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Friday 22 March 2013

UK National Screening for Bowel Cancer with Flexiscope

Update 10 April 2013: 

I was referred by my GP to Bournemouth Nuffield [private] Hospital who say 'I am sorry but the self-fund initial appointment with Mr Howell is £180.00. If you have to have a flexible sigmoidoscopy no doubt he would be able to move you into the NHS to have it performed. If he performed a rigid sigmoidoscopy in outpatients at the same time as your initial appointment it would incur an extra £50 for Mr Howell and the Nuffield would send you an invoice for around £100.00 for the use of consumables etc.'

£330 for a rigid sigmoidoscopy! Ouch!! I think I'll wait till the NHS gets its free flexisig act together by 2016!

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I blogged about Bowel Cancer Screening December 2010 and prompted by investigations on AAA, I understand Bowel Cancer Screening with a Flexiscope is available free on the NHS for those over 55 but is being rolled out to the whole country by 2016. The screening is called Bowel scope screening. See your GP for details.

LifeScanUK.org do a virtual colonoscopy for £650. NB. NOT the same test as flexible sigmoidoscopy. I can't find anybody in UK who does Flexiscope testing other than NHS trials, so booked appointment with my Doctor for further info.

"A large UK clinical trial looked into a new bowel screening test. The trial followed more than 170,000 people over 11 years to see who developed bowel cancer. More than 40,000 of those people between the ages of 55 to 64 had a test called flexible sigmoidoscopy. This test may also be called Flexi-Scope, flexi-sig or bowel scope. It involves having a thin, bendy tube put a short way into the rectum and lower bowel. The tube has a tiny camera and light on the end, allowing the doctor to look at the inside wall of the bowel and remove any small growths or polyps. 
The researchers found that the people who had screening with Flexi-Scope reduced their risk of bowel cancer by a third because any polyps were removed at an early stage. In England, the Flexi-Scope test is now being introduced into the NHS bowel screening programme. This is called bowel scope screening. This will be a one off test for all men and women aged 55. The FOB test will continue from age 60 as before. Bowel scope screening will be slowly rolled out across the country over the next few years" sourceCancer Research UK

Beating Bowel Cancer say:-


'Pilot programmes for bowel scope screening are scheduled to commence in Norwich, South of Tyne, St Mark’s London, Surrey, West Kent and Wolverhampton from March 2013. 

Beating Bowel Cancer have a factsheet (January 2013)

Flexible-sigmoidoscopy (flexi-sig) or bowel scope screening: The Department of Health in England has announced that it will fund a new, one-off, flexi-sig screening programme for men and women in England aged 55 years. This screening will be offered IN ADDITION to the FOBt (Faecal Occult Blood test) programme offered at 60 years. The decision was made following the results of a long term study,funded by CRUK. The research found that a single flexi-sig test, in those aged 55 to 64 years, reduced the risk of individuals dying from bowel cancer by 43% and the risk of individuals developing bowel cancer by 33%.

NHS Bowel Cancer Screening:-

For more information, you can read or download the excellent NHS leaflet on NHS bowel scope screening.
What about people in areas where the pilot isn't happening?It isn't possible to introduce a new type of screening test everywhere at the same time. If you don't live in one of the pilot areas, this means that bowel scope screening is not yet available to you. The plan is to make bowel scope screening available to all 55 year olds in England by 2016.

 2011/12 development year for Flexi-sig (pdf)
•2012/13 piloting of Flexi-sig
•2013/14 first wave roll out of Flexi-sig
= 30% country open by 31 March 2014
•2014/15 second wave roll out of Flexi-sig
= 60% country open by 31 March 2015
•2016 roll out complete
•“Opt-in” for those aged 55 -59 
Self referrals (Opt ins)•Registered with GP linked to SC offering FS Screening
•Age 56-59 inclusive 

Wednesday 13 March 2013

What are the benefits of Chiropractic?

reposted from: http://www.nhs.uk/conditions/chiropractic/Pages/Introduction.aspx
crabsallover highlightskey pointscomments / links.

Tuesday 12 March 2013

Superbug threat is 'ticking time bomb'

reposted from: http://www.nhs.uk/news/2013/03March/Pages/Superbug-threat-is-ticking-time-bomb.aspx
crabsallover highlightskey pointscomments / links.


There are claims across the media that antibiotic resistance is a ‘ticking time bomb’, with the Daily Express claiming “Superbug threat 'ranks alongside terrorism'”.
These headlines reflect the views of England’s Chief Medical Officer, and arguably could be viewed as understated.
The Chief Medical Officer, Professor Dame Sally Davies, warned of the growing threat from antibiotic resistance ahead of the publication of an in-depth report on the issue (PDF, 3.5MB). In her report, Professor Davies says antimicrobial resistance represents a threat that may be ‘as important as climate change for the world’.
Antimicrobials (drugs used to treat infections from bacteria, viruses and fungi) include antibiotics, which are an essential component of modern medicine and used to treat bacterial infections.
Increasingly widespread use of antimicrobials, and antibiotics in particular, is leading to the organisms causing these infections adapting and surviving. As this resistance develops, it can render treatment of infections less effective and eventually the infections may become untreatable.
Antibiotic-resistant infections, such as MRSA and multi-drug resistant tuberculosis have been increasing over the last two decades; yet few new antibiotics have been developed. While the spread of antimicrobial resistance can be slowed (for example, by good hygiene), new antibiotics are needed to more fully address the problem.

