Pharmaceutical importance of Vitamin D in human body
SUBMITTED TO THE PHARMACEUTICAL CHEMISTRY DEPARTMENT /
COLLEGE OF PHARMACY / HAWLER MEDICAL UNIVERSITY IN
PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF
B.SC. OF PHARMACY
BY
Omer rashko omer
5th stage
Supervised by:
Lecturer
Dr. Idrees B. Qader
1443 A.H
2722K
1
2022 A.D
Acknowledgment
First I want to express my gratitude for Allah for his constant blessing throughout my
research work to complete the research successfully.
I would like to express my deep and sincere gratitude to my research supervisor Dr. Idrees
B. Qader
I am extremely grateful to my parents for their love, prayers, and supporting me during
work with this research.
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Table of contents
1- Introduction of vitamin D ……………………………......................................................7
2- Classification of vitamins…………………………….......................................................7
3- Intorduction of fat soluble vitamin D………………….....................................................9
4- History of vitamin D……………………………………………………………………10
5- Chemistry of vitamin D :………………………………………………………………..10
-Structure…………………………………………………………………………….….10
-characterestic and properties……………………………………………………….…..11
-metabolosm………………………………………………………………………….…12
-Excretion…………………………………………………………………………….…13
6- Sources of vitamin D……………………………………………………………….…..14
7- Physiological and biological functions of vitamin D…………………………………...15
8- Vitamin D deficiency…………………………………...................................................16
-Prevalence and detection of vitamin D deficiency………………………………….…17
-Stages of vitamin d deficiency………………………………………………..…..........17
-Clinical signs vitamin d deficiency……………………………………………….........18
9- Treatment of vitamin d deficiency………………………………………………..……..20
10- Vitamin d and mortality…………………………………………………………..……..21
11- Clinical benefites of vitamin D…………………………………………………...……..22
12- Covid 19…………………………………………………………………………...….…24
-Vitamin D and covid19…………………..……………………………………………..24
-Role of vitamin D in covid19………………….……………………………………….26
13- Drug interaction with vitamin D……………………………………………....………...26
14- Conclusion…………………………………………………………………….....……...27
15- Refrences………………………………………………………………………………..28
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List of figures and tables
Title
Page
Figure 1: classification of vitamins
8
Figure 2: chemical structure of vitamin d3 and d2
11
Figure 3: metabolism of vitamin d in liver and kidney
13
Figure 4: vitamin d synthesis and metabolism
15
Figure 5: causes and potential health consequences of vitamin d deficiency
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Table1:Diatery intake of vitamin d
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Table 2: RDI of vitamin d
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4
List of abbreviations
Abbreviation
Full meaning
RDI
Recommended diatery intake
COVID
Corona virus disease
ARDS
Acute respiratory disease syndrome
VDR
Vitamin d receptor
VDT
Vitamin d toxicity
VDD
Vitamin d dificiency
IL
Interlukin
PTH
Parathyroid hormone
ACE
Angiotension converting enzyme
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Abstract
Vitamin D is an important determinant of bone health at all ages. The plasma
concentrations of 25-hydroxy vitamin D (25-OH D) and other metabolites are used as
biomarkers for vitamin sufficiency and function. To allow for the simultaneous
determination of five vitamin D metabolites, 25-OH D3, 25-OH D2, 24,25-(OH)2 D3,
1,25- (OH)2 D3, and 1,25-(OH)2 D2.
Vitamin D plays a pivotal role in calcium homeostasis and skeletal metabolism throughout
life. This vitamin is also important for the functioning of many other systems, such as the
immune, cardiovascular, and reproductive systems. Vitamin D appears in two forms: the
naturally occurring vitamin D3 in mammals and vitamin D2 derived from plant sources
and chemical synthesis.
Vitamin D deficiency has been linked to viral respiratory tract infections and acute lung
damage in epidemiological investigations.
More than half of COVID19 cases and nearly 70% of COVID19 deaths in Chicago were
found among AfricanAmericans who are at higher risk for vitamin D deficiency.
This research review focuses on several aspects of vitamin D, including its pharmaceutical
and biological role, treatment and its deficiency.
