The Role of Trace Elements in Human Nutrition and Metabolism - ACS

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The Role of Trace Elements in Human Nutrition and Metabolism R. W. TUMAN and R. J. DOISY Department of Biochemistry, State University of New York, Upstate Medical Center, Syracuse, Ν. Y. 13210

Introduction The ultimate goal of nutritionists, food chemists, and food technologists is to answer the question: What is adequate nutrition? The answer to this most important question requires know ledge of the nutrients required for good health, the amounts needed, and food sources which can supply the necessary nutrients. In the past, efforts to define human requirements have been preoccupied with discussions of the major essential nutrients, including: clarification of amino acid, vitamin and macro element requirements, recommending a proper balance of carbohy drate, fat and protein, and defining appropritate energy require ments (1). Very little attention has been given to the so-called trace elements. Only recently, however, have scientists begun to appreciate the full extent of the biochemical role of trace elements and their interactions with human health and nutrition. At the present time, the 14 trace elements listed in Table 1 have been identified as being essential for either human or animal nutrition (2). These include iron, iodine, copper, man ganese, zinc, cobalt, molybdenum, selenium, chromium, tin, vana dium, fluorine, silicon, and nickel. It i s i n t e r e s t i n g to note (Table l ) that during the f i r s t 100 p l u s years s i n c e i r o n was found to be e s s e n t i a l , only f i v e a d d i t i o n a l t r a c e elements were discovered to be r e q u i r e d f o r good h e a l t h , i n c l u d i n g i o d i n e , copper, manganese, z i n c , and c o balt. In c o n t r a s t w i t h t h i s r a t h e r slow e a r l y r e c o g n i t i o n of the importance of trace elements, during the 20 year p e r i o d from 1953-1973, a t o t a l o f e i g h t a d d i t i o n a l trace elements have been found to be e s s e n t i a l , i n c l u d i n g molybdenum, selenium, chromium, t i n , vanadium, f l u o r i n e , s i l i c o n , and n i c k e l . Furthermore, no l e s s than 5 of these 8, namely, n i c k e l , t i n , s i l i c o n , f l u o r i n e , and vanadium, have emerged as e s s e n t i a l n u t r i e n t s only i n the

156 Jeanes and Hodge; Physiological Effects of Food Carbohydrates ACS Symposium Series; American Chemical Society: Washington, DC, 1975.

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Trace Elements in Nutrition TABLE 1

DISCOVERY OF ESSENTIAL TRACE ELEMENTS REQUIREMENTS 1. 2.


3.

Iodine . . . . Copper . . . .

4. 5.

Manganese.

. .

6.

Cobalt

7.

Molybdenum . .

8. 9. 10. 11.

Selenium . . ., Chromium . . ., , Tin Vanadium . . .,

12. 13.

Fluorine Silicon.

14.

N i c k e l . . . .,

. . . .

. . .. . . ..

Adapted from:

17th Century 1850 C h a t i n , A. 1928 Hart, Ε . Β . , H. Steenbock, J. Waddell, and C A. Elvehjem 1931 Kemmerer, A. R. and W. R. Todd 1934 Todd, W. R., C A. Elvehjem, and Ε . B. Hart 1935 Underwood, E. J. and J. F. F i l m e r ; Marston, H. R.; L i n e s , E. W. 1953 DeRenzo, E. C., E. K a l e i t a , P. H e y t l e r , J. J. Oleson, W i l l i a m s ; R i c h e r t , D. A. and W. W. Westerfeld Schwarz, K. and Schwarz, K. and Schwarz, K., D. Schwarz, K., D. and H. E. Mohr 1972 Schwarz, K. and 1972 Schwarz, K. and Ε . M. 1973 N i e l s e n , F. H.

1957 1959 1970 1971

Schwarz, K.,

C. W. B. B.

M. F o l t z Mertz M i l n e , and E. Vinyard M i l n e ; Hopkins, L. L.

D. B. Milne D. B. M i l n e ; C a r l i s l e ,

Federation Proceedings, ( £ ) .

Jeanes and Hodge; Physiological Effects of Food Carbohydrates ACS Symposium Series; American Chemical Society: Washington, DC, 1975.


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l a s t 3-4 y e a r s . I n d i c a t i v e of the i n c r e a s e d r e c o g n i t i o n trace elements are r e c e i v i n g i n human, as w e l l as animal n u t r i t i o n , i s the r a p i d i t y with which the l i s t of e s s e n t i a l t r a c e elements i s growing. Table 2 describes the p e r i o d i c d i s t r i b u t i o n of those elements g e n e r a l l y considered to be m i c r o - n u t r i e n t elements. Examination of Table 2 r e v e a l s s e v e r a l i n t e r e s t i n g p o i n t s : l) With the recent a d d i t i o n of vanadium and n i c k e l to the l i s t of e s s e n t i a l t r a c e elements, a continuous set of 8 e s s e n t i a l e l e ments i s created i n the f i r s t t r a n s i t i o n s e r i e s , from vanadium (atomic number 23) through zinc (atomic number 30). Furthermore, when one i n c l u d e s molybdenum (atomic number 42), 9 of the Ine s s e n t i a l t r a c e elements are t r a n s i t i o n elements. Therefore, the t r a n s i t i o n s e r i e s elements, i n g e n e r a l , c o n s t i t u t e a r e g i o n of the p e r i o d i c t a b l e with s p e c i a l i n t e r e s t and importance (2). 2) With the exception of f l u o r i n e (atomic number 9) and s i l i c o n (atomic number 14), a l l of the e s s e n t i a l t r a c e elements are l o c a t e d above calcium (atomic number 20) and none of the 39 elements beyond i o d i n e (atomic number 53) have ever been shown to be e s s e n t i a l f o r animals or man (2). 3) More than 20 other t r a c e elements shown i n Table 2 are p o t e n t i a l l y important and are c u r r e n t l y under s p e c i a l c o n s i d e r a t i o n w i t h respect to e s s e n t i a l i t y (2). Progress i n d i s c o v e r i n g new e s s e n t i a l t r a c e elements has r e l i e d on improved research techniques. In t h i s r e s p e c t , e s t a b l i s h i n g the e s s e n t i a l i t y of the newer t r a c e elements ( t i n , vanadium, f l u o r i n e , s i l i c o n , and n i c k e l ) has r e l i e d on the development and i n t r o d u c t i o n of the u l t r a - c l e a n environment and p l a s t i c i s o l a t o r techniques, as w e l l as the use of pure c r y s t a l l i n e amino acids and vitamins i n p r e p a r i n g the d i e t s of l a b o r a t o r y animals. Recent developments i n trace element a n a l y s i s , p a r t i c u l a r l y s e n s i t i v e methods i n v o l v i n g atomic absorption spectroscopy and neutron a c t i v a t i o n , have f u r t h e r advanced the s t a t e of trace element n u t r i t i o n . At the present time, the l i s t i s composed of 14 e s s e n t i a l t r a c e elements, however, the absolute number o f r e q u i r e d trace elements i s s t i l l not known. I t i s probable that some or a l l o f the elements l i s t e d i n Table 2 as p o t e n t i a l l y important w i l l be found to p a r t i c i p a t e i n v i t a l processes as s t i l l newer experimental techniques are r e f i n e d and a p p l i e d . S e v e r a l trace elements and t h e i r d e r i v a t i v e s , f o r example, cadmium, mercury, a r s e n i c , and l e a d have been shown to be t o x i c . The d e t r i m e n t a l e f f e c t s o f l e a d and methyl-mercury on the c e n t r a l nervous system are w e l l known. B e r y l l i u m and a r s e n i c are h i g h l y carcinogenic i n l a b o r a t o r y animals, and n i c k e l carbonyls and c h r o m â t e s have been i m p l i c a t e d as a cause of lung cancer (_3)· However, i t i s obvious from past r e s u l t s , that t o x i c i t y cannot be used as a v a l i d argument a g a i n s t p o t e n t i a l e s s e n t i a l i t y . Most e s s e n t i a l elements become t o x i c at s u f f i c i e n t l y high l e v e l s and the margin between t o x i c and b e n e f i c i a l doses may be s m a l l . For example, the t o x i c i t y of selenium was demonstrated w e l l



