Hydrogen Peroxide as a Depressant of Gastric Acidity By

C. U. CULMER, B.A.%, A. J. ATKINSON, M.S., M.D. and

A. C. IVY, Ph.D., M.D. CHICAGO, I L L I N O I S

A G R E A T amoun t of work has been done in search of methods fo r dec rea s ing the ac id i t y of t he

g a s t r i c contents . One of the subs tances which has been used fo r th is pu rpose is h y d r o g e n peroxide . P e t r i (1) in 1908 r epo r t ed t h a t l a rge quan t i t i e s of a d i lu te solut ion (300 c.c. of a 0.5% solu t ion) in t roduced into an empty s tomach m a r k e d l y lowered the ac id i ty of the ga s t r i c contents and recommended i t s use in the t r e a t - men t of hype rac id i t y . Since then a n u m b e r of cl ini- c ians (2, 3, 4, 5, 6 and 7) have r e p o r t e d t h a t d i lu te h y d r o g e n pe rox ide is a means of r educ ing the secre- t ion of ga s t r i c acid and of i nc rea s ing the secre t ion of mucus. All ag reed t ha t acid sec re t ion was reduced, but not all r ecommended i ts t h e r a p e u t i c use. The de- g ree of inh ib i t ion of acid r epo r t ed var ied . H u r s t (8) in 1931 r epor t ed iJhe use of hydrogen pe rox ide for re- l iev ing the ach lo rhyd r i a or h y p o c h l o r h y d r i a seen in chronic ga s t r i t i s . He used so lu t ions v a r y i n g f rom 0.013% to 0.095~, as a g a s t r i c lavage. I t is to be noted t ha t H u r s t used h y d r o g e n pe rox ide in much more d i lu te so lu t ions than did the others . He supposed t ha t i t was an effective mechanica l means of d i s lodg ing the excessive mucus which was p r e sen t in chronic gas- t r i t i s . He sugges ted t ha t excessive mucus p reven ted acid secre t ion by b locking the mou ths of the acid- s ec re t ing glands.

F o r some t ime one of us (A . J .A . ) has been i n t e r - es ted in s t u d y i n g expe r imen ta l l y the effects on ga s t r i c secre t ion of va r ious agen t s when appl ied to the g a s t r i c mucosa of an imals . Our rev iew of the l i t e r a t u r e indi- cated t ha t the effect of hyd rogen perox ide on gas t r i c secre t ion should be s tud ied under control led labora- t o ry condi t ions . This we have done ; in add i t ion we have ex tended our s tud ies to include a few h u m a n subjec ts .

M E T H O D S Five Pavlov pouch dogs and three do.~s with intact

stomachs were used. All were in good health at the time the experiments were initiated. Five clinic patients were studied; the clinical diagnosis was duodenal ulcer in three, and gastr ic ulcer in one; one had a normal stomach inso-

fa r as could be determined by physical findings and labora- tory tests, but he complained of dyspepsia and epigastr ic distress.

The secretion of the pouch dogs was collected by the orthodox method. In the dogs with intact stomachs the gastr ic contents were aspirated by means of a number 32 French colon tube which was passed each time a sample was to be withdrawn. We first t r ied using a retained Rehfuss tube; it worked well during the control tests, but af ter hydrogen peroxide had been administered there was so much mucus on subsequent aspirat ions tha t the small

*From the Depar tments of Medicine and Physiology and Pharmacology, Northwestern Univers i ty Medical School, Chicago, niinois.

tAtkinson Fellow. Pa r t of the expense of this invest igat ion was defrayed by contribution

from the E. L. Dawes Fund. Submitted J a n u a r y 23, 1937.

tube invariably became occlude~t. In the human subjects a Rehfuss tube was used.

Two methods of s t imulat ing the gastr ic secretion were used. Histamine was used in all three groups of subjects; in each case 1.0 mgm. of ergamine acid phosphate was in- jected subcutaneously. In addition, on the dogs with pouches, tests were made in which the stimulus was a test meal.

In the dogs with pouches when histamine was used as the stimulus, a control test s tar ted with the injection of the histamine, the gastr ic samples being collected several times during a period of 90 minutes. At the end of 90 minutes another mil l igram of histamine was injected and the collection of juice continued. In the dogs with intact stomachs and the human subjects, only one test period of 90 minutes was employed. In the case of the dogs with pouches when a meal was used as a stimulus, the secretion was collected for a period of eight hours af ter feeding.

