1. Vitamin D References
By- Chintan Chavda
1. Vitamin D3 in Infection
―Subclinical vitamin D deficiency and nonexclusive breastfeeding in the first
4 months of life were significant risk factors for severe ALRI (acute lower
respiratory infection) in Indian children‖.
Wayse V, Yousafzai A, Mogale K, Filteau S, Association of subclinical vitamin D deficiency with severe acute lower
respiratory infection in Indian children under 5 y: Eur J Clin Nutr. 2004 Apr;58(4):563-7.
―We found a high rate of vitamin D deficiency in critically ill children‖
Madden K, Feldman HA, Smith EM, Gordon CM, Keisling SM, Sullivan RM, Hollis BW, Agan AA, Randolph AG, Vitamin
D Deficiency in Critically Ill Children; Pediatrics. 2012 Aug 6.
―We conclude that a large bolus dose of vitamin D is associated with
reductions in two inflammatory cytokines, IL-6 and TNF-α. This study
supports the concept that vitamin D may help regulate inflammation in CF‖
Grossmann RE, Zughaier SM, Liu S, Lyles RH, Tangpricha V, Impact of vitamin D supplementation on markers of
inflammation in adults with cystic fibrosis hospitalized for a pulmonary exacerbation; Eur J Clin Nutr. 2012 Jul 18. doi:
10.1038/ejcn.2012.82
―This suggests that vitamin D(3) may down regulate the recruitment and
activation of T-cells through CXC chemokines at the site of infection and may
act as a potential anti-inflammatory agent‖.
Selvaraj P, Harishankar M, Singh B, Banurekha VV, Jawahar MS. Effect of vitamin D(3) on chemokine expression in
pulmonary tuberculosis; Cytokine. 2012 Jul 14.
―A truncated isoform of vitamin D binding protein (VDBP) is present at
significantly reduced levels in the SF of oligoarticular patients at risk of
disease extension, relative to other subgroups (p<0.05). Furthermore,
sialylated forms of immunopurified synovial VDBP were significantly reduced
in extended oligoarticular patients (p<0.005).Reduced conversion of VDBP to
a macrophage activation factor may be used to stratify patients to determine
risk of disease extension in JIA patients‖.
Gibson DS, Newell K, Evans AN, Finnegan S, Manning G, Scaife C, McAllister C, Pennington SR, Duncan MW, Moore
TL, Rooney ME, Vitamin D binding protein isoforms as candidate predictors of disease extension in childhood arthritis.
J Proteomics. 2012 Jul 6.
―This study opens up the issue of recognising severe vitamin D deficiency
( < 25 nmol/l) as a possible risk factor for diabetic foot infections and the
need for vitamin D supplementation in such patients for a better clinical
outcome‖.

2. Tiwari S, Pratyush DD, Gupta B, Dwivedi A, Chaudhary S, Rayicherla RK, Gupta SK, Singh SK.
Prevalence and severity of vitamin D deficiency in patients with diabetic foot infection. Br J Nutr. 2012 Apr 3:1-4.
―25-hydroxycholecalciferol deficiency was associated with active tuberculosis
(odds ratio 2·9 [95% Cl 1·3—6·5], p=0·008), and undetectable serum 25-
hydroxycholecalciferol (<7 nmol/L) carried a higher risk of tuberculosis (9·9
[1·3—76·2], p=0·009). 25-hydroxycholecalciferol deficiency may contribute
to the high occurrence of tuberculosis in this population. Polymorphisms in
theVDR gene also contribute to susceptibility when considered in
combination with 25-hydroxycholecalciferol deficiency‖
Robert J Wilkinson PhD a b, Martin Llewelyn MRCP b, Zahra Toossi MD a, Punita Patel MSc b, Geoffrey
Pasvol DPhil b, Ajit LalvaniMRCP c, Dennis Wright PhD b, Mohammed Latif MRCP b, Dr Robert N Davidson MD b.
Influence of vitamin D deficiency and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in
west London: a case-control study; The Lancet, Volume 355, Issue 9204, Pages 618 - 621, 19 February 2000
―We report here that TLRactivation of human macrophages up-regulated
expression of the vitamin D receptor and the vitamin D1–hydroxylase genes,
leading to induction of the antimicrobial peptide cathelicidin and killing of
intracellular Mycobacterium tuberculosis. We also observed that sera from
African-American individuals, known to have increased susceptibility‖.
Toll-Like Receptor Triggering of a Vitamin D–Mediated Human Antimicrobial Response; www.sciencexpress.org / 23
February 2006 / Page 1/ 10.1126/science.1123933
―Observational studies have demonstrated important links between rickets
or vitamin D deficiency and higher rates of infectious diseases that have
significant burden of disease, such as pneumonia and tuberculosis.
