Vitamin D Part 3-Vitamin D in Diseases and Dose Recommendations

A CME Series on Vit D In 3 Weekly Sessions
facebook.com/dermatologist.drhanish
Covid19 & Vit D: Fri. 14/08/2020 @ 4.30 PM (UAE) [6.00 PM (IST)]
Vit D in Health: Fri. 21/08/2020 @4.30 PM (UAE) [6.00 PM (IST)]
Vitamin D in Disease & Recommendations :
Fri. 28/08/2020 @ 4.30 PM (UAE) [6.00 PM (IST)]
Dermatologist, Ajman & Sharjah, UAE
Overseas Associate Editor, IMALive
Immediate Past President, AKMG Emirates
Dr Hanish Babu, MD
Co-Host: Rajesh Rajan, Science Global
Vitamin D in Health & Disease

Dr Hanish Babu, MD, 2020
Please use this presentation along with the 3 talks on the
FB Page to get full info on Vitamin D:
As a service to the public healthcare system, these presentations may be reproduced for any
educational purpose, with proper acknowledgement.
Links to talks:
Talk 1 : Covid 19 and Vitamin D
Talk 2 : Vitamin D in Health
Talk 3 : Vitamin D in Diseases & Dose Recommendations

Vitamin D in Diseases
& Dose Recommendations

Vitamin D in Health and Disease
Vitamin D in Diseases
Part 3 A

Vitamin D
deficiency has
been linked to
a large number
of human
diseases.
Berridge MJ. Vitamin D, Cell Signalling Phenotypic Stability and Alzheimer’s Disease. Austin J Clin Neurol 2015;2(3):
1033.
3% of the human
genome is regulated
by the vitamin D
endocrine system

What does Vitamin D do to make such a difference in
health?
Genes don’t want to be making proteins continuously .
Vitamin D is the major regulator in humans with Over 230
VDRs in the nuclei of most tissues.
Vitamin D affects gene expression.
It turns genes on & off

Overview of Vit D
Metabolic Pathway
Immune
Regulation
1. Bulk of Vit D
utilization:
autocrine
2. After the action,
Calcitriol
degraded
immediately
3. There is much
higher
requirement of
calcitriol than is
thought of.

Why is Vitamin D Important?
• Serve as a part of the biochemical apparatus to access the
information stored in the DNA, enabling the required
function of the cell.
• Vitamin D deficiency  improper functioning of body parts
• It is necessary for the body to absorb enough calcium from
our food

In its deficiency, proper cellular functions will not be able to be carried out, which could lead
to different disease manifestations.

Vit D and the Cardiovascular System
Decrease Vascular inflammation:
• suppresses the renin-angiotensin system
• promotes endothelial nitric oxide release
• decreases vascular inflammatory markers and cholesterol
deposition
• regulates immune cells with antiinflammatory properties
Vitamin D deficiency or VDR deletion promotes renin-dependent hypertension
and accelerates atherosclerosis
Consistent, but conflicting, associations between low 25(OH)D levels and
increased CVD.
The VDR and the 1 α-hydroxylase enzyme are present in critical cells implicated in the
development of vascular disease.

Vit D and the Cardiovascular System
Al Mheid I. et al. J Am Coll Cardiol.2017;70(1):89-100
• Vitamin D regulates blood pressure;
and endothelial, smooth muscle cell,
and cardiac functions
• Epigenetic modifications subdue
cellular inflammation
• Vitamin D sufficiency important in
preventing cardiovascular and other
chronic diseases.
SJ.Wimalawansa. Review.Vitamin D and CVS: Causality. The
Journal of Steroid Biochemistry and Molecular Biology. 2018:
175:29-43 Dr Hanish Babu, MD, 2020

Kim IM, Norris KC, Artaza JN: Vitamin D and cardiac differentiation. Vitam Horm 2016; 100: 299–320.
Experimental studies have established that
calcitriol and VDR are critical regulators of
the structure and function of the heart and
blood vessels.
Vit D
Reno
Protection
Vasodilation
Prevention
of insulin
resistance
Anti
inflammatory
effects
Renin
Angiotensin
Aldosterone
System
Prevention
of 2ry
Hyperparat
hyroidism
Smooth muscle
migration
Foam Cell
Formation
T Cell
Activation
Adhesion and
aggregation of
platelets
Adhesrance
and entry of
granulocytes

Vitamin D and Heart Disease Risk
Brandenburg VM, Vervloet MG, Marx N. The role of vitamin D in cardiovascular disease: from present
evidence to future perspectives. Atherosclerosis. 2012;225(2):253-263.
• Experimental data is strongly supported by epidemiological and observational human data that link
vitamin D deficiency to the incidence, degree and prevalence of cardiovascular risk factors and disease
conditions.
• High quality, large, and randomized controlled trials aiming primarily on cardiovascular end-points are
required
Podzolkov VI, Pokrovskaya AE, Panasenko OI. Vitamin D deficiency and cardiovascular pathology. Ter
Arkh. 2018;90(9):144-150.
• Low Vitamin D levels in humans are associated with the unfavorable cardiovascular risk factors, such as
arterial hypertension (AH), diabetes mellitus, and dyslipidemia, which are the predictors of the severe
cardiovascular diseases, including strokes and infarctions.
• This article provides data of Russian and foreign studies demonstrating the effect of Vitamin D
deficiency on the development of atherosclerosis, AH, heart rhythm disorder and progression of chronic
heart failure.

Vitamin D
and Cancer
Wu Xu, et al. Repurposing vitamin D for treatment of human malignancies via targeting tumor
microenvironment. Acta Pharmaceutica Sinica B (2018), http://dx.doi.org/10.1016/j.apsb.2018.09.002Dr Hanish Babu, MD, 2020

Slide courtesy: Department of Pharmacology, MIMER Medical College, Pune

Chakraborti CK. Vitamin D as a promising anticancer agent. Indian J Pharmacol. 2011;43(2):113-120.
Lopes N, Paredes J, Costa JL, Ylstra B, Schmitt F. Vitamin D and the mammary gland: a review on its
role in normal development and breast cancer. Breast Cancer Res. 2012;14(3):211..
Trump DL, Deeb KK, Johnson CS. Vitamin D: considerations in the continued development as an
agent for cancer prevention and therapy. Cancer J. 2010;16(1):1-9.
Ma Y, Johnson CS, Trump DL. Mechanistic Insights of Vitamin D Anticancer Effects. Vitam Horm.
2016;100:395-431.
Krishnan AV, Swami S, Feldman D. The potential therapeutic benefits of vitamin D in the treatment of
estrogen receptor positive breast cancer. Steroids. 2012;77(11):1107-1112.

Vitamin D
supplements
Could reduce
cancer incidence
and death rates.
Linked with GI cancer,
prostate and breast
cancers, lymphomas,
endometrial and lung
cancers.

