Original Contribution

The clinical anti-aging effects of topical kinetin and niacinamide in

Blackwell Publishing Ltd

Asians: a randomized, double-blind, placebo-controlled, split-face

comparative trial
Pin-Chi Chiu, MD,1,2 Chih-Chieh Chan, MD,1 Hui-Min Lin,1 & Hsien-Ching Chiu, MD1
1
Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
2
Center of Anti-aging and Health Consultation, National Taiwan University Hospital, Taipei, Taiwan

Summary Background Kinetin and niacinamide are used in the cosmetic industry as anti-aging
agents. Neither the interactive/additive effects of these compounds nor the anti-aging
efficacy on Asian skin has been studied.
Objective To assess the clinical anti-aging effects and efficacy differences between kinetin
plus niacinamide and niacinamide alone vs. vehicle placebo in an Asian cohort.
Methods Fifty-two Taiwanese subjects were enrolled in a randomized, double-blind,
placebo-controlled, split-face comparative study. Group 1 subjects were treated with
kinetin 0.03% plus niacinamide 4%, whereas group 2 subjects received niacinamide 4%.
The treatment formulation was applied on one side of the face, whereas a placebo was
applied on the other for a period of 12 weeks. We used noninvasive biometrological
instruments to evaluate a variety of skin parameters at baseline and at weeks 4, 8, and 12.
Results Persistent and significant reductions in spot, pore, wrinkle, and evenness counts
were found at weeks 8 and 12 in group 1. A significant increase in corneal hydration
status was also evident at week 12, whereas persistent decreases in erythema index were
apparent at 8 and 12 weeks. In group 2, significant reductions in pore and evenness
counts at week 8 and wrinkle counts at week 12 were noted.
Conclusion We found kinetin and niacinamide exert a synergistic anti-aging effect. Our
data suggest that these compounds have multiactive, multifunctional, and pluripotent
effects on skin. They are also both promising to be included in the cutaneous anti-aging
cosmeceuticals in the future.
Keywords: kinetin (N6-furfuryladenine), niacinamide, cosmeceuticals

The aging process encompasses gradual and continuous
physiological changes during a lifetime that ultimately
lead to senescence. There are two general theories of
aging. One suggests that the process is genetically deter-
mined (intrinsic aging), whereas the other emphasizes
the importance of the environment (extrinsic aging). The
Correspondence: Pin-Chi Chiu, MD, Department of Dermatology, National
Taiwan University Hospital, No. 7, Chung San South Road, Taipei, Taiwan
100. E-mail: pinchichiu@ntu.edu.tw
Accepted for publication July 14, 2007
renewing, metabolic, productive, protective, immunological,
endocrinological, and neural functions of skin cells all
decline with age.1 The clinical signs associated with aging
include dyspigmentation (hyperpigmentation and hypo-
pigmentation), loss of elasticity and laxity, yellowish and
dull skin tone, fine lines and wrinkles, telangiectasia,
uneven texture, enlarged pores, eye bags, keratosis, etc.
Many cosmetic and cosmeceutical products have
been purported to exert anti-aging effects, but few have
been examined in an evidence-based setting. Well-known
anti-aging ingredients such as retinoids and l-ascorbic

© 2007 Blackwell Publishing • Journal of Cosmetic Dermatology, 6, 243– 249 243

Anti-aging effects of kinetin and niacinamide • P-C Chiu et al.
acid are somewhat irritating to the skin and can be unstable
in many cosmetic formulations. Hence, the search for
more pluripotent, but less irritating, anti-aging ingredi-
ents continues. Two recently proposed anti-aging agents
include kinetin (N6-furfuryladenine) and niacinamide.