C a

Mg

20

12

4jBe

IIA

IIIB

Adapted from:

55çs

37Rb

K

Na

19

n

Group IA

VIII Co

l Fe 2 7

1 2 6

^ Pd

Ni

1

6

2 8

C

I IB

7

9Au

S 0

HÊ

l 9 u l WZn 2

IB

31fe

Schwarz, K., F e d e r a t i o n Proceedings, (2^).

1 1 Elements w i t h known e s s e n t i a l i t y . — Elements p o t e n t i a l l y important. ( 3 Elements important i n normal carbohydrate metabolism.

2

h Mo|

ZhQ

23v l i ^ c r

22

T i

VI IB

VIB

VB

TVB

13M

IIIA

DISTRIBUTION OF TRACE ELEMENTS OF KNOWN AND POTENTIAL IMPORTANCE FOR HUMAN AND ANIMAL NUTRITION

PERIODIC TABLE

Table 2


8 2

51Sb Pb

S n

50

P

33AS

15

VA

3 Ge 2

^Si

IVA

34

S e

S

0 16

8

VIA

C1

F

53i

35_Br

1 7

9

VI IA

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before i t s e s s e n t i a l i t y , and i t i s now known that selenium possesses both t o x i c and b e n e f i c i a l p r o p e r t i e s , depending on the dose and chemical form ( O . A more recent example of t h i s concept i s the report by Schwarz (5) of a growth-promoting e f f e c t o f very low doses of l e a d i n r a t s maintained i n an i s o l a t o r environment. Thus, i t would not be s u r p r i s i n g i f other t r a c e elements, u s u a l l y regarded as t o x i c , w i l l a l s o be found to be b e n e f i c i a l or e s s e n t i a l . The b i o l o g i c a l p r o p e r t i e s of the 14 trace elements now r e cognized to be e s s e n t i a l are very diverse (Table 3)·


I n d i v i d u a l Trace Elements Iron. I t i s w e l l recognized that i r o n i s e s s e n t i a l as an i n t e g r a l component of hemoglobin and as a component of some f l a v o p r o t e i n s and the o x i d a t i v e r e s p i r a t o r y c h a i n . Suboptimal d i e t a r y i r o n intake r e s u l t s i n i r o n - d e f i c i e n c y anemia. The wide-spread incidence of marginal i r o n d e f i c i e n c i e s i n segments of the United S t a t e s p o p u l a t i o n was r e c e n t l y documented i n the Ten-State N u t r i t i o n Survey ( 6 ) . The RDA f o r i r o n i n the 8th e d i t i o n of Recommended Dietary Allowances published by the Food and N u t r i t i o n Board of the National Research C o u n c i l has remained at 10 mg/day f o r a d u l t males and post-menopausal females and 18 mg/day f o r women of c h i l d b e a r i n g age (7). This l a t t e r amount i s d i f f i c u l t to o b t a i n by d i e t a r y means since i t has been estimated that a balanced, average American d i e t provides only about 6 mg i r o n per 1,000 k c a l (8). Therefore, women of c h i l d b e a r i n g age would be r e q u i r e d to eat a 3,000 k c a l d i e t to meet the recommenda t i o n of 18 mg i r o n , an undesirable c a l o r i c intake f o r most women. Thus, the major change i n the 1974· RDA f o r i r o n i s a recommendation f o r supplemental i r o n intake (30-60 mg) f o r c h i l d b e a r i n g women ( 7 ) . The use of i r o n enriched foods has been suggested as a means to meet the RDA f o r i r o n . 1

Iodine. The only known f u n c t i o n of i o d i n e i n human and animal physiology i s i t s e s s e n t i a l r o l e i n formation of the t h y r o i d hormones, t h y r o x i n , and t r i i o d o t h y r o n i n e . Iodine d e f i ciency r e s u l t s i n g o i t e r . The d i e t a r y allowance f o r i o d i n e reported i n the l a t e s t RDA s has not changed. For the prevention of g o i t e r , an i o d i n e intake of 1 ug/kg body weight i s recommended w i t h a d d i t i o n a l i o d i n e intake recommended f o r growing c h i l d r e n and pregnant women ( 7 ) . The adequacy of an i n d i v i d u a l s i o d i n e intake i s d i f f i c u l t to assess and intakes vary widely. Thus, i t i s s t i l l suggested that to prevent d e f i c i e n c i e s only i o d i z e d s a l t be used. f

Zinc. Zinc plays an e s s e n t i a l r o l e i n a number of important processes i n c l u d i n g : l ) enzymatic f u n c t i o n , 2) p r o t e i n synthesis and 3) carbohydrate metabolism ( 9 ) . There are at l e a s t 18 known z i n c - c o n t a i n i n g enzymes, i n c l u d i n g l a c t a t e dehydrogenase, carbon-


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Table 3 TRACE ELEMENTS WITH BENEFICIAL EFFECTS IN MAN AND ANIMALS

Iron

Element

Adult RDA

(Fe)

10-18 mg

Iodine

(I)

100-150 ]ig

(Cu)

Estimated 80 yg/kg


Copper

Manganese (Mh)

Zinc

(Zn)

Cobalt

15 mg

(Co)

^Molybdenum (Mo)

Selenium (Se ) Chromium

Tin

(Cr)

(Sn)

Vanadium

(V)

Fluorine

(F)

Silicon

Nickel

Estimated 2-3 mg

(Si)

(Ni)

3 Ug as V i t . Bi2 Estimated 2 yg/kg Not e s tablished Not e s tablished Not e s tablished Not e s tablished Not e s tablished Not e s tablished

Not e s tablished

B i o l o g i c a l Function i n t e g r a l component of Hb, cytochrome and enzymes. e s s e n t i a l f o r thyroxine formation and p r e v e n t i o n of g o i t e r , component of s e v e r a l enzymes, eg. cytochrome oxidase c; r o l e i n t i s s u e Fe m o b i l i z a t i o n and Hb s y n t h e s i s , r e q u i r e d by s e v e r a l enzymes, eg. glucokinase, phosphoglucomutase, a c e t y l CoA synthetase, a r g i n a s e . component of s e v e r a l Zn dependent enzymes, eg. l a c t a t e dehydrogenase, carbonic anhydrase, peptidases i n t e g r a l component of V i t . B]_2 and RBC formation. i n t e g r a l component of s e v e r a l e n enzymes, eg. xanthine oxidase, a l d e hyde oxidase. i n t e g r a l component of g l u t a t h i o n e peroxidase. i n t e g r a l p a r t of Glucose Tolerance F a c t o r ; r e q u i r e d f o r normal i n s u l i n response and CHO metabolism, r e q u i r e d f o r optimal growth by r a t s (1-2 ppm of d i e t ) , r e q u i r e d f o r optimal growth by r a t s and chickens. p r e v e n t i o n of d e n t a l c a r i e s and maintenance of normal s k e l e t o n ; r e q u i r e d f o r optimal growth by r a t s . r e q u i r e d f o r optimal growth by r a t s and chickens; important r o l e i n normal bone c a l c i f i c a t i o n and s t r u c t u r a l connective t i s s u e , r e q u i r e d f o r normal l i v e r f u n c t i o n by r a t s and chickens.