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1. Introduction
Vitamins are naturally organic structure, extensively complex compound, and catalysts for
the body’s metabolic reactions; they also act as electron donators, antioxidants, and
transcription effectors. Vitamin is a combination term from vita and amine meaning amine
of life which was discovered by Funk. Vitamins are different in nature comparative to fats,
carbohydrates and proteins. They are separated from other groups by their organic nature,
and their category depends on chemical nature and function (Mallakpour and Sadaty,
2016)
We need small amount of vitamins for growth, development, health and reproduction.
Human body is incapable to synthesize the vitamins. so, their intake through diet is
necessarily vital. But Some vitamins are perverted from usual description and we can’t get
them from food alone, i.e. ascorbic acid, vitamin D and niacin. Ascorbic acid is
synthesized by animals, Niacin synthesized from tryptophan amino acid and vitamin D
synthesized from UV radiation from sunlight. So, in special species and under certain
conditions vitamin D, ascorbic acid and niacin does not fit in the definition of vitamins.
They are important for human body functions, so severe conditions are caused by
insufficiency of vitamins like, vitamin A associated with Blindness, vitamin B1 with
beriberi, vitamin B3 with pellagra, vitamin B6 with anemia, vitamin C with scurvy
and vitamin D with rickets, whereas, resupply of these nutrients can cure the
insufficiency symptoms (Yadav et al., 2016).
In this research review, we focus on the vitamin D which has a number of applications.
1.1 Classification of vitamins
In 1915, depend on their solubility, absorption, storing and removing from the body,
Mc Collum and Davis
classified the vitamins as water soluble and fat soluble
vitamins. Vitamin A, E, K and D are fat soluble vitamins, they have the same
mechanism as for absorption of fats and they will be stored in the body. whereas,
vitamin B1, B2, B3, B5, B6, B9, B12, biotic and vitamin C are water soluble vitamins.
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Water soluble vitamins: They are soluble in water, not in lipids and they can not be
stored in the body, Such as B-complex and vitamin C.
fat soluble vitamins: They are soluble in lipid, also can be stored in the body, Such as
Vitamin A, K, E, D (Ugli and Bekchanovich, 2020).
Figure.1 : Classifications of vitamins (Ugli and Bekchanovich, 2020).
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1.1 Fat soluble vitamin D
Vitamin D is a group of fat-soluble structures that were first recognized due to their antirachitic function. there is seven types of vitamin D, which are Vitamin (D1-D7). but the
major two forms relative to human healthiness are vitamin D2 and D3. Vitamin D2 is
derived from ergosterol which is the plant steroid and Vitamin D3 (cholecaliferol) is made
from its precursor which present on the skin, 7-dehydrocholesterol, when exposed to the
ultraviolet (UV) irradiation of the sun. and It must have two hydroxylations in the body
for activation, first converted by enzymes in the liver to 25-hydroxycholecalciferol
(calcidiol), which is a stable circulating form of vitamin D and then converted by
mitochondrial enzyme in the kidney to 1α,25-dihydroxycholecalciferol (calcitriol), which
is the active form of vitamin D. It acts by cell-specific genomic and nongenomic
pathways. (Wolf, 2004).
Vitamin D is produced in the body endogenously, so it doesn't meet the classical standard
of a vitamin. It's classed as a secosteroid hormone, with an endocrine system that produces
calcitirol initially in the kidney but which acts in other places, such as intestine, bone,
Parathyroid gland, and kidney. Also there is other tissues like macrophages, colon,
prostate, brain, breast which have the enzymatic machinery to locally produce
1,25(OH)2D ( Holick MF 2004).
Vitamin D is responsible for keeping of the calcium/ phosphate homeostasis, regulation of
bone remodelling. So severe vitamin D deficiency is linked with progression of the
diseases
like rickets, osteo-porosis,osteomalacia, myopathy, severe hyperactive-
parathyroidism, impaired immun and cardiac Actions, and death (Hruska et al., 2007).
So we can say it is a pathogenic factor that can be measured, monitored, and manipulated.
