Supplementation in Preventing Micronutrient Deficiency MND Conditions: An Evolving Science

1
Supplementation in Preventing Micronutrient
Deficiency (MND) Conditions An Evolving Science

• TH Tulchinsky MD MPH
• Braun School of Public Health for
• Academies of Science Meeting on MNDS
• Jerusalem, 23-24 May 2005

2
UN Millenium Development Goals 2015

• Eliminate extreme poverty and hunger
• Achieve universal primary education
• Promote gender equality and empower women
• Reduce child mortality
• Improve maternal health
• Combat HIV/AIDS, malaria and other diseases
• Ensure environmental sustainability
• Develop a global partnership for development

Public health
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Factors in Public Health Interventions
Society and culture
Behavioral psychology
Public policy and management
Population Health
Law and regulation

• Biomedical Science

Professional awareness
Resource allocation
Leadership
4
Public Health Nutrition Strategies

• Education public, political, professional,
  technical
• Food based strategy
• Socio economic factors
• Food supply/costs
• Socio economic variables
• Supplementation for target groups
• Infants and children
• Women
• Elderly
• Fortification of basic foods
• Surveillance and monitoring
• Laboratory support

5
Nutritional Bipolar Disorder

• Over nutrition
• Under nutrition
• Fortification
• Supplementation

6
WHO and MNDs

•  MNs needed in miniscule amounts to enable body
  to produce enzymes, hormones and other substances
  essential for proper growth and development
• Consequences of their absence are severe
• Iodine, vitamin A and iron are most important in
  global public health terms
• MNDs are major threats to health and development
  of populations the world over, particularly to
  preschool children and pregnant women in
  low-income countries

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UNICEF

• It's no longer acceptable to simply identify
  symptoms of micronutrient deficiency in
  individuals and then treat them," said UNICEF
  Executive Director, Carol Bellamy.
• "We have to protect entire populations against
  the devastating consequences of vitamin and
  mineral deficiency, especially children."
• The report summarizes results from nutritional
• UNICEF supports micronutrient supplementation, in
  the form of iron-cum-folic acid and vitamin A.
• Supplements are administered during routine
  immunization and acceleration campaigns, at MCH
  centers and via traditional birth attendants.

Carol Bellamy. UNICEF 2004
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UNICEF Iron, Vitamin A, Iodine, Folate

• Iron deficiency impairs mental development in
  young children with lowering of national IQs,
  undermines adult productivity (loss of 2 of GNP)
• Anemia from severe ID causes deaths during
  childbirth of some 50 000 women per year.
• Vitamin A defiiciency affects 40 of lt5 years old
  in developing world, compromises immune systems
  with early deaths of 1 million children per year.
• Iodine deficiencies cause up to 20 million babies
  to be born with mental defects every year.
• Folate deficiency 200,000 severe Neural Tube
  Defects annually (spina bifida, encephalocoele
  and anencephaly)

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American Academy of PediatricsCommittee on
Genetics Folic Acid for the Prevention of Neural
Tube Defects

• AAP endorses USPHS recommendation that all women
  of childbearing age should take 400 (0.4 mg) µg
  of FA daily because of unplanned pregnancies (50
  in US)
• AAP encourages food fortification to provide all
  women a daily intake of 400 µg of folic acid.
• Women should consume 400 µg of folic acid daily
  in addition to eating a healthy diet with a
  multivitamin with 400 µg of FA
• Routine prenatal screening for NTDs is still
  advisable.

AAP. Pediatrics1999104, 325-8.
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Folic Acid (FA) -American College of Obstetrics
and Gynecology (January, 2005)

• ACOG promotes consumer and physician education on
  importance of FA for reproductive-age women to
  prevent neural tube defects (NTDs) in newborns
• Women who could become pregnant should take a
  multi-vitamin containing 0.4 milligrams of FA
  daily
• Women with an NTD child should take more4
  milligrams dailystarting at least 1 month before
  pregnancy and during first 3 months of pregnancy.
  
