lect #8 vitamin d
TRANSCRIPT
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THE CRITICAL ROLE OF VITAMIN D IN
INFANTS, CHILDREN AND
ADOLESCENTS
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DISCLOSURE
y Commissioned work developed by Dr. Melanie Alcausin,
Pediatric Genetics Specialist and Dr. Benjamin Sablan,
Ambulatory Pediatrician both from the University of the
Philippines College of Mediciney No product endorsement in the lecture
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Vitamins
Essential substances needed fornormal functioning of the body
At the end of the 20th century,increased interest in Vitamin C and E
In the more recent years, focusshifted to Vitamin D
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Vitamin D Prohormone
Two forms
Vit D2 (ergocalciferol) yeast and plantsVit D3 (cholecalciferol) oily fish
skin synthesis
Serum 25-OH Vit D- most reliable
indicator of Vitamin D status Essential in calcium homeostasis most
well-studied function of Vit D
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Vitamin D
Vitamin D (parent compound) synthesized inthe skin from cholesterol
Liver converts Vit D to 25-OH Vit D
Kidney synthesizes 1,25-(OH)2 Vit D from 25-OH Vit D
Vitamin D is transported in the circulation byvitamin D binding proteins
Mechanism of action of 1,25-(OH)Vit D is similarto other steroid hormones interacts withvitamin D receptors (VDRs) in the cell nucleusto promote gene transcription
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American Family Physician, 2009
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Sun exposure and Vitamin D Vitamin D requirement can be
obtained from sunlight exposure
Increased melanin in the epidermisreduces production of D3 in the skin
Concerns regarding increasingincidence of skin cancer AAPrecommendation no sun exposureuntil 6 months of age
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Sun exposure and Vitamin D Full body exposure during summer for
10-15 minutes 10,000-20,000 IU
Vitamin D3 in an individual with fairskin
In a darker pigmented individual, 5-10 times longer exposure
Pediatrics, 2008
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Dietary Sources of Vitamin D Breast milk 20 IU/L
Cod liver oil 400 IU/tsp
Egg yolk 20 IU
Mackerel (canned) 250 IU/3.5 oz Salmon (canned) 300-600 IU/3.5 oz
Salmon (fresh,farmed) 100-250 IU/3.5 oz
Salmon (fresh, wild) 600-1000 IU/3.5 oz
Sardines (canned) 300 IU/3.5 oz Tuna canned 230 IU/3.5 0z
Fortified milk 100 IU/8 OZ
American Family Physician,2009
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1,24 dihydroxy vitamin D Stimulates absorption of calcium and
phosphorus in the intestines
Affects calcium transport in thekidneys by enhancing the action ofPTH and by inducing TPRV5 andcalbindins
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Role in the Musculoskeletal System
Increasing Ca and P absorption would
increase incorporation into bone 45-65% increase in calcium transport
when 25-(OH) Vit D levels increasefrom 20 to 32 ng/ml (American Societyfor Bone and Mineral Research Primer, 2008)
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Role in the Musculoskeletal System Maintaining optimal Ca intake during
childhood and adolescence important
for attainment of peak bone mass
reduced risk of fractures andosteoporosis later in life (Pediatrics,2006)
Positive correlation of 25-(OH) Vit Dlevels and BMD
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Role in the Musculoskeletal System Vit D and calcium supplementation
improved BMD in older individuals
Positive association between 25-(OH)Vitamin D and muscle function
Vitamin D supplementation of at least800IU improved lower extremityfunction, decreased body sway andreduced falls - fractures
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What is a Normal 25-OH
Vitamin D Serum Level? Serum level 27 nmol/L - lowest level
that prevents physical signs of rickets ininfants (IOM report, 1997)
Adult Vit D deficiency < 30-37 nmol/L
Adult Vit D insufficiency < 50-80 nmol/L
Adult Vit D sufficiency 80-160 nmol/L
Toxicity > 200 nmol/L
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Vitamin D deficiencyMANIFESTATIONS non specific
Bone discomfort/pain in low back,
pelvis, lower extremities (symmetriclow back pain in Women)
Muscle aches
Proximal muscle weakness
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Vitamin D deficiency Growth failure
Lethargy
Irritability Seizures
Increased respiratory infections in
infancy
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Risk Factors for Vit D deficiency Age older than 65 years
Exclusively breastfed without Vit Dsupplementation
Dark skin
Insufficient sunlight exposure
Obesity (BMI >30kg/m2)
Sedentary lifestyle
Medications ( anticonvulsants,steroids)
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Rickets
Not a historical condition anymore
Resurgence in developed countries
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Rickets in Growing Infants
Children Vitamin D Deficiency Rickets in the US
occurs most commonly between 6 and
18 months of age, and is rarelyreported after the age of 5 years.
