prevention against micronutrient malnutrition
DESCRIPTION
Micronutrident disorders are common and a major cause of morbidity in all populations. In this presentation we discuss the importance of iodine, folic acid and vitamin D deficiency. Prevention is the solutionTRANSCRIPT
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PREVENTION AGAINST MICRONUTRIENT MALNUTRITIONIODINEFOLIC ACIDVITAMIN D
3RD SUMMER SCHOOLMANI, GREECE2014
Professor Steven C. BoyagesWestmead HospitalSydney, Australia
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Sydney, Australia
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Nutrition Related Disorders
MicronutritionMicronutritionUndernutrition PCMUndernutrition PCM
Minerals and VitaminsMinerals and VitaminsFolic AcidFolic Acid
Vitamin D deficiencyVitamin D deficiencyVitamin A deficiencyVitamin A deficiency
Fe deficiencyFe deficiencySelenium deficiencySelenium deficiency
Iodine deficiencyIodine deficiency
MicronutritionMicronutritionUndernutrition PCMUndernutrition PCM
Minerals and VitaminsMinerals and VitaminsFolic AcidFolic Acid
Vitamin D deficiencyVitamin D deficiencyVitamin A deficiencyVitamin A deficiency
Fe deficiencyFe deficiencySelenium deficiencySelenium deficiency
Iodine deficiencyIodine deficiency
MacronutritionMacronutritionObesityObesity
HyperlipidemiaHyperlipidemiaInsulin ResistanceInsulin Resistance
DiabetesDiabetesAlcoholAlcohol
MacronutritionMacronutritionObesityObesity
HyperlipidemiaHyperlipidemiaInsulin ResistanceInsulin Resistance
DiabetesDiabetesAlcoholAlcohol
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PAMM
Iodine
Folic Acid
Vitamin D
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Iodine Deficiency Disorders
Thyroid Thyroid autonomy Nodular thyroid
disease Goitre Thyroid
Malignancy
Brain Endemic cretinism Deafness Subclinical
deafness intellectual
disability ?Attention deficits ? Colour
perception deficitsIodine Deficiency Disorders (IDD)Iodine Deficiency Disorders (IDD)1000 million people at risk for 1000 million people at risk for
the development of IDDthe development of IDD
Iodine Deficiency Disorders (IDD)Iodine Deficiency Disorders (IDD)1000 million people at risk for 1000 million people at risk for
the development of IDDthe development of IDD
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Iodine Deficiency Disorders
Iodine Deficiency Disorders (IDD) refers to all of the ill effects of iodine deficiency in a population that can be prevented by ensuring that the population has an adequate intake of iodine
Iodine deficiency at critical stages during pregnancy and early childhood results in impaired development of the brain and consequently in impaired mental function.
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Endemic Goitre
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Pathogenesis of goitre
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Adaptation to iodine deficiency
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Iodine Deficiency Disorders
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Early recognition of goitre with impaired mental ability"Hence while travelling in a
certain region in the County Tyrol, under the jurisdiction of the Bishop of Gurk, I was astonished at the very large number of madmen, fools and dolts; but when I considered the frigidity and the humidity of the air, and also perceived the crudity of the waters from the very frequent occurrence of goitre... all astonishment ceased entirely."
EUSTACHIUS RUDIUS, A PHYSICIAN FROM UTRECHT
(1551-1611)
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Endemic Cretinism
Occurs in areas of severe iodine deficiency and almost universal endemic goitre
Geographic clustering
Two predominant clinical phenotypes
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Endemic Cretinism: Clinical Phenotypes Neurological
Euthyroid Goitrous Severe mental
disability Deafness Neurological
abnormalities More frequent
Myxedematous Hypothyroid Thyroid atrophy Severe mental
disability Deafness Neurological
abnormalities Less frequent
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Timing of insult
Timing of Timing of insultinsult
PrenatalPrenatal PostnatalPostnatal
TargetTarget Fetal brainFetal brain
Fetal thyroidFetal thyroid
Maternal Maternal thyroidthyroid
Child and Child and AdultAdult
ThyroidThyroid
OutcomeOutcome Endemic Endemic cretinismcretinism
Impaired IQImpaired IQ
Endemic Endemic GoitreGoitre
Short Short StatureStature
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Why are certain parts of brain predisposed? Timing of the insult and preferential sites for thyroid hormone action
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Differential expression of TH receptors
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ARE IODINE LEVELS FALLING?
Are we at risk?
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Are iodine levels falling?
