NUTRITION FOR IMMUNITY

AND
SKIN HEALTH

Suwaldi Martodihardjo
PSPA FK UNISSULA

Dipresentasikan dalam Webinar PSPA FK UNISSULA pada 13 Juni 2021

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Immunity

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Immunity
⮚The immune
system protects
the body against
infection and
disease.
⮚It is a complex
system of organs,
tissues, and cells
located throughout
the body.

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Functional Divisions and Components of the Immune Response

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KEY FEATURES OF THE IMMUNE RESPONSE

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KEY FEATURES OF THE IMMUNE RESPONSE

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KEY FEATURES OF THE IMMUNE RESPONSE

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❖ Calder, P.C., Nutrition, Immunity and Covid-19, BMJ Nutrition, Prevention & Health, 2020; O.doi:10.1136/bmjnph – 2020-000085.
• Gombart, A.F.,et al., 2020, A Review of Micronutrients and the Immune System–Working in Harmony to Reduce the Risk of Infection, Nutrients, 12, 236; doi:10.3390/nu12010236

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• Calder, P.C., et al., 2020, Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect against Viral 12
Infections, Nutrients, 12, 1181; doi:10.3390/nu12041181
Certain micronutrients have key roles in the immune system

• Gombart, A.F.,et al., 2020, A Review of Micronutrients and the Immune System–Working in Harmony to Reduce the Risk of Infection, Nutrients, 12, 236; doi:10.3390/nu12010236 13
 Certain micronutrients have key roles in the immune system

• Gombart, A.F.,et al., 2020, A Review of Micronutrients and the Immune System–Working in Harmony to Reduce the Risk of Infection, Nutrients, 12, 236; doi:10.3390/nu12010236 14
 Certain micronutrients have key roles in the immune system

• Gombart, A.F.,et al., 2020, A Review of Micronutrients and the Immune System–Working in Harmony to Reduce the Risk of Infection, Nutrients, 12, 236; doi:10.3390/nu12010236 15
 Certain micronutrients have key roles in the immune system

• Gombart, A.F.,et al., 2020, A Review of Micronutrients and the Immune System–Working in Harmony to Reduce the Risk of Infection, Nutrients, 12, 236; doi:10.3390/nu12010236 16
 Certain micronutrients have key roles in the immune system

• Gombart, A.F.,et al., 2020, A Review of Micronutrients and the Immune System–Working in Harmony to Reduce the Risk of Infection, Nutrients, 12, 236; doi:10.3390/nu12010236 17
Impact of micronutrient deficiencies and supplementation on immune
functions.

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Impact of micronutrient deficiencies and supplementation on immune
functions.

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Impact of micronutrient deficiencies and supplementation on immune
functions.

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Impact of micronutrient deficiencies and supplementation on immune
functions.

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Impact of micronutrient deficiencies and supplementation on immune
functions.

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Impact of micronutrient deficiencies and supplementation on immune
functions.

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Impact of micronutrient deficiencies and supplementation on immune
functions.

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NUTRITION FOR IMMUNITY

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 Long-chain Omega-3 Fatty Acids

• General
❖Essential fatty acids are polyunsaturated fatty acids (PUFAs) that
cannot be synthesized in the body and must come from the diet.
⮚PUFAs have several double bonds in their structure that give them
complex shapes and influence their function.
❖Essential fatty acids are structural components of every cell in the
body and are converted to compounds that influence inflammation
and immunity.
❖There are two classes of essential fatty acids: omega-6 PUFAs and
omega-3 PUFAs.

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Long-chain Omega-3 Fatty Acids

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Long-chain Omega-3 Fatty Acids

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Long-chain Omega-3 Fatty Acids

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 Protein-energy Malnutrition (PEM)

General
∙ PEM is the result of extreme deficiency of calories and/or protein in the diet.
∙ Clinical conditions of severe PEM are termed marasmus (deficiency of both
dietary protein and calories) and kwashiorkor (deficiency of dietary protein).
∙ PEM is most common in developing nations, the elderly, hospitalized individuals,
and those with chronic disease that interferes with nutrient absorption and
utilization.
Immune-specific
∙ Without protein and calories, all of the body’s essential functions suffer, including
immune function. In PEM, there are insufficient building blocks and energy to
make immune cells and immune factors that protect the body from infection and
disease.
∙ There is considerable data to suggest that PEM suppresses the functioning of the
acquired immune system.
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 Protein-energy Malnutrition (PEM)

∙ According to the World Health Organization, more than one-third of the world’s
underprivileged, preschool-age children (80 percent living in Asia, 15 percent in
Africa, and 5 percent in Latin America) are affected by PEM; this malnutrition
stunts physical growth and mental development, with lasting effects into
adulthood. PEM also drastically increases the risk of disease and death.

∙ PEM increases the susceptibility to infection by adversely affecting nearly all

aspects of acquired immunity.

∙ PEM is usually accompanied by deficiencies in essential micronutrients required

for proper immune function, especially vitamin A, vitamin B6, folate, vitamin E,
zinc, iron, copper, and selenium

∙ Nutritional intervention can improve nutrient status, reduce the occurrence of

disease, and increase survival in children and chronically ill patients with PEM.