1.2 History of vitamin D
In the begining of 1900s, Professor C. Funk and Sir Edward Mellanby determined that the
cause of rickets was deficiency of fat-dietary, In 1919, Mellanby found that cod liver oil
or butterfat has antirackitic factor, he suggest that vitamin A was a factor, But in 1922,
antirackitic factor in cod liver oil was determined by McCollum's laboratory, this was
called vitamin D. In 1919, Huldschinsky showed that sunlight exposure had effect in
healing rickets.
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In 1925, Hess and Weinstock determind that there is a connection between UV light and
vitamin D, and they suggest that a provitamin D which was 7-dehydrocholesteol, might
exist in skin and converted to vitamin D with sunlight. In 1932, D2 (ergocaliferol) was
determined by Windaus in german and Angus in ingland. In 1936, D3 (cholecalciferol)
was determined by Windaus. In 1970, the production of 1,25(OH)2D3 in the kidney was
determined by Fraser and Kodicek, which was act as steroid hormone, this concept
supported by baker in 1989.
There is a relationship between Vitamin D and steroid hormones. Vitamin D has an
important role in health promotion, curing of disease, homeostasis (DeLuca, 2014).
1.4 Chemistry of vitamin D
1.4.1 Structure of vitamin D
The cyclopentanoperhydro-phenanthrene ring system gives rise to a family of steroid
hormones known as vitamin D. Except for three unbroken rings, vitamin D and its
metabolites are structurally linked to cholesterol. In all D vitamins, the fission of the 9,10carbon bond opens the B ring, resulting in a conjugated triene system.
The distinctions between members of the vitamin D family (vitamin D2, D3, etc.) are
found solely in their side chains. The C-5 to C-8 diene system is transoid and virtually
planar within the conjugated triene system of vitamin D, whereas the C-6 to C-19 diene
system is cisoid and not planar.
Vitamin
D’s
C
and
D
rings
are
stiff,
with
long
side
chains.
The A ring, on the other hand, has two potential chair conformations, both of which are p
resent in equilibrium in all vitamin D metabolites in solution and undergo fast interconve
rsion (Holick, 2003).
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Figure2 :Chemical structures and production of vitamin D 3and vitamin D 2from their
precursors(Holick, 2003).
1.4.2 Characteristics and properties:
Vitamin D 3(C27H44O)
Molecular weight: 384.65
Melting point: 84–85°C
UV absorption: 264–265 nm with a molar extinction coefficient of 18,300 in alcohol or
hexane, αD 20 + 84.8° in acetone
Solubility: Soluble in benzene, chloroform, ethanol, and acetone; insoluble in H2 O.
Stability: Stable to heat, acid, and alkali; unstable in light; undergo oxidation if exposed
to air 24–72 h, best stored in evacuated ampules at 0°C
Vitamin D 2(C28H44O)
Melting point: 121°C
UV absorption: 265 nm with a molar extinction coefficient of 19,400 in alcohol or hexane,
αD 20 + 106° in acetone
Solubility and stability properties are the same as vitamin D3(Zempleni et al., 2013).
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1.4.3 Metabolism
25-Hydroxyvitamin D
Vitamin D undergoes its first transformation mostly in the liver. The 25-carbon is given a
hydroxyl group, resulting in 25(OH)D, the most widely circulated form of vitamin D.
Vitamin D 25-hydroxylase is the enzyme that catalyzes the synthesis of 25(OH)D. The
25-hydroxylase belongs to the cytochrome P 450 superfamily of enzymes, which is found
largely in the mitochondria and microsomes of the liver. In humans, at least four enzymes
with vitamin D 25-hydroxylase activity have been identified, including mitochondrial
CYP27A1 and microsomal CYP2R1, CYP2J2, and CYP3A.
1,25-dihydroxyvitamin d
The 25(OH)D generated in the liver is released into the bloodstream and delivered to the
kidney, which is where vitamin D is activated. The binding of sDBP to the particular
receptors megalin and cubilin at the apical membrane of tubule epithelial cells causes
25(OH)D reabsorption in the kidney. 25(OH)D may be hydroxylated at the C-1 position
in the kidney, resulting in 1,25(OH)2 D, the biologically active form of vitamin D.
