Acta Med Scand 200: 309-3 14, 1976
Serum Vitamin BI2Levels in the Aged L. Elsborg, V. Lund and P. Bastrup-Madsen From the University Department of Medicine and Haematology, Arhus Amtssygehus, and the Geriatric Centre, Arhus Municipality, Arhus, Denmark
ABSTRACT. In an attempt to throw light on the question of age-related variations in the normal blood content of cobalamin and on the frequency of deficiencies of antimegaloblastic nutriments in the elderly, 273 geriatric patients have been investigated. Low serum vitamin B,, values were found in one third of these patients, due to latent pernicious anaemia in five and malabsorption in seven cases, and probably caused by nutritional deficiency of folate or cobalamin in 78 cases. In that part of the series with apparently normal vitamin B,, levels, the mean value (379f14 pg/ml) was lower than the mean (465f20 pg/ml) for a younger control group. However, this cannot be taken as a sign of a physiological lowering of the cobalamin values with age, as nutritional deficiencies could not be ruled out in this part of the series. It is concluded that serum vitamin B,, assays should be performed rather liberally in the aged. Patients with nutritional deficiency of cobalamin or folate should be treated, even if frank megaloblastic anaemia is not present.
Measurements of serum vitamin B,, concentration in the general population have shown that the level remains relatively constant throughout life (9, 10, 18, 21, 24, 26). Some investigators ( 5 , 6, 12, 16, 17, 19, 25, 27, 28, 31) have, however, reported a tendency to decreasing values with advancing age. As pernicious anaemia is predominantly a disease of old age, and as nutritional deficiencies are found more frequently at this stage of life, it is of importance to evaluate the clinical significance of serum vitamin B,, assays in the aged. This study was performed in an attempt to throw light on the question of age-related variations in the normal blood content of cobalamin and on the fre-
quency of deficiencies of antimegaloblastic nutriments in a group of elderly people who were in need of geriatric care.
MATERIAL AND METHODS During a period extending over 12 months a total of 349 patients, 236 women and 113 men, who had been admitted to the Geriatric Centre, Arhus, for various social and medical reasons, were studied. Some of these patients died shortly after admission; others were transferred to another home for the aged, and a few failed to attend the investigation for various technical reasons. Patients treated with vitamin BIZfor previously diagnosed pernicious anaemia, gastrectomy or other gastrointestinal disorders were primarily excluded, as were patients treated with antibiotics at the time of admission. In the remaining 273 patients, a venipuncture was performed immediately on admission for an assay of vitamin BIZby the Lactobacillus leichmannii method (performed by the Research Laboratories of Dumex Ltd., Copenhagen) (15). Patients with normal serum vitamin B12 levels, i.e. above 200 pglml, were not subjected to any further study. In patients with low concentrations of vitamin BIZan investigation programme was instituted, comprising peripheral blood studies (WBC, MCV, platelets), serum iron, total iron-binding capacity, marrow examination, hydrochloric acid in gastric juice after histamine stimulation, Schilling test I, D-xylose test, formiminoglutamic acid (FIGLU) excretion in 5-hour urine samples after histidine load and daily excretion of fat in the stools. Finally, barium-meal studies of the total gastrointestinal tract were performed. The diagnostic criteria for pernicious anaemia were ( a ) low serum vitamin H12 concentration, (b) megaloblastic maturation disturbances in the bone marrow, either in the myeloid or erythroid series or in both (2), ( c ) achlorhydria, (d) pathological Schilling test (3) and ( e ) absence of anatomical defects in the gastrointestinal tract on Xray. Only patients fulfilling all five criteria were regarded as suffering from genuine pernicious anaemia and treated with injections of vitamin BIZat regular intervals (4). All Acto Med Scand 200
.
310
-
L . Elsborg et al.
Table I. Serum vitamin B in 89 geriatric patients
,, concentrations related t o various haematological and malabsorption studies Serum vitamin BIZ(pglml)
No. of patients
IOO-ISO
150-200
9
30
so
89
13
72 73 73 72 71 69 67 67
MCV>100 fl
Leucocytes4 g/24 h
3 2
I
6
4 4 4 4 2 2 7
S
9
11 4
1s 7
6 9 17
11 26
other patients with low serum vitamin BIZlevels were kept under observation without any substitution therapy for 6 months, after which period their serum vitamin BIZlevels
were again assayed. RESULTS Vitamin B,, values above 200 pg/ml were found in the serum of 184 patients. Based on the levels of serum vitamin B,,, the remaining 89 patients were divided into three groups (Table I). In the first group (serum vitamin B,,< 100 pglml) of nine patients, four had non-anaemic genuine pernicious anaemia. Increased urinary excretion of FIGLU suggested folate deficiency in two, and in three patients increased excretion of faecal fat indicated some kind of malabsorption. The second group (serum vitamin B,, 100-150 pg/ ml) consisted of 30 patients, of whom only one suffered from pernicious anaemia. Folate deficiency was indicated by the FIGLU test in nine patients. Table 11. Barium-meal studies in 76 geriatric patients with hypovitaminosis B12 Bone marrow findings
X-ray findings Normal gastrointestinal tract Dilated hypotonic small intestine Duodenal diverticulum Hiatus hernia of oesophagus Neoplasia of gastrointestinal tract Acta M e d Scand 200
Total no. ofpats.