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 Vitamin A

General
∙ Vitamin A (retinol) is a fat-soluble vitamin that is essential for normal vision, reproduction,
cell growth and development, and immune function.
Immune-specific
∙ Vitamin A helps maintain the integrity of the skin, eye, respiratory, gastrointestinal, and
genitourinary tracts, thereby reinforcing our barriers against disease-causing organisms.
∙ Vitamin A is required for the proper function of immune cells that generate antibodies. Good
vitamin A status is essential for vaccines to work properly.

∙ For children in developing nations, vitamin A deficiency causes severe visual impairment,
blindness, and increases vulnerability and death from common childhood infections like
measles and diarrheal disease.
∙ In low- and middle-income countries, preventative vitamin A supplementation in children
older than 6 months of age reduces the occurrence of diarrhea and measles and
significantly improves child survival.
∙ Because of potential adverse effects, vitamin A supplements should be reserved for
undernourished populations and those with evidence of vitamin A deficiency. 33
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 Vitamin B6

General
∙ Vitamin B helps convert food into usable energy and assists in the
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formation of neurotransmitters, red blood cells, proteins, and DNA.

∙ Additionally, the B-vitamins folate, vitamin B , and vitamin B work
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together to convert homocysteine to methionine, an amino acid

used in countless essential cellular activities.
Immune-specific
∙ Because immune cells have high metabolic activity and high rates
of proliferation, they require vitamin B to form new immune cells
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and mount a proper immune response.

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 Vitamin B6

∙ Animal studies and a few, small randomized controlled

trials indicate that vitamin B deficiency impairs immune
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function.
∙ Specifically, several aspects of acquired immunity are
reduced, such as lymphocyte production, antibody
formation, and cytokine production.
∙ Correcting the vitamin B deficiency appears to restore the
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affected immune functions.

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Vitamin B6

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 Folate (Vitamin B9)

General
∙ Folate is a B-vitamin required for DNA synthesis and the formation of new cells.
∙ Additionally, the B-vitamins folate, vitamin B12, and vitamin B6 work together to convert
homocysteine to methionine, an amino acid used in countless essential cellular activities.

Immune-specific
∙ Because immune cells have high metabolic activity and high rates of proliferation, they
require folate to form new immune cells and mount a proper immune response.

∙ Animal studies and a few observational studies indicate that folate deficiency is
associated with an increased susceptibility to infection.
∙ In patients with severe folate deficiency, known as megaloblastic anemia,
decreased numbers and activity of T lymphocytes have been observed.
∙ Correcting the folate deficiency appears to restore the affected immune functions.

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Folate (Vitamin B9)

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 Vitamin B12

General
∙ Vitamin B12 helps convert food into usable energy, is required for proper nerve
function, and assists in the formation of red blood cells, proteins, and DNA.
∙ Additionally, the B-vitamins folate, vitamin B12, and vitamin B6 work together to
convert homocysteine to methionine, an amino acid used in countless essential
cellular activities.
Immune-specific
∙ Because immune cells have high metabolic activity and high rates of proliferation,
they require vitamin B12 to form new immune cells and mount a proper immune
response.
▪ Severe vitamin B12 deficiency, known as pernicious anemia, suppresses natural killer cell
activity and decreases numbers of circulating T lymphocytes.

▪ Correcting the vitamin B12 deficiency appears to restore the affected immune functions.

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Vitamin B12

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 Vitamin C

General
∙ Vitamin C (ascorbic acid) is a water-soluble vitamin that neutralizes a variety of reactive
oxygen species and recycles important cellular antioxidants.
∙ Vitamin C is also a cofactor in numerous enzymatic reactions involved in the making of
collagen, L-carnitine, and several neurotransmitters, and in the regulation of gene
expression.

Immune-specific
Immune cells generate reactive oxygen species to kill invading organisms; vitamin C
may protect immune and nearby cells from damage by these substances.

In vitro studies suggest that vitamin C may increase the production and function of
certain immune cells that help engulf and kill foreign invaders.

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 Vitamin C

∙ Immune cells accumulate and concentrate vitamin C and then quickly use it up
during an active immune response.
∙ The scientific evidence regarding the effect of vitamin C supplementation on immune
function is hampered by several methodological shortcomings. Important considerations
for research studies on vitamin C and infections include:
o the baseline vitamin C status of the study population. A beneficial effect of vitamin C
supplementation on the immune system may occur only in those with low vitamin C
intake and status to begin with.
o the presence of modifying factors. Physical stress, oxidative stress, smoking, and
disease may be accompanied by an increased demand for vitamin C.
∙ Routine use of vitamin C supplements may have a mild, beneficial effect on the duration of
the common cold in certain individuals.

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Vitamin C

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 Vitamin D

General
▪ Vitamin D is a fat-soluble vitamin that helps maintain calcium and phosphorus balance,
promotes bone health, regulates immune function, and influences cell growth and
development.
▪ Vitamin D can be made in the skin (upon exposure to ultraviolet B [UVB] radiation from the
sun) and obtained from dietary and supplemental sources.

