CONTINUING MEDICAL EDUCATION

Akreditasi PB IDI–2 SKP

The Role of Vitamin D in Enhancing Immunity

and Its Recommendations
Adianto Jaya Nagara, Andry Gonius
Brawijaya University, Faculty of Medicine, Malang, Indonesia

ABSTRACT
Vitamin D is a fat-soluble vitamin with a very important role in regulating the body’s calcium balance. It also plays an important role in cell
growth, even optimizing the immune system. American Academy of Dermatology recommends supplementation of oral vitamin D to meet
daily vitamin D requirements.

Keywords: Immunity, vitamin D

ABSTRAK
Vitamin D adalah vitamin larut dalam lemak yang penting untuk mengatur kadar kalsium tubuh, juga berperan dalam pertumbuhan sel dan
sistem imun. Untuk memenuhi kebutuhan vitamin D dalam tubuh, American Academy of Dermatology menganjurkan suplementasi oral vitamin
D. Adianto Jaya Nagara, Andry Gonius. Peran Vitamin D dalam Meningkatkan Imunitas dan Rekomendasinya

Kata kunci: Imunitas, vitamin D

Introduction of contracting the COVID-19 virus, including deficiency is one of the public health problems
Vitamin D is a fat soluble vitamin that has a sunbathing. The study described a country faced by many countries. The population that
very important role in regulating the body’s where most of its population had relatively experiences vitamin D deficiency is most
calcium balance. It also plays an important low levels of vitamin D (Italy), had a high represented by the group of people who are
role in cell growth, even optimizing the infection and death rate due to COVID-19. In elderly, obese, and long bed rest patients in
immune system. contrast, countries where populations have the hospital.3,6,7
relatively sufficient vitamin D levels (Norway
Based on research, approximately 50% of and Finland) have a relatively low infection Large number of people who are deficient in
the world’s population is deficient in vitamin and death rates due to COVID-19.1 Given vitamin D is thought to be caused mainly by
D. This problem of vitamin D insufficiency these facts, some experts recommend that the modern lifestyle that has a lot of activity
and deficiency is one of the public health people optimize their immunity by meeting indoors and several other environmental
problems faced by many countries. Vitamin their vitamin D requirements by sunbathing factors that cause less exposure to
D deficiency is mostly found in elderly, obese, regularly.2 ultraviolet-B (UVB), and lack of vitamin D
and patients with long bed rest in hospital.3 intake from food. The high prevalence of
Sunbathing can help the body to produce Vitamin D Deficiency as Global Problem vitamin D deficiency and insufficiency is a
vitamin D, which in turn can optimize the Vitamin D status in the human body is serious public health problem because this
body’s immunity against viral infections.1-3 classified based on 25-OH-D levels in serum:4 is a risk factor for several deaths that occur in
Ultra violet light obtained from sunlight, 1. Normal: >30 ng/mL the wider community. Recent research has
especially UVB, can help the formation of 2. Insufficiency: 21-29 ng/mL shown that vitamin D deficiency has been
vitamin D in human skin.1 3. Deficiency: <20 ng/mL linked to cancer, cardiovascular disease, type
2 diabetes, autoimmune diseases, influenza,
In the midst of the COVID-19 outbreak that Based on research, about 50% of the world’s and depression.2,6,8
struck almost all countries, including Indonesia, population is deficient in vitamin D. This
people did a variety of ways to reduce the risk problem of vitamin D insufficiency and
Alamat Korespondensi email: Adianto.jn@gmail.com

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New Role of Vitamin D in Immunity

Classically, vitamin D has always been
implicated in bone health by increasing
calcium absorption in the intestine and
regulating calcium and phosphate levels
in the blood, but in the last 2 decades, a
new role in vitamin D has been discovered.8
Vitamin D also plays a role in cell proliferation
and differentiation, regulation of the immune
system, preventive effects on cardiovascular
and neurodegenerative diseases, even
anticancer and antiaging effects.2,8

Calcitriol has an important immunomodulatory

role, including strengthening the innate
immune system, inhibiting the response
of the adaptive immune system, related to
the synthesis of interleukin (IL) -4 by helper
T-lymphocytes (Th) -2 cells, and upregulation
of regulatory T lymphocytes (T-reg) cells.8,9