Kinetin was first isolated from autoclaved herring
sperm DNA in 1955 and was the first cytokinin identi-
fied.2,3 It is an essential plant growth hormone that regu-
lates aspects of growth and differentiation, retards leaf
yellowing and senescence, and slows down fruit ripening
and degeneration.2,3 Kinetin has also been reported to be
present in the human cell extracts4 and urine5 and has
been identified as a naturally occurring base modification
of DNA.6 Kinetin is a multiactive molecule reported to have
anti-aging effects on cultured cells7,8 and in fruitflies,9
antioxidative characteristics,10,11 antithrombotic activity,12,13
and cell differentiation promoting effects.14–16 However
only two reports regarding associated clinical anti-aging
effects on hairless dogs17 and human skin18 have been
published.
Niacinamide, also known as nicotinamide, is the physio-
logically active amide of niacin and the precursor of
important cofactors niacinamide adenine dinucleotide
(NAD) and its phosphate derivative (NADP). These cofac-
tors and their reduced forms (NADH and NADPH) serve
as redox coenzymes in over 40 cellular biochemical reac-
tions. Although the nutritional value of niacinamide is
well recognized, its skin care benefits have been less well
studied until recently. There have been a number of
reports published regarding the beneficial effects of topi-
cal niacinamide on the skin. These include prevention of
photoimmunosuppression and photocarcinogenesis,19
prevention of dermal collagen loss in photoaging skin,20
anti-inflammatory effects in acne,21,22 improvement in
bullous pemphigoid,23 reduction of cutaneous pigmentation
and suppression of melanosome transfer,24 and increased
intercellular lipid synthesis with enhanced stratum cor-
neum barrier function.25 In more recent studies, topical
niacinamide has been shown to improve aging facial
skin,26,27 moisturize atopic dry skin,28 reduce rosacea
symptoms,29 and lower sebum excretion rates or casual
sebum levels.30 Thus, niacinamide exerts multiple effects on
the skin and is a promising anti-aging cosmetic ingredient.
To date, there has been no report of the combined
effects of kinetin and niacinamide on the skin. Further-
more, the cutaneous efficacy of these compounds on
Asian skin has not been examined. Hence, we performed
a clinical trial to assess the efficacy and safety of kinetin
and niacinamide preparations in Asian subjects. We
utilized digital imaging analysis and biometrological
instruments to record and assess a variety of cutaneous
parameters and conditions.
244
Methods
This study was done between February and May 2006 in
Taipei, Taiwan. This was a double-blind, placebo-controlled,
split-face, left-right randomized clinical trial. The entire
protocol was reviewed and approved by the institutional
review board in our hospital. Before participating in the
clinical study, each subject signed a written informed
consent, which explained the type of study, the pro-
cedures to be followed, the general nature of the materials
being tested, and any known or anticipated adverse
reactions that might result from participation.
A total of 52 healthy Taiwanese female and male sub-
jects (age: 30–60 years; 90% female) were enrolled in the
study. All subjects had Fitzpatrick skin types II, III, or IV.
Subjects were not pregnant, nursing, or undergoing
any concurrent topical or surgical therapy on the face.
Subjects with any chronic skin disease or disorder (e.g.,
psoriasis, eczema, atopic dermatitis), visible skin cancers
on the face, a known allergy to any component of the
study formulations, or a proclivity to cutaneous hyper-
reactivity were excluded from the study. Additional exclu-
sion criteria included use of oral isotretinoin 6 months or
topical retinoic acid 2 months prior to the study, use of
topical alpha-hydroxyl acids skin-care products, chemical
peels, exfoliants or any abrasive substance on the face (all
1 month), or exposure of systemic (1 month) or topical
(2 weeks) corticosteroids.
Subjects were randomized to one of two treatment
groups. Group 1 received 12 weeks treatment of aqueous
serum containing kinetin 0.03% plus niacinamide 4% to
one side of the face and vehicle to the other side. Group 2
subjects received 12 weeks treatment of aqueous serum
containing only niacinamide 4% to one side of the face
and vehicle to the other side. The vehicle contained pure
water, propylene glycol, hydroxyethylcellulose, and sodium
hyaluronate. The application guidelines were printed on
the sticker attached to the vials. Subjects were instructed
to apply 0.4 cc (four drops) of test serum evenly to one
side of the face and vehicle to the other side twice daily, in
the morning and before bedtime. Subjects were further
instructed to apply a SPF 30 sunscreen in the daytime.