Some data is available on the numberof hospitalizations with rickets, though
it is estimated that less than half ofthe children with this diagnosis arehospitalized.
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Is there a level of 25-OHDthat is always associated
with rickets in infants andchildren?
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25-OH D levels in infants and
young children with Rickets
5 studies:Mean serum 25-OHD level 27.5 nmol/L to prevent rickets.
Clearly, cases of rickets have beendescribed with serum 25-OH D levels> 27.5 nmol/L even in the US.
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Can we use 25-OH Vit D levels andmeasures of bone health (serum PTH,
bone mineral content) to defineinsufficiency or sufficiency statesin infants and young children?
NO!
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Going beyond Rickets
Recent studies on Vitamin D
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Vitamin D and Cancer Vitamin D deficiency is associated
with various types of cancers with
most studies on breast, colon andprostate
Prospective 4-yr trial with Vitamin D1100 IU and 1400-1500 mg calcium
showed 77% reduction in cancer afterthe 1st yr of study (Lappe et alAm J ClinNutr, 2007)
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Vitamin D and the Immune
System Vitamin D deficiency and/or living in
higher latitudes (less sunlight)associated with autoimmune diseases
Type I DM
Multiple sclerosis
Crohns disease
(Ponsonby et al, Toxicology, 2002)
Childhood wheezing illnesses(Camargo et al,Am J Clin Nutr, 2007)
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1,25-(OH)2 Vitamin D
Non-Endocrine Function
Renal cells are not the only cells that
can synthesize 1,25-(OH)2 Vit D Placental cells can also do this
Certain immune cells
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1,25-(OH)2
Vitamin D
Macrophages can synthesize 1,25-(OH)2 vit D from 25-OH vit D wherethe hormone has a local (paracrine or
autocrine) effect on gene synthesis toproduce antimicrobial peptides
This implies that intracellularconcentrations of 25-OHD areimportant for the local effects ofvitamin D to occur
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Vitamin D Receptors and the
Immune System VDR's are found in monocytes,
macrophages, dendritic cells, natural
killer cells, T cells and B cells of theimmune system.
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Vitamin D Receptors and theImmune System
In CELL CULTURE, 1,25OH vitamin Dalters cytokine secretion patterns,suppresses T-cell activation, affectsmaturation and migration of dendriticcells, enhances phagocytic activity ofmacrophages, increases activity ofnatural killer cells.
Macrophages are capable ofaccumulating 25-OHD and locallyproducing 1,25OH Vit D
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Vitamin D Receptors and the
Immune System 1,25-OHD appears to have a local
effect within the cells of immune
system(as opposed to the general endocrine
effect we see with calcium metabolism)
These are the basis for the proposedrole of 1,25 OH D as an "immune
modulator" coupled with observationsassociating low 25-OH D levels withTB, influenza, cystic fibrosis, etc.
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Vitamin D and Metabolic Diseases
25-hydroxy Vitamin D levels areinversely associated with DM Type II
and metabolic syndrome Vitamin D and calcium
supplementation may preventprogression to DM in those with
glucose intolerance Improved insulin secretion and action
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RECOMMENDATIONS -AAP
VITAMIN D 400 IU/day supplemetation:
Breastfed and partially breastfed
infants beginning in the first fewdays of life
All non breastfed infants and olderchildren who ingests < 1L of fortified
milk
Adolescents who do not get 400 IUfrom diet
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RECOMMENDATIONS -AAP
Higher doses of Vitamin Dsupplementation in children withchronic malabsorption, on
anticonvulsants Serum 25(OH) Vitamin D in children
should be >=50 nmol/L (20ng/ml)
MDs to make Vitamin D readilyavailable to all children in theircommunity
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Vitamin D toxicity
Signs and symptoms of toxicity
Headache
Metallic tastePancreatitis
Nausea and vomiting
Nephrocalcinosis/vascular calcinosis
Has not been observed at doses
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In the Philippines.
