Health News from NHS Choices

 

Your subscribed feeds are not being updated automatically because this setting is turned off.

Turn on automatic feed updates

You’ve successfully subscribed to this feed!

Updated content can be viewed in Internet Explorer and other programs that use the Common Feed List.

View my feeds

You’ve successfully subscribed to this feed!

Health News from NHS Choices

You are viewing a feed that contains frequently updated content. When you subscribe to a feed, it is added to the Common Feed List. Updated information from the feed is automatically downloaded to your computer and can be viewed in Internet Explorer and other programs. Learn more about feeds.

Plus ButtonSubscribe to this feed

Health News from NHS Choices

‎28 ‎November ‎2010, ‏‎11:20:43

Encouraging results for anti-HIV pill

‎26 ‎November ‎2010, ‏‎17:05:00 | NHS ChoicesGo to full article

Scientists have tested the “first anti-HIV pill to provide effective protection against the disease”, The Independent has reported.

The news comes from an international study looking at whether a pill combining two antiviral drugs could reduce new HIV infections among 2,500 HIV-negative men and transgender women who have sex with men. This population is considered to have higher risk of exposure to the virus. Compared with a dummy placebo drug the daily pill reportedly cut the risk of contracting HIV by 44%. All participants had also received condoms and counselling on how to reduce the risk of contracting HIV.

While the group receiving antiviral drugs did have a lower rate of new infections it should be noted that the drug did not provide full protection – 36 people were newly infected, compared with 64 in the placebo group. While the rate of side effects was low in both groups over the three-year study, further research is also needed to establish dosage, safety and tolerance over longer periods.

While this preliminary research is encouraging, the eventual development of drugs to prevent HIV infection would not diminish the importance of awareness and condom use, which are two key tools for preventing the spread of HIV and other sexually transmitted infections.

Where did the story come from?

The study was carried out by researchers from The University of California at San Francisco and was funded by the US National Institutes of Health and the Bill & Melinda Gates Foundation.It was published in the peer-reviewed New England Journal of Medicine.

The research was covered well by the BBC, which highlighted that this treatment is not ready for widespread use. The BBC also indicated some of the potential issues that would need to be considered if a prophylactic HIV treatment were to become available, such as drug resistance and the impact it might have on attitudes towards practising safer sex. The Independent said that the pill provided effective protection against HIV, which some might wrongly assume to mean it was 100% effective in preventing HIV transmission. Further in the article they do, however, highlight that the antiviral drug only caused a reduction in transmission rate.

What kind of research was this?

This was a randomised controlled trial that looked at whether a prophylactic combination treatment of two drugs could lower the risk of infection with HIV in a group of men and transgender women who were considered to be at high risk of being exposed to the virus.

Antiretroviral therapies are used in the treatment of HIV (HIV is a type of virus known as a ‘retrovirus’). It is suggested that antiretrovirals may decrease viral transmission to uninfected partners and also decrease mother-to-child transmission. These drugs may also be used as a post-exposure prophylactic (preventative) treatment if a person has been exposed to fluids potentially infected with HIV. However, this use requires that people recognise that they might have been exposed and that they start therapy within 72 hours of exposure.

The researchers said that pre-exposure to antiretroviral drugs had been shown to lower infection rates in mice and primates that had been transplanted with HIV-infected human cells. They also said that a recently published study had demonstrated that a vaginal gel containing an antiretroviral drug had reduced HIV infection rates by 39% among women.

The researchers wanted to see whether a daily pill containing two antiretroviral drugs would reduce the transmission rates in a group of people at higher risk of being infected with the virus, and also to examine whether there would be side effects from the treatment. The two antiretroviral drugs, emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF), were combined into a single FTC-TDF pill (commercial name Truvada).

What did the research involve?

This was a multinational study, called the Preexposure Prophylaxis Initiative (iPrEX) trial. The study followed 2,499 HIV-negative people recruited from Peru, Ecuador, South Africa, Brazil, Thailand and the United States. The study was carried out from July 2007 to December 2009.

The study recruited participants that were male sex at birth and had sex with men. The participants were over 18 and were HIV-negative. The study included participants that were assessed to be at risk of HIV infection based on their sexual practices, such as having multiple partners, having sex without a condom, having an infected partner or having unprotected sex with a partner of unknown HIV status.

Study visits were scheduled every four weeks, and at each visit the participants received risk-reduction counselling and were provided with either the FTC-TDF study drug or placebo, as well as condoms. At each visit the participants were asked if they had missed taking any pills, and the pills left from the previous month’s prescription were counted. The participants were also tested for HIV antibodies every four weeks.

Every 12 weeks the participants were interviewed to see whether they had engaged in higher risk sexual behaviour over that time. Every 24 weeks the participants had a physical examination and were tested for sexually transmitted infections.

If the participants reported that they may have been exposed to HIV, they were given post-exposure prophylactics and temporarily stopped the study drug.

The participants were followed for up to 2.8 years but on average (median) for 1.2 years.

What were the basic results?

The researchers found that the sexual practices were similar in the placebo group and the FTC-TDF group. After enrolling in the study, the total number of sexual partners with whom the respondent had receptive anal sex decreased, and the percentage of those partners who used a condom increased. There was no difference between the groups in the number of other sexually transmitted infections.

The researchers said that the FTC-TDF drug can impair kidney function. They found that blood creatinine levels (a measure of kidney function) were elevated in five people in the FTC-TDF group (<1% of the group) but in none of the placebo group. More people reported nausea in the FTC-TDF compared with the placebo group (22 people compared with 10 people; p=0.04). Likewise, unintentional weight loss of 5% or more was reported among more of the FTC-TDF group than the placebo group (34 people compared with 19 people; p=0.04).

One hundred participants became infected with HIV during the study. Thirty-six of these were in the FTC-TDF group and 64 in the placebo group. This meant that there was a 44% reduction in the incidence of HIV in the FTC-TDF group compared with the placebo group (95% confidence interval 15 to 63; p=0.005).

The researchers found that, on average (median), the participants reported having taken 89-95% of the pills that they had been prescribed. The researchers measured the levels of the study drug in a blood sample provided by the participants. They found that 54% of participants who were considered “on treatment” on more than 50% of days had a detectable level of FTC-TDF in their blood. The researchers found that in the FTC-TDF group participants with detectable levels of the study drug in their blood had 12.9 times lower odds of HIV infection compared with those with undetectable drug levels (95% CI, 1.7 to 99.3; p<0.001).

How did the researchers interpret the results?

The researchers said the “once-daily oral FTC-TDF provided 44% additional protection from HIV among men or transgender women who have sex with men” when given alongside a comprehensive package of prevention services. However, they highlighted that, although this was a significant protection and “slowed the spread of HIV in this population”, it was lower than they had predicted it would be. The researchers said that they had chosen to study the treatment on men and transgender women who have sex with men as HIV prevalence is higher in this population than in other groups in almost all countries, but that the “optimal regimen for pre-exposure prophylaxis has not been established” and data from the participants in this study cannot be applied to other populations.

Current research is reportedly testing the drug as a pre-exposure prophylaxis in other populations.

Conclusion

This was a well-conducted study that assessed the use of an oral prophylactic treatment for HIV in a higher risk population. Although the treatment did reduce the number of new infections in this group compared with placebo, it did not prevent transmission entirely. The researchers also highlighted that the participants’ behaviour changed in some ways after enrolment in the study, including increased condom use and a reduction in higher risk behaviour. These changes may reflect the influence of the additional services, such as counselling, testing and dispensing of condoms, that were provided alongside the study drugs.

The researchers caution of the possible risk of prescribing the drug out of a trial setting. They suggest that the positive moves towards prevention displayed by the participants may not necessarily be adopted by users due to increased expectation of the benefits of the drug. Alongside these concerns, further research will be needed to establish the long-term safety and tolerance of the treatment and to define the minimum protective drug concentration.

As it stands, this research provides encouraging but preliminary evidence that prophylactic antiretroviral treatments could provide an additional benefit alongside safer sex practices and education among a specific high-risk population. As such, it may potentially slow down the spread of HIV within similar populations, but needs further testing among other social groups.

While the development of effective drug-based HIV prophylaxis would be an important step in the right direction, it should be emphasised that this would not diminish the importance of barrier methods of contraception, such as condoms, which remain the best method of preventing transmission of HIV and other sexually transmitted infections.

Links To The Headlines

HIV pill heralds new era in fight against Aids. The Independent, November 24 2010

Drug ‘can greatly reduce risk of HIV infection’. BBC News, November 24 2010

Links To Science

Grant RM, Lama JR, Anderson PL et al. Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men. New England Journal of Medicine, November 23 2010

2010 good hospital guide

‎26 ‎November ‎2010, ‏‎11:41:00 | NHS ChoicesGo to full article

“Nineteen hospital trusts are today exposed as having alarmingly high death rates in a major report that also reveals how hundreds of people are dying needlessly because of substandard NHS care”, reported The Observer.

The newspaper story is based on the annual hospital guide, published today by Dr Foster Intelligence, an independently run health information firm which is part owned by the Department of Health.

The guide is an annual publication that seeks to measure hospital performance in England with a growing series of comparative indicators. These indicators are constructed in partnership with Imperial College London. They are based on NHS hospital data and are free of political bias.

The Health Secretary, Dr Andrew Lansley, welcomed the report, writing a commentary in The Observer detailing the steps that are being taken to increase transparency and improve hospital safety and performance:

“We need a cultural shift in the NHS: from a culture responsive mainly to orders from the top down to one responsive to patients, in which patient safety is put first.”

What are the main areas of hospital performance covered by the hospital guide?

The guide is broken down into three main parts:

  • an analysis of hospital performance based on different measures of mortality
  • a detailed look at hospital performance in three major areas of care: stroke, orthopaedics and urology
  • an analysis of patient safety in terms of adherence to best practice, infection control and adverse incidents including accidents

There are also new analyses of efficiency, measured by hospital readmission rates and patient experience, measured by patient survey.

What are the main conclusions of the guide?

The guide contains both positive and negative findings. Under the heading ‘Good news’ it reports that:

  • Deaths in hospitals continue to fall, dropping 7% between 2008/09 and 2009/10 in crude terms.
  • The gap between the hospitals with the highest and lowest Hospital Standard Mortality Ratios (HSMRs) has narrowed, with eight fewer hospital trusts’ HSMRs above the expected range.
  • Safety standards have improved, with higher rates of compliance with safety alerts and better reporting of errors.
  • Four hospital trusts – Airedale, Royal Free Hampstead, Ipswich Hospital and East Kent Hospitals – are given accolades for exceptional performance.

Under ‘Areas of concern’, the guide reports that:

  • Variations in mortality ratios persist, with 19 hospital trusts having high HSMRs.
  • Four trusts have high ratios for the ‘deaths after surgery’ indicator. This means patients who, following surgery, developed another problem such as internal bleeding, and subsequently died. Two of these trusts – University Hospitals Birmingham Foundation Trust and Hull and East Yorkshire Hospitals Trust – also have high HSMRs.
  • Rates of emergency readmissions vary widely between hospital trusts, as do revisions and manipulations following common orthopaedic operations, where three trusts – Frimley Park Hospital NHS Trust, Northumbria Healthcare NHS Foundation Trust and Guy’s and St Thomas’ NHS Foundation Trust – have high rates.
  • Over 27,000 potential medical mistakes (or adverse events) were recorded in hospital data. Dr Foster says that this is almost certainly an undercount due to inconsistent recording.
  • Standards in the treatment of life-threatening conditions such as stroke and broken hips vary widely, with many trusts falling short of best practice.

The hospital guide also makes a call for more data to be made available, noting that there is information ‘we cannot tell you but would like to know’. It highlights a need for better recording of patients developing life-threatening blood clots following treatment, more information about community and primary care services, and better measurement of outcomes in private hospitals providing NHS care, among other things.