Vit D and Calcium and Cancer Risk in
Women
Women who regularly took vitamin D3 and calcium had a 60%
reduction in all-cancer incidence compared with a group taking
placebo and a 77% reduction when the analysis was confined to
cancers diagnosed after the first 12 months
Joan M Lappe, Dianne Travers-Gustafson, K Michael Davies, Robert R Recker, Robert P Heaney, Vitamin
D and calcium supplementation reduces cancer risk: results of a randomized trial, The American Journal
of Clinical Nutrition, Volume 85, Issue 6, June 2007, Pages 1586–1591

Vit D and Lung Cancer
1,25(OH)2D:
• Inhibits proliferation and induces differentiation of lung cancer
cell lines (Higashimoto, et al., 1996, Guzey, et al., 1998)
• Inhibits metastatic growth and locoregional recurrence of lung
cancer cells in mice (Wiers, et al., 2000)

Vit D and Breast Cancer
1,25(OH)2D:
• inhibits cell proliferation, induces differentiation & apoptosis,
and inhibits angiogenesis in normal and breast cancer cells
(Colston, et al, 1989, Saez, et al, 1993, Mantell, et al., 2000, Cui
& Rohan, 2006)
• suppresses high-fat diet-induced mammary tumorigenesis in
rats (Jacobson, et al., 1989, Xue, 1999)
• Prognosis 15 – 25% better for women diagnosed / treated in the
summer vs. winter (Knight , 2007)

Pancreatic Cancer & Vitamin D
• Prospectively collected diet and lifestyle data
• Nurses’ Health Study – 75,427 women
• Health Professionals Follow-up Study – 46,771 men
• Pancreatic cancer risk 41% lower among those who
consumed > 600 IU of vitamin D / day vs. those who
consumed < 150 IU / day
Skinner Hg et al. Vitamin D
intake and the risk for
pancreatic cancer in two
cohort studies. Cancer
Epidemiology Biomarkers
and
Prevention. 2006;15(9):1688–
1695.
• Vitamin D have a protective effect against pancreatic
cancer
Bulathsinghala, Pubudu et al.
“Role of vitamin d in the
prevention of pancreatic
cancer.” Journal of nutrition
and metabolism vol. 2010
(2010): 721365.

Cancer Survival in Melanoma.
• Intermittent sun exposure associated with
increased survival following a diagnosis of
melanoma
Mason, R., Sequeira, V. & Gordon-Thomson, C. Vitamin D: the light side of sunshine. Eur J
Clin Nutr 65, 986–993 (2011)

Simple, inexpensive, and
efficient therapeutic strategy
for the correction of
neurological disorders in
Alzheimers’ Disease

Vit D and Respiratory Infections:
Earlier Study
• 25 eligible RCTs
• Total 11321 participants, aged 0 to 95 years
• Vitamin D supplement protected against
acute respiratory tract infections.
AR Martineau et al. Vitamin D supplementation to prevent acute
respiratory tract infections: systematic review and meta-analysis of
individual participant data. BMJ 2017;356:i6583

Vit D and Pregnancy
Association of low intake of milk and Vit D during pregnancy
with decreased birth weight.
Women between ages 19-45yrs
• </= 250 ml of milk = low birth weight
• Milk or Vit D independent predictor of BW
• 1 cup milk = 41 gm increase in BW
• 1 Mcg increase in dietary Vit D = 11 gm increase in BW
Mannion CA, Gray-Donald K, Koski KG.Association of low intake of milk and vitamin D during pregnancy with decreased
birth weight. CMAJ 2006;174(9):1273-7. Dr Hanish Babu, MD, 2020

Maternal Vitamin D Status during Pregnancy and
Childhood Bone Mass at age 9yrs.
- 198 children born in 1991-92 in South Hampton UK
- Children were followed up at age 9yrs
- 31% mother had insufficient and 18% had deficient serum vit D during late
pregnancy
- Decrease vit D in mothers = decrease bone mineral content in children at age 9
yrs
- Mother’s exposure to UV rays and use of vit d predicted vit d and childhood bone
mass
M.K. Javaid, SR Crozeir at al. Lancet Jan 7 2006

Type 2 Diabetes
• Low serum levels of 25(OH)D are associated with impaired
pancreatic β cell function and insulin resistance
• Altered vitamin D and calcium homeostasis may play a role in
development of type 2 diabetes
• High calcium intake is inversely associated with body weight
Nurses’ Health Study – 83,779 women (98% Caucasian)
Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic
review and meta-analysis. J Clin Endocrinol Metab. 2007;92(6):2017-2029.

Type 1 Diabetes
• Birth-cohort study in Finland – all women due to give birth
in 1966 enrolled
• 10,366 children born alive and data collected in first year
• Followed till Dec, 1997 for Type 1 Diabetes.
• Dietary vitamin D supplementation is associated with
reduced risk of type 1 diabetes.
Hyppönen E. Vitamin D and increasing incidence of type 1 diabetes-evidence for an
association?. Diabetes Obes Metab. 2010;12(9):737-743.
Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM: Intake of vitamin D and risk of type
1 diabetes: a birth-cohort study. Lancet 358:1500-1503, 2001

Metabolic Syndrome and
Vitamin D
Strange RC, Shipman KE, Ramachandran S. Metabolic syndrome: A review
of the role of vitamin D in mediating susceptibility and outcome. World J
Diabetes. 2015;6(7):896-911.
• Meta-analysis of 28 studies (between
1990 and 2009) including 99745
participants (age range: 40.5-74.5
years).
• Effects of vitamin D on the risk of
CVD, diabetes and the metabolic
syndrome.
• There appears to be sufficient evidence for
the association between hypovitaminosis D
and the metabolic syndrome.

NASH (Non Alcoholic Fatty Liver) and Vit D
6800 patients : NHANES III Data base
Those with elevated serum alanine transaminase activity were
seen to have lower vitamin D concentrations compared to
matched controls with normal enzyme levels,
Liangpunsakul S, Chalasani N. Serum vitamin D concentrations and unexplained
elevation in ALT among US adults. Dig Dis Sci. 2011;56:2124–2129.
[The Third National Health and Nutrition Examination Survey (NHANES III), 1988-94, contains data for
33,994 persons ages 2 months and older]

• Vitamin D has an anti-
fibrogenic effect on HSCs
• Vitamin D
deficiency prevalent in
patients with chronic liver
diseases-
• Vitamin D supplements
may serve as a novel
treatment for liver fibrosis
in CLDs.
W.Udomsinprasert,J.Jittikoon. Vitamin D and liver fibrosis: Molecular mechanisms and clinical studies. Biomedicine &
Pharmacotherapy 109 (2019) 1351–1360
Vitamin D and liver fibrosis

Vitamin D and Autoimmune Diseases
• Vitamin D has pleiotropic effects on the immune system.
• Vitamin D, after metabolized into a biologically active form, 1,25(OH)2D,
and bound to VDR/RXR, can initiate gene transcription and exert its
immunomodulatory effects on immune cells.
• Both environmental trigger (insufficient sunshine exposure) and genetic
factor (VDR polymorphism) could contribute a poor vitamin D status.
• Vitamin D deficiency (low serum levels of 25(OH)D) is prevalent in multiple
autoimmune diseases, e.g. MS, TIDM, and SLE.
• Because the vitamin D status is highly associated with the risk of
autoimmunity, vitamin D has been implicated in prevention and protection
from autoimmune diseases
Yang CY, Leung PS, Adamopoulos IE, Gershwin ME. The implication of vitamin D and autoimmunity: a
comprehensive review. Clin Rev Allergy Immunol. 2013;45(2):217-226.

