Sunlight, the glaring brightness and the burning heat is all that are remembered forever.
This giant torch over the planet also gifts us vitamin D with every ray of light. Isn't that
an amazing gift that is never boasted about Production of Vitamin D is initiated when the
skin is exposed to UV-B present in the sunlight wherein 7-dehydrocholesterol, is absorbed
and converted into previtamin D3 that gets transformed into vitamin D3. UV-B radiation helps
the previtamins and vitamins for its conversion into various photo products consisting unique
biologic properties therefore, they absorb UVB radiations. Levels of vitamin D are influenced
by seasonal variations, latitude, altitude, air pollution, skin pigmentation, ageing, etc. Metabolism
of vitamin D takes place in the liver where it gets converted into 25 hydroxy vitamin D. 25 hydroxyvitamin
is a major circulating form of vitamin D.
Unusual Roles of Vitamin D - Immunity and Heart Disease
1,25-dihydroxyvitamin D is a biologically active form present in kidneys. Cells and tissues in the body
consist of vitamin D receptor (VDR) and are able to produce 1,25-dihydroxyvitamin D. 1,25-dihydroxyvitamin
D stimulates intestinal calcium absorption and regulates other metabolic functions and skeletal health.
It also influences various biological pathways that are associated with vitamin deficiency and helps
recognize the increased risk of many diseases such as cardiovascular diseases, autoimmune diseases,
infectious diseases, etc. Apart from the best-known functions of vitamin D in absorption of calcium and
bone health, vitamin D also plays different roles in Immunity and Heart Diseases.
Vitamin D and Immune Function
The immune system functions to protect the body/host from the environmental agents that are harmful
for our survival such as microbes or chemicals and thus preserve the integrity of the body. This defense
system works on its ability to recognize and differentiate between self and non-self cells, organisms and
substances. Immune response is classified as innate immunity and specific/adaptive immunity.
Functioning of innate immunity depends upon the group of proteins and phagocytic cells that recognize
the pathogens and take quick action on the invaders. It provides a general defense against foreign bodies
or invaders, hence called as non specific immune system. Whereas, adaptive immunity is specific to a
particular pathogen. Therefore, it is also called as learned defense system which can also fight against
those bacteria and viruses that reoccur. And in vertebrates, adaptive immune responses are activated
with the help of innate immunity. Both the defense system work together and are closely connected.
Tasks carried by the immune system are:
- Recognizing harmful substances from the environment.
- Neutralizing different classes and species of pathogens that invade and remove them from body,
- Fights against the body's own cells that are changed due to diseases such as cancerous cells,
Roles of Vitamin D in Immunity
Three potential sources that are responsible for the production of Vitamin D are nutritional sources,
UVB-dependent endogenous production and supplements. Synthesis of vitamin D is maximum in the
skin when exposed to UVB whereas, minimum is derived from dietary sources.
Metabolism of Vitamin D
In human skin, cholecalciferol (vitamin D3) is biologically inactive and binds with vitamin D that is
attached to proteins and albumin. This then enters the circulation and undergoes hydroxylation in
the liver with the catalysis of enzymes CYP2R1 and CYP27A1. This mechanism results in the production
of inactive form of 25-hydroxyvitamin D which represents the vitamin D metabolite that circulates and
is the most important parameter to identify the levels of vitamin D in humans. Further conversion of the
inactive form into biologically active form calcitriol (1,25(OH), D) is carried out in the kidney with the
help of enzyme 1-a-hydroxylase (CYP27B1). This enzyme is controlled by parathyroid hormone and
phosphaturic hormone called fibroblast growth factor 23 (FGF-23). Renal loop plays a major role in the
circulating levels of calcitriol and in metabolizes into inactive, water soluble form, calcitroic acid. Immune
cells and other cell types can convert the inactive circulating form 25(OH)D into the active hormone
in an autocrine and paracrine manner.
Vitamin D and the Innate Immune system
Recent studies specify the role of calcitriol that strengthens the antimicrobial effects of macrophages
and monocytes. They are the essential cells that fight against pathogens such as Mycobacterium tuberculosis.
Complex of calcitriol, VDR, and retinoid X receptor not only plays a role in enhancing the capabilities of
innate immune cells, but also coordinates to activate the transcription of antimicrobial peptides such as
defensin B-2 (DEFB) and cathelicidin antomicrobial peptide (hCAP18). New findings also report that the
status of vitamin D is essential for regulation of antimicrobial protein levels and also may be important in
the infection control. Low concentrations of calcitriol are linked with increased mortality caused by severe
infections in patients with renal diseases. Low level of serum 25(OH)D is associated with various diseases
and infections such as upper respiratory tract infections, influenza, chronic obstructive pulmonary diseases,
asthma, etc. Innate antigen presenting cells (APCs) in particular dendritic cells (DC) that fights against
microorganisms, also play an important role in targeting for the immune modulatory effects
Vitamin D and the Adaptive Immune System
Adaptive immune cells that demonstrate the effects of Vitamin D involve an expression of the nuclear VDR
along with vitamin D-activating enzymes in both T-cells and B-cells. These cells up-regulate significant
expression of VDR. The rate of regulation increases to around 500 vitamin D responsive genes that manifest
great impact on differentiation and proliferation of these cells.
In B-cell, anti-proliferating effects of calcitriol such as inhibition of differentiation, proliferation, etc. were
initiated indirectly. However, direct effects of B-cell homoeostasis, provides additional functions such as
inhibition of memory, plasma cell generation and promotion of apoptosis of immunoglobulin-producing B cells.
