Aging skin and food supplements: the myth and the truth

Claudia Rona, MD

a

, Enzo Berardesca, MD

b,

⁎

a

Department of Dermatology, University of Pavia, 27100 Pavia, Italy

b

San Gallicano Dermatological Institute, 0144 Rome, Italy

Abstract The frenzied rhythm of our times leads our patients not only to resource to diet integrators

—

remorselessly overcoming difficulties or prejudices

—to fulfill increasingly frequent nutritional needs

due to decreasingly

“correct” eating habits, but also to fight against a myriad of skin conditions. The

rationale of a combined approach for the antiaging treatment of skin is based on the synergic effect
between functional substances applied locally, where the problem arises, and other agents working from
the inside to correct a need, to restore altered functions or conditions and to guarantee the correct intake
of nutrients or active substances. This work discusses the active ingredients mostly used in the oral
treatment of skin aging, together with the scientific evidences that do or do not support their use.
© 2008 Elsevier Inc. All rights reserved.

Introduction

Beginning from 1990, food loses its exclusive nutritional

role, undertaking a more comprehensive one: nutrients begin
to represent a prevention tool to preserve health from chronic
and degenerative diseases, increasing wellness. Modern
nutrition science is trying to deepen the link between food
and health to highlight the biologic role that nutrients can
perform on the body in general and on the skin in particular.

Cosmetic industry in turn found the opportunity to

support traditional topical treatments with oral ones to
strengthen the effects on the skin. Skin is actually the most
visible organ and, at the same time, the first one exposed to
external injury: people desire to preserve it for aesthetic and
salutary concerns. Thus, the topic of nutritional supplemen-
tation invests all body components, skin being the first.
Today, nutritional supplements with cosmetic aims are
sought after and especially wished by those whose diet is
not quite balanced. Different names are used to identify this

supplementation, such as endocosmesis or nutricosmeceu-
tics. These terms are often controversial, although denoting a
new way to approach skin conditions.

Usually, food supplements consist of a nutritional

component (vitamins, minerals, fibers) and a more
generically salutary one (botanical or animal extracts).
By a regulatory point of view, in Italy, there are no
dedicated laws: food supplements are regulated as food
intended for special conditions. Companies interested in
the marketing of a food supplement need simply to notify
to the Health Board the label of the product they are going
to sell, saving time and money with respect to drugs'
market regulations.

In the last 10 years, chemists, nutritionists, and

physicians have been working together to develop new
nutritional applications to satisfy people's needs and
demands. People now are looking for products contributing
both to skin health and disease prevention. At first, the
supplements developed for such goals were those intended
to stimulate exceeding fluid drainage to alleviate cellulite;
since then, many different categories of supplements have
been developed, coping with different skin needs, both
dermocosmetic and dermatologic ones.

⁎ Corresponding author.

E-mail address:

[e-mail]

(E. Berardesca).

0738-081X/$

– see front matter © 2008 Elsevier Inc. All rights reserved.

doi:

10.1016/j.clindermatol.2007.09.002

Clinics in Dermatology (2008)

26, 641–647

This trend strongly influences the market: even pharma-

ceutical companies are moving to supplements to take
advantage from their popularity and because the develop-
ment and selling of supplements are less time- and money-
consuming procedures.

Today, the cosmetic companies introduce routine topical

treatments coupled with oral route products. This association
is based on a strong rationale, namely, the synergy between
the substances applied on the skin

—where the problem

arises

—and the substances acting from inside that replenish

gaps or support natural defense systems. The skin needs
plenty of nutrients and metabolites that a topical product
cannot supply by its own. We know that it is, moreover,
not enough to apply a substance to the skin to be sure it will
be absorbed and it will reach the target. This does not mean
that cosmetics are useless, but just that they can be
strengthened as to their effect. It is, however, even true that
substances taken by oral route can be destroyed or can have a
poor bioavailability.