Modification of the facial skin-care habits and concomi-
tant use of other skin-care products were not permitted
during the study.
Digital complexion image analysis and measurement
of physiological facial parameters on each side of the face
were performed at baseline and at weeks 4, 8, and 12. All
skin measurements were made on untreated skin at least
30 min after washing with an assigned facial cleanser.
Temperature (20 ± 5°C) and relative humidity (50 ± 10%)
were controlled, and subjects were required to acclimate
© 2007 Blackwell Publishing • Journal of Cosmetic Dermatology, 6, 243–249

to these conditions for 30 min prior to measurements. All
measurements were taken, and images were captured
under the same conditions (lighting, distance, head posi-
tion, and measurement methods, etc.) at all time points.
Facial skin was digitally photographed and analyzed
using the VISIA Complexion Analysis System (Canfield
Scientific, Inc., Fairfield, NJ). The system allows for the
measurement of several facial feature parameters such as
spots, pores, wrinkles, evenness, and porphyrin index. In
this study, we only evaluated spots, pores, wrinkles, and
evenness factors. Spots are typically brown or red skin
lesions including freckles, solar lentigines, seborrheic
keratoses, nevocellular nevus. or acne scars and are
distinguishable by their color and contrast from the
background skin tone. Pores are the surface openings of
follicles. Due to shadowing, pores appear darker than the
surrounding skin and are identified on the basis of color
and circular shape. Wrinkles are furrows, folds, or creases
in the skin and are identified by their characteristic long,
narrow shape. Evenness measures skin texture by identi-
fying graduations in color from the surrounding skin
tone as well as peaks and valleys on the skin surface.
Noninvasive measurements of facial skin elasticity were
conducted using a Cutometer. Skin corneal moisture
status was measured by Corneometer, and skin melanin
and erythema index were measured by Mexameter.
All three probes were attached on MPA 580 (Courage
+ Khazaka electronic GmbH, Cologne, Germany). The
Cutometer, Corneometer, and Mexameter are reliable
and valid instruments that create reproducible data and
are widely used in skin biometrology. The measurements
were conducted on four clearly defined sites for each
volunteer (see Fig. 1). We recorded R5 (net elasticity)
values in the Cutometer measurements.
Self-assessments were conducted at each follow-up
visit via questionnaire. Subjects were asked to provide an
assessment of improvement relative to baseline for skin
Figure 1 Measuring points for assessment
of facial skin physiological parameters.
Point A (using Cutometer), 1 cm distance
from lateral canthus. Point B (using
Cutometer), 2 cm beside mouth angle.
Point C (using Corneometer), 1 cm below
point A. Point D (using Mexameter), 2 cm
below pupil.
© 2007 Blackwell Publishing • Journal of Cosmetic Dermatology, 6, 243– 249
Anti-aging effects of kinetin and niacinamide • P-C Chiu et al.
texture, skin color, hyperpigmentation, fine lines, and
overall improvement. These variables were scored on a
scale of 1–6, indicating total (6), great (5), moderate (4),
slight (3), none (2), and aggravated (1) improvement,
respectively.
At each visit, the investigator assessed signs of cutane-
ous irritation (erythema, edema, dryness, and peeling
conditions) as either none, mild, moderate, or severe in
grade. The subjects were asked to grade the symptoms of
irritation (burning, stinging or itching) as none, mild,
moderate, or severe.
All measured values were reported as mean ± standard
deviation (SD). A two-way Student’s t-test was used to
determine within group differences (i.e., baseline vs. after
treatment). A one-way anova test was used to determine
between-group differences. Differences were considered
significant when P < 0.05.