C l i n i c a l evidence of d e f i c i e n c y i n ADULT man unknown.



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i c anhydrase, and s e v e r a l peptidases ( 1 0 ) . Zinc d e f i c i e n c y i n animals has r e s u l t e d i n decreased synthesis of b o t h DNA and RNA, and reduced p r o t e i n synthesis has been observed i n z i n c - d e f i c i e n t rats. The r o l e of z i n c i n carbohydrate metabolism i s s t i l l cont r o v e r s i a l ; however, impaired glucose t o l e r a n c e has been reported i n z i n c - d e f i c i e n t r a t s (11 ). More r e c e n t l y , p a t h o l o g i c a l conditions that appear to be a consequence of inadequate z i n c n u t r i t u r e have been i d e n t i f i e d i n man. Dietary d e f i c i e n c y of zinc i n man i s a s s o c i a t e d w i t h anorexia, hypogeusia (impaired t a s t e ) and hyposmia (impaired s m e l l ) , r e t a r d e d growth, delayed sexual maturation, and impaired wound h e a l i n g (12_, 13, 14_). Zinc d e f i c i e n c y was r e c e n t l y r e p o r t ed i n 8 percent of 150 c h i l d r e n from middle-income f a m i l i e s i n Denver, with another 36 percent of these c h i l d r e n probably marginal i n t h e i r z i n c i n t a k e . These d e f i c i e n t c h i l d r e n showed poor growth (below 10th p e r c e n t i l e ) , poor a p p e t i t e , impaired t a s t e a c u i t y , and low h a i r z i n c l e v e l s . Dietary h i s t o r i e s r e vealed that the d i e t s of these c h i l d r e n were low i n zinc and a l l symptoms improved with z i n c supplementation (15_). In the Middle E a s t , zinc d e f i c i e n c y , a s s o c i a t e d w i t h hypogonadism and dwarfism, has been demonstrated i n man ( 1 6 ) . These studies suggest that marginal z i n c d e f i c i e n c y may be more widespread than p r e v i o u s l y thought and that d i e t a r y intake of z i n c i n the United States cannot be assumed to be o p t i m a l . I t i s estimated that a t y p i c a l American d i e t s u p p l i e s b e tween 10 and 15 mg z i n c per day to meet an estimated d a i l y requirement of 10 mg/day (12). Thus, the average d a i l y intake i s only s l i g h t l y more than the estimated d a i l y requirement, and does not provide a s u f f i c i e n t s a f e t y margin. Therefore, people who consume foods which are lower than average i n a v a i l a b l e z i n c , such as meat analogs made from vegetable p r o t e i n , may s u f f e r from marginal z i n c intakes ( 1 2 ) . In view of the above, the 1974 RDA's f o r the f i r s t time i n c l u d e a recommendation f o r z i n c , w i t h 15 mg b e i n g suggested f o r a d u l t men and women, and 20 to 25 mg during pregnancy and l a c t a t i o n ( 7 ) . Chromium. Chromium i s e s s e n t i a l f o r the maintenance of normal carbohydrate metabolism i n at l e a s t three species of experimental animals. T r i v a l e n t chromium i s an i n t e g r a l p a r t of Glucose Tolerance Factor (GTF), and f u n c t i o n s as a c o f a c t o r f o r the p e r i p h e r a l a c t i o n of i n s u l i n . In the r a t , the f i r s t observed consequence of m i l d chromium d e f i c i e n c y i s an impairment of glucose t o l e r a n c e , caused by a reduced s e n s i t i v i t y o f p e r i p h e r a l t i s s u e s to i n s u l i n . A more severe degree of chromium d e f i c i e n c y leads to f a s t i n g hyperglycemia, g l y c o s u r i a , and m i l d growth r e t a r d a t i o n (17, 1 8 ) . There i s considerable evidence that chromium i s a l s o e s s e n t i a l f o r man. Impaired glucose t o l e r a n c e i s the hallmark of chromium d e f i c i e n c y i n man. There has been s p e c u l a t i o n that chromium d e f i c i e n c y may c o n t r i b u t e to the development of


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a t h e r o s c l e r o s i s ( 1 9 ) , and i t i s of i n t e r e s t that serum c h o l e s t e r o l l e v e l s increase w i t h age as t i s s u e chromium l e v e l s decrease w i t h age ( 1 9 ) . Evidence f o r the occurrence of chromium d e f i c i e n cy i n man and the e f f e c t of d i e t a r y chromium supplementation w i l l be discussed subsequently i n t h i s paper. Cobalt. Cobalt i s e s s e n t i a l to man only through i t s f u n c t i o n as an i n t e g r a l part of Vitamin B]_ and no other f u n c t i o n s f o r c o b a l t i n human n u t r i t i o n are known. Cobalt d e f i c i e n c y has never been produced i n a nonruminant animal and the r o l e of c o b a l t i n human n u t r i t i o n i s only a question of adequate d i e t a r y intake of Vitamin B , r a t h e r than o f c o b a l t i t s e l f ( ] J ) . RDA f o r Vitamin B i s 3 ug per day ( 7 ) . 2


1 2

T

n

e

1 2

Copper. The n u t r i t i o n a l e s s e n t i a l i t y of copper derives from i t s r o l e i n the s t r u c t u r e and f u n c t i o n of s e v e r a l cuproenzymes i n c l u d i n g cytochrome oxidase, ceruloplasmin, amine oxidase and a s c o r b i c a c i d oxidase. Copper-containing enzymes and copper-containing p r o t e i n s are r e q u i r e d f o r c e l l u l a r r e s p i r a t i o n , normal hemoglobin s y n t h e s i s , and normal bone formation. The copper-containing p r o t e i n ceruloplasmin i s reported to be i n t i m a t e l y i n v o l v e d i n t i s s u e i r o n m o b i l i z a t i o n (l_, 13). Absolute copper d e f i c i e n c y has never been observed i n human a d u l t s ; however, copper d e f i c i e n c y has been described i n p a t i e n t s s u f f e r i n g from general m a l n u t r i t i o n and i n i n f a n t s i n a d v e r t a n t l y f e d formulated d i e t s low i n copper (l). The normal d i e t a r y copper intake of between 2-5 mg per day i s s u f f i c i e n t to meet the recommended d i e t a r y allowance of 2 mg per day. Thus, copper d e f i c i e n c y does not appear to be a problem i n t h i s country ( 2 0 ) . Manganese. Manganese f u n c t i o n s as a c o f a c t o r f o r s e v e r a l metallo-enzymes i n c l u d i n g : glucokinase, phosphoglucomutase, a c e t y l CoA synthetase and a r g i n a s e . The existence of manganese d e f i c i e n c y has been demonstrated i n p i g s , p o u l t r y , r a t s , mice, c a t t l e , and sheep; however, evidence of human d e f i c i e n c y has never been obtained. Manganese d e f i c i e n c y was a c c i d e n t a l l y induced i n man through the feeding of a s y n t h e t i c r a t i o n (21 ). The manifestations of manganese d e f i c i e n c y i n animals i n c l u d e growth r e t a r d a t i o n , reduced f e r t i l i t y , s k e l e t a l abnormalities and d i s o r d e r s of the c e n t r a l nervous system ( a t a x i a of the newborn) (l_, l^). In a d d i t i o n , manganese plays an important r o l e i n normal carbohydrate metabolism, as suggested by the impaired glucose t o l e r a n c e and h y p o p l a s t i c p a n c r e a t i c i s l e t c e l l s observed i n manganese d e f i c i e n t guinea p i g s ( 2 2 ) . The d a i l y manganese requirements f o r man are unknown; however, from intake and balance s t u d i e s , i t i s estimated that a manganese intake of 2-3 mg/day i s adequate f o r a d u l t s ( 7 , 20). Molybdenum.