In the case of each subject a number of control tests were made to establish the normal response of the indi- vidual to the stimulus being used.

R E S U L T S

The complete da t a a re too bulky to be p resen ted . T h e r e f o r e we shall give a r e p r e s e n t a t i v e pro tocol of one of the expe r imen t s and will then s u m m a r i z e the resu l t s ob ta ined in the r ema inde r .

The effect of a single application of 3.0% hydrogen peroxide on the histamine response: Dog No. 1 had a Pavlov pouch. On in j ec t i ng 1.0 mgm. of h i s t a m i n e the pouch secre ted an ave rage of 14.0 c.c. of g a s t r i c ju ice con ta in ing 53 mgm. of f r ee HC1 and 63 mgm. of to ta l acid in 90 minutes . A f t e r the necessa ry cont ro l tes ts , the pouch was washed wi th 100 c.c. of 3.0% h y d r o g e n perox ide (see Table I ) . B e g i n n i n g 15 minu te s l a t e r the sec re t ion of the pouch was collected fo r two 30 m i n u t e per iods. D u r i n g th i s t ime the secre- t ion was mucoid in na tu re , amoun ted to 18.2 c.c., and conta ined no f ree acid, bu t had a s l igh t amoun t of to ta l acid. Then 1.0 mgm. of h i s t a m i n e was in jec ted subcutaneous ly . In 90 minu te s 23.2 c.c. of secretio.n were collected con ta in ing only 6.00 mgm. of f ree HC1 and 21.60 mgm. of to ta l acid. Then the in jec t ion of h i s t a m i n e and collection of secre t ion were r epea t ed wi th the resu l t s shown in Table I. The resu l t s of all these p a r t i c u l a r expe r imen t s on Dog No. 1 a r e in- cluded in Table I I . The resu l t s show c lear ly t ha t wash- ing the pouch w i th 3.0% h y d r o g e n pe rox ide m a r k e d l y depressed the s ec re to ry response to h i s t amine . The ju ice was r ich in mucoid secre t ion.

In the five dogs in which th i s e x p e r i m e n t was per - formed, the f ree HC1 secre t ion was reduced on the a ve r a ge 65.8% a f t e r the f i rs t in jec t ion of h i s t a m i n e and 56.5% a f t e r the second. The volume of mucoid secre t ion ob ta ined va r i ed wideIy, bu t was inc reased in all.

Fo l lowing a s ingle t r e a t m e n t of the pouch wi th

219

220 A M E R I C A N J O U R N A L OF D I G E S T I V E D I S E A S E S A N D N U T R I T I O N

hydrogen peroxide, the dogs were injected daily with histamine to determine the time at which the secre- tory response returned to normal. The time of re- covery varied widely. One dog had not returned to normal in 29 days. One returned to normal in 5 days,

results, as might be anticipated, showed that the stronger the concentration the greater the reduction in acid secretion. Concentrations of 0.5, 1.0, 1.5, 2.0, and 3.0% were employed.

The results with a meal as the stimulus: After the

TABLE I The effect of a single application of 3.0% hydrogen peroxide on the histamine response

Time

9:25

9:40

10:10

10:40

10:40

10:55

11:15

11:25

11:40

I1 :55

12:10

Vo]. in c.c.

12.0

6.2 18.2

2.8

7.5

3.0

3.3

2.6

4.0 23.2

C.U. Free Acid

-0-

-0-

-0-

8

18

13

-0-

-0-

mgm. Free Acid

-0-

-0-

-0-

2.25

2.10

1.65

-0-

-0- 6.00

C,V. Total Acid

½

4

mgm, Total Acid

0.12

0.62 0.74

8 0.84

25 6.75

68 7.50

35 4.29

18 1.82

4 0.40 21.60

Remarks

Pouch washed wi th 100 c.c. of 3.0°% hydrogen peroxide.

S ta r t ed collecting.

In jec ted 1.0 mgm. h i s tamine .

12:10

12:25

12:40

12:55

1:10

1:25

1:40

5.8

5.7

3.9

2.6

2.2

2.8 23.0

-0-

15

25

15

8

-0-

-0-

2.85

3.51

1.30

0.66

-0- 8.32

8

40

53

43

25

15

1.74

8.55

7.41

4.16

1.98

1.40 25.24

In jec ted 1.0 mgm. h i s tamine .

one in 9 days, one in 10 days, and one in 12 days. One secreted hypernormally at 12 days, one at 15 days, and another at 18 days.