So, food supplements with cosmetic aims should be

considered as a nonconventional alternative or as a
complementary way to approach skin problems, maintaining
the skin and its appendages in a good physiologic condition
and acting as a support to traditional cosmetics.

Background

In general, we have to consider that the skin is exposed to

daily environmental injuries and, at same time, is connected
with all parts the body. It is, therefore, reasonable to think
that the combination of topical and oral treatments could be
useful to protect/repair skin conditions. We should consider
that the skin can have some deficiencies of particular
oligoelements and vitamins, and that the supplementation is
a very effective approach to recover health (scurvy, pellagra,
zinc, and vitamin B

12

deficiencies, etc). Thus, we know that

some nutritional deficiencies can lead to skin diseases, but
we have no evidence that it is possible to treat some of these
(such as skin aging) only by oral route. A very close link
exists between skin and nutritional homeostasis: this could
be the rationale to develop and apply an oral route treatment
to support the skin itself. Analyzing some articles, we can
find a very interesting synergism between topical and oral
strategies in the treatment of skin conditions that acts through
metalloproteinase inhibition, reactive oxygen species chela-
tion, and an antiinflammatory effect. In this way, we can
obtain a decrease of the existing signs as well as the
prevention of skin aging processes. The cosmetic treatments
of the last generation, developed against wrinkles, rely on the
antioxidant properties of some ingredients, especially those
derived from plants. Among them, we remember Vitis
vinifera, olive tree, tomato, orange, green and white tea, saw
palmetto extracts, which exert antioxidant effects on the skin
after topical application, and systemic supply by food

supplements. In particular, a study conducted on 453
volunteers revealed that skin wrinkling (measured by a
cutaneous microtopographic method in a sun-exposed site in
older people of various ethnic backgrounds) may be
influenced by the types of food taken.

1

Namely, a high intake of vegetables, legumes, and olive

oil appeared to be protective against cutaneous actinic
damage thanks to their high content in antioxidant actives.
So, the rationale in using the oral route to treat skin
conditions is quite strong.

Now, the question is whether oral supplements do really

exert the effect they are designed and intended for. Hundreds
of supplements to specific skin conditions have been
developed. In general, oral supplements contain ingredients
(especially antioxidants) for the protection of the skin against
environmental injuries and for the repairing of senescence
feature, although only few of them have been assessed as
their real efficacy, besides a simple placebo effect. Reactive
oxygen species can cause harmful effects in keratinocytes
and fibroblasts when the antioxidative defense mechanisms
are exhausted. It would be, therefore, reasonable to prove if
oral supplementation with various nutrient antioxidants
could be useful in the prevention or treatment of skin
disorders, especially those mediated by UV irradiation.

β-

Carotene, ascorbic acid, and tocopherol have been tested
alone or in combination in the prevention of sunburns,
photodermatoses, and photocarcinogenesis, with divergent
results. Other candidates for oral antioxidative supplementa-
tion in humans are selenium and polyphenols. Clinical data
are, however, limited or lacking at present.

2

Experimental evidence

In the field of skin aging, a problem that concerns both

man and woman, we can find plenty of trials about the
opportunity of using the oral route alone or in association with
the topical one, both showing very good results. Likewise,
lacking data or divergent results arise when we review articles
testing ingredients alone or in combination, for example,
combinations of traditional antioxidant molecules.

In particular, a study investigated the extent of the

protective effects of oral

α- and β-carotene supplementation

for 24 weeks on UV-A

– and UV-B–induced erythema in

humans.

3

Twenty-two subjects, both sexes, were exposed to

UV-A and UV-B radiation while receiving a supplementation
of natural carotenoids for 24 weeks. Small skin areas (1 cm

2

)

were exposed to increasing doses of UV light (16-42 mJ/cm

2

)

to determine the minimal erythema dose. The minimal ery-
thema dose of solar simulator radiation, as well as

β-carotene

and

α-carotene serum levels, increased significantly. Serum

lipid peroxidation was significantly inhibited in a dose-
dependent manner. The data collected suggest that the
supplementation with natural carotenoids may partially
protect human skin from UV-A

– and UV-B–induced

642

C. Rona, E. Berardesca

erythema, although the extent of the protective effect is
modest. Other results do not show an antioxidant efficacy in
the photoprotection of oral vitamin E and

β-carotene in

human skin.