Antibiotic resistance – new threats

The main causes of resistant bacterial infections such as MRSA andClostridium difficile have fallen sharply in the UK due to simple but effective hospital hygiene measures.
Yet the Chief Medical Officer’s report highlights other causes for concern, such as:
  • multi-drug resistant tuberculosis – estimated to kill 150,000 each year globally
  • E. coli – which now accounts for one in three cases of bacterial infections in the blood in the UK
  • NDM-1 – a bacteria detected in India, of which some strains are resistant to all types of antibiotics

What is antibiotic resistance and how does it develop?

Antibiotics are often used to treat bacterial infections, and are a cornerstone of infectious disease care. They have transformed medical care since they became widely available after World War Two – resulting in a sharp drop in deaths from infectious disease.
However, bacteria evolve in response to their environment. Over time, they can develop mechanisms to survive a course of antibiotic treatment.
This ‘resistance’ to treatment starts as a random mutation in the bacteria’s genetic code, or the transfer of small pieces of DNA between bacteria. If the mutations are favourable to them, they are more likely to survive treatment, more likely to be able to replicate and therefore more likely pass on their resistant nature to future generations of bacteria. When taken correctly, antibiotics will kill most non-resistant bacteria, so these resistant strains can become the dominant strain of a bacteria. This means when people become infected, existing treatments may be unable to stop the infections.
We cannot stop the random DNA mutations that are one way antibiotic resistant strains of bacteria emerge. However, we can exert some control over the speed and spread of antibiotic resistance by several methods, such as:
  • Breadth of use: the more antibiotics are used, the more quickly resistance generally develops, this makes reducing unnecessary use important (both in healthcare and other fields such as veterinary medicine).
  • Incorrect use: resistance is more likely to spread if you do not finish a course of antibiotic treatment (as the drugs won’t have a chance to kill off all the bacteria), or if broad-spectrum antibiotics, which often serve as ‘last-line’ treatments, are used where a more narrow and targeted option is available and appropriate.
  • Infection control: containing and preventing infectious diseases – such as through diligent cleaning and hand washing – can reduce the need for antibiotic use.

How much of a danger is antibiotic resistance?

Antibiotic resistance can render previously treatable infections untreatable. For instance, tuberculosis (TB) cases have been increasing steadily in the UK for the past 20 years, with an increasing number of cases being resistant to the first-choice antibiotics traditionally used to treat the infection.
Widespread antibiotic resistance could have a far reaching healthcare impact. For example, emerging antibiotic resistance increases the chance that surgical sites could be infected by bacteria resistant to antibiotics and cause infection in people who may already be vulnerable as a result of their underlying illness or from having major surgery.
The Chief Medical Officer says that other treatments which lower our immune response – including immunosuppressants (for example, to prevent the body rejecting transplanted organs) or chemotherapy for cancer – would also not be viable in the face of widespread antibiotic resistance. 
Professor Davies, has said that “antimicrobial resistance poses a catastrophic threat. If we don’t act now, any one of us could go into hospital in 20 years for minor surgery and die because of an ordinary infection that can’t be treated by antibiotics. And routine operations like hip replacements or organ transplants could be deadly because of the risk of infection”.

Why have no new antibiotics been developed?

Critics of the pharmaceutical industry would argue that the reason is simple – there is no profit in it.

This has been disputed by the pharmaceutical industry. An industry spokesperson quoted in The Guardian pointed out that there are ‘pharmaceutical companies actively involved in
researching and developing new antimicrobial medicines’.

The Chief Medical Officer argues that the best way forward would be a public-private partnership, where governments help support and fund the work of drug companies in order to create new antibiotics.

What has the Chief Medical Officer called for?

The Chief Medical Officer wants action to tackle antibiotic/antimicrobial resistance in several areas. She wants to change the medical practices that increase the risk of developing or exacerbating resistance, to improve government monitoring of (and response to) emerging resistance, and to create incentives for new antibiotics to be developed.
In healthcare in particular, the Chief Medical Officer recommends:
  • antimicrobial resistance to be added to the national risk register (a series of contingency plans designed to co-ordinate government response to civil emergencies), and to be taken seriously by politicians worldwide
  • improving the monitoring and surveillance of resistance, both within the NHS and worldwide
  • co-ordination of efforts between the healthcare and pharmaceutical industries to prevent resistance to current antibiotics from developing and spreading, and to encourage the discovery and development of new antibiotics
  • improving hygiene measures to prevent the spread of healthcare-associated infections
The Chief Medical Officer also wants action on antimicrobial resistance beyond hospitals and other areas of healthcare, including:
  • better home and community based infection control measures
  • a focus on antibiotic resistance in animals, managed by the Department for Food, Environmental and Rural Affairs
  • co-operation between Public Health England and the NHS to improve the detection and treatment of infections acquired abroad
  • better promotion of vaccination programmes, reducing the need for some antibiotic treatments

What is likely to happen next?

The Department of Health is due to publish a UK Antimicrobial Resistance Strategy, outlining how it will take steps to address this issue. This will include plans to:
  • support responsible antibiotic use
  • improve surveillance mechanisms
  • encourage the development of new diagnostic tests, therapies and antibiotics

What can we do to prevent antibiotic resistance?

