Double fortified salt with iron and iodine for simultaneous prevention of iron deficiency anemia and iodine deficiency disorders

1. Central Salt & Marine Chemicals Research Insitute,
Bhavnagar
Fortification of edible salt- CSMCRI Technologies
Dr.J.R.Chunawala, Principal Scientist,
CSIR-CSMCRI
Jan 2016

2. Micronutrient deficiency
• Iron deficiency is the most common micronutrient deficiency in the
world affecting 2 billion people, 2 billion nearly people have
inadequate iodine nutrition, and approximately 250 million preschool
children are vitamin A deficient.
• About 2/3rd of under 5 years children, more than ½ of women in
reproductive ages including adolescents and pregnant women are
anaemic (NFHS- 3, 2005-06)
• Significantly higher prevalence in SC /ST population /clusters
• Micronutrient deficiencies account for about 7.3% of the global burden
of diseases.
• As per WHO, India falls under the category of severe public health
significance. (>40% Anaemia prevalence)
• Micronutrient deficiencies place a heavy burden on the health and
economy of nation
• 11 % Gross Domestic Product (GDP) lost in Asia and Africa as a result
of under nutrition
CSIR-CSMCRI

3. Recommended daily minimum requirements of some essential elements
Age (year)
Ca
(mg)
P
(mg)
I
(g)
Fe
(mg)
Mg (mg)
Zn
(mg)
Cu (mg)
Mn
(mg)
Infants 0 – 0.5 500 750 90 0.27* 30 3 0.6 0.6
0.5 – 1.0 500 750 90 05 45 5 0.6 0.6
Children 1 – 3 600 600 90 9 50 5 1.0 1.0
4 – 6 600 600 90 13 70 7 1.5 1.5
7 – 10 600 600 120 16 100 8 1.5 1.5
Males 11 – 14 800 800 150 21 120 9 2.0 4.0
15 – 18 800 800 150 27 195 11 2.0 4.0
19 – 22 800 600 150 17 340 12 2.0 4.0
23 – 50 800 600 150 17 340 12 2.0 4.0
51+ 800 600 150 17 340 12 2.0 4.0
Females 11 – 14 800 800 150 27 160 9 2.0 4.0
15 – 18 800 800 150 27 235 12 2.0 4.0
19 – 22 800 600 150 21 310 10 2.0 4.0
23 – 50 800 600 150 21 310 10 2.0 4.0
51+ 800 600 150 21 310 10 2.0 4.0
Pregnant
women
1200 1200 200 35 310 12 2.0 4.0
Lactating
mother
1200 1200 200 25 310 12 2.0 4.0

4. anaemia prevalence in Indian women
Iodine, Iron, Zinc, Vitamin A, Calcium,
Vitamin D, Vitamin B12, Folic acid
Micronutrient deficiency occur concurrently
IODINE DEFICIENCY
 In India, household coverage of adequately
iodized salt (83.2% in urban areas vs. 66.1% in
rural areas)
 350 million people are at risk of IDD as they
consume salt with inadequate iodine.
 Every year nine million pregnant women and
eight million newborns are at risk of IDD in
India.

5. Salt as a Carrier of Nutrients
 Uniform consumption levels within a country/region
 Cost
 Well distributed in all food preparations
 potential to quickly reach large populations without socio-economic
barriers
 low potential for excessive intake
Double fortified salt is an innovative new concept of fortified food
product – deliver small but required amounts of iodine and iron to human
body through diet
The major problem is the interaction between iodine and iron which results
in a loss of iodine.

6. Selection of Iodine Compound
Name
Chemical
Formula
%
Iodine
Mol.
Wt.
M.P.
0C
B.P.
0C
Solubility in Water (g/L)
00C 200C 300C 400C 600C
Iodine I2 100 253.8 113 184 - - 0.3 0.4 0.6
Calcium
Iodide
CaI2 86.5 293.9 740 1100 646 676 690 708 740
Calcium
Iodate
Ca(IO3)26H2O 65.0 498 35 - - 1.0 4.2 6.1 13.6
Potassium
Iodide
KI 76.5 166.0 686 1330 1280 1440 1520 1600 1760
Potassium
Iodate
KIO3 59.5 214.0 560 d. 47.3 81.3 117 128 185
Sodium
Iodide
NaI 2H2O 85.0 149.9 651 1304 1590 1790 1900 2050 2570
Sodium
Iodate
NaIO3 64.0 197.9 d. - - 25.0 90.0 150 210

