Dark chocolate cuts levels of stress hormones and rebalances other body chemicals, according to the Daily Mail. The Daily Express also featured the claim that chocolate reduces the risk of heart disease and high blood pressure and improves brain function.

The research behind these reports was commissioned by Nestlé. Researchers gave 30 healthy people 40g of dark chocolate a day for 14 days. They examined changes in metabolism and chemicals that are reportedly related to stress. The study’s methods have numerous limitations, including its small number of participants, short study period and selection of only young, healthy people to take part. Also, while the researchers measured levels of the “stress” hormones in urine, they did not directly look at changes in the participants’ stress levels.

By itself, the study is insufficient to provide evidence that dark chocolate has any benefits or effects on stress, psychological or mental health, or cardiovascular health.

Where did the story come from?

This research was conducted by Francois-Pierre J Martin and colleagues from Nestlé Research Center in Switzerland, and Metanomics GmbH in Germany. No external sources of funding were reported for this study. The study was published in the peer-reviewed Journal of Proteome Research.

Newspaper reports have mostly focussed on details from the presentation and conclusion of the study. However, the articles have not discussed the numerous limitations of this research. For example, while the Daily Mail mentions that the researchers work for Nestlé, it does not mention the small number of participants or the fact that effects were only measured over 14 days.

What kind of research was this?

This was a non-randomised experimental study in 30 individuals, which looked at the metabolic response to consuming 40g of dark chocolate a day for up to 14 days. The researchers particularly looked at how participants’ initial anxiety levels may affect changes in chemical measures related to stress.

This research model had a number of methodological flaws, including the small number of participants, the very short follow-up period and the lack of randomised groups. As such, only limited conclusions can be made from its results.

The trial could have been improved by randomising a larger number of people with equivalent anxiety levels to consume either dark chocolate or a placebo (if possible) and considering longer-term clinical effects (such as stress levels, weight gain and changes in cardiovascular health) over a longer follow-up period. The effects should also have been assessed by a researcher who was blinded to which group each participant had been assigned to.

What did the research involve?

The study recruited 30 ‘healthy and free living’ young adults: 19 women and 11 men, aged 18 to 34. The researchers excluded people who smoked, drank excessively, were overweight or obese, were on a diet or had medical disorders (including metabolic or eating disorders).

A validated psychological questionnaire was used to classify participants as having either low or high anxiety traits. According to the questionnaire, there were 9 high-anxiety women, 10 low-anxiety women, 4 high-anxiety men and 7 low-anxiety men.

Participants did not eat any chocolate in the eight days before the trial. They then received 40g of dark (74% cocoa) Nestlé chocolate a day for 14 days. They ate 20g mid-morning and 20g in the afternoon. On days one, eight and 15, the researchers took blood and urine samples. Metabolic changes following chocolate consumption were assessed using a number of different laboratory tests.

The study only analysed blood and urine samples, and did not provide any indication of the effects of chocolate consumption on the participant’s health, psychological status or wellbeing. This was another of the study’s limitations. It is also not known what other factors may have differed between the study participants, for example intake of other food and drinks or activity levels during the study period. In any case, the study’s duration was too short for questions about longer-term effects, such as cardiovascular disease or psychological changes, to be answered.

Stress hormones and energy levels in those who had higher anxiety at the start of the study were perceived to approach normal levels following chocolate consumption. However, as a psychological assessment was not performed at the end of the study, it is not clear whether these metabolic changes produced meaningful clinical differences.

What were the basic results?

The researchers noted that those who had higher anxiety traits initially demonstrated differences in energy metabolism in the body, hormone metabolism and microbe activity in the gut. Following dark chocolate consumption, there was a reduction in stress hormones excreted in the urine (cortisol and catecholamines) and reduced difference in energy metabolism and gut microbial activities in all participants.

How did the researchers interpret the results?

The researchers say that their study provides “strong evidence that a daily consumption of 40g of dark chocolate during a period of two weeks is sufficient to modify the metabolism of free living and healthy human subjects”. They say that these changes, seen after only two weeks, had “potential long-term consequences on human health”.

Conclusion

This study has numerous methodological flaws, and when considered in isolation does not provide any evidence that dark chocolate has benefits or effects on stress, psychological or mental health, or cardiovascular health.

• Although the researchers refer to their study as “randomised” in their report, there does not appear to be any control group, so it is unclear exactly what they mean by this term.
• The trial involved a small sample of 30 people. When the effects of chocolate were assessed in subgroups of people with different anxiety traits, the numbers were even smaller.
• All the people in this study were healthy young adults who were not overweight or obese, did not drink excessively or smoke, and did not have conditions such as diabetes. These results cannot be applied to people who are older, unwell or have less healthy lifestyles.
• While the researchers observed changes in metabolism or stress hormones, it is not definite that chocolate consumption was responsible for this. For example, being part of a trial situation and removing participants from everyday life may have caused this effect. Additionally, other measures that may have played a role in the metabolic changes, such as diet and physical activity, were not reported.
• A follow-up period of 14 days is far too short to make any conclusions about how long-term daily consumption may affect stress, mental health, cardiovascular health or weight gain. The researchers themselves do not state that dark chocolate has any of these effects.
• As the trial was conducted by the food manufacturer and confectioner Nestlé, the researchers may have had a vested interest in promoting the positive results of their trial.

Although this study provides little evidence to show that daily consumption of chocolate promotes mental or cardiovascular health, chocolate may still be enjoyed as part of a balanced diet. However, chocolate (even dark chocolate) is high in fat and calories and should only be eaten in moderate amounts.

Links To The Headlines

HOW A DAILY DOSE OF DARK CHOCOLATE CAN CURE STRESS. Daily Express, November 13 2009

How a bar of dark chocolate a day could cut your stress levels. Daily Mail, November 13 2009

Links To Science

Martin F-PJ, Rezzi S, Pere-Trepat E, et al. Metabolic Effects of Dark Chocolate Consumption on Energy, Gut Microbiota, and Stress-Related Metabolism in Free-Living Subjects. J. Proteome Res 2009; October 7

“About 145,000 people with dementia are wrongly being prescribed powerful anti-psychotic medication which causes around 1,800 deaths a year,” The Times reported. Many newspapers have reported this finding from a government-commissioned review. The government has responded to the report and agrees with its main findings.

The report makes several recommendations, mainly that people with dementia should receive antipsychotics only when they really need them, and that reducing their use in this group should be a priority for the NHS. It suggests this can be achieved by various means including training carers and medical staff to use alternatives to antipsychotics, providing psychological therapies for people with dementia and their carers, carrying out further research into alternative treatments, and audits.

The report estimated that antipsychotic use could be safely reduced to a third of its current usage over a period of three years.

Why are antipsychotics used in dementia?

Antipsychotics are used to manage the psychological and behavioural symptoms of dementia. These include aggression, agitation, shouting and sleep disturbance. It is important to find ways to deal with these symptoms as they can cause major problems for the person with dementia and their carers.

What is the basis for the news reports?

In 2008, the government asked Professor Sube Banerjee to carry out an independent report about the use of antipsychotic medication for people with dementia in the NHS in England. Professor Banerjee is a professor of mental health and ageing at the Institute of Psychiatry, part of King’s College London.

The review was commissioned as there have been “increasing concerns over the past years about the use of these drugs in dementia”. This report has now been published, along with the government’s response.