Immune-specific
▪ Vitamin D increases the expression of antimicrobial proteins.
▪ Vitamin D limits certain aspects of the acquired immune response, playing a protective role
and potentially reducing the risk of autoimmune disease and tissue transplant rejection.

⮚ Vitamin D is notoriously difficult to obtain from food sources alone and national surveys
indicate that 94% of the US population is not meeting the dietary requirement for vitamin D.
⮚ The LPI recommends 2,000 IU (50 micrograms) of supplemental vitamin D daily for generally
healthy adults.

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 Vitamin D

⮚ Low serum 25-hydroxyvitamin D3 (a reliable measure of vitamin D status) is linked to a

higher risk of upper respiratory tract infections.
⮚ Overall, randomized controlled trials indicate that daily or weekly supplementation with
vitamin D reduces the risk of upper respiratory tract infections.
⮚ Vitamin D deficiency is associated with an increased incidence and severity of the
coronavirus disease, COVID-19.
⮚ Low serum 25-hydroxyvitamin D3 has been observed in individuals with autoimmune
disease, including those with insulin-dependent (type 1) diabetes mellitus, multiple
sclerosis (MS), systemic lupus erythematosus, and rheumatoid arthritis.
⮚ In those with MS, lower vitamin D status is associated with increased disease activity and
risk of relapse.
Living at higher latitude (and thus, exposed to less UVB radiation from the sun) and low
vitamin D intake have been associated with an increased risk of developing MS.
Despite the well-documented association between low vitamin D status and multiple
autoimmune diseases, few randomized controlled trials have been conducted and the
clinical efficacy of vitamin D supplementation in the prevention and treatment of
autoimmune disease is not yet known.
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Vitamin D

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 Vitamin E

General
∙ Vitamin E is a fat-soluble vitamin that functions as an antioxidant in lipid (fat) environments.
∙ Vitamin E is an important antioxidant nutrient in cell membranes, where it functions to protect
cells from oxidative damage.

Immune-specific
∙ Vitamin E augments the functional activity of immune cells (T lymphocytes in particular) by
protecting their cell membranes and reducing the production of immunosuppressive factors.

∙ Several aspects of immune function decline with increasing age and older individuals are more
susceptible to infection and have a poor response to vaccination.
∙ Supplementation with vitamin E is able to reverse these deficits and enhance resistance to
respiratory infection in some individuals.
∙ However, the research in this area is still inconclusive; randomized controlled trials have reported
positive, neutral, and negative effects of vitamin E supplementation on pneumonia and the
common cold in certain subgroups of the population, including the elderly.

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Vitamin E

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 Probiotics

General
∙ Probiotics are live, beneficial bacteria that can be ingested and temporarily inhabit the
lower part of the gastrointestinal tract (the colon).

∙ The most commonly available probiotics are called Lactobacilli and Bifidobacteria.
Sources of these probiotics include traditionally cultured dairy products, some fermented
foods, and dietary supplements.

∙ Because probiotics stay in the colon only temporarily, regular consumption is necessary
to maintain their populations in the colon.

∙ Antibiotics can disrupt the protective barrier created by our gut microbiota. Probiotics
have been shown to prevent diarrhea associated with antibiotic use in hospitalized
children and adults.
∙ At this time, the scientific evidence is insufficient to advocate the use of probiotics to
reduce respiratory infections and improve vaccination response, especially in the elderly.
∙ Probiotics facilitate the colonization of beneficial microbes in the colon.
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 Probiotics

Immune-specific
▪ The human body coexists with millions of bacterial species that can influence
various aspects of health. The bacteria that live specifically in our colon
(collectively referred to as the gut microbiota) can influence several aspects of
immunity.
▪ The gut microbiota influences immune function by:
(1) creating a barrier against colonization by pathogens, and
(2) interacting with host immune cells to influence their function.
▪ The use of probiotics to influence immunity is an active area of research.
▪ Some ideas for how probiotics might help immunity are that they:
🡪 contribute to the maintenance of the antimicrobial barrier of the gut.
🡪 produce metabolic products, such as lactic acid and antibiotic proteins, that
directly inhibit the growth of pathogens and influence the activity of host
immune cells.
🡪 compete with some pathogenic bacteria for available nutrients.
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 Copper

General
∙ Copper is an essential mineral that assists in energy production, iron utilization,
antioxidant defense, and the synthesis of neurotransmitters and connective tissue.
Immune-specific
∙ Copper is a structural and functional component of an important antioxidant enzyme called
superoxide dismutase that protects immune cells from oxidative damage.
∙ Copper may also help cells of the innate immune response kill bacteria.

