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Malabsorption of vitamin B12 after vagotomy
Malabsorption of Vitamin B12 after Vagotomy Arthur M. Streeter, MSc, Concord, New South Wales, Australia Balasubramaniam Duraiappah, MB, BS, FRACS, Concord, New South Wales, Australia Robert Boyle, MB, BS, Concord, New South Wales, Australia Barry J. O’Neill, MRCPath, MRACP, FRCPA, Concord, New South Wales, Australia Murray 1. Pheils, MCh, FRCS, FRACS, Concord, New South Wales, Australia
Vitamin Blz from food sources is bound to protein. Release of protein-bound vitamin B12 prior to absorption probably occurs in the stomach and appears to involve acid and pepsin [I-3]. Conventional tests of vitamin BYZ absorption use unbound vitamin Blz as the test dose and thus do not detect any defect in the subject’s ability to release protein-bound vitamin Blz prior to absorption. Postgastrectomy subjects with normal absorption of unbound vitamin B12 sometimes have a vitamin Bl2 deficiency [4]. In a previous study, we noted a decrease in the mean serum level of vitamin Blz after vagotomy and drainage, although there was no defect in the absorption of unbound vitamin Blz. In this study, the effect of vagotomy and drainage procedures on vitamin B12 absorption was studied using a test dose of vitamin B12 that had been bound to chicken serum before ingestion. Material and Methods A group of twenty male patients were studied more than five years after they had undergone vagotomy combined with a drainage procedure. A control group of twelve male staff members and medical students were also studied. In addition, three male patients with proved pernicious anemia were investigated. Three patients were tested before they underwent vagotomy and a drainage procedure and were retested ten days after operation. Bound
Vitamin
B12 Absorption
Test. The oral dose
prepared by mixing 0.8 to 1.0 fig of cyanocobalamin tagged with radioactive cobalt (57Co B1z),‘ll&i/kg,‘with 3 ml of chicken serum and incubating the mixture at room temperature for at lea& fifteen minutes. After the dose was given to the subject, an intramuscular injection of 1,000 pg of nonradioactive vitamin Blz was adminiswas
From the Department of Surgery and Division of Haematology. Repatriation General Hospital, Concord, New South Wales, Australia. Reprint requests should be addressed to Mr Arthur M. Streeter, Haematology Division, Repatriation General Hospital, Concord, New South Wales, 2139, Australia.
340
tered, and the urine was collected for twenty-four hours. The radioactivity in the urine was measured and expressed as a percentage of the dose. Between eight and ten hours after the dose was given, a blood sample was collected and the radioactivity in the plasma was measured and expressed as a percentage of the dose present in 1 L of plasma [5,6]. The subjects were not fasted in order to disturb conditions as little as possible by the test procedure and to minimize subject inconvenience. The radioactivity of plasma and urine samples was counted in a crystal with a 3 inch well using pulse height analysis. Samples were routinely counted for thirty minutes each to minimize counting errors. The chicken serum used to bind the oral dose of 57Co Blz had a vitamin Blz binding capacity of 0.47 Ng/ml and a nonradioactive vitamin B12 content of 0.27 ng/ml. Oral doses prepared as just described were extracted with albumin-coated charcoal [7] to determine whether any of the 57Co B12 remained free. This technic showed that 97 to 101 per cent of the 57Co Blz in the dose was bound. Hollander Insulin Test. This test was carried out according to the method of Ross and Kay [8], except that fluoroscopic examination was used to ensure that the nasogastric tube was correctly positioned in the stomach. The results of this test were scored as positive or negative according to published criteria [8,9]. When there was no significant acid secretion on insulin stimulation, that is, a negative test result, vagotomy was considered successful. In Vitro Effect of Acid on 5lCo B12 Bound to Chicken Serum. Chicken serum was saturated with s7Co Blz and
excess unbound 57Co B12 was removed with albumincoated charcoal [7]. Aliquots of the bound 57Co Blz were added to tubes containing various concentrations of hydrochloric acid (2 to 200 mEq/L) and to a control tube containing phosphate buffer (pH 7.4) instead of hydrochloric acid. After thirty minutes of incubation at room temperature with occasional mixing, any 57Co B12 released was removed with albumin-coated charcoal. The radioactivity adsorbed to this albumin-coated charcoal was divided by the total radioactivity added to obtain the percentage of the bound vitamin B12 released by a given concentration of hydrochloric acid.
