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  • Obesity is common, serious and costly
  • Obese adults in the UK will soar by a staggering 73% to 26m by 2030
  • Obesity generates an annual loss equivalent to 3% of the UK’s GDP
  • Obesity cost NHS England £8bn in 2015
  • The obesity epidemic will only get worse unless we take effective action
  • Innovative research to control appetite could provide a cheap and scalable answer to the obesity epidemic
  • The UK’s obesity crisis should learn from the way AIDS was tackled 

Can the obesity epidemic learn from the way Aids was tackled?
 
Obesity is a common chronic health challenge, which is serious and costly.It is one of the biggest risk factors for type-2 diabetes (T2DM) and together - obesity and T2DM - form a rapidly growing global diabesity epidemic, which today affects some 9m people in England.
 
Experts forecast the incidence rate of obesity will rise sharply, and bankrupt the NHS. Conventional strategies to reduce obesity and prevent T2DM have failed. According to the Mayo Clinic it is common to regain weight no matter what weight loss treatment methods you try, and you might even regain weight after weight-loss surgery. This Commentary suggests that extra resources are urgently needed to accelerate and broaden innovative obesity research.
  
Efforts to tackle obesity are low priority and fragmented
 
Overweight and obesity lead to adverse metabolic effects on blood pressure, cholesterol, triglycerides and insulin resistance. Risks of coronary heart disease, ischemic stroke, and T2DM increase steadily with raised body mass index (BMI). High BMI also increases the risk of osteoarthritis; sleep apnoea, gallbladder disease, and some cancers. Cancer Research UK predicts that obesity related cancers are expected to increase 45% in the next two decades, causing 700,000 new cases of cancer. Mortality rates will increase with increasing degrees of obesity. It is therefore important that obesity is treated aggressively. According to a 2014 McKinsey Global Institute study, the UK’s Government efforts to tackle obesity are ''too fragmented to be effective'', while investment in obesity prevention is ''relatively low given the scale of the problem''.
 
A multi-generational problem
 
The 2014 Health Survey found that 61.7% of adults in England (16 years or over) are either overweight or obese, and the prevalence of obesity among adults rose from 14.9% to 25.6% between 1993 and 2014. The number of obese adults in the UK is forecast to soar by a staggering 73% to 26m over the next 20 years.

In 2014-15, there were 440,288 hospital admissions in England due to obesity: 10 times higher than the 40,741 recorded in 2004-5. In England one in five children in their first year at school, and one in three in year 6 are obese or overweight. Also, in the past 10 years there has been a doubling of children admitted to hospital for obesity. Over the past three years 2,015 overweight youngsters needed hospital treatment, and 43 of these have had to undergo weight-loss surgery to reduce the size of their stomachs. Today, diabesity is a multi-generational problem, which suggests that far worse is still to come.
 
Costs and spends
 
The UK spends less than £638 million a year on obesity prevention programs - about 1% of the country's social cost of obesity. But the NHS spends about £8bn a year on the treatment costs of conditions related to being overweight or obese and a further £10bn on diabetes.
 
Obesity is a greater burden on the UK’s economy than armed violence, war and terrorism, costing the country nearly £47bn a year, the 2014 McKinsey study found. Obesity has the second-largest economic impact on the UK behind smoking, generating an annual loss equivalent to 3% of GDP. The current rate of obesity and overweight conditions suggest the cost to NHS England alone could increase from £8bn in 2015 to between £10bn and £12bn in 2020.

 
19th century technologies for a 21st pandemic
 
A year after the publication of the McKinsey study, the UK government launched a national Diabetes Prevention Program (DPP) led by NHS England, Public Health England (PHE), and the charity Diabetes UK (DUK). The program offers people at risk of T2DM an intensive personalised course in weight loss, physical activity and diet, comprising of 13 one-to-one, two-hour sessions, spread over nine months, and is expected to significantly reduce the estimated five million overweight and obese people in England, and thereby prevent them from developing T2DM. A previous Commentary predicted that the DPP would fail because it is using a 19th century labour intensive method to address a 21st epidemic.
 
