises many different microbe species, yeast (solvent: 0.1% DMSO).
strains belonging to the genus Malassezia have been identified as a
major determinant of scalp health. Numerous studies have demon- The profound stimulation of HBD2 gene expression reflects
strated the key role that Malassezia strains play in the context of Sphinganine’s potential to stimulate innate immunity via produc-
scalp health, particularly with respect to dandruff and seborrheic tion of anti-microbial peptides (AMPs). As such, Sphinganine likely
dermatitis. Although Malassezia strains are part of normal cutane- strengthens the skin’s defenses and ultimately contributes to overall
ous microflora, they are known to be involved in the occurrence and skin and scalp health.
severity of certain human skin conditions, including dandruff, seb-
orrheic dermatitis, folliculitis, and others. Extended in vivo studies have confirmed that Sphinganine signifi-
cantly reduces hair loss by prolonging the anagen growth phase of
Another mechanism contributing to a healthy scalp is mediated hair and effectively improves hair quality and scalp health.
via the expression of anti-microbial peptides (AMPs). These peptides
act mainly by interfering with the cytoplasmic membrane of target
microbe strains, causing membrane leakage and ultimately cell Improvements in hair quality
death. One of the most prominent anti-microbial peptides is human and scalp health (in vivo)
␤-defensin 2 (HBD2). Expression of AMPs correlates with the ke-
ratinocytes’ differentiation status, and together with the mechanical The aim of the study was to investigate the potential effect of
stability conferred by the stratum corneum, AMPs efficiently help Sphinganine on prolonging the hair anagen phase and improving
maintain overall skin and scalp health. overall hair quality and scalp health.

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The TrichoScan® method was employed to objectively determine
state of the hair life cycle by determining the anagen and telogen
rate. Visible and otherwise detectable effects were assessed by ex-
pert rating and photographic documentation.

An ethanolic hair tonic containing 0.1 – 0.5% Sphinganine was


provided, and volunteers evenly applied this to their scalps (dry
hair) and hairlines in the morning and evening, aided by some gentle
massage. Measurements were conducted before the fi rst application
and after 8 and 16 weeks of product application. Data were consid-
ered from a total of 96 test subjects.

The TrichoScan® images clearly show the effects of Sphinganine


application (figure 9). The increase in anagen hair leads to a notice-
able increase in the amount of hair on the scalp. The TrichoScan®
images also indicated beneficial effects on scalp health.

Figure 10: Photographic documentation of the effect of sphinganine application on


two male study participants.

Figure 11:
Anagen rate as
determined by
TrichoScan®
measurements.
An increase in the
anagen rate was
detected that was
particularly
Figure 9: Sample photographic images recorded using the TrichoScan® method for
pronounced when
two male volunteers from the Sphinganine group, before application (left column)
compared to vehicle
and after 16 weeks (right column). Improvements in anagen hair and scalp health
control application.
are clearly visible.

Photographic documentation was standardized, hair was washed groups, the anagen rate increased, and the increase was highest in
the day before measurement, and no styling products were used. the 0.5% Sphinganine group (2.7% and 2.8% after 8 and 16 weeks,
Subjects did not use any hair tonic on the day of visit. respectively). In the 0.2% and 0.1% Sphinganine groups, increases of
1.8%/1.9% and 1.1%/1.1% were determined (after 8/16 weeks), re-
The photographs (figure 10) clearly show the effect of Sphinga- spectively.
nine application, and a noticeable increase in the amount of hair due
to improvements in hair anagen rate. The effects were achieved after Relative to vehicle control, the increase in the anagen rate in the
applying as little as 0.1% Sphinganine. 0.5% Sphinganine group was 4.3%/3.9% (after 8 and 16 weeks, re-
spectively), 3.3%/3.0% in the 0.2% Sphinganine group and 2.7%/2.3%
TrichoScan® images were analyzed as well. The difference be- in the 0.1% Sphinganine group.
tween the growing (anagen) and non-growing (telogen) hair can be
seen. The recorded images were used as a basis for calculating the In terms of the expert rating (figure 12), all hair quality and scalp
anagen hair rate [%] (figure 11). health parameters improved after application of Sphinganine, re-
gardless of the concentration. In particular, hair quality parameters
In the vehicle control group, the anagen rate decreased by 1.6% were greatly improved in all Sphinganine groups compared to vehi-
and 1.1% after 8 and 16 weeks, respectively. In all Sphinganine cle control, and improvements in hair volume scored best.

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Figure 12: Changes in hair quality and scalp health parameters as rated on a five-
point scale by experts on the basis of a questionnaire.

Conclusion
Overall, SPHINGONY (trade name for Sphinganine) is a naturally
occurring, skin-identical molecule particularly targeting male pat-
tern hair loss by balancing the hair cycle, strengthening the hair
follicle, and improving scalp health. SPHINGONY is COSMOS certi-
fied and approved by Ecocert Greenlife according to the Ecocert
Standard for Natural and Organic Cosmetics, available at http://cos-
metics.ecocert.com.

References
1. Driskell et al., J Cell Sci 2011, 124, 1179 – 1182
2. K.S. Stenn, R. Paus; Physiol Rev 2001, 81, 449 – 494
3. G. Hussler, G. Kaba, A.M. Francois, D. Saint-Leger, Int. J. Cosmetic Sci. 1995,
17, 197 – 206) ■

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