Regulation of innate immune responses to Figure RAS regulatory system and the role of vitamin D in it (Reproduced from Biesalski, 2020) .9
dendritic cells and macrophages.
Calcitriol increases the defense capacity of
macrophages by increasing cell differentiation, dendritic cells, thus leading to Th1 inhibition. converted by ACE2 to angiotensin 1-9 and
phagocyte capacity and antimicrobial Additionally, calcitriol works directly against 1-7. Angiotensin 1-9 and 1-7 will activate
activity (cathelicidin). Cathelicidin, a peptide T cells inhibiting the secretion of IL-2, which AT2R, so that there will be a decrease in blood
formed from vitamin D stimulation, exhibits is an essential cytokine for the formation of pressure, vasodilation, and inflammation. With
antimicrobial activity such as bacteria, additional lymphocytes and gamma IFN. the operation of these two systems, the body’s
fungi, and enveloped-viruses.9 In fact, Calcitriol also inhibits B cell differentiation and homeostatic balance can be maintained as
calcitriol inhibits monocyte proliferation and antibody production. In the case of psoriasis, long as RAS activity can be controlled.9
increases the differentiation of monocytes calcitriol inhibits keratinocyte proliferation
into macrophages. This effect is mediated and also facilitates cell differentiation.8 Several studies have shown an increase in
by upregulation of Fc cell surface receptors renin, angiotensin II, and the activity of the
and increased cell respiration. In addition, Covid-19 Association with Low Levels of renin-angiotensin-system (RAS) due to low
Calcitriol inhibits dendritic cell proliferation, Vitamin D levels of vitamin D in the body. the same
maturase, and also the effect of stimulation In a research model on inflammation induced thing also applies that the low activity of renin
of the immune system which ends with T-reg by lipopolysaccharides, vitamin D was able to is related to high vitamin D levels.9 Vitamin
cell induction. It can be concluded, vitamin D reduce levels of pro-inflammatory cytokines D decreases the expression of renin by
deficiency can result in the body becoming IL-6.10,11 It is IL-6 that plays an important role decreasing transcription activity in the renin
less tolerant of foreign antigens.8 in COVID-19 induced acute respiratory distress promoter gene. Low levels of vitamin D in the
syndrome (ARDS).10 body result in increased secretion of renin,
Inhibits the pro-inflammatory response of APC which activates RAS, resulting in an increase
Calcitriol inhibits cytokine expression from In the classic renin-angiotensin-system in blood pressure. If there is an imbalance in
APC, including IL-1, IL-6, IL-12, and TNF-α. As (RAS) system, renin produced will convert this system (where there is an increase in the
well as reducing the expression of the cell angiotensinogen to angiotensin I. Then activity of angiotensin II and renin), it will result
surface protein Major Histocompatibility angiotensin I is converted to angiotensin II in an increase in the inflammatory response.9
Complex (MHC) class II in macrophages, the by Angiotensin Converting Enzyme (ACE).
formation of Th1 and Th17 proinflammatory If angiotensin II activates angiotensin 1 SARS-CoV2 infection occurs by contacting
cells. By inducing T-reg and Th2 cells will receptors (AT1R), there will be an increase spike proteins with ACE2 receptors on the cell
automatically downregulate Th1 activity. in blood pressure and several other surface. After that the virus can enter the cell
Thus, Calcitriol inhibits IL-12 production effects (vasoconstriction, inflammation, with endocytosis. This also results in damage
and stimulates IL-10 production, while and catecholamine activity). To maintain to the ACE2 receptor resulting in an imbalance
downregulating the expression of some homeostasis, the body has an angiotensin in the RAS system. As a result, there is a change
molecules such as CD40, CD80, CD86 which 2 receptor (AT2R) activation system and a in vascular activity and the production of pro-
are needed in the activation of APC and Mas receptor. Where angiotensin I and II are inflammatory cytokines into the circulation.9