The American Journal of Surgery
Vitamin
.
81~ Malabsorption
after
Vagotomy
. .
.
. ..
0.
.
0 b.0
.
.
.
. :
.
. . .
: .
.
. .
l .
. 0
b..
.:&:a HIT +
L POST
HIT -
NORMALS
.
.
.
..
L POST
VAGOlOMY -I
.
.::.
.
a..
HIT+
P.A.
.
.
HIT -
NORMALS
F?A.
VAGOTOMY _I
Figure 1. Comparison of the twenty-four hour urinary excretion of an oral dose of bound 57Co 6s. HIT+ indicates patients who had posftive resufts on Holiander insulin testing more than five years atter vagotomy and drainage. HIT- indicates patients who had negative resutts on Hollander insulin testkg more than five years after vagotomy and drainage. P.A. indicates patients with proved pernicious anemia.
Figure 2. Ccmparfson of the pfasma level after an oral dose of bound s7Co &. HITS indicates patknts who had posftive resufts on Holiantkr InsuNn testing more than Nve years after vagotomy and drainage. HfT- indicates patfents who had negative resufts on Hollander testfng more than five years after vagotomy and drainage. P.A. indkates patients with proved pernicious anemia.
Results
Three patients had urinary excretion values of 2.73, 3.20, and 2.32 per cent before operation, which were markedly decreased to 0.91, 0.13, and 0.46 per cent, respectively, ten days after vagotomy and drainage. The possibility that excretion of the bound 57Co Bis was delayed was investigated by collecting an additional twenty-four hour urine sample in some cases. Table I shows the results, which do not suggest that any significant quantities of 57Co Bis
The results of the bound vitamin Bis absorption test are shown in Figures 1 and 2. The patients with successful vagotomy (as judged by the Hollander insulin test) had a mean twenty-four hour urinary excretion of 0.22 per cent of the test dose. This was much lower than that in the normal subjects (mean, 2.18 per cent) or in the patients with unsuccessful vagotomy (mean, 1.80 per cent). The results in the group with successful vagotomy were significantly different (p <
TABLE I
Urinary Excretion of %o B12after an Oral Dose of 0.8 to 1.0 pg of %o B12 Bound to Chicken
Serum Urinary Excretion (per cent of dose)
0 to 24 Hours Type of Subject Normal Normal Normal Postvagotomy Postvagotomy
-
after Dose
24 to 48 Hours after Dose
2.78 1.36
0.04 0.04
1.88
0.10
0.07 0.20
0.00 0.05
341
l
lm
.
0
.
Comments
b
a .
MAXIMUM
GASTRIC ACID
( mEq/hr )
Figure 3. Relationship between maximal gastric acid output and fhe absorption of an oral dose of bound 57Co BW in patients more than five years after vagotomy and drainage. Gastric acid outpui was measured before and affer insulin stimulation and the higher value was taken as the maximal gastric acid output. were excreted after the first twenty-fQur hour period. The gastric acid output of the postvagotomy patients before and after insulin stimulation is related to the bound vitamin B12 absorption in Figure 3. The amount of bound 57Co B12 absorbed appeared to be roughly proportional to the gastric
“iv
40
ACID
PRESENT
00
00
100
$I-200
( mEq HCI /Mei )
Figure 4. Effect of acid on viiamin B,, bound to chicken serum. Maximal release of the bound vitamin BI1 occurred at hydrochloric acid concentrations below 10 mEq/L.
342
acid output in these patients. The results of the in vitro experiments regarding acid release of bound vitamin B12 are shown in Figure 4. Low concentrations of acid released about 40 per cent of the 57Co Blz bound to chicken serum. Increasing the acid concentration actually reduced the proportion of bound 57Co Blz released until a plateau was reached at 40 to ‘200 mEq/L, when about 20 per cent of the bound 57Co B12 was released.
