In a ‘provocative’ commentary article, several scientists have called for sugar to be regulated as a harmful substance like alcohol and tobacco, prompting debate over individual liberty and the western diet.

In the article, published in the leading science journal Nature,  international scientists argue that added sweeteners pose dangers to health that justify controlling them like alcohol.

Highlighting the myriad of negative health impacts – and subsequent healthcare costs- caused by added sweeteners such as high-fructose corn syrup, the authors call for government intervention to reduce the level of sugar added to foods.

“Ultimately, food producers and distributors must reduce the amount of sugar added to foods. But sugar is cheap, sugar tastes good and sugar sells, so companies have little incentive to change”, the article states.

The authors suggest that the US Food and Drug Administration should no longer list sugar as ‘generally regarded as safe’ (meaning manufacturers can add as much as they want to foodstuffs) and that authorities should tax or place other limitations on high sugar foods.

Our colleagues at the Australian Science Media Centre contacted experts for further comment and context on the arguments put forward in the Nature article:

Prof Leonie Segal is Foundation Chair of the Health Economics & Social Policy Group at the University of SA, with an international profile in the economics of nutrition. She was a member of the Ministers Preventative Health Taskforce

“A focus on added sugar is most timely, with increasing evidence of its negative health effects.
“The public health arguments for intervening are indeed strong, with perhaps the most important consideration, not highlighted by the authors, the imperative of governments to protect vulnerable members of society, especially where the capacity for well-informed decision making is limited or non-existent.

“Because eating habits and taste tend to be influenced by what we eat as infants and young children, an unhealthy habituation or addiction to sugar, which influences lifetime health, can be established from a very young age when the ability and capacity to make informed eating choices are simply unavailable. This provides a strong case for governments to intervene to encourage healthy food choices, by children and thus families. And as the authors argue excess sugar is a crucial aspect of current poor food choices and thus an important focus of such policies.

“While at its extreme alcohol may have more damaging effects than sugar, excessive consumption of sugar is considerably more prevalent than excessive alcohol consumption, part of the reason why population level strategies make sense.”

Prof Peter Clifton is Head of Nutritional Interventions at Baker IDI Heart and Diabetes Institute

“Alcohol toxicity is not just metabolic – it causes violence and road deaths and sugar in any of its forms cannot compete with this statistic. Almost all of the evidence against sugar is epidemiological – that is association not necessarily causation.

“In intervention studies with fructose, up to 10% of calories show no metabolic effects while a few studies with fructose at 25% of energy do show a modest increase in triglycerides but not high enough to cause pancreatitis.

“There are no controlled interventions that show feeding fructose or sucrose causes hypertension and none that show that a controlled reduction in sugar alone reduces blood pressure. However, there is evidence to show that increasing sugar-sweetened beverage intake does cause modest weight gain as the liquid calories are not compensated by a reduction in calories from other foods.

“Sugar is just another form of over-consumed calories – easily available and very palatable but no more metabolically deadly than starch or fat calories and certainly not equivalent to alcohol.”

Dr Alan Barclay is an accredited practicing dietitian and nutritionist, Chief Scientific Officer for the Glycemic Index Foundation Ltd and head of research at the Australian Diabetes Foundation

“This commentary is a provocative piece intended to encourage debate. Many of the statements simply do not apply to Australia and on certain issues there is little evidence to support their views. ‘Sugar’ is not the issue, it is far more complicated than that.

“The authors state that over the past 50 years, consumption of sugar has tripled worldwide. However, in Australia sugar consumption has dropped 23% since 1980. Despite this, during that time cases of overweight or obese people have doubled, whilst diabetes has at least tripled.

“The authors believe that attention should be turned to ‘added sugar’, which they have defined as any sweetener containing the molecule fructose that is added to food in processing. The authors suggest that fructose can trigger processes that lead to chronic diseases including liver toxicity, however one would need to eat at least 135g, or about 32 teaspoons, of pure added fructose per day on top of what one already eats. Only one per cent of Americans eat more than 100g per day of total fructose. The only disease proven to be related to excess frequent sugar consumption is tooth decay – a significant problem – but even then, refined starch is at least equally as cariogenic but is rarely acknowledged as a problem.

“Lustig and his colleagues claim that sugar should be regulated like alcohol because it is unavoidable, toxic, has potential for abuse and has a negative impact on society. However, it is certainly not unavoidable, it is only ‘toxic’ in unrealistic amounts and to suggest that consuming sugar is a form of abuse is one of the worst cases of puritanism that I have seen in a while. It’s worth noting that soft drinks and other non-core ‘party’ foods are already taxed (GST) in Australia.

“Just like anything else, sugar should only be eaten in moderation. As we continue our research we are finding out more and more about the importance of refined starch and specific fatty acids and the average Australian can do a lot to improve their diet, but casting sugar as the ultimate villain and calling for regulation is misleading, unfounded and unnecessary.”