25-hydroxyvitamin D-1-hydroxylase (1-hydroxylase) is the enzyme responsible for this
reaction. The 1-hydroxylase is now known to be expressed in a variety of extrarenal
tissues, including skin, brain, colon, and adipocytes.
24,25-Dihydroxyvitamin D
Another dihydroxylated metabolite of vitamin D produced from 25(OH)D is 24,25(OH)2
D. The physiological role of 24,25(OH)2 D is controversial. Studies support that
24,25(OH)2 D is a catabolite of 25(OH)D and has no physiological functions other than
to inactivate circulating 25(OH)D (Tuckey et al., 2019).
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Figure.3: metabolism of vitamin d in liver and kidney (zemplini et al 2013).
1.4.4 Catabolism and excretion of vitamin D
The active metabolite 1,25(OH)2 D needs to be catabolized for excretion. The C-24
oxidation pathway is a major catabolic pathway for vitamin D metabolites in target tissues.
1,25(OH)2 D undergoes 24-hydroxylation and oxidative cleavage of the side chain to
produce 1,24,25(OH)3 D and form 24-oxo-1,25(OH)2 D, 1,25(OH)2 D-26,23-lactone, and
1,25,26(OH)3 D.
All of the metabolites are thus targeted for excretion. Vitamin D and its metabolites are
primarily excreted in the feces with the aid of bile salts. In humans, radioactive
24,25(OH)2 D is primarily eliminated in the feces as its glucuronide and sulfate form,
which are more polar metabolites. The half-life of the active metabolite is biphasic, with
only half of the administered radioactive 1,25(OH)2 D 3 remaining in the plasma within 5
min, followed by a slower component of the half-life with elimination in approximately
10 h (zemplini et al 2013).
1.5 Sources of vitamin D
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However, since it was first defined as a vital nutrient and dietary intake is needed in given
circumstances, therefore it's clas-sified as a vitamin and Dietary intake should be (600 IU)
in daily basis for young males and females .
Sunlight has long been the primary supply of vitamin D for most humans; however, oily
fish, such as salmon3, is a great source of vitamin D3, with 500–1000 IU per 3.5-ounce
dose. Salmon farmed in the United States, on the other hand, receive relatively little
vitamin D in their pelleted feed and have just 10–25 percent of the vitamin D 3
concentration seen in wild-caught salmon.
Milk, orange juice, various breads, margarines, cheeses, and yogurts are among the 12
foods fortified with vitamin D in the United States. Milk is fortified with vitamin D3 in
Europe, Sweden, and Finland, while most other European nations still prohibit vitamin D
fortification of dairy products. Margarine and other grains are also good sources
(Lamberg-Allardt, 2006).
Table.1: Dietary intake of vitamin D (Lamberg-Allardt, 2006).
1.6 Vitamin D synthesis and metabolism
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Figure.4: Vitamin D endogenous synthesis and metabolism. Endogenous vitamin D
synthesis occurs primarily through sunlight exposure which produces pre-vitamin D3.
It is hydroxylated in the liver and then in the kidney, producing 1,25D (1,25
dihyroxyvitamin D), the physiologically active form of vitamin D which acts in target sites
in bone and immune cells, as well as liver cells (Keane et al., 2018).
1.7 Physiological and biological Functions of vitamin D
The Main function of vitamin D is protecting the homeostasis of calcium and phosphorus
in the body tissues. Which Calcium is required in some physiological functions, like
blood clotting, neurotransmission, muscle contracting, and as a cofactor for enzymes.
And phosphorus is a constituent of ATP, nucleic acids, and membrane lipids.
The homeostasis of calcium and phosphorus will be achieved by increasing the absorption
of calcium in the gut, also by increasing calcium and phosphorus levels in the plasma by
increasing their mobility from bones, and by increasing the reabsorption of calcium ions
from the distal tubules, then their excretion will be decreased (Turner et al., 2012).