T-cells of adaptive immunity are another important target for immunomodulatory effects of varied forms
of vitamin D. Potential mechanisms of Vitamin D that may influence T-cells are:
1. System calcitriol helps in direct endocrine effects on T-cells mediation.
2. Direct, intracrine conversion of 25(OH)D to calcitriol by T-cells.
3. Localized APCs affected by calcitriol have indirect effects on antigen presentation to mediated T-cells.
Roles of vitamin D in Heart Diseases
Cardiovascular diseases (CVD), are conditions that narrow or block blood vessels that can lead to wide
range of diseases and disorders that include cardiac muscle and
vascular system supplying the heart, brain, and other organs. Risk of developing CVD depends upon various
aspects, may it be metabolic, genetic, hemodynamic, inflammatory factors or lipid abnormalities, obesity,
physical inactivity, lifestyle and behavioral patterns.
Vitamin D and Cardiovascular Diseases
It is interesting to understand that the potential functions of vitamin D are also associated with cardiovascular
diseases (CVD). One of the factors associated with CVD is vitamin D deficiency that includes diseases like hypertension
heart failure, ischemic heart diseases, etc. Though the mechanism of vitamin D deficiency exerting its cardio
and vasculoprotective effects are unknown, regulatory effects on renin-angiotensin system (RAS), glycemic control,
inflammatory cytokines, levels of parathyroid hormone (PTH) and calcium deposition in vascular smooth muscle etc.
can be considered.
Presence of vitamin D receptor in multiple tissues and multiple metabolic pathways in our body has been found
to benefit health by reducing the risk of cardiovascular diseases through its confounding effects. The mechanism
which prevents cardiovascular diseases, involve vitamin D receptor that suppresses or decreases the levels of
prostaglandins, cyclooxygenase-2, C-reactive protein, interleukin-6, tumor necrosis factor-alpha (TNF-a), matrix
metalloproteinase-9, and increases the expression of interleukin-10. This helps inhibit inflammation that reduces
the risk of atherosclerosis, therefore prevents cardiovascular diseases. Vitamin D decreases the Ca** cellular
influx and increases the level of Matrix Gla-Protein IMGP) that is found in various tissues regulates to inhibit the
proliferation of vascular smooth muscle and vascular calcification
Vitamin D as a negative regulator of Renin
Inappropriate stimulation of RAS is highly associated with hypertension and CVD. Clinical study involving knockout
mice favored the role of vitamin D in the regulation of RAS. Increased production of renin and angiotensin II with
lack of VDR in the mice, manifested hypertension, cardiac hypertrophy. This can be avoided by treating the mice
with an angiotensin converting enzyme inhibitor or an angiotensin II receptor blocker. This proves that renin biosynthesis
is suppressed by vitamin D. Vitamin D plays a major role in inhibiting renin expression in-vitro and declined activation
of reninangiotensin aldosterone system (RAAS) helps regulate blood pressure and volume homeostasis. It also develops
specific cardio selective vitamin D compounds for treating hypertension without calcemic effects.
Vitamin D as a factor in Improving insulin sensitivity
Pancreas consists of VDR and 1-a-hydroxylase. Vitamin D circulating as 25(OH)D converts into 1,25(OH),D
so as to work as a pancreatic hormone. Several studies have suggested that deficiency in vitamin D is associated
with insulin resistance or impaired insulin secretion, thus low levels of vitamin D possess increased risk of Diabetes.
Increase in the expression of insulin sensitivity regulates glucose metabolism. Thus, vitamin D is responsible
for mechanisms that support in prevention of cardiovascular diseases.
Vitamin D as a direct factor on cardiac tissues and its vasculature.
The role of vitamin D significantly affecting vasculature suggests positive correlation between Vitamin D and
arterial compliance. Clinical studies evaluated that mesenchymal multipotent cells were used by 1,25
dihydroxyvitamin D to inhibit profibrotic markers in-vitro, This implicated that vitamin D may also manifest
direct effect on the vasculature in response to injury. Therefore, diabetic patient ingested with doses of vitamin
D manifested significant improvement in endothelial function and decrease in blood pressure. This study helped
in administration of vitamin D dosage in subjects with heart failure showed significant reductions in
inflammatory cytokines.
1a-hydroxylase is produced by various cell types in the body such as vascular smooth muscle cells, endothelial
cells, cardiomyocytes. This 1-a-hydroxylase converts 25 hydroxyvitamin D to calcitriol which is the natural ligand
of the vitamin D receptor. This calcitriol is the factor that manifests to inhibit vascular smooth muscle cell,
proliferation, decrease coagulation, regulate the renin angiotensin system and exhibit anti-inflammatory properties.
Conclusion
A strong association is reported between vitamin D insufficiency and an increased risk of cardiovascular
diseases, diabetes, etc. Deficiency of vitamin D is a warning alarm that strikes and influences an individual
to an increased risk of arteriosclerosis, hypertension, heart failure or sudden cardiac death. Status of vitamin
D plays a significant role in the prevention of CVD or in its treatment.
Guidance on vitamin D management should be inculcated in our society as there are no guidelines for screening
and treating vitamin D insufficiency. In general, increasing the levels of vitamin D with a daily supplement, an intake
of at least 1000 IU is recommended." This intake recommendation can bring a great difference especially in areas
with increased latitude from the equator or during winter season.
Thyrocare offers Vitamin D Profile Testing for the qualitative and quantitative analysis of Vitamin D total,
Vitamin D2 and Vitamin D3 using advanced and sophisticated automated technology using
enzyme-linked immunosorbent assay (ELISA) at highly affordable rates.