What did the report find?

The report found that the current approach to treating the psychological and behavioural symptoms of dementia appears to be largely based on the use of antipsychotics. It also found that the evidence regarding the use of antipsychotics in people with dementia is complex, sometimes contradictory and contains gaps. Due to the gaps in the evidence, any conclusions need to drawn cautiously.

The report concluded that, overall, the evidence suggests that antipsychotics appear to have only a limited positive effect in treating these symptoms and cause significant harm to people with dementia.

However, it also said that some people with dementia do benefit from antipsychotics and there are  likely to be specific subgroups of people with dementia who benefit , such as those with severe symptoms. It said this has not yet been tested in rigorous trials.

Based on the best evidence available, Professor Banerjee estimated that:

• Each year, 180,000 people with dementia receive antipsychotics in England.
• Up to 36,000 of these people benefit to some degree from the treatment.
• Around 1,620 additional cerebrovascular adverse events (such as stroke), about half of which will be severe, will result from the treatment.
• Each year, about 1,800 additional deaths will be caused by the treatment in this frail population.

What did the report conclude?

Professor Banerjee concluded, “the current level of use of antipsychotics for people with dementia presents a significant issue in terms of quality of care, with negative impacts in patient safety, clinical effectiveness and the patient experience.”

He says that antipsychotic drugs appear to be used too frequently in dementia and that the potential benefits are likely to be outweighed by the risks. He suggests that this is a worldwide problem, but that actions can be taken to address it.

What recommendations does the review make?

The report makes 11 recommendations that aim to reduce the use of antipsychotics to a level where the benefits outweigh the risks. Professor Banerjee estimated that antipsychotic use could be reduced to a third of its current level, and that this could be done safely over 36 months.

Broadly, the report recommends that:

• People with dementia should receive antipsychotics only when they really need them.
• Reducing the use of antipsychotics in people with dementia should be a priority for the NHS.
• Care home staff are given a curriculum to develop skills in non-pharmacological treatment of behavioural disorder in dementia.
• Care homes could be assessed based on their use of antipsychotic medications and the availability of staff who are skilled in non-pharmacological management of behavioural and psychological symptoms in dementia.
• Psychological therapy resources should be made available for people with dementia and their carers.
• Further research should be carried out, including studies of non-pharmacological methods of treating behavioural problems in dementia and of alternative pharmacological treatments.

What was the government’s response?

The government welcomed the report and accepted its conclusions. It said that the level of additional deaths due to antipsychotic use in people with dementia was “totally unacceptable”.

It also agreed that “there should not be a ban on the prescribing of anti-psychotic medication to people with dementia, as there will undoubtedly be occasions when the use of drugs will be necessary and in the best interests of the person involved.” The Alzheimer’s Society has also given its support to the report.

Are there any other important points to note?

This report only looks at the use of antipsychotics in people with dementia. It does not apply to people who are prescribed antipsychotics for other conditions, such as schizophrenia. It is important that people with dementia do not stop taking any prescription medications without first consulting their doctor.

NICE recommendations on the use of antipsychotics in dementia include:

• People with dementia who develop non-cognitive symptoms (psychosis and/or agitated behaviour causing significant distress) or challenging behaviour should be offered a pharmacological treatment in the first instance only if they are severely distressed or there is an immediate risk of harm to the person or others. An assessment to establish likely factors that may cause, aggravate or improve such behaviour should be carried out at the earliest possible opportunity and a care plan drawn up.
• People with Alzheimer’s disease, vascular dementia, mixed dementias or dementia with Lewy Bodies (DLB) with mild-to-moderate non-cognitive symptoms should not be prescribed antipsychotic drugs because of the possible increased risk of cerebrovascular adverse events (e.g. stroke) and death. Those with DLB are at particular risk of severe adverse reactions.
• People with Alzheimer’s disease, vascular dementia, mixed dementias or DLB with severe non-cognitive symptoms may be offered treatment with an antipsychotic drug provided there is a full discussion with the person and their carers of the risks of adverse effects, there are specific treatment aims and goals and treatment effects which are regularly assessed and recorded. The drug should be selected on an individual basis, started at low dose, monitored regularly and changed or withdrawn as indicated.

How was the report produced?

Professor Banerjee looked at the available research evidence, legal issues and how antipsychotics are used in practice in dementia, both by the NHS and in other countries. He also asked for the views of people who have a professional or personal interest in the issue, including members of the public, people with dementia, carers, doctors, NHS managers and the pharmaceutical industry. These investigations were part of the development of the National Dementia Strategy.

Links To The Headlines

Chemical cosh’ for dementia kills 1,800 a year. The Times, November 13 2009

1,800 a year die from dementia ‘cosh’ pills. The Sun, November 13 2009

1,800 OAPS killed by dementia sedatives. The Mirror, November 13 2009

Chemical restraints killing dementia patients. The Guardian, November 13 2009

Dementia drug use 'killing many'. BBC News, November 13 2009

'Chemical cosh’ drugs 'killing thousands a year'. The Daily Telegraph, November 13 2009

Links To Science

The use of antipsychotic medication for people with dementia: Time for action. A report for the Minister of State for Care Services by Professor Sube Banerjee. Department of Health 2009 (PDF)

Government response: November 12 2009 (PDF)

Alzheimer’s Society response: Review calls for action on dangerous use of antipsychotic drugs for dementia. Published 12 November 2009

Last updated: 17.00 BST

UK swine flu cases have fallen for the first time since August, down to 64,000 new infections in the past week. It is thought the half-term break may be behind the drop of 20,000 from the previous week.

Despite a fall in cases the number of people needing hospital treatment for the virus has remained high, with 785 patients in hospital. Of these patients 173 are receiving critical care.

The UK has also seen 28 further deaths related to swine flu, raising the total to 182: 124 in England, 33 in Scotland 14 in Wales and 11 in Northern Ireland.

Vaccinations

Virtually all GPs have now received their first supplies of the swine flu vaccine. The 6.6 million doses delivered in the past month are now being used to protect those most susceptible to swine flu, including pregnant women and people with long-term conditions.

The government is also launching an advertising campaign that will explain the importance of receiving the vaccine, which is expected to offer several years of protection against swine flu.

In other swine flu news:

• Use of the National Pandemic Flu Service has levelled off.
• Priority groups continue to be vaccinated, and virtually all GPs have received their first delivery of swine flu vaccine.
• The Department of Health has published new guidelines for the treatment of swine flu in pregnancy. The new guidance contains detailed advice for clinicians caring for pregnant women. Also available is a leaflet for pregnant women.

The National Vaccination Programme

NHS hospitals are now vaccinating patients facing the greatest risk of complications. Healthcare staff dealing with the public are also being vaccinated to help keep medical services running smoothly and to prevent them from passing the virus to patients.

Virtually all GPs have received their first supplies of the vaccine. Patients will be contacted by their GPs if they fall into one of the at-risk categories.
The order of priority will be:

• People aged from six months to 65 years in current seasonal flu risk groups
• All pregnant women
• Those living with people with compromised immune systems, for example those recieving cancer treatment
• People aged over 65 in the current seasonal flu risk groups.

