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http://ernd.usm.my/journal/journal/TLSR%2021-2-8-%2891-99%29.pdf
Tropical Life Sciences Research, 21(2), 91–99, 2010
Effects of Tocotrienol Supplementation on Hair Growth in Human
Volunteers
1
Lim Ai Beoy,
2
Wong Jia Woei and
1
Yuen Kah Hay
*
1
School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 USM,
Pulau Pinang, Malaysia
2
Hovid Bhd, 121, Jalan Tunku Abdul
Rahman, 30010 Ipoh, Perak, Malaysia
Abstrak:
Kajian telah menunjukkan bahawa terdapat perhubungan di antara oksidatif
stres dengan keguguran rambut. Pesakit yang mengalami keguguran rambut secara
amnya mempamerkan paras anti-oksidan yang lebih rendah pada kawasan kulit kepala
serta index peroksidan lemak yang lebih tinggi. Tokotrienol merupakan vitamin E dan
mempunyai efek anti-oksidan yang tinggi. Oleh itu, satu kajian telah dijalankan untuk
mengkaji kesan suplementasi tokotrienol ke atas sukarelawan yang mengalami masalah
keguguran rambut. Dua puluh satu sukarelawan diagihkan secara rawak untuk menerima
100 mg tokotrienol campuran setiap hari secara oral manakala 17 sukarelawan diagihkan
untuk menerima placebo secara oral. Sukarelawan-sukarelawan tersebut dipantau pada
bulan ke-0 (sebelum menerima suplementasi tokotrienol), ke-4 dan ke-8 bagi menentukan
bilangan rambut pada kawasan kepala yang telah ditentukan terlebih dahulu serta berat
20 helai keratan rambut sepanjang 1 cm. Sukarelawan-sukarelawan yang menerima
suplementasi tokotrienol menunjukkan penin
gkatan bilangan rambut yang signifikan
berbanding kumpulan placebo. Kumpulan su
plementasi tokotrienol mencatatkan
peningkatan sebanyak 34.5% pada penghujung bulan ke-8 berbanding dengan penurunan
sebanyak 0.1% yang dicatatkan oleh kumpulan
placebo. Namum demikian, berat 20 helai
keratin rambut tidak banyak berbeza di antara kedua-dua kumpulan pada
penghujung tempoh kajian. Sebagai kesimpulan, kajian ini menunjukkan bahawa
suplementasi dengan kapsul tokotrienol meningkatkan bilangan rambut pada sukarelawan
yang mengalami masalah keguguran rambut berbanding dengan kumpulan placebo.
Kesan ini berkemungkinan disebabkan oleh
aktiviti anti-oksidan tokotrienol yang
membantu menurunkan peroksidan lemak dan oksidatif stres pada kulit kepala, dimana
kedua-duanya telah dihubungkaitkan dengan keguguran rambut.
Kata kunci:
Pertumbuhan Rambut, Tokotrienol, Anti-oksidan
Abstract:
Studies have shown an association between oxidative stress and alopecia.
Patients with alopecia generally exhibit lower levels of antioxidants in their scalp area as
well as a higher lipid peroxidation index. Tocotrienols belong to the vitamin E family and
are known to be potent antioxidants. Hence,
a study was conducted to investigate the
effect of tocotrienol supplementation on hair
growth in volunteers suffering from hair loss.
Twenty one volunteers were randomly assigned to orally receive 100 mg of mixed
tocotrienols daily while 17 volunteers were assigned to receive placebo capsule orally. The
volunteers were monitored for the number of hai
rs in a pre-determined scalp area as well
as the weight of 20 strands of 1 cm length ha
ir clippings at 0 (before supplementation), 4
and 8 months. The number of hairs
of the volunteers in the
tocotrienol supplementation
group increased significantly as compared to
the placebo group, with the former recording
a 34.5% increase at the end of the 8-mont
h supplementation as compared to a 0.1%
decrease for the latter. Nevertheless, the cumula
tive weight of 20 strands of hair clippings
91
*
Corresponding author:
khyuen@usm.my
Lim Ai Beoy et al.
did not differ much from the baseline for both
supplementation gro
ups at the end of the
study period. In conclusion, this trial dem
onstrated that supplementat
ion with tocotrienol
capsules increases hair number in volunteers suffering from hair loss as compared to the
placebo group. This observed effect was most likel
y to be due to the antioxidant activity of
tocotrienols that helped to reduce lipid pe
roxidation and oxidative stress in the scalp,
which are reported to be associated with alopecia.
Keywords:
Hair Growth, Tocotr
ienols, Antioxidants
INTRODUCTION
Scalp hair plays an important function in
humans. In addition to providing cranial
cushioning and shielding the scalp from direct sun rays, hair has sociological
meanings in terms of gender, age, values
and status (Cash 2001). Scalp hair is
also a vital aspect of an individual's physical appearance and helps to project a
positive image (Cash 2001). Hair loss and balding, on the other hand, are
associated with negative attributes (Rushton
et al
. 2002). Hair loss or alopecia is
a common problem suffered by both sexes and has been reported to cause
significant psychological effects, such
as diminished self-esteem, emotional
distress, embarrassment and social inadequ
acy, with these detrimental effects
being more significant in women (Cash
et al.
1993). Van der Donk
et al.
(1994)
observed that alopecia could severely affect
the quality of life of the majority of
the sufferers, whereby 88% of sufferers experienced negative effects in their daily
life and 75% and 50% encountered negativ
e self-esteem and social problems,
respectively.