Article: The toxic truth about sugar, A Comment piece, Lustig et al., Nature, 2012 (482), pp27-29

As New Zealand policy-makers examine ways to help consumers make healthy food choices, a new Otago study has shown that keeping it simple works best.  

Traffic Light Label

Researchers at Otago University have shown that a front-of-pack ‘Traffic Light system’ (see image) using a red-yellow-green colour code  for high, medium and low salt content helps consumers make healthy choices.

The full study, published in the journal Public Health Nutrition, is available to registered journalists in our Resource Library.

Last year the traffic light labelling system was recommended to a trans-Tasman food regulation forum by an expert review panel. The forum agreed that a standardised, easy-to-undertand front-of-pack nutrition label should be introduced – and now aims to have one in place by the end of the year. See more below.

It is estimated that consumers typically spend between four and ten seconds choosing a product in a supermarket.

The SMC contacted New Zealand experts for further comment on the research. Feel free to use these quotes in your reporting.  To talk to one of these experts, please contact the SMC (04 4995476; smc@sciencemediacentre.co.nz).

Dr Racheal McLean, a Research Fellow at the Edgar National Centre for Diabetes research, University of Otago, explained the study to the Science Media Centre:

“Reducing dietary salt intake is an important way to reduce blood pressure and risk of heart disease and stroke, especially if it is done across the whole population.  New Zealanders, on average, consume more salt than is recommended by dietary guidelines, as do people in most countries around the world.  In a western style diet, around three quarters of salt consumed is already in processed foods, with only around 10% added at home- in cooking or at the table.

“Ensuring that consumers are able to identify the amount of salt in processed food is vital if people are going to regulate their own intake.  Food labelling is an important tool, as many products that are high in salt do not necessarily taste salty.

Percentage Daily Intake

“Our research tested New Zealand consumers’ ability to use a range of currently available food labelling formats to discriminate between products when grocery shopping.  We used a large national online panel to simulate in-store behaviour.  We tested the Nutrition Information Panel (mandatory in New Zealand since 2002), two front of pack labels: the Percentage Daily Intake label used voluntarily by several food manufacturers in New Zealand, and the Traffic Light Label which has been in use as a voluntary system in the United Kingdom for a number of years.  We also tested the ‘low salt’ and ‘reduced salt’ nutrition claims currently in use in New Zealand in combination with the various labels.

Nutrition Information Panel

“The results showed that both front-of-pack labels (percentage daily intake and traffic light labels) enabled people to better identify products with high and low salt content, however the traffic light label enabled them to do this more effectively.  In particular, the traffic light label enabled people to identify the high-salt product more easily. The traffic light label also performed better than the percent daily intake label in enabling people to identify high and low salt products when they were faced with products labeled with a  ‘reduced salt’ nutrition claim.

“We believe that the simple colour coded message of the traffic light makes them easier to understand than the more detailed information in the other labels tested.

“These findings are consistent with international research that shows that people find simple colour coded food labels such as the traffic light allow them to easily identify more healthy foods across a range of nutrients.  Traffic light labels, if widely implemented, could be a useful tool to improve nutrition in New Zealand.

Prof Elaine Rush, Professor of Nutrition, AUT, commented:

“This report provides evidence that a front-of-pack traffic light labeling system is more effective than other labelling systems in allowing normo – and hypertensive consumers to discriminate between high and low sodium foods, even in the presence of misleading nutrition claims on the label. Those with known (self-reported) hypertension were more likely to have been advised to reduce the salt in their diet, read nutrition labels and choose a product with front of pack traffic light labelling that identified the product as low sodium.

“This evidence adds to the understanding of the effectiveness of clear front of pack labelling and supports its use.  The simplicity of three colours (red, amber, green) and four nutrients (fat, saturates, sugar and salt) is attractive but has a number of detractors.

“It is nutrient-based and does not give a rating to the whole food. The nutrients profiled are considered “bad” – what about the good ones – like fibre, protein and fruit and vegetable content – they should be shown too.  (Water would be a perfect food based on this system– low in salt, sugar and fat – but where are vitamins and minerals and macronutrients?) It is not black and white,

“People eat foods not nutrients.  Foods make up meals. Dietary advice should be in context. Once a condition is diagnosed and linked with a nutrient e.g. high blood pressure with salt, diabetes with sugar, obesity with fat, heart disease with saturates, then the importance o the overall nutritional quality of the diet and foods eaten may be lost.

“In New Zealand we have food based dietary guidelines for different ages and stages which guide the choice of foods – not nutrients.

“Front of pack labelling such as:

• Watties with the number of vegetable serves in a can,
• Sanitarium with their healthy eating system with gives dietary advice such as eat often, eat occasionally and eat sparingly, and
• Ministry of Health (school) food-based classification system of everyday, sometimes and occasional foods

should also be considered

“Another consideration for many New Zealand people and families is cost.

“There is a need for better communication with consumers about the quality of foods – front of pack labelling is one important step as is robust evidence that the communication is effective.”

A green light for front-of-pack labelling?