• Women can get FA from foods such as dark, leafy
  greens and fortified whole-grain breads, cereals
• However, most will not meet daily requirement
  from foods alone and should take a multi-vitamin
  to ensure enough FA

www.acog.org (January, 2005)
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Supplements Before Pregnancy

• Folic acid tablets recommended for women in age
  of fertility since mid 1990s
• Compliance variable
• Compliance in US lt35
• Same elsewhere
• Need for double strategy
• Fortification and supplementation with FA
• ACOG recommends multi vitamin supplements
• Continuing education

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Supplements in Pregnancy

• High rates of anemia in pregnancy, 1950s-60s
  Israel
• Supplementation longstanding practice
• Iron and folic acid during pregnancy
• Folic acid 400 mgm/day for 4 months before
  pregnancy (AAP, ACOG)
• Added during lactation
• Compliance variable
• Iron during lactation (Israel)
• Calcium and vitamin D during pregnancy and
  lactation (AAP)

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Vitamin K Supplements for Newborns

• Physiologic deficiency
• Hemorrhagic disease of newborn HDN
• Early (lt 1 week)
• Late (8-12 weeks)
• More in breast fed babies
• Bleeding enteric, intracranial, cord, skin
• Important cause of perinatal mortality and
  morbidity in developing countries
• Chaotic in Europe, UK

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Vitamin K for Prevention of HDN

• Hemorrhagic disease of newborn (HDN) 1850s Boston
• American Academy of Pediatrics (AAP) recommends
  prophylactic Vitamin K IM since 1961
• Implemented increasingly in Israel in 1970s
• Mandatory in Israel since 1985
• Controversy and confusion in Europe 1990s
• Ignored by WHO, UNICEF until today
• AAP recommendation renewed 2003
• Increasingly recognized in perinatal deaths in
  developing countries e.g. India

15
Renewed Interest in Vitamin K

• Since the 1980s, much attention in UK, Europe,
  Japan, Canada, Australasia and Middle East
• HDN and vit K deficiency reported in both
  developed and developing countries where not
  routinely used, or where use may be waning
• Controversy re oral versus parenteral use of
  routine Vit K largely resolved
• IM administration within the first 6 hours after
  birth more effective in preventing both early and
  late HDN

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Public Health Importance of HDN

• Japanese incidence of HDN reported as 11,700 in
  breast fed babies and 14,500 in all infants
• Of these, 82 reported intracranial hemorrhage
  (ICH)
• HDN increasing in India, Thailand, Singapore,
  Taiwan
• Thailand reports incidence of 35-72100,000
  births
• ICH not always identified as HDN and may be
  significant factor in birth-related cerebral
  palsies

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Supplementation in Infancy in Israel

• Cod liver oils common since 1920s
• Vitamin K (IM) mandatory since 1980s
• Routine vitamin and iron prophylaxis
• Compliance variable
• Vitamin A and D prophylactically
• for 30 years plus
• From 2 weeks to 12 months
• Iron prophylactically
• Since 1985
• From 4-12 months

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Prevention of Rickets and Vitamin D Deficiency
New AAP 2003 Guidelines

• Rickets in infants reported in US due to
  inadequate vitamin D intake and decreased
  exposure to sunlight
• AAP recommends all infants, especially breastfed,
  have a minimum supplement of 200 IU of vitamin D
  per day from first 2 months of life
• Recommend 200 IU vitamin D per day be continued
  in childhood and adolescence
• Sunlight exposure not easily determined for a
  given person
• New vitamin D intake guidelines based on US
  National Academy of Sciences recommendations

Gartner Greer. Am Acad Pediatrics Pediatrics.
2003111908-910
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Nutritional Rickets Among Children in the United
States Review of Cases, 1986-2003

• Reports of rickets in children in North Carolina,
  Texas, Georgia, and mid-Atlantic region
• Confirms vitamin D deficiency in US children
• New Am Acad Ped guidelines for prevention (2003)
• Reports of nutritional rickets 166 cases of
  rickets in 22 published studies 4-54 mo of age
• 83 of children with rickets were African
  American and 96 were breast-fed
• Among breast-fed children, only 5 vitamin D
  supplemented during breast-feeding

Weisberg P, Scanlon KS, et al.Am J Clin Nutr.
2004801697S-705S.
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Hemoglobin Levels Among Infants by Socio-Economic
and Ethnic Group, Akko, Israel, 1995

• 1995, 7,920 children born in Akko followed.
• Prophylactic iron Rx for all the infants aged
  4-12 months in MCH clinics. Routine Hbn test at
  12 months.
• Hbn test on 5,703 infants 30.8 had a Hbn lt11
  g/dl, and 24 had 10.0-10.9 g/dl, 6--between
  9.0-9.9 g/dl and lt 1 had a Hbn below 9.0 g/dl.
• Association of anemia and ethnicity (ArabsgtDruze,
  p 0.02). Arab settlements of higher
  socio-economic level had lower rate of anemia
  than low socio-economic level. Highest rate of
  anemia in Bedouin settlements.
• No. of children in family associated with anemia
  rates (p 0.0005) inverse correlation of
  maternal education and anemia rate (p 0.001)
  no association between birth weight and anemia
  rates.

