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Journal of the American College of Nutrition, Vol. 17, No. 6, 556-563 (1998)
Published by the American College of Nutrition

Zinc Metabolism in Patients with Exocrine Pancreatic Insufficiency

S.K. Dutta, MD, F. Procaccino, MD and R. Aamodt, PhD

Division of Gastroenterology, Department of Medicine, Sinai Hospital of Baltimore, Baltimore, Maryland; and Department of Nuclear Medicine, National Institute of Health, Bethesda, Maryland

Address reprint requests to: S.K. Dutta, MD, Sinai Hospital of Baltimore, Department of Medicine, Hoffberger Professional Center, Suite 51, 2435 West Belvedere Avenue, Baltimore, MD 21215-5271


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Objective: Metabolism of zinc was studied by administering radioactive zinc (Zn65), and by performing metabolic balance studies in eight patients with exocrine pancreatic insufficiency and eighteen control subjects.

Methods: Retention of radioactive zinc was measured by total body counter, and its urinary and fecal excretion by gamma scintillation counter. Metabolic balance studies were carried out by measuring dietary zinc intake as well as fecal and urinary excretion of zinc by atomic absorption spectrophotometry in this group of patients.

Results: These studies revealed a 50% reduction in intestinal absorption of Zn65 in patients with exocrine pancreatic insufficiency as compared to alcoholic and non-alcoholic control subjects. In addition, there was a 2 to 4 fold increase (p<0.05) in urinary excretion of zinc in subjects with pancreatic disease. In pancreatic insufficiency, reduced zinc absorption and increased urinary zinc excretion were balanced by lower (p<0.05) endogenous excretion of zinc as evidenced by reduced excretion of Zn65 in feces during the second 4-day period. The mean biological half-life of Zn65 tended to be lower in patients with pancreatic insufficiency as compared to alcoholic control subjects, however the difference did not reach statistical significance.

Conclusion: These observations indicate marked alterations in zinc metabolism in patients with advanced chronic pancreatic disease and provide greater insight into development of zinc deficiency in this group of patients.

Key words: zinc metabolism, exocrine pancreas, zinc excretion, zinc absorption, alcoholis


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The importance of zinc in the human disease process has been increasingly recognized in the last several decades [1–3]. Clinically, common gastrointestinal disorders associated with zinc deficiency include alcoholism, cirrhosis, malabsorption and pancreatitis [4,5]. Zinc deficiency and its malabsorption has been previously described in patients with alcoholic pancreatitis [5,6]. Using oral zinc absorption test, Boosalis et al have demonstrated impaired absorption of the pharmacological doses of zinc in patients with pancreatic insufficiency (PI) [7]. However, intestinal absorption of physiological amounts of zinc and its excretion has not been examined in patients with chronic pancreatitis. The effect of pancreatic disease on intestinal absorption of zinc is particularly interesting because it has been suggested that pancreatic gland produces a factor which facilitates zinc absorption in rats [8]. We reasoned that the pancreatic gland in man may also secrete a factor which facilitates intestinal absorption of zinc, and failure to secrete such a factor in advanced chronic pancreatic disease may lead to zinc malabsorption and alterations in zinc metabolism.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Study Subjects
Twenty-six male subjects with an average age of 50 years (range 28 to 62) were selected for the zinc metabolism studies. Eight subjects were patients with exocrine pancreatic insufficiency (PI) secondary to ethanol abuse. The diagnosis of exocrine pancreatic insufficiency was based on the previously published criteria [9]. The clinical features of all patients with PI are summarized in Table 1. All patients were clinically stable and were taking oral pancreatic enzyme therapy with meals at the time of the study. Each patient was taking 8 to 10 tablets of pancreatin (Lilly Co., Indianapolis, IN) three times daily with each meal. Six of the eight patients were also taking insulin therapy every day in variable doses. The mean (±SE) fecal fat excretion on enzyme therapy was 19.3 ± 10.3 g/day. Nutritionally, all patients had total body weight in the 10% range of ideal body weight based on Metropolitan Life Tables. Serum albumin was within normal range (3.5 to 5.2 g/dl) in all eight patients. Serum zinc levels were within normal range in six of the eight patients. Mildly low levels of serum zinc were observed in two cases (patient #2 and 7, Table 1).


