Vit d is it the mericle vitamine

VIT D IS IT THE
MIRCLE VITAMINE
DR : NAGLAA ABO BAKR
COSULTANT CLINICAL PATHOLOGY

What is vitamin?
Vitamin – VITAL AMINE – essential for health
“an organic compound, not made at all or in sufficient
amounts by the body”

Which is the most important ?
A (or beta carotene)
B 1,2,3,4,6,8,10,12
C
D
E
K

Which is the most important ?
A (or beta carotene)
B 1,2,3,4,6,8,10,12
C
D
E
K
The literature on Vitamin D
has exploded in recent years.

Vitamin D
– Vitamin D2 (ergocalciferol)
• (Pharmaceutical Form derived from Ergol found in Fungus)
– Vitamin D3 (cholecalciferol)
• (Natural Form found in food and synthesized in Skin)
• metabolites and analogues of these substances
• Vitamin D
– Precursor (sometimes referred to as a “prohormone”)
– Must be metabolized to become biologically active
• Active form of vitamin D: Calcitriol
Vitamin D

Production, Metabolism, and Biological
Function of Vitamin D
1,25(OH)2D3 1,25(OH)2D3
Vitamin D3 25(OH)D3
Prostate
Gland,
Breast,
Colon,
Lung
Calcium
Homeostasis
Muscle Health
Bone Health
Blood pressure regulation
Cardiovascular Health
Immunomodulation (prevention of
autoimmune diseases)
Regulation of
Cell Growth
(cancer prevention)
Liver
Kidney
25(OH)D3=25-hydroxyvitamin D3; 1,25(OH)2D3= 1,25-dihydroxyvitamin D3.
Holick MF. Am J Clin Nutr 2004;80(suppl):1678S-88S.
Skin
D D
Milk
Orange juice
Supplement
Cod liver oil
Salmon

Pathophysiology
Vitamin D deficiency leads to impaired intestinal absorption of calcium
Which results in decreased levels of calcium levels.
This hypocalcemia gives rise tosecondary hyperparathyroidism
It is a homeostatic response aimed at maintaining, initially, serum
calcium levels at the expense of the skeleton.
Following this PTH-induced increase in bone turnover, alkaline
phosphatase levels are often increased.

PTH not only increases bone resorption, but it also leads to
decreased urinary calcium excretion while promoting
phosphaturia.
This results in hypophosphatemia, which exacerbates
the mineralization defect in the skeleton.

Musculoskeletal Effects
• Maintenance of normal musculoskeletal function
– Skeletal muscle has receptors (VDR) for 1,25(OH)2D3
– Severe vitamin D deficiency is associated with
muscle weakness, limb pain & impaired physical
function
Vitamin D

Extraskeletal Effects
• Regulation of cell growth and effects on immune function
• Epidemiologic studies have shown that living at lower
latitudes 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

What do we measure ?
• Most assays for 25(OH)D cannot differentiate the two
distinct forms , 25(OH) D2 from 25(OH) D3, so the
abbreviation 25(OH)D is used.

What do we measure ?
• The serum 25-hydroxyvitamin D , 25(OH)D level
is the best indicator of overall vitamin D status.
because
This measurement reflects total vitamin D from
dietary intake and sunlight exposure, as well as
the conversion of vitamin D from adipose stores
in the liver
Half-life approximately 2 weeks

1,25(OH)2D3 should never be used to determine
vitamin D status
Determination of vitamin D status

Half-life :is approximately 4 h.
It circulates at 1000 times lower concentration than 25(OH)D.
The blood level is tightly regulated by serum levels of PTH,calcium, and
phosphate.
Serum 1,25(OH)2 D is frequently either normal or even elevated
in those with vitamin D deficiency, due to secondary
hyperparathyroidism.
Thus, 1,25(OH)2 D measurement does not reflect vitamin D
status.
Serum 1,25(OH)2 D does not reflect vitamin D reserves.

People with a granuloma disease such as sarcoidosis
can have a high level of serum 1,25-dihydroxy-vitamin
D but show a low testing level of serum concentration
of 25-hydroxy-vitamin D
because the granulomas, when active, produce
serum 1,25-dihydroxy-vitamin D.
The body is then protecting itself from a calcium
dump ( high calcium level) by having a low 25-
hydroxy-vitamin D.