4

The authors examined the ability of 2

liposoluble antioxidants, vitamin E and

β-carotene, to reduce

the markers of oxidative stress and erythema after UV
radiation (UVR) skin exposure in 16 healthy subjects who
received either

α-tocopherol (n = 8, 400 IU/d) or β-carotene

(n = 8, 15 mg/d) for 8 weeks. Biopsy samples before and after
supplementation were taken from unexposed skin and from
skin 6 hours after 120 mJ/cm

2

UVR exposure. Vitamin E or

β-carotene supplementation had no effect on skin sensitivity
to UVR. Although vitamin E supplements significantly
decreased skin malondialdehyde concentration, none of the
supplements affected other parameters of UVR-induced
oxidative stress in human skin, suggesting that the supple-
mentation did not induce photoprotection.

The same authors studied also the effects of vitamin C

supplementation on UVR-induced damages in human skin.

5

They hypothesized that an acute exposure of human skin to
UVR in vivo would lead to oxidation of cell biomolecules,
which could be prevented by prior vitamin C treatment. So,
they examined in detail a time course of the changes of
oxidative stress markers in the skin after exposure to
physiologic amounts of UVR in vivo. Oral vitamin C
supplements (500 mg/d) were taken by 12 volunteers for 8
weeks, resulting in a significant increase of vitamin C level in
plasma and skin. The supplementation had no effect on the
UVR-induced erythemal response. The malonaldehyde skin
content was reduced by vitamin C supplementation, but
surprisingly, reductions in the skin content of total
glutathione and protein thiols were also observed. They
speculated that this apparently paradoxical effect could be
due to the regulation of the total reductant capacity by skin
cells, such that vitamin C may have replaced other reductants
in these cells. No evidence was obtained for an effect of
supplementary vitamin C on the mild oxidative stress seen in
human skin after UVR exposure.

There is increasing evidence that reactive oxygen species

play a pivotal role in the process of aging. The skin, as the
outermost barrier of the body, is exposed to various
exogenous sources of oxidative stress, in particular, UV
irradiation. These are believed to be responsible for the
extrinsic type of skin aging, termed photoaging. It seems
reasonable, therefore, to try to increase the levels of
protective low molecular weight antioxidants through a
diet rich in fruits and vegetables or by direct topical
application. Indeed, various in vitro and animal studies
proved that low molecular weight antioxidants, especially
vitamins C and E, ascorbate and tocopherol, as well as lipoic
acid, exert protective effects against oxidative stress.
Controlled long-term studies on the efficacy of low
molecular weight antioxidants in the prevention or treatment
of skin aging in humans are, however, still lacking.

6

Presumably, the question about the efficacy of oral

supplementation directed to skin conditions lies in the

features of the formulation: the choice, the concentration,
and the quality of the active ingredients, as well as the
kinetics

—which depend on the drug delivery system—and

so on.

7

Most natural antioxidants such as

α-tocopherol,

ascorbic acid, and others are biologically unstable, poorly
soluble in water, and poorly distributed to target sites.
Because of these shortcomings, further prophylactic applica-
tions of dietary supplements have stagnated. This is partially
due to a lack of basic knowledge of the delivery mechanisms
of these dietary supplements and nutrients. Some authors in
this regard strongly advocate a serious consideration of the
bioavailability of dietary supplements,

2

and some others, not

finding a significant difference in the clinical and histologic
appearance of photoaging skin after placebo and treatment
with green tea extracts in a double-blinded placebo-
controlled trial, proposed an interesting hypothesis.

