CaPPtain's Blog

  • CaPPtain's Blog: John Burn, October 2022

    posted on Thursday, 27th October 2022

    Not tagged.

    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

  • CaPPtain's Blog: John Burn, May 2021

    posted on Thursday, 27th May 2021

    Not tagged.

    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.

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