Vit D and its Role
in Autoimmunity
Although various studies
have shown a beneficial
effect of cholecalciferol
supplementation in
autoimmune diseases,
there are also studies that
do not find any effect on
disease parameters. This
might be due to the
supplementation strategy
or the subjects included in
the study.
Dankers et al. Vitamin D in Autoimmunity: Molecular Mechanisms and Therapeutic Potential.
Front. Immunol., 2017:7: 697: 1-26. Dr Hanish Babu, MD, 2020

Vit D and Skin Diseases
• Vitamin D & Skin  synthesis, metabolism, and activity.
• Regulates many physiological processes in the skin
ranging from cellular proliferation, differentiation, and
apoptosis to barrier maintenance and immune functions.
• Important therapeutic option for many skin diseases
Meenakshi Umar et al. Vitamin D and the Pathophysiology of Inflammatory Skin Diseases. Skin Pharmacol Physiol
2018;31:74–86 Dr Hanish Babu, MD, 2020

Meenakshi Umar et al. Vitamin D and the Pathophysiology of Inflammatory Skin Diseases. Skin Pharmacol
Physiol, 2018;31:74–86
1. Inhibition of keratinocyte
proliferation
2. Promotion of keratinocyte
differentiation
3. Regulation of keratinocyte
apoptosis
4. Barrier maintenance
5. Immunomodulatory actions
6. Antimicrobial peptide synthesis
7. Inhibition of antigen
presentation
8. Cytokine suppression

F.J. Navarro-Trivino et al. Vitamin D and the Skin: A Review for Dermatologists. Actas Dermosifiliogr.
2019;110(4):262---272 Dr Hanish Babu, MD, 2020

Skin Diseases Related to Alterations in Vitamin D Levels
F.J. Navarro-Trivino et al. Vitamin D and the Skin: A Review for Dermatologists. Actas Dermosifiliogr.
2019;110(4):262---272 Dr Hanish Babu, MD, 2020

Vit D Supplementation in
Skin Diseases: Grades of
Recommendation and
Levels of Evidence
F.J. Navarro-Trivino et al. Vitamin D and the
Skin: A Review for Dermatologists. Actas
Dermosifiliogr. 2019;110(4):262---272
Grade of Recommendation
•A = Consistent level 1 studies.
•B = Consistent level 2 or 3 studies
or extrapolations from level 1
studies.
•C = Level 4 studies or extrapolations
from level 2 or 3 studies.
•D = Level 5 evidence or troubling
inconsistent or inconclusive studies at
any level.

Levels of
Evidence in EBM
Ackley, B. J., Swan, B. A., Ladwig, G., & Tucker, S.
(2008). Evidence-based nursing care guidelines:
Medical-surgical interventions. St. Louis, MO: Mosby
Elsevier Dr Hanish Babu, MD, 2020

Vit D and
Psoriasis
• Autoimmune: Dysregulation of the immune cells in the skin, particularly T cells, plays a
critical role in psoriasis development.
• Vit D: antiproliferative, anti-inflammatory, antiangiogenic
• Vit D: Supress Th1, Th17
• Topical Calcipotriol: Regulate Human Beta defensins(HBD 2 &3), Il-17, IL 8: Reduce
proliferation in Psoriasis
• Antiproliferative effect of Calcitriol on Epidermal cells and activated T lymphocytes is
mediated through induction of apoptosis of these cells.(Suravi C, 2014)
Wadhwa B, Relhan V, Goel K, Kochhar AM, Garg VK. Vitamin D and skin diseases: A review. Indian J Dermatol
Venereol Leprol 2015;81:344-55 Dr Hanish Babu, MD, 2020

Vitamin D and Atopic Dermatitis
Wadhwa B, Relhan V, Goel K, Kochhar AM, Garg VK. Vitamin D and skin diseases: A review. Indian J
Dermatol Venereol Leprol 2015;81:344-55 Dr Hanish Babu, MD, 2020

Vitamin D
and Atopic
Dermatitis
Wadhwa B, Relhan V, Goel K, Kochhar AM, Garg VK. Vitamin D and skin diseases: A review. Indian J Dermatol Venereol Leprol 2015;81:344-55
VD may exert effects that
contribute to AD etiology and
pathogenesis by
improvement of the
epidermal barrier,
strengthening of innate
immunity to skin bacteria,
promotion of tolerance and
reduction of Th2 immunity.

Studies evaluating the role of Vitamin D in atopic
dermatitis

Vitamin D and Vitiligo
• Vitamin D protects the epidermal melanin unit and restores melanocyte integrity via several
mechanisms
• Activation, proliferation, migration of melanocytes and pigmentation pathways by modulating T cell
activation,
• Autoimmunity correlated with melanocyte disappearance in vitiligo
• Vit D coordinates melanogenic cytokines, regulators of melanocyte viability and maturation.
• Anti-oxidant property
• Regulates apoptotic activity against melanocytes
• Vitamin D exert immunomodulatory effects on cytokins: dampen autoimmune pathway.
• A number of studies have reported on the treatment of vitiligo with vitamin D analogs alone
or in combination with ultraviolet light or corticosteroids to enhance repigmentation
Wadhwa B, Relhan V, Goel K, Kochhar AM, Garg VK. Vitamin D and skin diseases: A review. Indian J
Dermatol Venereol Leprol 2015;81:344-55 Dr Hanish Babu, MD, 2020

Vitamin D and
Vitiligo: A Few
Studies
Wadhwa B, Relhan V, Goel K,
Kochhar AM, Garg VK. Vitamin D
and skin diseases: A review.
Indian J Dermatol Venereol Leprol
2015;81:344-55

Vit D and Acne
• Inflammation resulting from the
immune response targeting
Propionibacterium acnes (P. acnes)
has a significant role in acne
pathogenesis.
• P. acnes is a potent inducer of Th17,
and that Vit D inhibits P. acnes-induced
Th17 differentiation.
• Sebocytes are Vit D responsive target
cells
• Fish oil found effective in the treatment
of Acne
Wadhwa B, Relhan V, Goel K, Kochhar AM, Garg VK. Vitamin D and skin diseases: A review. Indian J Dermatol
Venereol Leprol 2015;81:344-55 Dr Hanish Babu, MD, 2020

Vitamin D and Skin
Cancer
Promotion of cell differentiation and apoptosis along with
inhibition of cancer cell proliferation, inflammation and
angiogenesis by calcitriol may explain the cancer protective
benefits of vitamin D.
Oral vitamin D supplementation can be recommended to
significantly reduce the cancer mortality from melanoma
Manson JE, Mayne ST, Clinton SK. Vitamin D and
prevention of cancer- ready for prime time? N Engl J
Med 2011;364:1385-7.
Randerson-Moor JA, Taylor JC, Elliott F, Chang YM, Beswick S, Kukalizch K, et al. Vitamin D
receptor gene polymorphisms, serum 25-hydroxyvitamin D levels, and melanoma: UK case-
control comparisons and a meta-analysis of published VDR data. Eur J Cancer 2009;45:3271-81

Vitamin D and Skin Fibrosis
Inhibition of normal skin fibroblasts and keloid
fibroblasts by vitamin D has suggested a potential
therapeutic role in keloids.
Topical vitamin D analogs are an established treatment
modality in morphoea and lichen sclerosus et atrophicus
owing to its effects on immunoregulation, fibroblast
proliferation, collagen synthesis and endothelial cell
function.
Zhang GY, Cheng T, Luan Q, Liao T, Nie CL, Zheng X, et al.
Vitamin D: A novel therapeutic approach for keloid, an in
vitro analysis. Br J Dermatol 2011;164:729-37.
Boelsma E, Pavel S, Ponee M. Effects of calcitriol on fibroblasts
derived from skin of scleroderma patients. Dermatology
1995;191:226-33. Dr Hanish Babu, MD, 2020

Vitamin D and
Infections
Low vitamin D levels have been
associated with bacterial vaginosis.
Several studies have found a correlation
between the degree of skin infections in atopic
dermatitis and a low vitamin D level,
Amon U, Baier L, Yaguboglu R, Ennis M, Holick MF, Amon J. Serum 25-
hydroxyvitamin D levels in patients with skin diseases including psoriasis,
infections, and atopic dermatitis. Dermatoendocrinol. 2018;10(1)
Bodnar LM, Krohn MA, Simhan HN. Maternal vitamin D
deficiency is associated with bacterial vaginosis in the first
trimester of pregnancy. J Nutr 2009;139:1157-61.