8

It has

been postulated that green tea polyphenols protect human
skin from the cutaneous signs of photoaging, although no
significant changes could be clinically detected, suggesting
that maybe a longer supplementation could be required for
clinically observable improvements.

There are some reports of publications supporting the use

of supplements specifically formulated with ingredients
selected to help skin trophic, defense, or repair systems.
These authors,

9-11

strongly supported by their experimental

experience, suggested the opportunity to trust natural
carotenoids antioxidant effects: for a successful intervention,
a treatment with carotenoids is needed for a period of at least
10 weeks.

Protoprotection

The photoprotection exerted by a pool of antioxidants was

investigated in a study of the effects of oral supplementation
with carotenoids and a combination of carotenoids and
vitamin E against the development of erythema in humans
over 12 weeks.

12

Erythema was induced by a "blue-light

solar simulator.

β-Carotene and α-tocopherol serum concen-

trations and carotenoid skin levels were assessed by high-
performance liquid chromatography and reflection photo-
metry.

β-Carotene and α-tocopherol serum concentrations

increased after the supplementation. Erythema on dorsal skin
(back) was significantly diminished (P

b .01) after 8 weeks,

and erythema suppression was greater with the combination
of carotenoids and vitamin E than with carotenoids alone.
The antioxidants used in this study provided a protection
against erythema in humans, and they can be useful to
decrease sensitivity to UV light. Regarding the synergic
effect of a pool and the possible enhancing effect of the
excipient of a commercial product, another author reported a
randomized, double-blind, placebo-controlled study on the
clinical efficacy of an oral treatment of skin aging
symptoms.

13

Forty women with skin aging symptoms were

randomized to receive a formulation containing marine
proteins,

α-lipoic acid, pine bark extract, vitamins and

643

Aging skin and food supplements

minerals (n = 20), or placebo (n = 20), twice daily for
6 months. Objective measurements of skin thickness and
elasticity, together with subjective clinical assessments of
various parameters (fine wrinkles, coarse wrinkles, tactile
roughness, and teleangiectasia), were performed. Self-
evaluations were also made by the study participants.
There was a significant improvement in skin quality in
both objective and subjective parameters after treatment with
the product compared with placebo. Participants' self-
evaluations also showed a statistically significant difference
in favor of the active treatment.

Procyanidins from French maritime pine bark (Pycno-

genol) are among the most powerful natural antioxidants that
recycle and prolong vitamin C and E effects.

14,15

These

bioflavonoids neutralize collagenases and elastases,

16

improving skin aging features. Used since 1853, Pycnogenol
as a health supplement is a proven free radical scavenger,

17

50 times more potent than vitamin E and 20 times more
potent than vitamin C, according to European researchers. It
also efficiently protects from oxidative stress injury (lipid
peroxidation and cytotoxicity) induced by UVR. The
protective effects are dose related, with the highest
concentration providing the greatest benefits.

18

The ingre-

dient is effective even in protecting the skin from erythema
induced by UV-B rays.

19,20

Another study supporting the effects attributable to the

synergism of a pool was performed on a combination of
vitamins C and E, carotenoids, selenium, zinc, amino acids
and glycosaminoglycans, blueberry extract, and Pycno-
genol.

21

The pool induced an improvement in skin

smoothness and elasticity in a double-blind placebo-
controlled study involving 62 women. Another study
showed further evidence about the effect of an oral
supplement containing glucosamine, amino acids, minerals,
and antioxidants on cutaneous aging in a 5-week treatment of
53 female volunteers.

22

The hydration properties of the skin

as well as the textural analysis of women's fine lines and
wrinkles were assessed and compared with those of a control
group of 12 individuals who did not receive the supplement.
There was a statistically significant reduction (34%) in the
number of visible wrinkles, as measured by the Silflo
replicas (P

b .01), and a reduction (34%) in the number of

fine lines (P

b .06) in the group of women who took the

supplement. No significant changes in epidermal hydration
were observed in either the control or study groups.