There are many types of alopecia, su
ch as androgenetic alopecia (Androgenetic Alopecia),
alopecia areata, telogen effluvium, hair loss due to systemic medical problems
such as thyroid disease and adverse drug effects, as well as hair loss due to
scalp or hair trauma, discoid lupus er
ythematosus, lichen planus and structural
shaft abnormalities, to name a few (Hogan & Chamberlain 2000). The causes for
the above are numerous and va
ry between the different types of alopecia. In
most instances, the aetiology is still
unknown. However, one of the universal
causes of increased hair thinning or shedding is nutritional deficiency. It was
previously reported that children with pr
otein malnutrition would exhibit fragile
and finer hairs that easily fall or break off and display a lower daily rate of growth
(Bradfield & Bailey 1969; Sims 1968). Nutr
itional factors that have been identified
to be essential in preventing hair loss in
clude iron and an essential amino acid, L-
lysine (Rushton
et al.
1990; Rushton 2002). Rushton
et al.
(2002) reported that
women with chronic telogen effluvium have low serum ferritin levels and
proceeded to demonstrate that daily supplementation of iron and L-lysine for 6
months could cause significant increases in hair numbers.
92
Recently, Naziroglu and Kokcam (2
000) showed that there was an
association between oxidative stress and
alopecia. They reported that the levels
of reduced glutathione (GSH) and activities
of glutathione per
oxidase (GSH-Px),
which are present to protect against damages caused by reactive oxygen species
such as free radicals and peroxides, were significantly lower in patients with
alopecia than in controls, whereas the levels of thiobarbituric acid reactive
Effects of Tocotrienol Supplementation on Hair Growth
substances (TBARS), which indicate lipid peroxidation and oxidative stress, were
significantly higher.
Tocotrienols together with tocopherols are members of the vitamin E
family. They share similar structural f
eatures of a chroman head and a 16-carbon
phytyl chain. The structural difference
between them lies mainly in the latter
possessing a saturated phytyl chain wherea
s that of the former possesses three
unsaturated double bonds (Papas 1999; Theriault
et al.
1999). Tocotrienols also
possess more potent antioxidant property, and Serbinova
et al.
(1991) showed
that
α
-tocotrienol was 40- to 60-fold more potent than
α
-tocopherol against lipid
peroxidation in rat liver microsomal
membranes. This superiority has been
ascribed to the ability of tocotrienols to better distribute within the fatty layers of
the cell membranes and hence permit better interaction with lipid radicals.
Moreover, tocotrienols have been shown to afford protection to the skin against
UV light- and ozone-induced
oxidative stress (Traber
et al.
1997).
In view of the association between
alopecia and oxidative stress and the
high antioxidant potency of the tocotr
ienols, a study was thus performed in
volunteers with alopecia to evaluate the e
fficacy of tocotrienol supplementation in
improving hair coverage of the scalp
and preventing hair thinning in patients
suffering from alopecia.
MATERIALS AND METHODS
Patient Population
Thirty eight male and female volunteers ranging from 18 to 60 years old who met
the inclusion criteria were recruited into
the trial. Volunteers had varying levels of
hair loss, ranging from patchy loss of scalp hair to more severe loss of scalp hair.
Hair loss must have been present for at least 2 months and the alopecia area
could not have any visual evidence of new hair growth. All volunteers were in
good general health with no evidence of systemic illness including cardiac,
psychiatric, thyroid and scalp diseases.
Volunteers were excluded from the study if they had known
hypersensitivity to tocotrienols or if
they had undergone hair restoration
procedures, consumed hair growth medications or applied hair enhancement
products in the past 6 months. Pati
ents who had undergone chemotherapy and
experienced scalp trauma were also exclud
ed. Concomitant use of medications,
such as steroids, oral contraceptiv
es, cytotoxic agents, vasodilators,
antihypertensive agents, anti-convulsant drugs,
ß
-adrenergic receptor blockers,
diuretics, spironolactone, cimetidine, cyclosporine or ketoconazole, during the 6
months prior to the study was also not
allowed. Patients on iron and vitamin B12
supplementation were also excluded.
Volunteers were also instructed not to
alter their hairstyle, the hair care
products (such as shampoo or conditioner
) currently in use or dye their hair
during the study period.
93
Lim Ai Beoy et al.
Study Design
This study was an 8 month (32 week),
randomised, double-blind, placebo-
controlled trial conducted at the School of Pharmaceutical Sciences, Universiti
Sains Malaysia, Pulau Pinang. The protocol and informed consent form were
approved by an institutional review boar
d and written informed consent was
obtained from each volunteer prior to enr
olment into the study. Thirty eight
volunteers participated in the trial, and 21 volunteers were randomly selected to
receive tocotrienol supplementation (tocotri
enol supplementation group) while 17
were randomly selected to receive the placebo (placebo group). The placebo is a
soft gelatine capsule containing 600 mg of
soya bean oil (Hovid Sdn Bhd, Ipoh,
Malaysia), while tocotrienol supplementation consisted of mixed tocotrienols
formulated in a soft gelatine capsule (Hovid Sdn Bhd). Each tocotrienol capsule
contained 50 mg of mixed tocotrienols (30.8%
α
-tocotrienol, 56.4%
γ
-tocotrienol
and 12.8%
δ
-tocotrienol) as well as 23 IU of
α
-tocopherol. The volunteers were
required to take one capsule of either the placebo or tocotrienol twice daily after
meal over a period of 8 months. Hence, t
he total daily intake of tocotrienols for
each volunteer in the treatment group wa
s 100 mg. The capsules were provided
on a monthly basis and compliance with the supplementation regimen was
monitored by counting the capsules that were left over during the monthly visit.