We can all take steps to help slow the spread of resistant microbes.
Understanding when antibiotics are appropriate can be complicated. We often think of antibiotics being used to treat “a chest infection”, yet most common respiratory infections will go away on their own without any treatment. In addition; most coughs, colds and sore throats are caused by viruses, rather than bacteria, so an antibiotic would be not be an effective treatment for them. If we use antibiotics to treat these relatively minor viral complaints, not only is the treatment ineffective, it increases the chances of antibiotic resistance developing, making other more serious conditions such as TB more difficult to treat.
If your doctor does prescribe antibiotics for you, make sure that you’ve discussed and understood how to take them correctly, and that you take all the prescribed pills, regardless of whether you still have symptoms. This is because if you do not take the full prescribed dose, the chances are that some of the bacteria will not be killed, and that these are more likely to be resistant strains. This could be bad for you, and it could be bad for lots of other people too.
Read more about what you can do to tackle the problem of antibiotic resistance.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Resveratrol increases sirtuins.

reposted from: NHS Choices
crabsallover highlightskey pointscomments / links.

Further to the article by David Stipp in Scientific American blog, reviewed by me a few days ago...

Drugs that could help people 'to live to 150' could soon be a reality, according to headlines in The Daily Telegraph and the Daily Mail.
The news comes from molecular-level research into the compound resveratrol, which is found in red wine and dark chocolate, and has been shown to increase the activity of proteins called sirtuins.
These proteins are able to increase the lifespan of yeast, worms and flies, and it has been suggested that they may also play a role in human age-related diseases such as Alzheimer's disease.
This laboratory study looked at whether a synthetic version of resveratrol could stimulate the activity of sirtuins to such an extent that it could theoretically improve human life expectancy.  
Although the researchers found that these compounds directly activated the sirtuin proteins, it is far too early and optimistic to claim that a pill could be created that would allow people to live to 150.
This study was interested in biological processes in a laboratory, not the development of an anti-ageing pill. No pill has been made to improve life expectancy in humans, and the '150-year' claim seems to have been manufactured by the headline writers. Dreams of a pill that will allow you to live to 150 remain just that: dreams.

Red wine and resveratrol

Red wine only contains tiny amounts of resveratrol. Any hopes that a bottle of red will extend your lifespan are unfounded.

Where did the story come from?

The study was carried out by researchers from Harvard Medical School, the Massachusetts Institute of Technology, the US National Institutes of Health, the pharmaceutical company GlaxoSmithKline, and other institutions in Portugal and Australia.
The research was funded by research organisations throughout the US and Portugal. No funding support was reported for GlaxoSmithKline (GSK), although a GSK company (Sirtris) employs several of the researchers involved in the project, and one author is an inventor on patents licensed to this company.
Patents have also been filed by Harvard Medical School on the tests developed in their study, as well as by Sirtris and another company for some of the compounds tested.
The study was published in the peer-reviewed journal Science.
Headlines proclaiming that a pill has been developed that will help us live to 150 are highly flawed. It is also unclear what evidence these claims are based on, such as the Daily Mail stating that a pill could be "available within five years". Indeed, it is nearly two years since the last time the Mail ran a story on very similar news.
This laboratory research tested whether, and how, a class of compounds can increase the activity of a particular enzyme previously identified as being involved in a range of age-related diseases.
The research did not assess whether these compounds have the same effect when given to humans in a pill, if there is any effect on human disease or lifespan, or whether such a pill would be safe.
Much more research is needed before we know if these compounds could show any effect on human lifespan.

What kind of research was this?

This was a laboratory study that examined the ways that molecules called sirtuin-activating compounds (STACs) may increase the activity of the protein sirtuin-1 (SIRT1). 
Previous research has found that activating sirtuin proteins leads to a longer lifespan in yeast, flies and worms. It has been suggested that SIRT1 plays a role in many age-related conditions, including cancerAlzheimer's disease, and type 2 diabetes.
Researchers report that SIRT1 has been shown to be involved in several processes surrounding these conditions, including controlling DNA repair and natural cell death, insulin secretion and inflammatory pathways, among others.
These findings make it an attractive drug target, as researchers hope that drugs that safely activate this protein could improve human health and extend our lifespan.
Previous research has shown that both synthetic and naturally occurring STACs (including resveratrol) can activate SIRT1 in the laboratory.
However, there has been debate as to whether this activation was a real, direct effect of STACs, or if it was caused by fluorescent chemical compounds called fluorophores, which are used to monitor the effects of STACs during experiments.
Fluorophores are widely used in laboratory research, as they make it easier to measure chemical changes to these proteins. However, they do not occur naturally in the human body and they may change what naturally happens in the reactions being tested.
There is the risk of a kind of biological Heisenberg Uncertainty principle: the act of observation could change the system you are trying to observe. This means that if the STACs cannot really directly activate SIRT1 in the body, and only do so in the laboratory due to the presence of the fluorophores, they would no longer be potential candidates for treating age-related diseases or extending lifespan.
The set of experiments described in the current study were designed to determine whether STACs were able to directly activate SIRT1, and to identify the precise way that such activation occurs.

What did the research involve?

The researchers carried out a series of complex laboratory experiments to determine whether a range of STACs were able to activate SIRT1. They developed a new way of measuring SIRT1 activation that did not require the use of fluorophores, so that these compounds could not affect the reactions.
The SIRT1 protein acts by modifying a range of different proteins, and the researchers tested whether the STACs enhanced the effect of SIRT1 across this range of proteins, or only on certain proteins. They also assessed how STACs might be having this effect.

What were the basic results?