A recent government-commissioned review of food labelling in New Zealand and Australia, Labelling Logic, found that “existing labelling requirements do not appear to have been adequate to encourage reformulations in line with healthy eating principles.”

The review supported front-of-pack nutritional labelling which provides a simple way to understand nutrition content, so that children and adults with low literacy and numeracy skills can make informed, healthy choices easily.

Specifically, the review recommended a traffic-light style system stating: “the colour-coded multiple traffic lights system has been consistently found to be most effective in facilitating consumers’ understanding of the nutrient profiles of foods within and across food categories”.

Although they stopped short of recommending mandatory traffic light labels for all food products, the review panel did suggest that such a label be required for all foods making nutritional claims such as, ‘low in salt’.

A trans-Tasman policy forum responding to the report agreed to the need for an easily understood, interpretive front-of-pack labelling system for packaged foods. In June the forum will provide a report on front-of pack-labelling, with the aim to implement a system by the end of 2012.

Prominent scientists — including a New Zealander who is one of the world’s leading virologists — have published commentaries on whether American biosecurity experts were correct to call for suppression of details of Dutch-based research that created a potentially lethal strain of birdflu (H5N1) potentially capable of killing 50 percent of the people it infects.

The commentaries in the journal mBio included one by New Zealander Professor Robert Webster, an influenza expert at St Jude’s Children’s Hospital in Memphis, Tennessee, and a consultant to both the World Health Organisation and the US National Institute of Allergy and Infectious Diseases. He said: “The question before the scientific community is how to preserve scientific openness while minimising risk to the public”.

Professor Webster’s laboratory tracks emerging new flu viruses and guides the development of flu vaccines to stop them. His work is vital to meeting the yearly challenge of stemming the seasonal flu epidemics which circle the globe.

The journal, published by the American Society for Microbiology has also canvassed whether the biosecurity recommendations were necessary and what role biosecurity considerations should play in the dissemination of research findings.

The US National Science Advisory Board for Biosecurity (NSABB) is expected to today explain how it decided late last year to recommend “that two scientific papers describing research that created strains of bird flu potentially transmissible in humans should be published only if key details are omitted,” for fear “that terrorists or hostile nations could learn how to cause a pandemic.

A New York Times science editorial writer, Philip Boffey, has predicted the NSABB document is unlikely to settle the argument, as it fails to deal with the “even greater risk” should the virus escape or be stolen from the laboratory.

And Professor Vincent Racaniello of Columbia University, says in mBio that such redaction would undermine modern scientific publishing. Adapting viruses to living in lab animals is actually a common strategy for reducing their suitability and virulence to human hosts.

Professor Webster says that suppressing scientific knowledge was in the public interest in this instance, but that so-called dual-use research will continue to raise many questions about where to draw the line between freedom of information and public safety. He points to an urgent need for general guidance and indicates an international panel could consider approaches to promoting research while maintaining biosecurity.

Later in the week, the Emerging Infectious Diseases & Microbiology Discussion Group of the New York Academy of Sciences will also canvas the key issues.

Log into the SMC Resource Library to access the editorial and commentaries.

The Science Media Centre is gathering comment from New Zealand experts on the issue.

Comments gathered earlier from Dr Siouxsie Wiles — Auckland University’s HRC Hercus Fellow at Molecular Medicine & Pathology — are available here.

Barry Scott FRSNZ, Professor of Molecular Genetics and Head of Molecular BioSciences at Massey University, comments:

“While there is considerable uncertainty around whether the results obtained in ferrets will translate to humans the scientists were concerned that if such transmissibility could occur in humans then the global risk to human health would be very difficult to manage. Racaniello dismisses the arguments as “a severe case of scientific hubris”.

“He does raise some good points about how unlikely such an event might be to occur. Despite these criticisms the NSABB in weighing up the risks associated with the alternative usage of this scientific information decided to take a cautionary approach and restrict access to key scientific information, in particular the amino acid sequence changes that enhance transmissibility.

“As Webster, an ex pat, notes, the decision is reminiscent of the 1975 self imposed decision by the scientific community to put a moratorium on the use of recombinant DNA technology until working guidelines and practices were established to manage the risks. But in this case there is not universal acceptance of the approach been taken. Both Klein and Webster point out that the globe is ill prepared for an outbreak of a highly transmissible strain of H5N1 and therefore advocated this precautionary approach. This seems to be a wise decision at this point in time.

“Even without the key methodology the publications by the Fouchier and Kawaoka groups will be of considerable interest to the scientific community and bring greater awareness to the scientific community of dual-purpose research. It is very important at this juncture that public safety is not compromised by expediency in revealing all the information. The decision appears to be a wise one.”

Professor Scott’s comments are available in full here.

Prominent scientists — including a New Zealander who is one of the world’s leading virologists — have published commentaries on whether American biosecurity experts were correct to call for suppression of details of Dutch-based research that created a potentially lethal strain of birdflu (H5N1) potentially capable of killing 50 percent of the people it infects.