The volunteers were also counselled and advised to take the capsules regularly
as per the instruction given to ensure co
mpliance. The volunteers were required
to report any side/adverse reactions,
additional medication taken and any new
diagnosis during the trial period.
Efficacy Evaluation
Two parameters were chosen to evaluate the efficacy of tocotrienol
supplementation (Price
et al.
2002):
1.
Hair counts
Hair counts served as the primary effica
cy measure. An area of 2 × 2 cm was
selected in the area of hair thinning for each patient in the balding vertex
scalp, and the 2 opposing corners of
the square were permanently marked
(using a 4 cm
2
wire template) to ensure that the hair in same area was
counted at each visit. The count was done by an investigator who was
blinded to the treatment the volunteers were receiving. The resulting hair
counts were used to calculate the percentage change from baseline.
2.
Weight of hairs
A small tuft of hair (at least 20 strands) within the demarcated area was
clipped horizontally. Twenty strands were randomly chosen and cut to 1 cm
in length. The total weight was obtained using a microbalance and the
resulting mean weight was used to ca
lculate the percentage change from
baseline.
Both parameters were obtained at baseline, 4 months (16
th
week) after the
start of the study and at the end of 8 months (32
nd
week) for efficacy evaluation.
Altogether, there were three intervals.
94
Effects of Tocotrienol Supplementation on Hair Growth
Statistical Calculation
The data collected at baseline and du
ring the supplementation period for both
groups were compared using an analysis of variance procedure (ANOVA) for a
two-factor repeated measures split-plo
t experimental design (Kirk 1968). If a
statistically significant difference for the main effect of interval was observed,
Tukey’s post-hoc test was employed. When significant interaction between
supplementation and an interval was observed, simple main effect analysis
(pairwise comparison) was employed to
locate the pair that gave rise to the
observed difference. The homogeneity of
the baseline characteristics between
the two groups, namely the number and weight of hairs, was also assessed. A
statistically significant difference was considered at
p
< 0.05.
RESULTS AND DISCUSSION
Thirty eight volunteers with signs of hair
loss or balding were enrolled in the
study, with the supplementation group having 21 volunteers (19 male and 2
female) and the placebo group (controlled gr
oup) having 17 volunteers (all male).
The age of the study population ranged from
18 to 59 years. A wide range in the
age of volunteers was observed because hair loss is known to affect a wide
range of the population irrespective of age. Although it is more commonly seen
with increasing age, young adults are also affected. Moreover, hair loss may be
attributed to universal causes such as nutritional deficiency and oxidative stress,
which can affect a wide age group. The volunteers had hair loss problem for
approximately 2 to 5 years.
Comparability of the treatm
ent groups with respect to initial hair counts
as well as the weight of hair prior to
study commencement was also assessed.
The mean number of hairs of volunteers
in the placebo group at baseline was
289.0 ± 98.3, while that of the tocotrie
nol supplementation group was 284.8 ±
111.3. As for the mean weight of 20 str
ands of hair at baseline for the placebo
and tocotrienol supplementation groups, the values were 0.1002 ± 0.0639 g and
0.0920 ± 0.0565 g, respectively. The values between the placebo and
supplementation groups were comparable for both parameters and no
statistically significant difference (
p
> 0.05) was detected.
Thirty five volunteers completed the
entire study and were included in the
evaluation of the efficacy of tocotrienol
supplementation. Three volunteers were
lost to follow-up, one (female) from
the tocotrienol supplementation group and
two from the placebo group. Compliance with the supplementation regimen was
satisfactory, as evidenced by the capsul
e counts during their monthly visits. No
severe drug reaction related to the administration of the drug product and
placebo was recorded, thus indicating that
long-term administration of 100 mg of
tocotrienols for up to 8 months was tolerable. The compliance with the study
protocol was also deemed satisfactory
and no protocol deviation was recorded.
95
Table 1 shows the hair numbers at
baseline and at 4 and 8 months from
baseline for volunteers receiving placebo and tocotrienol supplementation
together with the percentage change from base
line. It is evident that volunteers in
the tocotrienol supplementation group showed a gradual mean increase in hair
Lim Ai Beoy et al.
numbers from baseline up to the 8
th
month interval with a mean percentage
increase of more than 34% at the end of
the study. In comparison, the number of
hairs for volunteers in the placebo group
did not show any appreciable increase
at the end of the 8 months study. A neg
ligible percentage change of 0.1% was
recorded by this group.
Table 1:
Mean numbers of hairs at baseline and
after 4 and 8 months of tocotrienol and
placebo supplementation (mean ± SD,
percentage change from baseline).
Intervals
Supplementation
Baseline
4 months
8 months
Tocotrienol supplementation
284.8 ± 111.3
328.0 ± 121.1
(15.2%)
383.1 ± 120.9
(34.5%)
Placebo
289.0 ± 98.3
298.2 ± 92.4
(3.2%)
288.7 ± 89.9
(–0.1%)
There was no statistically significant
difference in the main effect of
supplementation but a significant main e
ffect of interval was evident. Tukey’s
post-hoc test showed that the hair nu
mbers at the 8 month interval were
significantly greater than those at ba
seline and at the 4 month interval.