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  		Clinical Features of Patients with Exocrine Pancreatic Insufficiency

 
Eighteen male subjects in the age range similar to PI patients were studied as control subjects. Eight subjects in the control group were sober alcoholics without pancreatic or hepatobiliary disease, and 10 subjects were healthy non-alcoholics. All alcoholic control subjects had a history of alcohol abuse in the past, however, none had ingested alcohol for at least 3 months prior to and during the study. None of the non-alcoholic control subjects had a history of ethanol abuse. Informed consent was obtained from each study subject. All study protocols were approved by the human Volunteers Research Committee at the University of Maryland at Baltimore and the Research and Development Committee of Veterans Administration Medical Center, Baltimore, MD.

Study of Radioactive Zinc Absorption and Excretion
Study Subjects:
Of the eight patients with PI, six alcoholic control subjects, and ten non-alcoholic control subjects were included in this study. Collection of fecal and urinary samples requiring hospitalization was completed in only five cases with PI, and five alcoholic control subjects.

Measurement of Zn65 for Total Body Retention of Zn65:
Radioactive Zinc (Zn65, 10µCi, purity 99%, specific activity 1.0–2.4 mCi/mg, New England Nuclear, Boston, MA) was administrated orally in all study subjects. The dose of radioactive zinc was administered with carrier zinc (77 µmols or 5 mg of elemental zinc as zinc chloride in 100 ml of deionized water). Total body retention of Zn65 was measured with a total body counter located at NIH, Bethesda, MD using a method previously described by Aamodt et al [10,11]. The counting efficiency of total body counter for Zn65 was 3.5%. In addition to measuring total body retention 2 hours after administration of Zn65, total body retention of all subjects was measured every week for 12 weeks, bimonthly for an additional 3 months, and monthly for 6 months. Values for percent total body retention of Zn65 were also used to calculate intestinal absorption of Zn65 by using the modified method of Heth and Hoekstra [12]. This method does not require long term retention pattern of Zn65 to calculate zinc absorption. In this method, intestinal absorption of zinc was derived from the retention measurements made on days 7, 14, and 21 after oral administration of Zn65.

Additionally, the biological half-life of Zn65 for pancreatic disease patients and alcoholic control subjects was determined by plotting percent total body retention values versus time (days). The biological half-time (t1/2) equals the total duration of time that was necessary to excrete 50% of the absorbed Zn65.

Preparation of Fecal Samples:
All 24-hour fecal samples were collected in the plastic bags and placed in paint cans which were stored in a large freezer at 20°C. Charcoal tablets were used as fecal marker. In control subjects osmotic laxative (sorbitol 70%) was occasionally used for regular bowel movements. At the time of homogenization, the samples were thawed and mixed with equal volume (ml) of distilled water and an aliquots of the homogenized fecal sample were saved. For determination of Zn65 related radioactivity excreted in the feces, an aliquot of homogenized fecal sample (10 g) was placed in a glass vial and the radioactivity counted using gamma scintillation counting (Parkard Model 578).

Preparation of Urine Samples for Measurement of Radioactive Zinc:
All 24-hour urine samples were collected and the volumes recorded. An aliquot (100 ml) of urine sample was saved in a plastic container, labeled and stored in a freezer at -20°C. Another aliquot of urine sample (10 ml) was placed in a glass vial and the radioactivity was measured directly in a gamma scintillation counter.

Calculation of Radioactive Zinc Excretion in Fecal and Urine Samples:
Daily amounts of Zn65 excreted in urine and stool were calculated by the following equations were used in calculations:

Where: A = Zn65excretion in feces or urine per 24-hours

B = Total radio activity administrated decay efficiency

To calculate A, the following formulas were used:


and net CPM = total CPM—background CPM.

To calculate B, the following formulas were used:

Where: ET = Elapsed time in days

e = Decay of radioisotope

t1/2 = Half-life of Zn65

From these data, cumulative excretion of Zn65 on a 4-day basis via fecal or urinary route was calculated in all study subjects.

Zinc Balance Study
Study Subjects:
Five patients with PI, and five sober alcoholic subjects (age range 46–62) were included in the zinc balance study.

Dietary Zinc Measurements:
Each subject was admitted to the metabolic unit and placed on a diet containing a known amount of zinc, with a mean (±SE) 13.02 ± 0.68 mg of zinc per day. To determine accurately the amount of zinc present in the diet, representative diet samples were saved each day and stored in a freezer until the time of zinc analysis performed according to the protocol of minerals and vitamins lab, USDA, Beltsville, MD. An aliquot of digested food sample was placed in the atomic absorption spectrophotometer (AAS; Perkin Elmer, Model 460) to determine the concentration of zinc in diet samples.