This suggests that the diabesity epidemic will only get worse unless we take more urgent and effective action. A view supported by Majid Ezzati, Professor of Global Environmental Health at Imperial College, London, and the senior author of the most comprehensive review of obesity ever undertaken, and published in The Lancet in April 2016. According to Ezzati, “The epidemic of severe obesity is too extensive to be tackled with medications such as blood pressure lowering drugs or diabetes treatments alone, or with a few extra bike lanes”.

 
Radical action: weight loss surgery
 
The gravity of the UK’s obesity epidemic is demonstrated by the National Institute for Health and Care Excellence (Nice) 2016 suggestion to lower the threshold at which overweight people are offered weight loss surgery. The UK lags behind other European countries in this regard, and experts argue that lowering the threshold would mean the number of people who qualify for weight loss surgery would increase significantly.

According to a report prepared by English surgeons, weight-loss surgery would make people healthier and save the NHS money. The report concluded that after weight loss surgery obese people are 70% less likely to have a heart attack, those with T2DM are nine times more likely to see major improvements in their condition, and also the surgery has a positive effect on angina and sleep apnoea. If all the 1.4m most severely obese people in the UK had weight loss surgery, which costs the NHS around £6,000 per operation, the total cost would be £8.4bn.

 
Weight loss surgery and the brain
 
Initially it was thought that weight-loss surgery worked by reducing the amount of food that can be held by the stomach. However, some patients were found to have elevated levels of satiety hormones, the chemical signals released by the gut to control digestion and hunger cravings in the brain. Patients who had undergone surgery were also found to prefer less fatty foods, which supports the thesis that the hormones also change the patients’ desire to eat, and reinforce the gut brain relationship. This finding reinforces the important link between the gut and the brain on which some of the most promising obesity research is predicated.
 
Gut brain relationship
 
Dr Syed Sufyan Hussain, Darzi Fellow in Clinical Leadership, Specialist Registrar and Honorary Clinical Lecturer in Diabetes, Endocrinology and Metabolism at Imperial College London describes the gut-brain relationship and explains why we eat and why we stop eating:
 

 
Cheap, safe and scalable treatment for obesity
 
The person who has spent most of his professional life searching for cheap, safe and scalable alternatives to weight loss surgery and ineffective weight loss therapies is Professor Sir Steve Bloom, Head of Diabetes, Endocrinology and Metabolism at Imperial College London. Bloom believes that the answer to the UK’s obesity epidemic lies in the gut-brain relationship, and is working on two innovative methods of appetite control, which he and his colleagues believe could significantly reduce the burden of obesity.
 
Method 1: an implantable microchip
 
One method is comprised of a small implantable microchip attached to the vagus nerve to suppress appetite in a natural way. The chip reads and processes both electrical and chemical signatures of appetite within the vagus nerve, and then sends electrical signals to the brain to either reduce or stop eating. Bloom has proven the method’s concept, and in 2013 was awarded €7m from the European Research Council to continue his research. Early findings suggest that chemical rather than electrical impulses are more selective and precise, and the chip reduces both consumption and hunger pangs. All things being equal, it will take another 10 years before this treatment gets to market.
 
Method 2: naturally occurring hormones
 
Bloom is also working on another method to treat obesity, which uses naturally occurring hormones that reduce appetite. Early clinical studies suggest that people will consume 13% fewer calories when they eat a meal after taking the hormones. In 2013 Bloom received £2m from the Medical Research Council to develop this research. One of the significant challenges he faces is hormones normally last only a few minutes in the human body. To overcome this Bloom and his colleagues have had to develop versions of the hormones that can last up to a week before they start breaking down. This suggests that patients could take a single weekly injection to control their appetites. Another approach would be to develop a device, which delivers the hormones continuously. While promising, this method too will take 10 years to get to market.
 
Takeaway: treat obesity the same as Aids
 
Bloom believes that if we approached obesity as we did Aids, the time to develop a cheap, effective and scalable drug for weight control could be cut by half. "The obesity pandemic is the biggest disease that has hit mankind ever in terms  [of] numbers. It is killing more people than anything else has ever killed, . . . . . . . in terms of disease [there are] more deaths from obesity than anything we have known about. The time needed to develop an effective drug could be cut by more than half if conservative checks and balances were loosened. I think we might need to treat obesity in a hurry, and we are being held up. The Aids lobby forced Aids’ drugs on to the market before they had finished testing, but they turned out to be useful and lives were saved. Something similar should be considered for obesity,” says Bloom.
 