Barry Scott

The Science Media Centre gathered the following commentary on the issue from Barry Scott FRSNZ, Professor of Molecular Genetics and Head of Molecular BioSciences at Massey University

In a highly unusual move, and the first such recommendation of its kind, the National Science Advisory Board for Biosecurity (NSABB) has recommended to the US government that some of the experimental details be redacted from two papers about to be published on the transmissibility of H5N1 flu virus in ferrets.

This is a very controversial decision that has sparked outrage by some in the scientific community (e.g. see Palese 2012) as full and complete disclosure of methodology in publications is a key tenet of the scientific publication process as it enables others to repeat the experiments and design new experiments to progress the work and provide support for or against the hypotheses proposed. While the recommendation by the NSABB committee is not binding the journals involved in publishing this work have decided to abide by the recommendations of this committee.

Commentaries on the this extraordinary decision by the NSABB to redact scientific information is discussed in three commentaries published in mBio today; two in support of the decision (Klein 2012; Webster, 2012) and one against (Racaniello 2012).

These commentaries will help promote healthy and open debate on this very controversial issue. Given the scientific standing of the scientists on the NSABB committee and their considerable expertise on transmissible human viruses and other biosecurity risks, Prof Scott says it is important to respect their decision.

While there is considerable uncertainty around whether the results obtained in ferrets will translate to humans the scientists were concerned that if such transmissibility could occur in humans then the global risk to human health would be very difficult to manage.

Racaniello dismisses the arguments as “a severe case of scientific hubris”. He does raise some good points about how unlikely such an event might be to occur. Despite these criticisms the NSABB in weighing up the risks associated with the alternative usage of this scientific information decided to take a cautionary approach and restrict access to key scientific information, in particular the amino acid sequence changes that enhance transmissibility.

As Webster, an ex pat, notes, the decision is reminiscent of the 1975 self imposed decision by the scientific community to put a moratorium on the use of recombinant DNA technology until working guidelines and practices were established to manage the risks.

But in this case there is not universal acceptance of the approach been taken. Both Klein and Webster point out that the globe is ill prepared for an outbreak of a highly transmissible strain of H5N1 and therefore advocated this precautionary approach. This seems to be a wise decision at this point in time.

Even without the key methodology the publications by the Fouchier and Kawaoka groups will be of considerable interest to the scientific community and bring greater awareness to the scientific community of dual-purpose research. It is very important at this juncture that public safety is not compromised by expediency in revealing all the information. The decision appears to be a wise one.

Klein PS (2012). The NSABB recommendations: rationale, impact and implications. mBio 3: e00021-12

Palese P (2012). Don’t censor life-saving science. Nature 481: 115

Racaniello VR (2012). Science should be in the public domain. mBio 3: e00004-12

Webster RG (2012) Mammalian-transmissible H5N1 influenza: the dilemma of dual-use research. mBio 3: e00005-12

The odds of a major depressive episode are more than double for those working 11 or more hours a day compared to those working seven to eight hours a day, according to a new study.

Researchers followed about 2000 middle aged British civil servants (as part of the ‘Whitehall II Study‘) and found a robust association between overtime work and depression. This correlation was not affected when the analysis was adjusted for various possible confounders, including socio-demographics, lifestyle, and work-related factors.

The study, published in the journal PLoS ONE today, found that people working more than 11 hours a day were 2.43 times more likely to have a major depressive episode than those who work 7-8 hours a day.

Although the study was not designed to determine exactly how overtime increased depression risk, the authors noted that:

“Long working hours may in part affect mental health through factors not measured in our study, such as work-family conflicts, difficulties in unwinding after work or prolonged increased cortisol [a stress hormone] levels.”

The authors also called for more research to evaluate the effectiveness of limiting work hours, stating:

“Service and intervention studies are needed to examine whether interventions designed to reduce working hours would alter depression risk in working populations.”

New Zealand statistics

The most recent New Zealand Census figures from 2006 for 1.83m workers showed 415,641  working 50 or more hours each week, (22.68 per cent of the workforce and 29.08 percent of full-time workers). Among full-time workers 36 percent of men work 50 or more hours a week, and 19 per cent of women.

Those with the highest qualifications, such as masters’ and doctorate degrees, are significantly more likely to work long hours, but the largest group of long hours workers are those who have no qualifications.

The Science Media Centre gathered the following comments on the research from New Zealand experts.

Feel free to use these comments in your reporting. To speak to an expert, please contact the Science Media Centre (04 499 5476; smc@sceincemediacentre.co.nz).

Helena D Cooper-Thomas, Senior Lecturer, Psychology Department, The University of Auckland comments:

“The Whitehall studies have contributed significantly to our understanding of workplace health issues. The main result of this research is the finding that working long hours – in this study more than 11 hours per day – increases the risk of becoming severely depressed. This links well with research from Europe showing the importance of recovery activities in the evening after work.

