Contents - Previous - Next

This is the old United Nations University website. Visit the new site at http://unu.edu



Plasma iron tolerance of ferrous glycine sulphate and ferrous sulphate in women


K. Madhavan Nair, L. Raman, B. A. Ramalakshmi, and D. Sreeramulu

Abstract

Plasma iron tolerance curves of ferrous glycine sulphate (FGS) tablets containing 60 and 120 mg of elemental iron were compared with similar doses of ferrous sulphate (FS) tablets using a double-blind crossover design in six women volunteers. The plasma iron tolerance curves obtained with both doses of FGS were similar to those of doses of FS. The relative bioavailability of FGS was close to 1, identical to that of FS. Thus tablets containing ferrous glycine sulphate as the source of elemental iron for the prophylaxis of iron deficiency do not offer any advantage over the less expensive and more available ferrous sulphate.

Editor's note

The findings in the following article are not new. As the authors acknowledge, more precise studies [ref 8] have already confirmed that the iron in ferrous sulphate (FS) and ferrous glycine sulphate (FGS) is equally available. However, the more costly FGS continues to be favoured for its supposedly better absorption. This paper, reporting in vivo studies in a developing country, confirms that FS continues to be the compound of choice for effective supplementation at lowest cost.

Introduction

The major cause of anaemia in India is a deficiency of iron. The frequency of anaemia is relatively high among women of reproductive age and preschool children [1], and various corrective measures have been undertaken to combat iron deficiency in these two groups [2]. Despite the existence of a national anaemia prophylaxis programme over the last 20 years, however, the prevalence of anaemia continues to be high.

Besides other logistic and administrative problems, it has been suggested that the amount of elemental iron present in 60-mg ferrous sulphate (FS) tablets may not be adequate to control and prevent anaemia of the magnitude that exists. Alternatively, the poor response could be due to the low availability of iron in tablet form.

On the basis of results of in vitro studies, it has been suggested that ferrous glycine sulphate (FGS) might be a better source of iron in supplementation programmes. FGS is an organic form of elemental iron that is supposed to have better availability and increased tolerance. A recent study on the in vitro bioavailability of iron from salt fortified with FGS observed that about 80% of its iron is present in ionizable form [3]. A study was therefore carried out in women volunteers to assess the relative bioavailability of FGS and FS in vivo.

 

Materials and methods

Pharmaceutical preparations of FGS were obtained from Medcell Labs, Madras, and of FS from Indian Drugs and Pharmaceuticals Ltd., Hyderabad. They contained 60 mg of elemental iron and 500 g of folic acid.

Subjects

Twelve women volunteers (18-30 years old), four of whom were pregnant, were recruited for the bioavailability studies. They were alternately administered 60 and 120 mg of elemental iron on an empty stomach using a double-blind crossover design. To determine plasma iron tolerance, fasting blood samples were collected from all the subjects before each dose, and samples were collected at 2, 3, 4, and 6 hours after the dose. The subjects were allowed to have food only after the last sample was drawn. The second preparation was given after an interval of four days.

TABLE 1. Clinical and kinetic data of iron in subjects after an oral dose of 60 and 120 mg of FS and FGS

       

Ferrous sulphate

Ferrous glycine sulphate

 
Subject

Age (yr)

Hb (g/dl)

Basal SI

Time to peak

Peak SI

AUC

Time to peak

Peak SI

AUC

Relative bio-availability

60 elemental iron

1

22 (P)

7.8

74

3

238

1,018

2

232

1,135

1.11

2

18

-

145

3

312

1,535

3

230

1,104

0.70

3

21 (P)

10.0

140

3

285

1,375

4

238

1,323

0.96

4

22

12.5

220

3

635

2,253

4

419

2,219

0.98

5

22

11.1

130

3

201

971

4

223

1,075

1.11

6

22

12.0

128

4

278

1,195

3

231

1,085

0.91

Mean

21.7

10.7

140

3.2

325

1,391

3.3

262

1,324

0.96

SD

2.25

1.87

46.9

0.41

156.9

473

0.82

76.9

448

0.152

120 mg elemental iron

7

24

10.9

182

3

420

1,987

3

477

2,330

1.17

8

30

12.8

146

3

493

2,141

3

545

2,767

1.29

9

16 (P)

10.9

150

4

402

1,887

4

495

2,234

1.18

10

26 (P)

11.5

151

4

449

1,869

4

214

1,062

0.57

11

20

12.5

140

4

429

1,717

4

297

1,518

0.88

12

24

13.4

149

4

449

1,819

4

321

1,421

0.78

Mean

23.3

12.0

153

3.7

440

1,903

3.7

392

1,905

0.98

SD

4.84

1.05

14.8

052

31.4

146

052

131.9

663

0.279

P = pregnant woman.
SI = serum iron g/dl.
AUC = area under the curve.