Molybdenum plays an e s s e n t i a l r o l e as an i n t e -


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g r a l component of s e v e r a l enzymes i n c l u d i n g , xanthine oxidase, aldehyde oxidase and s u l f i t e oxidase. Molybdenum d e f i c i e n c y has been demonstrated i n lambs, c h i c k s , and turkey p o u l t s u s i n g h i g h l y p u r i f i e d d i e t s w i t h a low molybdenum content (approximate l y 20 yg/kg). Feeding t h i s low molybdenum d i e t r e s u l t e d i n depressed growth (23) and decreased a c t i v i t y of the enzyme xanthine oxidase ( 2 4 ) . Molybdenum d e f i c i e n c y has never been reported i n humans. An RDA f o r molybdenum has not been e s t a b l i s h e d ; however, balance s t u d i e s i n d i c a t e that p o s i t i v e balance i n man can be maintained w i t h a molybdenum intake of about 2 pg/kg body weight per day. Selenium (13, 2 3 ) . It has r e c e n t l y been demonstrated (29 ) that selenium i s an i n t e g r a l component of the enzyme g l u t a t h i o n e peroxidase. Glutathione peroxidase i s i n v o l v e d i n the r e o x i d a t i o n of reduced g l u t a t h i o n e . The enzyme has been i s o l a t e d from sheep r e d b l o o d c e l l s ; i t has a molecular weight of approximately 80,000; and i t contains one atom of selenium per p r o t e i n subunit of approximately 20,000 molecular weight (2). Selenium d e f i c i e n c y i s i n t i m a t e l y r e l a t e d to Vitamin Ε d e f i c i e n c y d i s e a s e s . For example, the simultaneous d e f i c i e n c y of selenium and Vitamin Ε causes a v a r i e t y of p a t h o l o g i e s i n animals i n c l u d i n g : f a t a l exudative d i a t h e s i s i n chicks and turkeys, l i v e r n e c r o s i s i n the r a t and p i g , m u l t i p l e n e c r o t i c degeneration of heart, l i v e r , muscle, and kidney i n the mouse, and muscular dystrophy i n lambs, c a l v e s , and chicks (white muscle d i s e a s e ) . Recent s t u d i e s i n chicks have demonstrated t h a t simple selenium d e f i c i e n c y , uncomplicated by inadequate Vitamin E, causes impaired growth, poor f e a t h e r i n g , and f i b r o t i c degenera t i o n of the pancreas (25). Selenium d e f i c i e n c y i n the r a t i s manifested by impaired growth, impaired h a i r coat development, and reproductive f a i l u r e ( 2 6 ) . Furthermore, feeding a seleniumd e f i c i e n t d i e t c o n t a i n i n g adequate Vitamin Ε to subhuman primates r e s u l t s i n h e p a t i c n e c r o s i s , nephrosis, degenerative changes i n c a r d i a c and s k e l e t a l muscle, weight l o s s and death ( 2 7 ) . As stated e a r l i e r , selenium possesses b o t h b e n e f i c i a l and toxic properties. N a t u r a l l y o c c u r r i n g selenium p o i s o n i n g i n animals r e s u l t s i n the acute t o x i c i t y syndrome, "blind staggers", and the chronic t o x i c i t y syndrome of " a l k a l i disease". In adult man, no evidence of e i t h e r selenium d e f i c i e n c y or t o x i c i t y has been demonstrated, however, selenium d e f i c i e n c y has been reported i n c h i l d r e n w i t h p r o t e i n - c a l o r i e m a l n u t r i t i o n ( 2 8 ) . Due to l a c k of s u f f i c i e n t information, i t has not been p o s s i b l e to e s t a b l i s h an RDA f o r selenium i n humans. T i n , Vanadium, F l u o r i n e ,

Silicon,

Nickel

The f i v e t r a c e elements discussed below have r e c e n t l y been found to be e s s e n t i a l f o r l a b o r a t o r y animals (2, 30, 31 ).


10.

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AND

DOiSY

Trace Elements in

Nutrition

165


T i n . T i n was r e c e n t l y found to be r e q u i r e d f o r o p t i m a l growth i n r a t s . T i n d e f i c i e n c y has been produced i n r a t s by housing i n an i s o l a t o r environment and be feeding h i g h l y p u r i f i e d amino a c i d d i e t s low i n t i n . S i g n i f i c a n t growth s t i m u l a t i o n was observed when the d i e t s were supplemented w i t h 1-2 mg t i n / k g (ppm) of d i e t (2, 30, 31, 32). Vanadium. Vanadium i s e s s e n t i a l i n at l e a s t two animal species, the chick and the r a t . Vanadium d e f i c i e n c y i n chickens ( d i e t s c o n t a i n i n g l e s s than 10 yg/kg) r e s u l t s i n poor f e a t h e r growth (33) and r e t a r d e d bone development (30, 31). In the r a t , d i e t s s u p p l y i n g l e s s than 100 ng vanadium/g of d i e t (100 ppb ) showed decreased body growth (3A_) and r e c e n t l y i t was shown that r a t s respond to 50-100 ng vanadium/g of d i e t w i t h s i g n i f i c a n t growth s t i m u l a t i o n (£). Fluorine. I n a d d i t i o n to the e s s e n t i a l r o l e of f l u o r i n e , as f l u o r i d e , i n the p r e v e n t i o n of d e n t a l c a r i e s and i n the main tenance of a normal body s k e l e t o n (13), r e c e n t l y f l u o r i n e has been shown to be e s s e n t i a l f o r o p t i m a l growth i n the r a t . S i g n i f i c a n t growth e f f e c t s were produced w i t h 250 yg f l u o r i n e / 1 0 0 g of d i e t (2.5 ppm) ( 2 ) . S i l i c o n . S i l i c o n has been shown to be e s s e n t i a l f o r normal growth i n animals. S i l i c o n d e f i c i e n c y i n chicks and r a t s causes depressed growth, and abnormal bone c a l c i f i c a t i o n . S i l i c o n a l s o p l a y s an e s s e n t i a l r o l e i n mucopolysaccharide metabolism and normal, connective t i s s u e development. S i l i c o n was r e c e n t l y r e ported to have a growth-promoting e f f e c t i n r a t s (2_, 30). N i c k e l . N i c k e l appears to be e s s e n t i a l f o r animals, and pathology c o n s i s t e n t w i t h n i c k e l d e f i c i e n c y has been produced i n c h i c k s , r a t s , and swine. N i c k e l d e f i c i e n c y i n these animals causes metabolic a b n o r m a l i t i e s i n the l i v e r , i n c l u d i n g a decreas ed oxygen uptake by l i v e r homogenates i n the presence of α-gly cerophosphate, increased l i v e r l i p i d s , i n c r e a s e d p h o s p h o l i p i d and c h o l e s t e r o l f r a c t i o n , and hepatocyte u l t r a s t r u c t u r a l abnormali t i e s (30, 31). Furthermore, i n the r a t , n i c k e l d e f i c i e n c y r e s u l t e d i n abnormal r e p r o d u c t i o n as suggested by increased f e t a l m o r t a l i t y (30). At the present time, no evidence f o r human e s s e n t i a l i t y has been demonstrated f o r these f i v e newer t r a c e elements. No estimate of man* s requirements f o r these newer e s s e n t i a l t r a c e elements can be o f f e r e d i n view of the c u r r e n t i n s u f f i c i e n t evidence and knowledge of i n t a k e s i n humans. Future Considerations As brought out at a recent symposium (35.) l i t t l e i s known about the i n t e r a c t i o n s that occur between e s s e n t i a l t r a c e e l e -