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Is cancer avoidable?

  • Cancer results when stem cells divide and mutate uncontrollably
  • Whether this is predominantly the result of intrinsic or extrinsic factors is unclear
  • Some experts say 65% of cancers result from intrinsic factors and are unavoidable
  • Other experts say most cancers result from extrinsic factors and are avoidable
  • Cancer strategy should not hide behind ‘bad luck’
  • Resources need to be allocated more smartly to prevent cancer

Is cancer the result of bad luck and unavoidable, or is it self-inflicted and prevented by simple lifestyles choices? Two 2015 studies arrive at strikingly different conclusions.
 
One, carried out by researchers from the John Hopkins Kimmel Cancer Centre and published in January 2015 in the journal Science, suggests that two thirds of cancers result from bad luck. Another, carried out by researchers from the Stony Brook Cancer Centre in New York and published in December 2015 in the journal Nature rebuts the findings of the Science paper, and suggests that 70 to 90% of cancer risk is self-inflicted and therefore can be avoided.

Which is right? And, why should this concern us?
 

Cancer


Cancer is a complex group of diseases characterised by the uncontrolled growth and spread of abnormal cells. If this is not checked it can cause death. Nearly 80% of all cancer diagnoses are in people aged 55 or older. Some facts about cancer In 2015 around 1.7m new cancer cases were diagnosed in the US, and about 330,000 in the UK. Each year, there are some 589,430 cancer deaths in the US, and some 162,000 in the UK. The annual treatment cost of cancer for the US is about $90bn and for the UK about £10bn. The causes of cancer include genetic, and lifestyle factors; certain types of infections; and environmental exposures to different types of chemicals and radiation.  Whitfield Growdon, Oncology Surgeon at Massachusetts General Hospital and professor at the Harvard University Medical School describes cancer and the causes of cancer:


         

         
            (click on the image to play the video) 


 

The Science paper: cancer is unavoidable

The Science paper found that 65% of cancer cases are a result of bad luck: random DNA mutations in tissue cells during the ordinary process of stem cell division; regardless of lifestyle and hereditary factors. The remaining 35% of cancer cases, say the authors, are caused by a combination of similar mutations and some environmental and hereditary factors. One implication of these findings is that preventative strategies will not make a significant difference to the incidence rates of most adult cancers. So accordingly, the optimal way to reduce adult cancers is early detection when they are still curable by surgery.
 
Stem cell division is the normal process of cell renewal, but the extent to which random cell mutations contribute to cancer incidence, compared with hereditary or environmental factors, is not altogether clear. This is what the John Hopkins researchers sought to address with their study. Scientists examined 31 tissue types to discover whether the sheer number of cell divisions increases the number of DNA mutations, and therefore make a given tissue more prone to become cancerous.
 
Researchers developed a mathematical model, which suggested that it is incorrect to assume that cancer may be prevented with “good genes” even though we smoke, drink heavily, and carry excess weight. Their study found that, "the majority [of adult cancer risk] is due to bad luck, that is, random mutations arising during DNA replication in normal, noncancerous stem cells."  And, "this is important not only for understanding the disease, but also for designing strategies to limit the mortality it causes," say the researchers.
 
According to the Science paper bad luck mutations account for 22 of 31 adult cancer types, including ovarian, pancreatic, bone and testicular cancers. The remaining nine, including lung, skin and colorectal cancers, occurred more often than the random mutation rate predicted. This suggests that in these cancers, either inherited genes or environmental factors have a significant influence on cases.
 
Our study shows, in general, that a change in the number of stem cell divisions in a tissue type is highly correlated with a change in the incidence of cancer in that same tissue,” says Bert Vogelstein, Clayton Professor of Oncology at the John Hopkins University School of Medicine, and co-author of the study. One example, he says, is in colon tissue, which in humans, undergoes four times more stem cell divisions than small intestine tissue. Likewise, colon cancer is much more prevalent than small intestinal cancer.
 