 

Analysis

Haemoglobin concentration was estimated by the cyanmeth method [4] and plasma iron by the bathophenanthroline method [5]. The area under the plasma iron tolerance curve was calculated according to the method described by Gibaldi and Perrier [6]. Data were analysed after decoding, and statistical tests were applied to test the differences, if any, between the preparations.

 

Results

Table 1 shows the individual details of subjects, basal serum iron, and kinetic data and their mean values.

FIG 1. Mean increase in serum iron after 60 and 120 mg doses of FS and FGS

Wide variations were seen in peak values and the area under the curve. However, both groups had comparable haemoglobin concentrations and basal plasma iron levels.

Identical plasma iron tolerance curves were obtained with both 60- and 120-mg doses of FS and FGS (fig. 1). Peak iron levels occurred between the third and fourth hours after administration and decreased slowly thereafter. No correlation was seen between either the basal plasma iron concentration or the haemoglobin and peak plasma iron levels. The mean peak plasma iron levels were 325 and 262 g/dl for 60 mg of FS and FGS respectively, and 440 and 392 g/dl for 120 ma. These differences were not statistically significant. Whereas there was wide individual variation in iron absorption from both preparations, plasma iron tolerance was essentially the same. The mean ratios of plasma tolerance of iron from FGS to that from FS for 60 mg and 120 mg were 0.96 and 0.98 respectively. Regardless of doses, pregnant women did not have any difference in plasma iron tolerance, area under the curve, and peak concentration compared with non-pregnant women.

 

Discussion

Because of its organic nature, it has been assumed that FGS is better tolerated than FS. In addition, its stability at acidic pH is good [7]. The in vitro bioavailability of common salt fortified with FGS was very high, and almost 80% of the elemental iron was in ionizable form [3]. Nevertheless, the in vivo bioavailability of the FS tablet was found to be identical. Similar results were observed in a comparison of the absorbability of different iron compounds including FGS using radioactive iron, a more exact method [8].

The higher bioavailability reported with FGS was based on an in vitro test applied in pure systems. However, in vivo, many factors, including stomach pH, the presence of food, gastric mobility, and mucosal integrity, influence the absorption of iron from the gastrointestinal tract. The in vitro study carried out earlier did not take these factors into consideration.

Thus, in view of similar bioavailability of iron in the two forms and the higher cost of FGS, it is not the preparation of choice for large-scale public health programmes aimed at preventing iron deficiency anaemia.

 

Acknowledgements

We thank Dr. Vinodini Reddy, Director of the National Institute of Nutrition, Hyderabad, for her encouragement in this study. We also thank Mrs. Sudha Srinvasan for typing the manuscript. The tablets were supplied by courtesy of M/s. Medcell Laboratories, Madras.

 

References

1. Vijayaraghavan K, Brahmam GNV, Madhavan Nair K, Akbar D, Prahlad Rao N. Evaluation of national nutritional anemia prophylaxis programme. Indian J Ped 1990;57:183-90.

2. Dana RN, Halder K, Krishnamurthy KA et al. Use of common salt fortified with iron in the control and prevention of anemia: a collaborative study. Am J Clin Nutr 1982;35:1442-51.

3. ICMR. Annual report of National Institute of Nutrition. Hyderabad, AP: Indian Council of Medical Research, 1991-92:60-61.

4. Wong SY. Colorimetric determination of iron and hemoglobin in blood. J Biol Chem 1928;77:409-12.

5. Bothwell TA, Conral ME, Cook JD et al. Proposed recommendations for measurement of serum iron in human blood. International Committee for Standardization in Hematology. Br J Haematol 1971;20:451-4.

6. Gibaldi M, Perrier D. Absorption kinetics and bioavailability. In: Drugs and the pharmaceutical sciences. Vol. 151, Pharmacokinetics. 2nd ed. New York: Marcel Dekker, 1982;145-98.

7. Subba Rao K, Narasinga Rao BS. In vitro studies on chelating agents as potential iron absorption promoters. Food Chem 1985;17:13-23.

8. Brise H, Hallberg L Absorbability of different iron compounds. Acta Med Scand 1962;171:(suppl.376)2337.


Contents - Previous - Next