vitamin d3 and iron supplementation in pregnancy

Veerendrakumar C.M.

MD.,DNB

Associate Professor

Dept of OBG,VIMS,Bellary

Thursday, December 22, 2011 1dr.veerendrakumar cm

Alien + Predator

Vitamin D & Iron Deficiency: Deadly Duo


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.


http://www.naturalnews.com/032533_sun_exposure_skin_cancer.html

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

Contents


Vitamin DVitamin 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.Thursday, December 22, 2011 11dr.veerendrakumar cm

Pregnancy -The most dangerous journey of mankind


ANEMIA

40-90% WOMEN AFFECTED

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

CHRONIC MORBIDITY


Thursday, December 22, 2011 14

Eradicating anemia can save at least

200 mothers a day!

dr.veerendrakumar cm

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

Public Health Significance

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http://images.google.co.in/imgres?imgurl=http://www.umweltbundesamt.de/whocc/titel/who4.gif&imgrefurl=http://www.umweltbundesamt.de/whocc/titel/titel21.htm&usg=__3yQVc6dfRFspKRLfJDtH-soE3MM=&h=947&w=1062&sz=21&hl=en&start=5&um=1&itbs=1&tbnid=YR30xkVY1U4EzM:&tbnh=134&tbnw=150&prev=/images?q=WHO&hl=en&sa=G&um=1

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Iron strengthens!

Gold glittersSilver shines

But…

Thursday, December 22, 2011 dr.veerendrakumar cm

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

Where possible, avoid blood transfusion.

Patients have a right to

Normal Hb and

Receive safe and efficient treatment;

17Thursday, December 22, 2011 dr.veerendrakumar cm

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!

Thursday, December 22, 2011 dr.veerendrakumar cm 18

Are we producinga 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


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

Vitamin D Deficiency: Gender Analysis


Am J Clin Nutr 2000;72:472-5. Am J Clin Nutr 2005;81:1060-4.

≈84% Indian women have 25(OH)D values < 22.5 ng/L.

Vitamin D deficiency in Pregnant women and their New born


Indian J Med Res. 2011;133:267-273

Deficiency: <15 ng/ml

Insufficiency: 15-20 ng/ml

Severe Deficiency: <5 ng/ml

81.1%

66.7%

11.6%19.8%

23.2% 27.1%

Vitamin D deficiency in Lactating Women and Breastfed infants


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

Vitamin D deficient Mother-Deficient Infant


Thursday, December 22, 2011 dr.veerendrakumar cm 26

Retards proliferation and

increases differentiation of cells

http://www.naturalnews.com/032533_sun_exposure_skin_cancer.html

Mayo Clin Proc. 2006;81(3):353-373

Vitamin D Deficiency:Health Implications

Osteomalacia & Rickets

Osteoporosis

Diabetes

Hypertension & CVD

&

Anemia


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


Arch Dis Childhood. 1986;61:843-848

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.


Vitamin D & Iron Deficiency Link in Children

BMJ. 1998;318:28Thursday, December 22, 2011 32dr.veerendrakumar cm

Mechanistic Evidence

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


Endocrinology.2006;147(12):5542-5548 2. Ann Hepatol. 2010;89:447-452

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


Vitamin D

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

Vitamin D supplementation will help the initial phase of erythropoesis.

Iron supplementation would be required for the latter phase.


Myelofibrosis was observed in children with Vitamin D deficiency induced rickets.1,2,3

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

Vitamin D Deficiency

Reduced activation of Vitamin D receptors in bone marrow

Myelofibrosis

Impaired Erythropoesis

Anemia

Vitamin D Deficiency causes Anemia Plausible Mechanism # 2


1. Am J Clin Nutr. 1992;56:533-536 2. Proc Soc Exp Biol Med. 1975;149:570-572

(Enterohepatic circulation)

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 as glucuronides) & is reabsrobed by enterohepaticcirculation.1,2


Iron Deficiency Anemia

Impaired Epithelial Regeneration & Function

Abnormal GI mucosa

Malabsorption of Fats

Pediatrics.1964;33:83-99

IDA Causes Vitamin D Deficiency Plausible Mechanism # 1


Malabsorption of Fats

Impairment in Bile secretion

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



Iron deficiency inhibits the metabolism of Vitamin D to 25(OH)D.

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

IDA Causes Vitamin D Deficiency Plausible Mechanism # 2

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.


Clinical Evidence



Clinical Evidence for the relationship: 1


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


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

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.


OR BOTH?




Increased inflammation or marrow myelofibrosis

Ineffective erythropoesis

Iron Deficiency Anemia

Impaired intestinal absorption of fats.

Inhibition of Vitamin D Metabolism

Impaired Vitamin D absorption & 25(OH)D reabsorption

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

Thus....

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

A Twin Epidemic

To Break the Cycle.......

Supplementation with IRON + VITAMIN D would provide optimum benefit


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

IU/ DayRDA

ng/mlIU/ Day

RDA

ng/ml

1-18 600 20 1000 30

19-50 600 20 1500-2000 30

50 & above 600-800 20 1500 -2000 30

Pregnancy &

Lactation400-600 20 1500-2000 30

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

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


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.


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.

Summary


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The ‘SUN’ god


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Thank youThursday, December 22, 2011 61dr.veerendrakumar cm

vitamin d3 and iron supplementation in pregnancy

Health & Medicine

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