Vit D and Viral Infections
The potential mechanisms include
• the antiviral immune induction
• The modulation of immunoregulatory defense induction of
autophagy and apoptosis
• Genetic or epigenetic regulation
Teymoori-Rad M., Shokri F., Salimi V., Marashi S.M. The interplay between vitamin D and viral
infections. Rev. Med. Virol. 2019;29

Vitamin D and Skin
Tuberculosis
The use of calciferol for treatment of
lupus vulgaris dates back to 1940s.
A series of cases from England, France,
Belgium and other countries showed that
calciferol had an excellent curative effect
on lupus vulgaris without causing much
toxicity.
Dowling GB, Gauvain S, Macrae DE. Vitamin D in treatment of
cutaneous tuberculosis. Br Med J 1948;1:430-5.

Vit D and Tuberculosis
Vitamin D deficiency
exists in patients with
tuberculosis and it is
possibly a cause
rather than effect of
the disease; deficiency
is due to decreased
dietary intake.

Vitamin D and Tuberculosis
Yuk et al. showed that LL-37, induced by physiological levels of
vitamin D, stimulates access to and killing of M. tuberculosis even
within autophagosomes.
Combined vitamin D and antitubercular therapy has been
observed to result in a higher degree of clinical improvement than
the latter given alone.
Yuk JM, Shin DM, Lee HM, Yang CS, Jin HS, Kim KK, et al. Vitamin D3 induces autophagy in
human monocytes/macrophages via cathelicidin. Cell Host Microbe 2009;6:231-43.
Miller J, Gallo RL. Vitamin D and innate immunity. Dermatol Ther 2010;23:13-22.

Vitamin D and Hairloss
• Stimulate hair follicle
differentiation
• VDR  Anagen initiation
• VDR  Hair cycle genes
• Vit D Deficiency associated
with telogen effluvium and
androgenic female pattern
hair loss S.M. Lee, et al. A humanized mouse model of
hereditary 1,25-dihydroxyvitamin D-resistant rickets
without alopecia
Endocrinology, 155 (2014), pp. 4137-4148
Gerkowicz A, Chyl-Surdacka K, Krasowska D,
Chodorowska G. The Role of Vitamin D in Non-
Scarring Alopecia. Int J Mol Sci. 2017;18(12):2653

This is the first study to show that genetic mutations in VDR are associated with OLP susceptibility, and
that rs2239185 and rs7975232 may be the genetic markers for OLP susceptibility in a Chinese Han
population. However, larger scale prospective studies and functional experiments are required to
validate the findings.
Photo credit: Dr Hanish Babu, MD (2020)

Other less-characterized roles of Vitamin D in skin

Indications for
Vitamin D
Supplementation
During
Corticosteroid
Therapy

The Other Side….
• Screening asymptomatic
individuals for vitamin D
deficiency and treating those
considered to be deficient do not
reduce the risk of cancer, type 2
diabetes mellitus, or death in
community-dwelling adults, or
fractures in persons not at high
risk of fractures.
• Randomized controlled trials of
vitamin D supplementation in the
treatment of depression, fatigue,
osteoarthritis, and chronic pain
show no benefit, even in persons
with low levels at baseline.

Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JP. Vitamin D and multiple health outcomes: umbrella review of
systematic reviews and meta-analyses of observational studies and randomised trials. BMJ. 2014
On the basis of the available
evidence, an association between
vitamin D concentrations and birth
weight, dental caries in children,
maternal vitamin D concentrations at
term, and parathyroid hormone
concentrations in patients with chronic
kidney disease requiring dialysis is
probable, but further studies and
better designed trials are needed to
draw firmer conclusions.
Vitamin D and multiple health outcomes: umbrella review of systematic
reviews and meta-analyses of observational studies and randomised trials.
The relation between vitamin D and 137 outcomes explore

Vitamin D
and Omega-
3 Trial -
VITAL
Presented during The North American Menopause Society (NAMS) Annual Meeting in
Chicago, Dr Hanish Babu, MD, 2020

Vitamin D and Omega-3 Trial – VITAL:
Results
• The findings indicate that “high-dose” vitamin D does not lower the risk of
developing cancer or cardiovascular disease in generally healthy men
and women, although it appears to lower the risk of cancer death.
• African Americans assigned to vitamin D did experience a suggestive 23%
reduction in cancer risk.
• People with low dietary intake of fish has a heart benefit from omega-3
fatty acid supplementation.
Presented during The North American Menopause Society (NAMS) Annual Meeting in
Chicago, Dr Hanish Babu, MD, 2020

The Vital Study Shadow
Vitamin D does not work!
Nothing can be far from the truth!

Major inconsistencies of the Vital Study
• Under dosage
• Inadequate Blood level monitoring
• Other confounding factors like nutritional status, life style,
comorbidities, hereditary factors, sun exposure, exposure to
pollutants, latitude, season etc not well addressed.
• VITAL study although an RCT showed many weaknesses in
its methodology
Infante M, Ricordi C, Baidal DA, Alejandro R, Lanzoni G, et al. (2019) VITAL study: an incomplete
picture? Eur Rev Med Pharmacol Sci 23: 3142-3147

Major inconsistencies of the Vital Study
Infante M, Ricordi C, Baidal DA, Alejandro R, Lanzoni G, et al. (2019) VITAL study: an incomplete
picture? Eur Rev Med Pharmacol Sci 23: 3142-3147

Vitamin D supplementation is not just about
disease prevention!
• It is a nutrient replenishment of an essential cellular factor
• It is about maintaining normal health parameters, and has to be
used along with other nutrients and a healthy life style .
• Continue to find and mitigate Vitamin D Deficiency, a public
health pandemic
• This is what we are going to do next!

Vitamin D in Health and Disease
Vit D: Dose Recommendations
Part 3 B

So what are the recommendations?
• Routine screening:
• Annual Testing.
• Best Time to test?
• During mid winter
• Aim should be to Rectify deficiency / insufficiency
• Maintain levels through a patient-specific combination of
diet, supplementation, and sun exposure
Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad H, Weaver CM. Evaluation,
treatment, and prevention of vitamin D deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol
Metab 2011;96:1911-30 Dr Hanish Babu, MD, 2020

How Do You Know If You Have a Vitamin D
Deficiency?
Blood tests are the only way to know if you are vitamin D
deficient.
• Severely Deficient: Less than 10ng/ml
• Deficient: Levels less than 20 ng/ml
• Insufficient: Levels between 20-30 ng/ml
• Sufficient: Levels between 30-100 ng/ml
• High: Levels greater than 100 ng/ml
• Toxic: Levels greater than 150ng/ml
Optimum
levels of
Vit D:
40-60ng/ml
Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad H, Weaver CM. Evaluation,
treatment, and prevention of vitamin D deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol
Metab 2011;96:1911-30 Dr Hanish Babu, MD, 2020

Severe Moderate
nmol/L 25 50 75 100 125 150
Severe
Deficiency Deficiency Insufficienc
y
Sufficiency Optimum

ng x 2.5 =
nmol

Vitamin D Assessment
• 25(OH)D closely reflects total amount of vit D produced
in the skin and from diet. Half life is approx. 15 days.
• DO NOT USE - 1,25-(OH)2 D. This can often be normal
with vit D deficiency. Half life is only 15 hrs

Vitamin D Assessment
• Growing evidence indicates significant limitations
of 25-OHD test, including analytical aspects and
interpretation of results.
• The relationships between 25-OHD and various
clinical indices, such as bone mineral density and
fracture risk, are rather weak and not consistent
across races.