∙ Severe copper deficiency results in neutropenia — an abnormally low number of immune

cells called neutrophils; neutropenia can increase one’s susceptibility to infection.
∙ On the other hand, long-term high intake of copper (7.8 milligrams/day for approximately
five months) has been shown to blunt antibody production in response to an influenza
vaccine.
∙ Although extreme copper deficiency and excess can adversely affect immune function, it
is very difficult to measure copper nutritional status and the effect of marginal copper
status on immune function is not yet known.
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Copper

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 Iron

General
∙ Iron, an essential mineral, helps make hundreds of vital proteins, facilitates oxygen
transport and storage, participates in energy production, and assists antioxidant enzymes.
∙ Dietary iron is found in two forms: heme and nonheme iron. Heme iron comes mainly from
meat, poultry, and fish. Nonheme iron is found in plants, dairy products, meat, fortified
food, and dietary supplements.
Immune-specific
∙ Iron is a structural and functional component of several metabolic and antioxidant
enzymes that are critical for normal immune function.
∙ Sufficient iron is necessary for many immune functions, including the production of T
lymphocytes and the generation of reactive oxygen species that kill pathogens.
∙ Iron is also required by most infectious agents for replication and survival. The human
body has developed strategies to withhold iron in response to infection or inflammation,
but many infectious agents have developed their own counter measures to acquire iron
while avoiding its toxic effects. Thus, a balance between host and pathogen iron
requirements must be maintained for optimal immune function.
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 Iron

∙ Both iron deficiency and iron overload are associated with impaired immune function and
increased susceptibility to infection.

∙ An estimated 30 percent of the world’s population (residing mainly in less developed

nations) is iron deficient and correcting this deficiency is critically important for growth,
development, immune function, survival, and quality of life.
∙ There is concern, however, that excess iron could increase the susceptibility to certain
infections. In regions with high rates of malaria, combining iron administration with
malaria detection and treatment strategies, and possibly screening for iron status, are
important components of iron supplementation efforts.

∙ Iron overload, studied mainly in individuals with genetic disorders of iron storage
(hemochromatosis), has numerous negative effects on immune cell function and can make
individuals especially vulnerable to pathogens.

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Iron

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 Selenium
General
∙ Selenium is an essential trace mineral that is a structural component of several antioxidant
enzymes and influences thyroid hormone function.
Immune-specific
∙ Selenium is an integral component of two antioxidant enzymes, glutathione peroxidase
and thioredoxin reductase, that protect immune cells from oxidative damage.
∙ Selenium also influences the production of cytokines and eicosanoids — chemical
messengers that regulate inflammation and immune cell function.

∙ Selenium deficiency increases oxidative stress, which impairs immune function.

∙ Selenium supplementation appears to improve some, but not all, immune functions:
o Selenium supplementation improves the acquired immune response in selenium-
deficient individuals and enhances the immune response to viruses.
o On the other hand, selenium supplementation may worsen allergic asthma and impair
the immune response to parasites.
⮚ Correcting a deficiency rather than supplementing selenium-adequate individuals may be
best for optimal immune function 57
Selenium

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 Zinc

General
∙ Zinc is an essential trace mineral that is required for the synthesis of hundreds of essential
proteins, needed for normal cell growth and development, facilitates oxygen transport and
storage, and assists several antioxidant enzymes.
Immune-specific
∙ Zinc is required for the growth and development of immune cells involved in both innate
and acquired immunity.
∙ Zinc is important for the synthesis of antibodies.
∙ Zinc is also a structural and functional component of proteins and enzymes critical for
normal immune function.
∙ One such zinc-containing antioxidant enzyme, superoxide dismutase, protects immune
cells from reactive oxygen species that are generated to kill invading pathogens during an
immune response.

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 Zinc

∙ Zinc deficiency is associated with an increased susceptibility to infection, especially in the

elderly and children in developing countries.
o Zinc supplementation (in combination with oral rehydration therapy) reduces the
frequency, severity, and duration of diarrheal episodes in children.
o The efficacy of zinc supplementation in elderly individuals is unclear at this time. Some
randomized controlled trials have found that zinc supplementation reduces the number
of infections, while others have found no effect.

∙ Taking zinc lozenges upon the onset of common cold symptoms can reduce cold duration.

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Zinc

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NUTRITION FOR SKIN HEALTH

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SKIN

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SKIN

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SKIN

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SKIN

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 SKIN

⮚ Nutritional status plays an important role in the maintenance of healthy skin.

⮚ Macronutrients (carbohydrates, proteins, and lipids) and micronutrients (

vitamins and nutritionally essential minerals) work together to maintain the
barrier functions of skin in the face of everyday challenges.

⮚ Changes in nutritional status that alter skin structure and function can also
directly affect skin appearance.

⮚ Unlike many organs, skin nutrition may be enhanced directly through topical
applications.

⮚ Topical application of micronutrients can complement dietary consumption,

leading to a stronger, healthier protective barrier for the body.