SEMIRA MANASEKI, Vitamin D for Childhood Pneumonia, INDIAN PEDIATRICS; VOLUME 49__JUNE 16, 2012
―Increased production of 1,25- dihydroxyvitamin D3 result in synthesis of
cathelicidin, a peptide capable of destroying M. tu-berculosis as well as other
infectious agents. When serum levels of 25-hydroxyvitamin D fall below 20
ng per milliliter (50 nmol per liter), the monocyte or macrophage is
prevented from initiating this innate immune response, which may explain
why black Americans, who are often vitamin D–deficient, are more prone to
contracting tuberculosis than are whites, and tend to have a more
aggressive form of the disease‖.
2. Vitamin D3 in Immunity System
―Vitamin D(3) affects both the innate as well as adaptive immune responses.
Epidemiological studies have established that vitamin D(3) deficiency plays
an important role in tuberculosis (TB) and viral influenza prevalence as well
as susceptibility to active disease in TB. Vitamin D(3) status has been

3. associated with the clinical course of HIV infection and drug interaction with
anti-retroviral therapy‖.
Khoo AL, Chai L, Koenen H, Joosten I, Netea M, van der Ven A. Radboud University Nijmegen Medical Center,
Department of Laboratory Medicine, Laboratory Medical Immunology , Nijmegen , Netherlands. Translating the role of
vitamin D(3) in infectious diseases; Review of infectious diseases vitamin D trials – Feb 2012
―An efficient immune response against the intracellular pathogen
Mycobacterium tuberculosis is critically dependent on rapid detection of the
invader by the innate immune response and the activation of the adaptive
immune response. Toll-like receptors (TLRs) contribute to innate immunity
by the detection of Mycobacteria-associated molecular patterns and
mediating the secretion of antibacterial effector molecules. TLRs influence
the adaptive immune response by upregulation of immunomodulatory
molecules supporting the development of a Th1-biased T cell response. In
this manner, activation of TLRs contributes to defense against microbial
infection.‖
Stenger S, Modlin RL, Control of Mycobacterium tuberculosis through mammalian Toll-like receptors; Curr Opin
Immunol. 2002 Aug;14(4):452-7.
―The net effect of the vitamin D system on the immune response is an
enhancement of innate immunity coupled with multifaceted regulation of
adaptive immunity. Epidemiological evidence indicates a significant
association between vitamin D deficiency and an increased incidence of
several autoimmune diseases, and clarification of the physiological role of
endogenous VDR agonists in the regulation of autoimmune responses will
guide the development of pharmacological VDR agonists for use in the clinic.
The antiproliferative, prodifferentiative, antibacterial, immunomodulatory
and anti-inflammatory properties of synthetic VDR agonists could be
exploited to treat a variety of autoimmune diseases, from rheumatoid
arthritis to systemic lupus erythematosus, and possibly also multiple
sclerosis, type 1 diabetes, inflammatory bowel diseases, and autoimmune
prostatitis.‖
Nat Clin Pract Rheumatol. 2008 Aug;4(8):404-12. Epub 2008 Jul 1. Control of autoimmune diseases by the vitamin D
endocrine system. Adorini L, Penna G.
―As the vitamin D receptor is expressed on immune cells (B cells, T cells,
and antigen-presenting cells), and these immunologic cells are all capable of
synthesizing the active vitamin D metabolite, vitamin D has the capability of
acting in an autocrine manner in a local immunologic milieu. Vitamin D can
modulate the innate and adaptive immune responses. Deficiency in vitamin
D is associated with increased autoimmunity and an increased susceptibility
to infection. As immune cells in autoimmune diseases are responsive to the

4. ameliorative effects of vitamin D, the beneficial effects of supplementing
vitamin D-deficient individuals with autoimmune disease may extend beyond
the effects on bone and calcium homeostasis‖.
Aranow C., Vitamin D and the immune system; J Investig Med. 2011 Aug;59(6):881-6.
―Vitamin D3 has wide-ranging effects on the immune system. Due to its
actions on both Th1 and Th2 mediated immune responses, vitamin D
deficiency has been purported as a potential unifying factor in the rise of the
prevalence of both Th1 disorders (autoimmunity) and Th2 disorders
(allergies) over a similar time span. Vitamin D may be of particularly critical
importance at early stages of development to ensure proper immune
function later in life‖.
ADVANCES in orthomolecular research, Volume 3 Issue 5 page 25-27
―Vitamin D has been linked to immune system and lung development in
utero, and our epidemiologic studies show that higher vitamin D intake by
pregnant mothers reduces asthma risk by as much as 40% in children 3 to 5
years old‖
Augusto A. Litonjua, MD, MPH, and Scott T. Weiss, MD, MS, Boston, Mass, Is vitamin D deficiency to blame for the
asthma epidemic?; J ALLERGY CLIN IMMUNOL NOVEMBER 2007.