In a BBC Radio 4 interview Cristian Tomasetti, co-author of the study said: “Let’s say my parents smoked all their lives, and they never got lung cancer. If I strongly believed cancer was only environment, or the genes that are inherited, then since my parents didn’t get cancer, I may think I must have good genes, and it would be OK to for me to smoke. On the contrary, our study says ‘no’, my parents were just extremely lucky, and played a very dangerous game.


Related Commentaries


Liquid biopsies to detect pancreatic cancer are near 
Full circle in cancer research
Is immunotherapy a breakthrough in cancer treatment?
Is patient engagement the new blockbuster drug? 
We should give up trying cure cancer



The Nature paper: cancer is avoidable

In a BBC interview, Yusuf Hannun, Director of the Stony Brook Cancer Center, Joel Strum Kenny Professor of Cancer Research and one of the authors of the Nature paper, challenged the findings of the ‘bad luck’ study. He suggests that hiding behind ‘bad luck’ is like playing Russian roulette with one bullet; one in six will get cancer. "What a smoker does is add two or three more bullets to the revolver and pulls the trigger. Although there is still an element of luck, because not every smoker gets cancer, they have stacked the odds against themselves. From a public health point of view, we want to remove as many bullets as possible from the revolver," says Hannun.
 
The Nature paper rebuts the John Hopkins ‘bad luck’ thesis. Its lead author, Song Wu, from the Department of Applied Mathematics and Statistics at Stony Brook University, notes that the Science paper had not conducted an alternative analysis to determine the extent to which external risk factors contribute to cancer development, and it assumes that the two variables: intrinsic stem-cell division rates, and extrinsic factors, are independent. “But what if environmental factors affect stem-cell division rates, as radiation is known to do?” asks Wu.
 
Wu and his colleagues provide an alternative analysis by applying four analytical approaches to the data that were used in the earlier Science paper and arrive at a radically different conclusion: that 70 to 90% of adult cancer cases result from environmental and lifestyle factors, such as smoking, drinking alcohol, sun exposure and air pollution. Wu admits that some rare cancers can result from genetic mutations, but suggest that incidence rates of cancers are far too high to be explained primarily by mutations in cell division.
 
According to the Nature paper, if intrinsic risk factors did play a key role in cancer development, the total number of divisions in tissue stem cells would correlate with lifetime cancer risk, and the incidence rates of the disease would be less than it actually is. Wu and his colleagues analyzed the same 31 cancer types as in the earlier Science paper, and evaluated the number of stem cell divisions in each. They then compared these rates with lifetime cancer incidence among the same cancer types. This allowed them to calculate the contribution of stem cell division to cancer risk.
 
Wu et al also pursued epidemiological evidence to further access the contribution of environmental factors to cancer risk. They analyzed previous cancer studies, which show how immigrants moving from regions of low cancer incidence to regions with high cancer incidence soon develop the same tumor rates, suggesting that the risks are environmental rather than biological or genetic.
 
The researchers’ findings suggest that mutations during cell division rarely accumulate to the point of producing cancer, even in tissues with relatively high rates of cell division. In almost all cases, the Nature paper found that some exposure to carcinogens or other environmental factors would be needed to trigger disease, which again suggested that the risks of the most prevalent adult cancers are due to environmental factors. For example, 75% of the risk of colorectal cancer is due to diet, 86% per cent of the risk of skin cancer is due to sun exposure, and 75% of the risk of developing head and neck cancers is due to tobacco and alcohol.
 
The Nature paper concludes that bad luck, or intrinsic factors, only explain 10 to 30% of cancer cases, while 70 to 90% of adult cancer cases result from environmental and lifestyle factors. "Irrespective of whether a subpopulation or all dividing cells contribute to cancer, these results indicate that intrinsic factors do not play a major causal role," say the authors. This suggests that many adult cancers may be more preventable than previously thought. 
 

