On the Excretion of Calcium and Magnesium in human Urine1

BY

(From the Institute of Medical Chemistry, Lund, Sweden) - Lars Lundgren

(With 4 figures in the text)

From experiments with rats in this Institute G. Hamimarsten has proved ( I 937) that the excretion of calcium in the urine of these animals can be lowered to a minimum of 0.002 in molarity by the supply of food rich in vitamins, calcium, and magnesium, if the pro- portion of acid-base-equivdents is at the same t h e adapted so that urine. pH = 6.2. The following experiments have been made in order to test wether the conditions are the same in man as in the rat, and wether the excretion of calcium in the urine can be lowered by. a large supply of calcium and magnesium to food that is in other respects adequate.

Experimental.

The experimental subject (the author) is a male student, age 20 years, weight about 75 kg. The time of experiment was March-August, 1937, divided into five periods, A-E. Between periods C and D there was a period of normal food of ab. 45 days. In the same manner, between periods D and E there was a period of normal food of ab. 75 days. The composition of the food is pven in tables I and 2.

By normal food is meant the daily fare of the Lund Students Refectory. It is good, homely fare of high quality. Table 3 shows the quantities of calcium and magnesium that the body is supplied with by the food in the various periods. The additional supply of calcium is given as an increased quantity of cheese and milk in the food. Extra magnesium is conveyed as citrate or secondary phosphate. The proportion af mineral in the food is calculated accordhg to Berg’s tables and is thus approximate only. According to Sherman (1920), the minimum of the quantity of Ca that ought to be conveyed to a grown-up every day for him not to lapse into negative Ca-balance is 0.4gr.

1 Recieved for publication the 16. December 1938.

30

0.61. 60 g. 20 g. Two 85 g. 125 g. 60 g. 30 g. 80 g. 30 g.

LARS LUNDGREN

Table I

0.79 0.07 20 400 Traces 540

0.01 5 70 0.29 0.06 0.01 I 0 150 0.01 0.02 I 80 0.02 0.03 20 30 0.04 0.02 I 0 200

0.01 0.01 3 75

0.01 0.01 3 75 0.04 0.02 8 200

Number Period of days

_ _

Food ___ .-. _ _ _ _ - ~ - --

Mixed food without milk, cheese, and vegetables

Mixed food - I lit. milk + 45 g. cheese + 50 g. wheatgerms + I orange + 2 teaspoonsful of cod- liver oil

Normal food Normal food Normal food

Normal food Orange: vitamin C Wheatgerms: B and E Cod-liver oil: A and D

Additional mineral supply

___ 0

0.6 g. Mg as citrate 1.2 g. Mg . . . .

0

0.6 g. Mg as citrate 0.6 g. Mg as MgHPO,

0

Table 2

T h e composi t ion of t h e normal food

Substance

Milk. . . . . . . . . . Butter . . . . . . . . . Cheese . . . . . . . . . Eggs . . . . . . . . . Potatoes . . . . . . . . Meat . . . . . . . . . Pork (fat) . . . . . . . Black bread . . . . . . White bread . . . . . . Bread of coarse meal . .

Sum

Ca I Mg 1 Protein 1 Gal. Quantity I

M. by

'The above total figures for Ca and Mg are recalculated in E., 63 and 16 respectively. Since extra mineral is also supplied sauces etc. the figures 7 0 M. E. for Ca and 20 M. E. for Mg will

be those most closely corresponding to the quantity in the food. Simil- arly, mainly due to the administration of sugar, the total amount of calories is increased to 2000.

Lei tch (1937), who has made investigations on the need of Ca at dif- ferent ages, has found ,that it is highest a t the age of fifteen or sixteen with about z g. per diem. At 20 or ZI a Ca-supply of 0.8 g. per diem is - according to L. - sufficient. It is clear from table 3 that during the whole time of ex- periment, period A only has a food calcium that lies under this value ( 0 . 2 g.

ON THE EXCRETION OF CALCIUM AND MAGNESIUM IN HUMAN URINE 31

per diem). With regard to the supply of Mg, the minimum need of a grown, up is according to Renval l (1904) 0.45g: and according to Bunge (1901, 1904) 0.6 g. per day. D a n i e l s och Everson (1936) say that ))preschool children receive a minimum of 13 mg. Mg per kg. bodyweight((, i. e. about 0.25 g. per diem. If these figures are compared with those of table 2, it will be seen that our food contains far too little magnesium, a fact that has been pinbed out before by J a v i l l i e r (1930). My own experiences of the periods of experiments have been that I have not noticed any change whatever of the general condition of health parallel to the Mg-content of the different kinds of fare excepting the latter part of period Bz, when my digestion was incommoded by diarrhoea. The cause of this is probably the rich supply of Mg, and it is likely that the large quantities of Mg have had a disturbing k f l m c e on the absorption.