Subsequent simple main effect analysis i
ndicated that a statistically significant
difference occurred between baseline and
post-supplementation at the 8 month
interval for volunteers supplemented with tocotrienols only. All other pairwise
comparisons (baseline vs. 4 month interval for placebo and supplementation
group and baseline vs. 8 month interval for placebo group) did not show
statistically significant differences. This
indicates that there was no placebo effect
and the increase in the number of hairs observed in the volunteers could be
ascribed to tocotrienol supplementation.
Pairwise comparison also demonstrated that the hair numbers of
volunteers of the tocotrienol suppl
ementation and placebo groups were
significantly different at the 8 month interv
al. At this interval, the number of hairs
was much higher for the tocotrienol supplementation group volunteers than those
in the placebo group. Nevertheless,
the same could not be ascribed for
observations obtained at the 4 month interv
al, whereby no statistically significant
difference was observed between the 2 groups at this interval. In this regard, it
can be summarised that tocotrienol supplementation for a period of 8 months
resulted in significant increases in the num
bers of hairs as compared to that in
the placebo group.
96
All volunteers with the exception of one in the tocotrienol
supplementation group showed a positiv
e response at the end of the 8 month
study, recording an increase in the num
ber of hairs in the area of scalp
evaluated. Eight volunteers (4
0.0%) showed hair increases of more than 50%, 1
volunteer (5.0%) had a 25% to 50% increase, 9 volunteers (45.0%) had
increases between 10% to 25% while 1 vo
lunteer (5.0%) showed a hair increase
of less than 10%. Only 1 volunteer (5.0%)
in the tocotrienol supplementation
group had a slight decrease in the number
of hairs. On the other hand, only 8
volunteers in the placebo group showed an increase in the number of hairs after
Effects of Tocotrienol Supplementation on Hair Growth
8 months, with 1 (6.7%) showing more than 20% increase and the remaining 7
(46.7%) showing negligible increases. Seven volunteers (46.7%) had a decrease
in the number of hairs.
However, there was no statistically sign
ificant increase in the weight of
hair (
p
> 0.05) between pre- and post-supplementation for both groups of
volunteers (tocotrienol supplementat
ion and placebo group). The mean
percentage of weight increment after 8 m
onths of supplementation was 5.9% in
the tocotrienol supplementation group, while that of the placebo group had a
slight decrease of 2.0% (Table 2).
Table 2:
Mean weight (g) of 20 strands of hair
at baseline and after 4 and 8 months of
tocotrienol and placebo supplementation (Mean ± SD, percentage change from baseline).
Intervals
Supplementation
Baseline
4 months
8 months
Tocotrienol
supplementation
0.0929 ± 0.0565
0.0935 ± 0.0590
(0.6%)
0.0984 ± 0.0680
(5.9%)
Placebo
0.1002 ± 0.0639
0.0975 ± 0.0547
(–2.7%)
0.0982 ± 0.0563
(–2.0%)
Recently, Naziroglu and Kokcam (
2000) showed that an association
existed between oxidative stress and alopecia. Specifically, the levels of GSH
and activities of GSH-Px were significantl
y lower in patients with alopecia than in
controls, whereas TBARS le
vels, which indicate lipid peroxidation and oxidative
stress, were significantly higher. Similar observations were also reported by Koca
et al.
(2005) and Akar
et al.
(2002), whereby the authors in the former observed
an increased lipid peroxidation and a decre
ase in superoxide dismutase (SOD)
levels in patients with alopecia areata compared to controls. In the latter, TBARS
levels in the scalp of patients with alopecia areata were higher than those of
controls, although the authors reported a hi
gher levels of SOD and GSH-Px in
alopecia patients. Girat
et al.
(1996) similarly reported that TBARS levels
increased 2-fold and glutathione content
was reduced 2.5-fold in sebaceous
gland-enriched scalp skin of men affected by male pattern baldness as compared
to the controls. Moreover, Naziroglu an
d Kokcam (2000) demonstrated that both
the
ß
-carotene and
α
-tocopherol levels in plasma were lower in patients with
alopecia, albeit the latter was not statistically significant. This led to the authors’
postulation that antioxidant treatment such as using
ß
-carotene, vitamin E and
selenium may benefit patients with alopecia. Hence, the positive effect of
tocotrienol supplementation in the current study could most likely be ascribed to
its potent anti-oxidant activities.
97
Nevertheless, other mechanisms merit further investigations such as
those that play a role in Androgenetic Alopecia. It has bee
n shown by Hee (2008) that incubation of
a synthetic androgen with rat vibrissae dermal papilla cells (DP6) led to increased
production of reactive oxygen species (ROS) intracellularly. In addition, the
authors also reported that androgen-inducible
transforming growth factor beta 1
(TGF-
ß
1), a key mediator in the formati
on of Androgenetic Alopecia, was mediated by ROS and
could be prevented by antioxidants or ROS inhibitors in the hair follicle dermal
Lim Ai Beoy et al.
papilla cells (Hee 2008; Inui
et al.
2003). The above observations led the authors
to suggest that antioxidants could pot
entially be used to control androgen-
mediated pattern hair loss.
CONCLUSION
In conclusion, this trial demonstrated
that supplementation with tocotrienol
capsules increases hair numbers in volunteers suffering from hair loss as
compared to the placebo group. A possib
le explanation for the effects could be
due to the potent antioxidant activity of
tocotrienols that help to reduce lipid
peroxidation and oxidative stress in the
scalp, which are known to be associated
with alopecia.