Preventing cancer 

Even the Science study concedes that extrinsic factors play a role in 35% of the most common adult cancers, including lung, skin and colorectal cancers. This, together with the Nature study, and the rising incidence of avoidable cancers, should be a wake-up call because a substantial proportion of cancers can be prevented.
 
Hannun is right! Whatever the causes of cancer, we should not ‘hide behind bad luck’.  We should act on evidence, which suggests that it is within everyone’s capabilities to make simple lifestyle changes that can prevent common adult cancers.  Although maintaining a healthy lifestyle is no guarantee of not getting cancer, the Nature paper underlines the fact that a healthy lifestyle stacks the odds in your favor.  The paper supports preventative cancer strategies.
 
In 2015, tobacco smoking caused about 171,000 of the estimated 589,430 cancer deaths in the US. The Nature paper suggests that the overwhelming majority of these could have been prevented. In addition, the World Cancer Research Fund has estimated that up to 33% of the cancer cases that occur in developed countries are related to being overweight or to obesity, physical inactivity, and/or poor nutrition, and thus could also be prevented.
 
It seems reasonable to suggest that the risk of cancer can be significantly reduced by: (i) a cessation of smoking, (ii) drinking less alcohol, (iii) protecting your skin from the sun, (iv) eating healthily, (v) maintaining a healthy weight, and (vi) exercising regularly.
 

The UK Position

Everyone understands the enormity of the burden of cancer, and what to do to reduce its risk. In the UK, as in other wealthy countries, there is no lack of money, no lack of resources, and no lack of expertise for cancer care. The annual spend on cancer diagnosis and treatment alone in the UK is about £10 billion. The UK also has a government appointed Cancer Czar charged with producing a national cancer plan to bring Britain's cancer survival rates up to those of European levels. Despite our understanding and all these resources, a 2014 study published in the Lancet suggests that cancer survival rates in the UK still lag more than 20 years behind many other European countries, and that people are dying needlessly.  Why is this?
 

Fear of preventative medicine 

Writing in The Times in January 2016, Sir Liam Donaldson, a former UK Chief Medical Officer, suggested that although preventative healthcare strategies are vital “to provide safe, high quality care without running out of money”, governments avoid helping the public to mitigate the risks of modern living, which can cause cancer, because of  “two primal political forces: the mortal dread of being labeled a ‘nanny state’, and a fear of removing people’s perceived pleasures.
 
During Donaldson’s tenure between 1998 and 2010, the government rejected his recommendation for a minimum unit price for alcohol, and for the same reasons in 2014, the government rejected a tax on sugar recommended by Public Health England. Excess sugar increases the risk of cancer, heart disease and diabetes. According to Donaldson, without effective government action to lower the vast and escalating burden of cancer, and other chronic diseases, the NHS is unsustainable.
 
The missing link in preventative strategies is behavioral techniques that engage people who are at risk and help them change their behaviors. Such techniques have been demonstrated to be successful in both the UK and US. They explain how people behave, and encourage them to reduce unhelpful influences on their health, and change the way they think and act about important health-related issues such as diets, lifestyles, screenings and medication-management. See: Behavioral Science provides the key to reducing diabetes
 

Takeaway 

It is crucial that the UK government now embraces behavioral techniques to curb the curse of cancer.  Donaldson is right: if cancer, and other chronic diseases, which together consume the overwhelming percentage of healthcare expenditure, are not prevented the NHS will become unsustainable.

 
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A breakthrough in the treatment of prostate cancer

  • Experts describe new prostate cancer study as the disease’s ‘Rosetta Stone’

  • Prostate cancer kills nearly 11,000 men each year in the UK alone

  • Men with untreatable prostate cancer could benefit from standard drugs

  • Study opens black box of genetics to treat previously untreatable cancer

  • Mediterranean diet lowers mortality risk for men with prostate cancer

A new UK-US cancer study could transform prostate cancer treatment, and give hope to sufferers whose cancers have become resistant to treatment. Experts’ hail the study as “incredibly exciting and ground breaking”. According to Professor Johann de Bono, of the Institute of Cancer Research, London, who led the British team, the study opens up a new era of treatment, in which men will be given drugs tailored to their tumours. 