7. Loss of iodine in iodised salt
Iodide oxidation and iodate reduction leads to the formation of iodine:
2I- → I2 + 2e- ( oxidation )
2I5+ + 10e- → I2 ( reduction )
Solar sea salt contains magnesium and calcium chlorides as impurities, hydrolysis of
these salts in water produces an acid:
MgCl2 → Mg(OH)Cl + HCl ( in presence of H2O)
MgCl2 → MgO + 2HCl( in presence of H2O)
Decomposition of iodide or iodate :
4I- + O2 + 4 H+→ 2I2 +2H2O (presence of acid, sunlight and oxygen)
IO3
- + 5I- +6H+→ 3I2 +2H2O ( at elevated temperature)
IO3
- + 6 Fe2+ + 6 H+ → I- + 6 Fe3+ + 3H2O
IO3
- +5I- + 6H+ →3I2 + 3H2O
Fe3+ + 2I- → 2Fe2+ + I2
CSIR-CSMCRI

8. Demonstration of iodine loss by heating the mixture
of moist KIO3 (1 g) and MgCl2.6H2O on a sand bath
CSIR-CSMCRI

9. Demonstration of iodine liberation by heating
KIO3 with tamarind and 2-3 drops of water
CSIR-CSMCRI

10. Iodine Estimation Kit for Iodized Salt
CSIR-CSMCRI

11. CSMCRI Iodizing agent with improved stability
Key innovation:
• Reaction of iodine crystals and aq.alkali generates iodide –iodate couple in 5: 1
mole ratio and the use of resultant solution for preparation of iodized salt.
• Gastric juice would convert the latent iodine into its elemental form – more facile
absorption by body.
• Process easier and cost effective .
US Patent Application No. 20110008497
Canadian Patent No. 6,27,154
Preparation of iodising agent:
3 I 2 +6 OH - → 5 I - +IO3
- +3 H 2 O
Exposure to Stomach condition:
IO 3
- +5 I -+6 H + → 3 I 2 +3 H 2 O
0.0
5.0
10.0
15.0
20.0
25.0
30.0
35.0
0 3 6 12 16 18 24 30 36 40 46 48
Iodine,ppm
Months
CSIR-CSMCRI

12. CSMCRI- ultra stable iodizing agent
US Patent No .7695707, April, 2010 ,EP No. 1,575,874
US Patent Appl. No. 20090188810
PCT Appl. No. PCT/IN2004/000405, Pub. No. WO/2006/067798
Anion exchange reaction:
Mg(1-x)Alx(OH)2(Basic Layer)
(Inter Layer)
(Basic Layer) Mg(1-x)Alx(OH)2
H2O CO3
2- H2O + 2IO3
-
Mg(1-x)Alx(OH)2
Mg(1-x)Alx(OH)2
H2O 2 IO3
- H2O
* exchangeable x – 0.20-0.33
Anion exchange reaction:
Mg(1-x)Alx(OH)2(Basic Layer)
(Inter Layer)
(Basic Layer) Mg(1-x)Alx(OH)2
H2O CO3
2- H2O + 2IO3
-
Mg(1-x)Alx(OH)2
Mg(1-x)Alx(OH)2
H2O 2 IO3
- H2O
* exchangeable x – 0.20-0.33
CSMCRI
0
5
10
15
20
25
30
35
0 10 20 30 40 50 60 70
Iodine(ppm)
No. of Months
Stability Data
Magnesium aluminum hydroxide Octahedral
forms positively charged layers and balancing
anionic carbonate ions are located between the
layers as interlayer anions.
Basic Magnesium Aluminum Hydroxy Carbonate
Hydrate
Key Innovations
Process for preparation of stable iodizing agent with proven
performance.
Process simplicity and economy in iodate consumption.