What does the guide say about hospital mortality?

It says that Hospital Standard Mortality Rates (HSMRs) are decreasing (i.e. improving) across the NHS in England. Only 19 of the 147 hospital trusts now have ‘significantly high’ HMSRs, compared to 27 in last year’s guide, and 26 trusts have HSMRs that are ‘significantly low’, down from 32 a year ago.

‘The overall improvement suggests greater consistency across trusts, both in terms of data recording and perhaps in the quality of care,’ it says.

The use of HSMRs to measure hospital performance has proved controversial in recent years, with experts pointing out that the measure is ‘imperfect’ and warning that it should not be used to construct simplistic league tables of best and worst hospitals.

Nevertheless, they should not be ignored. Earlier this year, the Department of Health stated: ‘A high HSMR is a trigger to ask hard questions. Good hospitals monitor their HSMRs actively and seek to understand where performance may be falling short, and action should not stop until the clinical leaders and the board at the hospital are satisfied that the issues have been effectively dealt with.’

In a bid to construct a better picture of hospital mortality, the hospital guide published a second mortality indicator measuring deaths after surgery for the first time this year. This looked at surgical patients who had a secondary diagnosis such as internal bleeding, pneumonia or a blood clot, and subsequently died.

The guide reports that there is wide variation between hospitals on this new measure. It says four hospital trusts – Hull and East Yorkshire Hospitals NHS Trust; The Newcastle upon Tyne Hospitals NHS Foundation Trust; University Hospitals Birmingham NHS Foundation Trust; and University Hospital of North Staffordshire NHS Trust – have ‘significantly high’ ratios. Two trusts – Chelsea and Westminster Hospital NHS Foundation Trust and Winchester and Eastleigh Healthcare NHS Trust – have ‘significantly low’ death after surgery results.

‘This measure uses a very different approach from the HSMR, so trusts that have high ratios on both measures – University Hospitals Birmingham NHS Foundation Trust and Hull and East Yorkshire Hospitals Trust – will want to understand the possible causes,’ says Dr Foster.

The Observer reports that sources from the Care Quality Commission have said that they have no concerns about University Hospitals Birmingham on either account or North Staffs on deaths after surgery.

The chief executive of Hull and East Yorkshire, Phil Morley, said, “We are confident that we are providing safe care of a high quality to our patients”.

The hospital guide also notes, that the focus on mortality ratios in recent years has caused some trusts to revisit how they ‘code’ or report patient deaths. This has resulted in some trusts increasing the number of deaths they identify as occurring in ‘palliative care’. This in turn improves the trusts’ mortality ratio because death is the expected outcome.

In the interests of transparency, Dr Foster now publishes the percentage of deaths coded as palliative care for each hospital trust. These range from less than 1% in some trusts to over 40% in others. Basingstoke and North Hampshire NHS Foundation Trust reports 45.5% of deaths as palliative care and Medway NHS Foundation Trust reports 44.5% of deaths in this way.

Two other trusts – Pennine Acute Hospitals Trust and Royal Bolton Hospital NHS Foundation Trust – are noted in the guide as having been in the ‘higher than expected’ HSMR category for the past six years.

What does the guide say about hospital safety?

Overall, safety standards have improved. Dr Foster says a key way of improving safety is to accurately measure and monitor the way in which it is being addressed. Hospitals were rated on a range of aspects of patient safety in 2009. A comparison with this year’s results shows:

  • Higher rates of compliance with safety alerts compared to 2009. However, three trusts still fall short on the immediacy of their compliance, including Southend University Hospital NHS Foundation Trust, St George’s Healthcare NHS Trust, and the Western Sussex Hospitals NHS Trust.
  • An increase in the number of hospitals routinely screening for and treating patients admitted to hospital for infections, along with a special ‘antibiotic pharmacist’ on staff, from 86% last year to 97% this year.
  • Better reporting of patient safety incidents. Though the average number of incidents has increased (from 5% to 5.7%), this is a ‘positive sign’ because it shows ‘awareness of errors and near-misses and a culture of freedom to report’.
  • More hospitals using ‘track and trigger’ systems, which are regular observations by nurses designed to pick up deterioration in a patient’s condition (79% of trusts compared to 64% last year).

Dr Foster says there is room for improvement in how data is recorded. It lists the available figures for several types of avoidable harm, such as pulmonary embolisms and post-operative sepsis, which it cannot put into context due to the lack of complete data.

It identifies the same problem regarding data on the rate of medical mistakes (or adverse events) that happen in hospitals. The guide says again, that trusts with higher rates of incidents also tend to have more complete records about their patients.

The prevention of blood clots also features highly. The report says that all patients admitted to hospital now must be risk assessed for the risk of venous thromboembolism (VTE, of which DVT [deep vein thrombosis] is a common type). However, trusts gave varying responses when asked ‘What percentage of patients are risk-assessed for VTE on admission?’ Most trusts were able to report how many patients were risk-assessed, but 15 responded that they were either not assessing patients for VTE or were unable to provide the information.

A spokesperson for the Department of Health said:
“We accept that VTE is underreported, and are taking steps to change that position.

“At a national level, DH are enabling the NHS to improve accuracy of reporting incidence of hospital acquired VTE.”

What does the guide say about stroke care?

Stroke is the third most common cause of death in the UK, costing the economy an estimated £8 billion a year. Dr Foster says there have been measurable improvements in the way the NHS deals with strokes but still notes ‘a worrying level of variation in care’.

The report identifies six best performing and eight worst performing trusts based on an analysis of six key indicators:

  • the proportion of patients having a brain scan on the same or next day: this ranged from 87% to 42%, with North Middlesex University Hospital NHS Trust having the highest rate
  • the proportion of patients given ‘clot busting’ drugs (thrombolysis) within 24 hours: Rates varied from 0.2% to 17%
  • the proportion of stroke admissions that lead to pneumonia due to swallowing problems: rates varied from 2% to 12%
  • the proportion of patients return home from hospital within 56 days: rates varied from 55% to 85%
  • the rate of emergency readmissions: this varied from 44% below average to 58% above
  • standardised mortality ratio for stroke (a measure that can highlight preventable deaths): rates varied from 34% below average to 66% above average

What does the guide say about orthopaedic care?

Hip and knee replacements, as well as hip fractures, are a major expense for the NHS. The guide analyses some key indicators of the quality of care in these cases:

  • The percentage of patients readmitted to hospital within 28 days of a hip or knee replacement
    Most hospitals performed as expected. However, for hip replacements, two trusts had high rates – Leeds Teaching Hospitals NHS Trust (75% above average) and Newcastle upon Tyne Hospitals NHS Foundation Trust (63% above average). Two trusts had low rates – Northern Devon Healthcare NHS Trust (67% below average) and Royal Devon and Exeter NHS Foundation Trust (35% below average).
  • The number of patients requiring revision of a knee or hip replacement
    Hip replacement revision rates varied from 0 to 3.5 % for knees, rates varied from 0 to 2.1%. Sixteen trusts performed particularly well on this indicator, while three had high rates.
  • Standardised mortality ratio for hip fractures
    Hip fractures are the most common reason for orthopaedic admission and about 10% of people with a hip fracture die within a month. All trusts performed as well as expected and Cambridge University Hospitals NHS Foundation Trust performed particularly well, with a mortality ratio 46% below average.
  • Hip fractures operated on within two days.
    Operating straight away increases a patient’s chances of survival. However, Dr Foster found only 21% of trusts had rates of delayed surgery that were significantly low. The percentage operated on within two days varied from 34% to 94%.

Dr Foster identified six trusts as the best performers across its orthopaedic indicators and singled out Leeds Teaching Hospitals NHS Trust as the worst performer.

What does the guide say about care in urology?

Surgery for urological cancers should ideally be performed in large hospitals where these procedures are carried out more frequently. NICE guidelines state that pelvic urological cancer surgery should only take place in units where more than 50 procedures are carried out each year.

The guide identifies 19 trusts that carried out high numbers of prostate and bladder cancer operation between 2007 and 2010. It also identifies eight trusts performing high numbers of keyhole prostate operations, which enable quicker surgery and recovery.

Overall, the guide notes that more operations are being performed for prostate cancer, more of these operations are taking place in large hospitals and more keyhole procedures are being carried out.

There is a similar trend towards performing cystectomy (removal of the bladder) in large units. In 2006/07 large trusts performed only 21% of cystectomies but by 2009/10 this had risen to 63%.

The guide notes that operations to treat benign urological conditions are performed in a wider range of units than for cancer with varying quality. Dr Foster looked at the need for repeat surgery following one such procedure, transurethral resection of the prostate (TURP), as an indicator of care quality. The report lists 13 trusts that perform best on this indicator and three that perform worst.

Should I worry about the findings in the hospital guide?

No, the guide shows that overall things are improving. Although there are some trusts that are poor performing relative to the average, the vast majority are in the ‘as expected’ range and there are many batting well above average.

The key is to compare hospitals before making an appointment with a specialist and then to make use of your right to choosing which hospital you go to. For more on hospital choice go here.

How can I compare hospitals myself?

NHS Choices’ Find and choose hospitals function allows you to compare hospitals on a wide and growing range of measures, including:

  • overall quality of service (judged by the regulator)
  • mortality rates
  • waiting times
  • infection rates
  • food quality
  • parking facilities
  • disabled access

NHS Choices also allows patients to record their views on NHS services they have used. Users can leave comments about a hospital and say whether they would recommend it to a friend. They can also rate it on the following:

  • Cleanliness
  • How well staff work together
  • Whether they are treated with dignity and respect
  • Whether they were involved in decisions about their care
  • Whether the hospital offers same-sex accommodation

You can view these comments and ratings for any hospital using NHS Choices’ Find and choose services function.

Find more information about your right to choose where you are treated on our page about choosing a hospital.

The hospital guide is published in full on the Dr Foster website.

Links To The Headlines

Exposed: the hospitals whose high death rates are failing the NHS. The Observer, November 28 2010

Andrew Lansley: An open, transparent NHS is a safer NHS. The Observer, November 28 2010

The ‘catalogue of errors’ that cost this father his life. The Observer, November 28 2010

NHS death rates better – but some trusts still too high. BBC News, November 28 2010

Alarm over ‘high nhs death rates’. Daily Star, November 28 2010

Death rates at 19 hospitals ‘alarmingly high’ says report. The Daily Telegraph, November 28 2010

Alarmingly high death rates at 19 NHS hospital trusts, influential report reveals. Daily Mail, November 28 2010

Links To Science

The 2010 Dr Foster hospital guide [downloadable pdf].

Retirement and mental health

‎25 ‎November ‎2010, ‏‎17:40:00 | NHS ChoicesGo to full article

“Taking early retirement is beneficial, at least for your mental health,” BBC News has reported. The website said that a study of French national grid workers has shown that early retirement has positive benefits for mental health but makes no difference to physical illness.

Researchers studied a group of over 14,000 employees of an energy company, who retired between 1990 to 2006. In the years before retirement, participants had completed annual questionnaires about their physical health and levels of mental and physical fatigue. Retiring did not seem to have any effect on the rate of physical health problems, such as diabetes and coronary heart disease, which increased with age as expected. However, they found that fatigue significantly decreased in the year after retirement compared to the year before, especially in those with a long-term illness. Depressive symptoms also fell.

This was an interesting study that suggested that retirement may have some benefits on mental health and perceived fatigue. However, the nature of the research makes it difficult to know for sure that the benefits seen were the result of retirement, and there is still a need for similar research in other countries and populations to clarify the impact of retirement.

It should be noted that the study did not actually compare early and later retirement, as nearly all employees from the company retired before 60, meaning there were no older retirees to compare participants with.