Cancer is lethal when it metastasises and becomes resistant to drugs. The study, published in the journal Cell in 2015, involved 150 men close to death whose prostate cancers had spread throughout their bodies, and were not responding to available drugs. 
     

Prostate cancer’s ‘Rosetta Stone’

The research has opened up a black box in cancer genetics, and changes the way we think about and treat prostate cancer. Now that doctors have a map of which mutations to look for, they could search for them using a £200 test. 

De Bono, extracted samples of the cancer from metastatic tumors, and analysed their DNA, which showed that 90% of the men carried genetic mutations in their tumors, which matched drugs already on the market. A third of the men studied had tumors suitable for treatment with new drugs called PARP inhibitors.

‘’We're describing this study as prostate cancer's Rosetta Stone because of the ability it gives us to decode the complexity of the disease, and to translate the results into personalised treatment plans for patients. What's hugely encouraging is that many of the key mutations we have identified are ones targeted by existing cancer drugs - meaning that we could be entering a new era of personalised cancer treatment," says de Bono.

According to de Bono, “We are changing how long these men are living. This gives me hope that I can make a difference for men dying of prostate cancer. There is still a lot of work to do. This is not a cure, but it is a huge step forward.” 
 

Prostate cancer

In an earlier Commentary we discussed the dilemmas men face when they have been diagnosed with prostate cancer. Prostate cancer is the most common cancer in men, and each day in the UK alone 110 men are diagnosed with the disease. Cancer begins to grow in the prostate, a gland in the male reproductive system, and develops slowly. Although it can be cured if diagnosed early, there may be no signs that you have it for many years, and symptoms often only become apparent when your prostate is large enough to affect the urethra. Here cancer expert Professor Karol Sikora describes the symptoms of advanced prostate cancer:

         
                (click to play the video) 

Once prostate cancer begins to spread it becomes difficult to treat, and each year nearly 11,000 men die of the disease in the UK. Treatment options include watchful waiting, surgery, radiation, hormone therapy, chemotherapy, biological therapy and bisphosphonate therapy.
 

Mediterranean diet

According to research published in the journal Cancer Prevention Research, a Mediterranean diet rather than a Western diet may improve survivorship for men diagnosed with prostate cancer.

This is welcome news because there is a dearth of evidence to counsel men living with prostate cancer on how they can modify their lifestyle to lower the risk of mortality. The new study from Harvard’s Chan School of Public Health, investigated the diets of 926 men with prostate cancer for an average of 14 years after their diagnosis, and in 2015 published their findings, which suggest that people living with prostate cancer who ate a predominantly Western diet, high in red and processed meat, fatty dairy foods, and refined grains, were two-and-a-half times more likely to die from prostate cancer, and had a 67% increased risk of all-cause mortality, compared with participants who followed a Mediterranean diet, rich in vegetables, fruits, fish, whole grains, and healthy oils. In comparison, men who follow a Mediterranean diet had a 36% lower risk of all-cause mortality.

Lead author Meng Yang suggests treating the findings cautiously, "Given the scarcity of literature on the relationship between post-diagnostic diet and prostate cancer progression, and the small number of disease-specific deaths in the current study.”
 

Dietary supplements and vitamins

Researchers continue to look for foods (or substances in them) that can help lower prostate cancer risk. Scientists have found some substances in tomatoes (lycopenes) and soybeans (isoflavones) that might help prevent prostate cancer. Studies are now looking at the possible effects of these compounds more closely. Scientists are also trying to develop related compounds that are even more potent, and might be used as dietary supplements. 
 

Takeaways

Some studies suggest that certain vitamin and mineral supplements (such as vitamin E and selenium) might lower prostate cancer risk. But a large study of this issue, called the Selenium and Vitamin E Cancer Prevention Trial (SELECT), found that neither vitamin E nor selenium supplements lowered prostate cancer risk after daily use for about five years. In fact, men taking the vitamin E supplements were later found to have a slightly higher risk of prostate cancer.

De Bono’s breakthrough in cancer genetics means that many men whose prostate cancer was thought untreatable could be given drugs that are already on hospital shelves. Some patients have already benefited, and are alive more than a year on, despite only having been given weeks to live.

 
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