3. Vitamin D3 in Respiratory System
―In children with asthma treated with inhaled corticosteroids, vitamin D
deficiency is associated with poorer lung function than in children with
vitamin D insufficiency or sufficiency’.
Ann Chen Wu1,2,3, Kelan Tantisira3,4,5, Lingling Li1,3, Anne L. Fuhlbrigge3,4, Scott T. Weiss3,4,5, Augusto
Litonjua3,4,5 and for the Childhood Asthma Management Program Research Group. Effect of Vitamin D and Inhaled
Corticosteroid Treatment on Lung Function in Children Am. J. Respir. Crit. Care Med. September 15, 2012 vol. 186 no.
6 508-513
―Vitamin D deficiency causes deficits in lung function that are primarily
explained by differences in lung volume. This study is the first to
provide direct mechanistic evidence linking vitamin D deficiency and lung
development, which may explain the association between obstructive lung
disease and vitamin D status‖.
Graeme R. Zosky1,2, Luke J. Berry1,2, John G. Elliot3, Alan L. James3, Shelley Gorman1,2 and Prue H. Hart,
Vitamin D Deficiency Causes Deficits in Lung Function and Alters Lung Structure; Am. J. Respir. Crit. Care Med.May 15,
2011 vol. 183 no. 10 1336-1343
4. Vitamin D3 in Digestive System
―Vitamin D receptors (VDRs) and vitamin D metabolic enzymes have been
identified in many other tissues aside from bone and the intestine,

5. suggesting involvement in the metabolism and function of many cell types.
Specifically, VDR is expressed in cells of the immune system, such as T cells,
activated B cells, and dendritic cells‖.
Augusto A. Litonjua, MD, MPH, and Scott T. Weiss, MD, MS, Boston, Mass, Is vitamin D deficiency to blame for the
asthma epidemic?; J ALLERGY CLIN IMMUNOL NOVEMBER 2007.
―The reviewed data for vitamin D and its oxygen analogue OCT indicate
genomic effects on multiple target tissues of the digestive system that
involve cell proliferation and differentiation, endo- and exocrine secretion,
digestion and absorption for maintaining optimal functions, with potentials
for health prophylaxis and therapies.‖
Eur J Drug Metab Pharmacokinet. 2008 Apr-Jun;33(2):85-100. Vitamin D and the digestive system. Stumpf WE.
―we have considered the importance of vitamin D as a real hormone
responsible for both muscle and bone strength. With aging there is a
significant reduction in the genomic and non-genomic effect of vitamin D
which has been associated with increasing incidence of falls and fractures‖.
Manuel Montero-Odasso, Gustavo Duque. Vitamin D in the aging musculoskeletal system: An authentic strength
preserving hormone; Molecular Aspects of Medicine 26 (2005) 203–219
5. Vitamin D3 in nervous system & Brain development
―The relationship of many of these diseases and aging related changes in
physiology show a U-shaped response curve to serum calcidiol
concentrations. Clinical data suggest that vitamin D3 insufficiency is
associated with an increased risk of several CNS diseases, including multiple
sclerosis, Alzheimer’s and Parkinson’s disease, seasonal affective disorder
and schizophrenia. In line with this, recent animal and human studies
suggest that vitamin D insufficiency is associated with abnormal
development and functioning of the CNS. Overall, imbalances in the
calcipherol system appear to cause abnormal function, including premature
aging, of the CNS‖.
P. Tuohimaa, T. Keisala, A. Minasyan, J. Cachat, A. Kalueff, Vitamin D, nervous system and aging; 26 March 2009;
received in revised form 4 July 2009; accepted 6 July 2009.
―Experimental data suggest that cerebral white matter is vitamin D
responsive and oligodendrocytes in the brain and spinal cord and express
vitamin D receptors. It is possible that differentiation and axonal adhesion of
oligodendrocytes are influenced by vitamin D level during brain development
and a relative lack of vitamin D may increase oligodendroglial apoptosis‖

6. Abhijit Chaudhuri, Department of Neurology, Institute of Neurological Sciences, 1345 Govan Road, Glasgow G51 4TF,
UK, Why we should offer routine vitamin D supplementation in pregnancy and childhood to prevent multiple sclerosis;
14 June 2004; accepted 24 June 2004
―The widespread distribution of 1a-OHase and the VDR suggests that
Vitamin D may have autocrine/paracrine properties in the human brain.‖
Darryl W. Eyles, Steven Smith, Robert Kinobe, Martin Hewison, John J. McGrath, Distribution of the Vitamin D receptor
and 1a-hydroxylase in human brain; Journal of Chemical Neuroanatomy 29 (2005) 21–30
―The VDR is expressed in the neurons and glial cells, and induces nerve
growth factor – exerting a potent inhibitory effect upon mitosis and
promoting cell differentiation‖.