The government has produced a swine flu vaccination leaflet with more information. The chief medical officer, Sir Liam Donaldson, said: "I urge everyone in the priority groups to have the vaccine - it will help prevent people in clinical risk groups from getting swine flu and the complications that may arise from it."

Who is a priority for vaccination with the H1N1 swine flu vaccine?

People who are most at risk from swine flu need to be vaccinated first. These groups are, in order of priority:

• People aged between six months and 65 years in the seasonal flu vaccine at-risk groups.
• All pregnant women, subject to licensing. The European Medicines Agency, who license the vaccine, will indicate whether it can be given to all pregnant women or whether it should only be offered at certain stages of pregnancy.
• People who live with those whose immune systems are compromised, such as cancer patients or people with HIV/AIDS.
• People aged 65 and over in the seasonal flu vaccine at-risk groups.

Frontline health and social care workers will also be offered the vaccine at the same time as the first clinical at-risk groups. Health and social care workers are both at an increased risk of catching swine flu and of spreading it to other at-risk patients.

What are the seasonal flu vaccine at-risk groups?

These are people with:

• chronic respiratory disease, such as chronic obstructive pulmonary disease (COPD),
• chronic heart disease, such as heart failure,
• chronic kidney disease, such as kidney failure,
• chronic liver disease, such as chronic hepatitis,
• chronic neurological disease, such as Parkinson's disease,
• diabetes requiring insulin or oral hypoglycaemic drugs, and
• immunosuppression (a suppressed immune system), due to disease or treatment.

Why are healthy people over 65 and children not a priority for the swine flu vaccine?

Healthy people aged over 65 appear to have some natural immunity to the swine flu virus. And while children are disproportionately affected by swine flu, the vast majority make a full recovery - therefore the experts do not advise that children (other than those in at-risk groups) should be vaccinated initially.

Revised planning assumptions

It was announced on September 3 that estimates of deaths in the worst-case scenario for swine flu have been lowered. The government's expert advisers on swine flu, the Scientific Advisory Group for Emergencies (SAGE), said that new data from the UK, north America, Australia and elsewhere give a better picture of how the virus might spread in the autumn.

The revised planning assumptions have cut the estimated death toll in a worst-case scenario from 65,000 people in the UK to 19,000, assuming that 30% of the population is infected.

These forecasts and others in the report are based on a "reasonable worst case" value and should not be taken as a prediction of how the pandemic will develop. Planning against the reasonable worst-case scenario will ensure, however, that plans for all likely scenarios are robust.

The Department of Health said: “In light of this new information, the estimates for the number of people who might need hospitalisation and the proportion of people with swine flu who could die have been reduced.”

Vaccination should cut hospitalisation

These new planning assumptions do not take account of the vaccination programme which, once it has begun, will help to further reduce the number of people needing hospitalisation. However, the department added, we must not be complacent. While in the majority of people it is mild, for some this virus can be a serious illness.

Who is at greatest risk of serious complications from swine flu?

Some people are more at risk of complications if they catch swine flu, and need to start taking antivirals as soon as it is confirmed that they have the illness. Doctors may advise some high-risk patients to take antivirals before they have symptoms, if someone close to them has swine flu.
It is already known that people are particularly vulnerable if they have:

• chronic (long-term) lung disease,
• chronic heart disease,
• chronic kidney disease,
• chronic liver disease,
• chronic neurological disease (neurological disorders include motor neurone disease, multiple sclerosis and Parkinson's disease),
• immunosuppression (whether caused by disease or treatment), or
• diabetes mellitus.

Also at risk are:

• patients who have had drug treatment for asthma in the past three years,
• pregnant women,
• people aged 65 and over, and
• children under five.

National Pandemic Flu Service

The National Pandemic Flu Service was launched in July. This online service assesses patients for swine flu and, if required, gives them an authorisation number that can be used to collect antiviral medication.

The system, which can also be accessed by phone, will take the strain off GPs as swine flu spreads. For the moment, it is being used only in England.

“The National Pandemic Flu Service is a new self-care service which will give people with pandemic swine flu symptoms fast access to information and antivirals,” said a Department of Health spokesman.

“This new service will free up GPs, enabling them to deal with other illnesses that need their urgent attention.”

The launch of the system brought important changes to the official advice that is given to people who think they may have swine flu. That advice – and the new system – is supported by the Royal College of General Practitioners.

Advice for antivirals

Several newspapers reported that the World Health Organization (WHO) had changed its advice regarding use of antivirals for swine flu. Its advice suggests that while antivirals should always be given in serious cases, they may not always be necessary for otherwise healthy people.

The papers pointed out that this appeared to differ from the approach taken in the UK, where Tamiflu is being widely used.

However, the Department of Health said:
"We believe a safety-first approach of offering antivirals, when required, to everyone remains a sensible and responsible way forward. However, we will keep this policy under review as we learn more about the virus and its effects.

"The WHO recommendations are in fact in line with UK policy on antivirals. We have consistently said that many people with swine flu only get mild symptoms, and they may find bed rest and over-the-counter flu remedies work for them.”

Links To The Headlines

Links To Science

“Scientists have found a way to disarm a protein thought to play a key role in leukaemia and other cancers,” the BBC has reported. It said that the protein in question, called Notch, is often damaged or mutated in patients with a certain form of leukaemia.

The researchers used an experimental technique called hydrocarbon stapling. This uses a chemical ‘scaffold’ to mould short sections of protein (called peptides) into specific three-dimensional shapes. The researchers hoped that these 'stapled peptides' would interact with the Notch protein and block its actions. The researchers found that one of their peptides was able to stop Notch from working and to reduce the growth of leukaemia cells in mice.

This research has identified a way to target the Notch protein, which has previously been an elusive target. The technique may lead to the development of new drugs to treat this type of leukaemia (called T-ALL), and to potential ways of using stapled peptides in other areas of research.

Where did the story come from?

Dr Raymond Moellering and colleagues from Harvard University carried out this research. The study was funded by several organisations, including the Leukaemia & Lymphoma Society and the National Institutes of Health in the US.

One of the researchers declared that they were a paid consultant and shareholder of Aileron Therapeutics, a company which has been granted a license to develop stapled peptide technology by Harvard University and the Dana Farber Cancer Institute. The study was published in the peer-reviewed journal Nature.

The BBC has covered this complex study in a balanced way.

What kind of research was this?

This was a laboratory study that included both biochemical and animal experiments. The researchers wanted to see if they could develop a method to block the action of transcription factors (a type of protein) in cells. Transcription factors switch on genes and, as such, they control the processes that occur within cells. While transcription factors play a role in normal cell function, they are also involved in the development of cancer. This means that they may be a good target for new cancer drugs, but their chemical characteristics have so far made it difficult to design drugs that block their function.

This study describes the early development of a new type of molecule that could be used in future drugs. This work will be followed by further research in animals to investigate the molecule’s effectiveness and safety. If this research proves promising, it may be followed by research in humans.

What did the research involve?

The researchers were interested in developing a drug that could block the action of a transcription factor called NOTCH1. Mutations can cause this transcription factor to be active when it shouldn’t be, which can lead to a form of leukaemia called T-cell acute lymphoblastic leukaemia (T-ALL).

Inside the cell, a protein called MAML1 binds to a complex of proteins that contains the NOTCH1 transcription factor. Laboratory tests have shown that a fragment of the MAML1 protein (called dnMAML1) can block the action of NOTCH1 in T-ALL leukaemia cells, stopping them from dividing.