13. STL,Jaipur
y = 0.0074x + 31.099
R2
= 0.0659
0.00
10.00
20.00
30.00
40.00
0 50 100 150 200
No of Days
Iodineinppm
STL,Jaipur
Linear (STL,Jaipur)
STL,Tuticorin
y = 0.0277x + 28.953
R2
= 0.6195
0.00
10.00
20.00
30.00
40.00
0 50 100 150 200
No of Days
Iodineinppm
STL,Tuticorin
Linear (STL,Tuticorin)
STL,Bhubneshwar
y = 0.0123x + 31.601
R2
= 0.1949
0.00
10.00
20.00
30.00
40.00
0 50 100 150 200
No of Days
Iodineinppm
STL,Bhubneshwar
Linear
(STL,Bhubneshwar)
S.N0.
No Of
Days
STL,Jaipur STL,Tuticorin STL,Bhubneshwar
1 0 28.87 29.95 33.06
2 15 34.06 29.39 31.60
3 30 29.80 29.95 30.50
4 49 32.91 29.72 33.46
5 64 32.65 29.62 29.96
6 79 30.96 30.26 33.07
7 94 30.88 30.83 33.07
8 109 30.71 31.35 32.28
9 124 33.20 35.70 32.81
10 141 31.81 33.34 36.16
11 156 33.74 33.04 33.18
12 171 31.19 32.83 32.76
Iodine stability in iodised salt
Prepared using novel compound
- tested by Salt Department
CSIR-CSMCRI

14. KEY:
G=Good, F=Fair, P=Poor,
-=Information not available
R=Recommended, V=Variable,
NR=Not Recommended
%IronContent
Bioavailability
inHumans
Bioavailability
inAnimals
Salt
Relativecost
factor
Freely water soluble
Ferrous sulphate 7H2O 20 G G V 5.0
Ferrous gluconate 12 G G V 8.3
Ferrous lactate 19 G G NR 5.3
Ferric ammonium citrate 18 G G NR 5.5
Ferrous ammonium sulphate 14 - G - -
Ferric choline citrate 14 - G NR -
Slowly Soluble
Dried Ferrous Sulphate 33 G G V 3.0
Ferric glycerophosphate 15 G G NR 6.6
Ferric citrate 17 P V 17.6
Ferric sulphate 22 P G NR 13.6
Ferric saccharate 3-35 F G - 5.7-6.6
Ferric chloride 34 F G NR 5.9
Poorly Soluble
Ferrous fumarate 33 G G R 3.0
Ferrous succinate 35 G G - 2.8
Ferrous tartrate 22 F F - 9.0
Ferrous citrate 24 F F V 8.4
Almost insoluble or soluble
Ferric pyrophosphate 25 P P R 12.0
Ferric orthophosphate 28 P P R 10.7
Sodium iron pyrophosphate 15 P P NR 20.0
Reduced elemental iron
a. reduced by hydrogen 96 F F NR 2.1
b. reduced by carbon monoxide 96 F F NR 2.1
c. Carbonyl Iron 98 F F NR 2.1
d. Reduced by electrolysis 97 F F NR 2.1
Ferric oxide 70 P P NR 4.2
Ferric hydroxide 62 P P NR 4.8
Ferrous carbonate 35 P P NR 8.5
Iron complex compound
Sodium ferric EDTA 13 G G - 7.7
Commercially available Iron Compounds
Relative cost factor
= 100 x bioavailability factor in human / % of iron
Bioavailability factor
= G(1) ; F (2); P (3)

15. Types of
DFS
Iron Compound
(1000 ppm)
Iodine
Compound
(40ppm)
Additives
In-Vitro
Results
In-Vivo
Results
Clinical
Trial
Results
Type 1
Ferrous Fumarate
(Diosady, 2002)
(Encap.)
KIO3
Soy Stearine, TiO2,
SHMP
Unknown Unknown Unknown
Type 2
Ferrous Sulphate
Heptahydrate
(Shivkumar, 2001)
KIO3
(Encap.)
SHMP Unknown Yes Unknown
Type 3
Ferrous Sulphate
Monohydrate
(Encap.)
KIO3
(Encap.)
Malic acid, SHMP,
Sodium dihydrogen
phosphate, NaHCO3
Unknown Unknown Unknown
Type 4
Ferrous Sulphate
hydrate
(Encap.)
KIO3
Cellulose acetate
phthalate, Silicon,
Partially hydrogenated
vegetable oil
Unknown Unknown Unknown
Type 5
Ferric
Pyrophosphate
(FePP)
(Micronized)
KIO3 Yes Yes Unknown
Type 6
Sodium Ferric
EDTA
KIO3
Stabilizers, Colour
masking agent
Unknown Unknown
Unknown
CSIR
CSMCRI
Inorganic iron
( premix)
IO3
-
( premix)
No additives Known Known Unknown
Characterisation of the most recent produced formulation by type of
Double Fortified Salt (DFS)

