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Advanced Nutrition
Vitamin D
MargiAnne Isaia, MD MPH
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VITAMINS MINERALS
VITAMIN D Resurgence of interest in vitamin D,
reasons Vitamin D deficiency is a worldwide
problem with health consequences
Rickets Current research indicating Vitamin D
deficiency plays a role in causing varieties of
Cancer, Heart Disease, Stroke, Autoimmune
Diseases, Diabetes, Depression, Chronic Pain,
Osteoarthritis, Osteoporosis, muscle weakness,
muscle wasting, birth defects, Periodontal
Disease. 1billion people worldwide have Vitamin
D deficiency of insufficiency.
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VITAMINS MINERALS

• VITAMIN D
• not really a vitamin in the strictest sense (our
  body manufactures it)
• must be regarded as a pro-hormone
• Two forms
• - D2 Ergocalciferol,
• Found in wild mushrooms or formed by
  irradiation of Ergosterol in yeast
• - D3 Cholecalciferol,
• Found in animal sources, or formed under
  condition of adequate UV irradiation of
  7-Dehydrocholesterol (skin).

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VITAMINS MINERALS
VITAMIN D Functions BONE HEALTH Maintains
normal blood levels of Calcium and Phosphorus
(absorption of calcium) (Without Vitamin D, only
10 to 15 of dietary Calcium and about 60 of
Phosphorus are absorbed) Promotes bone
mineralization REGULATION OF IMMUNE
FUNCTION REGULATION OF CELL GROWTH
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VITAMINS MINERALS
VITAMIN D
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VITAMINS MINERALS
VITAMIN D SOURCES Exposure to sunlight (UV
exposure affected by season, latitude, time of
day, cloud cover, smog, sunscreen etc) Food
sources (cod liver oil, salmon, cooked, egg, wild
mushrooms) Fortification (milk is fortified with
10 mcg400 IU D3 per quart)  
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VITAMINS MINERALS
VITAMIN D Latitude and Vitamin D production in
the skin Except during the summer months, the
skin makes little if any vitamin D from the sun
at latitudes above 37 degrees north (in the
United States, the shaded region in the map) or
below 37 degrees south of the equator. People
who live in these areas are at relatively greater
risk for vitamin D deficiency.
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VITAMINS MINERALS
VITAMIN D BIOCHEMICAL TRANSFORMATION
Conversion to active form - Liver
25-hydroxylase a 25-(OH) D3 -
Kidneys 1 a-hydroxylase a 1,
25-(OH)2D3 24-hydroxylase - Activated by 1,
25-(OH)2D3 - Involved in catabolism of 1,
25-(OH)2D3 to water-soluble biologically
inactive Calcitroic Acid Active form (hormone)
1, 25-(OH)2D3 Major circulating form 25-(OH) D3
assessment of Vitamin D status Rate limiting
enzyme 25-hydroxycalciferol-1-hydroxylase -
stimulated by low serum P and low serum Ca -
stimulated by PTH and other factors (fibroblast
growth factors 23, FGF-23)
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VITAMINS MINERALS
VITAMIN D
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VITAMINS MINERALS
VITAMIN D
Beneficial circulating level of 25-(OH) D3
Reference range 20 -100 ng/ml (preferred range
30 -60 ng/ml) Deficiency lt 20 ng/ml
Intoxication gt 150ng/ml Level for healthy bones
30 ng/ml Optimal health 50-60 ng/ml Cancer
prevention 55-90 ng/ml Very controversial data
regarding the recommended level Importance
Vitamin D plasma status level must be on the
annual check-up In the absence of adequate sun
exposure 800-1000 IU Vitamin D/day (90 of our
Vitamin D in the blood is related with sun
exposure) Vitamin D2 equally effective with
Vitamin D3 in maintaining circulating level of
25-(OH) D3
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VITAMINS MINERALS
VITAMIN D
Actions of 1, 25 (OH)2 D3 h Calcium absorption
in small intestine - by interacting with the
Vitamin D receptor-retinoic acid x-receptor
complex (VDR-RXR) to h Expression of the
epithelial Calcium channel protein h Expression
of the Calcium-Binding Protein (CaBP) h Calcium
resorption h Expression of the Receptor Activator
of Nuclear factor-kB ligand (RANKL) Involved in
inducing preosteoclasts to become mature
osteoclastes Mature osteoclasts remove Ca2 and
HPO42- from bone, maintaining Ca and P levels in
the blood Adequate Ca and P levels promote
mineralization of the skeleton
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VITAMINS MINERALS
VITAMIN D
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VITAMINS MINERALS
VITAMIN D AND NON-SKELETAL FUNCTIONS -
Maintains normal cell proliferation Tissues in
the body, including brain, prostate, breast,
colon, and others have the enzymatic machinery to
locally produce 1, 25-(OH)2 D . It controls more
than 200 genes responsible for the regulation of
cellular proliferation, differentiation,
apoptosis, and angiogenesis. - Potent
immune-modulator Monocytes and macrophages
exposed to a lipopolysaccharide or to M.
tuberculosis up-regulate the vitamin D receptor
gene and 25-(OH) D-1a-hydroxylase gene.