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Tropical Life Sciences Research, 21(2), 91–99, 2010
Effects of Tocotrienol Supplementation on Hair Growth in Human
Volunteers
1
Lim Ai Beoy,
2
Wong Jia Woei and
1
Yuen Kah Hay
*
1
School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 USM,
Pulau Pinang, Malaysia
2
Hovid Bhd, 121, Jalan Tunku Abdul
Rahman, 30010 Ipoh, Perak, Malaysia
Abstrak:
Kajian telah menunjukkan bahawa terdapat perhubungan di antara oksidatif
stres dengan keguguran rambut. Pesakit yang mengalami keguguran rambut secara
amnya mempamerkan paras anti-oksidan yang lebih rendah pada kawasan kulit kepala
serta index peroksidan lemak yang lebih tinggi. Tokotrienol merupakan vitamin E dan
mempunyai efek anti-oksidan yang tinggi. Oleh itu, satu kajian telah dijalankan untuk
mengkaji kesan suplementasi tokotrienol ke atas sukarelawan yang mengalami masalah
keguguran rambut. Dua puluh satu sukarelawan diagihkan secara rawak untuk menerima
100 mg tokotrienol campuran setiap hari secara oral manakala 17 sukarelawan diagihkan
untuk menerima placebo secara oral. Sukarelawan-sukarelawan tersebut dipantau pada
bulan ke-0 (sebelum menerima suplementasi tokotrienol), ke-4 dan ke-8 bagi menentukan
bilangan rambut pada kawasan kepala yang telah ditentukan terlebih dahulu serta berat
20 helai keratan rambut sepanjang 1 cm. Sukarelawan-sukarelawan yang menerima
suplementasi tokotrienol menunjukkan penin
gkatan bilangan rambut yang signifikan
berbanding kumpulan placebo. Kumpulan su
plementasi tokotrienol mencatatkan
peningkatan sebanyak 34.5% pada penghujung bulan ke-8 berbanding dengan penurunan
sebanyak 0.1% yang dicatatkan oleh kumpulan
placebo. Namum demikian, berat 20 helai
keratin rambut tidak banyak berbeza di antara kedua-dua kumpulan pada
penghujung tempoh kajian. Sebagai kesimpulan, kajian ini menunjukkan bahawa
suplementasi dengan kapsul tokotrienol meningkatkan bilangan rambut pada sukarelawan
yang mengalami masalah keguguran rambut berbanding dengan kumpulan placebo.
Kesan ini berkemungkinan disebabkan oleh
aktiviti anti-oksidan tokotrienol yang
membantu menurunkan peroksidan lemak dan oksidatif stres pada kulit kepala, dimana
kedua-duanya telah dihubungkaitkan dengan keguguran rambut.
Kata kunci:
Pertumbuhan Rambut, Tokotrienol, Anti-oksidan
Abstract:
Studies have shown an association between oxidative stress and alopecia.
Patients with alopecia generally exhibit lower levels of antioxidants in their scalp area as
well as a higher lipid peroxidation index. Tocotrienols belong to the vitamin E family and
are known to be potent antioxidants. Hence,
a study was conducted to investigate the
effect of tocotrienol supplementation on hair
growth in volunteers suffering from hair loss.
Twenty one volunteers were randomly assigned to orally receive 100 mg of mixed
tocotrienols daily while 17 volunteers were assigned to receive placebo capsule orally. The
volunteers were monitored for the number of hai
rs in a pre-determined scalp area as well
as the weight of 20 strands of 1 cm length ha
ir clippings at 0 (before supplementation), 4
and 8 months. The number of hairs
of the volunteers in the
tocotrienol supplementation
group increased significantly as compared to
the placebo group, with the former recording
a 34.5% increase at the end of the 8-mont
h supplementation as compared to a 0.1%
decrease for the latter. Nevertheless, the cumula
tive weight of 20 strands of hair clippings
91
*
Corresponding author:
khyuen@usm.my
Lim Ai Beoy et al.
did not differ much from the baseline for both
supplementation gro
ups at the end of the
study period. In conclusion, this trial dem
onstrated that supplementat
ion with tocotrienol
capsules increases hair number in volunteers suffering from hair loss as compared to the
placebo group. This observed effect was most likel
y to be due to the antioxidant activity of
tocotrienols that helped to reduce lipid pe
roxidation and oxidative stress in the scalp,
which are reported to be associated with alopecia.
Keywords:
Hair Growth, Tocotr
ienols, Antioxidants
INTRODUCTION
Scalp hair plays an important function in
humans. In addition to providing cranial
cushioning and shielding the scalp from direct sun rays, hair has sociological
meanings in terms of gender, age, values
and status (Cash 2001). Scalp hair is
also a vital aspect of an individual's physical appearance and helps to project a
positive image (Cash 2001). Hair loss and balding, on the other hand, are
associated with negative attributes (Rushton
et al
. 2002). Hair loss or alopecia is
a common problem suffered by both sexes and has been reported to cause
significant psychological effects, such
as diminished self-esteem, emotional
distress, embarrassment and social inadequ
acy, with these detrimental effects
being more significant in women (Cash
et al.
1993). Van der Donk
et al.
(1994)
observed that alopecia could severely affect
the quality of life of the majority of
the sufferers, whereby 88% of sufferers experienced negative effects in their daily
life and 75% and 50% encountered negativ
e self-esteem and social problems,
respectively.
