EFFECTS OF CHRONIC ETHANOL ADMINISTRATION ON INTESTINAL ABSORPTION IN MAN IN THE ABSENCE OF NUTRITIONAL DEFICIENCY * John Lindenbaum Medical Service, Harlem Hospital Center New York, New York 10037 and College of Physicians and Surgeons Columbia University New York. New York 10032 Charles S. Lieber Department of Medicine Mount Sinai School of Medicine New York, New York I0029 and Section of Liver Disease and Nutrition Bronx Veterans Ad m inistra ti0 n Hospital Bronx, New York I0468 INTRODUCTION

Chronic alcoholism is frequently associated with impaired intestinal absorption.Id6 A high incidence of malabsorption of xylose, fat, vitamin Blz, folic acid, and thiamine has been documented in malnourished chronic alcoholics, with recovery of absorptive function after withdrawal of alcohol and ingestion of a nutritious Acute ethanol administration has been reported to cause impairment in intestinal absorption in hamsters? and man,I0 and chronic ethanol feeding in rats results in malabsorption of vitamin B l z l 1 and carbohydrates,l2 and decreased jejunal enzyme activitiesI3 despite adequate vitamin and protein intake. Chronic ethanol administration in man with a nutritious diet causes ultrastructural abnormalities in intestinal villous cells.I4 Since malnutrition alone may result in m a l a b ~ o r p t i o n ,l6~ ~the * relative importance of ethanol ingestion and depletion of nutrients in causing malabsorption in chronic alcoholic patients has been uncertain. To determine whether ethanol alone, in the absence of associated nutritional deficiency, causes impairment of small bowel function in man, we studied the effects of chronic alcohol administration under controlled metabolic ward conditions on intestinal absorption in human volunteers. SUBJECTS AND METHODS

The experimental design was similar to that used in several previous ~ t u d i e s . ' ~ *Eight ' ~ adult male volunteers, ages 43-56, with a history of chronic alcoholism, participated after giving informed consent. They had been hospitalized for 1 month or more before the study began and had been maintained on a hospital diet with vitamin supplements. At the time of study each subject *This work was supported in part by grants AA 00249, AA00224, and AM 12511 from the U.S. Public Health Service, and VA Project Number 5251-04.

228

79

10.6

14.4

17.3 17.8 8.8

14.5 10.2

5.9 3.1 6.lt

15.4 18.8 19.4

30.0 25.3

13.1

24 hr 27.4 11.9 5.9 6.7

48 hr 51.4 50.6 16.2 16.8 17.5 21.0

Ethanol

23.1 25.5 11.0

22.7 10.5

10.2 3.9 I .9

17.4

48 hr 33.0 20.6 9.1 11.0

t [ *7Co] BIZ given with 9 g pancreatin (Viokasea).

*Postethanol period, 8-22 days after cessation of alcohol administration.

8

7

10.2

20.9 15.4

6

5

3 4

2

1

24 hr 42.4 40.7* 12.1 12.1* 11.2* 17.0 10.5 18.3 14.7 *

Subject

Control (Pre- and/or Postethanol)

TABLE 1

25 33 25

23 37

34 21 28

21

Number of Days on Ethanol When Tested 13 26 21 31

46

46

46

66 46

60

60

46

Maximum Ethanol Dose % Total Caloric Intake

Biz During Control Periods and Ethanol Administration in Human Volunteers

% Urinary [57C0] BIZ Excretion

Percent Urinary Excretion of [ 57Co] Vitamin

1

\o

N

N

a

g -0

*%

5

g.

cc n,

CI

3

0-

F

*5

s

4

c 1

230

Annals New York Academy of Sciences

was asymptomatic and had a normal hemogram, liver function tests and biopsy morphology, serum folate and B12 concentrations, and xylose and B12 absorption test. Throughout each of 3 study periods on a metabolic ward, (preethanol control, ethanol, and postethanol control) they received daily vitamin supplements." The daily dose of supplemental folic acid was 200 pg, except in subjects 1 through 4, who took 1200 pg of pteroylglutamic acid by mouth daily. In addition, subjects 2 , 3, 5, 6 and 7 received 30 mg of folic acid parenterally during the control and ethanol periods. Protein intake comprised 12.5% of total calories (76-86 g/d) in 6 subjects and 25% in 2 (150 g/d, subjects 3 and 5). Fat intake in the subjects in whom lipid balance studies were performed is shown in TABLE 4. During the alcohol period, ethanol was substituted isocalorically for carbohydrate as in previously reported s t u d i e ~ , ' ~and ~ ' ~comprised 46-6676 of total caloric intake (TABLE 1) or 173-253 g/day. Absorption studies were performed after 11-38 days of ethanol administration.