Figure 1. (A) Median U.S. urinary iodine concentrations in males and females, 1971-2002 (B) Median U.S. urinary iodine concentrations in pregnant and non-pregnant women of child-bearing age (15- 44 years old), 1971-2002.[Adapted from Hollowell et al, JCEM 1998; 83:3401-8 & Caldwell et al, Thyroid 2005;15:692-9]
Figure 1. (A) Median U.S. urinary iodine concentrations in males and females, 1971-2002 (B) Median U.S. urinary iodine concentrations in pregnant and non-pregnant women of child-bearing age (15- 44 years old), 1971-2002.[Adapted from Hollowell et al, JCEM 1998; 83:3401-8 & Caldwell et al, Thyroid 2005;15:692-9]
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Pregnancy increases risk of iodine deficiency
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Iodine Deficiency in Australia
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TasmaniaUrine Iodine Distribution
Median UIE 84mcg/lMedian UIE 84mcg/l
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Thyroid Size: Boys and Girls
24.6%24.6% 20.7%20.7%
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Other States
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NINS study Overall, children in mainland Australia are
borderline iodine deficient, with a national median UIE of 104 mcg/L.
On a state basis, NSW and Victorian children are mildly iodine deficient, with median UIE levels of 89 mcg/L and 73.5 mcg/L, respectively. South Australian children are borderline iodine deficient, with a median UIE of 101 mcg/L.
Both Queensland and Western Australian children are iodine sufficient, with median UIE levels of 136.5 mcg/L and 142.5 mcg/L, respectively.
There was no significant association between UIE and thyroid volume.
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Just eat sushi! Is that ok?
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What is normal intake?Too little and Too much can be a problem
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ENDEMIC GOITRE IN CENTRAL CHINA CAUSED BY
EXCESSIVE IODINE INTAKE
Thyroid status was examined in children from two villages in China where the iodine concentrations in drinking water were 462.5 and 54 μg/1
Goitres were present in 65% (n = 120) and 15.4%
(n=51), respectively.
Children from the high-iodine village had a lower mean serum triiodothyronine and higher serum free thyroxine and serum thyroid-stimulating hormone concentrations than the children from the control village. 2 cases of overt hypothyroidism were detected in the high-iodine village.
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TOPICAL IODINE-CONTAINING ANTISEPTICS AND NEONATAL HYPOTHYROIDISM IN VERY-LOW-BIRTHWEIGHT INFANTS: P. Smerdely, S. C. Boyages, et al. Lancet 1989
The thyroid function of very-low-birthweight (VLBW; below 1500 g) infants admitted to neonatal intensive-care units was studied at two hospitals; one routinely used topical iodinated antiseptic agents and the other used chlorhexidine-containing antiseptics.
Serial Urinary iodine excretion rose dramatically in the 54 iodine-exposed infants and was up to fifty times greater than in the 29 non-exposed infants.
Within 14 days, 25% (9 of 36) of the infants exposed to iodine had serum thyrotropin levels above 20 mIU/l, compared with none of the control group.
The mean serum thyroxine level in these 9 infants (44·1 nmol/l) was significantly lower than that in exposed infants with normal thyrotropin levels (83·1 nmol/l) and in the non-exposed control group (83·0 nmol/l), thyroxine levels fell before serum thyrotropin rose.
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Medications
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Amiodarone related thyroid disease
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FOLIC ACID
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Sources of folate intake
Folate sources Folate Folic acid
(FA)Dietary Folate Equivalents
(DFE)
Food (natural) + - 1 DFE = 1 μg food folate
Food (fortified): ECGP + RTE
cereals+ + 1 DFE = 1 μg food folate or 0.6 μg
FA from fortified food
Supplements - + 1 DFE = 0.6 μg FA taken with food or 0.5 μg FA on empty stomach
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Association of folate with health outcomes
• NTD’s and other birth defects
• Cardiovascular disease• Cognition• Cancer
• Acceleration of cancerous growth • Masking of vitamin B12 deficiency• Twinning• Immunity• Epigenetic changes
Cause and effect has not been proven
Potential adverse
effects; basis is observational
data
Proven effectiveness of folic acid intervention
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Monitoring of the impact of folic acid fortification
Changes in dietary intake
Changes in blood levels
Changes in NTD rates
Folic acid fortification
policy
Changes in other health outcomes
Benefits Risks
anes
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Changes in biomarker levels of folate status
How much did folate blood levels change after the
introduction of fortification?
What are the challenges associated with assessing
folate status through biochemical measurements?
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Serum folate levels have nearly tripled
• Serum folate levels have increased much more than expected from FDA intake modeling and short-term FA supplementation trials – demonstrating the value of biomonitoring.