The amount of zinc present in pancreatic enzyme tablets was also measured by AAS after appropriate sample preparation. The mean (±SE) zinc content of these tablets was 30 ± 6 µg/tablet.

Preparation of Fecal Samples for Zinc Determination:
After equilibration period of five days, fecal samples were collected on a daily basis for ten days. Each 24-hour fecal sample was weighed, homogenized and an aliquot (10 g) of homogenized fecal sample was saved for zinc determination by AAS after proper digestion.

Preparation of Urine Samples for Zinc Determination:
A 24-hour urine sample was also collected daily for 10 days after an equilibration period of 5 days for each subject. The volume of 24-hour urine was recorded and an aliquot (100 ml) was saved in a plastic cup for zinc determination by AAS [13].

Measurement of Total Zinc Excretion:
The amount of total urinary and fecal zinc excretion on a daily basis was calculated by using the following formula:


Zinc balance (mg/day) for each study subject was calculated on a daily basis by subtracting the values of total urine plus fecal zinc excretion from the dietary zinc intake.

Statistical Analysis:
The statistical significance of the differences between test and control groups was assessed by analysis of variance [14].


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Zinc Absorption Study
Mean (±SE) percent intestinal absorption of radioactive Zn65 was significantly (p<0.05) lower in six patients with exocrine pancreatic insufficiently (PI) as compared to the six alcoholic controls (AC) subjects and 10 non-alcoholic control subjects (C)(C=61.3±2.8%, n=10; AC=59.5±7.8%, n=6; PI=32.3±5.3%, n=6) (Fig. 1). No statistically significant difference was noted in the percent Zn65 absorption between the two control groups.



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  		Fig. 1. Percent intestinal absorption of Zn65 was measured in six patients with pancreatic insufficiency (PI), six alcoholic control subjects (AC), and 10 non-alcoholic control subjects (C).

 
Total Body Retention for Zn65
Fig. 2 demonstrates mean (±SE) percent total body retention of Zn65 in two groups, each with five subjects. The percent retention of Zn65 in pancreatic insufficiently tended to be lower than in control subjects, however, the difference in the two groups was not statistically significant. Based on long-term total body retention curve of Zn65 in pancreatic disease as well as in control subjects, the biological half-life of Zn65 was calculated. As is shown in Fig. 3, despite impaired intestinal absorption and enhanced urinary excretion of Zn65 in pancreatic disease patients, the mean (±SE) biological half-life (t1/2) of Zn65 in pancreatic disease was not significantly different from control subjects (PI-t1/2: 368±18.4 days; C-t1/2: 358.6±29.0). These data indicate that the rate of excretion of absorbed Zn65 from the body was similar in both PI patients as well as in control subjects.



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  		Fig. 2. Percent total body retention of zinc was compared in six patients with pancreatic insufficiency (x---x) to six alcoholic control subjects (o---o) after oral administration of Zn65. The percent retention of Zn65 in patients with pancreatic insufficiency tended to be lower as compared to controls, however the difference was not statistically significant.

 


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  		Fig. 3. Biological half life of Zn65 in five patients with exocrine pancreatic insufficiency (PI), and five alcoholic controls based on total body retention of radioactive Zinc (Zn65). There was no statistical difference between the two groups.

 
Fecal Excretion of Zn65
Interestingly, mean (±SE) percent 4-day cumulative excretion of Zn65 in feces tended to be lower in patients with pancreatic insufficiency (PI) during all four periods of 4-days each (Fig. 4). The fecal excretion of Zn65 in patients with PI was significantly lower than in control subjects (P<0.05) during the second 4-day period only. These data suggest diminished endogenous zinc excretion in patients with advanced chronic pancreatic disease.



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  		Fig. 4. Mean (±SE) percent of 4-day cumulative excretion of Zn65 in feces in five patients with pancreatic insufficiency (hollow bar) and five alcoholic control subjects (solid bar) during four sequential periods (I, II, III and IV) after administration of radioactive zinc (Zn65). There was a significant reduction in percent excretion of Zn65 in patients compared to the control group (p<0.05) in the second 4-day period, suggesting reduced endogenous zinc excretion in patients with exocrine pancreatic insufficiency.