Vitamin D metabolism and assessment.In the liver vitamin D is hydroxylated in 25-hydroxy-vitamin D (25-OHD) by the enzyme CYP2R1. Subsequently, 25-OHD is hydroxylated to bioactive 1α,25-dihydroxy-vitamin D (1,25-(OH)2D) by the
enzyme CYP27B1, predominantly in the kidney. Vitamin D catabolism is predominantly due to CYP24A1, which metabolises 25-OHD to 24,25-dihydroxy-vitamin D (24,25-OH2D) and 1,25-(OH)2D to 1,24,25-dihydroxy-vitamin D (1,24,25-OH3D).
Circulating vitamin D is bound to carriers (vitamin D binding protein (DBP), albumin and lipoproteins). Bioavailable vitamin D (BAVD), vitamin D metabolite ratio (VMR), automated immunoassay (automated IA).
These parameters may
potentially change how we
assess vitamin D status in
the future
Herrmann, M., Farrell, C. L., Pusceddu, I., Fabregat-Cabello, N., & Cavalier, E. (2017). Assessment of vitamin D status – a
changing landscape, Clinical Chemistry and Laboratory Medicine (CCLM), 55(1), 3-26
Markers of Vitamin D status

Vit D Deficiency: Is there really a Pandemic? Or is
it a hype by the industry?
• The estimated average requirement and the recommended dietary
allowance both assume minimal to no sun exposure.
• Sufficient sun exposure to produce a light-pink skin hue (one minimal
erythema dose) is equivalent to 20,000 IU of oral vitamin D.
• Varies from person to person
• Ethnic and climactic differences
Manson JE, Brannon PM, Rosen CJ, Taylor CL. Vitamin D deficiency—is there really a pandemic? N Engl J
Med. 2016;375(19):1819.

Causes of Vitamin D Deficiency
1. Decreased production in skin
• Inadequate sun exposure: Indoors
• Obstructive clothes
• Increased melanin
• Age
2. Decreased Dietary intake
• Imbalanced diet: Fads, Vegans, Pure Non Veg, Milk allergy
• Deficency of Magnesium, Calcium, Zinc, Vit A, K2, C, Folate etc

3. Defective absorption: malabsorption of fats, medications
4. Impaired activation of Vitamin D in Liver
• Alcohol, NASH, Drugs, Infections, Toxins
5. Impaired activation in Kidneys
• Hypoparathyroidism: Poor diet, low magnesium
• Renal Disease: DM, HT
• 1α hydroxylase mutation
• Drugs : Ketoconazole

6. Accelerated loss of Vitamin D
• Barbiturates, Phenytoin, Rifampicin
7. Impaired Vit D Metabolism
• 1α hydroxylase mutation
• Vitamin D receptor mutation & heterogeneity
• Vit D Binding Protein mutation
8. Target organ Resistance
• Drugs, mutations

9. Phytic acids in commercially processed cereals, sodium
bicarbonate in baking soda, and aluminum hydroxide in
antacids: react with calcium or phosphorus to form
insoluble salts.

General Signs and Symptoms of Vitamin D
Deficiency
• Getting Sick or Infected Often
• Fatigue and Tiredness
• Bone and Back Pain
• Depression
• Impaired Wound Healing
• Bone Loss
• Hair Loss
• Muscle Pain

Mild to moderate Deficiency: asymptomatic
Long standing Vitamin D Deficiency
• Hypocalcemia
• Secondary hyperparathyroidism
• Impaired mineralization of the skeleton:
osteoporosis
• Proximal myopathy
• Aches and pains
• Difficulty in swallowing
• Muscle cramps
• Low back ache
• Rarely tetany: Trousseau’s sign & Chvostek’s
sign may be positive
• Bone pains
• Osteoarthrosis
• Cardiomyopathy
• Cervical and lumbar spondylitis
• IVDP
• Hypotonia of abdominal muscles
• Rarely primary hyperparathyroidism

OsteomalaciaRickets
Prior to epiphyseal fusion
After epiphyseal fusion

How to Diagnose Vitamin D Deficiency?
• Take diet and lifestyle history: anticipate!
• No sun exposure
• Not taking fish, non veg, vegetables, fruits
• Any liver/kidney problems
• Chvostek’s sign may be positive
• Blood Test: Serum 25OHD level, Serum Ca, PO4, Mg
• Increased ALP Levels (PTH induced bone turn over)
• Increased PTH
• Serum Ca often normal.

Laboratory Diagnosis of Vitamin D Deficiency
• Alkaline phosphatase is usually elevated in response to the
effect of PTH on calcium absorption from bone.
• The combination of a normal serum calcium, low phosphate,
and elevated alkaline phosphatase is suggestive of
disturbed vitamin D metabolism and Vitamin D deficiency.
Misra M, Pacaud D, Petryk A, Collett-Solberg PF, Kappy M, Drug and Therapeutics Committee of the Lawson Wilkins
Pediatric Endocrine Society Vitamin D deficiency in children and its management: review of current knowledge and
recommendations. Pediatrics 2008;122: 398–417

Diagnosis of Vitamin D Deficiency
• Elevated serum alkaline phosphatase (ALP) level is an
essential marker for the diagnosis of vitamin D deficiency.
• Some cases of vitamin D deficiency are diagnosed accidentally
on the basis of elevated ALP levels.
• Therefore, cases without high ALP may be excluded from a
diagnosis of REAL vitamin D deficiency.
Matsuo K, Mukai T, Furuya A, Suzuki S, Tanahashi Y, Azuma H. A Case of Vitamin D Deficiency without Elevation
of Serum Alkaline Phosphatase in a Carrier of Hypophosphatasia. Clin Pediatr Endocrinol. 2013;22(4):73-76.

Goals in Maintaining Vitamin D Levels
1. Prevent disease of deficiency – rickets, osteomalacia.
2. Prevent complications of insufficiency – impaired calcium
absorption and increased bone resorption.
3. Minimize risks of future disease – cancer, cardiopulmonary
diseases, diabetes, respiratory infections, allergies and other
immune-related diseases.

Target should be 40-60ng.ml
• The incidence of type 1 diabetes (T1D) has
been doubling every 20 years.
• In Finland, the recommendation for daily
vitamin D supplementation was gradually
reduced from 4000-5000 IU in 1964 to 400
IU in 1992. Concomitantly, T1D increased
by 350% in those aged 1-4 years, 100% in
those aged 5-9 years, and 50% in those aged
10-14 years.
However, since 2006, T1D has plateaued and
decreased after an increase in serum 25-
hydroxyvitamin D (25[OH]D) after the
authorities’ decision to fortify all dietary milk
products with cholecalciferol.
IOM (2010) : 400-600 IU!