Results
A total of 52 subjects were randomized to apply kine-
tin 0.03% plus niacinamide 4% (n = 27, mean age:
40.0 ± 7.4 years) or niacinamide 4% (n = 25, mean age:
43.4 ± 8.3 years) to one side of the face and vehicle to the
other side (n = 52).
Facial spot counts were significantly decreased by
7.0 (P = 0.0109) and 6.8% (P = 0.0264) in the kinetin
0.03% plus niacinamide 4% compared with the baseline
at weeks 8 and 12, respectively (Fig. 2). Niacinamide
treatment alone was not associated with any significant
change in spot counts. Facial pore counts were signifi-
cantly decreased by 20.8% (P = 0.0002) and 15.9%
(P = 0.0028) in the kinetin plus niacinamide group at
weeks 8 and 12, respectively. A significant decrease was
also apparent in the niacinamide alone group at week 8
only (14.7%, P = 0.0034; Fig. 3). Facial wrinkle counts
were significantly decreased by 59.1 (P = 0.0008) and
245
Anti-aging effects of kinetin and niacinamide • P-C Chiu et al.
Figure 2 Effects of vehicles (n = 52), niacinamide 4% alone
(B3; n = 25), and the combination of kinetin 0.03% and niacinamide
4% (KNT + B3; n = 27) on facial spot counts. Measurements were
done using VISIA Complexion Analysis System before initiation of
treatment and at 4, 8, and 12 weeks. Data are shown as mean ± SD.
*P < 0.05.
Figure 3 Effects of vehicles (n = 52), niacinamide 4% alone
(B3; n = 25), and the combination of kinetin 0.03% and niacinamide
4% (KNT + B3; n = 27) on facial pore counts. Measurements were
done using VISIA Complexion Analysis System before initiation of
treatment and at 4, 8, and 12 weeks. Data are shown as mean ± SD.
*P < 0.05; **P < 0.01; ***P < 0.001.
41.0% (P = 0.0258) in the kinetin plus niacinamide
group at weeks 8 and 12, respectively, whereas a signifi-
cant decrease (51.6%, P = 0.0456) was evident in the
niacinamide group at week 12 only (Fig. 4). Facial even-
ness counts were significantly decreased by 21.3%
(P = 0.0009) and 16.3% (P = 0.0036) in the kinetin plus
niacinamide group at weeks 8 and 12, respectively,
whereas a significant difference (29.5%, P = 0.0046)
was apparent in the niacinamide alone group at week 8
only (Fig. 5).
246
Figure 4 Effects of vehicles (n = 52), niacinamide 4% alone
(B3; n = 25), and the combination of kinetin 0.03% and niacinamide
4% (KNT + B3; n = 27) on facial wrinkle counts. Measurements
were done using VISIA Complexion Analysis System before
initiation of treatment and at 4, 8, and 12 weeks. Data are
shown as mean ± SD. *P < 0.05; ***P < 0.001.
Figure 5 Effects of vehicles (n = 52), niacinamide 4% alone
(B3; n = 25), and the combination of kinetin 0.03% and niacinamide
4% (KNT + B3; n = 27) on facial evenness. Measurements were
done using VISIA Complexion Analysis System before initiation of
treatment and at 4, 8, and 12 weeks. Data are shown as mean ± SD.
**P < 0.01; ***P < 0.001.
The combination of kinetin and niacinamide signifi-
cantly increased facial skin corneal moisture by 16.7%
(P = 0.0005) at week 12 (Fig. 6). There was no effect
of niacinamide alone. Reduced facial skin melanin
was apparent in both the kinetin plus niacinamide
(7.1%, P = 0.0315) and the niacinamide alone (9.3%,
P = 0.0325) groups after 4 weeks only. Facial skin erythema
was significantly reduced in the kinetin plus niacinamide
group by 7.3% (P = 0.0125) and 10.0% (P = 0.0007) at
weeks 8 and 12, respectively (Fig. 7). Niacinamide treat-
ment alone was not associated with any significant
change in facial skin erythema. There were no effects of
© 2007 Blackwell Publishing • Journal of Cosmetic Dermatology, 6, 243–249

Figure 6 Effects of vehicles (n = 52), niacinamide 4% alone
(B3; n = 25), and the combination of kinetin 0.03% and niacinamide
4% (KNT + B3; n = 27) on facial skin moisture. Measurements were
done using a Corneometer probe before initiation of treatment and at
4, 8, and 12 weeks. Data are shown mean ± SD. ***P < 0.001.