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The regulation of plasma calcium levels can act directly on pancreatic beta cells, which
regulate the secretion and synthesis of insulin, so this can improve glycemia.
There are some other biological functions of vitamin D, Which called noncalcemic
functions, such as immunomodulation, anti-inflammation, antifibroitic, and antioxidant.
And also it is important for maturation of white blood cells that is required for immunity
responses. it control genes which are responsible of cell proliferation, cell differentiation,
apoptosis and angiogenesis of a number of specific cells of the body (Jolliffe et al., 2013).
Also Vitamin D is important for the prevention of other disorders such as cancers; It
reduces colon,breast and ovarian cancer by 50%, autoimmune disease such as multiple
sclerosis, insulin dependent diabetes mellitus and rheumatoid arthritis, Also has a vital role
in preventing infection (Grant, 2006).
1.8 Vitamin D deficiency
Insufficiency of vitamin d affects almost %50 of the worldwide population, In all ages and
ethnicities nearly one billion people in the world have dificiency in the vitamin d levels in
the body. So we can say it is a pandamic hypovitaminosis.
Prevalence and detection of vitamin d dificiency
Only measuring the circulation amounts of 25(OH)D, which is created in the liver, can tell
if a person is vitamin D adequate, deficient, or inebriated. It is a measure of vitamin D
status with a half-life of 2 weeks in the blood. Although, in order to become active as
[1,25(OH)2 D], 25(OH)D must undergo further hydroxylation in the kidney.
Vitamin D status should never be determined using 1,25(OH)2 D concentrations in the
blood. The reasons for this are because 1,25(OH)2 D has a half-life of 4 hours in the
circulation, its concentrations are 1000 times lower than 25(OH)D, and, most crucially,
when a person becomes vitamin D deficient, (PTH) secretion increases, stimulating the
kidney to make more 1,25(OH)2 D. When a person is deficient in vitamin D and their
25(OH)D levels drop, their 1,25(OH)2 D levels stay in the normal range, if not slightly
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increased. As a result, 1,25(OH)2 D concentrations are ineffective and can cause clinicians
to believe that patients are vitamin D deficient when they are actually severely deficient
(Mogire et al., 2020).
The risk of some disorders will increase due to it is deficiency, such as
hyperparathyroidism, rickets, osteomalacia, common cancers, autoimmune disease and
infectious disease. The indication of vitamin D deficiency in the blood is a 50 nmol/L, or
20 ng/mL concentration of 25(OH)D (Holick, 2007).
Stages of vitamin D deficiency
According to the level of 25(OH)-D, there are three stages of vitamin D deficiency.
Stage 1
The amount of 25-OH-D drops, leading in hypocalcemia and euphosphatemia, while the
level of 1,25-OH2 -D may rise or unchanged.
Stage 2
The level of 25-OH-D continues to decline, PTH acts to maintain calcium through bone
demineralization, the patient remains eucalcemic and hypophosphatemic, and the skeletal
alkaline phosphatase level increases slightly, and the patient remains eucalcemic and
hypophosphatemic.
Stage 3
Severe 25-OH-D deficiency with hypocalcemia, hypophosphatemia, and increased
alkaline phosphatase, bones show clear signs of demineralization (Holick, 2007).
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Figure.5 :Causes of vitamin D deficincy and potential health consequences (Holick and
Chen, 2008).
Clinical signs of vitamin D deficiency
1-Dietary calcium absorption from the gut decreases from 30%–40% to 10%–15% when
there is vitamin D deficiency.
2-Low concentrations of 25-OH-D trigger the release of PTH in older infants, children,
and adolescents in an inverse relationship not typically seen with young infants; the
increase in PTH mediates the mobilization of calcium from bone, resulting in a reduction
of bone mass; as bone mass decreases, the risk of fractures increases.(wagnar2008).
3-Rickets
4-Enlargement of the skull, joints of long bones, and rib cage; curvature of spine and
femurs; generalized muscle weakness
5-Osteomalacia and osteopenia
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6-Abnormal immune function with greater susceptibility to acute infections and other
long-latency disease states..
7-Osteoporosis, a condition characterized by reduced bone mass denisty and increased
bone fragility.