The researchers found that STACs could activate SIRT1 in the laboratory, even if fluorophores weren't present.
They found that this increase in SIRT1 activity only affected proteins that had a specific type of amino acid in a particular position in the protein.
They found similar findings for all of the 118 STACs tested, including resveratrol.

How did the researchers interpret the results?

The researchers felt that their results meant that a range of STAC compounds can activate SIRT1, and that this process "remains a viable therapeutic intervention strategy for many diseases associated with ageing".

Conclusion

As yet, there is no pill that allows us to live to 150 years old. The research these claims are based on actually aimed to resolve debate about whether STACs, such as the resveratrol found in red wine, can activate the ageing- and disease-related SIRT1 protein. The results suggest that these compounds do in fact directly activate this protein.
Compounds that can activate the SIRT1 protein are of great interest to longevity researchers. This is because they have found that activating similar sirtuin proteins in yeast, flies and worms extends their lifespan. It remains to be seen whether or not producing these compounds can increase the human lifespan. 
Researchers have pointed out that the amount of resveratrol in red wine is significantly lower than the amounts fed to mice in previous research. The lead researcher said that, "at least 100 glasses [of red wine] would be needed each day to get the levels shown to improve health in mice". Research is also being conducted into similar synthetic chemicals, as some of these seem to have greater effects in the laboratory.
This type of study is a necessary and useful early step in the development of drugs. On its own, however, it is certainly not sufficient evidence for us to be able to say that STAC compounds can reverse human ageing or help us live for 150 years.
Media claims that such a pill is five years around the corner are ludicrously optimistic. While researchers suggest that pre-clinical studies in mice have been initiated, these studies would need to prove effective and safe, and then be followed by furtherrandomised control trials in humans.
It is important to note that the media coverage of this research failed to highlight the fact that the best way to reap the benefits of sirtuins is to take regular exercise.
Rather than waiting for scientists to develop a wonder drug, why not go for a walk in your local park, go for a swim or have a leisurely bike ride? Read more about the importance of exercise for older adults.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links to the headlines

Pill to live to 150. The Daily Telegraph, March 10 2013

Links to the science

Hubbard BP, Gomes A, Dai H, et al. Evidence for a Common Mechanism of SIRT1 Regulation by Allosteric Activators. Science. Published online March 8 2013

Sunday 10 March 2013

Bacon battered? Today’s headlines explained

reposted from: Cancer Research UK
crabsallover highlightskey pointscomments / links.



Posted on  by 


Sausages
Another study has linked processed meat to ill health
As if the horsemeat scandal wasn’t bad enough, this morning’s headlines brought further news of the dangers of eating too much processed meat: an increased risk of an early grave.
The news come from a huge Europe-wide study –called EPIC – that Cancer Research UK helps fund, and this is no flash in the pan – the findings are robust and important.
But many people are well aware of the downsides of a high-meat diet, and one could be forgiven for a certain amount of headline fatigue on this topic – after all it seems to come up at least once a year.
So what exactly does this study add to what we already know – and, importantly, should we care?

What’s the difference between ‘processed’ meat and ‘red’ meat?

The distinction is slightly artificial, as it’s basically a tool to allow researchers to classify elements of people’s diets into things like red meat, processed meat, poultry, fish, etc, and then carry out statistical analysis comparing these different groups (see below).
But there is a difference – as explained in this excellent interview from the BBC Today programme this morning. In essence, ‘processed’ meat is meat that has been either cured (like ham, salami etc), or salted or otherwise preserved (e.g. frozen supermarket mince – including burgers – sausages, and bacon).
But it doesn’t include fresh meat or mince – so if you make your own burgers from steak (lucky you), that’s counted as ‘red’, not processed meat.

What did we already know?

We’ve blogged before about meat and cancer, and this lengthy post from a few years back, on a similar large US study, is worth reading.
The long and short of it is a) that certain cancers – particularly bowel cancer – are more common among people who eat the most red or processed meat, b) that these people are also at higher risk of dying from these cancers and c) this is probably because of certain chemicals found in red meat (naturally occurring haem) and processed meat (‘nitroso’ preservatives).

Where do the new findings come from?

EPIC is an enormous study, and has been tracking the diets, lifestyles, medical records and death certificates of around half a million Europeans, from ten different countries, for well over a decade and a half.
This has allowed researchers to periodically pull all the data together and analyse them for patterns, using the sorts of statistical mathematics that make your brain hurt. We’re not going to go into them here, but take our word for it – they’re very complex and rigorous, and the researchers have gone as far as it’s feasible to go to account for other behaviours like smoking, weight, exercise and so on.
Even then, it has to be said, it’s impossible to do this 100 per cent – these factors may still have had a weak influence on the latest findings.
They also performed a statistical ‘stress tests’ on their results, called a ‘significance’ test, which allowed them to work out whether the results are valid. It’s a slightly unfortunate use of the word ‘significance’, as most people take it to mean ‘important’ – whereas here it just means ‘reliable’.
When stories like this hit the headlines, some tend to trot out the well-worn cliché, ‘there are lies, damned lies… and statistics’, and we wish they’d stop – this is a ‘real’ finding, from a large, well-run study… and it matters.

What did they find?