The effect of repeated applications of 3.0% hydrogen peroxide on the histamine response: In two of the dogs whose response to histamine had returned to normal in from five to nine days af ter a single appli- cation of hydrogen peroxide, 3.0% hydrogen peroxide was applied to the pouch twice daily, morning and evening, for 15 days. The response to histamine was determined on the third, fifth, eighth, eleventh, and fifteenth days. The secretion of free and total acid was reduced markedly in both dogs. In one dog the free acid was reduced by 96% (almost abolished), the total acid being reduced 83%. In the other the free acid was reduced 77% and the total acid 46%. The volume of secretion, chiefly mucoid, was reduced 23% in one and increased 48% in the other. From the first dog, on some days, a clear rather dilute mucoid secre- tion devoid of free acid (pH 4.2) was obtained.

The effect of a single application of vario~s concen- trations of hydrogen peroxide on the histamine re- sponse was studied in the three other, dogs with pouches. It was found that a 0.5% solution was effec- tive in reducing the secretion of acid, the average varying from 12% to 66% in the total acid and from 32% to 83% in free acid in the different dogs. The

pouches had returned to normal and suitable response to the test meal had been obtained, the hydrogen pero- xide was applied and the meal fed. The secretion of the pouch after the meal was collected for eight hours.

The data are shown in Table III . The results are exceedingly variable, much more so than the results obtained with histamine as a stimulus. This should be expected because the response to the stimulus of a meal is normally more variable than the response to histamine. The variation may be about 25% from day to day in the same dog. Further, af ter the first hour or two following the application of the peroxide and feeding, acid secretion starts to increase. The amount of secretion varies in the same and different dogs. I t must be recalled that the histamine response occurs only during a period of from one to one and one-half hours. It is to be noted that a 3% solution was re- quired to produce a definite reduction of the free acid in two of the three animals in series 2; and in series 1, dog No. 2 showed little decrease even to 3.0%.

In one dog (No. 8) a 2% solution was effective. Dog No. 11 manifested a definite increase in acid secretion after the application of each of the concen- trations of peroxide except the 3% solution. This is the animal that showed the most marked hypernormal response to histamine during the recovery of the pouch from the effect of 3% peroxide.

C U L M E R , A T K I N S O N A N D IvY--H202 A S A D E P R E S S A N T O F G A S T R I C A C I D I T Y 2 2 1

Dogs with no,Tnal stomachs. Three dogs with intact stomachs were treated with 100 c.c. of 3% hydrogen peroxide after several control responses to histamine had been obtained. The peroxide solution was with- drawn after three minutes. The secretion of free acid was reduced from 95% to 100%, and the total acid was reduced from 81% to 90%. The secretion of mucus

passed into the duodenum. Three per cent peroxide obviously was too irritating for the stomach of one of the animals.

HUMAN SUBJECTS

Because 3.0% hydrogen peroxide was found to be markedly irritating to humans, 1.0% and 2.0% solu-

TABLE II

Controls

1

2

3

4

A v e r a g e s

U s i n g 3% hydrogen peroxide

1

2

3

4

5

6

7

8

9

10

11

12

A v e r a g e s

1st Inject ion of H i s t a m i n e

Vol.

15.4

10.0

12.9

17.7

14.0

15.5

16.9

19.2

23.2

13.2

16.5

13.0

9.5

15.1

8.5

15.8

8.8

14.6

Free acid

M x C U m g m .

130 63.47

128 37.74

128 46.43

138 64.17

130 52.95

20 4.55

38 15.09

53 22.61

18 6.00

20 4.62

25 7.31 i

63 22.12

15 3.42

38 I 11.94

25 5.54

35 ~ 10.33 [

38 4.88

32 9.87

Total acid

M x C U m g m .

148 69.90

150 42.80

t45 58.80

143 79.98

146 62.87

Vol.

8.7

8.2

10.I

15.7

10,7

18.2

fi3.0

15,5

15.6

21.0

3.5

13.7

4.1

16.1

9.7

14.0

M x ~ U m g m .