7-Muscle aches, weakness, and twitching (fasciculation), due to reduced blood calcium
(hypocalcemia).
8-Periodontites, local inflammatory bone loss that can result in tooth loss
9-Respiratory infection and Covid-19: Vitamin D deficiency may increase the risk of
severe acute respiratory infections and COPD.
10-schizophrenia: Vitamin D deficiency is associated with the development of
schezophrenia, People with schizophrenia generally have lower levels of vitamin D
(Zhang et al., 2020).
1.9 Treatment of vitamin D dificiency
Many patients and physicians are wary of sun exposure guidelines due to concerns about
skin cancer. However, twice a week exposure of the arms and legs for 5 to 30 minutes
between 10 a.m. and 3 p.m. may be sufficient to prevent vitamin D deficiency.
Salmon, sardines, mackerel, tuna, cod liver oil, shiitake mushrooms, and egg yolk are all
natural sources of vitamin D. Milk, orange juice, baby formulae, yogurts, butter,
margarine, cheeses, and breakfast cereals are all fortified foods. 400 IU of vitamin D1, D2,
or D3 are often found in over-the-counter multivitamin pills. Vitamin D 3 pills in 400,
800, 1000, and 2000 IU doses are also available over-the-counter. Vitamin D 2
(ergocalciferol), which delivers 50,000 IU per pill, and vitamin D 2 liquid (drisdol), which
provides 8000 IU/mL, are two prescription-strength supplemental options.
19
Treatment recommendations vary depending on the cause of the deficiency. For example,
patients with chronic kidney disease are recommended to have 1000 IU of vitamin D 3
daily. The expected blood level response to a given vitamin D dose varies, probably
because of differences in the cause of the deficit as well as the starting point for correction.
A recent editorial reported that supple-mental intakes of 400 IU per day of vitamin D
increase 25(OH)D concentrations by only 2.8 to 4.8 ng/mL (7–12 nmol/L) and that daily
intakes of approximately 1700 IU are needed to raise these concentrations from 20 to 32
ng/mL (50–80 nmol/ L). (Adami et al., 2011).
Table.2: RDI of vitamin D (Norman and Bouillon, 2010).
1.10 Vitamin D and Mortality
Vitamin D has a significant immunomodulatory capacity; high VDR levels in
macrophages, dendritic cells, T lymphocytes, and B lymphocytes support the idea that it
plays a key role in fighting germs and avoiding autoimmune disorders and chronic
inflammation. 1,25(OH)2 D has been shown to improve the immune system (e.g.,
synthesis of beta-defensin and cathelicidin, and modification of production of anti20
inflammatory cytokines: IL-4, IL-5) [7,9,45–52] and enhances lymphocytic activity.
These findings assist to explain several of vitamin D's activities.
The availability of 25 (OH)D for endocrine, autocrine, and paracrine pathways appeared
to be critical in lowering the risks of cancers, autoimmune diseases (e.g., multiple
sclerosis, type 1 diabetes), asthma and recurrent wheezing, CVD and stroke, systemic
lupus erythematosus, atopic dermatitis, neurocognitive dysfunction such as Alzheimer's
disease, autism, and infectious diseases such as influenza and tuberculosis. It was also
suggested that low 25(OH)D concentrations are related to significantly increased risk of
mortality (Pilz et al., 2009).
Vitamin D deficiency and insufficiency are serious health problems that affect people all
over the world. Many chronic disorders have been linked to vitamin D deficiency
(25(OH)D 20 ng/mL) and insufficiency (25(OH)D: 20–29 ng/mL). Each 10 ng/mL
decrease in 25(OH)D was linked to a 16% greater risk of all-cause death(Vitamin D
deficiency and mortality). Some studies found that long-term vitamin D supplementation
(800 IU per day, for example) is beneficial in lowering overall mortality, but not if vitamin
D is taken for less than three years (Mithal et al., 2009).