“Employees who feel that they have used their leisure time to relax, recover, and experience a positive mood show more engagement and initiative at work the next day. This is also important for employers to take note of also – workers who have had more chance to recover are more engaged and proactive the next day.

“A second result that I also find interesting is that it is mid-level employees who are at higher risk of depression as compared to both more senior and the most junior employees. Workers in the middle ranks don’t have the same level of autonomy as those in the more senior roles, yet have considerable responsibility. Perhaps these workers are in the most precarious positions, balanced between potentially competing demands, and therefore experience more strain and consequently higher levels of depression.

“In New Zealand there is an emphasis on using leisure time well, and this suggests that workers in New Zealand should use their after-work hours to achieve relaxation and enjoyment. For anyone reading this who does not use their leisure time well, you should reflect on this further. A related issue is that, during work hours, we should use our time well and work efficiently to keep our leisure time free. Some organizations have macho long hours cultures, where being seen to work long hours is a sign of commitment to the organization or to one’s career.

“However research shows that working long hours is associated with poorer mental health, and that workers who use their leisure time to recover are more enthusiastic and proactive. Surely, then, both employers and employees should be aiming to work hard AND play hard.”

Dr Rebbecca Lilley, Research Fellow & Lecturer, Department of Preventive and Social Medicine, University of Otago, comments:

“The Whitehall II Study is a world renowned study of Public Sector workers that has contributed greatly to improving our understanding of work stress and it’s subsequent impact upon worker health, including the health conditions of cardiovascular disease and mental health.

“Examining overtime working hours as a form of a over-demanding work schedule is appropriate as there is little clear understanding of how over-demanding work schedules impact upon worker health.  The paper highlights how depression is a significant and rapidly growing public health concern internationally.  Increasingly we are understanding that work contributes significantly to the development of depression in workers.

“Little is known about the prevalence of depression in the New Zealand workforce.  A recently published study by myself and colleagues in New Zealand cleaners and clerical workers surveyed in May 2004-April 2005 found 11% of workers reported they were currently suffering from psychological distress and that job pressure was a risk factor for reporting psychological distress in this mainly female working population.

“The Whitehall II Study demonstrates with increasing overtime, over and above a standard working day of 7 hours per day, the risk of having a Major Depressive Episode increases, demonstrating a dose-response effect.  So the longer the overtime hours the greater the likelihood a person will develop a Major Depressive Episode.

“The authors carefully outline a long list of limitations to this study that need further investigation before plausible explanations of why long overtime work hours are associated with depression can be drawn.  One further limitation to this study is that while this group adjust their findings for potential socio-demographic, workplace, lifestyle and health explanatory factors there are some potential factors that have not been considered.   

“One such group of factors not examined by this group represent the lost opportunities by overtime workers to get sleep or to undertake physical activity.  As a person spends longer each day at work the opportunities to do these activities is reduced.  Both sleep quality and physical activity are risk factors for developing depression and could provide an alternate explanation for these findings.

“So, while this is an interesting analysis suggesting that working overtime is a risk factor for developing a Major Depressive Episode in Public Sector workers in the UK more research is required to fully understand the implications of the findings of this study for workers in general.  This paper will be important in stimulating further research in over-demanding work schedules and depression in working populations.”

Further commentary from the UK Science Media Centre:

Clare Bambra, Professor of Public Health Policy, Durham University, said:

“The link between working long hours and depression is very important. The UK has the longest working hours in Europe and many people are encouraged to work in excess of the EU working time directive – the 48-hour week.

“The economic crisis is likely to increase the pressure on those in-work to work longer hours. There is a strong public health need for employers and the government to consider limiting working hours and giving employees more control over their working hours.

“A recent Cochrane review led by Durham University researchers found that having more control over working hours improved physical and mental health.”

Dr Paul Keedwell, Honorary Consultant Psychiatrist, Cardiff University, said:

“This study confirms what we have long suspected – that we cannot expect to work long hours in stressful white-collar jobs without psychological ill effects. High socio-economic status does not protect you. More work is urgently required to examine if this link between overtime and depression is due to personality, job-specific strain, work-family conflict, neglecting important relationships, or all of the above.”

Professor Anthony Cleare, Professor of Affective Disorders, King’s College London Institute of Psychiatry, said:

“This important study reminds us that working conditions can markedly affect an individual’s mental health.  However, whilst there is a link between excessive hours and depression, it is important to be clear that many individuals do thrive on working longer hours and there should not be a blanket prohibition.

“Instead, we need to see long working hours as a potential risk factor in some people, and to understand more about which individuals are at particular risk.  One suggestion from this and other studies is that people lower down the working hierarchy, and who have less control over their jobs, may be especially at risk of depression.

“We should also not forget in these troubled times that being unemployed is probably even more detrimental to a person’s mental health.”

A new study has shown that men are more likely than women to develop a mild form of mental impairment known to be a risk factor for dementia.