However, protein fragments (peptides) may not be structurally robust, and may be susceptible to changing shape or being broken down. Research has suggested that peptides can last longer in the body and bind to other proteins more effectively if they are bonded to a chemically altered amino acid (the building blocks of proteins). This technique is called hydrocarbon stapling.

The researchers investigated whether a hydrocarbon-stapled form of dnMAML1 would still be able to block the action of NOTCH1. They designed six shorter hydrocarbon-stapled pieces of protein similar to dnMAML1, referred to as SAHM1, SAHM2 etc.

They examined how long these SAHMs took to get into the cell and selected those that looked most promising for further testing. They observed how well SAHMs bound to the complex of proteins that contained NOTCH1. They also looked at the effect of SAHMs on genes that are normally switched on by NOTCH1, and their effects on T-ALL cells in the laboratory. Finally, they looked at what effect the most promising SAHM had on a genetically engineered mouse model of T-ALL.

What were the basic results?

Laboratory tests on cells
The researchers found that some of the SAHMs, including SAHM1, were able to enter cells. SAHM1 could bind to the complex of proteins containing NOTCH1. SAHM1 also reduced the activity of genes in T-ALL leukaemia cells that would normally be switched on by NOTCH1. Treating T-ALL cells in the laboratory with SAHM1 stopped the cells from dividing as often as they normally would.

Animal testing
The researchers found that mice with progressive T-ALL that were given twice-daily SAHM1 injections experienced a reduction in the number of cancerous cells. Once-daily SAHM1 injections had a lesser effect, and T-ALL leukaemia progressed in untreated mice.

How did the researchers interpret the results?

The researchers concluded that the hydrocarbon-stapled peptide SAHM1 caused “potent, NOTCH-specific anti-proliferative effects” in both cells grown in the lab and the mouse model of T-ALL leukaemia. They say that their SAHM1 molecule should be useful in working out the role of NOTCH1 in normal and diseased tissues. It also provides a starting point for developing targeted drugs to treat NOTCH-related cancers and other conditions.

Conclusion

This study has developed a new method for targeting the NOTCH1 transcription factor. The technique may eventually lead to the development of new drugs for T-ALL and other Notch-related conditions. However, this will be a long-term goal as much more animal and human research will be needed to determine the effectiveness and safety of this new approach.

Links To The Headlines

Cancer protein 'can be disarmed'. BBC News, November 12 2009

Links To Science

Moellering RE, Cornejo M, Davis TN. Direct inhibition of the NOTCH transcription factor complex. Nature 2009; 462: 182-188

A headline in today’s Daily Mail stated: “Yoghurt drinks could beat bugs that pile the weight on.” It said scientists have shown that “bugs that live in our stomachs could be causing us to get fat.” The newspaper said the research could lead to probiotic yoghurts that can combat weight gain.

The newspaper’s claim about probiotic yoghurts is misleading. In fact, the study examined the effect of a change in diet on gut flora (microorganisms found in the gut) and weight in mice. The research was well conducted and should help advance investigations into gut flora. However, probiotic drinks such as Yakult, which was mentioned in the Daily Mail, did not feature in the study. While it is easy to see how the newspaper reached its interpretation, it is too great a leap, and the study's relevance to human diet needs more investigation.

While Yakult has had some more publicity because of this study, the research had nothing to do with probiotic yoghurts.

Where did the story come from?

The research was carried out by Dr Peter Turnbaugh and colleagues from Washington University School of Medicine and the University of Colorado. It was funded by the National Institutes of Health and the Crohn’s and Colitis Foundation of America. The authors declare that they have no competing financial interests. The study was published in the peer-reviewed medical journal Science Translational Medicine.

The Daily Mail and The Times reported this research, and both papers made confident statements that the findings show that diets high in fat and sugar are causing obesity. Both papers highlight that this study was in mice. The Daily Mail’s headline about probiotic yoghurts, such as Yakult, could be misleading as this research did not test probiotics (yoghurts or otherwise) and the researchers do not mention them.

What kind of research was this?

This study had several aspects, one of which was to examine the effect of modifying diet on gut flora and weight in mice. The researchers say that it is difficult to determine the relationships between diet, the behaviour of gut microbes and energy from food because of the effects of genes and environmental factors. By developing an ‘animal model’ of the complex ecosystem in the human gut, the researchers have provided a way forward for further studies.

What did the research involve?

This research involved several different experiments, all of which used ‘gnotobiotic mice’. These are animals which are raised in germ-free environments and deliberately colonised with specific microbes at particular times in their life. Mice such as these are useful in experiments about digestion as they can show how particular microbes and previously germ-free environments affect each other.

In the initial experiments, the researchers attempted to establish a mouse model of the human gut so that they could investigate the effect that diet had on it.

To make the mouse model, the researchers put microbes from human faecal matter into the guts of gnotobiotic mice to establish a human-like gut colony. The mice were fed a standard low-fat diet that was rich in plant matter. Researchers collected faeces from the mice one day, one week and one month after the mice were colonised with the human microbes. After a month, half of the mice were switched to a high-fat, high-sugar Western diet. The two groups remained on these diets for an extra two months, with weekly faecal sampling. The mice were then killed and the components of their guts compared.

In other experiments, the researchers assessed whether the human-like gut flora could be transferred between animals and whether this could be done using frozen faecal samples. In the experiment that the media has picked up on, the researchers examined whether diet-induced obesity could be caused in healthy mice by transplanting into them the gut flora from mice that were fed a Western diet.

What were the basic results?

The researchers developed a mouse model of the human gut using human faecal matter. These microbial colonies could be transplanted into other mice even through frozen faecal samples. This establishes this mouse model as useful for further research.

A Western diet caused mice to gain weight and changed the microbes in their gut. Transplanting the gut flora from these mice to healthy mice led to significant weight gain compared with mice that received gut flora from mice on a non-Western diet, even though there was no increase in food consumption.

The researchers identified the particular bacteria that were predominant in diet-related obesity, having found a bloom in bacteria called Erysipelotrichi and Firmicutes along the length of the gut.

How did the researchers interpret the results?

The researchers say that while human gut communities have been transplanted into germ-free animals many times in previous experiments, they used these methods to show that the human gut colony can be transferred to mice even if the starting material is frozen faeces.

They have also shown that this can be passed between mice and that the complement of microbes changes quickly and dramatically when the diet is switched from a low-fat diet to a high-fat, high-sugar Western diet. This diet-altered gut flora can be transplanted into other animals. Overall, the findings show that this is a potentially useful animal model for further study of the environment of the gut.

Conclusion

This animal study was well conducted. The purpose of the experiment, which is well described, was to establish an animal model for further studies of human diet and of the complex ecosystems that exist in the digestive system.

The study did not examine the effects of yoghurt or other probiotics on weight, as some news reports imply. Nor does it suggest that a probiotic yoghurt will soon be available that can aid weight loss. This extrapolation of the results is likely to have been based on the finding that a Western diet alters the microbial constituents of the gut. Researchers found that when the mice’s diet was changed from a low-fat diet to a Western-style high-fat, high-sugar diet, the component bacteria in their gut changed quickly and considerably. Stating that a probiotic yoghurt could “combat weight gain”, and including a picture of a normal yoghurt drink next to the article, could mislead people.