Lots of sunshine
BUT
Darker skin pigmentation Decreased sun exposure due to:
1. Increasing sedentary lifestyle
2. Increasing use of sunscreen, bothphysical and chemical
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Summary
Vitamin D plays a role in immunemodulation, has been implicated toprevent certain forms of cancer,autoimmune diseases and Type II DM
Most diets do not contain sufficientVitamin D
Vitamin D supplementation should beconsidered to assure adequate levelsin the body
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Vitamins
Essential substances needed fornormal functioning of the body
At the end of the 20th
century,increased interest in Vitamin C and E
In the more recent years, focusshifted to Vitamin D
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VITAMIN HYPOTHESIS
Group of organic substances that are requiredin the diet of humans and animals for:
normal growth
maintenance of life normal reproduction
Actions:
Catalysts Co-enzymes
Form integral parts of coenzymes
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RiskFact
ors&
D
egenerativ
Diseases
Genetics
Age
High Fat
Sedentary Lifestyle
Stress
Smoking & Tobacco Use
Excessive Alcohol Intake
Low Complex CHO / Fiber Intake
High Sugar Intake
Low Calcium Intake
Low Vitamin & Mineral Intake
Cancers
X
X
X
X
X
X
X
X
X
Hypertension
X
X
X
X
X
X
X
X
X
DM
II
X
X
X
X
X
Osteoporosis
X
X
X
X
X
X
X
At
herosclerosis
X
X
X
X
X
X
X
X
X
Obesity
X
X
X
X
X
X
Stroke
X
X
X
X
X
X
X
Diverticulosis
X
X
X
X
X
Dental&OralDiseas
eX
X
X
X
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GROWTH AND DEVELOPMENT
Increase in size and mass (Quantitative)
Cms., inches, kgs., lbs.
Before birth and after birth
Increased or enhanced maturation
function, and skills
Behavior, intellectual, mental,
social, creative, moral, spiritual,
aesthetic
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CASE # 1
RB is a 15 month old boy who suddenly changedfrom a happy eater to one who refuses to eat evenhis once favorite foods
Mom is worried because He is not gaining weight
He is very active (plays all day)
He changes food preferences day to day
Is he normal? Is he getting enough nutrients?
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CASE # 1
What are concerns in the
anticipatory guidance ofR.B.?
Nutrition Developmental Screening
Parenting
InjuryPrevention
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ANTICIPATORY GUIDANCE
Nutrition
Picky eating
Refusal to drink
milk
DevelopmentalScreening
Gross motor
Play around thehouse
Outside play
Parenting
Discipline
Injury Prevention
Safe homes/playground
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CASE # 2
G.F., is a 6 year old girl who looks healthy, is notsickly but doesnt like vegetables, does not eather breakfast, lunch, and just eats junk food.
Her weight is 16kgs and her height is 104cms. She does not gain weight, she seems so small for
her age
Concerns for parents School Performance
Extra Curricular Activities
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COMMON PARENTAL CONCERNS
Appetite enhancers/stimulants
Growth enhancers Immune boosters
Pampalakas ng resistensiya ( 45%)
>> Survey of 82 mothers in 2 tertiary hospitals (OPD/ER): What arevitamins?
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Vitamin Source Deficiency Excess
Animal foods (e.g.Liver, egg yolk, cream orbutter)
Beta-Carotene (Pigment inleafy green vegetables oryellow fruits)
Retarded SkeletalGrowth
Night Blindness
Abnormalities oflining of GIT andGUT
Irritability
Painful joints Growth retardation
Liver & Spleen enlargement
Hair Loss Birth defects
Vitamin d2 (found inirradiated yeast & used insome commercial
preparations of the vitamin) Vitamin d3 (found in fish
liver oils & in fortified milk
Rickets
Bow Legs Knock knees
Nausea
Loss of appetite Kidney damage
Insoluble Ca Saltdeposit
Vegetable oil; sunflower,safflower, canola & oliveoils
Green leafy vegetables
Wheat germ Some nuts
Eggs
Occurs rarely in human
Results from geneticabnormalities, fatmalabsorption and PEM
Neurological symptoms
Relatively non-toxic
Anticoagulant effect Nausea
Weakness Headache
Diarrhea
Fatigue
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Yeast, whole grains,lean pork, nuts,legumes
Thiamine-enrichedcereal products
Widely distributed inplant and animaltissues
Milk, organ, meats
Enriched cereal products
Lean meats
Peanuts
Legumes
Whole-grain orenriched bread and
cereal products
Beriberi
Fatigue, mentalconfusion, anorexia,
weakness, ataxia,peripheral paralysis
Vitamin Source Deficiency Excess
Fissures in corners of
the mouth, inflammationof tongue
Skin disease
Severe irritation of eyes
Skin disease,diarrhea,dementia, death
