vitamin d3 and iron supplementation in pregnancy

Veerendrakumar C.M.
MD.,DNB
Associate Professor
Dept of OBG,VIMS,Bellary

Thursday, December 22, 2011 dr.veerendrakumar cm 1

Vitamin D & Iron Deficiency:
Deadly Duo

Alien + Predator

Vitamin D vitamin or Hormone ??
("sunshine" vitamin)

 Vitamin D is a fat-soluble vitamin. Fat-soluble
vitamins are stored in the body's fatty tissue

 Very few foods naturally contain vitamin D.


Contents
 Vitamin D status & Deficiency Recap
 Clinical Data
 Health Implications
 Iron Deficiency Anemia status in India
 Vitamin D Deficiency & Iron Deficiency Anemia: is there a Link ?
 Prevalence
 Mechanistic Evidence
 Clinical Evidence
 Summary


Vitamin D
Vitamin D is found in the following foods:
 Dairy products
 Cheese
 Butter
 Cream
 Fortified milk (all milk in the U.S. is fortified with vitamin D)
 Fatty fish (such as tuna, salmon, and mackerel)
 Oysters

 Fortified breakfast cereals, margarine, and soy milk


 10 to 15 minutes of sunshine three times weekly is
enough to produce the body's requirement of vitamin D.
The sun needs to shine on the skin of your face, arms,
back, or legs (without sunscreen).

 Skin that is exposed to sunshine indoors through a
window will not produce vitamin D. Cloudy days, shade,
and having dark-colored skin also cut down on the
amount of vitamin D the skin makes.


RDA
 9 - 70 years: 600 IU (15 mcg/day)

 Safe upper limit -

4,000 IU/day for children 9 years and older, adults, and
pregnant and breast-feeding teens and women

 One microgram of cholecalciferol (D3) is the same as 40
IU of vitamin D.


 The greater absorption of iron in vivo from
ferrous ascorbate [Fe(HL)2] as compared with
ferrous sulfate has been ascribed both to
retardation or prevention of Fe(II) oxidation by
ascorbate and to the existence of Fe(II) as a
chelate with ascorbate.

Pharm Weekbl Sci 1984 Dec 14;6(6):245-8.


 Ascorbic acid (AA), is the most efficient enhancer of
non-heme iron absorption when its stability in the
food vehicle is ensured. The number of studies
investigating the effect of AA on ferrous sulfate
absorption far outweighs that of other iron
fortificants.
 The promotion of iron absorption in the presence of
AA is more pronounced in meals containing inhibitors
of iron absorption. Meals containing low to medium
levels of inhibitors require the addition of AA at a
molar ratio of 2:1 (e.g., 20 mg AA: 3 mg iron).

 Int J Vitam Nutr Res. 2004 Nov;74(6):403-19.

Pregnancy -The most dangerous journey of
mankind


ANEMIA

 40-90% WOMEN AFFECTED

 RESPONSIBLE FOR 65% MATERNAL DEATHS (FOGSI-
WHO 1996)

 CHRONIC MORBIDITY


Eradicating anemia can save at least

200 mothers a day!


Public Health Significance
WHO 2008

Prevalence of anemia (%) Public health significance

< 04.9 No PH problem
05.0 – 19.9 Mild
20.0 – 39.9 Moderate

> 40.0 Severe


Silver shines Gold glitters

But… Iron strengthens!


Patients have a right to

Normal Hb and

Receive safe and efficient treatment;

 It is the physician’s responsibility to ensure this and,

 Where possible, avoid blood transfusion.


Anemia is on the increase!!
 Economy is ‘better’
 More women are educated, empowered
 Tons of iron tablets distributed
 Fancy iron preparations flood the market
 Antenatal clinics are running full !

Iron is not reaching its destination!

Are we producing
a defective generation?


More doctors are finally testing patients for vitamin D
deficiencies…

 “Upwards of 70 percent of American adults are vitamin D
deficient or insufficient," said cardiologist James O'Keefe of
St. Luke's Mid-America

 Vitamin D prevents heart disease, too

 Vitamin D is essential for activating immune system
function


Vitamin D: Optimum status

Ideal >30 ng/ml
Acceptable 20-30 ng/ml
Insufficient 10-20 ng/ml
Deficient <10 ng/ml


Vitamin D Deficiency:
Gender Analysis

Indian J Med Res. 2008;127:211-218

Vitamin D deficiency in Pregnant
women and their New born
≈84% Indian women have 25(OH)D values
< 22.5 ng/L.