Where did the story come from?

The study was carried out by researchers from Stockholm University; University College London; the Finnish Institute of Occupational Health; the University of Turku; Versailles Saint Quentin University in France, and the Heinrich Heine University of Dusseldorf.

It was funded by the EDF-GDF energy company and a number of international research foundations, including the UK Economic and Social Research Council, INSERM and the French National Research Agency. Individual researchers also received funding by a range of other organisations. The study was published in the peer-reviewed British Medical Journal.

The study was reported on by BBC News. The coverage was mostly accurate but the emphasis on early retirement was misleading, as the French participants studied were entitled to retire between 55 and 60 years of age, with almost all retiring before 60. The researchers were mainly looking at people’s health status before and after retirement, rather than the effects of early retirement.

The Daily Telegraph covered this research well.

What kind of research was this?

This was a cohort study assessing the way retirement may affect health. It followed a large number of people over several years and measured trends in various health outcomes. Researchers measured these various aspects of health over an average of 15 years using annual questionnaires. They also analysed data gathered before and after people retired to make comparisons of their health status during these two periods.

Previous research has suggested that retirement can have an affect on health, with some studies finding it improved health but others finding health declined after retirement. As such, there is no consensus over the impact of retirement and there is a need for clearer evidence on this issue. There is also a need for further research in this area as many countries are experiencing a demographic shift towards an older population that may require new policies towards retirement age.

The study used an appropriate design to address this type of research question. Importantly, it assessed people’s health status for some time before retirement, allowing researchers to interpret any changes seen afterwards. However, all the participants worked for a single employer and greater insight may be gained from a study involving people from a wider range of job types and working environments.

It should be noted that the study did not set out to compare people who retired early with those who retired later.

What did the research involve?

A long-term cohort of people working for Electricité de France-Gaz de France (EDF-GDF) was set up in 1989, recruiting people aged between 35 and 50. There were 14,104 participants in this particular study (11,246 man and 2858 women), all of whom retired between 1990 and 2006.

Using company records the researchers collected data on retirement date, long-term illness or disability and sickness absence. People who had retired early because of disability or poor health were excluded from the analysis (610 people) because patterns of health for people in this situation are different and would make it harder to examine the relationship between standard retirement and health.

Participants were sent questionnaires every year from 1989 to 2007. They were asked questions about physical and mental tiredness, and whether they had experienced any of a number of chronic diseases (coronary heart disease, stroke, respiratory diseases and diabetes).

The researchers also collected data on the participants’ age, sex, marital status, as well as occupation category at retirement, which was categorised as high (managers), intermediate (technical staff, line managers, administrative associate professionals) and low (clerical and manual workers). In addition, further assessment was made of depressive symptoms on four occasions during the study.

The main analysis in this study looked at the annual trend in reported mental fatigue, depression or physical fatigue over the seven years before and seven years after retirement, whenever it occurred. The researchers also performed a second analysis in which retirement age was assessed, categorised as: 54 or under, 55, or 56 and over.

What were the basic results?

The mean average retirement age of participants was 54.8 years. A total of 80% were male, and the majority belonged to higher (34%) or intermediate (54%) job grades. After taking into account the effects of retirement age, sex, occupational grade and the data collection period, the researchers found that there was no difference in the occurrence of stroke, diabetes, respiratory disease or coronary artery disease before or after retirement.

Comparing the year before with the year after retirement, they found reductions in:

  • mental and physical fatigue (mental fatigue odds ratio (OR) 0.19, 95% confidence interval (CI) 0.18 to 0.21)
  • physical fatigue (OR 0.27, 95% CI 0.26 to 0.30)
  • and in depressive symptoms (OR 0.60, 95% CI 0.53 to 0.67)

How did the researchers interpret the results?

The researchers said that ‘the findings provide unique evidence that retirement is related to improvement in wellbeing, with little effect on chronic disease.’ They also suggest their results mean it is no longer necessary for future research to focus on how retirement may prevent chronic disease. However, they say that ‘fatigue is common among older workers’ and suggest that policy makers might need to consider the impact of this on ability to work, and consider what strategies might be necessary to reduce this problem.

The researchers also discuss the strengths and limitations of the study, and recommend that further research be carried out in other countries and work environments to see if the same associations apply to more general contexts.

Conclusion

This study’s strengths included its size, the fact that it monitored the same people for a number of years both before and after retirement, and the way the researchers collected measurements of health on multiple occasions. However, there were a number of limitations that should be considered when interpreting the findings:

  • France has a lower retirement age than many European countries, and many of EDF-GDF’s workers are entitled to retire around the age of 55. Therefore, the findings may be different if the same kind of study was carried out in countries or environments where the retirement age was later.
  • Participants in the study all worked for the same company, which is reported to have good job security and good opportunities for promotion (hence only 12% of people being of a low employment grade at retirement). Although the participants performed a variety of roles, people working in other types of jobs or different work environments may show different patterns of health before and after retirement. It is difficult, therefore, to predict how well these findings might apply to people in a wider range of job types.
  • In studies of this type, it is hard to work out the extent to which the factor being investigated (retirement) is a cause of the outcome being investigated (better health) or whether the observed association is caused by some other factor.
  • Employees who had retired early on health grounds were excluded from the study, so the research cannot tell us anything about the health impact of retirement on people in that situation.
  • The proportion of women in this study was quite small (20%), so further research may be needed to see whether the same effects are seen in men and women.
  • The study authors point out that the fact that occurrence of poor health relied on people’s own reports, means there may be an underestimation of the number of cases of some illnesses, as some might not yet have been diagnosed. They also state the method they used to measure fatigue has only been validated to a limited extent, so its reliability is not confirmed.

Overall, this is an interesting finding which suggests retirement is more important with respect to fatigue and mental health than prevention of chronic diseases such as stroke and diabetes.

However, a number of limitations in the study mean that it is hard to generalise the findings to other settings. As early retirement was not compared with later retirement (beyond age 60 years), the news source’s conclusion about early retirement being better is not warranted. As populations increase in age in many countries, further research on the health impacts of age at retirement are warranted.

Links To The Headlines

Early retirement ‘is good for us’, research shows. BBC News, November 24 2010

Retirement is good for your health, study suggests. The Daily Telegraph, November 25 2010

Links To Science

Westerlund H, Vahtera J, Ferrie JE et al. Effect of retirement on major chronic conditions and fatigue: French GAZEL occupational cohort study. British Medical Journal 2010; 341:c6149

Diets to ‘keep the weight off’ tested

‎25 ‎November ‎2010, ‏‎10:37:00 | NHS ChoicesGo to full article

“Protein-rich diets containing lots of lean meats, fish and egg – as popularised by the Atkins diet – are the best at keeping weight off,” reported The Daily Telegraph. It said that people who stick to this approach can simply eat until they feel full and not put on weight.

This study compared five diets to maintain weight loss in people who had recently lost at least 8% of their weight through dieting. None of the diets were calorie-controlled, but had different amounts of protein and varied in their glycemic index (GI – a measure of the effect that carbohydrates have on blood sugar levels and how fast food is digested).

There was less weight gain with high-protein diets than low-protein diets. People on a low-GI diet regained less weight than those on a high-GI diet. The only diet linked with significant weight regain was a low-protein, high-GI diet.

This large, well-conducted study appears to support the idea that high-protein, low-GI diets are better at maintaining weight loss than other types of diet. However, an Atkins diet was not tested, as the high-protein diet used in this study only included protein as 25% of the total energy consumed, compared with 50% in an Atkins diet. Also, the difference in protein levels between this and a low-protein diet was only modest (13%).

Finally, these diets were not compared to a conventional calorie-controlled diet for weight loss maintenance. The study does not support extreme diets that replace most carbohydrates with protein.

Where did the story come from?

The study was carried out by researchers from research centres in several European countries, including Denmark, the Netherlands, UK, Greece, Germany and Spain. It was funded by grants from and contributions from the European Commission and by several food companies. The study was published in the (peer-reviewed) New England Journal of Medicine.

The Daily Mail’s claim that calorie counting is ‘off the menu’ was misleading since the study did not compare calorie-counting diets with those which are not calorie-controlled. The rest of the paper’s report was accurate. The Daily Telegraph’s claim that ‘protein-rich’ diets are the best way to keep weight off is perhaps exaggerated since the high protein diet used in the study contained only 25% protein.

What kind of research was this?

This was a large randomised trial of over 1,200 adults, in which researchers compared the ability of five different diets aimed at preventing weight gain.

The researchers say that there is still uncertainty regarding the importance of the composition of diet for the prevention and management of obesity. There is increasing interest in diets high in protein or low in GI, but so far, scientists have been uncertain about their effectiveness for maintaining weight loss compared with other types of diets.

In this study, the researchers wanted to test how successful diets were at preventing weight gain in people who had recently lost weight.

Trials in which participants are randomly assigned to different interventions are more reliable than other types of studies (such as cohort studies) for answering questions about effectiveness. This is because randomisation trials help eliminate bias and confounding factors (where things such as sex and education, may influence results).

What did the research involve?

The researchers enrolled 773 overweight adults from eight European countries (Denmark, the Netherlands, the UK, Greece (Crete), Germany, Spain, Bulgaria and the Czech Republic) who had lost at least 8% of their initial body weight with a low-calorie diet over eight weeks previously all using the same diet. The participants were randomly assigned to one of five diets aimed at preventing weight gain for a 26-week period. Participants were allowed to eat as much food they liked from their assigned diet. All five diets were designed to have moderate fat content (25-30% of total energy).

The five different diets were as follows:

  • a low-protein (13% of total energy) and low GI diet
  • a low protein and high GI diet
  • a high protein (25% of total energy) and low GI diet
  • a high protein and high GI diet
  • a control diet that followed dietary guidelines and had moderate protein content

The difference in total energy from protein between high and low protein diets was 12% and the difference in GI between low- and high-GI diets was 15 units.

Participants were on average 41 years old and were all parents. The participants’ families, although not part of the trial, were assigned to the same diets. Families were given recipes and cooking, behavioural and nutritional advice. In some countries, families were also given free food from a shop that catered for their diets, while others only received advice.

The participants’ adherence to their diets was monitored using urine analysis. Urine samples were taken at various times through the trial. The participants also completed food diaries and the glycemic index and nutrient content of the food that they recorded was assessed in a standardised way using glucose as a reference point for high GI index.

Standard statistical methods were used to assess how the different diets affected weight, in particular, which diets worked best for continued weightloss. They used what is called an ‘intention-to-treat’ analysis, which means that all participants who started the trial were included in the analysis, regardless of whether they finished the trial or not. This method helps eliminate the bias that can occur when many people drop out of a trial.

What were the basic results?

The average initial weight loss with the low calorie diet used in the first phase of the study was 11kg. Out of the 938 people who entered this first phase, 773 completed it and were assigned to one of the five diets. A total of 548 people (71%) completed the 26-week diet trial period. Fewer people in the high-protein, low GI groups dropped out than in the low-protein, high-GI-group (26.4% and 25.6% respectively, compared to 37.4%).

In an analysis of the participants who completed the study, only those who were on the low-protein, high-GI diet were associated with significant weight regain (1.67kg, 95% confidence interval [CI] 0.48 to 2.87).

In the intention-to-treat analysis (all people who started the study):

  • weight regain was 0.93 kg less (95% CI 0.31 to 1.55) in groups assigned to a high-protein diet than in those on a low-protein diet
  • weight regain was 0.95 kg less (95% CI 0.33 to 1.57) in those on a low-GI diet than in those on a high-GI diet

How did the researchers interpret the results?

The researchers say that a ‘modest increase in protein content and a modest reduction in the glycemic index’ led to more people completing their diets and maintaining weight loss. The combination also appears to be ideal for preventing people regaining weight after a calorie-controlled diet.