The protein content of the food amounted to 80 g. per diem, i. e. c. I g;kg. bodyweight, and should be regarded as sufficient. The caloric supply was about 2000 per day. As no decrease in weight followed, it must be considered satis- factory.

Methods.

G. H a m m a r s t e n (1936). Calcium was ascertained according to Aron 's method modified by

Magnesium according to S t o l b a (1876). pH was ascertained electro-metrically with Bi i lmann ' s chinhydron-

electrode.

Results of experiments. As a normal Ca-excretion per day Beckman (1890) states 17.5

M. E., GroD 1 2 . 1 M.E., Neubauer 15.7 M.E.; and Schetelig (1880) finds variations between 6 and 20 M.E. I have found a excretion in periods C and E (normal food) of 12.29 f 0.52 and 14.44 f 0.57 M. E. respectively which means relatively good correspondence.

Normal Mg-excretion is according to Beckman (1890) 14.3 M.E., according to GroD 7.9 M.E., according to Neubauer 11.4 M. E. and according to Walker and Walker (1936) 8.5 M. E. on the average. Gui l lamin ( 1 9 3 1 ) found variations between 4.1 and 15.6 M. E. Thus in this respect, too, good correspondence With I 0.35&0.51 and I 1.89 i 0.44 M. E. respectively found in the cases before us.

What is of the greatest importance, however, is nut the total concentration of those salts in the urine but the molar, as rhis is decisive for the eventual sedimentation of Ca as for hstance phos- phate or oxalate. Especially remarkable is the low Ca-concentration of the urine in period B, in spite of the food's containing large quanti- ties of Ca and the diuresis not being abnormally large. The molar concentration is upon the whole the same, the total Ca-excretion by the urine is lower than in period E (cf. table 3).

From a comparison between periods B and D the following can be inferred: - If food containing much Ca is balanced against food

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C

a g.

I M.

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g.

10

0

.2

10

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.12

125

2.5

75

0.90

12

5 2.

5 12

5 1.50

70

1.4

19

0.24

70

1.4

69

70

1.4

69

0'84

0.

84

70

1.4

19

0.24

Tab

le 3

Tot

al e

xcre

tion

in u

rine

T

he c

onte

nt o

f ur

ine

Qua

ntity

O

f w

ine

mill

iequ

iv.

mol

arit

y x

103

r

6 71

5 f 1

9 5.

8 9.

98 * 0

.51

8.25

0.

24

7.0 f 0

.35

5.8

0.90

r

772

& 2

4 6.

2 1

1.0

2 f 0.

28

12.0

5 &

0.8

3 7.

6 f 0

.98

7.9 f 0.

39

870 f 2

9 6.

4 12

.39 f 0

.29

17.8

6 f 0.5

1 7.

2 f 0.

55

10.5

f 0.

51

X ,

897 f 4

0 6.

4 12.29 f 0.

52

10.3

5 5 0

.51

7.0

0.26

5.

8 0.

20

E

I pH

Ca

I M

g C

a I

@

%- __._____-

per

diem

cc

.

z 17

.54 f 0

.87

15.3

0 5

0.8

6 8.

8 f 0

.6j

9.0 f 0.

62

6'4

13.8

9 f 0

.49

15.4

9 0.

60

8.3

5 0.51

8.9 5

0.2

9

I022 f 58

6.

4 14

.44 f 0

.57

11.8

9 f 0

.44

7.4 f 0

.45

, 6

.1 f 0

.31

] 864

*

Peri

od

A

B,

B,

C

E

Skandinav. A r c h . 8s. 3

34 LARS LUNDGREN

a rather high Ca-concentration in the urine (see the end of periods €32 and D2, figures 3 and 4), and the risk of precipitatimon of the calcium increases. Here it is, however, difficult to determine whether the magnesium as such or a disturbance of the absorption is the cause of the relatively high Ca-concentration of the urine in D z . That a certain quite obviously balanced relation prevails between Ca and Mg in the urine is best seen from fig. 3 . There we sce how the urine con- c-eiltrations of Ca and Mg follow each other in the normal circumstan- ces prevailing in periods C and E. If Mg is given without the Ca- supply being increased at the same time, the Mg-supply seems in this case to have exercised an unfavourable influence on the Ca-excre- tion. Thie is not the case with adequate Ca-supply (cf. period B). Boger t and Mc Kittrick have proved before (1922) that an increased Mg-excretion, caused by increased Mg-supply in the food (6 g. Mg- citrate per day) entails an increased Ca-excretion by the urine. On the other hand Underh i l l , Hone i j , and Boger t (1920) could not find any relation whatever between the Ca- and Mg-conccntrations of the urine.