 
Excretion of Zn65 in the Urine
Mean (±SE) percent 4-day cumulative excretion of Zn65 in urine was noted to be higher in patients with PI as compared to the control subjects during all four periods of 4-days each (Fig. 5). This difference was statistically significant (p<0.05) during the first two periods. It is noteworthy that while percent cumulative excretion of Zn65 in urine remained fairly constant in control subjects, a trend towards gradual decrease in percent radioactivity in the urine was noted in PI patients.



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  		Fig. 5. Mean (±SE) percent 4-day cumulative excretion of Zn65 in urine in five patients with pancreatic insufficiency (hollow bar) and five alcoholic control subjects (solid bar) during four sequential periods (I, II, III and IV) after administration of radioactive zinc (Zn65). Urinary excretion of Zn65 was significantly (p<0.05) higher in pancreatic disease patients as compared to the control subjects during the first and second 4-day period after oral administration of radioactive zinc.

 
Zinc Balance Study
On mean daily dietary zinc intake of 13.0±0.7 mg, both patients with PI as well as controls were in positive zinc balance. The mean (±SE) daily positive zinc balance was slightly lower in pancreatic disease patient than in control subjects, however, the difference was not statistically significant (Fig. 6). Furthermore, mean zinc balance was negative on two separate days (day 1 and day 6) in pancreatic disease patients.



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  		Fig. 6. Mean (±SE) daily zinc balance (mg/day) was calculated for 8 consecutive days in five patients with pancreatic insufficiency (hollow bar) and five alcoholic controls (solid bar). Although, no statistically significant difference was observed between the two groups, the magnitude of positive zinc balance in pancreatic disease patients (PI) was lower than the alcoholic control subjects (AC), and found to be negative on 2 days.

 
Fecal Excretion of Zinc
During the balance study, the total excretion of fecal zinc (µg/g wet feces) was slightly higher during the entire period of balance study. However, the difference between the two groups was not statistically significant (Fig. 7). Despite a tendency for lower fecal zinc concentration in pancreatic disease (Fig. 8), mean fecal excretion of zinc on a daily basis (mg/day) was not statistically different in patients with PI as compared to controls due to higher stool weight secondary to mild persistent malabsorption. It is noteworthy that wide variations in fecal zinc excretions were observed in the same individual from day-to-day as well as in each group of study subjects.



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  		Fig. 7. Mean (±SE) total zinc excretion in feces (mg/day) was measured in five patients with pancreatic insufficiency (PI)(x---x), and five alcoholic control subjects (AC)(o---o) for 8 days during a zinc balance study. There was no significant difference between two groups. Fecal zinc in this study represents non-absorbed dietary zinc, and endogenous zinc excretion.

 


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  		Fig. 8. Mean (±SE) concentration of zinc in feces (µg/g wet stool) was measured in five patients with pancreatic insufficiency (PI)(x---x) and five alcoholic controls (AC)(o---o) during an eight day balance study. There was no significant difference between two groups during the 8-day period of study.

 
Urinary Excretion of Zinc
Mean urinary zinc excretion (mg/day) was two to four-fold higher (p<0.05) in PI patients as compared to the control subjects on day 1,2,3,5, and 7 of the balance study (Fig. 9). The increase in urinary zinc excretion in PI patients was associated with significant (p<0.05) increase in the concentration of zinc in urine in the same period (Fig. 10).



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  		Fig. 9. Mean (±SE) zinc excretion in urine (mg/day) was measured in five patients with pancreatic insufficiency (PI)(x---x) and five alcoholic controls (AC)(o---o) during an 8-day zinc balance study. There was 2 to 4 fold increase in urinary excretion in patients with pancreatic insufficiency as compared to alcoholic controls AC, which was statistically significant (*p<0.05).

 