Researchers involved in the Mayo Clinic Study of Aging reported today in the journal Neurology that more than 6 percent of Americans age 70 to 89 develop mild cognitive impairment (MCI) every year. Also, the condition appears to affect men and those who only have a high school education more than women and those who have completed some higher education.

In the video at right, Dr. Rosebud Roberts, Mayo Clinic neurologist and epidemiologist, discusses the findings of the research.

People with MCI are at the stage between suffering the normal forgetfulness associated with aging and developing dementia, such as that caused by Alzheimer’s disease.

People with MCI have mild problems with thinking and memory that do not interfere with everyday activities, although their forgetfulness is often apparent to them and their friends and family. While not everyone with MCI develops dementia, an estimated 5 to 10 percent do.

Symptoms of MCI include:

• Difficulty learning and remembering new information
• Difficulty solving problems or making decisions
• Forgetting recent events or conversations
• Taking longer to perform complex or difficult mental activities.

Our Colleagues at the UK Science Media Centre collected the following commentary:

Derek Hill, Professor of Medical Imaging Science, University College London, said:

“More women get dementia than men. Yet this new research shows that more men than women develop a complaint called Mild Cognitive Impairment (MCI),  frequently an early warning sign of dementia. Perhaps these gender differences, if better understood, could provide a clue to new ways of preventing dementia.

“By the time people get clinical dementia, it may well be too late to treat them.   People with “Mild Cognitive Impairment” or MCI are known to be at high risk of developing dementia. This study shows that MCI is a very complicated mix of factors, and that different types of MCI arise and progress quite differently. This information could be important in improving diagnosis to identify patients who will benefit from current or future treatments.”

Dr Anne Corbett, Research Manager, Alzheimer’s Society, said:

“Increasing our understanding of mild cognitive impairment (MCI) could help us unravel the many mysteries still surrounding Alzheimer’s disease and move us closer to treatments and a cure. This exciting research adds to previous evidence that men could be more susceptible to MCI than women. However we now need further research into why this is the case.

“One in three people over 65 will die with dementia and by 2021 there will be over a million people in the UK with the condition. Yet dementia research remains drastically underfunded. Only through more research can we find out more about MCI and its relationship with Alzheimer’s disease. We must invest now.”

Further information from the Alzheimer’s Society:

Mild cognitive impairment (MCI) may affect more men than women, research published in the journal Neurology claims today (Wednesday 25 January 2012). 1,450 people who had no signs of cognitive impairment were revaluated 15 months later. Men were 26% more likely to develop MCI than women, and 32% more likely to develop MCI with memory problems. The study also found that people with a low level of education (12 years in education or fewer) had a higher rate of MCI. MCI includes problems with memory or thinking beyond that explained by the normal rate of ageing and often leads to Alzheimer’s disease.

* ‘The incidence of MCI differs by subtype and is higher in men’ by Roberts et al. is published in Neurology.

New research shows that perfluorinated compounds (PFCs), widely used in manufactured products such as non-stick cookware, waterproof clothing, and fast-food packaging, are associated with lowered immune response to vaccinations in children.

Danish and American researchers analysed data from 587 children tested for immune response to tetanus and diphtheria vaccinations at ages 5 and 7 years. PFCs were measured in maternal pregnancy serum and in the serum of children at age 5 to determine prenatal and postnatal exposure.

The results of the study, published today in the Journal of the American Medical Association (JAMA), showed that PFC exposure was associated with lower antibody responses to immunisations and an increased risk of antibody levels in children lower than those needed to provide long-term protection. (Antibody concentrations in serum are a good indicator of overall immune functions in children.) A two-fold greater concentration of three major PFCs was associated with a 49% lower level of serum antibodies in children at age 7 years.

“Routine childhood immunizations are a mainstay of modern disease prevention. The negative impact on childhood vaccinations from PFCs should be viewed as a potential threat to public health,” said study lead author Philippe Grandjean, adjunct professor of environmental health at Harvard School of Public Health.

PFCs have thousands of industrial and manufacturing uses. Most Americans have the chemical compounds in their bodies. Prior studies have shown that PFC concentrations in mice similar to those found in people suppressed immune response, but the adverse effects on people had been poorly documented.

The UK Science Media Centre collected the following expert commentary:

Prof Alastair Hay, Professor of Environmental Toxicology at the University of Leeds, said:

“The work was well conducted. It suggests that perfluorocarbons (PFCs, chemicals comprised of carbon and fluorine) concentrations have an adverse effect on antibody levels for tetanus and diphtheria toxins, two antibodies chosen for investigation. A single birth cohort was followed and PFCs were measured in the mothers before birth and in the children when they were 5 and 7 years of age and before and after antibody booster vaccination.

“Twofold increases in PFC concentrations were associated with significant falls in antibody levels. In other words children with higher PFC concentrations had lower antibody levels. The study authors were careful to assess whether the type of vaccine, be it combination or single, played any role in their observations and this was taken account of in the analysis by the team.

“So what does this mean? Firstly, it must be an alert for all health and environment authorities. The chemicals, although present in low amounts in our bodies, have very long residence times before they are excreted.