Shehab S, Nutenko K, et al. Harefuah.
20011401002-5, 1120
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Five Decades of Trends in Anemia in Israeli
Infants Implications for Food Fortification
Policy

• Prevalence of IDA in Jewish infants declined from
  68 in 1946 to 50 in 1985 average annual
  reduction -1.43.
• Following iron supplementation directives,
  average annual rate of decline increased to -4.0
  and prevalence of anemia to about 11 in 1996.
• IDA rates in Arab infants declined by annual av.
  of 3.7, and were consistently almost twice as
  high as for Jewish infants.
• Despite iron supplementation program persistent
  high rates indicate low iron content in the diet.
  
• Emphasizes important role of a national food
  fortification program, using staple foods
  commonly consumed

Kaluski DN, Leventhal A, et al.Eur J Clin Nutr.
20015582-7.
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Zinc deficiency what are the most appropriate
interventions?

• Zinc deficiency common in developing countries
  with high mortality
• Regular zinc supplements can greatly reduce
  common infant morbidities in developing countries
  
• Zinc effective adjunct Rx for diarrhoeal disease
• Zinc deficiency commonly coexists with other MNDs
  including iron, so single supplements
  inappropriate
• Until results of trials of multiple MN
  interventions available, zinc supplements should
  be given to children with infections

Shrimpton et al. BMJ  2005330347-349 
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Dietary Reference Intakes

• National Academies of Science, 2000
• For US and Canada
• Panel on Micronutrients, Subcommittees on Upper
  Reference Levels of Nutrients and of
  Interpretation and Use of Dietary Reference
  Intakes, and the Standing Committee on the
  Scientific Evaluation of Dietary Reference
  Intakes
• Vitamin A, Vitamin K, Arsenic, Boron, Chromium,
  Copper, Iodine, Iron, Manganese, Molybdenum,
  Nickel, Silicon, Vanadium, and Zinc

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Summary MN Supplements in Infancy

• Vitamin K (IM) within 6 hours of birth to prevent
  HDN - USA, Canada, Israel, Australia, New Zealand
• Vitamin A at birth - developing countries, UNICEF
• Vitamin A and D from 2 weeks to 12 months,
  Israel
• Iron from 4-12 months
• Vitamin D to end of adolescence US, 2003
• Calcium and Zinc various recommendations
• Fluoride in water or infant supplements

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Fluoridation

• Recommended in North America since 1940s
• Voluntary fluoridation of larger cities and some
  small communities between 1980-1995
• Failure to reach majority of population
• MOH decides on mandatory fluoridation
• Challenged and upheld by Supreme Court of Israel
• Implemented 2003
• All communities over 5,000
• Fluoride tablets recommended for children in
  smaller communities or local fluoridation

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Elderly

• Osteoporosis and fractures (hip, wrist,
  vertebrae)
• Evidence of low vitamin D levels in hospitalized
  elderly
• Multi-vitamins for institutionalized elderly
  since 1990s
• Growing elderly population
• Subject to chronic disease and acute episodes
• Preventive care to sustain well elderly
• Growing self medication
• Cautions against sun exposure

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Selhub et al. Homocyst,eine and Alzheimers, NEJM
2001

• Results Over a median follow-up period of eight
  years, dementia developed in 111 subjects,
  including 83 given a diagnosis of Alzheimer's
  disease.
• The multivariable-adjusted relative risk of
  dementia was 1.4 (CI, 1.1 to 1.9) for each
  increase of 1 SD in the homocysteine value either
  at base line or eight years earlier.
• The relative risk of AD was 1.8 (CI, 1.3 to 2.5)
  per increase of 1 SD at base line and 1.6 (CI,
  1.2 to 2.1) per increase of 1 SD eight years
  before base line.
• With a plasma homocysteine level greater than 14
  µmol per liter, the risk of Alzheimer's disease
  nearly doubled.
• Conclusions Increased plasma homocysteine level
  is a strong, independent risk factor for the
  development of dementia and Alzheimer's disease.