The food generally contains so much vitamin that the additional supply in period B will be of little or no importance.

Of the periods that form part of the experimental series only the h s t can be regarded as corresponding to normal values. In period C, which is also based on normal food, the Mg-concentration has been influenced in an obvious way by the Mg that is left in the body after that which was supplied in period B2 (see fig. I and 4).

It is clear from period E that the average value of the quantity of Ca excreted per diem is I 4.44f 0 .57 M. E. If this value is compared with that obtained from period A ( 9 . 9 8 5 0.51 M.E.), it is seen that this lies far Mow the normal value. 'Towards the end of period A the Ca-content in the urine increases ('see fig. 4). The same phenomenon has been shown by, among others, Boekelmann and S t a a l (1907), and Ro th le in (1933). The quantity of Ca that is conveyed to the body in this period amounts to about 10 M. E. Thus I O O ~ / O of Ca supplied would be excreted in the urine. Many authors - e. g. Baue r W., Albr igh t F. and A u b J. C. (1929), v. Noorden and Be lga rd t ( I 894) - have proved, however, that 70-800/0 of the food calcium is excreted in the faeces. Experiments of balance made on too low a supply of Ca by She rman , von Wend t and Rose prove that under such c i r c u m s ~ c e s a negative Ca-balance is present. That there is a negative balance in our case, too, can be assumed with great proba- bilety. A large part of the calcium excreted must accordingly have been mobssed from the tissues of the body. In the former part of

AX

20

I5 10

5

Fig

. 4.

M

E excreted. C

a--,

Mg

Bet

wee

n C

and

D 4

5 da

ys of

norm

al f

ood.

Between

D a

nd E

75

days

of

norm

al food.

w +

36 LARS LUNDGREN

period B a large part of the calcium supplied was certainly usefd to cover these deficiencies. Of the 1 2 5 M. E. of the food only about I I .5 M. E. on an average are excneted in the urine, and so a positivc Ca-balance may be present in this case.

For periods C, D I , Dz and E the Ca-content of the food is 7 0 M. E. The quantity of Ca excreted is I 2.29 5 0 . 5 2 M. E., I 7.54 :! 0.87 M. E. I 3.89 f 0.49 M. E., and I 4.44 1- 0 . 5 7 M. E. respectively.

It can be said of the Mg-excretion that on the whole i t corre- sponds to the supply. Underh i l l , Honei j , Boger t , and Mc Ki t t - r ick (1922) have come to similar results, while Gievens ( 1 9 1 8 i could not prove any increase of the Mg-excretion with an Mg-content of the food of 1-2.5 g per diem (Mg given as citrate). As regards my own investigations, the following is clear from table 3 and fig. 4.

In period A, with its food magnesium of only 10 M. E., 8.25 0.24 M. E. are excreted by the urine. According to Renval l (1904) 29 to 340/0 of the magnesium is excreted with the urine. B e r - t r am, T ibbe t s , and Aub have also come to similar results. In the case under consideration a negative balance must probably be ;Lssumed.

In period B I , with a quantity of 7 0 M. E. of Mg supplied, the excretion is 12.05f0.83 M.E. In periods C and E, which corres- pond most closely to the normal values of the Mg content of the food (19 M.E.), the excretion is 10.35h0.51 and 11 .89f0 .44 M.E.res- pectively. It is not possible to infer anything as to the balance in t h e cases.

The increase of the Mg-concentration in the urine with consider- able Mg-content of the food is of great importance to hinder calcium oxalate from precipitating. Mg has a considerable tendency to form an undissociated but readily soluble compound with the oxalate ion (Schiifer 1905, Werner 1908), and is thus able to increase the solu- bility of calcium oxalate in a high degree (G. Hammarsten I 929).

It is of some interest that the supply of Mg as citrate or phos- phate does not seem to have any influence on the Mg-concentration in the urine. In the period D, (Mg as citrate), and in the period D2 (Mg as phosphate) the values of these concentrations are 9.0 f 0.62 and 8 . 9 5 0 . 2 9 respectively. (Values in mol. x 1 0 - 3 ) .