166

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CARBOHYDRATES

ments. Knowledge of t r a c e element i n t e r a c t i o n s i s of utmost importance to any v a l i d recommendation o f d i e t a r y i n t a k e . That i s to say, a h i g h d i e t a r y intake of a given element may reduce a v a i l a b i l i t y o f some other element. Such known r e l a t i o n s h i p s as high calcium intake antagonizing (or reducing) copper a v a i l a b i l i t y i s but one example of such an i n t e r a c t i o n . Tungstate i s known to antagonize molybdate, and copper and zinc a l s o i n t e r a c t . For example, people who are r e c e i v i n g therapeutic doses of zinc f o r burns may have an increased copper requirement. Thus, knowing the d a i l y intake of any given element i s only part of the problem. The intake of other ( i n t e r f e r i n g ) elements and t h e i r balance i s of utmost importance. These i n t e r r e l a t i o n s are o n l y beginning to u n f o l d and much more work i s needed on t h i s aspect of t r a c e elements i n n u t r i t i o n . Role of Chromium i n Human and Animal

Nutrition

Schwarz and Mertz i d e n t i f i e d t r i v a l e n t chromium as an i n t e g r a l component of the b i o l o g i c a l l y a c t i v e Glucose Tolerance F a c t o r (GTF) i n 1959 ( 3 6 ) . Since t h a t time a l a r g e body of convincing experimental evidence has accumulated suggesting that GTF i s r e q u i r e d f o r the maintenance of normal carbohydrate metab o l i s m by both animals and man (18^). Chromium n u t r i t i o n i n man has r e c e n t l y been reviewed by Hambidge (18) and Doisy, et a l . ( 37) and w i l l not be d e a l t with i n d e t a i l i n t h i s paper. The c h a r a c t e r i s t i c s of GTF as known at t h i s time are summarized below (17): GTF i s a n a t u r a l l y o c c u r r i n g , d i a l y z a b l e , heat and a c i d s t a b l e , organic compound of low molecular weight (400-600 d a l tons). ï t can be extracted and concentrated from brewers y e a s t , while l i v e r and kidney are a l s o recognized as p o t e n t i a l l y r i c h sources. The p r e c i s e s t r u c t u r e of GTF i s not yet known; however, Mertz (39) r e c e n t l y suggested t h a t the complex contains two n i c o t i n i c a c i d molecules per chromium atom. Furthermore, g l y c i n e , c y s t e i n e , and p o s s i b l y glutamic a c i d may be r e q u i s i t e amino a c i d s . The amino a c i d s may only be r e q u i r e d to make the complex water s o l u b l e , and the b i o l o g i c a l a c t i v i t y may be due to the chromium and n i c o t i n i c a c i d s i n a unique c o o r d i n a t i o n complex. Recently, Mertz has prepared b i o l o g i c a l l y a c t i v i e s y n t h e t i c chromiumn i c o t i n i c a c i d complexes which seem to be s i m i l a r t o , but not i d e n t i c a l w i t h , the n a t u r a l l y o c c u r r i n g GTF complex ( 3 9 ) . GTF contains t r i v a l e n t chromium as the a c t i v e metal i o n . The b i o l o g i c a l e f f e c t of chromium "in v i t r o " and "in vivo", i s s o l e l y dependent on the valency s t a t e and o n l y t r i v a l e n t chromium exhibits b i o l o g i c a l a c t i v i t y . The b i o l o g i c a l e f f e c t s of GTFchromium are q u a l i t a t i v e l y s i m i l a r , but q u a n t i t a t i v e l y much g r e a t e r than simple i n o r g a n i c chromium complexes. For example, much s m a l l e r q u a n t i t i e s o f chromium are r e q u i r e d "in vivo" to r e s t o r e normal glucose t o l e r a n c e i n r a t s i f given i n the form of GTF. Furthermore, the b i o - a v a i l a b i l i t y of chromium to animals



10.

TUMAN

A N D DOISY


167

and man i s dependent on the chemical form. Chromium i n the form of GTF, i s b i o l o g i c a l l y a v a i l a b l e and b e t t e r absorbed than simple i n o r g a n i c chromium s a l t s . For example, l e s s than 1 p e r cent of an o r a l dose of chromium i n the form of chromic c h l o r i d e i s absorbed as compared to 10-25 percent of the chromium i n an o r a l dose of GTF (38.)· The chemical form of chromium a l s o de termines i t s d i s t r i b u t i o n i n t i s s u e s . Only chromium i n the form of GTF i s concentrated i n the l i v e r and only GTF chromium i s a v a i l a b l e to the fetus through p l a c e n t a l t r a n s p o r t . "In v i t r o " s t u d i e s suggest that GTF f u n c t i o n s by p o t e n t i a t ing the a c t i o n of i n s u l i n and, as such, i t i s a r e q u i r e d c o f a c t o r f o r maximal i n s u l i n response i n a l l i n s u l i n - s e n s i t i v e t i s s u e s (17). As a r e s u l t of an uncorrected d e f i c i e n c y of chromium, a normal i n s u l i n response may only be achieved w i t h u n p h y s i o l o g i c a l l y high concentrations of i n s u l i n . Evidence f o r Chromium D e f i c i e n c y i n Man It i s w e l l e s t a b l i s h e d that chromium d e f i c i e n c y can be i n duced (both a c c i d e n t a l l y and d e l i v e r a t e l y ) i n animals by feeding a d i e t that i s low i n a v a i l a b l e chromium ( 3 6 , 40, 41., 42 ) . Evidence has accumulated which suggests that chromium d e f i c i e n c y a l s o e x i s t s i n c e r t a i n segments o f the human p o p u l a t i o n . This evidence i s i n d i r e c t and i s based on the f o l l o w i n g observations: l ) t i s s u e chromium l e v e l s decrease w i t h i n c r e a s i n g age i n the United States ( 4 3 , 4 4 ) ; 2) absence of an acute r i s e of serum chromium f o l l o w i n g an i n s u l i n or glucose challenge i n d i a b e t i c subjects ( 4 5 ) , and i n pregnant woment w i t h impaired glucose t o l e r a n c e Γ46 ); 3) diabetes i s a s s o c i a t e d w i t h low chromium l e v e l s i n h a i r (47.) and l i v e r (AS) compared to n o n d i a b e t i c con t r o l s ; 4 ) insulin-dependent d i a b e t i c s metabolize chromium i n a manner that i s abnormal as compared to n o n - d i a b e t i c subjects (49 ) and 5) subjects w i t h impaired glucose t o l e r a n c e , i n c l u d i n g some maturity-onset d i a b e t i c s ( 5 0 ) , middle-aged subjects (51 ), c h i l d r e n i n Jordan s u f f e r i n g w i t h kwashiorkor (52_), c h i l d r e n i n Turkey s u f f e r i n g from marasmus (22)' l subjects (37, 49, 54 ) show improved glucose t o l e r a n c e a f t e r o r a l chromium supplementation of the d i e t . Thus i t appears l i k e l y that marginal or overt chromium d e f i c i e n c y occurs i n the United States and elsewhere i n the world. a