Conclusion

While many overweight people can reduce their weight through diet, maintaining weight loss in the longer term is more difficult. This large, well-designed study found that a non-calorie-controlled diet moderately high in protein and with a slightly reduced GI index appeared to be more acceptable to people (more finished this diet than on other). The diet also helped maintain weight loss when compared with diets lower in protein and higher in GI.

This was a large well-conducted study that found that diets higher in protein and low on the GI scale worked better for maintaining weight loss than lower protein, high-GI diets. As a randomised study, the results are likely to be reliable and worth bearing in mind for individuals interested in keeping to a healthy weight. However, its findings do not support diets that include very high protein levels, or specific programmes such as the Atkins diet.

For a healthy diet, the current advice is to eat plenty of whole grains, fruit and vegetables, many of which are low on the GI scale. Protein is an important part of our diet, although requirements for protein (from fish, lean meat and poultry, eggs and small amount of dairy) vary depending on age and circumstances.

Links To The Headlines

Finally, largest ever study finds formula for lasting weight loss. The Independent, November 25 2010

The trick to keeping weight off for good? Eat as much as you like – and don’t count the calories. Daily Mail, November 25 2010

Protein-rich diets best at keeping weight off. The Daily Telegraph, November 25 2010

Links To Science

Meinert Larsen T, Dalskov S-M, van Baak M, et al. Diets with High or Low Protein Content and Glycemic Index for Weight-Loss Maintenance. New England Journal of Medicine 2010; 363: 2102-2113

HRT ‘brain boost’ is unproven

‎24 ‎November ‎2010, ‏‎17:15:00 | NHS ChoicesGo to full article

“Hormone replacement therapy can make a woman’s mind sharper,” according to the Daily Mail. The newspaper says that women taking hormone replacement therapy (HRT) performed better in tasks involving fine motor co-ordination skills than women of a similar age who were not taking HRT.

The story is based on a study that compared the results of finger-tapping tests in 33 menopausal women taking HRT with those of 26 menopausal women who had not used the therapy. Women not taking HRT showed less asymmetry between the performance of their left and right hands when performing simple tapping with the index finger, but more asymmetry between hands when performing a more complex sequential tapping task. The opposite findings were seen in women on HRT, a pattern that researchers say is normally observed in younger women.

Although these study findings shed some light on the possible effects of hormones upon brain activity, they have limited clinical implications. All of the women of this study were of comparable dexterity, and this single, experimental test of motor function in a small group of women does not provide much insight into whether their everyday lives were affected. Notably, despite what the press coverage has implied, this study has not investigated cognitive ability or intelligence and provides no evidence that HRT will give women “sharper minds” or boost IQ.

Where did the story come from?

The study was carried out by researchers from Durham University and was funded by grants from the Deutsche Forschungsgemeinschaft research foundation. The study was published in the peer-reviewed scientific journal Hormones and Behavior.

The headline featured in the Daily Mail is misleading in saying that HRT makes a woman’s mind “sharper” as the study only examined differences in hand tapping in a small sample of women. The body of the Mail’s story is representative of the research. The Daily Mirror, however, is completely incorrect in saying that HRT “boosts brain power”. This is not the conclusion of this research.

What kind of research was this?

There is a theory that activity in the right and left sides of the brain is affected by age, and that hormone manipulation can also have an effect. In this study, the researchers were specifically investigating whether HRT therapy affected “functional cerebral asymmetries” (FCAs), i.e. performance differences between the dominant and non-dominant hands when carrying out functional activities such as simple movement tasks. The experimental research was in older women taking HRT (two types were tested) and women not taking HRT.

Results of this type of study are of general scientific interest and shed some light on the possible effects of hormones upon brain activity. However, they have limited clinical application and provide limited information on the cognitive and functional abilities of women on hormone therapy or not.

What did the research involve?

The research recruited 62 postmenopausal women aged 46–71 who were put into three groups: women who had gone through menopause at least one year ago and had not used any HRT (26 women); women using continuous oestrogen HRT (15 women) and women using combined oestrogen and progestogen HRT (21 women). All were right-handed with good sight and normal dexterity. All groups were of the same educational level and there was no difference in the number of years since menopause.

The researchers used saliva samples to measure the participants’ oestrogen and progesterone levels. They then performed a finger-tapping task involving an apparatus consisting of four small, movable switches mounted on a metallic plate. The switches were positioned under each participant’s index, middle, ring and little finger. In the first test participants had to repeatedly tap the switch with the index finger as quickly as possible, and in the “sequential” test they had to repeatedly press buttons in the sequence of index finger, ring finger, middle finger, little finger. Participants repeated each test five times with each hand, and each 10-second trial was followed by a short break.

The mean tapping rate was calculated as the mean number of correct taps across the five trials. Manual asymmetry was calculated as the ratio of the differences between hands to overall performance (dominant and non-dominant hand).

What were the basic results?

A total of 59 women were included in the analysis after the exclusion of three participants in the HRT groups who had unusually low blood hormone levels. The basic findings were that postmenopausal women who were not taking HRT had little asymmetry between their right and left hands on simple (repetitive) finger-tapping. However, in sequential finger-tapping there was greater asymmetry, with better performance from their dominant hand.

In comparison, women on HRT (both types) demonstrated a lesser degree of asymmetry between hands when performing sequential finger-tapping. However, they demonstrated increased asymmetry when performing simple finger-tapping. Performance was related to oestrogen levels, with participants with higher oestrogen levels having greater asymmetry on simple tapping.

How did the researchers interpret the results?

The researchers conclude that their results suggest that HRT, and oestrogen therapy in particular, has a positive effect on the motor system and counteracts the changes normally seen with increasing age.

Conclusion

The researchers found that older women not taking HRT displayed less asymmetry when performing simple tapping, but asymmetry between hands when performing more complex sequential tapping with fingers. This, they suggest, reflects age-related changes in connectivity between motor areas of the brain. The opposite findings in women on HRT are, as they say, what has normally been observed when testing younger women (notably, no younger women were included in this study).

There are some limitations to this study, such as the small number of participants and the fact that women were not randomly assigned to the HRT or non-HRT groups, meaning that the results may have been affected by differences between the groups other than their use of HRT.

Although these study findings are of general scientific interest and shed some light on the possible effects of hormones upon brain activity, they have limited clinical implications. All of the women in this study were of comparable dexterity, and this small test of motor function in 33 menopausal women on HRT and 26 women not on HRT provides very limited information on their functional capacity. Despite its misleading news headlines, this study has not investigated cognitive ability and provides no evidence that women on HRT have sharper minds or higher IQ.

Links To The Headlines

How hormone replacement therapy can make a woman’s mind sharper. Daily Mail, November 24 2010

HRT boosts brain power. Daily Mirror, November 24 2010

Links To Science

Bayer U, Hausmann M et al. Hormone therapy in postmenopausal women affects hemispheric asymmetries in fine motor coordination. Hormones and Behavior, Volume 58, Issue 3, August 2010, Pages 450-456

Binge drinking ‘doubles heart risk’

‎24 ‎November ‎2010, ‏‎12:30:00 | NHS ChoicesGo to full article

‘Binge drinking doubles heart risk,’ BBC News reported today. This study was in almost 10,000 men aged 50 to 59 without heart disease from France and Northern Ireland. Most French men drank regularly (90%) compared to half of Irish men. However, Irish men were more likely to binge drink than French men (9.4% compared to 0.5%).

The combined outcome of heart attack or death from heart attack over 10 years was observed in 5.3% of men from Belfast and 2.6% of men from France. Risk was doubled for binge drinkers compared to those men who drank alcohol at least one day a week but did not binge drink. Compared to regular drinkers, non-drinkers also had a doubled risk of heart attack or death from heart attack, and former drinkers had an apparent tripled risk.

The study has a few limitations, but the adverse health effects of binge drinking are well established and these results are probably reliable. Men are advised to drink no more than 21 units a week (no more than four units a day), and women should drink no more than 14 units a week (no more than three units a day). Binge drinking (more than eight units a session for men and more than six for women) should be avoided.

Where did the story come from?

The study was carried out by researchers from Toulouse University School of Medicine, other institutions in France, and Queen’s University, Belfast. Funding was provided by grants from the Institut National de la Santé et de la Recherche Médicale (INSERM) and the Merck, Sharp & Dohme-Chibret Laboratory. The study was published in the peer-reviewed British Medical Journal.

Both BBC News and The Telegraph focused on the hazards of binge drinking. However, the research findings were not as straightforward as this because never drinkers and former drinkers were also at an increased risk of heart attack compared to regular drinkers.

What kind of research was this?

This cohort study investigated how different patterns of alcohol intake affect the risk of heart disease. It examined separate study populations in Northern Ireland and in France, due to the typically different lifestyles of these countries.

A cohort study is usually the best study design to investigate the association between an exposure that occurs in daily life (in this case alcohol) and an outcome (in this case heart disease).

Limitations may arise, however, in accurately quantifying how much a person drinks. A person’s consumption at the start of the study may not reflect their previous or future consumption. Participants also needed to be checked that they did not have heart disease at the time of assessment, something that may not be certain in all cases.

Potential confounders – factors that can affect results – also need to be taken into account. Therefore, attributing alcohol consumption as the cause of heart disease may be difficult.

What did the research involve?

This study enrolled 9,778 men between 1991 and 1994, with an average age between 50 and 59. Of these, 2,745 were recruited in Belfast, Northern Ireland (from industry, the civil service and general practice). The others were recruited from three areas in France (Lille [2633], Strasbourg [2612], and Toulouse [2610], through free medical health screening and occupational medicine settings).

At the beginning of the study, all men completed health and lifestyle questionnaires, which included their alcohol consumption. The London School of Hygiene & Tropical Medicine Cardiovascular Questionnaire for Chest Pain on Effort and Possible Infarction (the Rose questionnaire) was used, which is a validated tool to evaluate chest pain.

The particpants also had their BMI, blood pressure and blood cholesterol measured and an electrocardiogram (ECG) recording. Heart disease was established based on either a prior diagnosis by a physician, ECG evidence of past heart attack, or a positive Rose chest pain questionnaire.

Weekly alcohol consumption, assessed once by questionnaire, took into account frequency of consumption, times of day alcohol was drunk, and types of beverage and their alcohol content (e.g. 10% wine, 12% wine, 4% beer, or 5% beer). One drink of alcohol was standardised as 10-12g of ethanol. The participants were then categorised into the following groups:

  • never drinkers
  • former drinkers
  • regular drinkers (men who drank alcohol on at least one day a week, and, if drinking on only one occasion, consumed less than 50g of alcohol)
  • binge drinkers (alcohol >50g on at least one day a week)

Follow-up was by annual letter or telephone call, and participants were asked to complete a clinical event questionnaire, including hospitalisations, medical consultations, and so on. Possible coronary events were confirmed by further follow-up of medical records. Death certificates were examined where necessary. The relation between characteristics at the start of the study and major coronary events (heart attack or death due to heart disease), was then analysed.

What were the basic results?

About 50% of men in Belfast and 90% of French men reported drinking regularly, with an average daily consumption of 40.2g in Belfast and 36.4g in France. In Belfast, 12% of men drank daily compared to 75% of French men who drank daily. Only 0.5% of French men (33 out of 7373) were classified as binge drinkers, compared with 9.4% of men in Belfast (227 out of 2405). Non-drinkers (including never and former drinkers) comprised 39.5% of men in Belfast and 9.4% of men in France.

Over an average 10 years of follow-up, 5.3% of the men in Belfast suffered either heart attack or related death, compared to 2.6% of the men in France (combined – 3.3% [322] of the total 9,778 sample). A further 3.7% of the total sample (361 men) developed angina (chest pain related to heart disease).