Am J Clin Nutr 22, 2011
Thursday, December 2000;72:472-5.
dr.veerendrakumar cmAm J Clin Nutr 2005;81:1060-4. 23

Vitamin D deficiency in Lactating
Women and Breastfed infants

81.1%
66.7%

23.2% 27.1%
19.8%
11.6%

Deficiency: <15 ng/ml
Insufficiency: 15-20 ng/ml
Severe Deficiency: <5 ng/ml

Thursday, December 22, 2011 dr.veerendrakumar cm
Indian J Med Res. 2011;133:267-273 24

Vitamin D deficient Mother-
Deficient Infant

J Pediatr Endocrinol Metab. 2009;22(3):241-6.

Retards proliferation
and
increases differentiation of cells

Vitamin D Deficiency:
Health Implications
 Osteomalacia & Rickets
 Osteoporosis
 Diabetes
 Hypertension & CVD
&
Anemia

Thursday, December 22, 2011 dr.veerendrakumar cm Mayo Clin Proc. 2006;81(3):353-373 27

60-90% Indians have Vitamin D Deficiency

Indians have Vitamin D Deficiency

~ 50% of those have anemia

INDIA
Latitude of 22° 00’N
Longitude of 77° 00’W


Vitamin D Deficiency and Iron
Deficiency Anemia: Is there a Link?


Prevalence in Pregnant Women &
Infants
 Pregnant women with low serum 25(OH)D levels had 46%
higher risk of developing anemia.
Am J Clin Nutr. 1992;56:533-536

 > 50% infants with Iron Deficiency Anemia had low
25(OH)D levels.
Plos One2010;5(1):e8770


Vitamin D & Iron Deficiency Link in
Toddlers
 20% Asian children
had both Vit D
Deficiency & Anemia.
 Children with
Vitamin D deficiency
had low Hb and
serum iron.

Thursday, December 22, 2011 dr.veerendrakumar cm Arch Dis Childhood. 1986;61:843-848
31

Vitamin D & Iron Deficiency Link in Children

BMJ. 1998;318:28

Vitamin D & Iron Deficiency Link:
The Hen or Egg?

Mechanistic Evidence


Vitamin D Deficiency causes
Anemia Plausible Mechanism # 1
 Vitamin D receptors are present in bone marrow.
 Hematons (buffy coat of bone marrow containing
erythroid precursors) shown to contain high
concentration of D25 & 1,25-hydroxyvitamin D.
 Thus Vitamin D deficiency could result in reduced
activation of erythroid precursors, causing anemia.2

Endocrinology.2006;147(12):5542-5548
Thursday, December 22, 2011 2. Ann Hepatol. 2010;89:447-452
dr.veerendrakumar cm 34

High local concentrations of 1,25(OH)D in hematopoietic tissues
may directly activate erythroid precursors cells in a paracrine
fashion.

Vitamin D

 Vitamin D supplementation will help the initial phase of erythropoesis.
 Iron supplementation would be required for the latter phase.


Vitamin D Deficiency causes
Anemia Plausible Mechanism # 2
Myelofibrosis was observed in children with Vitamin D deficiency
induced rickets.1,2,3
Vitamin D Deficiency

Reduced activation of Vitamin D receptors in bone marrow

Myelofibrosis

Impaired Erythropoesis

Anemia
1. J Pediatr. 1989;114:213-217 2. Canad Med Assoc J. 1966;94:395 3. Indian Pediatr. 2005;42:482-484

Iron Deficiency Causes Vitamin D Deficiency
Background
 Dietary/supplementary
Vitamin D absorbed from
the intestine, is converted to
25(OH)D in the liver.
 Some of the 25(OH)D in liver
is secreted into bile (mainly (Enterohepatic
circulation)
as glucuronides) & is
reabsrobed by enterohepatic
circulation.1,2

Thursday, December 22, 2011 1. Am J Clin Nutr. 1992;56:533-536
dr.veerendrakumar cm 2. Proc Soc Exp Biol Med. 1975;149:570-572
38

IDA Causes Vitamin D Deficiency
Plausible Mechanism # 1
Iron Deficiency Anemia

Impaired Epithelial Regeneration & Function

Abnormal GI mucosa

Malabsorption of Fats

Pediatrics.1964;33:83-99

Malabsorption of Fats

Impairment in Bile secretion

Impaired Vitamin D absorption & 25(OH)D reabsorption in the
intestine



IDA Causes Vitamin D Deficiency
Plausible Mechanism # 2
Iron deficiency inhibits the metabolism of Vitamin D to 25(OH)D.