Brown J, Bianco JI, McGrath JJ, Eyles DW. 1,25-Dihydroxyvitamin D3 induces nerve growth factor, promotes neurite
outgrowth and inhibits mitosis in embryonic rat hippocampal neurons. Neurosci Lett 2003;343:139–143.
―Vitamin D could play a significant role in the brain in a way analogous to
the neuroactive steroids, modulating neuron excitability and the production
of specific neurotropins and nervous tissue growth factors in neurons and
glial cells, inducing the production of calcium-binding proteins, and acting
through the nitric oxide system‖.
FAUSTINO R. PE´ REZ-LO´ PEZ, Vitamin D: The secosteroid hormone and human reproduction, Department of
Obstetrics and Gynecology, Zaragoza Gynecological Institute, Zaragoza, Spain. 24 September 2006; accepted 1
October 2006.
―In a cross-section of older adults, vitamin D deficiency was associated with
low mood and with impairment on two of four measures of cognitive
performance‖.
Consuelo H. Wilkins, M.D., Yvette I. Sheline, M.D., Catherine M. Roe, Ph.D., Stanley J. Birge, M.D., John C. Morris, M.D.
Vitamin D Deficiency Is Associated With Low Mood and Worse Cognitive Performance in Older Adults. Am J Geriatr
Psychiatry 14:12, December 2006.
6. Vitamin D in Cardiovascular System
―Vitamin D may potentially affect the treatment and prevention of
hypertensive vascular disease, coronary artery disease, cardiac arrhythmias,
peripheral vascular disease, lipid metabolism, and diabetes mellitus.
Accumulating epidemiologic evidence suggests that hypovitaminosis D may
be associated with an increased risk of cardiovascular events and
experimental data generally support the hypothesis that vitamin D has a
protective role in cardiovascular health‖.
Artaza JN, Mehrotra R, Norris KC. Vitamin D and the cardiovascular system. Clin J Am Soc Nephrol 2009
Sep;4 (9):1515-22.
Lee JH, O'Keefe JH, Bell D, Hensrud DD, Holick MF. Vitamin D deficiency an important, common, and easily
treatable cardiovascular risk factor? J Am Coll Cardiol 2008 Dec 9;52(24):1949-56.
Levin A, Li YC. Vitamin D and its analogues: do they protect against cardiovascular disease in patients with
kidney disease? Kidney Int 2005 Nov; 68 (5):1973-81.

7. Wu-Wong JR, Nakane M, Ma J, Ruan X, Kroeger PE. Effects of Vitamin D analogs on gene expression profiling
in human coronary artery smooth muscle cells. Atherosclerosis 2006 May;186(1):20-8.
―Hypovitaminosis D is associated with disturbed glucose metabolism and
pancreatic cell dysfunction, lipoprotein alterations, hypertension, overweight
and obesity. The evidence highlights the importance of improving vitamin D
status in the general population for the prevention of adverse long-term
health risks, including cardiovascular health‖
Faustino R. Pérez-López, Vitamin D metabolism and cardiovascular risk factors in postmenopausal women,
department of Obstetrics and Gynaecology, University of Zaragoza, Faculty of Medicine, Hospital Clínico Universitario
de Zaragoza, Domingo Miral s/n, Zaragoza 50009, Spain; Maturitas 62 (2009) 248–262.
―Vitamin D deficiency is prevalent in neonates with congenital cardiac
defects, regardless of race. Second, 25(OH)D levels are not altered by CPB.
Third, higher 24 hour postoperative 25(OH)D levels are associated with a
reduction in inotropic requirement in neonates undergoing cardiac operations
with CPB. These findings provide support that vitamin D may play a role in
myocardial injury and postoperative recovery‖.
VITAMIN D STATUS IN NEONATES UNDERGOING CARDIAC OPERATIONS: RELATIONSHIP TO CARDIOPULMONARY
BYPASS AND OUTCOMES, March 24, 2012.
―Diastolic dysfunction is likely related to vitamin D deficiency as well since
secondary hyperparathyroidism in these patients is induced by chronic
vitamin D deficiency. The cardiovascular changes observed are not easily
reversible, hence early preventive therapy with vitamin D supplementation
before the onset of vitamin D deficiency is advocated‖.
Amit Patange; Rudolph Valentini; Wei Du; Michael Pettersen, VITAMIN D DEFICIENCY IS ASSOCIATED WITH
DIASTOLIC DYSFUNCTION IN CHILDREN WITH CHRONIC KIDNEY DISEASE, J Am Coll Cardiol. 2012;59(13s1):E2147-
E2147. doi:10.1016/S0735-1097(12)62148-2