Increased production of active Vit D results in
synthesis of Cathelicidin (bactericidal protein,
able of destroying M. tuberculosis and other
infectious agents). When there is vitamin D
deficiency, the monocytes and macrophages are
prevented from initiating this innate immune
response. - Inhibits Rennin synthesis -
Increases Insulin production Increases myocardial
contractility
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VITAMINS MINERALS
VITAMIN D
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VITAMINS MINERALS
VITAMIN D
Regulation of plasma Calcium Parathyroid
gland -Drop in serum Ca results in h PTH Role
of PTH hFormation of active Vitamin
D hRe-absorption of Ca by kidney hBone
resorption Role of Vitamin D hCalcium
absorption hRe-absorption of Ca by kidney hBone
resorption
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VITAMINS MINERALS
VITAMIN D
Clinical significance Vitamin D
deficiency Children Rickets Adults
Osteomalacia (bone pain including, associated
with joints pain, muscle pain and weakness).
Muscle weakness is associated with Vitamin D
deficiency (proximal muscles). Misdiagnosed as
Fybromyalgia, degenerative joint disease,
arthritis, chronic fatigue syndrome, etc.
Osteoporosis Increased risk for common cancers
(colon, prostate, breast), autoimmune diseases,
hypertension, infectious diseases (tuberculosis),
depression.
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VITAMINS MINERALS
VITAMIN D
Recommendations Sun exposure ten to fifteen
minutes of sun exposure at least two times per
week to the face, arms, hands, or back without
sunscreen Adequate Intake AI Children, birth to
13 years 200 IU 14 to 18 years 200
IU Adults, 19 to 50 years 200 IU 51 to
70 years 400 IU 71 years 600 IU
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VITAMINS MINERALS
Causes of Vitamin D Deficiency Reduced skin
synthesis Sunscreen use- absorption of UVB
radiation by sunscreen Skin pigment- absorption
of UVB by melanin Aging- reduction of
7-dehydrocholesterol in the skin Season,
latitude, and time of the day Patients with skin
grafts for burns Decreased bioavailability Mal-abs
orption- reduction in fat absorption resulting
from cystic fibrosis, celiac disease, by-pass
surgery, medication that reduce cholesterol
absorption, other. Obesity-sequestration of
Vitamin D in body fat
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VITAMINS MINERALS
Causes of Vitamin D Deficiency Increased
catabolism Anticonvulsants, glucocorticoids,
HAART (AIDS treatment), etc Breast-feeding-poor
Vitamin content in human milk Decreased synthesis
of 25-(OH) D liver failure Increases urinary
loss of 25-(OH) D nephritic syndrome Decreased
synthesis of 1, 25 (OH)2 D Chronic kidney
disease-stages 2 and 3 -stages 4 and
5 Heritable disorders-rickets Acquired disorders
tumors, hyperthyroidism, sarcoidosis, etc.
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VITAMINS MINERALS
VITAMIN D
Vitamin D supplementation to prevent
deficiency - infants who are exclusively
breastfed - older adults - persons with limited
sun exposure - persons with greater melanin skin
content - persons with fat malabsorption
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VITAMINS MINERALS
VITAMIN D
Current issues and controversies about Vitamin
D Vitamin D and Osteoporosis Vitamin D and
Cancer Vitamin D and steroids Vitamin D and
Alzheimers disease Vitamin D and
caffeine Caffeine may inhibit Vitamin D
receptors, limiting absorption
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VITAMINS MINERALS
VITAMIN D
Vitamin D toxicity Public Health concern for The
US High intake of Vitamin D in supplements Never
get toxic level from sun exposure excessive
exposure to sunlight degrades pre-vitamin D3 and
Vitamin D3 into inactive photoproducts. Can
cause nausea, vomiting, poor appetite,
constipation, weakness, weight loss. Raise blood
levels of Calcium (mental status changes, heart
rhythm abnormalities)
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LIPIDS
REFERENCES 1. Shils M et al, Modern Nutrition
in Health and Disease, 10th Edition 2. www.
Pubmed.org
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