Muyshondt and Schwartz [II] showed that vagotomy and pyloroplasty reduced the urinary excretion of an oral dose of vitamin B12 in dogs. The addition of intrinsic factor substantially increased the urinary excretion values, although the mean value was still less than half the mean value prior to operation. Cox et al [12] showed that urinary excretion was reduced in human subjects four years after vagotomy and gastrojejunostomy, but they attached little importance to this since the serum levels of vitamin Blz in their patients were considered normal. Since 1964 few authors have reported vitamin B12 absorption studies after vagotomy, but the incidence of serum levels of vitamin BQ that were low or in the low range of normal has been noted fairly often [12-161. In a previous survey of sixty-three patients after vagotomy and drainage, we could not demonstrate any defect in the absorption of unbound 57Co B12, although the mean serum level of vitamin Blz was depressed. Mahmud, Ripley, and Doscherholmen [4] showed that deficiency of vitamin B12 after gastrectomy may not be detected by absorption tests using unbound vitamin Blz. More recently Doscherholmen and Swaim [17] showed that a group of postgastrectomy patients with low serum levels of vitamin Blz and normal absorption of unbound vitamin Blz had malabsorption of 57Co Blz when this was incorporated into eggs. Our results suggest that a similar phenomenon occurs after vagotomy, that is, normal absorption of unbound vitamin Blz but subnormal absorption of bound vitamin B12. The release of bound vitamin Blz by acid in vitro and the rough correlation between gastric acidity and bound vitamin B12 absorption in vivo indicate that acidity may be a critical factor in the release of vitamin Blz from food sources prior to absorption. Thus, any disease OF surgical procedure that substantially reduces gastric acid may be suspected of reducing absorption of protein-bound vitamin Blz.
The American Journal of Surgery
Vitamin B12 Malabsorption after Vagotomy
Binding 57Co B12 to chicken serum considerably reduced the amount absorbed, even in normal subjects. Doscherholmen and Swaim [17] noted a similar effect when 57Co Blz was incorporated into eggs. Much higher absorption of @X20 B12 incorporated into meat protein has been reported 1181. It seems probable that the vitamin Blz value of a given food not only is a function of its vitamin B1z content but also is related to the ease with which the vitamin B12 is released by normal gastric juice. The good correlation between the results of the Hollander insulin test and the absorption of bound vitamin B12 in our patients suggests that the absorption test may have some potential usefulness as an alternative to the Hollander test. The results of the test for bound vitamin Blz absorption might be affected by the level of gastric intrinsic factor as well as by the Ievel of acid. However, since intrinsic factor output is known to be decreased after vagotomy [19], this should improve (or at least not reduce) the ability of the test to discriminate between successful and unsuccessful vagotomy. If desired, any effect of intrinsic factor output could be eliminated by administering a preparation of intrinsic factor with the oral dose. The Hollander test is time-consuming and involves nasogastric intubation and intravenous injection of insulin. Furthermore, the positioning of the nasogastric tube and the possibility of bile reflux may affect the reliability of this test. The proportion of gastric juice secreted that is actually recovered may also be subject to some variation. In contrast, the bound vitamin B12 absorption test is quick and safe, and the only inconvenience to the patient is the intramuscular injection of vitamin Blz and a twentyfour hour urine collection.
Summary After successful vagotomy, patients usually have normal absorption of s7Co Blz but serum levels of vitamin Blz are often low or in the low range of normal. To determine if low gastric acid levels might reduce the patients’ ability to free vitamin BIZ from food binders, the absorption of 57Co B12 bound to chicken serum was studied in twenty patients more than five years after they had undergone vagotomy and a drainage procedure. All of the twelve patients with successful vagotomy showed malabsorption of the bound 57Co B12. Seven of the eight patients with unsuccessful va-
voluma 128, September 1974