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A study explained that the administration 3. UV C = 100 - 280 nm overwhelm cells with DNA damage resulting
of vitamin D can reduce the expression of in mutations from p53. Keratinocytes with
renin, angiotensin II, and AT1R. It is also able Upon entering the atmosphere, almost all UV mutated p53 have a very fast growth profile
to increase ACE2 and angiotensin activities C will be retained in ozone layer and 90% UV due to their resistance from apoptosis. It can
1-7. Thus reducing the inflammatory process B will be absorbed by ozone, water vapor and be concluded that, cells that are resistant to
and reducing lung damage.11 Angiotensin other gases in the atmosphere. The majority apoptosis are an important requirement of
II activates some pro-inflammatory of UV A will be able to reach the earth’s carcinogenesis.17
stimulation in the immune system through surface. Thus, the majoroty of ultraviolet light
AT1R activation. This activity results in the contained in solar radiation when it reaches The American Academy of Dermatology
development of the inflammatory process the earth’s surface is UV A (90-99%) with a little does not recommend getting vitamin D by
that occurs, even aggravating the conditions UV B (<10%).13,14 sunbathing because it can increase the risk
of hypertension and diabetes. Vitamin D has of skin cancer, especially melanoma, the most
the opposite effect on this condition through Each scale has a UV Index equivalent to deadly type of skin cancer.18 Therefore, to
the vitamin D receptor (VDR) receptors found 0.025 Wm2 of ultraviolet radiation. The scale protect the body from the risk of skin cancer
in the immune system.1,9 was obtained based on spectral fluxes of due to light UV, some recent consensus
UV radiation with functions that correspond and recommendations suggest protecting
A comparative study studying mortality to photobiological effects on human skin, yourself from the sun, such as doing activities
index and the relationship of CRP (a cytokine integrated between 250 and 400 nm13 in the shade, using long clothes and hats
storm marker) and vitamin D in COVID-19 when the UV index is ≥3 (moderate to very
patients in various countries stated that Is It Enough to Maintain Vitamin D Levels high danger level). And if necessary use a
high CRP tends to be found in groups of With Sunbathing Only? broad-spectrum sunscreen, with SPF 30 or
people who have low vitamin D levels.9,12 A A portion of vitamin D is synthesized by the more.18,19 To meet daily vitamin D needs, AAD
study explained that people with low body body in the skin with the help of ultraviolet-B recommends eating foods that are rich in
vitamin D levels were associated with a rays. Therefore, some experts encourage vitamin D, or taking vitamin D supplements.18
risk of respiratory tract infections and were the community to optimize immunity by
more severe in people who had a history of fulfilling the needs of vitamin D by sunbathing Food sources rich in vitamin D include oily
lung disease. Other research also explains regularly.2 The World Meteorological fish groups such as salmon, anchovies, and
that vitamin D supplementation can reduce Organization (WMO) writes that lack of mackerel. A small portion of vitamin D is also
the risk of respiratory infections.1 European sunlight will affect our mood and also increase found in the liver and eggs. The need for
studies describe a country where a large the threat of vitamin D deficiency, while excess vitamin D is quite difficult to achieve through
proportion of the population has relatively has short-term and long-term effects that are food sources alone.19 Based on available
low vitamin D levels (Italy), experiencing high bad for skin health, such as aging and skin scientific sources, to meet daily vitamin D
infection and death rates due to COVID-19. In cancer.15 Data show that ultraviolet radiation requirements it is recommended to consume
contrast to countries where populations have is the cause of about 1.3 million cases of skin vitamin D supplements of:18
relatively sufficient vitamin D levels (Norway cancer per year in the United States.16 1. 400 IU for infants/ children 0-1 years
and Finland), they experience relatively low 2. 600 IU for children, teenagers, and adults
infection and death rates due to COVID-19.1 The process of carcinogenesis (formation 1-70 years
of cancer cells) begins when a cell’s DNA 3. 800 IU for adults 71+ years
Ultraviolet is damaged, which will be followed by
Ultraviolet light is part of the electromagnetic a series of cellular processes of tumor Conclusion
waves of solar radiation energy in the band formation. Ultraviolet (UV) radiation results Vitamin D has immunomodulatory effect and
100-400 nm. Solar radiation that reaches the in DNA damage, inflammation, erythema, in COVID-19 may serve as anti-inflammatory
earth’s surface itself is around a wavelength of immunosuppression, skin aging, gene agent. More studies are needed to prove
100 nm to 1 mm. Ultraviolet light which is in mutase, and skin cancer. After DNA damage this action. Vitamin D supplementation are
the wave band 100 - 400 nm is further divided occurs, the p53 tumor suppressor protein will mandatory to fulfil the daily average needs.
into UVA, UVB, and UVC:13 perform phosphorylation and translocation Sunbathing is not practical because of no
1. UV A = 315 - 400 nm of the nucleus to repair damaged DNA, or parameter on the duration, and lengthy
2. UV B = 280 - 325 nm make apoptosis. Excessive UV exposure will exposure may be harmful.

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