• Post-fortification serum folate levels have stabilized after several years.
http://www.cdc.gov/nchs/data/databriefs/db06.htm
http://www.cdc.gov/nutritionreport
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Prevalence of low RBC folate levels has decreased
Red blood cell folate levels have also stabilized after fortification and the prevalence of low levels in women of childbearing age was ~5% compared to ~40% at pre-fortification.
http://www.cdc.gov/nchs/data/databriefs/db06.htm
RBC folate <140 ng/mL
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Folate dietary intake data
Strengths ChallengesNon-invasive Self-reported data; flawed with
multiple errors
Relatively easy and inexpensive to conduct
Various sources of intake need to be captured
Easier to compare between countries
Computation of data is complex (DFE)
Requires two 24-h dietary recalls to calculate usual intakes
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VITAMIN D
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Health benefits of vitamin D
Low 25(OH)D levels linked to Osteoporosis and osteopenia Cancer Diabetes Cardiovascular disease Autoimmune disease Multiple sclerosis Respiratory Illness Mental Health
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Adequate vitamin D statusVitamin D (nmol/L*)Conventional guidelines
Newer recommendations+
Severe Deficiency <12.5
Moderate deficiency 12.5-25
Mild deficiency 25-50 <50
Insufficiency 50-75
Sufficiency >50 >75
*2.5 nmol/L = 1 ng/ml
+Bischoff Ferrari, AJCN 2006
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Australian Studies
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46974697
31131 25(OH)D assays1 July 2008 and 30 July 2010
31131 25(OH)D assays1 July 2008 and 30 July 2010
Primary test, complete data available for gender, age, patient setting, date of test, postcode**, known breast cancer case, 25(OH)D ≤400 nmol/L
Sample type
1083910839 1397913979
Diagnostic referralOutpatientPrivate outpatientEmergency
InpatientPrivate hospital patientPublic hospital patientPrivate patient
2951629516
2481924819
Yes
680668061801218012Female Male
6201620162516251Summer Winter
6121612162456245Autumn Spring
16151615
QC sampleResearchMiscellaneousUnknown
* *Matched to ARIA, SEIFA, Latitude, Longitude
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Mean 25(OH)D by gender
37% reductio
n by June
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Mean 25(OH)D by patient setting
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Mean 25(OH)D by gender and patient setting
Supporting Women with Breast Cancer Today and Every Day
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Mean 25(OH)D by age group
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Mean 25(OH)D by remoteness
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Results
Bilinski & Boyages MJA 197 (2) · 16 July 2012
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Requests per 100000 for FBC, bone densitometry and vitamin D
Bilinski & Boyages BMJ Open 2013;3: e002955
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Frequency of repeated testing
Bilinski & Boyages BMJ Open 2013;3: e002955
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Vitamin D intake recommendations
*Recommendations based on maintaining serum vitamin D > 75 nmol/L (30ng/ml)
Recognition that individuals who are obese or on certain medications be give 2-3 times more vitamin D
40 IU = 1 µg
Age NHMRC IOM US Endo Society*
0-1 200 400 1000
1-18 200 600 1000
19-49 200 600 1500-2000
50-69 400 600 1500-2000
70 and over
600 800 1500-2000
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Health Implications
Public health messages required to address high prevalence of vitamin D deficiency
Australians are not adequately supplementing - suitable guidelines are required
Implications regarding frequency and timing of testing
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Percentage of households with access to iodised salt
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Food Fortification
Eradication of iodine deficiency has always the highest priority.
Optimal prevention of thyroid disease by modification of
iodine intake in the population is achieved by keeping iodine intake in individuals within a relatively narrow interval around the recommended level.
To run an optimal iodization program it is necessary to have information on dietary habits in the population, and on iodine contents of different food items.
Iodine used for enrichment of food should be well distributed in different food items, e. g. by universal or nearly universal iodization of salt. Optimal methods may differ between European countries depending on dietary habits.
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Risks of iodisation programmes Sudden increase in the prevalence of
hyperthyroidism Jod Basedow phenomenon
Development of hypothyroidism in those with pre-existing autoimmune thyroid disease Positive anti-TPO antibodies
Change in the pattern of thyroid disease, rise in the prevalence of thyroid autoimmunity
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CONCLUSION
Thyroid hormone is essential for normal somatic and neurological development.
Iodine deficiency leads to thyroid hormone deficiency at critical periods of brain development that leads to irreversible neurological damage.
Prevention of iodine deficiency is essential
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Acknowledgements Australia
CJ Eastman JP Halpern John K Collins Li Mu
China Indonesia The Netherlands
Hemmo Drexhage USA, Atlanta
GF Maberly Italy, Pisa
Alessandro Antonelli