Annual incidence of hard coronary events was 5.63 per 1,000 ‘person years’ (the total sum of the number of years that each member of a study population has been under observation) in Belfast and 2.78 per 1,000 person years in France.

After adjusting for recognised cardiovascular risk factors and country of study, binge drinkers had almost double the risk of major coronary events compared to regular drinkers (hazard ratio 1.97, 95% confidence interval [CI] 1.21 to 3.22). Never drinkers and former drinkers also had greater risk compared to regular drinkers (hazard ratios 2.03, 95% CI 1.41 to 2.94, and 1.57, 95% CI 1.11 to 2.21, respectively).

How did the researchers interpret the results?

The researchers conclude that regular and moderate alcohol intake throughout the week is associated with a low risk of heart disease, whereas a binge-drinking pattern confers a higher risk.

Conclusion

This research assessed 9,778 men in Northern Ireland and France over an average period of 10 years. It has several strengths including its large size, consideration of various possible confounders, and confirmation of heart disease and heart disease events during follow-up using medical records and death certificates. However, there are still some points that need to be taken into account:

  • Alcohol consumption was only assessed once, and it is not known whether this measurement represents the participant’s previous or future consumption. Also quantifying the exact alcohol content of beverages can be difficult, and people may be reluctant to report their true levels of alcohol consumption. Therefore, there may be some inaccuracy when categorising people according to their alcohol consumption.
  • Though the researchers took great care to exclude anyone with heart disease when they were enrolled, it is still difficult to ensure that all participants were completely free of heart disease. A person was considered to have no heart disease if they had a never been diagnosed by a doctor, had no ECG evidence of heart disease, and gave a negative response to questions on chest pain and discomfort. However, there are various symptoms of heart disease, and sometimes a heart attack can occur suddenly in a person with no prior evidence of the condition.
  • Though the news focused on the doubled risk of heart attack in binge drinkers, it should be noted that this was compared to regular drinkers (men who drank alcohol on at least one day a week, and, if drinking on only one occasion, consumed less than 50g of alcohol). Compared to regular drinkers, non-drinkers also had a doubled risk of heart attack and former drinkers had an apparent tripled risk. This complex ‘U-shaped’ relationship between alcohol and cardiovascular risk has also been observed in other studies.
  • Many factors affect the risk of heart disease, and separating the effects of these factors is difficult. Although the researchers attempted to take into account factors that could affect results (potential confounders), some were not included, such as diet. They acknowledge that ‘it is difficult to conclude whether the pattern of alcohol intake has a major role in the incidence of ischaemic heart disease independent of other behaviours, such as diet’.
  • The study was carried out in men, and so the results may not be directly applicable to women. The average age of the men was also 50-59, so in younger men there may not be the same association between binge drinking and heart disease.

Men are advised to drink no more than 21 units of alcohol a week (no more than four units a day), and women should drink no more than 14 units of alcohol a week (no more than three units a day). One unit is considered to be 8g by weight of alcohol. Binge drinking (more than eight units a session for men and more than six for women) should be avoided.

Links To The Headlines

Binge drinking doubles risk of heart attack. The Daily Telegraph, November 24 2010

Binge drinking ‘doubles heart risk’. BBC News, November 24 2010

Links To Science

Ruidavets JB, Ducimetière P, Evans A, et al Patterns of alcohol consumption and ischaemic heart disease in culturally divergent countries: the Prospective Epidemiological Study of Myocardial Infarction (PRIME). BMJ 2010; 341: c6077

Diabetes drug for Alzheimer’s explored

‎23 ‎November ‎2010, ‏‎16:59:00 | NHS ChoicesGo to full article

“A common diabetes drug could be redeveloped as a new treatment for Alzheimer’s,” reported the BBC. It said that metformin may help prevent the formation of “tau tangles”, a key brain abnormality linked to the disease.

This study investigated whether metformin has any effect on the tau proteins that form these tangles. In studies of mouse cells, metformin increased the activity of an enzyme that can counteract the development of the tangles. Similar findings were also seen in live mice given the drug.

These are promising findings, but this is early research and many questions still need answering. It is not known if the drug can prevent or treat the brain changes seen in Alzheimer’s in humans or if it can help with memory, cognition and recognition problems. Also, the doses used in these experiments on mice were much higher than the equivalent doses used to treat diabetes in humans. It is not known if an equivalent human dose would be safe.

Where did the story come from?

This study was carried out by researchers from the Max-Planck Institute, the Charité Medical School, the German Centre for Neurodegenerative Diseases, and the University of Dundee and the University of Innsbruck in Scotland. It was published by the peer-reviewed journal Proceedings of the National Academy of Sciences.

The study was funded by the Volkswagen Stiftung, Tenovus, the Tyrolian Future Foundation, and the Integrated Center of Research and Therapy of the Medical University of Innsbruck.

The BBC covered the story accurately, noting this is early stage research not yet carried out in humans. The source of the Daily Mail’s claim that metformin could be administered in combination with resveratrol is unclear, as the researchers did not use resveratrol in their study, nor do they make any specific recommendations of combination treatments. Therefore, the claim that this research ‘brings hope of a brighter future for millions’ is premature.

What kind of research was this?

The aim of this study was to investigate whether metformin, a drug approved for the treatment of diabetes, had any effect on levels of proteins in the brain associated with Alzheimer’s disease. This laboratory study was on mouse cells and healthy mice without Alzheimer’s disease.

A sign of Alzheimer’s disease is the formation of clumps of protein, known as plaques and tangles, in the brain. Tangles are mostly made up of a protein called tau.

In healthy brains without Alzheimer’s, the tau protein plays an essential role in cell function. However, in Alzheimer’s disease, an abnormal version of tau is produced. Linked to this abnormal tau is a biological process called ‘phosphorylation’. In Alzheimer’s brains, this process does not work properly, and too much phosphorylation occurs, disrupting the normal activity of tau proteins and leading to the formation of tangles.

An enzyme called PP2A is known to reduce levels of phosphorylation and it has been discovered that, in people with Alzheimer’s disease, PP2A activity may be reduced.

Previous research has suggested that metformin can interact with PP2A. These researchers wanted to see whether metformin can reduce the extent of tau phosphorylation by increasing the activity of PP2A.

What did the research involve?

The researchers began by investigating whether PP2A was able to remove phosphorylation from tau in living cells. They then investigated whether metformin could increase activity of PP2A and whether this increase could lead to a reduction in phosphorylation in mouse neurone cells.

The researchers then confirmed that metformin influenced levels of tau phosphorylation through PP2A, and explored how the drug might be acting on PP2A. Finally, they looked at the effects of metformin on tau phosphorylation levels in living mice.

What were the basic results?

Metformin was found to increase the activity of PP2A in cells in the laboratory. Cells in which PP2A activity was stimulated by metformin had lower levels of tau phosphorylation. This applied to normal mouse cells, as well as cells from mice that had been genetically modified to produce the human form of the tau protein. The researchers confirmed that the metformin was indeed acting on tau phosphorylation through the activity of PP2A.

Finally, they found the mice that had been given metformin in their drinking water had reduced levels of tau phosphorylation.

How did the researchers interpret the results?

The researchers describe how metformin reduced the levels of tau phosphorylation in both cells and in live mice. They say their findings ‘suggest a potential beneficial effect of long-term metformin treatment and raise the hope that metformin would have a neuroprotective and prophylactic effect in patients with a predisposition to Alzheimer’s disease’.

Conclusion

This was an early stage laboratory study in healthy mice without Alzheimer’s disease, which gives insight into the biochemical effect that metformin has within nerve cells. These are promising findings but this study does not tell us whether metformin has the same effect on tau proteins in humans, what dose is safe and effective, and whether it would work in all patients.

It should be noted that this study used doses of metformin that were much higher than the equivalent doses used in people with diabetes. If further laboratory studies show that metformin is effective at preventing or treating Alzheimer’s disease in animal models, the next stage would be to start clinical trials. As metformin is already licensed for use in diabetes, the process of assessing its safety in humans could be shortened. However, identifying a safe and effective dose for dementia, and checking whether such a dose would have any additional side effects or possible harms, would still be necessary.

Links To The Headlines

Diabetes drug ‘Alzheimer’s hope’. BBC News, November 23 2010

Cocktail of cheap drugs ‘can prevent Alzheimer’s’ and keep the brain healthy into old age. Daily Mail, November 23 2010

Boost on dementia. The Sun, November 23 2010

Links To Science

Kicksteina E, Kraussa S, Thornhill P et al. Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling. PNAS, Published online before print November 22, 2010

Carrot chemical ‘may cut cancer risk’

‎23 ‎November ‎2010, ‏‎16:45:00 | NHS ChoicesGo to full article

Eating carrots can reduce the risk of suffering from heart disease and protect against cancer, The Daily Telegraph has reported.

The story comes from a large 14-year study that found participants with the highest blood levels of alpha-carotene, an antioxidant found in many orange vegetables, were at lower risk of dying from any cause, and from conditions specifically related to cardiovascular disease and cancer.

However, the study only measured people’s alpha-carotene levels. It did not measure blood levels of other antioxidants, so it is difficult to know if alpha-carotene alone is associated with health benefits or if other constituents were also involved. The study also used only one blood sample to measure people’s alpha-carotene levels, and levels may well have changed during the years of the study. These are important limitations.

Like other antioxidants, alpha-carotene is found in several vegetables, including carrots, and this study may be considered to support the health benefits of a diet high in fruit and vege.

However, the health benefits of antioxidant supplements are far from well established and the use of antioxidant supplements requires further research. The public should be aware that there are many different brands of antioxidants on the market and these may not all be subject to the same safety and efficacy regulations as conventional medicines.

Where did the story come from?

The study was carried out by researchers from the Centers for Disease Control and Prevention in Atlanta, Georgia and the University of California in the US. No external financial funding was reported. The study was published in the peer-reviewed medical journal, Archives of Internal Medicine.

Both the Telegraph and Daily Express reported on the study. While their message – that fruit and vegetables have health benefits – was correct, their stories overstated the findings from this particular study. The study did not measure the health effects of people’s diets, only of blood levels of one particular antioxidant. The Daily Express confusingly linked the study to other research on orange juice, concluding that both carrots and orange juice can cut the risk of heart disease and cancer.

What kind of research was this?

This was an analysis of data from a long-running cohort study of over 16,000 US adults, looking at health and nutrition. This particular study aimed to find out if there was any relationship between blood levels of alpha-carotene, an antioxidant found in many vegetables, and the risk of death due to any cause as well as from specific causes including heart disease, stroke and cancer.

The researchers point out that oxidative damage is now suspected of playing a role in the development of chronic disease and that antioxidants may help protect against this process. While many studies have linked high consumption of fruits and vegetables to lower risk of several chronic diseases, uncertainty remains about the specific constituents that may contribute to these health benefits.

The researchers also say consumption of beta-carotene supplements has been shown to have no effect on risk, suggesting the possibility that other carotenoids (such as alpha-carotene) may contribute to the reduction in disease risk. The results of studies on possible health effects of alpha-carotene are mixed and this subject warrants further investigation, they argue.

Cohort studies are useful to follow up large groups of people over many years and are often used to investigate the possible effects of lifestyle measures such as diet and exercise. This was a prospective cohort study, which means it tracked people over time. This is considered to be more reliable than retrospective studies, which look at a person’s history.

However, it can be difficult to prove cause and effect with this type of study due to the influence of possible confounding factors and also because it is hard to regulate participants’ diets and ensure that they have remained the same throughout the study.

What did the research involve?

For this study, the researchers used data from a national health and nutrition survey undertaken between 1988-1994. The study had recruited US adults aged 20 years and over, and was designed to be representative of the US population. Participants were interviewed in their homes, attended a medical centre for examination and provided a single blood sample.