100
Normo- Megaloblastic
blastic
30
5
IS 7 4
12 0 0
2
1
37
68 68
Of these, four had megaloblastic anaemia, and malabsorption of fat and D-xylose was observed in five, including one with malabsorption of vitamin Blz as well. In another 12 patients there was an excess of faecal fat excretion, including two in whom the Schilling test gave a pathologically low value. One patient had decreased absorption of vitamin B,, as assessed by the Schilling test, but did not fulfil the criteria for pernicious anaemia. In seven patients, low serum vitamin B,, levels were isolated findings. In the third group (serum vitamin B,, 150-200 pg/ ml) of 50 patients, no cases of pernicious anaemia were disclosed. Folate deficiency as indicated by the FIGLU test was seen in 26 patients. Of these, five also had malabsorption of vitamin B,,, while 13 had malabsorption of fat and/or D-xylose. In two patients, only the absorption of vitamin B12was depressed. In another 22 patients, faecal fat was increased. Seven patients with megaloblastic transformation in the marrow aspirate had a positive FIGLU test. All patients with sideropenia (low serum iron and high total iron-binding capacity) had normoblastic bone marrow. The patients subjected to barium-meal studies were divided into two groups, one with normoblastic and the other with megaloblastic bone marrow. Table I1 shows that most of the patients with a normal X-ray appearance of the gastrointestinal tract had normoblastic marrow. However, a dilated hypotonic small intestine was a fairly common finding, and many of these patients had megaloblastic bone marrow. An unsuspected neoplastic process in the gastrointestinal tract was revealed in three cases.
Vitamin B , , in the aged
TFl
I
/
F i g . I . Serum vitamin B,,
admission
after six
admission
months
Six months after admission, the serum vitamin BIZconcentration was determined again in 40 patients without pernicious anaemia (Fig. l ) . Among 17 patients with normal Schilling and FIGLU tests on admission, the serum vitamin BIZlevel had increased significantly in all but three (p
Serum Vitamin BI2Levels in the Aged L. Elsborg, V. Lund and P. Bastrup-Madsen From the University Department of Medicine and Haematology, Arhus Amtssygehus, and the Geriatric Centre, Arhus Municipality, Arhus, Denmark
ABSTRACT. In an attempt to throw light on the question of age-related variations in the normal blood content of cobalamin and on the frequency of deficiencies of antimegaloblastic nutriments in the elderly, 273 geriatric patients have been investigated. Low serum vitamin B,, values were found in one third of these patients, due to latent pernicious anaemia in five and malabsorption in seven cases, and probably caused by nutritional deficiency of folate or cobalamin in 78 cases. In that part of the series with apparently normal vitamin B,, levels, the mean value (379f14 pg/ml) was lower than the mean (465f20 pg/ml) for a younger control group. However, this cannot be taken as a sign of a physiological lowering of the cobalamin values with age, as nutritional deficiencies could not be ruled out in this part of the series. It is concluded that serum vitamin B,, assays should be performed rather liberally in the aged. Patients with nutritional deficiency of cobalamin or folate should be treated, even if frank megaloblastic anaemia is not present.
Measurements of serum vitamin B,, concentration in the general population have shown that the level remains relatively constant throughout life (9, 10, 18, 21, 24, 26). Some investigators ( 5 , 6, 12, 16, 17, 19, 25, 27, 28, 31) have, however, reported a tendency to decreasing values with advancing age. As pernicious anaemia is predominantly a disease of old age, and as nutritional deficiencies are found more frequently at this stage of life, it is of importance to evaluate the clinical significance of serum vitamin B,, assays in the aged. This study was performed in an attempt to throw light on the question of age-related variations in the normal blood content of cobalamin and on the fre-
quency of deficiencies of antimegaloblastic nutriments in a group of elderly people who were in need of geriatric care.