The results from this study will undoubtedly inform further research and the study has developed an important animal model for this type of research. Probiotics should not be seen as a ‘treatment’ for a poor diet, and eating a healthy, balanced diet and doing regular exercise remain the best ways to prevent overweight and obesity.

Links To The Headlines

Yoghurt drinks could beat bugs that pile the weight on. Daily Mail, November 12 2009

Sugar and fat-rich diets cause obesity by altering gut bacteria. The Times, November 12 2009

Links To Science

Turnbaugh PJ, Ridaura VK, Faith JJ et al. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med 11 November 2009: 1; 6ra14

“A new pill that could cure one of the most lethal forms of cancer is being developed by scientists,” reported The Daily Telegraph. The newspaper said that the treatment works by blocking the growth of the cancer cells and eventually causing them to self-destruct.

The researchers found that the drug, known only as PD173074, eliminated tumours in 50% of mice that were genetically engineered to develop the disease. The drug is designed to block the action of a hormone called FGF-2, which encourages the growth of small cell lung cancer. Surgery is not possible on this quick-spreading cancer, but chemotherapy and radiotherapy can initially reduce the tumour size. Theoretically, by blocking the hormone, the drug could make tumours more vulnerable to these treatments.

This is promising research, but the potential treatment is in its early stages and it is difficult to say when a drug that is developed from this research might be available. Further trials in animals will be needed before it can be tested in humans, and many drugs that appear to be effective in animals do not work in humans.

Where did the story come from?

This research was carried out by Dr Olivier E. Pardo and colleagues from the Cancer Research UK Laboratories and Clinical Sciences Centre at Imperial College London and elsewhere. Cancer Research UK and the Department of Health provided grant support. The study was published online in the peer-reviewed journal Cancer Research.

Most newspapers that reported this study have stressed the early nature of the animal research and the importance of finding better treatments for this lethal disease. The Daily Express says that “the tests offer hope that a cure could be on the horizon.”

What kind of research was this?

This laboratory research was conducted in mice. The researchers explain that small cell lung cancer (SCLC) accounts for 20% of all lung malignancies and that the disease recurs rapidly after a phase of initial treatment, after which it is usually resistant to further therapy. Overall survival rate is less than 5% three years after diagnosis.

There were several parts to this study. Researchers looked at the effect of a drug called PD173074 on cells from human tumours in the laboratory. They also studied the effect of the drug on two different types of human small cell lung cancer tumours that were grown in mice. This is known as a ‘mouse model of SCLC’ and is a common process for early drug development which can demonstrate if a drug has a therapeutic effect.

What did the research involve?

The drug PD173074 was first developed in 1998 to stop blood vessels from forming around tumours. The drug works by blocking the action of a hormone called fibroblast growth factor (FGF-2), which encourages the growth of these blood vessels. The researchers hoped that by blocking the action of the hormone, the tumour cells would die.

In the laboratory part of the study, the researchers looked at SCLC tumour cells in the test tube and observed how well they grew and became resistant to chemotherapy with and without the addition of the new drug.

They then tested the drug in two mouse models of SCLC. In one model, tumour cells were injected under the skin of mice. Once the tumours had grown to a measurable size, the animals were randomised to receive either PD173074 or no treatment for 28 days. In the second model, mice were also given intravenous injections of cisplatin, the usual chemotherapy agent for this disease, on days one and ten. The researchers counted the number of tumour cells affected by the new drug and also tested its effect in combination with standard chemotherapy.

In a third part of the research, the researchers used PET scanning on the mice. This imaging technique shows up fast-growing tumours as hot spots on the scan. It can be used to monitor the spread of the disease and how it responds to therapy.

What were the basic results?

The new drug stopped the cancer cells from growing and also prevented the hormone FGF-2 from triggering their survival mechanism. This meant the cells could be killed with standard chemotherapy.

The new drug also stopped cancer cells from proliferating and from becoming resistant to treatment in mouse models. In one animal model of small cell lung cancer, the drug eliminated tumours in 50% of the mice. In a second, similar mouse model, the drug enhanced the effect of standard chemotherapy.

When the drugs were combined, they slowed down tumour growth significantly faster than either drug on its own.

In the scanning part of the study, PET scans showed that treatment reduced DNA synthesis in the tumours. This indicates that the drug prevented the tumour cells from replicating. The researchers also found that the rate of cell death in the tumours increased after the drug was given to the mice.

How did the researchers interpret the results?

The researchers say that inhibiting the FGF-2 hormone, while improving the effectiveness of classic cancer therapy, might be efficient in a subset of lung cancer patients when used on its own.

Conclusion

This early research has shown, for the first time, a large effect of a novel drug in reducing the growth of SCLC tumours in mice. This is early research, but its results are promising and will probably lead to much interest in this class of drugs. Some strengths of this study should be noted:

• The effect of the drug was dose-dependent, which means the more drug the researchers added to the cells, the less the cells proliferated. This makes it more likely that the drug has a direct effect on the cells.
• The combination of treatment and PET scanning in one study means that the response to the drug was tested in several ways, adding further confidence in the results.

Although it is early days for this new drug and too soon to be heralding a cure for lung cancer, progress through the next phases of animal and human research will be followed with interest. Only by further rigorous safety testing in animals, followed by human studies looking at different doses of the drug and the effect of combining it with other agents, will its role in cancer treatment be known.

Links To The Headlines

Deadliest lung cancer breakthrough. The Daily Telegraph, November 11 2009

Could tumour-killing drug PD173074 cure lung cancer? Daily Mirror, November 11 2009

Drug 'shrinks lung cancer tumour'. BBC News, November 11 2009

Pill may cure lung cancer. Daily Express, November 11 2009

Links To Science

Pardo OE, Latigo J, Jeffery RE et al. The fibroblast growth factor receptor inhibitor PD173074 blocks small cell lung cancer growth in vitro and in vivo. Cancer Research, November 10 2009 (published online first) 
 

“People who walk slowly are three times more likely to die from cardiovascular disease than those who go at a brisk pace,” according to the Daily Express.

The news is based on a study that assessed the walking speeds of over 3,000 elderly people and compared them to death records for several years after. Researchers, who took into account any existing heart disease or other illnesses the participants had, found that 6.9% of the slowest walkers died of heart disease compared to just 1.9% of the fastest walkers. There are a number of possible explanations for the association between slow walking and heart disease. For example, people who already have undetected mild heart failure or early narrowing of the arteries in the legs could be slower walkers because of this.

While the reasons behind the relationship between slow walking and heart disease are open to debate, this study suggests that a simple measure of fitness may be suitable for assessing the health of people aged 65 and over. The benefits of physical activity to the heart are well known, and this research adds more weight to the principle that physical activity reduces rates of death.

Where did the story come from?

This research was conducted by Dr Julien Dumurgier and colleagues from the INSERM research foundation in Paris and other organisations in France. The study was supported by grants from INSERM, the Victor Segalen-Bordeaux II University and the Sanofi-Synthélabo Company. The study was published in the peer-reviewed British Medical Journal.

The Daily Telegraph also covered this story, reporting that the people who were judged to be slow walkers were also 44% more likely to die from any cause. The Daily Express pointed out that, in this study, the faster walkers did not have a lower risk of dying from cancer, despite evidence from previous research that exercise may reduce the risk of developing certain types of tumour.