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 SKIN AND NUTRITION

⮚ The primary fuel for skin cells is glucose; glucose oxidation rates in skin are similar to
those observed in resting skeletal muscle.
⮚ Glucose also provides carbohydrate backbones for modification of proteins (glycoproteins)
and lipids (glycoplipids) that comprise the extracellular environment of the epidermis.
Aberrant glucose handling drastically affects skin structure and appearance.
⮚ Specialized lipids required for the development of the stratum corneum, such as sterols
and ceramides, are synthesized in the epidermis from amino acids, carbohydrates, and
phospholipids.
⮚ However, differentiating keratinocytes also utilize fatty acids from circulating stores or
dermal fat layers for energy.
⮚ The extruded fatty acids that make up the mortar of the stratum corneum can absorb lipid-
soluble materials placed on the external surface of this outermost skin layer.
⮚ This is especially the case for sebum, a waxy substance secreted from the
sebaceous glands that are attached to hair follicles, but it is also true for topically applied
materials.
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 SKIN AND NUTRITION

⮚ Amino acids are essential for the production of both dermal and epidermal structures,
producing the extracellular matrix proteins and enzymes needed for the synthesis of the
epidermal barrier. The amino acid requirements of skin are poorly understood.
⮚ Much of the role of nutrition in skin health focuses on the effects of deficiency, since the
structural components of the skin are supported by a variety of nutritive factors, such as
small peptides, minerals, and vitamins, which serve as enzyme cofactors, activators, or
inhibitors.
⮚ The skin is also constantly exposed to high concentrations of oxygen, UV light, and
oxidizing chemicals, highlighting a role for antioxidant vitamins in skin function.
⮚ Further, nutritional support of the skin is important for inflammatory response during
wound healing.

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 SKIN AND NUTRITION

Nutrients in Skin Health

⮚ Changes in the appearance of skin were associated with poor nutrition long before any
biochemical relationships were discovered.

⮚ Among the first to make these associations was the Scottish physician James Lind, who
described the bleeding gums, skin discoloration, abnormal hair growth, and poor wound
healing associated with the vitamin C deficiency disease known as scurvy.

⮚ Other investigators would soon find skin abnormalities in vitamin deficiency diseases
(pellagra, ariboflavinosis, etc.) that could be corrected with an appropriate diet.

⮚ Thus, many micronutrients were initially identified for their impact on skin health.

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 Essential Fatty Acids and Skin Health

o Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) play a critical
role in normal skin function and appearance.

o Metabolism of the essential fatty acids (EFAs), linoleic acid (LA; 18:2n-6) and α-
linolenic acid (ALA; 18:2n-3), is limited in the skin; long-chain derivatives of LA and
ALA are therefore considered conditionally essential nutrients for skin.

o The omega-6 PUFAs have a particular role in structural integrity and barrier function
of the skin.

o Both omega-6 and omega-3 PUFAs give rise to potent signaling molecules, called
eicosanoids, which influence the inflammatory response in skin.

o Both topical application and oral supplementation are effective means of delivering
EFAs to the skin and systemic circulation.

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 Essential Fatty Acids and Skin Health

o Consuming oils rich in n-6 and n-3 fatty acids can alter the fatty acid composition
and eicosanoid content of the epidermis.

o Dietary supplementation and topical application of certain omega-3 PUFAs

attenuates UV-induced photodamage, extrinsic signs of skin aging, and inflammatory
skin responses.

o Dietary supplementation with certain omega-6 fatty acids alleviates symptoms

associated with skin sensitivity and inflammatory skin disorders.

o This PRESENTATION focuses on the role of EFAs in healthy skin and does not
discuss the abundant literature regarding EFA supplementation on psoriasis,
eczema, atopic dermatitis, and other inflammatory skin disorders.

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Essential Fatty Acids and Skin Health

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Essential Fatty Acids and Skin Health

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 Essential Fatty Acids and Skin Health

Deficiency
⮚ Essential fatty acid deficiency (EFAD) significantly affects skin function and appearance.
EFAD is characterized by hyperproliferation of the epidermis, dermatitis, and increased
transepidermal water loss (TEWL). TEWL reflects the integrity of the barrier function of the
skin and is directly related to the EFA composition of structural lipids in the
stratum corneum.
⮚ In humans, dermatitis may not be present for weeks to months, while the biochemical signs
of EFAD manifest within days to weeks.
⮚ Biochemically, EFAD is characterized by the presence of mead acid (20:3n-9) in plasma
phospholipids.
⮚ During EFAD, mead acid is produced from the disproportionate abundance of omega-9
fatty acids in the absence of omega-6 and omega-3 fatty acids. Because mead acid is not
produced in EFA-replete individuals, its presence in plasma and structural lipids in the skin
is diagnostic of EFAD.

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 Essential Fatty Acids and Skin Health

Conclusion for fatty acids for skin health

⮚ Omega-6 (n-6) and omega-3 (n-3) essential fatty acids (EFAs) are crucial to skin function and
appearance.
⮚ Both dietary and topical supplementation with EFAs can have profound effects on the fatty acid
composition and eicosanoid milieu of the skin. As a result, addition of various EFA-rich oils can
modulate the inflammatory response in both dermal and epidermal layers of the skin.
⮚ Supplementation with n-3 fatty acids in particular exerts protection from photodamage and
photoaging.
⮚ N-6 EFAs are required for skin barrier function and structural integrity. Supplementation with n-6
fatty acids alleviates symptoms associated with skin sensitivity and inflammatory skin disorders.
⮚ The mechanism by which EFAs influence skin reactions is likely through changes in the ratio of pro-
and anti-inflammatory eicosanoids derived from EFA precursors.
⮚ N-6 and n-3 fatty acids compete for the same enzymes; thus supplementation with specific EFAs can
alter the corresponding metabolites, significantly influencing skin function and appearance.