There are many types of alopecia, su
ch as androgenetic alopecia (Androgenetic Alopecia),
alopecia areata, telogen effluvium, hair loss due to systemic medical problems
such as thyroid disease and adverse drug effects, as well as hair loss due to
scalp or hair trauma, discoid lupus er
ythematosus, lichen planus and structural
shaft abnormalities, to name a few (Hogan & Chamberlain 2000). The causes for
the above are numerous and va
ry between the different types of alopecia. In
most instances, the aetiology is still
unknown. However, one of the universal
causes of increased hair thinning or shedding is nutritional deficiency. It was
previously reported that children with pr
otein malnutrition would exhibit fragile
and finer hairs that easily fall or break off and display a lower daily rate of growth
(Bradfield & Bailey 1969; Sims 1968). Nutr
itional factors that have been identified
to be essential in preventing hair loss in
clude iron and an essential amino acid, L-
lysine (Rushton
et al.
1990; Rushton 2002). Rushton
et al.
(2002) reported that
women with chronic telogen effluvium have low serum ferritin levels and
proceeded to demonstrate that daily supplementation of iron and L-lysine for 6
months could cause significant increases in hair numbers.
92
Recently, Naziroglu and Kokcam (2
000) showed that there was an
association between oxidative stress and
alopecia. They reported that the levels
of reduced glutathione (GSH) and activities
of glutathione per
oxidase (GSH-Px),
which are present to protect against damages caused by reactive oxygen species
such as free radicals and peroxides, were significantly lower in patients with
alopecia than in controls, whereas the levels of thiobarbituric acid reactive
Effects of Tocotrienol Supplementation on Hair Growth
substances (TBARS), which indicate lipid peroxidation and oxidative stress, were
significantly higher.
Tocotrienols together with tocopherols are members of the vitamin E
family. They share similar structural f
eatures of a chroman head and a 16-carbon
phytyl chain. The structural difference
between them lies mainly in the latter
possessing a saturated phytyl chain wherea
s that of the former possesses three
unsaturated double bonds (Papas 1999; Theriault
et al.
1999). Tocotrienols also
possess more potent antioxidant property, and Serbinova
et al.
(1991) showed
that
α
-tocotrienol was 40- to 60-fold more potent than
α
-tocopherol against lipid
peroxidation in rat liver microsomal
membranes. This superiority has been
ascribed to the ability of tocotrienols to better distribute within the fatty layers of
the cell membranes and hence permit better interaction with lipid radicals.
Moreover, tocotrienols have been shown to afford protection to the skin against
UV light- and ozone-induced
oxidative stress (Traber
et al.
1997).
In view of the association between
alopecia and oxidative stress and the
high antioxidant potency of the tocotr
ienols, a study was thus performed in
volunteers with alopecia to evaluate the e
fficacy of tocotrienol supplementation in
improving hair coverage of the scalp
and preventing hair thinning in patients
suffering from alopecia.
MATERIALS AND METHODS
Patient Population
Thirty eight male and female volunteers ranging from 18 to 60 years old who met
the inclusion criteria were recruited into
the trial. Volunteers had varying levels of
hair loss, ranging from patchy loss of scalp hair to more severe loss of scalp hair.
Hair loss must have been present for at least 2 months and the alopecia area
could not have any visual evidence of new hair growth. All volunteers were in
good general health with no evidence of systemic illness including cardiac,
psychiatric, thyroid and scalp diseases.
Volunteers were excluded from the study if they had known
hypersensitivity to tocotrienols or if
they had undergone hair restoration
procedures, consumed hair growth medications or applied hair enhancement
products in the past 6 months. Pati
ents who had undergone chemotherapy and
experienced scalp trauma were also exclud
ed. Concomitant use of medications,
such as steroids, oral contraceptiv
es, cytotoxic agents, vasodilators,
antihypertensive agents, anti-convulsant drugs,
ß
-adrenergic receptor blockers,
diuretics, spironolactone, cimetidine, cyclosporine or ketoconazole, during the 6
months prior to the study was also not
allowed. Patients on iron and vitamin B12
supplementation were also excluded.
Volunteers were also instructed not to
alter their hairstyle, the hair care
products (such as shampoo or conditioner
) currently in use or dye their hair
during the study period.
93
Lim Ai Beoy et al.
Study Design
This study was an 8 month (32 week),
randomised, double-blind, placebo-
controlled trial conducted at the School of Pharmaceutical Sciences, Universiti
Sains Malaysia, Pulau Pinang. The protocol and informed consent form were
approved by an institutional review boar
d and written informed consent was
obtained from each volunteer prior to enr
olment into the study. Thirty eight
volunteers participated in the trial, and 21 volunteers were randomly selected to
receive tocotrienol supplementation (tocotri
enol supplementation group) while 17
were randomly selected to receive the placebo (placebo group). The placebo is a
soft gelatine capsule containing 600 mg of
soya bean oil (Hovid Sdn Bhd, Ipoh,
Malaysia), while tocotrienol supplementation consisted of mixed tocotrienols
formulated in a soft gelatine capsule (Hovid Sdn Bhd). Each tocotrienol capsule
contained 50 mg of mixed tocotrienols (30.8%
α
-tocotrienol, 56.4%
γ
-tocotrienol
and 12.8%
δ
-tocotrienol) as well as 23 IU of
α
-tocopherol. The volunteers were
required to take one capsule of either the placebo or tocotrienol twice daily after
meal over a period of 8 months. Hence, t
he total daily intake of tocotrienols for
each volunteer in the treatment group wa
s 100 mg. The capsules were provided
on a monthly basis and compliance with the supplementation regimen was
monitored by counting the capsules that were left over during the monthly visit.