As regards the sun protective effect of supplements, the

literature reports a lot of evidence about the efficacy of
antioxidant ingredients, though mixed. About this, there are
very interesting results regarding some new stronger and
longer-lasting sun protectors, thanks to the presence of
carotenoids and vitamins.

23,24

Even strong smokers and

people undergoing severe sun exposure could benefit from
taking oral carotenoids: after 60 days, the plasmatic levels of
free radicals were proportionally lower with respect to type,
dose, and combination of carotenoids, being their association
with vitamins E and C the best treatment than single

ingredients alone. The study protocol used for carrying out
the evaluations let the authors determine the radical
protective factor, which is a very useful parameter to
calibrate supplements assumption, adapting their use to the
real individual needs. Further evidence from the same
authors concerned the protective effects of oral antioxidants
on skin and eye function.

25

They conclude that carotenoids

used as nutritional supplements can play an interesting
photoprotective role for both skin and eyes, increasing the
activity of topical sunscreens.

The role of the traditional molecules lutein and astax-

anthine

—which have been used for years in eye care—is

today under investigation for the potential application to skin
care, thanks to the antioxidant properties these molecules are
endorsed with.

Some interesting results about the photoprotective effects

of lutein on the skin, besides its effects on the eyes, are
disclosed by Krieger

26

and Alves-Rodrigues.

27

In turn,

lycopene has recently been the object of a patent. After its
linkage to lactoglobulin (lactolycopene), the lycopene was
made hydrosoluble, thus, becoming easier to handle in
cosmetic/oral formulations. Then, its combination with soy
isoflavones and vitamin C has been studied in a 6-month
treatment of 90 menopausal women taking 3 tablets a day (6
mg lycopene, 50 mg isoflavones, 60 mg vitamin C),
revealing a significant improvement in some biophysical
properties of the skin, such as density, viscoelasticity,
microrelief as average depth of fine lines, hydration, and
radiance, as indicated by instrumental evaluation.

28

Vitamin E

We should spend a few words for vitamin E also,

traditionally used for topical applications, but more recently,
as a precious ingredient of

“cosmetofoods.” In particular, the

term vitamin E is a generic word indicating a family of
substances endorsed with antioxidant activity, involving 2
classes of agents: tocopherols and tocotrienols. Generally, if
we speak about vitamin E, we refer to the tocopherol group

Fig. 1

Skin thickness (mean ± SD). Significant increase in

dermal thickness (P

b .0001) in the active-treated group. bas

indicates baseline; fin, final.

644

C. Rona, E. Berardesca

and, in particular, to

α-tocopherol, but tocotrienols are

gaining increasing popularity in dermocosmetic applications,
thus, being considered the third millennium vitamin E form.
They are stronger antioxidant than tocopherols and show a
better cutaneous bioavailability. They accumulate, moreover,
in the stratum corneum, and they exert a very important
action against free radicals elicited by actinic damage and
injury caused by environmental pollutants; the

δ-tocotrienol

form is particularly effective. They were born as nutraceu-
ticals, but they are suitable to be formulated both as topical
products and cosmetofoods, or as food supplements that
claim specific and positive effects on the skin, intended for
skin aging prevention or treatment.

29-34

Starting from the studies conducted on Imedeen,

35

to

prevent/treat skin aging, we have today more scientific
evidence of the protective and regenerative role on the skin
exerted by fish polysaccharides in association with antiox-
idants and capillary protectors.