MATERIAL AND METHODS During a period extending over 12 months a total of 349 patients, 236 women and 113 men, who had been admitted to the Geriatric Centre, Arhus, for various social and medical reasons, were studied. Some of these patients died shortly after admission; others were transferred to another home for the aged, and a few failed to attend the investigation for various technical reasons. Patients treated with vitamin BIZfor previously diagnosed pernicious anaemia, gastrectomy or other gastrointestinal disorders were primarily excluded, as were patients treated with antibiotics at the time of admission. In the remaining 273 patients, a venipuncture was performed immediately on admission for an assay of vitamin BIZby the Lactobacillus leichmannii method (performed by the Research Laboratories of Dumex Ltd., Copenhagen) (15). Patients with normal serum vitamin B12 levels, i.e. above 200 pglml, were not subjected to any further study. In patients with low concentrations of vitamin BIZan investigation programme was instituted, comprising peripheral blood studies (WBC, MCV, platelets), serum iron, total iron-binding capacity, marrow examination, hydrochloric acid in gastric juice after histamine stimulation, Schilling test I, D-xylose test, formiminoglutamic acid (FIGLU) excretion in 5-hour urine samples after histidine load and daily excretion of fat in the stools. Finally, barium-meal studies of the total gastrointestinal tract were performed. The diagnostic criteria for pernicious anaemia were ( a ) low serum vitamin H12 concentration, (b) megaloblastic maturation disturbances in the bone marrow, either in the myeloid or erythroid series or in both (2), ( c ) achlorhydria, (d) pathological Schilling test (3) and ( e ) absence of anatomical defects in the gastrointestinal tract on Xray. Only patients fulfilling all five criteria were regarded as suffering from genuine pernicious anaemia and treated with injections of vitamin BIZat regular intervals (4). All Acto Med Scand 200
.
310
-
L . Elsborg et al.
Table I. Serum vitamin B in 89 geriatric patients
,, concentrations related t o various haematological and malabsorption studies Serum vitamin BIZ(pglml)
No. of patients
IOO-ISO
150-200
9
30
so
89
13
72 73 73 72 71 69 67 67
MCV>100 fl
Leucocytes4 g/24 h
3 2
I
6
4 4 4 4 2 2 7
S
9
11 4
1s 7
6 9 17
11 26
other patients with low serum vitamin BIZlevels were kept under observation without any substitution therapy for 6 months, after which period their serum vitamin BIZlevels
were again assayed. RESULTS Vitamin B,, values above 200 pg/ml were found in the serum of 184 patients. Based on the levels of serum vitamin B,,, the remaining 89 patients were divided into three groups (Table I). In the first group (serum vitamin B,,< 100 pglml) of nine patients, four had non-anaemic genuine pernicious anaemia. Increased urinary excretion of FIGLU suggested folate deficiency in two, and in three patients increased excretion of faecal fat indicated some kind of malabsorption. The second group (serum vitamin B,, 100-150 pg/ ml) consisted of 30 patients, of whom only one suffered from pernicious anaemia. Folate deficiency was indicated by the FIGLU test in nine patients. Table 11. Barium-meal studies in 76 geriatric patients with hypovitaminosis B12 Bone marrow findings
X-ray findings Normal gastrointestinal tract Dilated hypotonic small intestine Duodenal diverticulum Hiatus hernia of oesophagus Neoplasia of gastrointestinal tract Acta M e d Scand 200
Total no. ofpats.
100
Normo- Megaloblastic
blastic
30
5
IS 7 4
12 0 0
2
1
37
68 68
Of these, four had megaloblastic anaemia, and malabsorption of fat and D-xylose was observed in five, including one with malabsorption of vitamin Blz as well. In another 12 patients there was an excess of faecal fat excretion, including two in whom the Schilling test gave a pathologically low value. One patient had decreased absorption of vitamin B,, as assessed by the Schilling test, but did not fulfil the criteria for pernicious anaemia. In seven patients, low serum vitamin B,, levels were isolated findings. In the third group (serum vitamin B,, 150-200 pg/ ml) of 50 patients, no cases of pernicious anaemia were disclosed. Folate deficiency as indicated by the FIGLU test was seen in 26 patients. Of these, five also had malabsorption of vitamin B,,, while 13 had malabsorption of fat and/or D-xylose. In two patients, only the absorption of vitamin B12was depressed. In another 22 patients, faecal fat was increased. Seven patients with megaloblastic transformation in the marrow aspirate had a positive FIGLU test. All patients with sideropenia (low serum iron and high total iron-binding capacity) had normoblastic bone marrow. The patients subjected to barium-meal studies were divided into two groups, one with normoblastic and the other with megaloblastic bone marrow. Table I1 shows that most of the patients with a normal X-ray appearance of the gastrointestinal tract had normoblastic marrow. However, a dilated hypotonic small intestine was a fairly common finding, and many of these patients had megaloblastic bone marrow. An unsuspected neoplastic process in the gastrointestinal tract was revealed in three cases.
Vitamin B , , in the aged
TFl
I
/
F i g . I . Serum vitamin B,,
admission
after six
admission
months
Six months after admission, the serum vitamin BIZconcentration was determined again in 40 patients without pernicious anaemia (Fig. l ) . Among 17 patients with normal Schilling and FIGLU tests on admission, the serum vitamin BIZlevel had increased significantly in all but three (p