The volunteers were also counselled and advised to take the capsules regularly
as per the instruction given to ensure co
mpliance. The volunteers were required
to report any side/adverse reactions,
additional medication taken and any new
diagnosis during the trial period.
Efficacy Evaluation
Two parameters were chosen to evaluate the efficacy of tocotrienol
supplementation (Price
et al.
2002):
1.
Hair counts
Hair counts served as the primary effica
cy measure. An area of 2 × 2 cm was
selected in the area of hair thinning for each patient in the balding vertex
scalp, and the 2 opposing corners of
the square were permanently marked
(using a 4 cm
2
wire template) to ensure that the hair in same area was
counted at each visit. The count was done by an investigator who was
blinded to the treatment the volunteers were receiving. The resulting hair
counts were used to calculate the percentage change from baseline.
2.
Weight of hairs
A small tuft of hair (at least 20 strands) within the demarcated area was
clipped horizontally. Twenty strands were randomly chosen and cut to 1 cm
in length. The total weight was obtained using a microbalance and the
resulting mean weight was used to ca
lculate the percentage change from
baseline.
Both parameters were obtained at baseline, 4 months (16
th
week) after the
start of the study and at the end of 8 months (32
nd
week) for efficacy evaluation.
Altogether, there were three intervals.
94
Effects of Tocotrienol Supplementation on Hair Growth
Statistical Calculation
The data collected at baseline and du
ring the supplementation period for both
groups were compared using an analysis of variance procedure (ANOVA) for a
two-factor repeated measures split-plo
t experimental design (Kirk 1968). If a
statistically significant difference for the main effect of interval was observed,
Tukey’s post-hoc test was employed. When significant interaction between
supplementation and an interval was observed, simple main effect analysis
(pairwise comparison) was employed to
locate the pair that gave rise to the
observed difference. The homogeneity of
the baseline characteristics between
the two groups, namely the number and weight of hairs, was also assessed. A
statistically significant difference was considered at
p
< 0.05.
RESULTS AND DISCUSSION
Thirty eight volunteers with signs of hair
loss or balding were enrolled in the
study, with the supplementation group having 21 volunteers (19 male and 2
female) and the placebo group (controlled gr
oup) having 17 volunteers (all male).
The age of the study population ranged from
18 to 59 years. A wide range in the
age of volunteers was observed because hair loss is known to affect a wide
range of the population irrespective of age. Although it is more commonly seen
with increasing age, young adults are also affected. Moreover, hair loss may be
attributed to universal causes such as nutritional deficiency and oxidative stress,
which can affect a wide age group. The volunteers had hair loss problem for
approximately 2 to 5 years.
Comparability of the treatm
ent groups with respect to initial hair counts
as well as the weight of hair prior to
study commencement was also assessed.
The mean number of hairs of volunteers
in the placebo group at baseline was
289.0 ± 98.3, while that of the tocotrie
nol supplementation group was 284.8 ±
111.3. As for the mean weight of 20 str
ands of hair at baseline for the placebo
and tocotrienol supplementation groups, the values were 0.1002 ± 0.0639 g and
0.0920 ± 0.0565 g, respectively. The values between the placebo and
supplementation groups were comparable for both parameters and no
statistically significant difference (
p
> 0.05) was detected.
Thirty five volunteers completed the
entire study and were included in the
evaluation of the efficacy of tocotrienol
supplementation. Three volunteers were
lost to follow-up, one (female) from
the tocotrienol supplementation group and
two from the placebo group. Compliance with the supplementation regimen was
satisfactory, as evidenced by the capsul
e counts during their monthly visits. No
severe drug reaction related to the administration of the drug product and
placebo was recorded, thus indicating that
long-term administration of 100 mg of
tocotrienols for up to 8 months was tolerable. The compliance with the study
protocol was also deemed satisfactory
and no protocol deviation was recorded.
95
Table 1 shows the hair numbers at
baseline and at 4 and 8 months from
baseline for volunteers receiving placebo and tocotrienol supplementation
together with the percentage change from base
line. It is evident that volunteers in
the tocotrienol supplementation group showed a gradual mean increase in hair
Lim Ai Beoy et al.
numbers from baseline up to the 8
th
month interval with a mean percentage
increase of more than 34% at the end of
the study. In comparison, the number of
hairs for volunteers in the placebo group
did not show any appreciable increase
at the end of the 8 months study. A neg
ligible percentage change of 0.1% was
recorded by this group.
Table 1:
Mean numbers of hairs at baseline and
after 4 and 8 months of tocotrienol and
placebo supplementation (mean ± SD,
percentage change from baseline).
Intervals
Supplementation
Baseline
4 months
8 months
Tocotrienol supplementation
284.8 ± 111.3
328.0 ± 121.1
(15.2%)
383.1 ± 120.9
(34.5%)
Placebo
289.0 ± 98.3
298.2 ± 92.4
(3.2%)
288.7 ± 89.9
(–0.1%)
There was no statistically significant
difference in the main effect of
supplementation but a significant main e
ffect of interval was evident. Tukey’s
post-hoc test showed that the hair nu
mbers at the 8 month interval were
significantly greater than those at ba
seline and at the 4 month interval.
