7 Effects of Phosphorus-Containing Compounds on Iron and Zinc Utilization A Review of the Literature J. L. GREGER Downloaded by CORNELL UNIV on August 19, 2016 | http://pubs.acs.org Publication Date: November 1, 1982 | doi: 10.1021/bk-1982-0203.ch007
University of Wisconsin, Department of Nutritional Sciences, Madison, WI 53706
A number of investigators have studied the effects of dietary phosphorus on the bioavailability of zinc and iron to animals and human subjects. The results of these studies have not been consistent. Possible reasons for discrepancies among studies include: differences in the types of phosphorus compounds fed; differences in the levels of iron, zinc, ascorbic acid, protein, and calcium fed; and differences in the methods used to assess zinc and iron bioavailability. Many i n v e s t i g a t o r s during the l a s t 50 years have t r i e d t o determine whether phosphorus-containing compounds a f f e c t t h e u t i l i z a t i o n o f z i n c and i r o n by animals. These s t u d i e s have produced divergent and o f t e n seemingly i n c o n s i s t e n t data. Thus the o b j e c t i v e s o f t h i s review a r e : 1) t o summarize the r e s u l t s of s t u d i e s i n which the e f f e c t of phosphorus on i r o n and z i n c metabolism were i n v e s t i g a t e d ; 2) t o examine the d i f f e r e n c e s i n experimental design and methodology among these s t u d i e s ; and 3) to suggest t o what extent these methodological d i f f e r e n c e s account f o r the d i f f e r e n c e s i n the data produced i n these s t u d i e s . B i o a v a i l a b i l i t y o f Iron From Inorganic Phosphorus and Iron
Compounds Containing
Both
A number of i n v e s t i g a t o r s have studied the r e l a t i v e b i o a v a i l a b i l i t y of i r o n from v a r i o u s compounds that contained both i r o n and phosphorus. Three such s a l t s that have been studied e x t e n s i v e l y are f e r r i c phosphate, f e r r i c pyrophosphate, and sodium-iron pyrophosphate. A l l three have been l i s t e d as Generall y Recognized as Safe (GRAS) i n the Code of F e d e r a l Regulations and have been added t o foods i n the United States as i r o n supplements (1). However, only small amounts of two of these phosphorus-containing s a l t s , f e r r i c pyrophosphate and sodium i r o n
0097-6156/82/0203-0107$06.00/0 © 1982 American Chemical Society Kies; Nutritional Bioavailability of Iron ACS Symposium Series; American Chemical Society: Washington, DC, 1982.
108
NUTRT IO INAL BO IAVAL IABL IT IY OF R ION
pyrophosphate, have been used as food a d d i t i v e s i n t h e United States s i n c e 1975. The reasons f o r t h e l i m i t e d use of these two compounds a r e t h e i r l i m i t e d b i o a v a i l a b i l i t y and t h e i r c o s t ( 2 ) . I r o n i n unprocessed f e r r i c phosphate and sodium i r o n phosphate has extremely low b i o a v a i l a b i l i t y as judged by hemoglobin r e p l e t i o n assays w i t h anemic r a t s and c h i c k s (3-8) (Table I ) . The a b s o r p t i o n of r a d i o - l a b e l e d i r o n from these compounds by nonanemic r a t s has a l s o been found to be low ( 9 ) . Table I :
B i o a v a i l a b i l i t y of i r o n from phosphate s a l t s Relative biological v a l u e (%)
Downloaded by CORNELL UNIV on August 19, 2016 | http://pubs.acs.org Publication Date: November 1, 1982 | doi: 10.1021/bk-1982-0203.ch007
Salts
Eats*
ferrous sulfate
100
Chicks^
Absorption of Fe (%)
Humans 6
100
100
Rats#
Humans**
\5.7
2.7-6.6
f e r r i c orthophosphate
12-33
9-18
7
2.9
0.7-1.1
sodium i r o n pyrophosphate
11-63
2-13
7
1.0
0.3-1.0
*Based tBased $Based //Based **Based
on on on on on
hemoglobin r e p l e t i o n assays (3.-6)• hemoglobin r e p l e t i o n assays ( 3 ) • change i n plasma i r o n a f t e r dose of 50 mg i r o n (4) • t o t a l body count f o r F e 1 week a f t e r do^se ( 9 ) . amount of F e i n blood or RBC two weeks a f t e r dose (10, 5 9
5 9
S i m i l a r l y the b i o a v a i l a b i l i t y of i r o n to human s u b j e c t s from f e r r i c orthophosphate and sodium i r o n pyrophosphate has been found to be much lower than the b i o a v a i l a b i l i t y of i r o n from f e r r o u s s u l f a t e (4, 10, 11). The s t u d i e s w i t h human s u b j e c t s d i f f e r e d i n the manner i n which i r o n b i o a v a i l a b i l i t y was judged. Two groups of i n v e s t i g a t o r s administered radiotagged i r o n s a l t s to s u b j e c t s and measured the l e v e l s of F e and F e i n the blood o r red blood c e l l s two weeks l a t e r (10, 11). P l a & F r i t z (4) measured t h e r i s e i n plasma i r o n l e v e l s two hours a f t e r a l a r g e dose (100 mg i r o n ) of the s a l t . D e s p i t e the d i f f e r e n c e s i n methodology i n the human and animal s t u d i e s , the data a r e f a i r l y c o n s i s t e n t . Iron i s not very a v a i l a b l e to men or animals when i t i s fed to them as an unprocessed i n o r g a n i c s a l t of phosphate. T h i s does not mean that the b i o a v a i l a b i l i t y of i r o n from a l l compounds c o n t a i n i n g both phosphorus and i r o n i s low. Wood, et a l . (12) and Theuer and h i s a s s o c i a t e s (7_, 8) have found t h a t t h e b i o a v a i l a b i l i t y of i r o n from sodium i r o n pyrophosphate and f e r r i c pyrophosphate was g r e a t l y improved when the foods c o n t a i n i n g these s a l t s were processed with heat and p r e s s u r e (Table I I ) • Such p r o c e s s i n g d i d not, however, improve the b i o a v a i l a b i l i t y of i r o n from f e r r i c orthophosphate or f e r r o u s s u l f a t e . The reason f o r t h i s e f f e c t i s not known but sugars i n the foods may have formed c h e l a t e s with the i r o n that f a c i l i t a t e d a b s o r p t i o n . 5 9
5 5
Kies; Nutritional Bioavailability of Iron ACS Symposium Series; American Chemical Society: Washington, DC, 1982.
7.
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GREGER
Phosphorus-Containing Compounds Table I I : E f f e c t of processing w i t h heat and pressure
on the b i o a v a i l a b i l i t y of i r o n from phosphate s a l t s to r a t s * Relative b i o l o g i c a l value Iron source
Unprocessed
Processed
% ferrous s u l f a t e
100
106
f e r r i c orthophosphate
-10
11
sodium f e r r i c pyrophosphate f e r r i c pyrophosphate
14
66^
7
90^
Downloaded by CORNELL UNIV on August 19, 2016 | http://pubs.acs.org Publication Date: November 1, 1982 | doi: 10.1021/bk-1982-0203.ch007