36

Topical agents

Topically applied cosmetic products can ameliorate aging

skin condition. Our study shows that an oral supplementation
with fish cartilage can be helpful in improving the treatment
of aging skin. We enrolled 30 healthy women with signs of
skin aging. Fifteen women were treated for 2 months with a

food supplement based on polysaccharides derived from
cartilage and a natural mix of antioxidants, whereas the
other 15 with a placebo. We performed a clinical
evaluation and measured some biophysical parameters
related to skin function and wrinkle severity, such as
silicone replica, skin thickness, mechanical properties, skin
color, and capacitance. The results showed statistically
significant changes in the active-treated group in compar-
ison to the placebo. In particular, dermal thickness
(treatment, 1.13-1.23 mm; P

b .001), skin wrinkling

(treatment, 9.5-3.5 Ra; P

b .002), viscoelasticity (treatment,

0.70-0.97%; P

b .02), and skin color (treatment, brighter

and less pigmented; P

b .02) showed a considerable

improvement. Most of these parameters were related to
changes occurring within the dermal matrix, which
improved after the treatment, whereas we know that most
of the topically applied cosmetic products have a short-
term effect only on superficial structures. So, the oral
supplementation can be integrated with topical products to
obtain an even more effective result.

Fig. 2

Mechanical properties. Skin viscoelasticity

—R6 (mean ±

SD). Statistically significant increase in dermal viscoelasticity after
treatment in the active-treated group (P

b .02).

Fig. 3

Elasticity

—R2 (mean ± SD). Improvement in skin

elasticity, although not statistically significant, after an 8-week
treatment of the active group (P = .07).

Fig. 4

Skin replica. Ra-3D-roughness and waviness (mean ±

SD). Relative changes in roughness (Rae) due to microrelief and
waviness-related deeper wrinkles (data expressed in % of
improvement). In the group supplemented with fish cartilage, we
recorded improvements of 9.5% and 13.5% in microrelief (P

b .02)

and waviness (P

b .002).

Fig. 5

Skin color (mean ± SD) luminosity or brightness.

Significant improvement in skin brightness (P

b .006) in the active

group due to increased skin reflectance.

645

Aging skin and food supplements

On the basis of our results, we can suggest the

prescription of this product for skin protection against
aging and for the recovering of its properties after an injury,
in dermocosmetic treatments, to prepare skin to plastic
surgery, as well as sun protector.

We report, hereafter, some graphics to show the data trend

(

Figs. 1-5

).

These results confirm that fish polysaccharides taken

orally can be helpful in ameliorating some aspects of skin
aging because of their peculiar properties. It could be
interesting to investigate a combination treatment with
topical retinoids/alpha hydroxyacids.

Another important skin feature is hydration, normally

affected because of aging.

A recent study carried out an interesting application for

ceramides formulated with lycopene, vitamin E, borago oil
rich in polyunsaturated fatty acids, and the amino acidic
precursors of collagen synthesis, such as lysine and
proline. The study showed the effects of oral supplementa-
tion in improving and preventing skin dehydration. A total
of 32 healthy female volunteers entered the study, 16 of
which were treated for 40 days with a food supplement
(vegetable ceramides, amino acids, fish cartilage, antiox-
idants, and essential fatty acids) and 16 of them with
placebo. At the beginning and at the end of the treatment
skin hydration, smoothness and desquamation were
assessed both instrumentally (Corneometer, Visioscan)
and by self-assessment. The results of the clinical and
instrumental evaluations carried out in this study have
highlighted how the active treatment is effective in
improving skin hydration and in reducing the cutaneous
roughness and the depth of furrows, in comparison to the
placebo. In fact, concerning several important parameters
as the stratum corneum hydration and skin roughness, the
improvements measured exceeded 25%.

Conclusions

On the basis of the data here reported, there are strong

evidence and rationale in using food supplements to support
traditional dermocosmetic treatments when approaching skin
conditions. Perhaps the divergent data about efficacy on skin
conditions are linked to the differences in the starting
experimental conditions: dosage, duration, combination of
ingredients, kind of excipients, skin conditions, and so on. To
face up to skin problems, we suggest that a complete
approach to skin dermocosmetic conditions could be
represented by the correct association of a topical treatment
with an oral one on the basis of their synergy, thus, fighting
both symptoms and their causes.

In the future, we can hypothesize even other opportu-

nities, such as the possibility to implement the scientific
research on functional ingredients, both new and newly
associated, and to screen some new potentially useful
natural ingredients.

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