1.11 Clinical benefits of vitamin D
Vitamin D and Cardiovascular Disease
Vitamin D receptors may be found in vascular smooth muscle, endothelium, and
cardiomyocytes, and they may have a role in heart disease. Low vitamin D levels have
been linked to high blood pressure, coronary artery calcification, and existing
cardiovascular disease in observational studies. In another study, which followed men and
women for 4 years, patients with low vitamin D concentrations (<15 ng/mL) were three
times more likely to be diagnosed with hypertension than those with high concentrations
(>30 ng/mL).
21
In another study of patients with hypertension who were exposed to ultraviolet B radiation
three times a week for 3 months, 25-hydroxyvitamin D levels increased by approximately
180%, and blood pressure became normal (both systolic and diastolic blood pressure
reduced by 6 mm Hg). Vitamin D deficiency is associated with congestive heart
failure and blood levels of inflammatory factors, including C-reactive protein and
interleukin (Norman and Powell, 2014).
Vitamin D and the Risk of Cancer
Observational research in people and animal models both support the idea that vitamin D
is helpful in cancer prevention and survival. The mechanism of action is most likely related
to its involvement in cell growth and differentiation control, It decreases cell proliferation
and increases cell differentiation, stops the growth of new blood vessels, and has
significant anti-inflammatory effects (Carlberg and Velleuer, 2021).
Mental health
Living at higher latitudes increases the risk of schizophrenia. It has been proposed that in
utero vitamin D deficiency alters brain development and It has also been suggested that
vitamin D plays a role in altering serotonin production, which may explain the association
with depression and vitamin D deficiency (Humble, 2010).
Lung function
Lung function has been related to vitamin D status. Men and women who had a 25(OH)D
>35 ng/mL had a 176 cc increase in their forced expiratory volume. Children mothers at
high risk of vitamin D deficiency in the inner city of Boston were reported to have a higher
risk of developing wheezing illnesses (Gruber-Bzura, 2018).
Influenza
The seasonal stimulant that drives influenza epidemics in the winter months might be
influenza VDD. Children given a daily vitamin D supplement of 1200 IU had a 40% lower
risk of influenza type A than those given a placebo in a Japanese randomized controlled
study (Gruber-Bzura, 2018).
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1.12 Covid19
Infection with the virus that causes SARS-CoV-2 (severe acute respiratory syndrome
coronavirus-2) has achieved pandemic status in 2020, COVID-19 poses a huge threat to
society and health-care systems across the world, with more than 700,000 deaths .
1.12.1 Vitamin D and Covid
The current epidemic and rapid spread of the severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) poses a global danger and is a major source of concern, with
an unknown result. Due to a lack of effective treatment, chemoprevention, and
immunization, concentrating on the rapid repurposing of current medications offers the
best opportunity for containing the pandemic. there have been no reports on the vitamin D
status of impacted people so far. On the other hand, a vast number of well-established
studies have shown that vitamin D has antiviral properties, including the ability to interfere
directly with viral replication as well as operate as an immunomodulator and antiinflammatory. (Bilezikian et al., 2020).
The latter effects may be critical for their presumed beneficial benefits during SARS-CoV2 infection, since it appears that SARS-CoV-2 exploits immune evasion strategies first,
followed by immunological hyperreaction and cytokine storm in certain individuals.
As a common pathogenic mechanism of acute respiratory disease syndrome (ARDS) and
systemic inflammatory response syndrome (SIRS) development, regardless of the
etiological reason Vitamin D has been demonstrated to protect patients from a range of
ailments, including pneumonia, cytokine hyperproduction, and ARDS.
Vitamin D has recently been presented as a potential repurposed medication for influenza
A H5N1 virus-induced lung damage (3). In addition, several research show that vitamin
D can be used as an adjuvant treatment with antiretroviral drugs in HIV patients (Mitchell,
2020).
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Furthermore, vitamin D pretreatment reduced lung permeability in animal models of
ARDS via modulating renin-angiotensin system activity and ACE2 expression . Vitamin
D's significance in viral infections is also reinforced by the discovery of particular vitamin
D receptor gene (VDR) variants linked to greater susceptibility to respiratory infections.
as well as with HIV infection progression.