Figure 7 Effects of vehicles (n = 52), niacinamide 4% alone
(B3; n = 25), and the combination of kinetin 0.03% and niacinamide
4% (KNT + B3; n = 27) on facial skin erythema. Measurements were
done using a Mexameter probe before initiation of treatment and at
4, 8, and 12 weeks. Data are presented as mean ± SD. *P < 0.05;
***P < 0.001.
either treatment on skin elasticity at time during the 12-
week period. In the one-way anova test, there were no
significant differences among vehicle group, niacinamide-
alone group, and kinetin plus niacinamide group at the
baseline and weeks 4, 8, and 12.
There were no significant differences in subject self-
assessment scores for either group at any point. There
were eight subjects in each group who experienced
one episode of a mild and transient adverse event. The
symptoms included erythema, dryness, peeling, burning,
stinging, or itching. The incidence rates in both groups
regarding each symptom were comparable and not
© 2007 Blackwell Publishing • Journal of Cosmetic Dermatology, 6, 243– 249
Anti-aging effects of kinetin and niacinamide • P-C Chiu et al.
statistically different. All adverse events spontaneously
resolved, and all afflicted subjects completed the trial.
Discussion
Kinetin is the first stable secondary DNA damage product
known to date with very well defined cytokinin and anti-
aging properties.31 It can be synthesized within the cell
as a result of oxidative stress processes and purported
to have direct antioxidant properties and/or to be an
indirect regulator of antioxidants.31 Currently, there is
only one published open-label study about the clinical
safety and efficacy of kinetin 0.1% lotion on human
skin.18 The results indicated that this formulation can
partially improve some of the clinical signs of mildly to
moderately photo-damaged facial skin (skin texture,
fine wrinkles, skin color, and blotchiness) and can
help restore normal skin barrier function within 12
to 24 weeks after application. Several conference
presentations have reported on the clinical effects of
kinetin;32,33 however, these studies were either lacking in
design, or sponsored by product companies.
The clinical effects of niacinamide are better studied
and there are some randomized, double-blind, split-face,
and placebo-controlled clinical trials published in the
literature. One study revealed that niacinamide 5% or
niacinamide 2% + UVB/UVA sunscreen moisturizer can
reduce facial hyperpigmentation in Japanese women.24
Another study with Caucasian subjects showed that
niacinamide 5% moisturizer provides a variety of benefi-
cial effects to the skin, such as improvements in the
appearance of facial skin texture, fine lines/wrinkles,
hyperpigmentation, red blotchiness, yellowing (sallow-
ness), and elasticity.26,27
Although the mechanisms underlying the cutaneous
anti-aging effects of kinetin and niacinamide are not fully
understood, the literature suggests that both molecules
have the capacity to modulate various cellular func-
tions.31,34–36 We speculate kinetin is not only an anti-
oxidant but also an intracellular oxdative metabolite with
possible feedback mechanisms of delaying cellular aging
and increasing metabolic capacity. Niacinamide also
serves as an important precursor of many endogenous
enzyme cofactors for antioxidant properties and cellular
activities. Thus, these two molecules may function
together and have synergistic effects. Both are also
nonirritating to facial skin, easily formulated, chemically
stable, compatible with other formulation components,
and are ideal agents for use in cosmeceuticals.
In this study, we investigated the anti-aging effects of
topical kinetin 0.03% and niacinamide 4% serum in
Asians. We found significant spot reduction following
247
Anti-aging effects of kinetin and niacinamide • P-C Chiu et al.