Discordance in
Recommendations Daily Dose (IU)
RDA/
Allowed Intake
TUIL
(Tolerable Upper Intake
Level)
400- 600 4,000
1,500-2,000 10,000
4,000
----
Ages 51-70
 IOM (2010)
 Endo Soc 2010
 Am Ger Soc 2014
One mcg of vitamin D (cholecalciferol) is equal to 40 international units, so 10 mcg is the same as 400
international units , used in some countries.

Why Test?
If majority are deficient, what is the need to check
levels?
Why not take supplements straight away?

How accurate are the lab test results?
Measurement techniques and precision varies.
10 % acceptable variance
In practice, this level of precision means that if the test value
from an assay is 30 ng per mL, clinicians can be 95% certain
that the true value is between 24 and 36 ng per mL (60 to 90
nmol per L)!
National Institutes of Health. Vitamin D: moving toward evidence-based decision making in primary
care. December 2–3, 2014. Summary of conference presentations and
discussions. https://ods.od.nih.gov/attachments/VitaminDConfSummary.pdf. Accessed July 28, 2020

Is widespread Testing for Vit D levels Justified?
• Unnecessary health care costs.
• In US Sales of vitamin D dietary supplements
have increased dramatically, from approximately
$108 million in 2007 to $713 million in 2013.
• Hype caused by industry manipulations?
Those against:

Is widespread Testing for Vit D levels Justified?
Those in favor:
• Prevention is better than cure
• Considering the skeletal and extra-skeletal functions of Vit D, it
is preferable to screen everyone.
• Monetary Vs Health considerations
• Reduce lab test costs

• Supplementation at
suggested daily intake
and tolerable upper
limit levels, depending
on age and clinical
circumstances.

Summary of Recommendations
1. Serum concentration of 25(OH)D is the best indicator of vitamin D
status.
2. It reflects vitamin D produced cutaneously and that obtained from
food and supplements and has a fairly long circulating half-life of 15
days.
3. Not clear to what extent 25(OH)D levels relate to health status or
outcomes
4. Serum 25(OH)D levels do not indicate the amount of vitamin D stored
in body tissues.
1.0 Diagnostic procedure

Healthy Individuals

Summary of Recommendations (Modified)
3. All adults who are vitamin D deficient
50,000 weekly x 8 weeks, then every two weeks for 4 months;
maintain 1000 – 6000 IU/day, depending upon sun exposure & diet
3.0 Treatment and Prevention Strategies.
1. For infants and toddlers aged 0–1 yr who are vitamin D deficient
10 - 20,000 weekly x 6 weeks, then maintenance: 1000 IU/Day
2. For children aged 1–18 yr who are vitamin D deficient,
20-50,000 weekly x 6 weeks, then maintenance: 1000- 2000 IU/Day

Summary of Recommendations
3.0 Treatment and Prevention Strategies.
4. Obese patients/Those with malabsorption
50,000 IU weekly twice x 8 weeks, Then weekly for 4 months,
then maintenance: 3000-6000 IU/Day
Higher doses of injections in very severe deficiency only:
<5ng/ml
Modified from: Kim MP, Jay HS. Vitamin D Deficiency, Its Role in Health and Disease, and Current
Supplementation Recommendations: An Evidence Based Clinical Review. J Am Osteopath Assoc.
2017;117(5):301-305 Dr Hanish Babu, MD, 2020

Maintenance Dosage : How much and How
Often?
•50,000 IU monthly Once : Sufficient?
•1000- 2000/day : Sufficient?

Maintenance dose of
2000 IU of Vitamin D
is not enough for
patients to keep the
25(OH)D levels
above 30ng/ml.

Vit D Deficiency is a Global Problem
• Studies from around the world
show that deficiency is above
50% in most countries.
• A two-year Dubai Health
Authority study presented in
2017 found an estimated 90
per cent of the UAE population
are vitamin D deficient.

Ref: vitamindwiki Dr Hanish Babu, MD, 2020

Vitamin D is not a standalone Nutrient!

Magnesium and Vitamin D metabolism.
Magnesium acts as a cofactor for the
vitamin D–binding protein and the
cytochrome hydroxylase enzymes. Low
Mg will result in low PTH.
Causes for Mg Deficiency
1. Inadequate Vegetables & fruits
2. Decreased intestinal
absorption
3. Excess Alcohol
4. Renal tubular loss

Vitamin A and Vitamin D are molecular partners

, Vit K2
Vit A
Vit E
Vit C
Vit K2
Folate
Modified from Dr Renu Mahtani: Reproduced with permission

Skin Color and UV Radiation and Vit D
• Skin colour of humans correlates with geographical latitude and
UV radiation levels.
• This also affects the absorption of UVB Rays and production of
Vitamin D
• The detrimental effect of UV on folic acid generation and DNA
mutations has to be balanced.
• Evolution has used skin pigmentation as a tool for that balance.
Holick MF, 2003 Evolution and function of vitamin D. Recent Results Cancer Res 164: 3-28.

Vitamin D Toxicity: Extremely rare!
• Taking extremely high doses of vitamin D3 for long
periods may lead to excessive build up in your body.
• Vitamin D intoxication occurs when blood levels rise
above 150 ng/ml (375 nmol/l).
• Effects of toxicity may last for several months after you
stop taking supplements .

Signs and Symptoms of Vitamin D Toxicity
• High Blood Levels: Vitamin D levels greater than 150 ng/ml
(375 nmol/l)
• Elevated blood calcium levels
• Nausea, vomiting, and poor appetite
• Stomach pain, constipation, or diarrhea
• Bone loss: Interfere with Vit K2 & Calcium: high bone loss.
• Kidney failure

(Menaquinone: Calcium metabolism: bone, hair, nail and teeth:
Animal sources (diary, liver, egg yolks) & Fermented food).
(Vegetables, pulses, nuts, Fish)

Vit D : How Much is Too Much?
Shroff R, Knott C, Rees L. The virtues of vitamin D – but how much is too much? Pediatr Nephrol. 2010;25(9):1607–20
There is emerging evidence that vitamin D may in fact have a
therapeutic window, at least from the effects on the
cardiovascular system.
More is not necessarily better!

The Lower and Upper Limits
In women from the United States, Finland and China, mortality
for 7 types of cancer (endometrial, esophageal, gastric, kidney,
non-Hodgkin's lymphoma, pancreatic, ovarian) increases below
45 nmol/L (18ng/ml)and above 124 nmol/L(50 ng/ml)
Helzlsouer KJ Steering Committee of Vitamin D Pooling Project of Rarer Cancers. Vitamin D: panacea or a
Pandora's box for prevention? Cancer Prev Res. 2010;3(1 Suppl 1):04–05.

Framingham Heart Study
The Framingham Heart Study concluded that cardiovascular disease
risk increases below 50 nmol/L (20ng/ml) and above 62.5 nmol/L (25
ng/ml), while the NHANES III found higher all-cause mortality above
122.5 nmol/L (49 ng/ml)
Davis CD. Vitamin D and health: can too much be harmful? Am J Lifestyle Med. 2009;3(5):407–8.