How do we Interpret report
Deficiency :level less than 10 ng/mL .
Insufficient : level between 10 to 30 ng/Ml .
Sufficient ..more than 30 ng/ml .

Frequency of measuring
• Measurement of serum 25-hydroxyvitamin D should
follow three to four months of adequate
supplementation and should not be repeated if an
optimal level(≥ 30 ng/mL) is achieved .

You may need more than the usual dose if
taking certain medicines which interfere with
vitamin D.
These include: carbamazepine, phenytoin,
primidone, barbiturates and some medicines
for the treatment of HIV infection

For example, in patients without clinical improvement
after D2
or D3
supplementation, lack of increase in the
corresponding 25(OH)D2
or 25(OH)D3
and total 25(OH) D
levels may indicate inadequate dosing, nonadherence, or
malabsorption.
 A single dose of 50,000 IU of D2
or D3
produces a similar
increase in the total 25(OH)D concentration, but the
apparent longer half-life of D3
suggests that less frequent
dosing may be needed

•Which one of the following biochemical tests
provides the best initial assessment of a person's
vitamin D status?
•Serum parathyroid hormone (PTH)
•Serum 25-hydroxyvitamin D
•Serum 1,25-dihydroxyvitamin D
•Serum bone alkaline phosphatase
•24-hour urine calcium excretion

What does Vitamin D do to
make such a difference in
health?
Vitamin D ‘affects gene expression”
It turns genes on and off.
In the nucleus of all of our cells are chromosomes– one
from mum and one from dad.
These are made of DNA – and segments of DNA are
genes.

The genes are the blueprint of the cells
•Makes proteins in the cell to
• build,
• repair,
• recover,
• fight
• function
These only action when
needed
For many processes –
vitamin D is essential for
the switch to work.

Protei
n
How the cells make
proteins
Messenger RNA makes
a copy of the DNA
Goes out of the nucleus
to the ‘production’ factory
– the ribosomes
The MRNA runs thru the
ribosome like a tape,
giving instructions on the
protein to make.
The DNA is the blue
print plan

Genes don’t want to be making
proteins continuously – they need to
be turned on and off – REGULATORS.
Vitamin D is a major regulator in the
human.
There are over 230 Vitamin D
receptors in the nucleus of most
tissues in our bodies.

Proein
Ribosome
The vitamin D receptors (VDR) up
or down regulate the activity of
the cell production.
VDRs have been found by genes
associated with:
•Diabetes
•Crohn’s disease
•Cancer
•Leukaemia
•Rheumatoid arthritis
•Multiple sclerosis
And we have only just started
looking………
This explains
why vitamin D may have a role in preventing cancer,
influenza, autism, asthma, multiple sclerosis, and
cardiovascular disease, not just curing rickets and
osteomalacia

Vitamin D also tells cells when to divide, stop dividing and also
when to die (apoptosis).
With low vitamin D levels, cells may
•Not die and become immortal
•Continue to divide out of control

Vitamin D affects cancer cells in a number
of ways:
•Switches apoptosis back on – programmed cell death

of ways:
•Slows down multiplication and spread of cancer cells

of ways:
•Reduces growth of new blood vessels to feed the cancer
and increase spread

Vitamin D also seems to do all the right
things for the heart.
• Vit D receptors in the artery walls and
heart muscle
• Lowers BLOOD PRESSURE via the
ACE system
• Improves insulin sensitivity
• Reduces inflammation
• Improves vessel wall recovery to injury

There are many diseases where low
Vitamin D levels are found:
Parkinson’s disease – reduced production of dopamine
in the substantia nigra.
Archives of Neurology, March 2011
American Heart Association's (AHA) Annual Scientific Sessions,
Chicago, IL November 15, 2010

Low Vitamin D doubles the risk of having a stroke
Journal of Allergy and Clinical Immunology June 8, 2010
Diabetes Care. 2011 Ma

Children with low Vitamin D levels doubled the risk of
admission to hospital

Risk of diabetes rises – 57%

Macular Degeneration – 59%

Depression is 11 TIMES as common
in those with low vitamin D levels
Serotonin, the brain hormone associated with mood elevation, rises
with exposure to bright light and falls with decreased sun exposure.
One study found low serum vitamin D
concentrations in patients with schizophrenia.
Vitamin D acts as a catalyst in glutathione
production.
Low glutathione levels have been implicated
in several mental health disorders.