gotomy showed normal absorption. The amount of bound 57Co Blz absorbed was roughly proportional to gastric acidity. Furthermore, acid was shown to release bound 57Co Blz in vitro. The test of absorption of bound 57Co Blz may be a convenient substitute for the Hollander insulin test. References 1. Cooper BA, Castle WB: Sequential mechanisms in the enhanced absorption of vitamin Bj2 by intrinsic factor in the rat. JC/in lnvest39: 199, 1960. 2. Schade SG. Schilling RF: Effect of pepsin on the absorption of food vitamin B12 and iron. Am J C/in Nutr 20: 636, 1967. 3. Adams JF, Kennedy EA. Thompson J, et al: The effect of acid peptic digestion on free and tissue-bound cobalarmins. BrJNutr22: 111, 1968. 4. Mahmud K, Ripley D. Doscherholmen A: Vitamin B12 absorption tests. Their unreliability in postgastrectomy states. JAMA 216: 1167, 1971. 5. Cottrall MF, Wells DG. Trott NG, et al: Radioactive vitamin BIZ absorption studies: comparison of the whole-body retention, urinary excretion, and eight-hour plasma levels of radioactive vitamin B12. Blood38: 604, 1971. 6. Alexander IS, Shum HY, Streeter AM, et al: Discrepancies between the urinary-excretion and plasma-level methods of measuring vitamin Eij2 absorption. &fed J A& 1: 179, 1972. 7. Shum H-Y, O’Neill BJ. Streeter AM: Effect of pH on albumincoated charcoal. J C/in Path 25: 834, 1972. 8. Ross B, Kay AW: The insulin test after vagotomy. Gastroenterology46: 379, 1964. 9. Bank S, Marks IN, Louw JH: Histamine and Insulin stimulated gastric acid secretion after selective and truncal vagotomy. G&8: 36. 1967. 10. Campbell RC: Statistics for Biologists. Cambridge, Cambridge University Press, 1967, p 49. 11. Muyshondt E, Schwartz SI: Vitamin B,, absorption following vagotomy and gastric surgery. Ann Surg 160: 788, 1964. 12. Cox AG, Bond MR, Podmore DA, et al: Aspects of nutrition after vagotomy and gastrojejunostomy. Br A&d J 1: 465, 1964. 13. Hopkinson BR: A comparison of the results of vagotomy and pyloroplasty with vagotomy and gastro-enterostomy for chronic duodenal ulcer. Br J Surg 53: 1046, 1966. 14. Schofield PF, Watson-Williams EJ, Sorrel1 VF: Vagotomy and pyloric drainage fdr chronic duodenal ulcer. Long term results. Arch Surg95: 615, 1967. 15. Johnson HD, Khan TA, Srivatsa R, et al: The late nutritional and haematological effects of vagal section. Br J Surg 56: 4, 1969. 16. Wheldon EJ, Venerables CW, Johnston ID: Late metabolic sequelae of vagotomy and gastroenterostomy. Lancet 1: 437, 1970. 17. Doscherholmen A, Swaim WR: Impaired assimilation of egg Co5’ vitamin B12 in patients with hypochlorhydria and achlorhydria and after gastric resection. Gastroenterology 64: 913, 1973. 18. Heyssell RM, Bozian RC, Darby WJ. et al: Vitamin B12 turnover in man. The assimilation of vitamin B12 from natural foodstuff by man and estimates of minimal daily dietary requirements. Am J Clin Nutr 18: 176, 1966. 19. Adams JF, Cox AG. Kennedy EH, et al: Effect of medical and surgical vagotomy on intrinsic factor secretion. Br Med J 3: 473, 1967.
343
Vitamin Blz from food sources is bound to protein. Release of protein-bound vitamin B12 prior to absorption probably occurs in the stomach and appears to involve acid and pepsin [I-3]. Conventional tests of vitamin BYZ absorption use unbound vitamin Blz as the test dose and thus do not detect any defect in the subject’s ability to release protein-bound vitamin Blz prior to absorption. Postgastrectomy subjects with normal absorption of unbound vitamin B12 sometimes have a vitamin Bl2 deficiency [4]. In a previous study, we noted a decrease in the mean serum level of vitamin Blz after vagotomy and drainage, although there was no defect in the absorption of unbound vitamin Blz. In this study, the effect of vagotomy and drainage procedures on vitamin B12 absorption was studied using a test dose of vitamin B12 that had been bound to chicken serum before ingestion. Material and Methods A group of twenty male patients were studied more than five years after they had undergone vagotomy combined with a drainage procedure. A control group of twelve male staff members and medical students were also studied. In addition, three male patients with proved pernicious anemia were investigated. Three patients were tested before they underwent vagotomy and a drainage procedure and were retested ten days after operation. Bound
Vitamin
B12 Absorption
Test. The oral dose
prepared by mixing 0.8 to 1.0 fig of cyanocobalamin tagged with radioactive cobalt (57Co B1z),‘ll&i/kg,‘with 3 ml of chicken serum and incubating the mixture at room temperature for at lea& fifteen minutes. After the dose was given to the subject, an intramuscular injection of 1,000 pg of nonradioactive vitamin Blz was adminiswas
From the Department of Surgery and Division of Haematology. Repatriation General Hospital, Concord, New South Wales, Australia. Reprint requests should be addressed to Mr Arthur M. Streeter, Haematology Division, Repatriation General Hospital, Concord, New South Wales, 2139, Australia.
