BLOOD GROUPS AND THE INTESTINE
alkaline phosphatase is an enzyme manufactured in the
small intestine, which has the primary function of
splitting cholesterol and long chain fatty acids. As the
article states, numerous reports have associated a lack
of secretion of this particular enzyme in individuals
with type A blood. Later studies suggested that it
was this inability to break down fat, which in part
predisposed type A to both higher levels of cholesterol
and increased incidence of heart attack, both of which
have indeed been associated with type A over the other blood groups. Additional research showed that the amino
acid phenylalanine was almost 100% effective in
inhibiting alkaline phosphatase, and indeed our research
has shown that many common sources of phenylalanine,
including yams and sweet potatoes, cause a marked
increase in the production of indican (a measurement of
bowel putrefaction) in our type A patients.
studies showed that type A not only secreted almost no
alkaline phosphatase in their intestines, but whatever
little they did secrete was in and of itself inactivated
by their own A antigen! Thus, we have here one of the
strongest indications for the long term benefit of a
low-fat diet in type A, both with regard to the susceptibility to cardiovascular disease, and (although
not mentioned here) their additional susceptibility to
cancer. Following the type A eating plan, with its
emphasis on a low-fat diet and the avoidance of foods
high in phenylalanine, is the best method to maximize
digestive efficiency in type As, lower their level of
intestinal dysfunction, and to influence their susceptibility to cardiovascular disease.
The descriptions by
AIRD and his colleagues of the associations of
blood group O with peptic ulcer (1) and of blood group A
with gastric cancer (1) have been confirmed by others;(3,4)
and the observations have been extended to cover
associations of blood group A with pernicious anemia,(1)
and with salivary tumors.(6,7) Moreover, inability to
secrete ABH blood group substances in the
gastrointestinal mucus (a genetically determined
characteristic) has been shown to be associated with
peptic ulcer (11,9) and possibly with gastric cancer and
pernicious anemia.(9,10) The causes of these associations
are not known. But a simple protective action of the
ABO(H) blood group substances in the mucus seems an
unlikely explanation, because the total titer of
blood group substance is the same for ABH secretors as
for non-secretors (in non-secretors Lewis substance is
substituted for the A, B, and H mucopolysaccharides).
Furthermore a blood group effect on peptic ulcer can be
shown in non-secretors alone. But the
large quantities of blood group mucopolysaccharides found
in the gastrointestinal mucosa suggest that they have
Since the prevalence of
both pernicious anemia and gastric cancer is higher in
individuals of blood group A, and duodenal ulcer in those
of blood group O, a hypothesis relating blood group effects to
acid secretion naturally followed. Early work seemed to
confirm that acid output tended to be greater in blood group O
than in blood group A subjects,(14,15) but the observed
differences, which were in elderly subjects, could well
have been due to gastric atrophy (which would, by analogy
with pernicious anemia, probably be more frequent and
severe in blood group A than in blood group O individuals). Studies
in younger healthy subjects have given conflicting
results. In one series (16) gastric
secretory potential, as measured by serum-pepsinogen
levels, differed little between blood groups O and A;
acid output was higher in blood group O subjects. In another
study (17) however, gastric acid output was found to be
higher in individuals of blood group O than in those of blood group A
and slightly but not significantly greater in
non-secretors than secretors.
Another approach has
been to study possible associations between ulcer
symptoms and prognosis and the ABO blood group and
secretor characteristics. Although earlier work was
inconclusive, LANGMAN and DOLL (8) found a higher
frequency of blood group O among patients with bleeding
gastric or duodenal ulcers than among those with
non-bleeding ulcers. Non-secretors seemed more liable to
need operation for ulcer, though blood group did not seem
to have any striking effect on likelihood of operation,
nor did secretor status seem to influence the likelihood
of hemorrhage. The association of blood group O with
hemorrhage has been confirmed by others,(19) and the
strength of the association of blood group O with
liability to ulcer rather than with bleeding clearly must
be reassessed. All surveys of blood groups in ulcer
patients so far reported have been largely retrospective,
and since the individuals for whom blood group data are
readily available are those with bleeding ulcer, a strong
bias in favor of blood group O is introduced. The same
kind of error may well be present in data collected on
secretor status, and an unselected consecutive ulcer
series will be required to solve these problems.
