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61
R.R. Watson and S. Zibadi (eds.), Bioactive Dietary Factors and Plant Extracts in Dermatology,
Nutrition and Health, DOI 10.1007/978-1-62703-167-7_6, © Springer Science+Business Media New York 2013
R. Saini
Molecular Biology Laboratory , Center of Hematology and Hemotherapy-HEMOCENTRO,
University of Campinas (UNICAMP) , Rua Carlos Chagas, 480 , Campinas , Sao Paulo , Brazil CEP-13083-970
S. L. Badole, M.Pharm., Ph.D. (Pharmacology) (*)
Department of Pharmacology , PE Society’s Modern College of Pharmacy ,
Sector 21, Yamuna Nagar , Nigadi, Pune 411044 , Maharashtra , India
e-mail: sachinbadole@rediffmail.com; sachinbadole8880@gmail.com
A.A. Zanwar
Interactive Research School for Health Affairs, Bharati Vidyapeeth University, Medical college campus,
Off satara road, Dhankawadi, Pune 411043, Maharashtra, India
e-mail: anandzanwar@rediffmail.com; anandzanwar10@gmail.com
Key Points
Vitamin C, also called • l -ascorbic acid, is derived from glucose in many animals.
Vitamin C is a potent antioxidant. •
It is an essential component for collagen synthesis. •
Ascorbic acid is an effective depigmenting agent. •
It inhibits synthesis of melanin. •
It is used in repairing past damage to skin by age and sun. •
Keywords Vitamin C • Ascorbic acid • Antioxidant • Skin cancer • Depigmenting agent
Introduction
Vitamin C has received a great deal of attention being considered one of the safest and most effective
nutrients. Over a hundred studies from the previous 10 years revealed a growing list of bene fi ts of
vitamin C as published in Preventive and Alternative Medicine recently. The bene fi ts of vitamin C
include protection against immune system de fi ciencies, cardiovascular disease, prenatal health problems,
eye disease, cancer, and even skin wrinkling. Higher blood levels of vitamin C may be the ideal nutrition
marker for overall health, says study researcher Mark Moyad, MD, MPH, of the University of
Michigan. The more we study vitamin C, the better our understanding of how diverse it is in protect-
ing our health, from cardiovascular, cancer , stroke , eye health, and immunity to living longer.
Chapter 6
Vitamin C ( l -Ascorbic Acid): Antioxidant
Involved in Skin Care
Rashmi Saini , Sachin L. Badole, and Anand A. Zanwar
62 R. Saini et al.
l -Ascorbic Acid (Vitamin C)
Vitamin C, also called l -ascorbic acid, is derived from glucose and many animals can make it starting
from glucose. Primates like humans cannot synthesize it (we lack an enzyme in that pathway), making
ascorbic acid a vitamin because we cannot make it but need it, so we have to ingest it from a source.
It is water-soluble, which means it is easily absorbed through the water in your body. Our body does
not store vitamin C, so we must replace our supply every day and excess amounts are fl ushed out
through your kidneys. Vitamin C is needed for the growth and repair of tissues in all parts of our body.
It helps the body make collagen, an important protein used to make skin, cartilage, tendons, liga-
ments, and blood vessels. Vitamin C is essential for healing wounds, and for repairing and maintain-
ing bones and teeth. Due to its bene fi cial effects on skin, it has become a popular natural ingredient in
skin care cosmetics.
Structure
Vitamin C is purely the l -enantiomer of ascorbate; the opposite d -enantiomer has no physiological
signi fi cance. Both forms are mirror images of the same molecular structure. When l -ascorbate, which
is a strong reducing agent (Fig. 6.1 ), carries out its reducing function, it is converted to its oxidized
form, l -dehydroascorbate (Fig. 6.2 ). l -Dehydroascorbate can then be reduced back to the active
l -ascorbate form in the body by enzymes and glutathione . Its IUPAC name is 2-Oxo- l -threo-hexono-
1,4-lactone-2,3-enediol.