What kind of research was this?

This was a prospective cohort study which explored the relationship between slow walking speed and risk of death in older people. The researchers followed 3,208 French men and women aged 65 or older. Subjects were all people living in the community and were followed for an average of 5.1 years from 1999–2001.

The researchers explain that it is already known that lower walking speed has been associated with an increase in rates of death from all causes, but it is currently unknown whether this overall increase in mortality is due to specific causes of death. The researchers conducted a cohort study, which is the best design for looking at these associations. Other study models that randomise participants into fast- and slow-walking groups may not be possible.

What did the research involve?

The researchers had data from the 3C study, an ongoing study that recruited participants from the electoral rolls in three French cities (Bordeaux, Dijon and Montpellier). In total, 37% of the people who were approached by letter and phone agreed to participate. This walking study only used the data from Dijon, which included details of the participants’ motor function.

A wide range of tests and questionnaires was given by trained psychologists. As they aimed to use the data for several future analyses, they asked the participants about their education, history of coronary artery disease, peripheral artery disease, stroke, Parkinson’s disease and recent hip fracture (in the two preceding years). Blood pressure was measured and blood tests were used to diagnose diabetes or high blood cholesterol. Smoking status was classified as current, past or never. Weight and height were measured and used to calculate body mass index (BMI). Physical activity was also assessed through the participants’ self-reporting of their daily walking and athletic activities.

For the walking test, participants were first asked to walk at their usual speed and were then invited to walk down the corridor as fast as possible without running. They started walking three metres before the start line so that their acceleration phase did not count towards their walking speed. The researchers excluded data on participants who, at the start of the study, had been diagnosed with conditions that are strongly associated with decreased walking speed (for example, dementia, hip fracture in the previous two years and disabling stroke).

The researchers’ exclusion criteria mean that the study may still have included people with undiagnosed conditions or conditions not yet severe enough to be noticed. These may affect walking speed and could be responsible for “reverse causality”, a type of bias where the outcome affects the exposure. For example, a heart problem may have led to a slow walking speed, rather than the other way around.

Walkers were divided by sex, as women were likely to have slower walking speeds than men, and each sex was split into three speed ranges:

• Men with a maximum speed of 1.50 m/s (metres per second) or less.
• Men between 1.51 and 1.84 m/s.
• Men with a maximum speed of 1.85 m/s or more.
• Women with a maximum speed of 1.35 m/s or less.
• Women between 1.36 and 1.50 m/s.
• Women with a maximum speed of more than 1.50 m/s.

After the initial tests, the researchers followed participants for around five years, recording information on deaths, from any cause and according to the main causes of death. They related these to the walking speed at the beginning of the study (measured as a maximum speed over six metres), which was adjusted for several potential confounding factors, including age, sex, median age, median body mass index (BMI), education, mental state and level of physical activity.

The links shown in the ‘all causes of deaths’ and cardiovascular disease groups remained significant after all the adjustments. This suggests that the association with walking was strongest for these causes of death (and not so strong for cancer or other causes).

What were the basic results?

The researchers say that over the follow-up period, 209 participants died: 99 from cancer, 59 from cardiovascular disease and 51 from other causes.

The unadjusted figures showed that participants in the lowest third of walking speed had an increased risk of death from any cause compared with those in the upper two-thirds (hazard ratio [HR] 1.44, 95% confidence interval [CI] 1.03 to 1.99).

After the researchers had adjusted for nineteen separate factors, their analyses for specific causes of death showed that participants with low walking speed had about a threefold increased risk of cardiovascular death (HR 2.92, 95% CI 1.46 to 5.84) compared with participants who walked faster. After adjustment, there was no relationship between walking speed and cancer mortality (HR 1.03, 95% CI 0.65 to 1.70).

How did the researchers interpret the results?

The researchers say that “slow walking speed in older people is strongly associated with an increased risk of cardiovascular mortality.”

Conclusion

This relatively large, well-conducted study of older people suggests that the main benefit of physical activity in the form of fast walking is to protect against heart disease and not cancer. This association was shown in a population of healthy older adults and reinforces the message that physical activity and walking have major lifetime benefits.

However, the study cannot completely rule out the possibility that heart disease or another disease, common in this age group, was somehow related to slower walking at the start of the study. It is possible that some other factor caused the association seen by reducing walking speed and contributing to heart disease risk. Equally, undiagnosed heart problems might be the cause of slower walking speed, rather than the other way around.

Although the exact cause-and-effect relationship seen in this study is unclear, the strong link between mobility and mortality suggests that a simple walking-speed test may play a role in the assessment of fitness in older people. Other research has clearly shown that the heart benefits from physical activity, and this should be promoted.

Links To The Headlines

Older people who walk slowly 'three times as likely to die from heart problems'. The Daily Telegraph, 11 November 2009

Why walking slowly could be the death of you. Daily Express, 11 November 2009

Links To Science

Dumurgier J, Elbaz A, Ducimetière P. Slow walking speed and cardiovascular death in well functioning older adults: prospective cohort study. BMJ 2009; 339: b4460

Cervical cancer could be wiped out by “pioneering use of 'amazing' osteoporosis drugs”, the Daily Mail has declared. The newspaper says that drugs used to treat breast cancer and osteoporosis “eliminated the cancer in 11 out of 13 cases”. What it mentions only later in the article is that these 13 “cases” were mice.

This research gave an osteoporosis drug called raloxifene, a cancer drug called fulvestrant or no treatment to mice that were genetically engineered to develop cervical cancer when treated with oestrogen. The drugs reduced the incidence of cancer, but the authors of the research note that “further study is needed to determine whether this proposed model is relevant to human cervical cancer.”

The results suggest that these drugs may be worth investigating further for potential use in human cervical cancer. However, until human studies are carried out, it is not possible to say whether these drugs will play a role in the treatment of cervical cancer.

Where did the story come from?

Sang-Hyuk Chung and Paul Lambert from the University of Wisconsin School of Medicine and Public Health carried out this research. The study was funded by the National Institutes of Health in the US and published in the peer-reviewed scientific journal Proceedings of the National Academy of Sciences of the United States of America.

This story has been reported in the Daily Mail and Daily Mirror. The Mail states near the start of the article that one of the treatments “eliminated the cancer in 11 out of 13 cases”, but only later mentions that this was in mice rather than humans. The coverage in the Mirror article is very brief, but does point out that the research was in mice and quotes one researcher’s opinion that there are many similarities to how cervical cancer manifests itself in women and mice.

What kind of research was this?

This was laboratory research on mice, which looked at how cervical cancer is affected by drugs that block oestrogen receptors. Oestrogen receptors, known as ERs, are proteins that bind to the female hormone oestrogen. This allows the hormone to alter the way that the body interprets certain genes.

Early research into the effects of drugs needs to be carried out in animals before they can be tested in humans. This type of animal research can indicate whether a drug shows promise and is safe enough to try in humans. It does not guarantee that the drug will work or be safe in humans. Only subsequent human studies can establish this.

What did the research involve?

In this study, the researchers used mice that had been genetically engineered to develop a form of cervical disease. This resembled cervical disease associated with the human papilloma virus (HPV) in women, which can develop into cervical cancer.