177 37.10

188 32.69

130 39.05

138 68.92

144 44.44

2nd Inject ion of H i s t a m i n e

Free acid Total acid

M x C U m g m .

193 40.71

143 36.13

138 43.90

145 75.69

49.11

88 42.32

25 8.32

55 19.54

40 16.13

88 47.25

0 00.00

33 5.80

25 3.55

43 15.52

78 24.87

48 18.33

155

;-

103

53

80

65

118

26

48

48

65

95

70

38 12.15

53 23.54

65 31.51

68 21.60

53 16,85

50 16.76

88 32.76

38 9.95

58 21.01

48 12.00

55 11.85

55 9.83

56 18.32

52.27

25.24

34.84

30.31

68.42

2.34

15,06

7,03

27.20

16.96

27.97

Per cent of change

from control averages

Inc .

4.3

Dec.

75.4

L I [ I i Dec.

81.4

Dec.

61.6

Dee.

70.8

Inc .

30.8

Dec.

66.6

Dec. Dec. Dec.

58.7 54.8 ; 43.0 I

Vol. - - volume in c.c. :MxCU - - m a x i m u m c l in ica l units m g m . - - mil l igrams of free or total acid in t erms of HC1 Inc. - - increase Dec. - - decrease

was so copious that a colon tube had to be used to aspirate the gastric contents. The dogs were nauseated and retched after the aspiration of the peroxide. One of the dogs on being treated again on the following day showed a large amount of blood in the gastric contents.

This depression of secretion was anticipated. The greater viscidity of the secretion probably was due to stimulation of the mucosa of the pyloric antrum in addition to that of the fundus. Nausea and vomit ing did not occur in the dogs with Pavlov pouches for several reasons. The area to which the peroxide was applied was smaller. The nauseating effects of the stomach tube were absent. In the animals with whole stomachs some of the hydrogen peroxide undoubtedly

tions usually were emplQyed. A 3.0% solution was used in the "normal" individual in a few tests. Hista- mine was used as a stimulus. The entire content of the stomach was removed every ten minutes for 90 minutes after the injection of histamine. From three to five control responses to histamine were obtained prior to the commencement of treatments with hydro- gen peroxide. The stomach was lavaged with from 100 to 300 c.c. of the peroxide which was withdrawn after three to five minutes. This procedure was re- peated two or three t imes a week, until four to twenty treatments had been given.

In one patient with duodenal ulcer in which only 1.0% peroxide was used, the acid secretion after five treatments was increased by about 35% in spite of the

222 A M E R I C A N J O U R N A L OF D I G E S T I V E D I S E A S E S A N D N U T R I T I O N

formation of considerable mucus. Because the lavage caused discomfort and because the symptoms were augmented, the treatment was discontinued. In a second duodenal ulcer patient similarly treated, the free acid secreted was decreased by 45% and the total

T A B L E I I I

1st series 3%

Dog No. 1

Dog No. 2

2nd series ~%

Dog No. 1

Dog No. 8

Dog No. 11

1% Dog No. 1

Dog No. 8

Dog No. 11

1 ~ %

Dog No. 1

Dog No. 8

2%

Dog No. 1

Dog No. 8

Dog No. 11

s%

Dog No. 1

Dog No. 11

Free acid Total acid

The figure shows the average per cent of change from the control response; those marked wi th an asterisk represent percentage increases, the others decreases.

acid by 18%; this patient secreted much mucus. Be- cause the symptoms were not decreased, the treatment was discontinued. The stomach of the third patient with duodenal ulcer was lavaged eight times with 1.0% and 2.0% solution of peroxide. Five tests were per- formed during a three week period. Discomfort from the lavage occasionally was reported. The two per cent solution of peroxide decreased the free acid values by about 90% and the total acid values by about 30%. The symptoms of this patient disappeared with this regime without other medication or dietary changes. In the patient with a gastric ulcer, 1.0% solution of peroxide increased the secretion of both acid and mucus; 2.0% caused a decrease of about 50% in the acid values. The t reatment was discontinued because the patient 's symptoms were not relieved af ter nine treatments during a period of four weeks, and because there so frequently was considerable blood in the gastric contents following hydrogen peroxide. In the individual with a "normal" stomach, concentrations of peroxide varying from 1.0% to 3.0% were used. Twenty treatments were given and nine tests were done during this time. More patients were not used

because of the discomfort and bleeding experienced by those we did treat in this way.