• Seshadri, Beiser, Selhub, Rosenberg,et al.
• NEJM, 2001346476-483

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FA Supplements and Fortification and Risk for
NTDs, CVDs and Cancer Evolving Science

• FA supplements reduce the risk of NTDs and may be
  reduce risk for CVD and cancer.
• Observational and controlled intervention studies
  support existing PH policies re FA and NTDs.
• Education to promote daily intake of FA
  supplements by women of reproductive age have not
  led to increased use.
• Food fortification associated with a reduction in
  neural tube defects in the United States and
  Canada.
• FA supplements to reduce CVD and cancer is the
  focus of major research efforts including
  clinical trials.

Bailey et al. J Nutr. 20031331961-1968S
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Plasma Homocysteine as a Risk Factor for Dementia
and Alzheimer's Disease

• In cross-sectional studies, elevated plasma
  homocysteine levels have been associated with
  poor cognition, dementia.
• Studies of newly diagnosed dementia needed to
  establish whether the elevated homocysteine
  levels precede onset of dementia or result from
  dementia-related nutritional and vitamin
  deficiencies.
• A total of 1092 subjects without dementia (667
  women and 425 men mean age, 76 years) from the
  Framingham Study constituted our study sample.
• Examined the relation of the plasma total
  homocysteine level measured at base line and that
  measured 8 years earlier to the risk of newly
  diagnosed dementia on follow-up

• Seshadri, Beiser, Selhub, Rosenberg,et al.
• NEJM, 2001346476-483

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Selhub et al on Folate and Cognitive Decline Am J
Med 2005

• Measures of multiple cognitive functions
  administered at baseline and again after 7 years.
  
• Those with elevated homocysteine levels, or low
  levels of folate or vitamin B(6), had worse
  baseline cognitive function.
• Adjusting for multiple covariates, those in the
  bottom quartile of folate had a 1.6-fold
  increased risk (95 CI1.01 to 2.31 P 0.04) of
  being in the worst quartile of 7-year cognitive
  decline.
• Low folate levels largely accounted for a trend
  towards greater cognitive decline with elevated
  homocysteine level.
• The risk of developing cognitive decline might be
  reduced through dietary folate intake.

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Recommended Micronutrient Supplementation for
Institutionalized Elderly

• Israel MoH committee reviewed literature, local
  and international recommendations. Suggested a
  daily MN supplements for institutionalized
  elderly living in institutions supervised by the
  MoH
• Preparation tailored for this population contains
  half the RDA for most of the vitamins and some
  microelements. Calcium, magnesium and phosphorus
  are excluded and should be supplied separately.
  Vitamin K and iron are also excluded.
• Fat-soluble vitamins should be microencapsulated.
  
• MN supplementation for institutionalized elderly
  is part of the MoH nutrition policy.
• Recommendations also applicable to free-living
  elderly population

Dror Y, Stern F, et al. J Nutr Health Aging.
20026295-300.
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Homocysteine vs. folate, B6, and B12 as
predictors of cognitive function and decline in
older high-functioning adults Studies of
Successful Aging.

• Elevated plasma homocysteine concentration may be
  a risk factor for cognitive decline and Alzheimer
  disease
• High homocysteine levels associated with low
  vitamin status, but unknown if homocysteine
  toxicity or vitamin insufficiency is responsible
  for the observed cognitive dysfunction.
• Cohort of 499 high-functioning community-dwelling
  persons 70-79 years to determine effect of
  homocysteine and related vitamin concentrations
  on cognitive function and cognitive decline.
• Nonfasting plasma concentrations of homocysteine,
  folate, vitamin B(6), and vitamin B(12) were
  measured at baseline

Kado DM Selhub J. Am J Med. 2005118161-7.
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Summary

• Supplements essential in public health nutrition
• Vital before and during pregnancy
• Vital for infancy and childhood
• Vital for adults and elderly
• Still evolving science e.g. role of FA in
  reducing coronary heart disease, stroke, cancer
  and dementias
• Implementation essential for infants, women,
  adults and elderly

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Thank You