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 Vitamin A and Skin Health

⮚ The term “retinoids” refers to vitamin A and the various compounds derived from
vitamin A. Skin is a major retinoid-responsive tissue.

⮚ Cells in both the epidermis and dermis contain proteins and receptors that
mediate the biological effects of vitamin A metabolites in the skin.

⮚ A commonly experienced side effect following topical application of retinoids is

"retinoid dermatitis." Adjusting the dose and frequency of retinoid application can
reduce adverse skin reactions.

⮚ Topical retinoids have a well-documented effect on skin health, with the majority of
clinical evidence relating to their treatment of acne vulgaris and certain signs of
photoaging.

⮚ Pretreatment with topical retinoids can mitigate some of the ultraviolet radiation
(UVR)-induced changes that damage dermal collagen.

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 Vitamin A and Skin Health

⮚ Topical retinoids induce clinical improvements in photoaged skin, including a

reduction in fine wrinkling, increased smoothness, and diminished
hyperpigmentation.

⮚ The longevity of topical retinoid effects is uncertain and a long-term maintenance

regimen is necessary in order to sustain retinoid-induced clinical improvements.

⮚ Studies in animals demonstrate that vitamin A mitigates cortisone-induced defects

in wound healing.

⮚ Topical tretinoin is considered a very safe and effective treatment for mild to
moderate acne, while oral isotretinoin is used to treat severe cases of acne that
are resistant to topical therapies.

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 Vitamin A and Skin Health

⮚ The term "retinoids" refers to vitamin A and the various molecules derived from vitamin A,
which itself is also known as retinol (ROL).

⮚ In the skin, ROL is converted to retinaldehyde (RAL) and then to retinoic acid (RA).

⮚ RA modulates gene expression and influences cellular processes in both the epidermis and
dermis, thereby exerting potent effects on skin health.

⮚ Keratinocytes and fibroblasts convert ROL first to retinaldehyde (RAL) and then to all-trans-
retinoic acid (at-RA)

⮚ A very common side effect of topical retinoid therapy is "retinoid dermatitis," also referred
to as retinoid irritation or retinoid reaction.

⮚ Retinoid dermatitis is characterized by erythema, scaling, dryness, and pruritis.

⮚ Topical retinoids induce changes in the epidermis that lead to increased proliferation and
altered differentiation of keratinocytes; this in turn disrupts the barrier of the skin.

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 Vitamin A and Skin Health

Deficiency

⮚ Feeding rats diets devoid of vitamin A affects epithelial tissues in various parts of
the body, including the respiratory, alimentary, and genitourinary tracts, and the
eyes and paraocular glands.

⮚ Specifically, there is widespread keratinization, meaning that normal epithelium is

replaced by stratified keratinizing epithelium, which has different functional
properties.

⮚ There is also atrophy of many glands, including sweat and sebaceous glands.

⮚ Based on experimentation in animals, vitamin A deficiency is also associated with

delayed wound repair

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 Vitamin A and Skin Health

Deficiency (cont’d)

⮚ In addition to their known role in the treatment of photodamaged skin,

pretreatment with retinoids might prevent ultraviolet (UV)-induced damage in the
first place.

⮚ Ultraviolet radiation (UVR) damages skin via many mechanisms. One way UVR
contributes to photodamage is by modulating signaling pathways that influence
collagen homeostasis in skin cells.

⮚ UVR induces the transcription factor AP-1, which increases the expression of
several matrix metalloproteinases (MMPs) (collagenase, gelatinase, stromelysin),
proteolytic enzymes that degrade dermal collagen and fibrillin.

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 Vitamin C and Skin Health

⮚ The antioxidant properties of vitamin C (ascorbic acid) and its role in collagen
synthesis make vitamin C a vital molecule for skin health.
⮚ Dietary and topical ascorbic acid have beneficial effects on skin cells, and some
studies have shown that vitamin C may help prevent and treat ultraviolet (UV)-
induced photodamage.
⮚ Vitamin C is a normal skin constituent that is found at high levels in both the
dermis and epidermis.
⮚ The vitamin C content of the epidermis is higher than the dermis, although the
vitamin C concentrations in both layers are approximately equal to that of other
water-soluble antioxidants, including uric acid and glutathione.
⮚ Aging, however, causes a decline in vitamin C content in both the epidermis and
dermis.
⮚ Excessive exposures to UV light or pollutants (e.g., cigarette smoke and ozone)
may also lower vitamin C content, primarily in the epidermis

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 Vitamin C and Skin Health

⮚ Symptoms of vitamin C deficiency (knowns as scurvy) appear once plasma

concentrations of ascorbic acid drop below 10 micromolar (μM), a level that can
be prevented by consuming as little as 10 mg of ascorbic acid daily.

⮚ Cutaneous manifestations of scurvy result from declines in collagen synthesis,

leading to disruption of connective tissue and fragility of blood vessels.

⮚ Early symptoms in the skin include a thickening of the stratum corneum and spots
of small subcutaneous bleeding.

⮚ As scurvy progresses, wound healing is impaired due to the loss of mature

collagen, which allows wounds to remain open.