From the 16,573 adults who attended the examination centres, a total of 15,318 (92.4%) were included in the study. The rest were excluded for various reasons, for example, failing to have a blood test or because important data was missing.

After taking blood samples, researchers used standard laboratory techniques to measure the amount of alpha-carotene, reported in terms of μg/dL (micrograms per 100ml of blood). They also measured cholesterol levels. Researchers then divided participants into five categories, depending on their blood levels of alpha-carotene, ranging from 0-1 μg/dL to 9 or more μg/dL.

In the years following to December 2006, they matched participants to the National Death Index, to determine their survival status. They used a standard classification of diseases to determine underlying cause of death. They divided the causes of death into three major categories: cardiovascular disease, cancer and all other causes.

They used standard statistical methods to assess the relationship between blood levels of alpha-carotene and the risk of death during the follow-up period, which was 14 years on average. The findings were adjusted to take account of other things that might have affected the results (called confounders), such as age, lifestyle, education, blood pressure and cholesterol measurements.

What were the basic results?

Of the 15,318 participants, 3,810 died during the follow-up period.

Overall, the researchers found that people with higher blood levels of alpha-carotene were at lower risk of dying from any cause over the 14-year follow-up period than people with low levels. People with higher levels were also at lower risk of specifically dying from any cardiovascular disease and from cancer (P < .001 for linear trend). This lowered risk was independent of factors such as lifestyle habits, blood pressure, age and sex.

The following are the risk reductions for death from any cause (adjusted for potential confounders):

Compared with participants with alpha-carotene concentrations of 0 to 1 µg/dL

  • those with alpha carotene levels of 2 to 3 µg/dL, were 23% less likely to die from any cause (relative risk 0.77, 95% confidence interval 0.68 to 0.87)
  • those with levels of 4 to 5 µg/dL were 27% less likely to die from any cause (RR 0.73, 95% CI, 0.65 to 0.83)
  • those with levels of 6 to 8 µg/dL were 34% less likely to die from any cause (RR 0.66, 95% CI, 0.55 to 0.79)
  • Those with levels of 9 µg/dL or higher were 39% less likely to die from any cause (RR 0.61, 95% CI 0.51-0.73).

Researchers also found a significantly lower risk between higher alpha-carotene levels and risk of death from cardiovascular disease (P for trend 0.007) and cancer (P for trend 0.02). Associations between death from individual cancers and from specific cardiovascular causes (e.g. heart attack, stroke) were, however, non-significant.

How did the researchers interpret the results?

The researchers say that their results suggest further research is needed into the possible health benefits of alpha-carotene. Although chemically similar to beta-carotene, some studies suggest it may be more effective as an antioxidant in protecting against some diseases. They also say that blood levels of alpha-carotene, which is not currently found in supplements, is a reliable biomarker for fruit and vegetable consumption. Therefore, their study supports previous findings that fruit and vegetable consumption is beneficial to health.

Conclusion

Overall, this study supports other findings that high consumption of fruit and vegetables is beneficial to health. Its strengths include its large size and relatively lengthy follow-up period. However, it also has some limitations, which make the results less reliable:

  • Researchers only took one measurement of blood levels of alpha-carotene. Blood levels may change for various reasons, including variations in diet.
  • In particular the researchers did not measure blood levels of other substances (such as other antioxidants), which might have had an effect on results.
  • The results may been affected by other unidentified factors (confounders) despite efforts to adjust for some of these.
  • The researchers carried out a large number of statistical comparisons between levels of alpha-carotene and mortality from an extensive number of causes. This increases the possibility of chance findings.
  • Of note is the fact that alpha-carotene levels were associated with both death from any cause and from cardiovascular causes and cancer. However, when it was subdivided into specific types of disease, the association was no longer significant.

Also, the study provided no indication as to how many vegetables (and of what type) would need to be consumed to match the blood level measurements used in the study.
There is no doubt that carrots and other vegetables have health benefits. Whether this is due to the alpha-carotene they contain, to other antioxidants or to a complex balance of nutrients and vitamins they contain, remains uncertain.

Of importance is the fact that the health benefits of antioxidant supplements are far from well established. Other large reviews have found no evidence to support any benefit from taking antioxidant supplements, and have instead identified potentially harmful effects of taking certain supplements, including beta-carotene. As such, the use of antioxidant supplements requires further research.

The public should be aware that there are many different supplement brands on the market and these may not all be subject to the same safety and efficacy regulations as conventional medicines.

Links To The Headlines

Carrots ‘help protect against cancer’. The Daily Telegraph, November 23 2010

How orange juice can help to ward off heart disease. Daily Express, November 23 2010

Links To Science

Li C, Ford ES, Zhao G et al. Serum -Carotene Concentrations and Risk of Death Among US Adults. Archives of Intern Medicine, [Published online] November 22, 2010.

Confusion over red wine and diabetes

‎22 ‎November ‎2010, ‏‎16:15:00 | NHS ChoicesGo to full article

“Super-food” compounds in wine “can work as well as a daily dose of medication for people with type 2 diabetes,” the Daily Express has claimed. The newspaper says that “drinking a small glass of red wine every day can help treat diabetes”.

This story is based on laboratory research that looked at how well polyphenol compounds found in red wine can bind to a protein called PPARγ. The protein, which is targeted by the anti-diabetes drug rosiglitazone, plays an important role in glucose and fat metabolism in the body. However, while the research found that these polyphenol compounds were also able to bind to PPARγ in the laboratory, this does not mean they will have the same effects on the body as rosiglitazone. It is important to note that rosiglitazone can no longer be marketed in the EU for the treatment of diabetes as it was found to be associated with an increased risk of certain cardiovascular problems.

Further studies in cells and animals would be needed to determine whether the compounds identified in this study could potentially have anti-diabetic effects in humans. Until this is proven, it is inaccurate and premature to suggest that people can treat their diabetes with red wine.

Where did the story come from?

The study was carried out by researchers from the Christian Doppler Laboratory for Receptor Biotechnology and the University of Natural Resources and Life Sciences in Austria. No sources of funding were reported by the study. The study was published in the peer-reviewed scientific journal, Food and Function.

The Daily Express and Daily Mail both report on this study. Both suggest that red wine could help “treat” diabetes and the Express states that certain compounds found in wine “can work as well as a daily dose of medication for people with type 2 diabetes”. These conclusions are not supported by this research, which only looked at the ability of red wine and some of the compounds it contains to bind to a particular protein in the laboratory. The Daily Mail does point out that “the study didn’t look at the effects of wine on people”, and includes a quote from an expert who notes the lack of clinical relevance of these findings. It also adds that “the alcohol in wine is high in calories and can lead to weight gain, which can outweigh the benefits of these chemicals”.

Both papers report benefits of a “small glass of wine” but include pictures of women drinking what appear to be large glasses. Depending on its alcoholic strength, a large glass of wine (275ml) will typically meet or exceed a woman’s recommended maximum alcohol intake of two to three units a day.

What kind of research was this?

This was a laboratory study looking at the chemical properties of red wine. In particular, it looked at how different chemicals found in red wine bind to a protein called “peroxisome proliferator-activated receptor γ” (PPARγ), which has an important role in glucose and fat metabolism in the body.

The researchers wanted to look at this because moderate consumption of red wine has been linked to a lower risk of cardiovascular disease as well as type 2 diabetes, obesity and high blood pressure. Certain compounds found in wine called polyphenolic compounds, such as resveratrol, have been found to bind strongly to PPARγ. The researchers wanted to identify which polyphenolic compounds in wine bind most strongly to PPARγ, and calculate the equivalent concentration of the antidiabetic drug rosiglitazone needed to match the effect.

This type of study can show how molecules bind to each other in the laboratory, but cannot prove what effect a molecule will have once in the body. This type of study cannot tell us what effect red wine or the compounds it contains would have on the risk of diabetes or on people with diabetes.

What did the research involve?

The researchers assessed twelve Austrian wine varieties for their binding to PPARγ: two whites and ten reds. They also looked at the PPARγ-binding abilities of the polyphenolic compounds found in one of the wines that was particularly rich in these compounds.

The researchers used special techniques to assess the chemical composition of the wines and to separate their components. They tested a total of 121 compounds. They also used other chemical techniques to determine the antioxidant ability of the wines. Finally, they looked at the ability of the wines or isolated compounds from the wines to bind to PPARγ, using an assay where the test substances “compete” with a fluorescently labelled compound to bind to PPARγ. Substances binding to PPARγ more strongly will stop more of the fluorescently labelled compound from binding to PPARγ, which can be measured in the laboratory.

The researchers compared the ability of the wine compounds to bind to PPARγ with that of rosiglitazone, using available data on how well the drug binds to PPARγ. Rosiglitazone is a drug that was used up until recently to treat type 2 diabetes and acts by binding to PPARγ.

What were the basic results?

The researchers found that two polyphenolic compounds found in wine, ellagic acid and epicatechin gallate, were the compounds that bound to PPARγ the strongest. These compounds had a similar affinity for PPARγ to the anti-diabetes drug rosiglitazone.

The researchers found that all of the red wines tested had the ability to bind PPARγ, with 100ml of the various tested red wines having an equivalent binding effect as about 1.8mg to 18mg of rosiglitazone. This is between a quarter and four times the daily dose of rosiglitazone.

How did the researchers interpret the results?

The researchers suggest that the ability of red wine to reduce the risk of metabolic diseases such as diabetes may be explained in part by the fact that it contains compounds that can bind to PPARγ.

Conclusion

This laboratory study has looked at the ability of red wine and its polyphenol compounds to bind to PPARγ, an important protein in glucose and fat metabolism within the body. Some of the compounds were found to be capable of binding to PPARγ with a strength similar to that of the anti-diabetes drug rosiglitazone.

However, just because these compounds can bind to PPARγ in the laboratory does not mean that they or red wine can be used as a treatment for diabetes. Although these compounds may share certain chemical properties with rosiglitazone, they may differ in other ways, meaning that they are likely to have differing effects on the body. It is also important to note that rosiglitazone can no longer be marketed in the EU, as it was found to be associated with an increased risk of certain cardiovascular problems, a risk that was judged to outweigh its potential benefits.

Further studies in cells and animals would be needed to determine whether the PPARγ-binding compounds identified in this study could potentially have anti-diabetic effects.

Links To The Headlines

How red wine fights diabetes. Daily Express, November 22 2010

Glass of red wine a day ‘treats diabetes by helping body regulate blood sugar levels’. Daily Mail, November 22 2010

Links To Science

Zoechling A, Liebner F and Jungbauer A et al. Red wine: A source of potent ligands for peroxisome proliferator-activated receptor γ. Food and Function, 2011, Advance Article

Moderate drinking and heart health

‎22 ‎November ‎2010, ‏‎10:01:00 | NHS ChoicesGo to full article

The Daily Telegraph has reported that scientists have discovered a molecule that may explain “why moderate drinking might be good for you”.

This was a study of cells and mice in the laboratory. The researchers found that alcohol inhibits the growth of “smooth muscle cells”, a type of cell known to have a role in atherosclerosis.

Previous studies have found that light to moderate alcohol consumption is associated with a reduced cardiovascular risk, but it is difficult to say whether the effect of alcohol seen in this study is the reason. Much more research will be needed to fully understand these effects and how they relate to cardiovascular risk.

The NHS says there is evidence to suggest that “a regular pattern of drinking small amounts of alcohol can reduce the risk of heart disease in men over the age of 40 and post-menopausal women. No more than one to two units a day is needed”.

Where did the story come from?

The study was carried out by researchers from the University of Rochester Medical Center and Dublin City University. It was funded by the National Institutes of Health and the American Heart Association.

The research was published in the peer-reviewed medical journal Arteriosclerosis, Thrombosis and Vascular Biology. The Daily Telegraph provides balanced coverage of this study.

