lect #8 vitamin d

8/7/2019 Lect #8 Vitamin D

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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


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


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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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



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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



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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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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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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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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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lect #8 vitamin d

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