Vitamin D in Children in health and disease

1. Vitamin D in health
and disease
Professor Khaled Saad,
MD, MSc, PhD

2. FIRST and LAST
• Vitamin D deficiency in several populations
remains an under-recognized clinical
problem, and its significance extends beyond
skeletal health to non-classical actions of
vitamin D, including a range of immune-
related diseases.
• There is solid evidence that vitamin D
supplementation can reduce the rates of
infections in pediatric populations.
• There is also growing evidence for a
beneficial role of supplementation in
preventing autoimmune disorders, and there
is promising data linking vitamin D
deficiency to increased rates of childhood
asthma and other allergic conditions.

3. Agenda
Vitamin D deficiency
Historical note
Vitamin D
Metabolism
Vitamin D in health
and Diseases

4. Major milestones in the discovery of the origin
of vitamin D and nutritional rickets.
19191890
Sniadeck: discussed
the cure of rickets
and recommended:
“Take the children
out into the country
and deep them in the
dry open and pure
air” or at least
“exposure them to
Palm:
advocated
“sunbathing
to treat and
prevent
rickets
McCollum
concluded that
cod liver oil
contains a new
vitamin, called
vit D as vitamin
A, B and C
were already
known in 1922.
Huldschinsky
Rickets in
children can
be cured by
artificial UV
light (mercury
vapor lamp)
Windaus group
finally realized the
chemical syntheses
of the vitamin D
compounds,
confirming their
structures. Windaus
received a Novel
price in 1928
Vitamin D
192819221822

9.  The term “Vitamin D” refers to a family
of related compounds biosynthesized from
cholesterol and ergosterol.
 Vitamin D3 (cholecalciferol) is synthesized
from 7-dehydrocholesterol in sun-exposed
skin and found naturally in animal
products such as eggs, fish and liver.
 Vitamin D2 (ergocalciferol) is another
form of vitamin D synthesized by certain
fungi and is used in many supplements.
Vitamin D
Metabolism

10. (Ergocalciferol)
VITAMIN D2
(Cholecalciferol)
VITAMIN D3
*Found in plant life*Synthesized in the body
*Synthetically derived supplement*Naturally, derived supplement
*Moderately increases vitamin D levels
in the body
*Significantly increases vitamin D
levels in the body
*Alternative form appropriate for
vegetarians
*Recommended by experts for optimal
bone and immune support
Vitamin D Metabolism

11. • However, vitamin D3 is the preferred
form for humans as its bioavailability is
twice that of vitamin D2.
• After absorption from foods or
production in the skin, vitamin D is
stored as 25-hydroxy-vitamin D3 in the
liver. When needed by the body, it is
then activated by the kidney to 1, 25-di
hydroxy vitamin D3.
• NB: A healthy liver and kidneys are
essential for optimum vitamin D status.

12. Vitamin D Metabolism

13. Biosynthesis and Activation of Vitamin D3

15. 1. Calcium metabolism (main function):
Vitamin D regulates Ca++ levels in the blood and tissues. A fall in
blood Ca++ stimulate active vitamin D production stimulates
Ca++ absorption from food + release of Ca++ from bones + renal
excretion of Ca++.
FUNCTIONS OF VITAMIN D

16. 2.Essential for normal bone growth
during childhood (as it increases Ca++
absorption from foods + increases Ca++
deposition into the skeleton).
3.Integrated function with parathyroid
hormone in stabilization of Ca++ level in
blood.
4.Regulation of cell growth and
development (particularly WBCs and
epithelial cells).

17. PEOPLE AT
GREATER
RISK OF
DEVELOPING
VITAMIN D
DEFICIENCY
• Newborn infants: who are absolutely
breastfed require vitamin D supplements
because mother milk does not contain
significant levels of the vitamin.
• Lactating women: The serum concentration
of vitamin D and Ca++ falls rapidly.
• Dark-skinned and obese people.
• Patients with chronic liver disease or
malabsorption or parathyroidectomy.

18. Vitamin D Deficiency
SUBCLINICAL DEFICIENCY
1. Silent epidemic, Present in
approximately 30% to 50% of the
general population.
2. More prevalent in infants.
3. Often unrecognized by clinicians.