•Whenever there is a risk of infection, make sure your Vitamin D
levels are optimal.
•Is it a coincidence that flu and infections are higher in the low
sun winter months?

Vitamin D switches on the production of over 200
antimicrobial peptides – the most important one we know of
is CATHELICIDIN – a naturally occurring broad-spectrum
antibiotic.

Vitamin D is essential for our immune
system
The T cells have vitamin D receptors on
their surface, allowing them to transform
into KILLER cells and also to multiply
“Without vitamin D the
white cells lie dormant!”
An army of specific killer cells attacks and kills the invader

Once the diseases have developed,
Vitamin D levels still make a difference:
•High vit D Doubles the survival in people with colon cancer
•High vit D Reduces heart failure hospitalisation and mortality
•Women taking vitamin D lowered heart deaths by 33%
•Women given Vitamin D supplements reduced cancer by up
to 60%
British Journal of Cancer September 15, 2009; 101(6):916-23
European Society of Cardiology (ESC) Congress 2010 August
28-September 1, 2010, Stockholm, Sweden
2nd annual conference on Cardiovascular Disease and
Epidemiology Prevention in Honolulu, Hawaii. April 23, 2002

These results are almost too good to
be true – BUT ARE THEY TRUE.

Fracture and Vitamin D Deficiency
Case Study 1
• 26 year old male of Middle Eastern heritage with 2 1/2 years of service,
lived in Northern U.S. last 9 years.
• Sustained stress fracture of left tibia during training (AIT).
– X-rays reveal stress fracture at 4 weeks.  Placed in cast for 12
weeks.  Cast removed and given tramadol for chronic pain.
• Deployment to Iraq
– Exposed to 5 blasts, 2 with brief loss of consciousness
– Changed to Percocet for pain, later evacuated for acute
psychosis
• Psychosis resolved and bone scan revealed non-union of stress
fracture at 17 months.
• Patient referred to Deployment Health Clinical Center
– PTSD, anxiety, and co-morbid chronic left tibial pain.
• Screening 17 months after fracture: vitamin D level of 11 ng/ml
(normal > 30).

Case Study 2
• 36 year old African American with 6 years of service, signed up
after 9/11 while living in the northern U.S.
• Deployment to Iraq
– 3rd month: rolled off cot during mortar attack and injured right
wrist. Negative X-rays. Conservative measures for chronic pain.
– 4th month: re-injured right wrist when 84 pound machine gun was
dropped on it.
– 9th month: chronic pain leads to medical evacuation.
• Arthroscopy performed with some improvement in pain,
Conservative management continued.
• Nuclear scan for chronic pain 7 months after injury:
– stress changes in lunate wrist bone and posttraumatic changes
in triquetrum. Conservative management remains indicated.
• Patient referred to Deployment Health Clinical Center for co-morbid
PTSD, anxiety, and chronic right wrist pain.
• Screening 14 months after injury: vitamin D level of 12 ng/ml
(normal > 30).

Deployment Health Clinical Center
• Of 94 referrals seen from March 2005 until
September 2006, 83 (88%) were screened.
– > 90% with chronic musculoskeletal pain
– Either multiple unexplained physical symptoms . 14
with fibromyalgia.
• 46% (n= 38) have low Vitamin D (< 30 ng/ml)
– Average for those deficient: 13 ng/ml (range: 6-19)

• Pathophysiology for the association of chronic pain
and Vitamin D Deficiency is not known
• However, Vitamin D receptors have been
recognized in the CNS, as well in many other
tissues, suggesting vitamin D has essential
functions as a hormone outside of bone
metabolism
• Chronic pain has been associated with CNS
dysfunction
• Vitamin D receptor knock-out mice demonstrate
anxiety behaviors

The Planet is Vitamin D
Deficient

All That Glitters is not GOLD…

Vit d is it the mericle vitamine

Vit d is it the mericle vitamine

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