VISIA Complexion Analysis; however, the melanin index,
as measured by Mexameter, did not change significantly
finally. The former method evaluates the number of
hyperpigmented spots by digital imaging, while the later
only measures skin color change at a single point. Hence,
it is apparent that kinetin plus niacinamide treatment
can reduce the extent and number of hyperpigmented
spots on the face but does not have an obvious skin
complexion brightening effect. In other words, hyper-
pigmented areas showed better improvements than
normal skin-colored areas.
We found that topical application of niacinamide 4%
serum led to improvements in skin texture (pore numbers,
wrinkle counts, and evenness status). When combined
with kinetin 0.03%, the effects of reducing hyperpig-
mented spots and red blotchiness and increasing stratum
corneum hydration status were more persistent. This
indicates that kinetin plays a decisive and important role
in the formulation and the kinetin plus niacinamide can be
used as an adjunctive therapy for acne, rosacea, xerosis, and
sensitive skin and even for anti-aging purposes of the skin.
We also found subjective self-assessments may not
reflect the actual clinical changes in this study, and this
situation also happened in previous clinical trial before.24
That 8-week trial of topical niacinamide + sunscreen,
sunscreen, and vehicle showed significant skin lighten-
ing effects between treatment and vehicle group by com-
puterized image analysis. But the test subjects perceived
that their basal skin color showed no change or became
only slightly lighter during the study regardless of treat-
ment. This may be attributed to imprecise subjective
observations of subtle differences between sides of the
face during the test period or indefinite meanings of the
terms and scores in the self-assessment questionnaire for
the subjects. Therefore, objective professional biometro-
logical measurements and image assessments are important
adjuncts in clinical evaluations.
Facial pore counts and evenness status in VISIA Com-
plexion Analysis evaluation worsened at weeks 12 vs.
weeks 8 in both vehicle and treatment groups. This may
be due to the influence of seasonal weather warming
from the beginning the study (winter) to the end of the
study (late spring). Warmer season and higher tempera-
ture are known to increase sebum secretion.37 Enlarged
pore sizes are associated with higher sebum output
level,38 and the extents of peaks and valleys on the skin
surface may increase. This may be the reason why the
facial pore counts increased and evenness status
decreased at weeks 12. Even so, the kinetin plus niacina-
mide group showed better results than niacinamide
group and vehicle placebo. Although, the vehicle showed
significant results at some clinical parameters during the
248
study, this could be due to the seasonal change or the
hydrating property of the excipients in the formulation.
Small sample size and short test duration may have
hampered the detection of statistical significance
between groups in these facial feature measurements,
but the kinetin plus niacinamide group still showed
better improvements than other two groups.
Eight subjects in each group had experienced mild and
transient discomforts during the trial. Aqueous formula-
tion with less moisturizing effect and weather variation
may be the causes. In this study, only one concentration
for each agent and one kind of formulation were tested.
We need further studies to find out the optimal and most
effective concentrations and formulations for the kinetin
plus niacinamide combination. This study lacked the topi-
cal kinetin along group. This is because there were more
clinically proven tests of topical niacinamide in recent
years, and we wanted to know whether the combination
of kinetin and niacinamide can have enhanced effects.
Due to limited sample size, we could just divide the test
subjects into two treatment groups.
In conclusion, we have demonstrated for the first time
that the combination of kinetin and niacinamide can
effectively improve many facial aging signs in Asians.
The study is not conducted restrictedly due to the restrain
of measuring instrument, personnel variation, and in-
adequate sample size. No significant differences between
niacinamide alone group and kinetin plus niacinamide
group are revealed in the final results, but the clinical
effects of kinetin plus niacinamide seem to be better. Our
data suggest that both compounds have the capacity to
exert multiactive, multifunctional and pluripotent effects
on the skin. And they are promising candidates for poten-
tial use in future cutaneous anti-aging formulation.
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