THE DIAMINE OXIDASE HYPOTHESIS
It is widely believed that bile salts may have
some role in the aetiology of CRC.20 It has also
been suggested that the enzyme diamine
oxidase (DAO) may play a part.21 DAO is a
major catabolic enzyme for histamine. It is
found in highest concentration in the ileal
mucosa, and also in the colon.22 DAO is
thought to have a role in colonic mucosal
regulation.23 DAO activity is reduced in vitro by
detergent and also by glycochenodeoxycholic
acid.24 25
The role of secondary bile acids, including
deoxycholic acid, in the development of colorectal
carcinoma has been well documented.5 6
Deoxycholic acid appears to be reduced in
vegetarians.19 26 The inhibition of DAO by
deoxycholic acid is as yet speculative but
possible, in view of in vitro inhibition of
DAO by glycochenodeoxycholic acid.25 There
seems to be a significant reduction in the
cholic acid and chenodeoxycholic acid pool in
rats given an olive oil diet.27 In discussing the
role of meat in CRC development, Owen and
Hill have suggested that meat, too, may influence
deoxycholic acid5 6 with higher levels of
faecal bile acid in populations with a normal
western mixed diet. Increases in faecal steroid
levels seem to be associated with higher
mucosal proliferation rates or colonic
adenomas.28–30
If meat increases deoxycholic acid in the
human colon and rectum, it might be expected
that meat could increase CRC incidence
because of the inhibition of DAO. If functional
DAO is necessary for in vivo control of
mucosal proliferation, and if olive oil reduces
deoxycholic acid in the human colon and rectum,
then it might be expected that olive oil
would have a protective eVect on CRC
incidence because of the greater availability
of DAO. It is therefore noteworthy that, in
two human studies of the relation between
olive oil and CRC, high consumption of olive
oil was associated with a decrease in cancer
risk.31 32
In summary, the DAO hypothesis is that
deoxycholic acid, which may be increased
by meat consumption and reduced by olive
oil consumption, may influence polyamine
metabolism in the colorectal mucosa leading
to changes in mucosal turnover, polyp
formation and the adenoma/carcinoma sequence.
In conclusion, we provide some further ecological
support for the involvement of meat in
the development of CRC and we show new
evidence supporting the hypothesis that olive
oil may protect against CRC. We appreciate
that the mechanism we have suggested is
speculative and also that ecological studies are
limited. We suggest that further study is
merited, including studies of DAO activity in
the colorectal mucosa of people who develop
CRC, and further epidemiological studies of
CRC and olive oil.