Lifespan Curve and Vit D
Animal and human studies
have indicated a U-shaped
response curve for lifespan,
with premature ageing
associated with both too little
and too much vitamin D.
Vitamin D, nervous system and aging.Tuohimaa P, Keisala T, Minasyan A, Cachat J, Kalueff A
Psychoneuroendocrinology. 2009 Dec; 34 Suppl 1():S278-86.
20 50ng/ml

Optimum Levels of Vit D
or

Sources of Vitamin D
• Sunlight is the best source of vitamin D, but many
people can’t get enough for various reasons.
Theoretically we should get 80% from sunlight.
• Foods and supplements that are high in vitamin D
include cod liver oil, fatty fish, egg yolks and
mushrooms.

Food Sources
of
Vitamin D

Who Needs More Vitamin D
1. Imbalanced diet & less sun-exposure
2. Older people
3. People with darker skin
4. Obese
5. Those who live farther from the equator
6. People who can’t absorb fat properly
7. Poor outdoor activities
8. Whoever is deficient!

I am taking Vit D supplements
Do I need to expose to sunlight?

Sun Exposure & Vit D
• Approximately 5–30 minutes of sun exposure between 10 AM and 3
PM at least twice a week to the face, arms, legs, or back without
sunscreen usually lead to sufficient vitamin D synthesis.
• Individuals with limited sun exposure need to include good sources of
vitamin D in their diet or take a supplement to achieve recommended
levels of intake.
• Sun exposure and vitamin D may have independent effects on disease
risks.
Hartley M, Hoare S, Lithander FE, et al. Comparing the effects of sun exposure and vitamin D supplementation on
vitamin D insufficiency, and immune and cardio-metabolic function: the Sun Exposure and Vitamin D
Supplementation (SEDS) Study. BMC Public Health. 2015;15:115. Published 2015 Feb 10.

Enhanced Sun Exposure Advise (ESEA)
• Amount of the body surface area vs Vit D production
• Prolonged sun exposure  result in degradation of Vit D
• ESEA focuses on short, frequent sun exposure, with as much
skin exposed as is feasible for the circumstances.
• Longer sun exposure  use sun protection
Vitamin D status: multifactorial contribution of environment, genes and other factors in healthy Australian adults
across a latitude gradient.Lucas RM, Ponsonby AL, Dear K, Valery PC, Taylor B, van der Mei I, McMichael AJ,
Pender MP, Chapman C, Coulthard A, Kilpatrick TJ, Stankovich J, Williams D, Dwyer T
J Steroid Biochem Mol Biol. 2013 Jul; 136:300-8.

Non Vitamin D benefits of Sunexposure
During summer and winter, even non UVB time , ie, early morning and
afternoon sun exposure may also be beneficial.
Hart PH, Gorman S, Finlay-Jones JJ. Modulation of the immune system by UV radiation: more than just the effects
of vitamin D? Nat Rev Immunol. 2011;11(9):584–96.
Lucas RM, Ponsonby AL, Dear K, Valery PC, Pender MP, Taylor BV, et al. Sun exposure and vitamin D are independent
risk factors for CNS demyelination. Neurology. 2011;76(6):540–8

Extra Vitamin D Benefits of
Sun Exposure
(Pro-opiomelanocortin responsive neurons)
(arcuate nucleus)
Beneficial in cardiometabolic
dysfunctions and obesity

A. Seasonal variation of 25-hydroxyvitamin D in 58 Aboriginal Australian
men (solid circle) and women (solid triangle).
Vanlint SJ, Morris HA, Newbury JW, Crockett AJ. Vitamin D insufficiency in Aboriginal Australians. Med J Aust. 2011;194:131–4.
Seasonal
variation of Vit D
levels is a very
well established
factor, falling to
the lowest during
winter months.

Comparison of serum 25(OH)D
concentrations in healthy adults who
were either in a bathing suit and
exposed to suberythemal doses (0.5
MED) of UVB radiation once a week
for three months compared with
healthy adults who received 1,000
units of vitamin D3 daily during the
winter and early spring for a period of
11 weeks.
Holick MF. Vitamin D deficiency. N Engl J
Med. 2007;357:266–81.
UV exposure even once in a
week was superior to Vit D
supplement of 1000 IU per day.
Sun exposure is anytime better
than supplements!

Ethnic Differences in Vit D requirements
Northern inuit natives and Amerindian aborigins: low levels of Vit D.
But no sign of Rickets!
Natural selection should have progressively reduced their vitamin D
requirements.
increased conversion to active form of Vit D
More effective binding with receptors
Alternate pathways for calcium metabolism
High meat diet, fish diet
Tuohimaa P, Keisala T, Minasyan A, Cachat J, Kalueff A. Vitamin D, nervous system and
aging. Psychoneuroendocrinology. 2009;34(Suppl 1):S278–86. Dr Hanish Babu, MD, 2020

Vit D in African Americans
• African Americans, despite having lower total 25(OH)D levels, have
normal levels of free 25(OH)D [ie, 25(OH)D is not bound to the
circulating protein and is “bioavailable”] similar to Caucasians.
• Because the free form of the substance is likely the form used by
cells, African Americans may not be at greater risk of deficiency, as
had been assumed in the past .
Christine L. Taylor et al. Questions About Vitamin D for Primary Care Practice: Input From an NIH Conference. The American
Journal of Medicine. VOLUME 128, ISSUE 11, P1167-1170, NOVEMBER 01, 2015.

Other Ethnic Variations
• For risk of pancreatic cancer, the optimal range seems to be
lower among Chinese than among European Americans.
(Stolzenberg-Solomon RZ et al, 2010)
• For risk of atherosclerosis, the optimal range is likewise lower
among African Americans than among European Americans.
(Freedman BI et al.)
Frost P. Vitamin D deficiency among northern Native Peoples: a real or apparent problem?. Int J Circumpolar
Health. 2012;71:18001.

Vit D Levels and Calcium Levels
• Serum levels of the circulating form of vitamin D, 25-
hydroxyvitamin D, and calcium were measured in 104 Saudis, 44
Jordanians , 17 Egyptians and 10 other subjects aged between
18 and 23 years.
• The percentages of subjects with serum 25-hydroxyvitamin D
levels below 10 ng/ml were 35, 45, 53 and 50% for normal
Saudis, Jordanians , Egyptians and others, respectively.
• All subjects had normal serum calcium concentrations.
Sedrani SH. Low 25-hydroxyvitamin D and normal serum calcium concentrations in Saudi Arabia: Riyadh
region. Ann Nutr Metab. 1984;28(3):181-185.

Adaptation to Low Levels of Vit D
Humans have successfully adapted to environments where
vitamin D is much less available through solar UVB
synthesis in the skin or through dietary intake
Our vitamin D norms may simply reflect what is normal for humans
whose physiology has adapted to lighter skin, lower latitudes and more
solar UVB.
Frost P. Vitamin D deficiency among northern Native People: a real or apparent problem?. Int J
Circumpolar Health. 2012;71:18001. Published 2012 Mar 19.

Standardization of Normal Vitamin D Levels
Need for standardization of normal, deficient and toxic levels
among ethnic groups and populations depending upon the skin
color and latitudes.

Medical conditions where sun exposure or Vitamin D
supplementation may have adverse effects
• Sarcoidosis
• History of renal calculi
• Uncontrolled endocrine disease
• Hepatic or Renal disease
• Photosensitivity diseases such as systemic lupus
erythematosus with cutaneous manifestations

CHRONIC DISEASES: PERSPECTIVE
• A chronic disease is the breakdown of structure and/or function of a
body system
• Its origin is usually multifactorial
• Genes
• Environment
• Nutrition
• Infection
• Toxins
• Injury
Low vitamin D
status impairs the
protective/reparative
activity

CHRONIC DISEASES: PERSPECTIVE
It is advisable for physicians to ask this questions while treating
a patient:

What is Healthy Life Style?
&
Relationship to Vitamin D?
We need a paradigm shift from
illness oriented healthcare to
Wellness oriented healthcare!