Dietary Sources
Some excellent sources of vitamin C are oranges, green peppers, watermelon, papaya, grapefruit,
cantaloupe, strawberries, kiwi, mango, broccoli, tomatoes, Brussels sprouts, cauli fl ower, cabbage,
and citrus juices or juices forti fi ed with vitamin C. Raw and cooked leafy greens (turnip greens, spin-
ach), red and green peppers, canned and fresh tomatoes, potatoes, winter squash, raspberries, blueber-
ries, cranberries, and pineapple are also rich sources of vitamin C. Vitamin C is sensitive to light, air,
and heat, so its advisable to get the most vitamin C by eating fruits and vegetables raw or lightly
cooked.
Fig. 6.1 Ascorbic acid
(reduced form)
Fig. 6.2 Dehydroascorbic
acid (oxidized form)
636 Vitamin C (l-Ascorbic Acid): Antioxidant Involved in Skin Care
Role in Skin Care
Potent Antioxidant
Vitamin C is a potent antioxidant. Antioxidants block some of the damage caused by free radicals,
which occur naturally when our bodies transform food into energy. The build-up of free radicals over
time may be largely responsible for the aging process and can contribute to the development of
health conditions such as cancer, heart disease, and arthritis. Free radicals caused by exposure to
sunlight and pollutants cause premature skin aging. Vitamin C being highly effective antioxidant
counters these highly damaging compounds and reduces skin damage, wrinkles by soaking up harmful
free radicals [ 1 ] .
Augments Collagen Production
Vitamin C is an essential component for collagen synthesis [ 2 ] . Collagen is a part of normal cartilage.
Cartilage is destroyed in osteoarthritis (OA), putting pressure on bones and joints. In addition, some
researchers think free radicals—molecules produced by the body that can damage cells and DNA,
may also be involved in the destruction of cartilage. Antioxidants such as vitamin C appear to limit
the damage caused by free radicals. Collagen in the skin is malformed and skin and gums would not
heal properly without adequate vitamin C. This is obvious in patients who are clinically de fi cient of
vitamin C, a condition called scurvy. Among other problems, scurvy patients have bleeding from their
gums and poorly healing wounds. Topical ascorbic acid accelerates the healing of wound as it aids in
stabilizing and generation of collagen. This vitamin stimulates collagen synthesis, production of stable
collagen, and triggers the production of enzymes that is necessary for the cross-linking of collagen
molecule which in turn gives better tissue strength. Moreover, it helps to thicken the skin and dimin-
ishes fi ne lines and wrinkles.
Effective Depigmenting Agent
Ascorbic acid is an effective depigmenting agent and is known to inhibit synthesis of melanin, probably
because melanin is made by our skin in response to stress, and ascorbic acid is in the fi rst line of
defense, preventing the damage before melanin synthesis can be initiated.
Skin Protection
Ascorbic acid and its derivatives promote wound healing, controls in fl ammation, and reduces
erythema. In short, ascorbic acid is a safe, active that will bring multiple bene fi ts to your skin, by
improving blood fl ow, preventing future damage but also repairing past damage to skin by age and
sun. The exposure to solar ultraviolet radiation increases in summer, often resulting in a higher inci-
dence of skin lesions. Ultraviolet radiation is also a genotoxic agent responsible for skin cancer,
through the formation of free radicals and DNA damage. Studies analyzing the effect of sustained
exposure to a vitamin C derivative, ascorbic acid 2-phosphate (AA2P), in human dermal fi broblasts
revealed that genes responsible for skin regeneration are activated in these cells [
3 ] .
64 R. Saini et al.
It has been also demonstrated that vitamin C improve wound healing by stimulating quiescent
fi broblasts to divide and by promoting their migration into the wounded area. Vitamin C could also
protect the skin by increasing the capacity of fi broblasts to repair potentially mutagenic DNA lesions.