n

d

s

o

m

e

e

d

e

r

l

y

E f f e c t s of Chromium and GTF Supplementation of the Diet The f a c t that t i s s u e chromium l e v e l s decrease w i t h age i n the United States and are e x c e p t i o n a l l y low i n e l d e r l y s u b j e c t s , i s compatible w i t h , but not proof of chromium d e f i c i e n c y . How ever, these data suggest a r o l e f o r chromium i n e x p l a i n i n g the e t i o l o g i c a l b a s i s f o r impaired glucose t o l e r a n c e which i s ex h i b i t e d by the m a j o r i t y of e l d e r l y subjects over 70 years of age. Hence, a tempting c o n c l u s i o n i s that many e l d e r l y i n d i v i d u a l s



168

PHYSIOLOGICAL

EFFECTS

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CARBOHYDRATES

have impaired glucose tolerance on the b a s i s of n u t r i t i o n a l chromium d e f i c i e n c y . Therefore, i f a d e f i c i e n c y i s suspected, i n c r e a s i n g the d i e t a r y intake of chromium should r e l i e v e the d e f i c i e n c y and normalize the glucose t o l e r a n c e . This has been done with e l d e r l y subjects thought to be chromium d e f i c i e n t . In the o r i g i n a l study by Levine, et a l . (37, 54), 86 percent of the e l d e r l y p o p u l a t i o n l i v i n g i n the Onondaga County Home d i s p l a y e d abnormal glucose tolerance t e s t s . Table 4 summarizes the r e s u l t s obtained when ten e l d e r l y s u b j e c t s , with abnormal glucose t o l e r a n c e , were t r e a t e d with 150 y g d a i l y of supplemental i n o r g a n i c chromium f o r periods up to four months. In a d d i t i o n , two young subjects o r i g i n a l l y thought to be normal and one subj e c t with hemochromatosis are i n c l u d e d . Shown are the mean two hour glucose t o l e r a n c e t e s t s on seven s u b j e c t s , before and a f t e r d i e t a r y chromium supplementation. The c r i t e r i a used f o r abnorm a l i t y i n these and subsequent s t u d i e s are a peak plasma glucose l e v e l above 185 mg/dl and/or a two hour l e v e l above 140 mg/dl ( c r i t e r i a adapted from Conn and F a j a n s ) . As shown i n Table 4> the mean plasma glucose l e v e l s while on the chromium supplement, p a r t i c u l a r l y at 60, 90, and 120 minutes, are lowered c o n s i d e r ably i n a l l seven subjects compared to the pre-chromium b a s e l i n e control tests. In a d d i t i o n , the mean peak plasma glucose l e v e l of the four "responding" e l d e r l y subjects as a group was lowered from 182 to 146 mg/dl and the mean plasma sugar l e v e l 2 hours a f t e r a glucose l o a d d e c l i n e d from 156 to 115 mg/dl. Thus, i n o r g a n i c chromium supplementation of the d i e t was e f f e c t i v e i n r e s t o r i n g the impaired glucose tolerance to normal i n these seven s u b j e c t s , and i t was concluded that these subjects were, i n f a c t , chromium d e f i c i e n t . It should be noted that of the ten e l d e r l y subjects t r e a t e d , only four (40%) responded f a v o r a b l y to chromium supplementation. However, i t should a l s o be pointed out that there are many e t i o l o g i e s f o r impaired glucose tolerance, i n c l u d i n g i n f e c t i o n , emotional s t r e s s , e t c . , and only those subjects w i t h a p r e - e x i s t i n g chromium d e f i c i e n c y would be expected to b e n e f i t from chromium supplementation. On the other hand, a f a i l u r e to respond to i n o r g a n i c chromium does not exclude the p o s s i b i l i t y of a GTF d e f i c i e n c y . It i s poss i b l e that the subjects that d i d not respond to i n o r g a n i c chromium may have l o s t the a b i l i t y to convert i n o r g a n i c chromium to GTF. These subjects may have a more favorable response to d i e t a r y supplementation w i t h GTF. More r e c e n t l y , the e f f e c t of d i e t a r y GTF supplementation on abnormal glucose tolerance i n e l d e r l y subjects was s t u d i e d ( 3 7 ) . In t h i s case, 45 percent (14/31) of the subjects over the age of 65 d i s p l a y e d impaired glucose t o l e r a n c e . Each of twelve s u b j e c t s , who volunteered to go on a commercial brewers yeast e x t r a c t c o n t a i n i n g GTF, r e c e i v e d a d a i l y supplement (4^g Yeastamin/day) f o r a p e r i o d o f one to two months. Yeastamin has been See

footnote f o l l o w i n g L i t e r a t u r e C i t e d .


10.

TUMAN

AND

DOiSY

Trace Elements in Nutrition Table 4

MEAN GLUCOSE TOLERANCE TESTS OF RESPONDERS - Cr PLASMA GLUCOSE CONCENTRATION mg/dl Elderly Subjects/

Age

30

60

90

120

No. of Tests

143

149

+

84 82

138

129

163 125

170 106

2 2

78

+

67 83

122 132

186 139

197 126

167 123

2 2

88

+

82 81

153 136

180 157

165 140

153 131

2 3

98

96

+ 101

148 142

181 152

152 111

135 100

2 3

HH Downloaded by UNIV OF NEW ENGLAND on February 11, 2017 | http://pubs.acs.org Publication Date: June 1, 1975 | doi: 10.1021/bk-1975-0015.ch010

Ο

79

GF

Ech

FW

Young Subjects

Cr

Age

22

+

90 91

161 161

192 126

151 82

115 104

2 3

24

+

81 81

146 160

194 147

127 132

120 118

2 3

-ι-

111 97

209 155

225 170

166 150

125 139

2 2

AG

LS

Subjects w i t h Hemochromatosis

Age

49

Supplement: 50 yg of Cr three times d a i l y (CrCl3'6H20 ). ^Reprinted by permission of p u b l i s h e r . Doisy, et a l . , "Effects and Metabolism of Chromium i n Normals, E l d e r l y S u b j e c t s , and D i a b e t i c s " , In: Trace Substances i n Environmental H e a l t h - I I , D. D. Hemphill, E d . , U n i v e r s i t y o f M i s s o u r i , Columbia, pp. 75-82 (37).