Sausages
More than 160g of processed meat
Fortunately, this research is published in an ‘open access’ journal, so you can go and read its findings here, free of charge, if you so wish. However, if you don’t speak science, here are the key findings:
  • Over an average of nearly 13 years, 26,344 study participants died.
  • Of these, about 5,500 died of cardiovascular diseases, nearly 10,000 of cancer, about 1,000 of respiratory diseases, 700-odd of digestive tract diseases, and about 9,000 of ‘other causes’.
  • People who ate more than 160g of processed meat per day (NB, that’s a lot of daily meat) were 18 per cent more likely to die than those who ate between 10 and 20g a day.
  • The link between red meat and premature death wasn’t statistically significant after the researchers had corrected for possible biases.
  • There was no link between eating more poultry and an early death.
  • Those who ate the most processed meat also ate the fewest fruit and vegetables and were more likely to smoke, while men who ate a lot of meat also tended to drink heavily – this is significant, in both senses of the word (see below).
  • If everyone on the study had eaten 20g of meat or less daily – about a sausage day – then the researchers reckon that overall death rate would have dropped by 3 per cent. We reckon that works out as about 800 deaths (out of a total of just over 26,000) over the study period (using the famous ‘back of an envelope’ method).

What does it all mean?

Firstly, this research emphatically doesn’t mean that meat is ‘bad for you’. What it means is ‘too much processed meat, regularly, over too long a time period’ is bad for you. This is an important distinction, and one that often gets lost in the media hullabaloo over ‘Salami Suicide’ and the like.
And meat is good for you, in moderation. As the researchers write:
A diet rich in meat has several potential nutritional benefits… Meat is rich in protein, iron, zinc and B-vitamins, as well as vitamin A. The bioavailability of iron and folate from meat is higher than from plant products such as grains and leafy green vegetables.
The downside is that it’s also often high in cholesterol and saturated fats, as well as the cancer-linked nasties we discussed above. It’s all about balance.
Secondly, as the authors note,
Meat consumption has increased since World War II. While this increase has long been confined to the Western world, that is, North America, North and Western Europe, and Australia/New Zealand, meat consumption is now also on the rise in other countries, such as China, due to their economic development.
This research is more evidence that growing rates of meat consumption across the world are a contributing to increased levels of disease and premature death, and that this should be taken seriously. We saw only yesterday how the world’s cancer leaders want action to tackle the growing global cancer burden, and earlier in the week how the UK’s health outcomes are sliding down international league tables.

And another thing

But there’s another story here too.
As we noted above, the study showed high levels of processed meat consumption tended to go hand in hand with a diet low in fruit and veg, and with high levels of alcohol consumption and smoking. These are generally behaviours that are found more often in lower income groups, and point to an underlying problem – growing income and health inequality (a point excellently summarised by Ally Fogg in the Guardian earlier this week).
So we think access to good quality, affordable food; information about healthy diets (including properly labelled food); and restrictions on how ‘risky’ foods like processed meat are marketed (particularly to children), are all necessary in these straitened times if we’re to prevent the health gap between top and bottom, mapped out so eloquently by Sir Michael Marmot in 2010, from widening further.
And finally, if you’re someone who enjoys a really ‘meaty’ diet (you know who you are), but your diet contains lots of salami, chorizo, ham and other cured meats, you’d do well to occasionally, maybe, think about swapping these for chicken, fish or (thinking environmentally here) vegetables like beans or lentils. We don’t want to wag fingers, nor apportion blame.
We just want people to be aware of what the evidence says.
And basically, it says ‘everything in moderation’ (except smoking).
But you knew that already.
Henry Scowcroft

Reference

  • Rohrmann S., Overvad K., Bueno-de-Mesquita H.B., Jakobsen M.U., Egeberg R., Tjonneland A., Nailler L., Boutron-Ruault M.C., Clavel-Chapelon F. & Krogh V. & (2013). Meat consumption and mortality – results from the European Prospective Investigation into Cancer and Nutrition, BMC Medicine, 11 (1) 63. DOI: 

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Saturday 9 March 2013

Sirtuin mechanism, resveratrol & calorie restriction by David Stipp

reposted from: Scientific American Blogs
crabsallover highlightskey pointscomments / links.


What is it about sirtuins? Few research topics have engendered fiercer controversy in recent years than these enzymes, channels through which the famous red-wine ingredient resveratrol appears to exert effects like those of calorie restriction, a reduction of food intake known to slow ageing in many species.

The most basic bone of contention is whether resveratrol really activates sirtuins. The idea that it revs up the enzymes dates from the first study that suggested it has anti-ageing power—a 2003 investigation led by Harvard University’s David Sinclair. Two years later, other researchers published studies suggesting that resveratrol only stimulates sirtuins in misleading test-tube assays—and probably not in living cells. The skeptics’ findings put a cloud over Sinclair’s research and raised questions about work at Sirtris Pharmaceuticals, a biotech he cofounded.

But now Sinclair’s group has marshalled evidence that sirtuin activators really do stimulate the enzymes as originally proposed—at least in certain situations. Their new findings are reported in the March 8 issue of Science in a study coauthored by Sirtris researchers. A second study led by Clemens Steegborn at the University of Bayreuth in Germany, published this week in Aging, supports the Harvard group’s analysis.

Together the studies “appear to elegantly resolve” the mechanism controversy, according to a commentary in Aging by Sita Kugel and Raul Mostoslavsky, researchers at Massachusetts General Hospital in Boston. Mostoslavsky is a member of Sirtris’s scientific advisory board.

The new data won’t end the sirtuins debate, which concerns issues besides the mechanism question—the most hotly contested one is whether sirtuins are centrally involved in calorie restriction’s anti-aging effects. But the studies should restore lost luster to Sinclair’s work on sirtuins. They’re also good news for GlaxoSmithKline, which bought Sirtris in 2008 for a hefty $720 million—the skeptics’ reports had suggested that Glaxo’s effort to develop sirtuin activators as drugs was based on a cracked foundation.