Absorption Studies

Vitamin B12 absorption was studied by the urinary excretion method of S ~ h i l l i n g 'after ~ 7Co-cyanocobalamin(0.75 pg;specific activity 0.6-1 .O pCi/pg) was given orally with intrinsic factor concentrate. Two I-mg "flushing" doses of nonradioactive B12 were given at 2 and 24 hours and urine collected for 48 hours. Five-hour urinary xylose excretion and 2-hour serum xylose concentrations were measured by the method of Roe and RiceZo after the oral administration of 25 g of D-xylose in the fasting state. Three subjects also received 20 g of pyrogen-free xylose as a 10% solution intravenously over a 30-minute period on other occasions; serum xylose was measured at 30-minute intervals for 3 hours and urinary xylose excretion for 5 and 24 hours after the infusion. Fecal fat excretion was determined by the method of van de Kamer2* in continuous 72-hour specimens obtained throughout the ethanol and control periods.

TABLE 2 Urinary Xylose Excretion After an Oral Dose During Control Periods and Ethanol Administration in Human Volunteers* Subject

Reethanol Period

1 2 3 5 6

5.6 7.1 6.4 8.5 6.4 5.1

I

Ethanol Period 8.2(21) 9.9(24), 11.5(30) 8.7(24) t4.4(11), 12.0*(14), 11.1*(16) 8.0(14), 10.6*, 8.0*(32) 5.1*(16), 8.5(20), 8.0*(32)

Postethanol Period 6.3 6.0 8.5 6.0 6.1

*The urinary excretion of xylose in grams over a 5-hour collection period after the oral administration of 25 grams is shown before, during, and after chronic ethanol ingestion. Numbers in parenthesis indicate days on alcohol. Asterisks denote occasions on which ethanol was withheld during the 5 hours of the test. Postethanol studies were done 5-12 days after cessation of alcohol administration.

Lindenbaum 8c Lieber: Intestinal Absorption 14

23 1

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In

; 12 -

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2

c

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W

a 0 X W W V)

8 6 -

0 J

>-

*

4 -

a

a

5

a

2 -

3

0-

I

I

Before

Ethonol

I After Etbuno/

Ethonol

FIGURE 1. Urinary xylose excretion after an oral 25g dose in 6 subjects during control and ethanol periods. In 4 subjects who were tested more than once during the ethanol period. mean values are shown.

RESULTS

Vitamin B12Absorption

The 24- and 48-hour urinary excretion of 57Co-cyanocobalamin is shown in TABLE 1 . The data from the first 4 subjects have been previously reported.22 B12 excretion during the period of ethanol administration was less than control values in subjects 1-6 (p 0.05 at both 24 and 48 hours). In 3 subjects the 24-hour excretion during the ethanol period fell below the lower limit of normal for the test in our laboratory (7.5%). In 2 subjects (nos. 7 and 8), both on the lowest daily ethanol dose, no depression of vitamin B12 absorption was seen during alcohol administration. Thus, a decrease in B12 absorption was seen in each of the 3 subjects ingesting ethanol as 60-66% of caloric intake but only in 3 of the 5 receiving alcohol as 46% of intake. There was no significant difference in 24-hour urine volumes between ethanol and control periods (mean f 1 SD, control periods 1837 f 7 2 0 ml, ethanol 2146 f 929 ml, p > 0.5). The concomitant administration of a pancreatic extract did not result in normal vitamin B12 absorption during the alcohol period (subject 5 , TABLE 1).

Effects of chronic ethanol administration on intestinal absorption in man in the absence of nutritional deficiency.

EFFECTS OF CHRONIC ETHANOL ADMINISTRATION ON INTESTINAL ABSORPTION IN MAN IN THE ABSENCE OF NUTRITIONAL DEFICIENCY * John Lindenbaum Medical Service,...
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