340
tered, and the urine was collected for twenty-four hours. The radioactivity in the urine was measured and expressed as a percentage of the dose. Between eight and ten hours after the dose was given, a blood sample was collected and the radioactivity in the plasma was measured and expressed as a percentage of the dose present in 1 L of plasma [5,6]. The subjects were not fasted in order to disturb conditions as little as possible by the test procedure and to minimize subject inconvenience. The radioactivity of plasma and urine samples was counted in a crystal with a 3 inch well using pulse height analysis. Samples were routinely counted for thirty minutes each to minimize counting errors. The chicken serum used to bind the oral dose of 57Co Blz had a vitamin Blz binding capacity of 0.47 Ng/ml and a nonradioactive vitamin B12 content of 0.27 ng/ml. Oral doses prepared as just described were extracted with albumin-coated charcoal [7] to determine whether any of the 57Co B12 remained free. This technic showed that 97 to 101 per cent of the 57Co Blz in the dose was bound. Hollander Insulin Test. This test was carried out according to the method of Ross and Kay [8], except that fluoroscopic examination was used to ensure that the nasogastric tube was correctly positioned in the stomach. The results of this test were scored as positive or negative according to published criteria [8,9]. When there was no significant acid secretion on insulin stimulation, that is, a negative test result, vagotomy was considered successful. In Vitro Effect of Acid on 5lCo B12 Bound to Chicken Serum. Chicken serum was saturated with s7Co Blz and
excess unbound 57Co B12 was removed with albumincoated charcoal [7]. Aliquots of the bound 57Co Blz were added to tubes containing various concentrations of hydrochloric acid (2 to 200 mEq/L) and to a control tube containing phosphate buffer (pH 7.4) instead of hydrochloric acid. After thirty minutes of incubation at room temperature with occasional mixing, any 57Co B12 released was removed with albumin-coated charcoal. The radioactivity adsorbed to this albumin-coated charcoal was divided by the total radioactivity added to obtain the percentage of the bound vitamin B12 released by a given concentration of hydrochloric acid.
The American Journal of Surgery
Vitamin
.
81~ Malabsorption
after
Vagotomy
. .
.
. ..
0.
.
0 b.0
.
.
.
. :
.
. . .
: .
.
. .
l .
. 0
b..
.:&:a HIT +
L POST
HIT -
NORMALS
.
.
.
..
L POST
VAGOlOMY -I
.
.::.
.
a..
HIT+
P.A.
.
.
HIT -
NORMALS
F?A.
VAGOTOMY _I
Figure 1. Comparison of the twenty-four hour urinary excretion of an oral dose of bound 57Co 6s. HIT+ indicates patients who had posftive resufts on Holiander insulin testing more than five years atter vagotomy and drainage. HIT- indicates patients who had negative resutts on Hollander insulin testkg more than five years after vagotomy and drainage. P.A. indicates patients with proved pernicious anemia.
Figure 2. Ccmparfson of the pfasma level after an oral dose of bound s7Co &. HITS indicates patknts who had posftive resufts on Holiantkr InsuNn testing more than Nve years after vagotomy and drainage. HfT- indicates patfents who had negative resufts on Hollander testfng more than five years after vagotomy and drainage. P.A. indkates patients with proved pernicious anemia.
Results
Three patients had urinary excretion values of 2.73, 3.20, and 2.32 per cent before operation, which were markedly decreased to 0.91, 0.13, and 0.46 per cent, respectively, ten days after vagotomy and drainage. The possibility that excretion of the bound 57Co Bis was delayed was investigated by collecting an additional twenty-four hour urine sample in some cases. Table I shows the results, which do not suggest that any significant quantities of 57Co Bis
The results of the bound vitamin Bis absorption test are shown in Figures 1 and 2. The patients with successful vagotomy (as judged by the Hollander insulin test) had a mean twenty-four hour urinary excretion of 0.22 per cent of the test dose. This was much lower than that in the normal subjects (mean, 2.18 per cent) or in the patients with unsuccessful vagotomy (mean, 1.80 per cent). The results in the group with successful vagotomy were significantly different (p <
TABLE I
Urinary Excretion of %o B12after an Oral Dose of 0.8 to 1.0 pg of %o B12 Bound to Chicken
Serum Urinary Excretion (per cent of dose)
0 to 24 Hours Type of Subject Normal Normal Normal Postvagotomy Postvagotomy
-
after Dose
24 to 48 Hours after Dose
2.78 1.36
0.04 0.04
1.88
0.10
0.07 0.20
0.00 0.05
341
l
lm
.