The mechanism debate began after Sinclair and colleagues discovered in 2003 that resveratrol sped up the action of SIR2, a yeast sirtuin thought to mediate calorie restriction’s effects, and of SIRT1, a mammalian version of SIR2, in test-tube assays. Using a fluorescent molecule called Fluor-de-Lys to flag the enzyme’s activity, their experiments indicated that resveratrol interacted with the sirtuins in a way that accelerated their normal function. (SIR2 and SIRT1 regulate the activity of various “substrate” molecules in cells by removing pieces from them called acetyl groups.) The sirtuin stimulation extended yeast cells’ lifespans by up to 60%, according to the report.

But in 2005, skeptics reported that resveratrol failed to boost sirtuins’ action without the presence of Fluor-de-Lys. (Attached to substrates, the fluorescent molecules generated a telltale glow when acetyl groups were removed by sirtuins.) That suggested Fluor-de-Lys inadvertently had played a central role in producing the sirtuin-boosting effect—and that the effect didn’t occur outside the test tube. 
In 2009 and 2010, respectively, researchers at Amgen and Pfizer reported similar findings.

Meanwhile, many studies in living organisms were reported that indicated resveratrol and other sirtuin activators induce calorie-restriction-like effects by stimulating the enzymes. But many observers found them suspect. Indeed, soon after the Pfizer report, a scientist tracking the debate emailed me that it seemed “sirtuins and resveratrol and the entire Sirtris enterprise are a house of cards that is in the process of crumbling badly.”

It appeared to the skeptics that purported sirtuin activators, at most, might indirectly boost the enzymes via unknown knock-on effects in cells. That led many to conclude that Glaxo had made a costly blunder when it bought Sirtris in hopes of turning its compounds into drugs targeting SIRT1 and other sirtuins.

But Sinclair theorized that the fluorescent molecules may have acted a lot like naturally-occurring parts of sirtuin substrates in the test-tube assay. If so, his team’s apparently misleading experiments with Fluor-de-Lys could have pointed, fortuitiously, to a correct conclusion: That resveratrol can rev up sirtuins in living cells.

The new studies support this theory. Both indicated that the fluorescent molecules, which are hydrophobic (repelling water molecules), mimic hydrophobic amino acids found at two locations in certain SIRT1 substrate molecules. In fact, sirtuin activators appear to rev up SIRT1 only when it is interacting with a limited number of substrates that contain hydrophobic molecules at one or both of the two locations.

By a twist of fate, the substrate used by both Sinclair and his critics in their early test-tube experiments lacked the critical hydrophobic amino acids. That’s why resveratrol’s sirtuin-revving effect only occurred, as the skeptics reported, when that substrate was gussied up with Fluor-de-Lys—the fluorescent molecules substituted for the missing hydrophobic amino acids.

Importantly, according to the Sinclair group’s new data, substrates with such amino acids include ones thought to help induce some of calorie restriction’s key health-promoting effects, such as the “stress response,” which hardens cells against damage by DNA-mangling molecules.

In its latest study, Sinclair’s group also went beyond test-tube experiments to probe SIRT1’s action in living cells. This step was based on their discovery that the SIRT1 protein includes a single amino acid that’s critical for the boosting of the enzyme’s activity by resveratrol and other activators—when another amino acid is substituted for it, SIRT1 does its normal enzymatic thing but can’t be artificially revved up.
That enabled a revealing experiment: Sirtuin activators added to cells containing normal SIRT1 were found to enhance the cells’ mitochondrial function in a way reminiscent of calorie restriction’s effect. (Mitochondria, cells’ energy dynamos, are spruced up by calorie restriction.) But when the activators were added to cells whose SIRT1 lacked the critical amino acid, the mitochondrial boost didn’t occur. The results imply that SIRT1 serves as a key channel for inducing the mitochondrial effect, which the Sirtris compounds can amplify in cells.

Besides clearing up the mechanism issue, said Mostoslavsky, the new findings should aid drug development since they’ve illuminated how different sirtuin activators exert selective effects on SIRT1 substrates. That promises to lead to sirtuin-boosting medicines that confer specific therapeutic benefits, with few side effects, by targeting certain SIRT1 substrates and not others.



References:

Hubbard B.P. et al. (2013). Evidence for a common mechanism of SIRT1 regulation by allosteric activators. Science, 339, 1216-1219.

Kugel S., Mostoslavsky R. (2013). SIRT1 Activators: The Evidence STACKs Up. Aging, 5.
Lakshminarasimhan M., et al. (2013). SIRT1 activation by resveratrol is substrate sequence-selective. Aging, 5.

Yuan H., Marmorstein R. (2013). Red Wine, Toast of the Town (Again), Science, 339, 1156-1157.