Previous studies in these mice have shown that oestrogen must be present for cervical cancer to develop. They have also showed that the actions of the oestrogen receptor are key in the early stages of cervical disease, before the cells become cancerous. The researchers wanted to investigate whether drugs that block oestrogen receptors might be able to prevent or treat cervical cancer in these mice.

The researchers investigated two drugs, fulvestrant and raloxifene. Fulvestrant blocks all oestrogen receptors in the body, which results in menopausal symptoms in humans. Fulvestrant is currently used to treat breast cancer. Raloxifene is more selective in its effects, blocking oestrogen receptors in some tissues but not others. Raloxifene is used in the treatment of osteoporosis and has been trialled for the prevention of breast cancer in humans. The researchers say that it “has no major common side effects in women”. The British National Formulary lists possible side effects of raloxifene as hot flushes, leg cramps, peripheral oedema and flu-like symptoms.

In their first set of experiments, the researchers took the genetically engineered mice and treated them with oestrogen for six months to promote the development of cervical cancers. After this time, some of the mice were examined for cervical cancers, some received no further treatment for a month, some received fulvestrant injections for a month and some received raloxifene injections for a month. The researchers examined the effects of these different treatments on the presence of cervical cancers.

In a second set of experiments, the researchers looked at whether treatment with fulvestrant or raloxifene could prevent the development of cervical cancers in these mice. To do this, they treated the mice with oestrogen for six months, but also gave fulvestrant treatment during the fourth month of oestrogen treatment. At the three-month stage, the mice would have begun to develop precancerous cervical disease, but not cancer itself.

What were the basic results?

The researchers found that all of the six genetically engineered mice that had been treated with oestrogen for six months and then examined had developed cervical cancer. Eleven of the 14 mice (79%) that stopped receiving oestrogen treatment for a month still had cervical cancer at the end of this month.

Only one of the 13 mice (8%) treated with fulvestrant for a month had cervical cancer at the end of the month. None of the seven mice treated with raloxifene for a month had cervical cancer by the end of the month. This represented a statistically significant reduction in the proportion of mice with cervical cancer in those given fulvestrant or raloxifene compared to those left untreated for the month.

The researchers found that in six mice treated with oestrogen for three months, all had pre-cancerous cervical lesions at different stages of development, but none had cancer. Of the six mice treated with fulvestrant for a month at the three-month stage, none had pre-cancerous cervical lesions or cancer by six months.

How did the researchers interpret the results?

The researchers concluded that “these findings point to the potential value of ER antagonists in controlling gynecological disease in the lower reproductive tracts in women”.

Conclusion

This small study has shown that the oestrogen receptor blockers fulvestrant and raloxifene can treat cervical cancers in genetically engineered mice with this disease. Although these results suggest that the drugs may be worth investigating further for potential use in human cervical cancer, they may not represent the effects that the drugs would have in humans. As the researchers note, “Although our transgenic mouse model for HPV-associated cervical cancer recapitulates most aspects of human cervical cancer, it is obvious that further study is needed to determine whether this proposed model is relevant to human cervical cancer.”

HPV vaccination and screening programmes are likely to remain the best way of preventing this disease for the foreseeable future.

Links To The Headlines

Cervical cancer wiped out by pioneering use of 'amazing' osteoporosis drugs. Daily Mail,  November 10 2009

Breast and cervical link. Daily Mirror, November 10 2009

Links To Science

Lambert PF and Chung SH. Prevention and treatment of cervical cancer in mice using estrogen receptor antagonists. PNAS, November 9 2009(published online before print)

Researchers have identified a gene that causes deafness in the elderly, The Daily Telegraph reported.

It said that about four in 10 people experience a reduction in their hearing ability as they age as a result of gradually losing hair cells and nerve cells in the ear that are essential for hearing.

The researchers removed a gene, called Bak, in mice and found that these mice had better hearing as they aged than mice that had the gene. The Bak gene causes the hair cells in the ear to ‘self-destruct’ as people age.

Further studies will be needed to confirm the findings in humans. There may be other genes involved in age-related hearing loss, and it is likely that environmental factors, such as noise exposure, also contribute.

Where did the story come from?

The research was carried out by Dr Shinichi Someya and colleagues from the University of Wisconsin and other universities in the US and Tokyo. The study was funded by the National Institutes of Health in the US, the Ministry of Education, Culture, Sports, Science and Technologies in Japan and the Marine Bio Foundation. Two of the researchers have filed a patent for any future treatments that use Bak inhibition for age-related hearing loss.

The study was published in the peer-reviewed scientific journal Proceedings of the National Academy of Sciences of the United States of America.

The Daily Mail and Daily Telegraph gave generally accurate and balanced reports of the study, and both said that a drug treatment making use of this genetic discovery is a long way off.

What kind of research was this?

This laboratory research examined whether a gene called Bak is involved in age-related hearing loss.

To investigate this, mice were genetically engineered so that they were missing this gene, and their hearing was then tested as they aged to see what effect this had.

This type of experiment can be informative as similar genes tend to perform similar roles in different species. However, there are differences, and this means that what is observed in mice may not be the same as what will occur in humans.

What did the research involve?

As mammals age, they gradually lose hair cells and nerve cells in their ears. These cells are essential for hearing and, as they are not replaced, their loss leads to a reduction in hearing ability. This is called age-related hearing loss (AHL). The researchers suggested that over 40% of people aged over 65 in the US have AHL.

One gene that the researchers suspected might be involved in hearing loss was Bak. This gene causes cells to self-destruct and has been found to be less active in mice with lower levels of AHL. In order to investigate the role of Bak, the researchers genetically engineered mice that were lacking the gene, and looked at the effects on the mice’s hearing and the cells in their ears. The type of mice they used would normally show AHL by 12 to 15 months of age if they were not genetically engineered.

One theory for how ageing affects cells is that reactive chemicals produced inside the energy-generating part of a cell (the mitochondria) damage DNA and proteins inside the mitochondria. This is called oxidative stress. The accumulation of this damage over time is thought to lead to the ageing of the cell, and to contribute to AHL.

Believing that AHL is at least partly caused by oxidative stress, the researchers looked at the effect of chemicals that cause oxidative stress on the Bak gene in cells taken from the cochlea, a part of the inner ear. They also looked at whether supplementing the diets of normal mice with any of 17 different antioxidants from the age of four months to 15 months reduced AHL.

What were the basic results?

The researchers found that 15-month-old mice lacking the Bak gene had better hearing than normal mice of this age. Mice lacking Bak had less loss of nerve cells and hair cells in the ear than normal mice. The researchers showed that in normal mice, more nerve cells and hair cells were self-destructing than in the mice lacking Bak.

It was also found that, in cells taken from the cochleas of normal mice, exposure to a chemical that causes oxidative stress leads to Bak being ‘switched on’, which causes the cells to die. Cells from the cochleas of mice lacking Bak were more resistant to this happening.

Feeding the mice certain antioxidant chemicals (α-lipoic acid or coenzyme Q10) reduced the activity of the Bak gene in the ear cells and slowed the development of AHL.

How did the researchers interpret the results?

The researchers conclude that their findings support the theory that mitochondria-related oxidative stress triggers Bak-induced cell death in the ear, which leads to AHL.

Conclusion

This study has identified the role of the Bak gene in age-related hearing loss (AHL) in mice. The gene may play a similar role in humans and further studies in human ear cells will help confirm this.