0
.
Comments
b
a .
MAXIMUM
GASTRIC ACID
( mEq/hr )
Figure 3. Relationship between maximal gastric acid output and fhe absorption of an oral dose of bound 57Co BW in patients more than five years after vagotomy and drainage. Gastric acid outpui was measured before and affer insulin stimulation and the higher value was taken as the maximal gastric acid output. were excreted after the first twenty-fQur hour period. The gastric acid output of the postvagotomy patients before and after insulin stimulation is related to the bound vitamin B12 absorption in Figure 3. The amount of bound 57Co B12 absorbed appeared to be roughly proportional to the gastric
“iv
40
ACID
PRESENT
00
00
100
$I-200
( mEq HCI /Mei )
Figure 4. Effect of acid on viiamin B,, bound to chicken serum. Maximal release of the bound vitamin BI1 occurred at hydrochloric acid concentrations below 10 mEq/L.
342
acid output in these patients. The results of the in vitro experiments regarding acid release of bound vitamin B12 are shown in Figure 4. Low concentrations of acid released about 40 per cent of the 57Co Blz bound to chicken serum. Increasing the acid concentration actually reduced the proportion of bound 57Co Blz released until a plateau was reached at 40 to ‘200 mEq/L, when about 20 per cent of the bound 57Co B12 was released.
Muyshondt and Schwartz [II] showed that vagotomy and pyloroplasty reduced the urinary excretion of an oral dose of vitamin B12 in dogs. The addition of intrinsic factor substantially increased the urinary excretion values, although the mean value was still less than half the mean value prior to operation. Cox et al [12] showed that urinary excretion was reduced in human subjects four years after vagotomy and gastrojejunostomy, but they attached little importance to this since the serum levels of vitamin Blz in their patients were considered normal. Since 1964 few authors have reported vitamin B12 absorption studies after vagotomy, but the incidence of serum levels of vitamin BQ that were low or in the low range of normal has been noted fairly often [12-161. In a previous survey of sixty-three patients after vagotomy and drainage, we could not demonstrate any defect in the absorption of unbound 57Co B12, although the mean serum level of vitamin Blz was depressed. Mahmud, Ripley, and Doscherholmen [4] showed that deficiency of vitamin B12 after gastrectomy may not be detected by absorption tests using unbound vitamin Blz. More recently Doscherholmen and Swaim [17] showed that a group of postgastrectomy patients with low serum levels of vitamin Blz and normal absorption of unbound vitamin Blz had malabsorption of 57Co Blz when this was incorporated into eggs. Our results suggest that a similar phenomenon occurs after vagotomy, that is, normal absorption of unbound vitamin Blz but subnormal absorption of bound vitamin B12. The release of bound vitamin Blz by acid in vitro and the rough correlation between gastric acidity and bound vitamin B12 absorption in vivo indicate that acidity may be a critical factor in the release of vitamin Blz from food sources prior to absorption. Thus, any disease OF surgical procedure that substantially reduces gastric acid may be suspected of reducing absorption of protein-bound vitamin Blz.
The American Journal of Surgery
Vitamin B12 Malabsorption after Vagotomy
Binding 57Co B12 to chicken serum considerably reduced the amount absorbed, even in normal subjects. Doscherholmen and Swaim [17] noted a similar effect when 57Co Blz was incorporated into eggs. Much higher absorption of @X20 B12 incorporated into meat protein has been reported 1181. It seems probable that the vitamin Blz value of a given food not only is a function of its vitamin B1z content but also is related to the ease with which the vitamin B12 is released by normal gastric juice. The good correlation between the results of the Hollander insulin test and the absorption of bound vitamin B12 in our patients suggests that the absorption test may have some potential usefulness as an alternative to the Hollander test. The results of the test for bound vitamin Blz absorption might be affected by the level of gastric intrinsic factor as well as by the Ievel of acid. However, since intrinsic factor output is known to be decreased after vagotomy [19], this should improve (or at least not reduce) the ability of the test to discriminate between successful and unsuccessful vagotomy. If desired, any effect of intrinsic factor output could be eliminated by administering a preparation of intrinsic factor with the oral dose. The Hollander test is time-consuming and involves nasogastric intubation and intravenous injection of insulin. Furthermore, the positioning of the nasogastric tube and the possibility of bile reflux may affect the reliability of this test. The proportion of gastric juice secreted that is actually recovered may also be subject to some variation. In contrast, the bound vitamin B12 absorption test is quick and safe, and the only inconvenience to the patient is the intramuscular injection of vitamin Blz and a twentyfour hour urine collection.