No known toxicity
No known toxicity fromexcess intake from foodsources
Liver damage may occurfrom high intake of
supplemental niacin
No known toxicity
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Liver, meat, corn,
Whole grain cereal
Seeds
Vitamin Source Deficiency Excess
Seizure
Inadequate growth
Weight lossAnemia
Green leafy vegetables
Fruits (apples andoranges)
Dried beans
Avocado
Sunflower seeds
Wheat germs
Anemia
Neural tubedefects
Severe nerve
damage has been
reported frommegadoses
No known toxicity
from food sources
Adverse effectsreported from themisuse of thesyntheticcompound
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Vitamin Source Deficiency Excess
Animal tissue asthe liver, kidneyand heart ofruminants
Bivalves (clams oroysters)
Fresh green
Yellow vegetables
White potatoes
Sweet potatoes
Berries
Pernicious anemia(megaloblastic)
Nervous system
degenerationamenorrhea
Scurvy
InadequateCollagen Synthesis
No known toxicity
Diarrhea, abdominalbloating
Iron over-absorption
Hyperoxaluria
Hyperuricosuria
Hyperoxalemia
Hemolysis in G6PD
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Breast milk
Infant formulas
Dairy Products
Cereal grains
Milk, Meat
Seeds, Nuts
Eggs
Skeletalfragility
Decreased bonemass
Practically
unknown inhumans
Muscle weakness
Osteomalacia inprolonged cases
Hypercalcemialeading to tetany
and formation ofrenal stones
Rare because of
efficient renalexcretion
Abnormalcalcification ofsoft tissues
Vitamin Source Deficiency Excess
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Fortified cereals
Red meat, Liver
Fish, Sardines,
Seafood, Mushrooms
Egg yolk
Human milk for the 1st 6months of life
Iron-fortified cereals Baked goods
Whole grains, wheatgerm
Dried peas, spinach,beans
Organ meats, liver
Sardines
Growth retardation
Delayed sexual maturity
Diarrhea
Allopecia Increase susceptibility to
infections
Iron deficiency anemia
Rare
Chronic toxicity leads toimpairment of copperand iron status, anemiaand immune deficiency
Acute zinc poisoning;nausea, vomiting,diarrhea, fever andlethargy
Cellular damage likefatty acids, proteins
and nucleic acid
Vitamin Source Deficiency Excess
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Type of Drug
Mechanism ofaction
Antihistamine
Modulateserotogenic,noradregenic, andacetyl cholinereceptors in the cns(increases appetite)
Buclizine Pizotifen Dibencozide Lysine
Antihistamine Primary co-activeenzyme form of
vitamin b12
Amino acid
Increasesserotonin levelsin the brain(increasesappetite)
Directly involved in
the building of leanmuscle tissue
Stimulates proteinmetabolism forincreased conversionof amino acidcomponents
Benefits the
production ofenzymes,hormones,antibodies, andcollagen
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CHLORELLA GROWTH FACTOR
good source of nucleic acids (RNA andDNA)
responsible for cellular growth ( due to itsrapid rate of reproduction ) and repair
tissue repair and protection against toxicsubstances (cadmium, carbon)
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CHLORELLA GROWTH FACTOR
Causes the benign lactobacillus to
multiply 4 times the normal rate May promote rapid growth in childrenAlleviates constipationBeing studied for the treatment of gastric
ulcers
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CHLORELLA GROWTH FACTOR
Nakamura and Yamagashi
Results Obtained- Increases in height and weight
in the primary students givenCGF compared to the placebo
(Source: Scientific Reports on Chlorella in Japan,
Silpaque Publishing, Inc.)
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Graph 1. Rate of height increase
CGF children: 2.14 cm
Non-CGF children: 1.65 cm
Graph 2. Rate of weight increase
CGF children: 2.6 lbs.
Non-CGF children: 0.8 lbs.
Source: Scientific Reports on Chlorella in Japan, Silpaque Publishing, Inc.
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CHLORELLA GROWTH FACTOR
Has been developed as a food additive orsupplement
Further studies preferably double blinded,randomized clinical trials needed.
Local study in V. Luna hospitalIn Low birth weight and premature infants
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U.S. Facts About Vitamins And Minerals(Picciano, MF, et al. Neonatal and Pediatric Pharmacology, 3rd ed., 2005)
Multivitamins and Multimineral products arethe most widely used dietary supplements inthe US.
Between 1988 and 1994, children aged 1 to 5years were major users of dietarysupplements.
The supplements most commonly taken bychildren aged 2 months to 11 years were
multiple vitamins or combinations of multiplevitamins and minerals. Supplement use in the US continues to
increase every year.
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