19. HARRT: highly
active
antiretroviral
therapy;
IBD:
inflammatory
bowel diseases;
MS: multiple
sclerosis;
PsA:
Psoriatic arthritis;
T1DM: type 1
diabetes mellitus;
T2DM: type 2
diabetes mellitus;
RA: rheumatoid
arthritis.

20. Vitamin D
Deficiency

21. Consequences of Vitamin D Deficiency
Rickets

23. There are 2 strategies for administration of
vitamin D:
• Stoss therapy , vitamin D (300,000-600,000
IU) is administered orally or
intramuscularly as 2-4 doses over 1 day.
• The alternative strategy is oral daily
vitamin D3 with a minimum dose of 2,000
IU/day for a minimum of 3 months.
• Either strategy should be followed by daily
vitamin D intake of 400 IU/day if <1 year
old or 600 IU/day if >1 year old.

24. Muscular health
Vitamin D deficiency is
associated with:
◦ Diffuse muscle pain. Muscle
weakness predominantly in
the proximal muscle groups.
◦A reduction in performance
speed.
◦ Limb pain & impaired
physical function.

26. Extra-skeletal Effects
*Regulation of cell growth and effects on immune
function:
• Epidemiologic studies have shown that vitamin D
deficiency is associated with a decreased risk of
many chronic diseases: Multiple sclerosis,
hypertension, and cancer of the colon, breast, and
prostate.
• Some studies have shown that increasing vitamin D
intake decreases the risk of certain chronic diseases:
Diabetes, rheumatoid arthritis, hypertension, and
colon cancer.

27. Which of the following is not a function of vitamin D?
a) Lipid-soluble antioxidant in cell membranes
b) Fast responses to increase calcium absorption with no
change in gene expression
c) Regulation of differentiation of adipocytes
d) Regulation of bone turnover

29. Association
of Vitamin
D
Deficiency
and
Neurologic
Disorders
Epidemiological studies

30. Affects of Vitamin D on
Brain Function
• Active form of Vitamin D is synthesized
and eliminated in the brain
• Numerous Vitamin D receptors in
cortical neurons, and glia
• Enzymes involved in metabolism of
Vitamin D also expressed in brain cells
• Metabolites of Vitamin D reported in
CSF
• Holmoy,T. & Moen,S.M. (2010). Assessing vitamin D in the central nervous system. Acta
Neurol Scand. 122: 88-92.

31. Vitamin D affects the
development of
neurons as well as
their maintenance
and survival.

32. Vitamin D
and the
Brain
• Influences brain development:
cell growth, neuronal
differentiation, axonal
connectivity, neurotransmitter
function, brain structure,
learning, memory.
• Crucial role in
neuroprotection,
neurotransmission and
neuroplasticity.
• Regulates catecholamine levels.
• Synthesizes acetylcholine,
serotonin and dopamine.

33. Vitamin D
deficiency and
childhood asthma

34. There is solid evidence that
vitamin D supplementation can
reduce the rates of infections in
pediatric populations. There is
also growing evidence for a
beneficial role of
supplementation in preventing
autoimmune disorders, and
there is promising data linking
vitamin D deficiency to
increased rates of childhood
asthma and other allergic
conditions.

35. • Cognition
• Chronic Pain
• Multiple Sclerosis
• Parkinson’s Disease
• Migraines
• Myopathy
• Stroke
• Fibromyalgia
• Seizures
• Sleep Disorders/Restless Leg

36. Vit D supplementation
According to the Endocrine Society Practice
Guidelines:

37. Treatment of deficiency

38. FIRST and LAST
• Vitamin D deficiency in several populations
remains an under-recognized clinical
problem, and its significance extends beyond
skeletal health to non-classical actions of
vitamin D, including a range of immune-
related diseases.
• There is solid evidence that vitamin D
supplementation can reduce the rates of
infections in pediatric populations.
• There is also growing evidence for a
beneficial role of supplementation in
preventing autoimmune disorders, and there
is promising data linking vitamin D
deficiency to increased rates of childhood
asthma and other allergic conditions.

39. THANK YOU
Khaled Saad