“Grandjean and his co-authors say that the effect they observed occurs at PFC levels which also affect immune function in animals. This is even more concerning because it indicates that the effect occurs across species and at levels of the chemicals which are present in our blood. How the chemicals operate on the immune system is not understood.

“Grandjean and his team’s work will have to be replicated in other human studies. In parallel, work should be done to investigate possible mechanisms by which the PFCs may affect cells in the immune system. We also need to know if there is safe exposure to these chemicals and what it might be. Does the effect change as we get older and well past the stage when there are booster vaccinations?

“The implication of this work is that everyday exposure to these chemicals makes us more vulnerable to infections. We cannot afford to ignore the research, but equally we should not panic. What we need is a measured response to test the findings in a robust way and assess their implications for our health and particularly that of our children.”

Prof Anthony Dayan, independent toxicologist, said:

“Exposure of mothers and children is proven as an analytical methodology so this looks OK. But the association between PFC levels in maternal serum taken late pre-birth, and antibody levels to two standard antigens taken in children aged 5 and after a ‘booster’ using a different vaccine (they admit this complicates interpretation), is not strong.”

“The statement that the antibody levels were below the level accepted for adequate immunity is not properly referenced. The measured level related to immunity (following immunisation or boosting) falls, and the level taken as ‘protective’ must be justified.

“More to the point there is ample information that polyunsaturated fatty acids (PUFAs) are found in marine organisms and they suppress many immune responses. This paper uses neither a control nor even any mention of that well proven fact. So, as eating is claimed to be the source of PFCs and it is the source of the immunosuppressive PUFAs, the study proves nothing.”

The human first trial to use embryonic stem cells for the treatment of macular degeneration has published its results,representing a milestone in the use of the controversial therapy.

An new trial published in the leading medical journal The Lancet, reports on the the use of human embryonic stem cells to treat macular degeneration in two patients. It is the first report of the use of such cells in humans for any purpose.

The study involved one elderly patient and one young patient with different forms of macular degeneration that had led to severe vision loss. The transplants appeared safe after four months, and both patients had some improvement in vision.

In an associated press release lead author Dr Robert Lanza said:

“It has been over a decade since the discovery of human embryonic stem cells. This is the first report of hESC (human embryonic stem cell) -derived cells ever transplanted into patients, and the safety and engraftment data to-date looks very encouraging. Although several new drugs are available for the treatment of the wet type of AMD, no proven treatments currently exist for either dry-AMD or Stargardt’s disease.

“Despite the progressive nature of these conditions, the vision of both patients appears to have improved after transplantation of the cells, even at the lowest dosage. This is particularly important, since the ultimate goal of this therapy will be to treat patients earlier in the course of the disease where more significant results might potentially be expected.”

There is an ongoing ethical debate surrounding whether or not embryonic stem cells should be used in treatments (on the basis that an embryo can be regarded as the earliest form of human life).

Our colleagues at the UK Science Media Centre collect the following expert comments.

Professor Daniel Brison, Co-Director of the North West Embryonic Stem Cell Centre, Manchester, said:

“This is a very exciting moment for embryonic stem cell therapies.  This is the first peer-reviewed scientific report showing that cells derived from human ES cells can be transplanted safely into a patient with no sign of complications.  Although the study is limited to safety considerations, very small in scope, and at a very early stage, this is nonetheless a ground breaking moment for embryonic stem cell therapies.  It is also very significant for the UK that the second trial of these therapies has now begun in London, only 4 months behind the US trial.  These trials have used human ES cells created at research grade and this was possible as they were transplanted into the eye which is a very localised site in the body.  In order to realise the full potential of ES cell therapies in the future, it will be very important to use the new generation of clinical grade ES cells now being produced in the UK.”

Professor Chris Mason, Chair of Regenerative Medicine Bioprocessing, University College London, said:

“The preliminary data on the two US patients treated using human embryonic stem cell-based therapies in June 2011 is highly encouraging, but is only the start of gathering the necessary safety data before it is possible to test if the therapy will have an impact on patients’ vision. Overall the process of testing for safety and efficacy is likely to take a minimum of 5-10 years before the potential therapy could enter routine clinical practice.

“It is not surprising that the first European human embryonic stem cell-based therapy was carried out in London, given that the UK is a world leader in cell therapy.

“The safety of embryonic stem cell-based therapies in patients is now slowly starting to emerge with both Geron data for spinal cord injury and now ACT for retinal disease. It is still a long way to go before we will have the answer as to whether embryonic stem cell-based therapies will be safe and efficacious, but progress continues to be made towards striving for the ultimate goal of life-changing therapies for patients and their carers.”