⮚ Skin lesions caused by vitamin C deficiency are remediated by an adequate intake

of vitamin C.

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 Vitamin D and Skin Health

⮚ Sunlight exposure is the primary source of vitamin D.

⮚ Solar ultraviolet-B radiation (UVB; wavelengths of 290 to 315 nanometers) stimulates the
production of vitamin D3 from 7-dehydrocholesterol (7-DHC) in the epidermis of the skin.

⮚ Vitamin D3 enters the circulation and is transported to the liver, where it is hydroxylated to
form 25-hydroxyvitamin D3 (calcidiol; the major circulating form of vitamin D).

⮚ In the kidneys, the 25-hydroxyvitamin D3-1-hydroxylase enzyme catalyzes a second

hydroxylation of 25-hydroxyvitamin D, resulting in the formation of 1,25-dihydroxyvitamin
D3 (calcitriol, 1α,25-dihydroxyvitamin D] — the most potent form of vitamin D.

⮚ Most of the physiological effects of vitamin D in the body are related to the activity of 1,25-
dihydroxyvitamin D3.

⮚ Keratinocytes in the epidermis possess hydroxylase enzymes that locally convert vitamin D
to 1,25-dihydroxyvitamin D3, the form that regulates epidermal proliferation and
differentiation

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 Vitamin D and Skin Health

Control of epidermal proliferation and differentiation

⮚ The bottom or basal layer of the epidermis, called the stratum basale, consists of a layer of
round, undifferentiated keratinocytes that is supported by the underlying dermis.

⮚ Cells in the stratum basale are constantly proliferating in order to produce new cells that
will comprise the upper epidermal layers.

⮚ Once a keratinocyte leaves the stratum basale, it begins the process of differentiation
(specialization of cells for specific functions) known as keratinization and also undergoes
cornification, a process in which keratinocytes become corneocytes.

⮚ Thus, new cells from the stratum basale replace the outer layer of skin cells that is shed
over time.

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 Vitamin D and Skin Health

Control of epidermal proliferation and differentiation (cont’d)

⮚ Along with various co-regulators, 1,25-dihydroxyvitamin D 3 and its receptor, the VDR,
regulate the abovementioned processes that replenish skin.

⮚ In general, vitamin D inhibits the expression of genes responsible for keratinocyte

proliferation and induces the expression of genes responsible for keratinocyte
differentiation.

⮚ In addition to its steroid hormone actions, vitamin D regulates biochemical steps that result
in a cellular influx of calcium, which is important in cell differentiation.

⮚ The processes of epidermal proliferation and differentiation are essential for normal cell
growth, wound healing, and maintaining the barrier function of skin.

⮚ Because uncontrolled proliferation of cells with certain mutations may lead to cancer,
vitamin D may protect against certain cancers

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 Vitamin E and Skin Health

⮚ Vitamin E is a fat-soluble antioxidant that is essential for the maintenance of healthy skin.
⮚ Naturally occurring vitamin E is not a single compound; instead, vitamin E is a group of
molecules with related structures, some of which may have unique properties in skin.
⮚ Vitamin E is also found as vitamin E conjugates that increase stability but require cellular
metabolism for activation.
⮚ Vitamin E is normally provided to the skin through the sebum.
⮚ Topical application can also supply the skin with vitamin E and may provide specific vitamin
E forms that are not available from the diet.
⮚ As an antioxidant, vitamin E primarily reacts with reactive oxygen species.
⮚ In addition, vitamin E can also absorb the energy from ultraviolet (UV) light. Thus, it plays
important roles in photoprotection, preventing UV-induced free radical damage to skin.
⮚ Vitamin E may also have related anti-inflammatory roles in the skin.

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 Vitamin E and Skin Health

⮚ Vitamin E is an integral part of the skin’s antioxidant defenses, primarily providing

protection against UV radiation and other free radicals that may come in contact with the
epidermis.
⮚ Oral supplementation with only vitamin E may not provide adequate protection for the skin,
and co-supplementation of vitamin E and vitamin C may be warranted to effectively increase
the photoprotection of skin through the diet.
⮚ However, topical vitamin E seems to be an effective mechanism for both delivery to the skin
and providing a photoprotective effect.
⮚ Additional anti-inflammatory effects of topical vitamin E have been seen in the skin.
⮚ Vitamin E is available commercially as a variety of synthetic derivatives, but the limited
cellular metabolism in skin layers makes the use of such products problematic.
⮚ Use of unesterified vitamin E, similar to that found in natural sources, has provided the
most consistent data concerning its topical efficacy.

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 Minerals and Skin Health

⮚ Minerals are found in the skin as essential components of various enzymes and inside a
special metal-binding protein, metallothionein.

⮚ Insoluble mineral oxide formulations remain on the upper layers of the skin and are not
systemically absorbed.

⮚ The organic form of selenium, L-selenomethionine, is absorbed through the skin and
reaches the bloodstream.

⮚ Mineral oxides absorb and filter UVA and UVB, reducing the amount of UVR that penetrates
the layers of the skin.

⮚ Minerals may also augment antioxidant defense mechanisms in the skin.