The results of the tests confirmed the observations on the dogs, that 3.0% solution of peroxide reduced acid values in response to histamine to a greater ex- tent than the 1.0% solution. In the patient with gastric ulcer and in one of three patients with duo- denal ulcer a 1.0% solution of hydrogen peroxide in- creased the acid values of the stomach contents af ter histamine. In the other two patients with duodenal ulcer either 1.0% or 2.0% solution of hydrogen pero- xide reduced the acid values af ter histamine. In the individual with a "normal" stomach 1.0% to 3.0% solution of hydrogen peroxide lowered the acid values in response to histamine, the s tronger solution being the more effective.

DISCUSSION OF RESULTS The preceding results indicate tha t in general the

lavaging of the stomach with hydrogen peroxide solu- tion (~ -3%) produced a decrease in the acid of the gastric contents when either a meal or subcutaneous injection of histamine was used to stimulate acid secretion. This decrease was observed in the per cent of acid in the gastric contents and in the total milli- grams of acid, both free and total, in each case. The stronger the solution of hydrogen peroxide used the greater was the decrease of acid response. This de- crease varied widely in different subjects, and also, from time to time, in the same subject. However, one of the dogs and two of the five human subjects con- sistently showed increases in acid secretion rather than decreases. The mucous secretion always was augmented.

At times there was a complete absence of free acid (but no instances of complete absence of total acid) in response to histamine stimulus. This was observed four times in dog No. 1, once in dog No. 2, twice in dog No. 8, twice in dog No. 6, twice in dog No. 9, and twice in dog No. 12. However, it was the exception rather than the rule. This type of secretion was oh- served by Ivy (9) and Dawson (10) in the gastritis produced in Pavlov pouch dogs by X-rays.

While no chemical analyses for content of mucus were made, it was obvious that generally an increase in mucoid or mucus secretion paralleled a decrease in acidity. This observation certainly was true in those tests in which no free acid was found. In several instances when there was no free acid, determinations of the chloride in the secretion were made; and it was found that the chloride content was no higher than that which is normal for mucus or mucoid secretion.

Other investigators have reported using 300 c.c. of a 0.5% solution for gastric lavage of peptic ulcer patients. Petri, Poly, Hall, Kelling, and Dienst were enthusiastic in regard to the use of hydrogen peroxide in the treatment of peptic ulcer because the secretion of acid is reduced and that of mucus is increased. Hall stated, however, that it did not seem to benefit cases with active ulcer. Winternitz found that it decreased acidity for only short intervals, and discarded its use. Nielson also observed a depression of free acid with a return to normal values or nearly normal values in 24 hours. Hurst used dilute solutions (0.013-0.095%) in chronic gastritis, observing an increase in acid secre- tion.

Our results show that to obtain a significant reduc-

F E L D M A N , MORRISON, CARR AND K R A N T Z - - E T I O L O G Y OF G A L L S T O N E S 223

tion in acid secretion in response to histamine or a meal, stronger concentrations of peroxide (one and two per cent) must be employed. Even then stimula- tion, as observed by Hurst with very weak solutions, may occasionally occur. A three per cent solution is

too irritating. When the weaker solutions are used the return of the secretory response to normal is re- ]atively rapid. In the case of a "susceptible" stomach, however, a 0.5% solution applied every other day will reduce acid secretion significantly. However, we sus- pect that it might cause active ulcers to bleed; for the gastric ulcer patient showed bleeding with one and two per cent solutions, and one of the dogs with "normal" stomach showed marked bleeding after 3%. Although it would be desirable to have some simple and innocuous method for reducing the secretion of acid by the stomach, we do not feel that the use of hydrogen peroxide can be recommended without con-

siderable reservation.

CONCLUSIONS

1. Hydrogen peroxide in solutions varying from one-half to three per cent when used as a gastric lavage may depress the acidity of the gastric contents. This may be true even when using histamine as the gastric secretory stimulus. However, in an occasional

dog and human subject a one or two per cent solution may induce a stimulating effect. The individual sus- ceptibility varies widely, a three per cent solution being required to depress significantly acid secretion to histamine in some individuals.

2. The stronger the solution of peroxide used, the greater is its effect in depressing the acidity.

3. Hydrogen peroxide influences the volume of gastric secretion in response to a stimulus. The volume of secretion may be either increased or de- creased. The volume changes do not correlate with the changes in acidity.