170

PHYSIOLOGICAL

EFFECTS

O F FOOD

CARBOHYDRATES

shown by Mertz to possess potent GTF a c t i v i t y . I t i s recognized that the observed responses may or may not be due to the GTF content of Yeastamin. That GTF i s the a c t i v e component must await the a v a i l a b i l i t y of pure GTF. The mean e f f e c t o f s u p p l e mentation of the d i e t on glucose t o l e r a n c e i n s i x "responding" e l d e r l y subjects i s shown i n Table 5. The subjects d i s p l a y s e v e r e l y impaired glucose t o l e r a n c e p r i o r to GTF supplementation, w i t h a peak plasma glucose l e v e l greater than 200 mg/dl and a two hour glucose value of 178 mg/dl. Following d i e t a r y GTF supplementation, however, s i x of the e l d e r l y subjects show an improved glucose t o l e r a n c e to values w i t h i n normal l i m i t s , with the one and two hour plasma glucose l e v e l s being s i g n i f i c a n t l y reduced to 162 and 132 mg/dl r e s p e c t i v e l y . In a d d i t i o n (Table 5 ) , the serum i n s u l i n l e v e l s measured during the t e s t s are decreased while on the supplement, p a r t i c u l a r l y at two hours. Thus, the work l o a d of the pancreas i s decreased and l e s s endogenous i n s u l i n , as i n d i c a t e d by lower serum l e v e l s , i s needed to maintain normal glucose tolerance when adequate amounts of GTF are a v a i l a b l e . This i s i n agreement w i t h the r o l e of GTF as a c o f a c t o r f o r normal i n s u l i n response. Furthermore, i n a d d i t i o n to the r e d u c t i o n i n plasma glucose and i n s u l i n l e v e l s , some subjects a l s o respond to GTF supplement a t i o n with a s i g n i f i c a n t r e d u c t i o n i n f a s t i n g serum c h o l e s t e r o l levels. C h o l e s t e r o l l e v e l s were s i g n i f i c a n t l y reduced i n these s i x subjects from a mean value of 245 to 205 mg/dl, a decrease of 40 mg/dl. In those subjects w i t h elevated t r i g l y c e r i d e l e v e l s there i s a l s o a r e d u c t i o n i n plasma t r i g l y c e r i d e . Another group of subjects d i s p l a y i n g an incidence of i m p a i r ed glucose t o l e r a n c e which i s c l e a r l y greater than that observed i n the general p o p u l a t i o n are the s i b l i n g s o f known d i a b e t i c s . The e f f e c t s of d i e t a r y GTF supplementation on the glucose t o l e r ance of a s i b l i n g o f an i n s u l i n - r e q u i r i n g d i a b e t i c are described i n Table 6 ( 3 7 ) . It i s apparent from the two i n i t i a l screening GTT s that t h i s subject d i s p l a y s " d i a b e t i c - l i k e " glucose t o l e r ance, with elevated plasma glucose l e v e l s g r e a t e r than 200 mg/dl and serum i n s u l i n l e v e l s g r e a t e r than 200 yU/ml, at two time p o i n t s during each t e s t . In a d d i t i o n , the subject i s h y p e r t r i glyceridemic. A f t e r approximately e i g h t months of d i e t a r y supplementation with 4 - 8 grams o f Yeastaiiin/day, glucose t o l e r ance i s normalized. In the l a s t t e s t (4/19/74) normal glucose l e v e l s are accompanied by a s i g n i f i c a n t r e d u c t i o n i n g l u c o s e induced plasma i n s u l i n l e v e l s . Furthermore, plasma t r i g l y c e r i d e s have been reduced to w i t h i n normal l i m i t s . As of t h i s w r i t i n g , approximately 80 other subjects with impaired glucose tolerance are on a d i e t a r y supplement c o n t a i n i n g GTF. Although not a l l subjects respond with improved glucose t o l e r a n c e , the r e s u l t s d e s c r i b e d here are more or l e s s t y p i c a l of the responses obtained i n the m a j o r i t y of s u b j e c t s . One major d i f f e r e n c e between subjects i s the v a r i a t i o n i n the length o f time on the supplement before improvement i s observed. This i s f



I

70 -

™ ;178 δ

δ 5

I 17

δ3 -

118

0.001

178 J 132 -

2

0.01

245 J 9t 205 - 10

Cholesterol mg/dl

NS

121 ΐ δ 112 - 12

(37).

Triglyceride mg/dl

IN

Number o f t e s t s i n parentheses. Mean - SE tUsing paired t t e s t , difference i s s i g n i f i c a n t . Supplement: 4 g of Yeastamin/day. GTT: 100 g o r a l l o a d . Reprinted by permission of p u b l i s h e r : N u t r i t i o n Foundation Monograph, Academic P r e s s , NY,

24 5 6 26 - 12

microunits/ml

Mean Serum I n s u l i n Levels

Before GTF A f t e r GTF

1 201 7 162 - 11 0.01

106 ΐ 4 9 9 - 4 NS

Before GTF ( l l ) * A f t e r GTF (9) Significance

Mean Plasma Glucose Levels mg/dl Time i n hours — 0

EFFECT OF GTF* SUPPLEMENTATION OF THE DIET ON GLUCOSE TOLERANCE TESTS ELDERLY SUBJECTS WITH IMPAIRED TOLERANCE

Table 5


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PHYSIOLOGICAL

EFFECTS

O F FOOD

CARBOHYDRATES

Table 6 EFFECT OF GTF SUPPLEMENT ON GLUCOSE TOLERANCE/SIBLING OF DIABETIC, AGE 30, MALE Time Glucose Insulin ChoiesTriglycerDate mg/dl yunits/ml t e r o l ides


8/10/73

0 30 ' 60» 120' 180»

117 251 267 150 96

35 >200 >200 95 27

194

265

0'

38 200 >200 183 163 138 39

198

256

30 » 45 ' 60» 90' 120'

108 176 220 206 167 158 97

0' 15» 30' 45' 60' 90' 120' ISO 180'

112 162 212 204 185 156 85 73 76

5 52 110 125 166 130 25 12 12

150

68

0' 30' 60' 90' 120' 150' 180'

92 154 131 126 117 75 63

10 57 52 44 35 22 10

206

134

T

8/23/73

15'

GTF 8/24/73 1/4/74

1

4/19/74

Subject gained 8 l b s . between 1/4/74 to 4/19/74. Supplement: 4 g of Yeastamin per day 8/24/73 - 11/9/73. 8 g of Yeastamin per day 11/10/73 - 4/19/74. Reprinted by permission of p u b l i s h e r : N u t r i t i o n Foundation Monograph, Academic Press, NY (37).



10.