These findings might be provisionally generalized to SARSCoV-2 infection due to the
absence of specific treatment and urgency to act, justifying the use of vitamin D as a viable
adjuvant therapy. The suggestion of extensive supplementation as a potential prophylactic
might also be evaluated from a public health standpoint. Because even high dosages of
vitamin D are well tolerated and safe, this technique adheres to the primum non nocere
principle (Mitchell, 2020).
Investigations on vitamin D status and VDR polymorphisms of affected subjects could
contribute to explain “unusual be- havior” of SARS-CoV-2 spreading and a tremendous
variety of COVID-19 clinical presentations and outcomes.
1.12.2 Role of the vitamin D in covid
VitD supplementation protects against acute respiratory tract infections, according to a
major meta-analysis of 25 randomized controlled trials, especially in individuals with
extremely low VitD levels (25(OH)D 10 ng/mL).
Vitamin D deficiency has been linked to viral respiratory tract infections and acute lung
damage in epidemiological investigations.
More than half of COVID19 cases and nearly 70% of COVID19 deaths in Chicago were
found among AfricanAmericans ,who are at higher risk for vitamin D deficiency (Panfili
et al., 2021).
In respiratory epithelial cells and immunological cells, vitamin D receptors (VDRs) are
widely dispersed (B cell, T cell, macrophages, and monocytes). In the bronchial epithelium
24
and immune cells, 25-hydroxyvitamin D (25OHD), the predominant circulating form of
vitamin D, may be converted to the active form (1,25-dihydroxyvitamin D).
Vitamin D's protection against COVID-19 is linked to a suppressed cytokine response and
a lower severity/risk of ARDS. Regular oral vitamin D2 /D 3 consumption (at doses up to
2000 IU/d without extra bolus) is safe and protective against acute respiratory tract
infection, according to findings from a meta-analysis, notably in people with vitamin D
insufficiency (Ali, 2020).
1.13 Drug interactions with vitamin D
The first hydroxylation event that transforms both vitamin D 2 and D 3 to the predominant
circulating form of vitamin D, 25-hydroxycholecalciferol (25(OH)D), takes place in the
liver. Hepatic 25-hydoxylases, which comprise the cytochrome P450 (CYP) enzymes 2R1,
3A4, and 27A1, are responsible for this conversion. 1,25-dihydroxycholecalciferol
(1,25(OH)2 D), the active steroid hormone form of vitamin D, is generated from 25(OH)
D at both the local tissue level and in the kidney by an extra hydroxylation of 25(OH)D
through 1-hydroxylase (CYP27B1),(Antunes et al., 2015).
Many medicines have a phase 1 biotransformation called CYP3A4, which transforms
ergo-cholecalciferol to 25(OH)D. As a result, vitamin d might affect the metabolism that
need CYP3A4 activation.
Also some drugs like bile acid sequestrants and lipase inhibitors will interfere with vitamin
d absorption (Antunes et al., 2015).
2. Conclusion
This research review showed that vitamin D has an essential pharmaceutical role in human
body.
Closer attention should be paid to vitamin D deficiency in medical and pharmaceutical
practice than has been the case hitherto. The data available to date on vitamin D from
experimental, ecological, case-control, retrospective and prospective observational
25
studies, meta-analysis as well as smaller intervention studies, are significant and confirm
the sunshine vitamin’s essential role in a variety of physiological and preventative
functions
In summary, given the high prevalence of vitamin D deficiency and in order to rapidly,
safely, and significantly raise serum concentrations, high-dose vitamin D intervention with
potential benefit in decreasing risk of COVID-19 severity and mortality is suggested,
which is a safe and noninvasive treatment. Patients would take large doses of vitamin D
for a week, followed by several thousand IU/d vitamin D for a period of 2 weeks.
This will provide a quick and sustainable restoration of serum vitamin D levels, thus,
potentially triggering an improvement in clinical status and prognosis. However,
prospective clinical studies are required to address this speculation and overcome the
obstacles in our current understanding of vitamin D role as an adjuvant therapy in patients
with COVID-19.
In this study it was shown that vitamin D is considered one of the essential vitamins in
living systems.
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