4. Hydrogen peroxide stimulates the secretion of mucus by the stomach.

5. The effects of hydrogen peroxide on gastric secretion are most marked immediately af ter lavage. Recovery occurs in f rom 24 hours to 15 days, depend- ing on the individual susceptibility and the concentra- tion of peroxide used.

6. Hydrogen peroxide is not a satisfactory means of depressing gastric acidity in patients. I t may be active in inducing hemorrhage from an ulcer. When used in the most effective concentrations it causes too much discomfort, and its effect in concentrations which do not cause discomfort cannot be predicted.

R E F E R E N C E S 1. Petri, A. : l lber den Einfluss des Wasserstoffsuperoxyds auf die

Sekretion des Magens. Arch. f . Verdauungskr. , 14:479-495, 1908. 2. Poly, F. : Klinische und experimentelle Er fahrungen fiber den

Einfluss des Wasserstoffsuperoxyds auf Hyperchlorhydrien und auf die Magensekreticn, Arch. f . Verdauungskr. , 16:700-703, 1910.

3. Hall, G. W. : The Trea tment of Gastric Hyperacidity with Hydrogen Peroxide. Boston l e d . and Surg. Jeer . , 164:846-848, 1911.

4. Winternitz, H . : Zur medikamentSsen Therapie der Hyperazidit~t, insbesondere fiber die Anwendung des Wasserstoffsuperoxyds. Deutsche reed. Wchnsvhr., 37:1390-1391, 1911.

5. Neilson, C. H. : Some Points in the Trea tment of Hyperacidity, Especially with Reference to the Use of Hydrogen Dioxide. J . A . M. A., 62:434-436, 1914.

6. Kelling, G. : Uber die Anwendung der verschledenen medikamen-

tSsen Mittel zur Herabsetzung der Salzsiiure beim Magengeschwiir, unter Beriicksichtigung der Physiologie der SalzsKure-Sekretion. Arch. f. Verdauungskr. , 26:287-350, 1920.

7. Dienst, C. : Uber den Einfluss des Wasserstoffsuperoxydes und des Magnesiumperhydrols auf die Magensekretion. Arch. I, Ver- dauungskr., 38:325-338, 1926.

8. Hurst , A. F. : Recent Advances in the Trea tment of Gastric n ~ - orders. Clin, Jour., 69:109-112. 1931.

9. Ivy, A. C., McCarthy, J . E. and Orndoff, B. H . : Studies on th e Effect of Roentgen Rays on Glandular Activity. J . A. M. A., 83:1977-1983, 1924.

10. Dawson, A. B. : Histological Changes in the Gastric Muco~a (Par ley Pouch) of the Dog Following Irradiation. Am. J ~ r . Roentgen- elegy and Radium Therapy, 13:320-325, 1925.

A Contribution to the Etiology oF Gall Stones II1. A study of the hydrogen-ion concentration of gall bladder bile and itsleffect upon gall stones

MAURICE FELDMAN, M.D., SAMUEL MORRISON, M.D., C. JELEFF CARR, M.S.

and JOHN C. KRANTZ, Jr., Ph.D.t

BALTIMORE, MARYLAND

I T has been definitely established that the hydrogen- ion concentration of gall bladder bile varies in dif-

ferent animals. In the herbivorous animals the bile is normally alkaline (1), while in the carnivorous

~ F r o m the research section of the Depar tment of Gastro-Enterology and the Depar tment of PharmaeoIogy, School of Medicine, Univer- sity of Maryland.

?Respectively, Assistant Professors of Gastro-Enterologyo Instructor in Pharmacology and Professor of Pharmoeology. The expense of this work was defrayed in pa r t by the Julius Friedenwald Experimental Fund.

Read before the American Association for the Advancement of Science. Atlantic City, N. J., December 28, 1936.

Submitted March 17, 1937.

animals the bile is more likely to be acid (2). On the other hand, in the human subject an omnivorous species, the hydrogen-ion concentration is close to the neutral point (3).

The fact has been well established that human gall stones wilt readily dissolve in dog's bile, the reaction of which is acid, the pH. averaging about 6.1 (1). We have observed that human gall stones do not dissolve in the guinea pig's gall bladder bile, which is normally definitely alkaline (4).