16. CSMCRI - Double fortified salt ( DFS)using novel Iron
fortifying agent
Key Innovations
 Use of waste bittern as magnesium source
 Aluminum is replaced by Fe
 White in colour
 Prevented chemical interaction between iron and
iodine in salt medium
 Safe ,affordable, stable, used without compromising
appearance, stability, taste, and texture of the salt
 Process simplicity.
A white coloured synthetic hydrotalcite of approximate formula
[Mg4.1±0.4Fe(III)(OH)10.2±0.7][CO3]0.5 .3H2O], as iron source for iron fortification.
Fortification of edible salt with a novel iron fortifying agent and iodizing agent has been developed
prepared cost effectively using synthetic hydrotalcite.
Process has been scaled up and optimized (30 gm to 3 kg) for fortifying agent)
CSIR-CSMCRI

17. Bioavailability and toxicity studies of DFS
The bioavailability study has been initiated with Govt. Medical college,
Bhavnagar. Prof. C.B.Tripathi, Head, Pharmacology Deptt, is carrying out the
study for which CSMCRI will give the DFS salt samples and assist in in vitro
study and they will help in in vivo studies( rats and human ).
CSIR-CSMCRI

18. Group Type of salt Initial
(Hb)
After
depletion
(6 months)
(Hb)
After repletion
(1 month period)
(Hb)
II Salt with
Ferrous
sulphate
12 - 15 11 - 12 14 - 14.6
III Common salt
( No Fe)
13.7 - 14.6 12.4 - 14 13.5 - 14.2
IV DFS-CSMCRI 12.9 – 15.1 12 – 13.5 14 – 18
I DFS-CSMCRI 13.9-14.6 12.8-14.4 Cont.- 8 months
13.3- 18.5
 Preliminary studies of bioavailability tested at Department of Pharmacology,
Government Medical college, Bhavnagar, using wistar rats.
The results indicated clearly that the iron contained in DFS prepared by this institute is more effective
than the other conventional iron fortified salt
Bioavailability of the iodine have been be conducted at Department of Pharmacology, Government
Medical college, Bhavnagar using 50 wistar rats and results are awaited.
The cost of fortification for fortifying salt to contain 1000 ppm of iron and 30 ppm of iodine works
out to be Rs. 1.5 per kg of salt.
Bioavailability of iron and iodine in Double Fortified Salt
CSIR-CSMCRI

19. CSIR-CSMCRI patents on salt fortification
1. Iodizing agent and process for preparation thereof
International Application No.PCT /IN 2004 /000190 ,Granted on 13 th April,2010,
US patent No. 7695707
2. Process for the Preparation of Stable Iodate-Exchanged Synthetic Hydrotalcite
with Zero Effluent Discharge.
International Application No.PCT /IN 2008 /000615 Granted on 14 th August ,2012, US patent
No. US 8,241,483 B2
3. Iodized salt and a process for its preparation.
International Application No. PCT/IN2004/000405, Pub.No. WO/2006/067798
Granted on 14 th May ,2010, US patent No. US 8,440,252
4. Novel double fortified salt compositions containing iron and iodine and process of
preparation thereof.
International Publication Number WO 2013/128474 A1, publication date 6th Sept. 2013.US patent
publication No.US2015/0037466 A1,5 th Feb.2015
The cost of fortification for fortifying salt to contain 1000 ppm of iron and 30 ppm of
iodine works out to be Rs. 1.5per kg of salt.
CSIR-CSMCRI

20. MOU with District Administration

21. THANK YOU CSIR-CSMCRI