Summary After successful vagotomy, patients usually have normal absorption of s7Co Blz but serum levels of vitamin Blz are often low or in the low range of normal. To determine if low gastric acid levels might reduce the patients’ ability to free vitamin BIZ from food binders, the absorption of 57Co B12 bound to chicken serum was studied in twenty patients more than five years after they had undergone vagotomy and a drainage procedure. All of the twelve patients with successful vagotomy showed malabsorption of the bound 57Co B12. Seven of the eight patients with unsuccessful va-
voluma 128, September 1974
gotomy showed normal absorption. The amount of bound 57Co Blz absorbed was roughly proportional to gastric acidity. Furthermore, acid was shown to release bound 57Co Blz in vitro. The test of absorption of bound 57Co Blz may be a convenient substitute for the Hollander insulin test. References 1. Cooper BA, Castle WB: Sequential mechanisms in the enhanced absorption of vitamin Bj2 by intrinsic factor in the rat. JC/in lnvest39: 199, 1960. 2. Schade SG. Schilling RF: Effect of pepsin on the absorption of food vitamin B12 and iron. Am J C/in Nutr 20: 636, 1967. 3. Adams JF, Kennedy EA. Thompson J, et al: The effect of acid peptic digestion on free and tissue-bound cobalarmins. BrJNutr22: 111, 1968. 4. Mahmud K, Ripley D. Doscherholmen A: Vitamin B12 absorption tests. Their unreliability in postgastrectomy states. JAMA 216: 1167, 1971. 5. Cottrall MF, Wells DG. Trott NG, et al: Radioactive vitamin BIZ absorption studies: comparison of the whole-body retention, urinary excretion, and eight-hour plasma levels of radioactive vitamin B12. Blood38: 604, 1971. 6. Alexander IS, Shum HY, Streeter AM, et al: Discrepancies between the urinary-excretion and plasma-level methods of measuring vitamin Eij2 absorption. &fed J A& 1: 179, 1972. 7. Shum H-Y, O’Neill BJ. Streeter AM: Effect of pH on albumincoated charcoal. J C/in Path 25: 834, 1972. 8. Ross B, Kay AW: The insulin test after vagotomy. Gastroenterology46: 379, 1964. 9. Bank S, Marks IN, Louw JH: Histamine and Insulin stimulated gastric acid secretion after selective and truncal vagotomy. G&8: 36. 1967. 10. Campbell RC: Statistics for Biologists. Cambridge, Cambridge University Press, 1967, p 49. 11. Muyshondt E, Schwartz SI: Vitamin B,, absorption following vagotomy and gastric surgery. Ann Surg 160: 788, 1964. 12. Cox AG, Bond MR, Podmore DA, et al: Aspects of nutrition after vagotomy and gastrojejunostomy. Br A&d J 1: 465, 1964. 13. Hopkinson BR: A comparison of the results of vagotomy and pyloroplasty with vagotomy and gastro-enterostomy for chronic duodenal ulcer. Br J Surg 53: 1046, 1966. 14. Schofield PF, Watson-Williams EJ, Sorrel1 VF: Vagotomy and pyloric drainage fdr chronic duodenal ulcer. Long term results. Arch Surg95: 615, 1967. 15. Johnson HD, Khan TA, Srivatsa R, et al: The late nutritional and haematological effects of vagal section. Br J Surg 56: 4, 1969. 16. Wheldon EJ, Venerables CW, Johnston ID: Late metabolic sequelae of vagotomy and gastroenterostomy. Lancet 1: 437, 1970. 17. Doscherholmen A, Swaim WR: Impaired assimilation of egg Co5’ vitamin B12 in patients with hypochlorhydria and achlorhydria and after gastric resection. Gastroenterology 64: 913, 1973. 18. Heyssell RM, Bozian RC, Darby WJ. et al: Vitamin B12 turnover in man. The assimilation of vitamin B12 from natural foodstuff by man and estimates of minimal daily dietary requirements. Am J Clin Nutr 18: 176, 1966. 19. Adams JF, Cox AG. Kennedy EH, et al: Effect of medical and surgical vagotomy on intrinsic factor secretion. Br Med J 3: 473, 1967.
343