 Clinical evidence
 > 50% Infants with IDA had decreased concentration of 25(OH)D &
24,25(OH)2D despite receiving daily supplements of Vitamin D.
 Treatment with iron increased the concentrations of both iron & vitamin D
metabolites.
 Increase in serum vitamin D metabolites occurred even when no change
was made in the diet or vitamin D supplements.

Am J Clin Nutr. 1992;56:533-536


The Hen or Egg?

Clinical Evidence


Clinical Evidence for the
relationship: 1


relationship: 2


Study Answers the Crucial
Question
Why is Vitamin D deficiency disease (rickets) prevalent in
tropical countries (India) with abundant sunlight?
 IDA contributes to the high prevalence because the
amount of Vitamin D synthesized in the skin is
insufficient. Does not satisfy the infants’ requirements.
 Moreover, the absorption of vitamin D in the small
intestine is limited, due to IDA resulting in the
development of rickets.


Study Recommendations


relationship: 3


Study Snapshot
 Significant association, not a mere overlap of the two
deficiencies.
 Children with low Vitamin D concentration had lower
hemoglobin and serum iron concentrations.
 This was particularly noticeable in winter. 50% of children
with low Vitamin D concentration were anemic
compared to none with vitamin D sufficiency.

A combined approach to prophylaxis against iron and
vitamin D deficiency should be considered.


The Hen or Egg?

OR BOTH?



Impaired Vitamin D
absorption & 25(OH)D
reabsorption
Ineffective Increased
erythropoesis inflammation or
marrow
Impaired myelofibrosis
Inhibition of
intestinal
Vitamin D
absorption of
Metabolism
fats.

Iron Deficiency Anemia

1.Thursday, December 22, 2011
Am J Clin Nutr. 1992;56(3):533-6 2. Plos One2010;5(1):e8770
dr.veerendrakumar cm 3. Ann Hematol. 2010;89:447-452 50

Thus....

Vitamin D & Iron Deficiency
The Never-ending Vicious Cycle leads to……

A Twin Epidemic

To Break the Cycle.......
Supplementation with IRON + VITAMIN D would provide optimum benefit


Recommended Dietary intakes of Vitamin D for patients at
risk for Vitamin D Deficiency

Age (Year) IOM(Institute of Medicine) Endocrine Society

RDA RDA
IU/ Day IU/ Day
ng/ml ng/ml

1-18 600 20 1000 30

19-50 600 20 1500-2000 30

50 & above 600-800 20 1500 -2000 30

Pregnancy &
400-600 20 1500-2000 30
Lactation

Endocrine society guidelines are suitable for Indian Patients to raise the blood
level of 25(OH)D consistently above 30 ng/ml


Thus, at a minimum, lactating women may need to take
1400–1500 IU/d, and to satisfy their infant’s
requirement, they may need 4000–6000 IU/d


Evidence of Vitamin D supplement in
adults Older than 51 yr

 Participants receiving 800 IU/d
 Had a 72% lower rate of falls than those taking
placebo or a lower dose of vitamin D.

 Resulted in a 4–11% gain in lower extremity
strength or function and up to 28% improvement
in body sway.


Summary
 Vitamin D deficiency with Iron Deficiency Anemia is
prevalent in Indians of all age groups.
 The mechanism of IDA leading to Vitamin D Deficiency or
vice versa is not fully established.
 The available clinical data indicates a vicious cycle of the
twin deficiencies.
 Supplementation with 1000 IU Vitamin D + 100 mg Iron
daily would synergistically improve the status in Indians.


More news on…

Non calcemic benefits of
vitamin D


 Vitamin D triggers natural immune response against
tuberculosis, study finds
 Increased vitamin D in blood adds years to life and helps
prevent colon cancer

 8000 IUs of vitamin D daily necessary to raise blood
levels of "miracle" anti-cancer nutrient, declares
groundbreaking new research
 Low vitamin D levels linked to Parkinson's disease


 Vitamin D grows hair, prevents the flu and reduces
arthritis pain
 Scientists say higher vitamin D intake will slash
cancer, MS, and diabetes risk by half

 Crucial vitamin D discovery: deficiency alters lung
growth, harms lung function
 Low vitamin D levels linked to Parkinson's disease
 Diabetics with low vitamin D have high risk of death


The ‘SUN’ god


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Thursday, December 22, 2011 dr.veerendrakumar cm Thank you
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vitamin d3 and iron supplementation in pregnancy

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