Thursday 7 March 2013

Limiting processed meat consumption 'could prevent three per cent of premature deaths'

source: http://www.nhs.uk/news/2013/03March/Pages/Diet-high-in-processed-meat-threatens-health.aspx

I conclude I should eat ave. 50g/day red meat and 20g/day processed meat; 70g/day total meat (Dept. Health guideline)

Diet high in processed meat 'threatens health'



Processed meats include bacon, sausages and salami
The big health news of the week is the claim that eating a diet high in processed meat can increase the risk of premature death due to cancer and heart disease. 
The current media scare stems from a large Europe-wide study looking at diet and mortality, involving just under half a million people who were followed for an average of 12.7 years.
One of the main findings was that people in the study who ate the most processed meat (160g or more per day) had a 44% increased risk of dying during follow-up compared to those who ate the least (10g or less).
The link to red meat was less conclusive.
The researchers estimated that if we all ate less than 20g of processed meat (which is around a single small piece of bacon) a day, then 3.3% of all deaths could be avoided – which is where the media reports came from that processed meat is responsible for 1 in 30 deaths.
However, an important limitation (rightly highlighted by the authors) is the possibility that other health and lifestyle factors could be contributing towards premature death risks.
Nevertheless, the study does highlight the importance of eating a healthy balanced diet, containing a high amount of fruit and vegetables.

Processed meat

Processed meat refers to meat that has been preserved by smoking, curing, salting or adding preservatives. This includes sausages, bacon, ham, salami and pâtés.

Processed meat is usually high in fat and cholesterol, which can increase heart disease risk. A diet high in processed meat (regularly eating more than 90g a day) has also been linked to an increased risk of bowel cancer.

This study found that people who ate more than 160g a day had the highest risk of premature death – this is equivalent to eating a full English breakfast every morning.

The Department of Health recommends that you do not eat more than 70g of red or processed meat a day.

Where did the story come from?

The study was carried out by researchers from the Institute of Social and Preventive Medicine, University of Zurich, Switzerland, and a large number of other institutions across Europe.
Financial support was provided by a range of European organisations including, government, charity and academic institutions.
The study was published in thepeer-reviewed journal BMC Medicine, which is available on an open access basis.
The media stories are generally representative of the findings of this research, with most including the common sense advice that eating an occasional bacon sarnie won’t kill you – just don’t do it every day.
The claims that processed meat is responsible for 1 in 30 deaths are based on the researchers’ estimate that 3.3% of the deaths in this study could have been prevented if all those who took part in the study ate less than 20g of processed meat a day.

What kind of research was this?

Many past observational studies have suggested that high levels of red meat and processed meat consumption could be linked to a range of diseases, including cardiovascular diseases and various cancers, such as bowel cancer.
However, it can be difficult in such studies to exclude the possibility that the effect is not directly due to red and processed meats as such, but is due to the influence of other health and lifestyle factors. For example, people who eat a small amount of red and processed meat may also be eating higher amounts of fruit and vegetables, exercising more, be less likely to be overweight, smoke, or drink excess amounts of alcohol.
In the same vein, people who eat lots of processed meat may have other unhealthy habits such as drinking lots of alcohol and being heavy smokers.
This was a large cohort study using data collected as part of the European Prospective Investigation into Cancer and Nutrition (EPIC) study.
EPIC is an ongoing cohort study including more than 500,000 participants from 10 European countries.
The researchers took data from the EPIC study to look at the association between red meat, processed meat, and poultry meat consumption, and the risk of overall mortality and cause-specific mortality.

What did the research involve?

Men (aged 40 to 70) and women (aged 35 to 70) were recruited to EPIC between 1992 and 2000 (depending on the European study centre). After excluding those with self-reported cancer or heart disease, or those who did not report on smoking status at the time of enrolment, there were 448,568 people in the study.
Dietary assessment was performed slightly differently depending on the country:
  • seven countries gave self-administered dietary questionnaires (including data on 300-350 food items)
  • three countries administered a similar questionnaire by direct interview
  • two of the countries (UK and Sweden) also combined the questionnaires with a seven-day food diary
For the purposes of analysis, they grouped food products as follows:
  • red meat (beef, pork, mutton/lamb, horse, goat)
  • processed meat (including ham, bacon, sausages, or a small amount of minced meat as part of a ready-to-eat product – processed meat is mainly taken to be red meat, but it could be white as well)
  • white meat (poultry, including chicken, hen, turkey, duck, goose, unclassified poultry, and rabbit) 
Various other sociodemographic, health and lifestyle questions were also assessed at recruitment, including age, education, height and weight, medical history, alcohol consumption, and smoking history (current, past or never, including questions on frequency and type of tobacco smoked).
Follow-up of outcomes was to 2005-09, depending on the country, with an average follow-up of 12.7 years. Information on deaths and cause of death was obtained through record linkage with cancer registries, Boards of Health, and death indices in seven countries, and through active follow-up of participants (for example, mail, telephone, and medical records) in three countries.
Information on vital status could be obtained for 98% of the cohort, which is impressive given the size of the study.
Hazard ratios were calculated to examine the association between different types and quantities of meat and processed meat consumption and risk of death.
They adjusted analyses for the following cofounders:
  • age
  • study centre
  • weight and height
  • smoking history
  • alcohol intake
  • overall energy intake
  • physical activity levels
  • educational level

What were the basic results?