Slide Courtesy Dr P K Sasidharan

1. Balanced food : everyday and every time: Vit D, Magnesium and
other nutrients
2. Exercise in sunlight : Gives Vitamin D, reduces HT/DM
3. No smoking, excess alcohol, addictions: avoids liver disease,
cancer, HT, deficiencies
4. Adequate safe drinking water; Cells hydrated, kidney function
normal
5. Avoid overeating: obesity, no Liver disease
6. Avoid junk foods: No liver disease, HT,DM, decreased salt & sugar,
7. Adequate sleep: repair mechanism
8. Stress management: Relaxation, immunity, hormonal homeostasis

Why no balanced food?
• Wrong concepts and beliefs (cultural/religious/social)
• Vegetarians do not take supplements to make up deficit, even do not
eat balanced vegetarian food!
• Non Vegetarians do not take vegetables and fruits
• Wrong combination of food: Aloo-roti, Rice and Potato
• Many avoid pulses saying it produces dyspepsia or gas
• Food fads: too much or too less of anything is bad for your health in
the long run
• And, so on……….

History of Vit D
• Hess and Unger, Chick: 1921: sunlight is good for rickets, along
with cod liver oil
• Huldschinsky, 1921: UV Lamp also cures rickets
• McCollum& Co: 1922: Named the antiricket factor Vitamin D
• Hess et al(1925): Cholesterol in the skin become activated to
sunlight and UV light into antirachitic nutrient.
• Windaus and Thiele 1925-1936: Structure of ergosterol,
calciferol or vitamin D-2, 7-dehydrocholesterol , and
cholecalciferol or vitamin D-3
Elmer McCollum
How to have a balanced diet, 1926

Should Vitamin D be scripted on every prescription?
• The answer to this question is still far from clear, but at least we
could clearly recommend routine evaluation of its level, with
particular focus on those who are at risk of its deficiency e.g.
elderly, obese, lacking proper sun exposure or with
malabsorption disorders.
• Vitamin D supplementation could represent an important
adjuvant treatment if deficient or insufficient.
• Keeping optimum levels are also important from the preventive
point of view.

Vitamin D3 has Synergistic Effects With Other
Vitamins
• Vit D3 acts synergistically with other vitamins like Vit K2, Vit A ,
Vit C and Vit E, along with minerals like Magnesium and Zinc.
• Hence need to give multivitamin and multimineral supplements
along with Vit D for optimum results.
FP Antoine et al. Focus on 1,25-Dihydroxyvitamin D3 in the Peripheral Nervous System.
Frontiers in Neuroscience. 2019: 13: 348-364.

Summary and Take Home Message
• Vitamin D functions as one of several micronutrient co-factors,
needed for cell function
• Serum 25(OH)D levels below 40ng.mL are not enough for most
body systems
• Levels of 30ng/mL to 50ng/mL may be considered safe for all
individuals.
• Inputs from all sources combined (needed to sustain 40ng.mL)
are in the range of approx. 5000 IU/d and higher.

• Getting enough vitamin D from sunlight and foods is necessary
for optimal health.
• It helps maintain healthy bones, aids your immune system and
may reduce the risk of many harmful diseases. Yet despite its
importance, many people don’t get enough vitamin D.
• In addition, older people, people with darker skin, those who
live farther away from the equator and people who can’t absorb
fat properly have higher dietary vitamin D needs.

• The current recommendations suggest consuming
1000-4000 IU (25–100 mcg) of vitamin D per day. This
may be raised to 5000-6000 in the deficient.
• Vitamin D3 is preferred over Vitamin D2
• Best time for sun exposure: 10 am to 3 pm

• If you lead a healthy lifestyle with balanced nutritious
diet, optimum sun exposure, regular exercise, proper
hydration, rest and relaxed life style, you do not require
supplements.
• If you are not taking supplements, do regular check ups
to rule out nutritional deficiencies including that of Vit D.

We can confidently answer these questions now!

Special Acknowledgements
Dr. Robert P Heany (1927-2016) Retd
Prof of Medicine, Creighton Uty, World
renowned researcher in bone biology
and Vit D.
50 years of Vitamin D research and papers!
Author of first paper from India on Vitamin D and Tuberculosis

Major Reference Text
Editors: David
Feldman J. Wesley
Pike Roger
Bouillon Edward
Giovannucci David
Goltzman Martin Hewison
2017
Page Count: 1180
Page Count: 1266

Other References
1. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Calcium and Vitamin D. Washington,
DC: National Academy Press, 2010.
2. U.S. Food and Drug Administration. Food Labeling: Revision of the Nutrition and Supplement Facts Labels. 2017.
3. Wolpowitz D, Gilchrest BA. The vitamin D questions: how much do you need and how should you get it? J Am
Acad Dermatol 2006;54:301-17.
4. Wagner CL, Greer FR; American Academy of Pediatrics Section on Breastfeeding; American Academy of
Pediatrics Committee on Nutrition. Prevention of rickets and vitamin D deficiency in infants, children, and
adolescents. Pediatrics 2008;122:1142-1152
5. Kim MP, Jay HS. Vitamin D Deficiency, Its Role in Health and Disease, and Current Supplementation
Recommendations: An Evidence Based Clinical Review. J Am Osteopath Assoc. 2017;117(5):301-305
6. PradhanAD,MansonJE.UpdateontheVitaminDandOmegA-3Trial (VITAL). J Steroid Biochem Mol Biol. 2016;155(pt
B):252-256.
7. Sundaram ME, Coleman LA. Vitamin D and influenza. Adv Nutr. 2012 Jul 1;3(4):517-25

A CME Series on Vit D by Dr Hanish Babu, MD in 3 Weekly Sessions
Friday 14thAug, 2020 @ 4.30 PM (UAE), 6.00 PM (IST)
Inaugural Session Covid19 & Vit D
Inauguration : Prof. P.K.Sasidharan
Emeritus Professor, Department of Family Medicine, Retd Prof & HOD,
Department of Medicine, Medical College, Kozhikode, Kerala
Address : Dr George Jacob A
President, Association of Kerala Medical & Dental Graduates, UAE
Chair Person: Prof.G.S Patnaik
Prof & Head, Post Graduate Dept of Orthopedics,,
Narayan Medical College, Sasaram, Bihar
Vote of Thanks : Dr Sughu M Koshy
Secretary General, AKMG EmiratesDr Hanish Babu, MD

A CME Series on Vit D in 3 Weekly Sessions
Talk 2 of the
Series
Vit D in Health
Dr Hanish Babu, MD
4.30 PM | UAE
6.00 PM | IST
1.30 PM | GMT
Watch all the talks on FB
https://us02web.zoom.us/j/86125727802
Join on Zoom
Friday 21st Aug, 2020
Chairpersons
Dr R C Sreekumar
Chairman, IMA Research
Cell & Digital IMA,
IMA, KSB
Dr Jamaludeen
Abubacker
Chairman, AKMG CME

Please post your
queries on
After watching the videos, as
most of the doubts have
already been answered
during the talks!
End of Final Part 3

Thank You!

Vitamin D Part 3-Vitamin D in Diseases and Dose Recommendations

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