Thus vitamin C contributes signi fi cantly to the maintenance of a healthy skin by promoting wound
healing and by protecting cellular DNA against damage caused by oxidation. Free radicals are associ-
ated with premature skin aging, and antioxidants, such as vitamin C, are known to counter these
highly damaging compounds. This new evidence suggest that, in addition to “mopping up” free radicals,
vitamin C can help remove the DNA damage they form, if they get past the cell’s defences. Topical
Vitamin C increases the immune function of skin cells and keeps a control over acne. Vitamin C
increases skin hydration by preventing moisture loss and makes aged dull and dry skin radiant, and
glowing. Improvement in skin texture and skin tone, reduction in fi ne lines and wrinkles is easily
noticeable after several days of its use. Vitamin C also protects and lessens the effects of sunburns.
Ultrastructural evidence of elastic-tissue repair con fi rmed the clinical improvement in the skin associ-
ated with vitamin C. It also has the potential to enhance the density of dermal papillae, perhaps
through the mechanism of angiogenesis. Topical vitamin C thus has therapeutical effects for partial
corrections of the regressive structural changes associated with the aging process.
Boosts Effectiveness of Vitamin E
Ascorbic acid boosts the effectiveness of Vitamin E, which is important in protecting our cell’s
membranes. The regeneration of vitamin E from tocopheryl radical by vitamin C via the donation of
a hydrogen atom has been well characterized by in vitro studies [ 4, 5 ] . Vitamin C works with other
antioxidants, including vitamin E to protect the eyes against developing macular degeneration
(AMD), the leading cause of legal blindness in people over 55 in the USA. The people who seem to
bene fi t are those with advanced AMD. It is not known whether this combination of nutrients helps
prevent AMD or is bene fi cial for people with less advanced AMD. Some studies suggest that taking
vitamin C along with vitamin E may help prevent pre-eclampsia in women who are at high risk. Pre-
eclampsia, characterized by high blood pressure and too much protein in the urine, is a common
cause of pre-term births [ 6 ] .
Treatment of Cancer
The most common form of skin cancer, basal cell carcinoma, often responds to a remarkably simple,
safe, at-home treatment with vitamin C. Physicians and patients report that vitamin C, applied directly
to basal cell skin cancers, causes them to scab over and drop off. Basal cell carcinomas are slow grow-
ing and it is rare for them to metastasize. This provides an opportunity for a therapeutic trial of
vitamin C [ 7 ] , other forms of skin cancer, such as melanoma, are faster growing and more dangerous.
Successful use involves a highly concentrated vitamin C solution, directly applied to the blemish two
or three times a day. Vitamin C is selectively toxic to cancer cells, but does not harm healthy skin cells.
This is also the basis for high-dose intravenous vitamin therapy for cancer [ 8 ] . Ascorbate protects
against cancer by increasing collagen synthesis. It has been hypothesized that ascorbate has anti-
cancer action by inhibiting hyaluronidase and thereby preventing cancer spread. Ascorbate is toxic to
a variety of cancer cell lines [ 9– 11 ] . Extracellular concentrations as low 100–200 mM are toxic to
some cell lines, but many types of malignant cells are killed only at concentrations approaching the
mM range. Although ascorbate toxicity to cancer cells appears to be a result of high extracellular,
rather than high intracellular concentrations, the mechanism of toxicity is unknown. Possibilities
656 Vitamin C (l-Ascorbic Acid): Antioxidant Involved in Skin Care
include stimulatory effects on apoptotic pathways, accelerated pro-oxidant damage that cannot be
repaired by tumor cells and increased oxidation of ascorbate at high concentrations in plasma to the
unstable metabolite dehydroascorbic acid, which in turn can be toxic [ 12 ] .