However, the Bak gene may not be the only gene involved in AHL, and it is likely that environmental factors, such as noise exposure, also contribute to hearing loss.

Due to the differences between mice and humans, it is not clear whether taking supplements containing α-lipoic acid or coenzyme Q10 (which reduced the activity of the Bak gene in mice) would help reduce AHL in humans. Studies in humans would be required to determine if this is the case.

Links To The Headlines

Deafness gene discovered by scientists. The Daily Telegraph, November 10 2009

Deaf gene is traced that causes hearing loss in old age. Daily Mail, November 10 2009
 

Links To Science

Shinichi Someya S, Xu J, Kondo K et al. Age-related hearing loss in C57BL/6J mice is mediated by Bak-dependent mitochondrial apoptosis. PNAS, November 9 2009 (published online before print)

“Gym workouts ‘can hit pregnancy hopes’,” warned the Daily Express. It said research has apparently found that “superwoman workouts” triple the likelihood of fertility problems.

This study found that women who performed high-frequency, high-intensity exercise had a lower rate of fertility. However, it does not prove that exercise actually caused these fertility problems, as this type of study can only show associations, not cause and effect. There are also other limitations, including an assumption that the participants’ physical activity levels remained the same over a 10 year period and a failure to take into account the fertility of the women’s partners. Several other factors, such as diet, may also explain the assocation.

This finding should be viewed in the context of other studies in the same field, which have shown that maintaining an optimum weight is good for fertility. Moderate exercising (rather than excessive, exhausting workouts) is also likely to be the most appropriate type of activity for healthy women.
 

Where did the story come from?

The study was carried out by Dr Sigridur Gudmundsdottir and colleagues from the Norwegian University of Science and Technology and the Emory University in Atlanta. The research was funded by the Norwegian University of Science and Technology, Trondelag County Council and the Norwegian Institute of Public Health. The study was published in the peer-reviewed medical journal Human Reproduction.

What kind of research was this?

This was a cohort study which investigated the association between physical activity, fertility and parity (number of children) in a group of several thousand healthy Norwegian women. These women were recruited to the study between 1984 and 1986 and their final follow-up assessments took place between 1995 and 1997. The researchers are careful throughout their study not to suggest that exercise causes infertility, and are mindful of the numerous other factors (confounders) that may affect this relationship.

What did the research involve?

All male and female residents of the Nord-Trøndelag county of Norway were invited to take part in this research. An initial assessment involved a health questionnaire and a physical examination, which was given to participants between 1984 and1986. They were later asked to participate in further follow-up assessments that took place between 1995 and 1997.

A total of 24,837 women participated in both assessments. This study only looked at the link between physical activity and fertility in a subset of 3,887 participants. These were all healthy, pre-menopausal women who were under the age of 45 at the second assessment. By excluding women who had conditions that were known to affect fertility (including poor health, use of oestrogen tablets, hysterectomy, oophorectomy and fertility problems), the researchers attempted to make their findings relevant to healthy young women. It’s important to note that the number of women with undiagnosed problems would not have been known to the researchers.

Physical activity was assessed at entry into the study (baseline). The participants completed a validated questionnaire, which defined the levels of exercise they did during work and leisure time. This was determined by asking them to report the intensity, duration and frequency of the exercise. Exercise frequency was categorised as ‘never’, ‘less than once a week’, ‘2-3 times a week’ and ‘almost every day’. Exercise intensity was categorised as ‘take it easy’, ‘lose breath’ and ‘to exhaustion’.

Fertility was assessed at the follow-up assessment, where women reported the number of children they had, their age at childbirth, whether they had difficultly conceiving within one year of trying (and at what age), contraceptive use and status of menstruation and pregnancy.

Of the women who had attempted to conceive, those who succeeded within one year were considered ‘fertile’, while those who did not were categorised as ‘infertile’. Infertile women were divided into the ‘involuntarily childless’ (women who had problems conceiving within a year and had no child) or the ‘subfertile’ (if it took longer than one year to conceive). Women who had no problems conceiving and had no children were labelled as ‘voluntarily childless’.

Other factors such as age, education, marital status, body mass index (BMI), smoking and alcohol consumption were considered in the analyses. The fertility status at follow-up was then compared across groups who had different exercise levels at baseline.

What were the basic results?

The average age of the women at baseline was 27.2 years. Average BMI was 22.7 kg/m2 (with a wide range from 14.5 to 44.1). At the follow-up assessment, 90% of the women were classified as fertile, 5% as subfertile, 0.7% as involuntarily childless and 4% as voluntarily childless. In total, 62.4% of the infertile women had visited a doctor for fertility problems.

Increased frequency and intensity of physical activity was associated with increased infertility, even after the researchers adjusted their analysis for likely confounders. Women who were active on most days of the week were 3.2 times more likely to be infertile than inactive women. Women who exercised 'to exhaustion' were 2.3 times more likely to be infertile than women who said they 'take it easy'. The link between physical activity and fertility was not significant for frequencies or intensities of exercise below this level. The effect of exercise on fertility was more pronounced in women under the age of 30.

How did the researchers interpret the results?

The researchers conclude that fertility is negatively affected by physical activity of an extreme intensity and frequency. They say that their results conflict with those of other studies, but that their study has found a link between heavy exercise and infertility. They say that the potential role of regular physical activity in the prevention and treatment of infertility needs further investigation.

Conclusion

This cohort study cannot prove that heavy exercise causes infertility, a suggestion the researchers themselves are careful to avoid making. While this particular study has found an association between heavy exercise and fertility problems, this may be due to another factor, which could mean that the women who exercise most are systematically different from those who exercise less. For example, it is possible that, irrespective of their current weight, those women who exercise the most may be on low-calorie diets, and this intentional dieting may also affect their fertility.

There are other factors which affect the interpretation of these results:

• Of the 3,887 women, 1,000 of them had no available record of the intensity of their physical activity, so the results linking intensity of exercise to fertility should be interpreted with more caution than the other results.
• The researchers do not appear to have adjusted for the multiple statistical testing that they performed. Using multiple statistical testing means that it is more likely that their positive results are due to chance alone.
• About 30% of participants in the baseline survey did not participate in the follow-up. If these women were systematically different from participants in terms of their physical activity or fertility, this could have given the study different results.
• Exercise habits were only measured at baseline and are unlikely to have remained consistent in the 10 years until follow-up, particularly if during that time women had children. Women also self-reported their exercise intensity, which may have led to bias.
• It is possible that women incorrectly remembered their fertility history as they were asked to recall a period of up to 10 years. The researchers say that this is unlikely.
• Importantly, the fertility of the women’s partners was not considered.

The researchers put forward a number of possible theories to explain their findings, including that fertility problems may be caused when women of a normal weight do a lot of exercise but do not consume enough energy (have a negative energy imbalance). This and their other hypotheses remain to be tested.

Links To The Headlines

Spending too much time in gym 'can reduce woman's fertility'. The Daily Telegraph, November 9 2009

Gym workouts 'can hit pregnancy hopes'. Daily Express, November 9 2009

Links To Science

Gudmundsdottir SL, Flanders WD and Augestad LB. Physical activity and fertility in women: the North-Trøndelag Health Study. Hum. Reprod. October 3 2009 (advance online publication)