intriguing blood group association with a serum isoenzyme
of alkaline phosphatase has been described.(20)
Serum alkaline phosphatase can be divided by starch-gel
electrophoresis into two fractions, a faster moving
component of liver or bone origin and a slower moving
band probably derived from small intestine.(21) BECKMAN
and his colleagues found that the frequency with which
the slow-moving isoenzyme appeared in the serum was much
affected by the subject's ABO blood group.(20) This
observation has been confirmed (22-24) and it is now
clear that the presence of the slow-moving band in the
serum is affected by both ABO blood group and secretor
status. It is rarely found in non-secretors, whatever
their ABO blood group, but in secretors it can be
distinguished progressively more often in those of
blood groups A, AB, and O or B (the last two have equal
A natural question is
whether the blood group associations noted in disease
could be more readily explained by relationships with the
serum isoenzyme patterns of alkaline phosphatase. For
instance, is absence of the slow-moving intestinal
component in blood group A patients correlated with
liability to gastric cancer? An association between
peptic ulcer and the presence of the intestinal isoenzyme
seems unlikely, because the disease is common in
individuals of blood group O but not in those of blood group B. But
simple comparisons of serum isoenzyme patterns in healthy
individuals and patients with gastric cancer are
impossible, for the presence or absence of the intestinal
isoenzyme in the blood seems to depend greatly on diet. H. HARRIS and his colleagues
(25) have shown that in normal individuals after an
overnight fast the slow-moving component is present in
considerably reduced amounts and can be clearly detected
only in blood group O and B secretors. After normal meals the band of
activity becomes much stronger in blood group O and B secretors; in
blood group A secretors a weaker though distinct band appears;
while in non-secretors little or none is detectable. Fat
ingestion seems to stimulate the appearance of the
intestinal isoenzyme in the serum. In blood group O or B
secretors a synthetic breakfast of protein and
carbohydrate did not seem to alter the
serum alkaline phosphatase isoenzyme characteristics, but
the substitution isocalorically of fat for part of
protein and carbohydrate resulted in a notable increase
in serum alkaline phosphatase activity. These
findings agree well with independent observations showing
that the administration of fat, but not protein or
carbohydrate, increases the alkaline phosphatase content
of human thoracic-duct lymph.(26,21) Further
study of intestinal alkaline phosphatase should, however, increase
our understanding of the relation between blood groups
and alimentary function, and perhaps give us some idea of
the physiological role of one form of alkaline phosphatase.
- Aird, I.,
Bentall, H. H., Mehigan, J. A., Roberts, J. A. F.
Br. Med. J. 1954, ii, 315.
- Aird, I.,
Bentall, H. H., Roberts, J. A. F. ibid. 1953, i,
- Clarke, C.
A., Cowan, W. K., Edwards, J. W., Howel Evans, A.
W., McConnell, R. B., Woodrow, J. C., Sheppard,
P. M. ibid. 1955, ii, 643.
J. A. F. Br. Med. Bull. 1959, 15, 129.
J. A. F. Br. J. Prev. Soc. Med. 1957, 11, 107.
J. M. Lancet, 1958, i, 239.
R. H., de George, F. V. Am. J. Hum. Genet. 1963,
- Clarke, C.
A., Edwards, J. V., Haddock, D. R. W., Howel
Evans, A. W., McConnell, R. B., Sheppard, P. M.
Br. Med. J. 1956, ii, 725.
- Doll, R.,
Drane, H., Newell, A. C. Gut, 1961, 2, 352.
S. T., Denborough, M. A., Sneath, J. Br.
Haematol. 1957, 3, 107.
- Glynn, L.
E., Holborow, E. J., Johnson, G. D. Lancet, 1957,
A. E. J. Exp. Med. 1960, 111, 785.
A. E. ibid. 1962, 115, 977.
- Koster, K.
H., Sindrup, E., Seele, V. Lancet, 1955, ii, 52.
M. L. Am. J. Med. 1959, 27, 246.
J. C., Gilbert, E. C., Spiro, H. M. Ann. Intern.
Med. 1962, 56, 564.
- Hanley, W.
B. Br. Med. J. 1964, i, 936.
M. J. S., Doll, R. Gut, 1965, 6, 270.
G., Christakopoulos, P., Petropoulos, E. Am. J.
Dig. Dis. 1966, 11, 790
- Arfors, K.
E., Beckman, L., Lundin, L. G. Acta Genet.
Statist. Med. 1963, 13, 89.
- Hodson, A.
W., Larner, A. L., Raine, L. Clin. chim. Acta,
1962, 7, 255. 22. Arfors, K. E., Beckman, L.,
Lundin, L. G. ibid. p. 363.
D. C. Am. J. Hum. Genet. 1965, 17, 71.
K. F., Harris, H., Luffman, J. E., Robson, E. B.,
Cleghorn, T. E. Lancet, 1965, i, 530.
M. J. S., Leuthold, E., Robson, E. B. Harris, J..
Luffman, J. E., Harris, H. Nature, Lond. 1966,
212, 4 1.
N. R. Clin. Sci. 1964, 26, 29 1. 27. Blornstrand,
R., Werner, W. Acta chir. Scand. 1965, 129, 177.