Vitamin C De fi ciency
Many people may be mildly de fi cient in vitamin C, although serious de fi ciencies are rare in industrialized
countries. Smoking cigarettes lowers the amount of vitamin C in the body, so smokers are at a higher
risk of de fi ciency. Signs of vitamin de fi ciency include dry and splitting hair; gingivitis (in fl ammation
of the gums) and bleeding gums; rough, dry, scaly skin; decreased wound-healing rate, easy bruising;
nosebleeds; and a decreased ability to ward off infection. A severe form of vitamin C de fi ciency is
known as scurvy. Low levels of vitamin C have been associated with a number of conditions, includ-
ing high blood pressure, gallbladder disease, stroke, some cancers, and atherosclerosis (the build-up
plaque in blood vessels that can lead to heart attack and stroke). Getting enough vitamin C from your
diet (by eating lots of fruit and vegetables) may help reduce the risk of developing some of these
conditions.
Vitamin C Supplements: Good, Bad, or Ugly
Vitamin C needs to be in acidic environment and in a high concentration in order to penetrate the skin.
In addition, topical vitamin C is highly degradable. When exposed to air it oxidizes and its free radical
soaking capabilities are muted, i.e., it becomes inert. To improve the practicability of vitamin C in
skin care, scientists have been looking for its relatives with comparable or superior skin bene fi ts.
An ideal vitamin C derivative should be able to easily penetrate into skin cells and release l -ascorbic
acid in amounts suf fi cient to boost collagen synthesis. Also, it should be more stable and less irritating
than vitamin C. So far, two compounds have found their way into the broad skin care market: ascorbyl
palmitate and magnesium ascorbyl phosphate. A few other highly promising derivatives are on the
horizon. We need only 90 mg of vitamin C daily which can be found in a couple of orange slices.
Eating a whole orange or other citrus fruit will easily give many times the amount of vitamin C we
need. There is no evidence that taking vitamin C supplements or consuming huge amounts of vitamin C
will have any impact on your skin. Once you have an adequate supply of vitamin C to make collagen,
having a huge oversupply is not likely to lead to more collagen production. But it certainly will lead
to lots more vitamin C in your urine, it is simply eliminated by kidneys. American Dietetic Association
spokeswoman Dee Sandquist, RD, suggests do your best to work more fruits and vegetables into your
diet before taking vitamin C supplements .
Vitamin C: Side Effects
Vitamin C should not be used by people with very sensitive skin. Topical vitamin C produces stinging
sensation on areas where it is applied. Products with very low concentration of vitamin C do not pro-
duce the familiar sting. Magnesium ascorbyl phosphate and ascorbyl palmitate do not produce the
characteristic sting. The practical use of vitamin C in skin care presents some dif fi culties due to its
lack of stability. When exposed to air, vitamin C solution undergoes oxidation and becomes not only
ineffective but also potentially harmful (oxidized vitamin C may increase the formation of free radicals).
66 R. Saini et al.
Ascorbic acid interacts with several medications like aspirin and nonsteroidal anti-in fl ammatory
drugs (NSAIDs), acetaminophen (tylenol), aluminum-containing antacids, barbiturates, nitrate medi-
cations for heart disease, Oral contraceptives, protease inhibitors, tetracycline, warfarin (coumadin),
and thus should be taken only after consulting a doctor.
Conclusion
Vitamin C is widely used by the people, probably with little harm. Vitamin C protects the skin by
promoting fi broblast proliferation, migration and replication-associated base excision repair of poten-
tially mutagenic DNA lesions. Genome-wide effects of vitamin C on gene expression in primary
dermal fi broblasts helps to gain new insights in the participation of vitamin C in important processes in
human skin, such as wound healing or the repair of oxidative DNA lesions in skin cells. In summary,
while the activation of speci fi c signalling pathways remains to be elucidated, recent researches reveal
that vitamin C repletion in skin cells is required for ef fi cient wound healing and replication-associated
repair of potentially mutagenic products of DNA oxidation. Vitamin C is thus being effectively used
for skin care and is recognized as a major component in cosmetics used for skin treatment.
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