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  		Fig. 10. Mean (±SE) concentration of zinc in urine (µg/ml) was measured in five patients with pancreatic insufficiency (PI)(x---x) and five alcoholic controls (AC)(o---o) during an 8-day zinc balance study. Mean urinary zinc concentration in patients with pancreatic disease was significantly higher (p<0.05) than in alcoholic controls.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Our data indicate about 50% reduction in intestinal absorption of small amounts of orally ingested zinc chloride in clinically stable patients with exocrine PI as compared to control subjects. To date, we are not aware of any other investigation which has examined in detail intestinal absorption of a physiological dose (5 mg) of orally ingested zinc in patients with PI receiving oral pancreatic enzyme therapy. A significant reduction in plasma zinc levels has also been reported after oral ingestion of a single pharmalogical dose (25 mg elemental zinc) of zinc sulfate in patients with PI and alcoholic subjects [7]. However, plasma zinc levels after a single large oral dose of zinc do not provide a precise quantitative measurements of zinc absorption. This is particularly true because plasma zinc levels are dependent on extraction of zinc by the liver and redistribution of zinc from the plasma pool [10,11]. Furthermore, the mechanism of intestinal zinc uptake and mucosal transport may be quite different for a small dose of orally-ingested zinc compound as compared to a large pharmalogical dose. Although there is no perfect method to measure zinc absorption from the intestines due to simultaneous endogenous excretion of zinc in the intestines, radioactive zinc administration with and without carrier zinc has been used to examine zinc absorption in healthy human subjects as well as in a variety of gastrointestinal disorders such as patients with alcoholism, inflammatory bowel disease, malabsorption, and colectomy [15]. Utilizing total body retention of Zn65 as indicator of zinc absorption, Aamodt et al reported percent zinc absorption of 62±11% in healthy control subjects who were administrated 10 µCi of carrier-free zinc [10]. Payton et al also reported 56±22% Zn65 absorption in healthy control subjects who were administrated 90 µmole (6 mg) of carrier-free zinc with 4 µCi of Zn65 [15]. We have also observed Zn65 absorption to be in the similar range in alcoholic and non-alcoholic control subjects (AC: 59±8%, C: 61±3%). Administration of 77 µmole (5 mg) of zinc chloride as carrier zinc in alcoholic control subjects did not significantly change percent absorption of Zn65 in our study. Similar observations have been made by Payton et al when the amount of carrier zinc administrated was limited to 180 µmole (12 mg).

The magnitude of reduction in (mean±SE) zinc absorption in PI patients appears to be similar to zinc malabsorption reported in Celiac Sprue (30±18%). Lesser magnitude of impairment in intestinal absorption of Zn65 has been reported in patients with inflammatory bowel disease [15,16]. Our observations clearly establish significant malabsorption of zinc in advanced chronic pancreatitis, however, the mechanism of zinc malabsorption in chronic PI remains quite unclear. Most of our understanding about the epithelial uptake, transcellular transport, and zinc fluxes from epithelial cells to vascular compartment is based on isolated intestinal rings and isolated vascularly perfused intestinal preparation from the rodents. Several studies have shown that zinc uptake across brush border into the enterocyte is in part an active energy dependent process and, in part, a passive carrier-mediated, diffusion process [17,18].

Several factors which modulate intestinal absorption in rodents and in man include: zinc nutriture, dietary factors, intraluminal factors, metallothionein and zinc binding ligand [19–23]. Several lines of evidence indicate that zinc absorption in man is homoeostatically regulated and depletion of zinc stores is associated with increase in zinc absorption [21]. Conversely, parenteral zinc load has been documented to impair zinc absorption by decreasing transfer of zinc from intestinal mucosa to systemic circulation. Zinc nutriture of patients with pancreatitis in our study was not significantly different from control subjects as determined by total body retention of radioactive zinc and plasma zinc levels (Fig. 2, Table 1). Thus, alterations in zinc nutriture cannot explain reduced zinc absorption in patients with pancreatic insufficiency.

Dietary factors are well known to alter zinc absorption from the intestine in rodents and humans. Utilizing the isolated intestinal perfusion preparation in rats, Smith et al demonstrated decrease in radioactive zinc uptake by phytate and prostaglandin E2 [24]. Significant reduction in zinc absorption as reflected by reduced area under curve of post prandial plasma level, has been reported after ingestion of a meal containing cheese, milk and coffee in human subjects [25]. Similarly, presence of calcium, phosphorus and copper have been noted to impair zinc absorption while ascorbic acid and citric acid have been demonstrated to enhance zinc absorption [25,26]. However, in our patients, zinc was administrated after an overnight fast, and no dietary ingestion was permitted for 2 hours after oral ingestion of Zn65 and zinc carrier. Therefore, dietary factors cannot account for reduced Zn65 absorption in patients with pancreatic disease.