⮚ Zinc oxide may enhance the wound healing process, potentially by meeting the increased
demands of cell proliferation that occur during the early phases of healing.

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 Minerals and Skin Health

Zinc
⮚ Six percent of total body zinc is located in the skin. Zinc is present in both the epidermis
and dermis and at levels five-fold higher in the epidermis.
⮚ In skin physiology, zinc stabilizes cell membranes, serves as an essential cofactor for
several metalloenzymes, and participates in basal cell mitosis and differentiation.
⮚ Metallothionein (MT) is a zinc and copper storage molecule that protects cells from excess
levels of zinc while providing a locally accessible pool of these minerals.
⮚ In normal human skin, MT is expressed in basal keratinocytes of the epidermis and in hair
follicle cells .
⮚ MT is significantly induced in proliferating basal keratinocytes upon chemical stimulation or
wounding.
⮚ The high levels of MT observed in mitotically active keratinocytes has thus implicated a role
for zinc in epidermal proliferation.
⮚ Zinc is also present in a number of zinc-dependent metalloenzymes in the skin, including
matrix metalloproteases (MMPs), superoxide dismutase (SOD), alkaline phosphatase, and
RNA/DNA polymerases.
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 Minerals and Skin Health

Selenium

⮚ Selenium is present in the cells of the skin as a component of various

selenoproteins, including phospholipid hydroperoxide glutathionine peroxidase
(PHGPx) and thioredoxin reductase (TDR).

⮚ PHGPx and TDR are antioxidant enzymes that inactivate peroxides, thereby
protecting skin cells from the harmful effects caused by these free radicals.

⮚ TDR is associated with keratinocyte cell membranes, and its levels appear to
correlate with susceptibility to UVB-induced damage.

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 Minerals and Skin Health

Deficiency
⮚ The skin relies on the circulatory system to supply it with nutrients.
⮚ Systemic nutritional deficiencies often manifest in skin abnormalities, and meeting the
Recommended Dietary Allowance (RDA) for each mineral is important for healthy skin.

Zinc
⮚ Severe zinc deficiency (low serum zinc concentration) resembles
acrodermatitis enteropathica, an inherited disorder of impaired zinc absorption
characterized by erosive dermatitis, diarrhea, and alopecia.

⮚ Moderate zinc deficiency causes pigmentation changes, decreased hair and nail growth,
and skin lesions on body sites exposed to repeated pressure and friction in particular.

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Selenium Deficiency
⮚ Selenium deficiency is associated with an increased risk of several types of cancer,
including skin cancer.
⮚ Selenium imbalance, both deficiency and excess, causes skin abnormalities.
⮚ Mice fed diets with either excessive or deficient selenium for 24 weeks developed alopecia
with poliosis (a decrease or absence of color), altered hair follicle cycling, and epidermal
atrophy, possibly due to increased apoptosis in keratinocytes.
⮚ Genetically altered mice with keratinocyte-specific depletion of selenoproteins developed
skin and hair defects within six days after birth, including malformed hair follicles,
hyperplastic epidermis, alopecia, and keratinocytes with adhesion and growth defects that
underwent apoptosis.
⮚ It appears that a reduction in selenoprotein levels drive the observed skin abnormalities of
selenium deficiency.

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 Minerals and Skin Health

⮚ Topical treatment with zinc and selenium can protect the skin from UV radiation (UVR).

⮚ Mineral oxides of zinc and titanium operate by blocking UV penetration of the skin,
providing a safe and effective means to reduce UVR exposure.

⮚ Topical zinc also induces metallothionein (MT), which provides a locally accessible pool of
mineral for zinc-dependent metalloenzymes while serving as a free radical scavenger.

⮚ Oral and topical L-selenomethionine may protect the skin from UV damage by increasing
the levels of selenium-dependent antioxidant proteins prior to UV exposure.

⮚ Selenium is thought to protect the skin from UVR by increasing the activities of the
selenium-dependent antioxidant enzymes glutathione peroxidase (GPx) and thioredoxin
reductase (TDR).

⮚ TDR is present in the plasma membrane of human keratinocytes, and in vitro experiments
support a role for TDR in the protection of the outer keratinocyte membrane against damage
from oxygen radicals.

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 Minerals and Skin Health

⮚ Mineral oxides such as zinc oxide (ZnO) and titanium dioxide (TiO 2) protect the skin from
photodamage by reflecting and absorbing ultraviolet radiation (UVR) across the UV
spectrum, thus reducing the level of radiation that penetrates the skin.
⮚ Zinc oxide has been in use for decades as a safe and effective physical sunscreen.
⮚ Microfine zinc oxide preparations appear transparent in films, block UVB and UVA radiation,
remain intact upon UV exposure, and do not photoreact with organic compounds in
sunscreens.
⮚ Soluble forms of zinc (i.e., zinc ions, zinc chloride) may also provide antioxidant protection
in the skin. Proposed mechanisms include the displacement of redox active molecules,
such as iron and copper with zinc, which does not participate in redox (electron transfer)
chemistry, and the induction of metallothionein (MT).
⮚ In addition to functioning as a metal-storage depot, MT exerts free radical scavenging
activity.

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