Compared to men and women who ate lower amounts of red and processed meat, those who ate the highest amounts tended to also eat fewer fruit and vegetables, be more likely to smoke, and less likely to have a university degree. Men who ate the highest amounts of red meat also drank more alcohol than those who ate lower amounts. This result was not seen in women.
During the average 12.7 year follow-up, there were 26,344 deaths (6% of the cohort), of these, 37% were due to cancer, 21% due to cardiovascular disease, 4% due to respiratory disease, 3% to digestive tract diseases, and the remainder due to various other causes.
Overall, there was a link between increasing processed meat consumption and risk of all-cause mortality. In the model adjusted for all confounders:
  • people who ate the highest amount of processed meat (160g per day) had 44% increased risk of death compared to those who ate 10-20g per day (hazard ratio (HR) 1.44, 95% confidence interval (CI) 1.24 to 1.66)
  • people who ate 80-160g a day had 21% increased risk (HR 1.21, 95% CI 1.14 to 1.28) and those who ate 40-80g a day had 9% increased risk (HR 1.09, 95% CI 1.05 to 1.14) compared to those who ate 10-20g per day
  • compared to those who ate 10-20g per day, there was no difference in risk with eating 0-10g or eating 10-40g
  • overall, eating an additional 50g of processed meat a day gave 18% increased mortality risk (HR 1.18. 95% CI 1.11 to 1.25)
  • eating an additional 50g of processed meat a day also gave a 30% increased risk of dying from any cardiovascular disease (HR 1.30, 95% CI 1.17 to 1.45), and an 11% increased risk of dying from any cancer (HR 1.11, 95% CI 1.03 to 1.21)
The link with red meat was not as strong as for processed meat:
  • eating the highest intake of red meat (160g per day) was associated with 14% increased risk of all-cause mortality compared to eating 10-20g per day (HR 1.14, 95% CI 1.01 to 1.28)
  • people who ate 20-160g of red meat a day were at no higher risk than those who ate 10-20g per day
  • people who ate the lowest amount (0-10g a day) also had increased mortality risk compared to those who ate 10-20g per day.
  • unlike with processed meat, the researchers found no overall significant increase in mortality risk for eating an additional 50g of red meat a day


There was no link between death risk and poultry consumption.
The researchers estimated that 3.3% of all deaths could be avoided if all people ate less than 20g per day of processed meat.

How did the researchers interpret the results?

The researchers conclude that their analysis supports a ‘moderate association’ between increased processed meat consumption and increased mortality, in particular due to cardiovascular diseases, but also cancer.

Conclusion

This is a useful study examining whether there is an increased risk of dying from any cause, and from specific causes, with increased consumption of red meat and processed meat. The link to red meat was less conclusive, but there appeared to be a consistent link between increasing processed meat consumption and mortality risk.
The study has many strengths, including that it followed a large number of adults from across 10 European countries for an average 12.7 years, with almost complete follow-up.
The study used reliable methods to assess mortality outcomes. Food frequency questionnaires will unavoidably include some inaccuracy (for example, inaccurate recall or estimation of intake).
However, the researchers did attempt to validate the information through a series of 24-hour recalls.
The researchers have adjusted their analyses for age, study centre, weight and height, smoking and alcohol intake, overall energy intake, physical activity levels and educational level.
However, as the authors rightly conclude, the main limitation of the study is that it cannot completely exclude the possibility of residual confounding – that is, that the effects of these demographic, health and lifestyle factors, or others unmeasured, have not been fully accounted for.
These limitations apart, the study provides reasonably good evidence to support the importance of eating a healthy balanced diet, containing a high amount of fruit and vegetables. At the same time, it is important to moderate your consumption of foods high in salt, fat and sugar, which includes many processed foods.
The occasional bacon sandwich or full English breakfast probably won’t do significant damage to your health. But these should be occasional treats and not a staple of your diet. 
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.



reposted from: Cancer Research UK
crabsallover highlightskey pointscomments / links.


Cancer News
Limiting processed meat consumption 'could prevent three per cent of premature deaths'
Thursday 7 March 2013

If everyone ate less than 20g of processed meat a day, there would be a three per cent drop in premature deaths from cancer and heart disease, according to new European research.

High consumption of red and processed meat has previously been linked to an increased risk of several types of cancer, particularly bowel cancer, as well as cardiovascular diseases.

The European Prospective Investigation into Cancer and Nutrition (EPIC) study - part-funded by Cancer Research UK - is following the diets, medical records and death certificates of half a million men and women from 10 European countries.

Its latest analysis, published in the journal BMC Medicine, looked at patterns of consumption of meat among participants, and how this related to their cause of death.

Over an average of nearly 13 years, 26,344 study participants died. Of these, 5,556 died of cardiovascular diseases, 9,861 of cancer, 1,068 of respiratory diseases, 715 of digestive tract diseases, and 9,144 of other causes.

Analysis showed that a person's risk of premature death from cancer or heart disease increased with the amount of processed meat they ate, even once other lifestyle variables were factored in.

No link was seen between red meat or poultry.

Those who ate the most processed meat also ate the fewest fruit and vegetables and were more likely to smoke, while men who ate a lot of meat also tended to drink heavily, the study found.

Yinka Ebo, senior health information officer at Cancer Research UK, said: "There's a clear link between eating too much processed meat and bowel cancer, but this study suggests that cutting down on these meats could also reduce the risk of dying prematurely.

"There's no need to abandon meat altogether, but if you eat a lot of processed meat it's worth cutting down by eating smaller and fewer portions, or eating fish, poultry or beans instead," she added.

Copyright Press Association 2013

Rohrmann S, et al. Meat consumption and mortality - results from the European Prospective Investigation into Cancer and Nutrition (2013) BMC Medicine



Nonparametric regression curve for the relation of processed meat intake at recruitment with all-cause mortality, European Prospective Investigation into Cancer and Nutrition (EPIC), 1992-2009. Solid line, effect estimate; dotted lines, 95 percent confidence interval.
Rohrmann et al. BMC Medicine 2013 11:63   doi:10.1186/1741-7015-11-63