What kind of research was this?

The researchers say that previous studies have suggested that moderate alcohol intake is associated with a reduced risk of cardiovascular disease, but it is not understood why. One theory is that alcohol’s effects on smooth muscle cells (SMCs) might be involved. SMCs are involved in the development of atherosclerosis by forming a fibrous covering over the fatty plaques that build up in blood vessels. Laboratory research has shown that one effect of alcohol is to reduce the proliferation of SMCs.

SMCs also proliferate as part of the healing process for injured blood vessels. A protein called Notch 1 is known to be involved in controlling the proliferation of SMCs, and the researchers wanted to test whether alcohol might affect SMCs by modifying Notch 1 signalling in the cells.

This type of study is an appropriate way to work out exactly how a compound such as alcohol might have an effect on cells in the body.

What did the research involve?

The researchers treated human coronary artery SMCs with alcohol (ethanol), and examined the effect this had on the activity of the genes that produce the Notch 1 protein, and on a gene that the Notch 1 protein usually switches on in the cells. They also looked at the effect that alcohol had on the proliferation of the SMCs.

The researchers then studied how alcohol affected human coronary artery SMCs that had been genetically engineered always to have an active form of the Notch 1 protein.

The researchers then looked at the effect of alcohol on SMCs in live mice. They reduced blood flow through the mice’s left coronary arteries by partially tying them off. This procedure leads to thickening of the artery walls caused by proliferation of SMCs. This vessel wall thickening is similar to what happens in the vessels in human cardiovascular disease. Some of the mice were given a moderate amount of alcohol daily, and vessel healing was compared between these mice and mice that were not given alcohol.

What were the basic results?

The researchers found that alcohol reduced the activity of the gene that produces the Notch 1 protein in human coronary artery SMCs, and also the activity of a gene that Notch 1 usually switches on in the cells. At the same time, alcohol also reduced the proliferation of the SMCs. Cells that were genetically engineered so that the Notch 1 protein was always active were not affected by alcohol: they did not show reduced proliferation when treated with alcohol.

In mice with partially tied off carotid arteries, drinking a moderate amount of alcohol reduced the proliferation of the SMCs in the vessel walls. It also reduced the normal thickening of the vessel wall that was seen in mice not drinking alcohol. The mice that drank alcohol also had a reduced activity in the gene that produces Notch 1 and in a gene that the Notch 1 protein usually switches on in the cells.

How did the researchers interpret the results?

The researchers conclude that alcohol inhibits Notch 1 signalling and therefore SMC proliferation both in the laboratory and in mice. They say that this effect may be relevant to the effects of moderate alcohol consumption on cardiovascular health that has been suggested in epidemiological studies.

Conclusion

This study has identified one way that alcohol affects smooth muscle cells. It is difficult to say whether this contributes to the effects of moderate alcohol consumption on cardiovascular risk.

The mice used had surgically created vessel injuries rather than atherosclerosis, and therefore may not be fully representative of the disease process in humans. It has also not been clearly established exactly what dose of alcohol is needed for a protective cardiovascular effect in humans, and therefore it is not possible to say how well this corresponds to the amount of alcohol given to the mice in this study.

It is important to keep the tentative conclusions of this study in context. The effects of alcohol on the cells in the body are likely to be complex, and much more research will be needed to understand them fully.

The NHS recommends no more than one to two units a day are needed for a protective effect, saying there is evidence that “a regular pattern of drinking small amounts of alcohol can reduce the risk of heart disease in men over the age of 40 and post-menopausal women”.

One unit is the amount of pure alcohol in a 25ml single measure of spirits (ABV 40%), a third of a pint of beer (ABV 5 to 6%) or half a 175ml ‘standard’ glass of red wine (ABV 12%).

Links To The Headlines

Why moderate drinking might be good for you. The Daily Telegraph, November 22 2010

Links To Science

Morrow D, Cullen JP, Liu W, et al. Alcohol Inhibits Smooth Muscle Cell Proliferation via Regulation of the Notch Signaling Pathway. Arteriosclerosis, Thrombosis, and Vascular Biology. 2010;30:2597-2603

Does tomato juice fight osteoporosis?

‎19 ‎November ‎2010, ‏‎10:38:00 | NHS ChoicesGo to full article

“Two glasses of tomato juice a day strengthens bones and can ward off osteoporosis,” The Daily Telegraph reported. It said scientists have found that an ingredient in the drink, called lycopene, slows down the breakdown of bone cells, protecting against the disease.

This news story is based on a small pilot study that compared the effects of lycopene supplements and tomato juice on chemical signs of bone loss in postmenopausal women. Women taking lycopene from either juice or pills had lower levels of the chemical by-product associated with osteoporosis.

The findings of this study highlight an avenue for further research. However, it is too soon to conclude that tomato juice will help fight bone disease. The researchers, though optimistic, make it clear that their study is a pilot and that larger studies that measure actual bone loss or fractures, rather than the signs of the disease, will provide better evidence.

Where did the story come from?

The study was carried out by researchers from St Michael’s Hospital in Toronto and the University of Toronto, Canada.

The study was funded by tomato juice manufacturers, the makers of the lycopene supplements and  various other organisations. These included the Canadian Institutes of Health Research, the research and development departments of Genuine Health Inc., the HJ Heniz Co, Millennium Biologix Inc., Kagome Co (Japan) and LycoRed Ltd (Israel).

The study was published in the peer-reviewed medical journal Osteoporosis International.

The Telegraph covered the research well, although it is important to highlight some of the study’s shortcomings including its small size and the fact that it measured a surrogate marker of bone loss, rather than actual bone loss or fractures.

What kind of research was this?

This small randomised controlled trial investigated whether levels of a substance called N-telopeptide, a marker of bone loss, in the body could be affected by lycopene supplementation in pill form and from tomato juice. Lycopene is a type of antioxidant. It is found in fruit and levels of lycopene are especially high in tomatoes. Antioxidants in general are thought to help prevent damage to cells by neutralising substances called “reactive oxygen species” (ROS), which are by-products of the metabolic process (how the body breaks down food).

The researchers enrolled early postmenopausal women, aged 50 to 60 years old. Women at this age lose bone at an accelerated rate and, according to the researchers, some studies have shown that the rate of bone loss and damage to bone cells is increased by rising levels of ROS.

In this study, the researchers wanted to see whether lycopene supplementation would reduce evidence of bone loss in women at high risk.

What did the research involve?

The researchers enrolled 60 women who had been postmenopausal for at least a year and who were aged between 50 and 60 years. Women were excluded if they were smokers or if they were taking any medications that might affect their bone metabolism or have antioxidant properties (for example, treatments for heart disease, high blood pressure or diabetes). They were asked not to consume any vitamins that may contain antioxidants or foods containing lycopene, such as grapefruit and watermelon, for the duration of the study.

The women were randomly allocated to one of four groups: 15mg of lycopene from regular tomato juice, 35mg of lycopene from lycopene-rich tomato juice, 15mg of lycopene from a capsule, and a placebo capsule containing no lycopene.

All the women were asked to refrain from eating foods that contained lycopene for one month before the start of the study. Height, weight, blood pressure and a blood sample for analysis were also taken before the study started.

The women took the supplement twice a day with meals. Further blood samples were taken for analysis after two and four months of supplementation. The women kept a daily food diary to record the other food and drinks they consumed in the seven days before a blood test. The study lasted for four months. The researchers were mainly interested in blood levels of the substance N-telopeptide. This is one of several substances whose concentration in the blood will increase if bone is being broken down. The researchers also measured a number of other substances in the blood including proteins and enzymes, and also tested blood samples for antioxidant capacity.

The researchers compared the levels of N-telopeptide in the three lycopene supplementation groups with those in the placebo group. They also merged the three lycopene supplementation groups into one group to compare it separately against placebo. This was the main analysis they presented. The analyses were adjusted for factors that might affect the relationship between lycopene and bone health, such as BMI, age, blood pressure, years since menopause and levels of antioxidants and bone-loss markers at the start of the study.

What were the basic results?

The total amount of lycopene absorbed by the body was the same for both women taking supplements and those taking tomato juice. As expected, women taking supplements had more lycopene in their blood than those on placebo at the two- and four-month follow-ups.

After two months, blood levels of N-telopeptide were reduced in the supplementation group, while the placebo group showed increased levels. This difference between the treatment and placebo groups was significant and present at four months. The blood levels of other substances also increased, such as beta-carotene (a pro-vitamin also found in tomato juice and a product of lycopene metabolism).

How did the researchers interpret the results?

The researchers concluded that the levels of reduction in N-telopeptide in the groups receiving lycopene are comparable to those seen in postmenopausal women who are supplemented with calcium and vitamin D, both of which are recommended for preventing osteoporosis.

Conclusion

This was a small randomised controlled trial which the researchers themselves called a pilot study. It provides preliminary evidence of an effect, but must be followed by larger, more robust studies that have clinically meaningful outcomes.

The researchers delivered an in-depth and insightful report of their research, highlighting the main shortcomings of their study. While they are optimistic about their findings, reporting that the size of the reduction in N-telopeptide was similar to that seen as a result of calcium and vitamin D supplementation, they admit that they did not measure bone mineral density (BMD) or follow the participants for long enough to observe any significant changes in BMD.

This means we do not know what effect the reduction in N-telopeptide has on BMD or other outcomes such as fracture rates, which are the important clinical outcomes for women at risk of osteoporosis. As such, the research does not provide evidence that lycopene has a clinically important benefit for postmenopausal women. Longer studies would be needed to determine whether lycopene has a role in preventing osteoporosis.

Importantly, giving the women supplements with greater concentrations of lycopene did not affect the total amount absorbed by the body. This suggests that the body may only absorb what it needs and does not take in more simply because it is given more.

The relationship between beta-carotene and lycopene may also need further research, as it is not clear which of these antioxidants (or both) might be responsible for the changes seen. The potential harms of taking too much of either substance need further investigation.

Links To The Headlines

Study shows two glasses of tomato juice a day helps beat bone disease. Daily Mail, November 19 2010

Tomato juice can strengthen the bones. The Daily Telegraph, November 19 2010

Tomatoes bone aid. The Sun, November 19 2010

Links To Science

Mackinnon ES, Rao AV, Josse RG and Rao LG. Supplementation with the antioxidant lycopene significantly decreases oxidative stress parameters and the bone resorption marker N-telopeptide of type I collagen in postmenopausal women. Osteoporosis International, June 15 2010 (published online)

Study looks at ‘anti-ageing’ in mice

‎19 ‎November ‎2010, ‏‎10:29:00 | NHS ChoicesGo to full article

“A pill that could add decades to the average lifespan moved a step closer yesterday,” reported the Daily Express. It said that scientists have found an anti-ageing enzyme that protects cells from decay.

This research looked at how a calorie-restricted diet and the action of a protein called Sirt3 affected the development of age-related hearing loss in mice. It found that mice that were capable of producing Sirt3 in response to having a calorie-restricted diet had slower development of age-related hearing loss than those unable to produce Sirt3.

This laboratory study gives us a new insight into how restricting calories may protect cells against some of the processes of ageing, through the role of Sirt3. However, it cannot tell us whether this process occurs or has the same effect in humans, nor does it give any indication of whether it is possible to develop an anti-ageing pill based on this knowledge.

Where did the story come from?

The study was carried out by researchers from the University of Wisconsin, University of Tokyo and University of Florida. It was funded by the US National Institutes of Health, National Projects on Protein Structural and Functional Analyses from the Ministry of Education, Culture, Sports, Science, and Technologies of Japan, and the Marine Bio Foundation. The study was published in the peer-reviewed scientific journal Cell.