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173

understandable s i n c e the degree of chromium and/or GTF d e f i c i e n c y might be expected to vary w i t h each s u b j e c t . For example, the e l d e r l y subjects responded i n 1-2 months time, whereas i n some s i b l i n g s of d i a b e t i c s 6 - 8 months are r e q u i r e d before n o r m a l i z a t i o n occurs. Thus, evidence i s accumulating suggesting that chromium d e f i c i e n c y does e x i s t i n c e r t a i n segments of our p o p u l a t i o n . The r i s k and incidence of chromium d e f i c i e n c y appears to be g r e a t e s t i n the f o l l o w i n g p o p u l a t i o n groups: l ) i n o l d e r age groups, 2 ) i n c h i l d r e n w i t h p r o t e i n - c a l o r i e m a l n u t r i t i o n , 3) i n i n s u l i n - r e q u i r i n g d i a b e t i c s , 4 ) i n pregnant women, p a r t i c u l a r l y multiparae ( g e s t a t i o n a l d i a b e t e s ) , and 5) subjects maintained on formulated d i e t s f o r long periods of time may be a high r i s k f o r chromium d e f i c i e n c y . I t i s proposed that chromium d e f i c i e n c y may be caused by inadequate d i e t a r y intake and/or poor a v a i l a b i l i t y o f chromium from f o o d s t u f f s . The average American d i e t s u p p l i e s o n l y small q u a n t i t i e s of chromium, with intakes i n the USA varying from 5 yg/day to over 100 yg/day ( l , 18). The average chromium intake f o r the e l d e r l y subjects (54T was 52 yg d a i l y . The d a i l y u r i n a r y l o s s of chromium i n normal a d u l t s ranged from 3-50 yg/day ( 4 6 , 55.) thus, t h i s i s the minimal amount that must be r e p l a c e d i n order to m a i n t a i n balance i n the a d u l t . As i n d i c a t e d e a r l i e r , absorption of chromium can vary from l e s s than 1 percent to 25 percent of a given dose, depending on the form i n which i t i s p r e s e n t . Theref o r e , the d i e t a r y intake r e q u i r e d to balance the u r i n a r y l o s s could vary from 50 yg to 500 yg. D i e t s e x c e p t i o n a l l y low i n chromium which do not adequately r e p l a c e l o s s e s could l e a d to chromium d e f i c i e n c y . The importance of e v a l u a t i n g f o o d s t u f f s on the b a s i s of b i o l o g i c a l l y meaningful chromium r a t h e r than t o t a l chromium content was r e c e n t l y d i s c u s s e d (56_). Due to inadequate knowledge of the forms and b i o l o g i c a l a v a i l a b i l i t y of chomium i n foods, an RDA cannot be e s t a b l i s h e d . However, i t has been suggested that a d a i l y intake of 10-30 yg of chromium i n the form of GTF would meet our d a i l y requirement ( 2 0 ) . I t has a l s o been suggested that inadequate d i e t a r y i n t a k e of chromium may occur because of l o s s e s of chromium i n food r e f i n i n g processes (57, 58). The chromium content of various wheat and sugar products and the marked l o s s o f chromium that occurs during the r e f i n i n g of these food s t a p l e s are described below. Whole g r a i n wheat contains 1.75 yg chromium/g Dry Wgt. compared to 0.23 yg/g Dry Wgt. f o r r e f i n e d white f l o u r and 0.14 yg/ g Dry Wgt. f o r white b r e a d . This represents an 87% l o s s of chromium i n the refinement of whole wheat to white f l o u r and a 92% l o s s of chromium i n going from n a t u r a l wheat to the consumer item of white b r e a d . Whole wheat bread r e t a i n s a l i t t l e more of the o r i g i n a l chromium, but there i s s t i l l a g r e a t e r than 70% l o s s of chromium i n the r e f i n i n g p r o c e s s . S i m i l a r l o s s e s of chromium occur i n the r e f i n i n g of sugar.



174

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EFFECTS

O F FOOD

CARBOHYDRATES

Refined white t a b l e sugars r e t a i n very l i t t l e of the o r i g i n a l chromium contained i n the raw sugars. There i s a 77-94% l o s s of chromium on a dry weight b a s i s i n going from u n r e f i n e d raw sugar to the r e s u l t i n g consumer item which the American people use much of (106-120 lbs/person/annum). Raw sugar provides 6 - 8 . 8 yg Cr/100 k c a l compared to only 0 . 5 - 2 . 5 yg Cr/100 k c a l f o r r e f i n e d sugar. Most of the chromium i s removed during the r e f i n i n g p r o c e s s , i . e . , f i n a l molasses (47 yg Cr/100 k c a l ) . Therefore, i t i s obvious from data of t h i s k i n d that modern methods o f food p r o c e s s i n g remove a l a r g e percentage of chromium from two very important food items, wheat and sugar. Thus, d i e t s h i g h i n r e f i n e d sugar and r e f i n e d wheat products could c o n t r i b u t e to marginal chromium i n t a k e s . However, chromium i s not the only e s s e n t i a l t r a c e element that i s s i g n i f i c a n t l y decreased during the process of r e f i n i n g of wheat ( 5 9 ) . The l o s s e s of s i x other e s s e n t i a l t r a c e elements that occur during the r e f i n i n g of wheat are described below. In a d d i t i o n to 76% of the ash content, from 48 to 99% of s i x e s s e n t i a l trace metals are removed during the m i l l i n g of wheat to white f l o u r . The l o s s e s i n f l o u r i n c l u d e : 76% of the o r i g i n a l i r o n content, 78% of the z i n c , 86% of the manganese, 68% of the copper, 48% of the molybdenum, and 89% of the c o b a l t . As with chromium, the h i g h e s t c o n c e n t r a t i o n of these trace elements i s found i n the l e s s r e f i n e d f r a c t i o n s l i k e germ and b r a n . S i m i l a r l o s s e s of e s s e n t i a l t r a c e elements occur when other important food items are d i v i d e d i n t o t h e i r component parts by e i t h e r refinement or e x t r a c t i o n (58_). As a r e s u l t of p a r t i t i o n ing r i c e , s i g n i f i c a n t amounts of f i v e e s s e n t i a l trace elements are l o s t , i n c l u d i n g : 75% o f the chromium, 46% of the manganese, 75% of the z i n c , 27% of the copper, and 38% of the c o b a l t . In a d d i t i o n , 83% of the magnesium i s removed i n the p o l i s h i n g p r o cess. In going from corn to corn meal, there i s a marked l o s s of three e s s e n t i a l trace elements i n c l u d i n g : a 56% l o s s of chromium, a 56% l o s s o f manganese, and a 51% l o s s of z i n c . In a d d i t i o n to the a l r e a d y noted h i g h l o s s of chromium i n r e f i n e d sugar, there i s a greater than 80% l o s s of f o u r other e s s e n t i a l t r a c e elements i n the p r o d u c t i o n of white t a b l e sugar. These l o s s e s i n c l u d e 90% of the manganese, 98% of the z i n c , 83% of the copper, 88% of the c o b a l t , as w e l l as 98% of the macro-element magnesium. From these d a t a , i t i s apparent that the t r a c e mineral cont e n t of many of our major f o o d s t u f f s , i n c l u d i n g r e f i n e d f l o u r , c e r e a l products, r e f i n e d sugar and r i c e , are markedly reduced during the r e f i n i n g p r o c e s s e s . Increased consumption of h i g h l y r e f i n e d foods, snack foods, and food analogs could l e a d to American d i e t s that may be marginal w i t h respect to adequate intakes of s e v e r a l t r a c e element e s s e n t i a l f o r good h e a l t h , and i n t e n t i o n a l excessive consumption of these low n u t r i e n t foods might l e a d to n u t r i t i o n a l d e f i c i e n c y diseases through replacement of conventional food n u t r i e n t s .


10.

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175


The N a t i o n a l Research C o u n c i l has r e c e n t l y recommended "enrichment" o f foods made from wheat, corn, and r i c e w i t h ten vitamins and m i n e r a l s , i n c l u d i n g i r o n , z i n c , calcium, and magnesium. It can be a n t i c i p a t e d that f u t u r e recommendations may i n clude a d d i t i o n a l e s s e n t i a l t r a c e elements not now i n c l u d e d i n t h i s suggested enrichment program. S c i e n t i f i c proof of marginal or overt d e f i c i e n c y must be obtained before any f u t u r e a d d i t i o n s would be considered. The evidence f o r chromium d e f i c i e n c y i s slowly a c c r u i n g , but f u r t h e r work remains to be done. Acknowledgement: This i n v e s t i g a t i o n was supported by part by USPHS Grants AM 15,100 and RR 229.

Literature Cited

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The Role of Trace Elements in Human Nutrition and Metabolism - ACS

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