posted on Thursday, 27th October 2022
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CaPPtains Blog - CAPP2 Resistant Starch Update
A diet supplement of resistant starch doesn't reduce colorectal
cancers in Lynch syndrome but does reduce other types of Lynch
syndrome cancer by more than half. This is the important
result from "the other half" of CAPP2, our international research
trial which began more than 20 years ago. It appeared in the
highly regarded research journal, Cancer Prevention Research in
September 2022. It has taken a long time to reach publication
because the result is surprising.
Our CAPP2 trial was double blind, which means no-one knew
whether they were taking the resistant starch or ordinary corn
starch. They mixed 2 sachets with their food each day for
between 2 and 4 years. Some people weren't able to complete
the study, but the effect was so big that the difference was clear
even if the "early dropouts" were included. This is called an
"intention to treat" analysis. The biggest effect was on cancers in
the upper gastrointestinal tract near the stomach and including
cancers in the pipes that let bile out of the liver.
Resistant starch is turned into short chain fatty acids by
bacteria in the gut. The most important of these short chain
fatty acids is butyrate which has been known for a long time to
help reduce cancer. In addition, we think the supplement of
resistant starch may have caused a long-term change in the types of
bacteria in the gut and reduced the production of chemicals called
secondary bile acids which are released in the bile and can cause
genetic damage.
Whatever the reason, the effect on cancer risk is real and it
lasts a long time. There are no important side effects so we
think that everyone with Lynch syndrome should try to increase the
amount of resistant starch in their diet.
The name resistant starch comes from the fact that some starch
is not broken down to glucose in the upper gut. This can be
because they are inside seeds, for example, or because their
chemical structure prevents the digestive enzymes from
working. The best known example is in bananas where the
starch is crystalline but gradually breaks down to glucose as the
banana ripens; hence our advice to eat a green tipped banana a
day. There are lots of other ways to increase resistant
starch. The simple answer is to aim for a "high fibre"
diet.
The important type is resistant starch, also called fermentable
fibre in America because it reaches the bowel bacteria to be broken
down by fermentation. When starches are heated they become
easier to break down in the upper gut. I once suggested that
yesterday's pizza or cold mashed potato would work too which caused
quite a social media flurry!
The take home message is that a high fibre diet is good for you,
reduces cancer risk and can help control your weight because
resistant starch has fewer useful calories. It takes us
nearer to the wild diet eaten by our ancestors.
Speaking of ancestors, the whole CAPP story began when Professor
John Mathers invited me over 30 years ago to speak at a Newcastle
University nutrition seminar where the late great Dennis Burkitt,
who first showed that fibre is good for you, was in the audience. I
think he would approve.
John Burn
October 2022
posted on Thursday, 27th May 2021
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CaPPtain's Blog: Taking aspirin and getting old
Two papers have been published recently based on the ASPREE
trial1,2; ASPirin in Reducing Events in the Elderly
recruited 19,114 people aged 70 and over in Australia and the USA
(65 and over for US minorities) to receive 100mg aspirin or an
identical placebo. They have now been followed for an average
of 4.7 years. The papers are a follow up analysis of the
earlier trial report in 20183.
Given the extensive evidence, gathered over 30 years, that
regular aspirin use reduces the burden of colorectal and
other cancers, the original ASPREE report was a surprise as it
suggested there might be more cancers in the people randomised to
receive aspirin. This new information shows that, so far, the
overall number of cancers in the two groups is about the
same. However, the people in the aspirin group who developed
cancer did less well. There were more cases of cancers that
had spread and more deaths in the aspirin group. In both cases,
there were about 5 in the aspirin group for every 4 in the placebo
group.
Back in the 90's, when a long series of studies reported aspirin
was probably protective, a study led by Dr Paganini-Hill
based on older people in residential care homes, reported a higher
cancer risk in the over 80s4.
As expected in the ASPREE trial, there were more cases of
bleeding events. The main difference was due to ulcers in and
around the stomach with about 8 cases in the aspirin group for
every 5 in the placebo group, though the only two who died were in
the placebo group. There was a wide variation in bleeding
risks across the people who took part; for example the chance of a
bleed in a fit 70 year old was about 1 in 400 over five years
whereas the risk in an 80 year old with risk factors was 1 in 20
over five years. The main risk factors apart from age were
smoking, being significantly overweight and having kidney disease
or high blood pressure.
What are we to make of this new information? The first thing to
say is that it doesn't change the overall plan in CaPP3. The
protection against cancer in CAPP2 was very clear and there was no
difference between the two groups when it came to major side
effects. This was because the average age of the people in
the study was only 45 when they joined. The risk of bleeds
caused by aspirin rises sharply from about 65 years of age
onwards. It's also probably worse in someone who starts
aspirin at this older age, as people who have been on aspirin a
long time seem to have fewer bleeds at any given age.
As for the effect on cancer, again the result wasn't a complete
surprise. Given the observations by Paganini-Hill and
colleagues, there was already a suggestion that starting people on
aspirin after the age of 70 might not be as successful in
preventing cancers. It's also important to remember that all
studies have suggested that it takes about 5 years before the
preventive effect of aspirin becomes apparent, and in the Women's
Health Study where participants took a 100mg of aspirin every other
day, the benefit didn't appear until 10 years after starting the
trial, so there is still time for the ASPREE trial to show long
term benefit. It is possible, though, that the effects of
getting older may make aspirin become less effective as we
age. Our group is now collaborating with Dr Laura Greaves, an
expert in mitochondrial genetics and ageing, at Newcastle
University to explore this possible link.
Finally, some definite good news. The American Society of
Clinical Oncology ASCO has declared our CAPP2 paper last year as
the most significant advance in cancer prevention of
20205.
John Burn
May 2021
References:
1. McNeil JJ, Gibbs P, Orchard SG, et al.
Effect of Aspirin on Cancer Incidence and
Mortality in Older Adults.Journal of the National Cancer
Institute.2021;113(3):258-265.
2. Mahady SE, Margolis KL, Chan A, et al. Major
GI bleeding in older persons using aspirin: incidence and risk
factors in the ASPREE randomised controlled
trial.Gut.2021;70(4):717-724.
3. McNeil JJ, Nelson MR, Woods RL, et al.
Effect of Aspirin on All-Cause Mortality in the Healthy Elderly.New
England Journal of Medicine.2018;379(16):1519-1528.
4. Paganini-Hill A. Aspirin and colorectal
cancer: the Leisure World cohort revisited.Prev
Med.1995;24(2):113-115.
5. Smith SM, Wachter K, III HAB, et al.
Clinical Cancer Advances 2021: ASCO's Report on Progress Against
Cancer.JClinOncol.2021;39(10):1165-1184.