Of all the intraluminal factors, changes in intraluminal pH of the upper small intestine may also play a role in reduced zinc absorption in pancreatic disease. Low intraluminal pH has been recorded in this group of patients during fasting and postprandial periods by our group and others [9,27]. In fact, altered folic acid absorption in pancreatic disease has been linked to low intraluminal pH in a group of patients with pancreatitis by Russell et al [28]. Although we did not examine this issue in our current study, we suspect that low intraluminal pH in the upper small intestine due to pancreatic disease can potentially alter zinc uptake by the enterocyte, its transcellular transport and flux into vascular compartment [22,24]. Other factors which appear important in modulating zinc absorption by the enterocytes include zinc metallothionein and zinc binding ligands. Zinc metallothionein is a low molecular weight, intracellular zinc binding protein which regulates the transcellular transport of newly absorbed zinc into the portal circulation [29,30]. Whether alterations in zinc metallothionein proteins in the enterocyte play a role in impaired zinc absorption in PI needs further investigation.

Finally, a variety of low molecular weight zinc binding ligands have been identified which facilitate zinc absorption [8,17,31]. Presence of citrate or picolinic acid in the diet promotes zinc absorption in young rats [26]. We suggest that a similar type of ligand may be secreted by the pancreatic gland in man which may be reduced or absent in patients with advanced chronic pancreatic disease resulting in impaired zinc absorption. This hypothesis can be tested by giving radiolabeled zinc with and without pancreatic enzyme supplements in patients with PI. However, these studies could not be performed in our patients due to: 1) long biological half-life of Zn65, and 2) cumulative radiation exposure of the patients.

In addition to impaired intestinal absorption, zincuria was observed in all cases with pancreatic insufficiency. Zinc loss in the urine was three times greater than the loss of zinc in control subjects. Zincuria of this magnitude has also been reported in patients with alcoholism, cirrhosis, diabetes mellitis, and nephrotic syndrome [32,33]. The precise mechanism of zincuria in patients with PI is not clearly understood. Zinc in plasma is carried by albumin and alpha 2 macro-globulin. In vitro studies by Prasad and Oberleas have demonstrated that 2 to 8% of the total serum zinc to be ultrafiltrable in man. Furthermore, addition of certain amino acids such as histidine, cysteine and glutamine increased ultrafiltrable zinc several folds [34]. Alterations in plasma proteins which normally carry zinc in the blood may account for zincuria in this group of patients. More recently, increased urinary zinc excretion has been linked to microalbuminuria in Type I diabetic patients [35]. Six of the eight patients in our study were insulin dependent diabetics. Furthermore, increased hyperzincuria has also been reported due to renal tubular dysfunction in patients with cancers [36]. Zincuria in patients with PI may be multifactorial occurring due to increased ultrafiltrable zinc in the plasma, microglobuminuria and/or impaired handling of filtered zinc by renal tubular cells. However, from a quantitative point of view, urinary loss of zinc constitutes a relatively small portion of daily zinc turnover.

Despite impaired zinc absorption and increased urinary zinc excretion, patients with pancreatic insufficiency maintained zinc balance for the most part on 15 mg/day zinc intake. This is most likely related to reduced endogenous fecal zinc loss due to diminished zinc excretion by the pancreas and intestines [5,36]. It is well recognized that pancreatic and biliary secretions in human contain large amount of zinc. Matsesh et al recovered highest amounts of zinc in the post-prandial samples collected from ligament of treitz of normal human subjects [37]. We suspect that markedly impaired pancreatic secretion in PI cases may have reduced endogenous zinc loss in feces. However, it is noteworthy that in the balance study, fecal zinc excretion (mg/day) was not statistically different from controls due to malabsorbed dietary zinc contributing to total fecal zinc.

Thus, several pieces of data from our investigations suggest significant alterations in zinc metabolism in patients with advanced chronic pancreatic disease. Interestingly, impaired intestinal absorption and enhanced urinary excretion of zinc is balanced by reduced endogenous zinc excretion in this group of patients receiving pancreatic enzyme therapy. However, a slight change in this delicate metabolic balance by clinical events such as noncompliance of pancreatic enzyme intake, reduced dietary zinc intake due to an attack of acute pancreatitis or ingestion of alcohol can lead to negative zinc balance and manifestations of zinc deficiency in this group of patients. These observations suggest that patients with exocrine pancreatic insufficiency are at high risk of developing zinc deficiency and should be carefully monitored for its clinical manifestations.


   ACKNOWLEDGMENTS
 
Supported by the Veterans Administration.

Received December 1, 1997. Accepted June 1, 1998.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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