The relatively constant quotient (under normal conditions) bet- ween urine-Ca and urine-Mg is remarkable. The quotient between total-Ca and total-Mg expressed in M. E. for period E is I .22, and the quotient b e e n the concentratims in mol x 1 0 - 3 almost precisely

total- Ca, 2 (2.02). Fig. 2, which represents graphically the relation

total-hlg

ON THE EXCRETION OF CALCIUM AND MAGNESIUM IN HUMAN URINE 37

shows also the desirability of a balanced Ca-Mg-proportion in the food. In period B, which is relatively well balanced, the quotient falls rather considerably under I , while in period D, with an Mg-surplus without a corresponding Ca-supply, i t is very little below I .

The pH of the urine was all the time relatively constant about 6.4. Only in period A with its marked meat-diet did the urine-pH f a l l to about 5 . 5 . The base-acid-equivalents of the food are then balanced so that optimum-pH prevails for the Ca-metabolism (cf. intro- duction), if we dare to assume the same optimum-pH in man as in the rat.

Summary With n o d food and urine-pH 6.4, the calcium excretion of

the experimentee was in Mol. 7.4x 1 0 - 3 on the average. In the single case in question it has not been possible to reduce

the Ca-excretion in the urine below the above value in the same way as G. Hamimarsten has shown by rats by supply of Mg.

The individual urine calcium excretion is probably subject to variations, which may possibly be connected with a more or less intensified ammonia defence.

With a surplus of Mg in the ordinary food the Ca-excretion in the urine has increased. (Disturbed absorption?) When on the other hand food with a relatively high Ca- and P-content has been balanced against food containing much Mg, the Ca-concentration of the urine has not increased.

This research has been carried out with the help of funds placed at the disposal of G. Hammarsten from the ThCr&se and Johan An- derssons Memorial Foundation.

References

Bauer, W., F. Albright , and J. C. Aub, J . CZin. Invest. 1927. 7 . 75. Beckmann, W., 261. med. Wiss. 1890. 266. Berg, R., Die Nahrungs- und GenuGmittel. Dresden 1923. Boekelman, W. A., und J. P. Staal, Arch. exp. Path. Phnrmak. 1907, 56. 260. Bogert , L. J., and E. J. McKittrjick, I . biol. Chem. 1922. 54. 363. v. Bunge, G., 2. Biol. 1901. 41. 15s. v. Bunge, G., Ibidem 1904. 45. 532. Cox, W. M. J:r, and M. Imboden, .I. Nutrition 1936. 11. 147. Danie ls , A. L., and G. J. Everson, Ibidem 1936. 11. 327. Gievens, M. H., I . biol. Chem. 1918. 34. 119.

38 LARS LUNDGREN, ON THE EXCRETION OF CALCIUM ETC.

G r o s s , Cf. N e u b a u e r , C.. and C. H. H u p p e r t , Analyse des Harns. W i e s

G , u i l l a u m i n , C. O., Progris med. 1931. 1. 97. H a m m a r s t e n , G., C. r. Lab. Carlsherg 1929. 17. no. 1 1 .

H a m m a r s t e n , G., This Archio 1936. 75. 189. H a m m a r s t e n , G., Calciumoxalat als Steinbildner in den Harnwegen. Diss.

J a v i l l i e r , M. M., Bull. Soc. Chim. biol. Park ~ g j o . 12. 709. h i t c h , I., Nutrition dbstracts and Rev. 1937. 6. 553. v. N o o r d e n , und K. B e l g a r d t , Bed . Klin. Wschr. 1894. 31. 235. R e n v a l l , G., This Archk 1904. 16. 94. R o t h l e i n , E., Schweir. Med. Wsclrr. 1933. 63. 529. S c h a f e r , H., 2. anorg. Chem. 1905. 45. 2 g j . Sche te l ig , Arch. e x p . Path. Pharmak. 1880 82. 437. S h e r m a n , H. C., J . biol. Chem. 1920. 44. 21. S t o l b a , F., S.-B. Bohm. Ges. Wiss. 1876. H. 5 . Ref. in Z. arzalyt. Chemie

U n d e r h i l l , F.P., J . A . H o n e i j , and L. J . B o g e r t , J. exp.Med. 1920. 32. 65. W a l k e r , B. S., and E. W. Walker, J . Lab. Clin. Med. 1936. 21. 713. Werner, A., Neuere Anschauungen auf &m Gebiete der anorg. Chemie. Braun-

baden 1910.

Lund 1937.

1877. 16. 100.

ochweig 1908.