The story was covered by the Daily Express and Daily Mail, both of which overstated the implications of the current findings. While the results of this study may one day contribute to medical therapies, it is too early to announce that an anti-ageing pill is on the way, and the claim that it could “add decades” to life is speculative.

What kind of research was this?

This was a laboratory study on mice with age-related hearing loss. It is thought that a process called oxidative stress causes damage to the cochlear cells in the inner ear, which can lead to age-related hearing loss. Oxidative stress is a process in which substances called free radicals cause damage to cells. This is thought to contribute to ageing. Previous research in animals has suggested that calorific restriction (a reduction of food consumption by 25–60%) can protect cochlear cells from this damage, but it is not fully understood how. Here, the researchers used mice to explore how this protective mechanism might work.

The researchers looked at the role of a group of proteins called sirtuins, known to be involved in the regulation of cell specialisation in mammals. They specifically focussed on Sirt3. Pervious studies have found that levels of Sirt3 increased in response to calorific restriction, in processes that suggest it has a role in delaying the effect of oxidative stress on ageing.

Extreme calorific restriction has been associated with increased lifespan in animal studies, but few studies have been able to explore this relationship properly in humans. It is not known if equivalent extreme calorie reduction in humans would have a similar effect, and how beneficial such an effect would be. This study did not investigate the effects of calorific restriction on human health or lifespan.

What did the research involve?

The researchers fed mice a diet that contained only 75% of their usual calorific intake. Some of these mice were able to produce Sirt3, while others lacked the gene that enables Sirt3 to be made. The researchers then examined the development of age-related hearing loss in both sets of mice after 12 months of calorific restriction.

They then looked at oxidative damage to DNA in a variety of cell types from the normal and Sirt3-deficient mice. Further experiments were carried out in different cell types from both sets of mice to examine the biochemical processes by which Sirt3 might reduce levels of oxidative stress and the damage this may cause to cells.

What were the basic results?

The researchers found that calorific restriction slowed the progression of age-related hearing loss in mice, but only in the mice that were naturally able to produce Sirt3. Mice that were Sirt3-deficient had typical rates of hearing loss. Similarly, the protection against DNA damage caused by oxidative stress was detected in the mice with normal Sirt3 production on a calorie-restricted diet, but was not seen in the Sirt3-deficient mice on the same diet.

The researchers found that calorific restriction triggered Sirt3 to activate a biochemical process that decreased the levels of oxidative stress and gave some protection to inner-ear cells. In turn, this reduced the risk of age-related hearing loss in those mice. They said that Sirt3 appears to have an important role in helping calorific restriction protect against the effects of ageing processes.

How did the researchers interpret the results?

The researchers propose that the biochemical mechanism they observed “may be a major mechanism of ageing retardation” due to the effects of calorific restriction. They propose that artificial stimulation of Sirt3 activity using pharmaceutical therapies may have a similar protective effect against the damage caused to cells by ageing processes.

Conclusion

This interesting laboratory study gives us a new insight into how calorific restriction may protect cells against some processes of ageing through the role of Sirt3. However, it cannot reveal whether this process occurs or has the same effect in humans, nor does it give any indication of whether it is possible to develop an anti-ageing pill based on this knowledge. Much further research is needed before this would be possible.

Links To The Headlines

Pill to arrest ageing on way. Daily Express, November 19 2010

Links To Science

Someya S, Yu W, Hallows WC, et al. Sirt3 Mediates Reduction of Oxidative Damage and Prevention of Age-Related Hearing Loss under Caloric Restriction (PDF, 1.17Mb). Cell 2010

‘Kidney zapping’ eases high blood pressure

‎18 ‎November ‎2010, ‏‎16:41:00 | NHS ChoicesGo to full article

“Simple surgery offers hope to millions with high blood pressure,” The Independent has reported. The newspaper said that a small trial of a new surgical procedure has shown success in reducing high blood pressure.

Currently, around half of people who are treated for high blood pressure do not respond to their recommended drug treatment. This study explored a new approach to reducing blood pressure through using radio waves to deactivate nerves in the kidneys, which is thought to increase blood flow to the kidney and reduce the activity of the hormone renin, itself linked to raised blood pressure.

In the randomised trial, 52 people received the procedure and 54 people carried on with the normal drug treatment alone. The researchers found that patients who had the surgical treatment showed a much greater reduction in blood pressure over a six-month period than the patients who did not. No serious side effects were detected during the six-month follow-up.

This study has demonstrated a promising new avenue for the treatment of high blood pressure in people who do not respond to conventional treatment. Further trials are needed to monitor the long-term safety and effectiveness in larger numbers of people. Reducing high blood pressure is important in lowering the risk of a number of diseases.

Read our guide to making lifestyle changes that can help you reduce your blood pressure.

Where did the story come from?

The study was carried out at a number of hospitals in Australia, New Zealand and Europe and was funded by Ardian, the US company that manufactures the surgical device used in the study. The study’s researchers are from a number of other medical institutions, including Ardian, the Baker IDI Heart and Diabetes Institute and The Alfred Hospital in Melbourne, Australia. It was published in the peer-reviewed medical journal The Lancet.

In general, the study was accurately reported in a number of newspapers. The description by one paper of the process involving ‘electrical energy’ was slightly inaccurate, as the technique actually uses radio waves, which are part of the electromagnetic spectrum.

What kind of research was this?

This was a small randomised controlled trial looking at an alternative strategy for blood pressure reduction through a process called ‘sympathetic denervation’ of the kidneys. This new technique uses a catheter passed into the blood vessels that supply blood to the kidneys. Bursts of radio-frequency energy are applied to reduce the nerve activity in the walls of the blood vessels. This in turn increases blood flow to the kidney and then a reduction in the activity of the hormone renin, itself linked to raised blood pressure, which is thought to be eventually responsible for the reduced blood pressure.

It is important that new techniques for tackling hypertension are developed, as the condition can have a variety of causes and is associated with an increased risk of a number of serious conditions, including stroke and cardiovascular disease.

Another problem with hypertension is that it can be hard to manage effectively. Although there are a number of drugs that can be used to lower blood pressure, around half of the people treated still have blood pressure higher than the recommended levels. This treatment failure may be due to a number of reasons, including forgetting to take medication regularly, and a biological variation that means some patients do not physically respond to the drugs.

In this research, patients who had agreed to participate were randomly allocated to receive either a surgical procedure and their regular medication or to carry on with their usual drug treatment alone. This is an appropriate way of testing whether or not a new medical procedure works.

Unlike trials of drugs, there was no placebo used here, which means that people knew whether or not they were receiving the treatment being studied. This knowledge can sometimes influence how people respond to a treatment, although the main effect being monitored (blood pressure) is an objective outcome and less likely to be influenced by a person’s knowledge of their allocation to either group.

What did the research involve?

The researchers recruited 106 patients aged between 18 and 85, who had been diagnosed with hypertension (systolic blood pressure of 160mmHg or more, or 150mmHg or more if they had type 2 diabetes). All the participants had been treated with three or more antihypertensive drugs without successful reduction of their blood pressure to target levels. Participants were randomly allocated to receive either the denervation surgery or to carry on with drug treatment. In both groups, patients continued whatever medication they were taking prior to the start of the study.

The patients who received the surgical procedure had a long narrow tube passed up to the kidneys through an artery in their leg. Low-power radio frequency signals were applied to the arteries that supply blood to the kidneys, deactivating the nerves around them.

All the patients had their blood pressure monitored before the study, after six months, and at a number of points in between. As well as repeated measurements undertaken by doctors, the patients were given blood pressure machines to take their own readings at home for two weeks before the study started, as well as three times in the morning and three times in the evening and again at the end of the six months. The researchers used averages of the home measurements at the start of the study and the six month visits for the analysis.

This careful and frequent home measurement helped researchers to check the consistency of their measurements, as sometimes blood pressure can be raised by the experience of having it monitored or treated in a clinical setting.

What were the basic results?

The patients in the surgery group had an average blood pressure reading of 178/96mmHg. Six months after the procedure, their blood pressure had lowered by 32/12mmHg on average. The average reduction in the people who did not have the surgery was 1/0mmHg from a starting average of 178/98mmHg. The difference in blood pressure reduction between the two groups was statistically significant (p<0.0001).

A proportion of people experienced no decrease in systolic blood pressure after six months – 10% of people in the surgery group and 47% of the control group. The target of a systolic blood pressure of less than 140mmHg was achieved by 39% of the people who had the surgery, and 6% of those who did not.

These findings were based on the measurements taken by the researchers when people visited the clinics. Similar effects were seen when they looked at the measurements people had taken themselves at home – 32 patients from the surgery group had an average reduction of 20/12mmHg, while 40 people from the control group showed an average increase of 2/0mmHg.

The researchers did not report any serious side effects of the treatment.

How did the researchers interpret the results?

The researchers say that ‘a significant reduction in blood pressure can be achieved with catheter-based renal denervation’ in patients who had not been successfully treated using conventional drug treatments.

Regarding kidney function, they say ‘there was no evidence of worsening function, suggesting this procedure is safe even in those with mild-to-moderately impaired renal function’.

Conclusion

This study demonstrated that using a simple surgical procedure was effective at lowering the blood pressure of people whose hypertension had not been managed successfully with standard drug treatments. There are, however, some limitations to the study and its findings:

  • This study was quite small, and although it detected a significant difference in blood pressure reduction in the treatment and control groups, such a treatment would not become part of routine clinical practice until larger trials are carried out to further assess safety and effectiveness.
  • Participants were followed up for six months after the procedure. Future trials following people for longer periods are important to verify that the effects of the treatment are long lasting. They could check, for example, that the nerves do not regrow and to see whether the treatment makes any difference to the risk of other conditions associated with hypertension, such as stroke.
  • Although the number of people achieving the target systolic blood pressure of less than 140mmHg was greater in the group who received surgery than in those who did not, 61% of the people who had surgery had still not reached this target six months after the procedure.
  • The researchers did not find any significant harmful effects of the procedure, but longer studies may be needed to verify whether any serious adverse events develop over time.
  • The people involved in the study knew what treatment they were receiving. Sometimes knowledge of whether or not a treatment has been received can influence participants’ behaviour. For example, the people who knew they were treated might be more motivated to stick to lifestyle choices that reduce blood pressure, or be more accurate when measuring their blood pressure at home. A ‘blinded’ study (such as when the control patients receive ‘sham surgery’) would reduce this problem.
  • Those in the surgery group still continued to use their regular medication. Therefore, the study cannot tell us whether or not people receiving the treatment could cease taking their daily medication.

Overall, this research shows a promising new avenue for treatment of hypertension that has not responded well to conventional management with drugs. Larger, long-term trials will help to explore whether the effects of the surgery are long lasting, and whether it helps to reduce the risk of other conditions associated with hypertension.

Links To The Headlines

Operation to ‘cure’ high blood pressure could benefit thousands. The Daily Telegraph, November 18 2010

Simple surgery offers hope to millions with high blood pressure. The Independent, November 18 2010

How a burst of electrical energy can help beat high blood pressure. Daily Mail, November 18 2010

Kidney zap lowers blood pressure. BBC News, November 18 2010

Links To Science

Symplicity HTN-2 Investigators: Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. The Lancet, Early Online Publication, November 17 2010

Show all items

Displaying

13 / 13

All

13

New

13

Sort by:

List Order

Date

Title

Author

Filter by category:

Cancer

1

Diabetes

2

Food/diet

5

Heart/lungs

3

Lifestyle/exercise

2

Medical practice

3

Medication

2

Neurology

2

Older people

3

QA articles

1

CheckedMark feed as read

View feed properties…

Health News from NHS Choices

Posted in Uncategorized | Leave a comment

Hello world!

Welcome to WordPress.com. This is your first post. Edit or delete it and start blogging!

Posted in Uncategorized | 1 Comment