Subsequent simple main effect analysis i
ndicated that a statistically significant
difference occurred between baseline and
post-supplementation at the 8 month
interval for volunteers supplemented with tocotrienols only. All other pairwise
comparisons (baseline vs. 4 month interval for placebo and supplementation
group and baseline vs. 8 month interval for placebo group) did not show
statistically significant differences. This
indicates that there was no placebo effect
and the increase in the number of hairs observed in the volunteers could be
ascribed to tocotrienol supplementation.
Pairwise comparison also demonstrated that the hair numbers of
volunteers of the tocotrienol suppl
ementation and placebo groups were
significantly different at the 8 month interv
al. At this interval, the number of hairs
was much higher for the tocotrienol supplementation group volunteers than those
in the placebo group. Nevertheless,
the same could not be ascribed for
observations obtained at the 4 month interv
al, whereby no statistically significant
difference was observed between the 2 groups at this interval. In this regard, it
can be summarised that tocotrienol supplementation for a period of 8 months
resulted in significant increases in the num
bers of hairs as compared to that in
the placebo group.
96
All volunteers with the exception of one in the tocotrienol
supplementation group showed a positiv
e response at the end of the 8 month
study, recording an increase in the num
ber of hairs in the area of scalp
evaluated. Eight volunteers (4
0.0%) showed hair increases of more than 50%, 1
volunteer (5.0%) had a 25% to 50% increase, 9 volunteers (45.0%) had
increases between 10% to 25% while 1 vo
lunteer (5.0%) showed a hair increase
of less than 10%. Only 1 volunteer (5.0%)
in the tocotrienol supplementation
group had a slight decrease in the number
of hairs. On the other hand, only 8
volunteers in the placebo group showed an increase in the number of hairs after
Effects of Tocotrienol Supplementation on Hair Growth
8 months, with 1 (6.7%) showing more than 20% increase and the remaining 7
(46.7%) showing negligible increases. Seven volunteers (46.7%) had a decrease
in the number of hairs.
However, there was no statistically sign
ificant increase in the weight of
hair (
p
> 0.05) between pre- and post-supplementation for both groups of
volunteers (tocotrienol supplementat
ion and placebo group). The mean
percentage of weight increment after 8 m
onths of supplementation was 5.9% in
the tocotrienol supplementation group, while that of the placebo group had a
slight decrease of 2.0% (Table 2).
Table 2:
Mean weight (g) of 20 strands of hair
at baseline and after 4 and 8 months of
tocotrienol and placebo supplementation (Mean ± SD, percentage change from baseline).
Intervals
Supplementation
Baseline
4 months
8 months
Tocotrienol
supplementation
0.0929 ± 0.0565
0.0935 ± 0.0590
(0.6%)
0.0984 ± 0.0680
(5.9%)
Placebo
0.1002 ± 0.0639
0.0975 ± 0.0547
(–2.7%)
0.0982 ± 0.0563
(–2.0%)
Recently, Naziroglu and Kokcam (
2000) showed that an association
existed between oxidative stress and alopecia. Specifically, the levels of GSH
and activities of GSH-Px were significantl
y lower in patients with alopecia than in
controls, whereas TBARS le
vels, which indicate lipid peroxidation and oxidative
stress, were significantly higher. Similar observations were also reported by Koca
et al.
(2005) and Akar
et al.
(2002), whereby the authors in the former observed
an increased lipid peroxidation and a decre
ase in superoxide dismutase (SOD)
levels in patients with alopecia areata compared to controls. In the latter, TBARS
levels in the scalp of patients with alopecia areata were higher than those of
controls, although the authors reported a hi
gher levels of SOD and GSH-Px in
alopecia patients. Girat
et al.
(1996) similarly reported that TBARS levels
increased 2-fold and glutathione content
was reduced 2.5-fold in sebaceous
gland-enriched scalp skin of men affected by male pattern baldness as compared
to the controls. Moreover, Naziroglu an
d Kokcam (2000) demonstrated that both
the
ß
-carotene and
α
-tocopherol levels in plasma were lower in patients with
alopecia, albeit the latter was not statistically significant. This led to the authors’
postulation that antioxidant treatment such as using
ß
-carotene, vitamin E and
selenium may benefit patients with alopecia. Hence, the positive effect of
tocotrienol supplementation in the current study could most likely be ascribed to
its potent anti-oxidant activities.
97
Nevertheless, other mechanisms merit further investigations such as
those that play a role in Androgenetic Alopecia. It has bee
n shown by Hee (2008) that incubation of
a synthetic androgen with rat vibrissae dermal papilla cells (DP6) led to increased
production of reactive oxygen species (ROS) intracellularly. In addition, the
authors also reported that androgen-inducible
transforming growth factor beta 1
(TGF-
ß
1), a key mediator in the formati
on of Androgenetic Alopecia, was mediated by ROS and
could be prevented by antioxidants or ROS inhibitors in the hair follicle dermal
Lim Ai Beoy et al.
papilla cells (Hee 2008; Inui
et al.
2003). The above observations led the authors
to suggest that antioxidants could pot
entially be used to control androgen-
mediated pattern hair loss.
CONCLUSION
In conclusion, this trial demonstrated
that supplementation with tocotrienol
capsules increases hair numbers in volunteers suffering from hair loss as
compared to the placebo group. A possib
le explanation for the effects could be
due to the potent antioxidant activity of
tocotrienols that help to reduce lipid
peroxidation and oxidative stress in the
scalp, which are known to be associated
with alopecia.
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