Dr Dusko Ilic, Senior Lecturer in Stem Cell Science, Kings College London, said:

“The most important thing is that Robert Lanza and his team at the Advanced Cell Technology get across a message to the media and the public that ongoing clinical trials for dry age-related macular degeneration and Stargardt’s disease with retinal pigment epithelium (RPE) derived from hES cells are safety trials. Even though in preclinical trials, the RPE were capable of extensive photoreceptor rescue in an animal model of retinal disease, resulting in improvement in visual performance without evidence of untoward pathology, we should keep in mind that people are not rats. The number one priority of initial clinical trial is always patient safety. If everyone expects that the blind patients will see after being treated with hES cell-derived RPE, even if the treatment ends up being safe (which is what Advanced Cell Technology are trying to determine in this trial), they risk being unnecessarily disappointed.”

Professor Peter Coffey, Director of the London Project to Cure Blindness said:

“At last seeing fruits of human embryonic stem cell research entering clinical trials. This will help determine the safety of these therapies. I am immensely happy that this has happened in the eye. And will only help those patients with, until now, blinding eye diseases. Hopefully we will be able to enter our own clinical trials using embryonic stem cell therapy soon.”

Biotech regulators in Britain have started public consultation on experimental reproductive procedures proposed to treat rare mitochondrial diseases, and scientists have been given 5.8 million pounds ($NZ11.1m) to investigate the safety of the techniques.

And the  Nuffield Council on Bioethics is conducting an ethical review on the imnplications of the DNA-swapping technologies, which involve transferring the nuclear DNA of an egg with defective mitochondria to an egg with healthy mitochondria that has been stripped of its nucleus. Tabloid media have portrayed this as producing children with three parents.
The mitochondrion is a cytoplasmic organelle of endosymbiotic origin, responsible for energy production, apoptosis regulation and formation of reactive oxygen species within the cell. It contains a circular DNA with 37 genes with strict maternal inheritance.

Read about mitochondrial diseases in this SMC factsheet

Mitochondrial DNA mutations (mtDNA) passed from a mother to her child have been  linked to a number of conditions, such as some  forms of muscular dystrophy and type 2 diabetes. As many as 1 in 250 people carry a potentially disease-causing mitochondrial mutation, and recently a number of eye diseases have been shown to be caused by such mutations.

The UK research funding will set up a  Wellcome Trust Centre for Mitochondrial Research at Newcastle University, headed by neurologist Professor Doug Turnbull, who will check the  safety of two DNA-swapping procedures called pronuclear transfer and maternal spindle transfer. Professor Turnbull has already carried out pronuclear transfer — shifting the nucleus of a fertilised egg into another fertilised egg that lacks mitochondrial mutations and has been stripped of its nucleus — in human eggs that were not suitable for implant and found that 18 out of the 80 resulting embryos developed to the 8-cell stage, and a small number reached the 100-cell blastocyst stage at which implantation normally occurs.

Maternal spindle transfer (MST) involves transferring the chromosomes of an unfertilised egg into another woman’s egg that has been stripped of its nucleus. That hybrid cell is then fertilised in vitro. In 2009, scientists in Oregon reported that two rhesus macaques conceived this way developed normally.

In April last year, Britain’s  Human Fertilisation and Embryology Authority (HFEA) called for specific experiments to be done before the technolgy was tried in humans, and the new work will include some of those experiments.

Our colleagues in the UK Science Media Centre collected these responses from scientists:

Professor Sir John Tooke, President of the Academy of Medical Sciences, said

“We warmly welcome news that research to understand, and address the impacts of, mitochondrial disease will continue to be undertaken by scientists in the UK, and that views of the public on this exciting area of research are to be sought.

New techniques to prevent the hereditary transmission of mitochondrial disease could be of clinical benefit in the near future. The views of the public and patients should be taken into account, alongside scientific evidence and expert ethical opinion, when deciding whether new techniques such as these should be permitted. We appreciate the Government’s approach and look forward to hearing the outcomes of this important public dialogue.”

Alastair Kent, Director of Genetic Alliance UK said

“The techniques under development at Newcastle University hold great promise for families affected by conditions caused by faults in mitochondrial DNA, and we are delighted that this work will be able to continue. We hope this next stage of research will bring us closer to being able to offer couples the option to have a child free from these devastating conditions.

“This is a complicated and sensitive area, about which the public must be well informed. We look forward to participating in the Government’s public dialogue, and to highlighting the clear value of a technique which allows couples affected by this problem to have healthy children.”

Professor Robin Lovell Badge, MRC National Institute for Medical Research, said

“Creation of a new research centre and a public consultation will both help to ensure that innovative methods to avoid mitochondrial disease can be developed and, if deemed safe, adopted in a timely fashion. It is important that research on mitochondrial diseases, including the development of innovative methods to avoid these occurring in children, is conducted in a way that recognises the needs and concerns of patients, but also that it has the support of society at large. The new Centre will bring many of the stakeholders together, while the public consultation will be an opportunity to convey the underlying science, including the nature of these often devastating diseases, and to dispel some of the impressions gained from headlines or from those who seem to be against progress in general.

“If the pronuclear and/or spindle transfer methods are adopted clinically, and I shall await with great interest the results of the experiments requested by the HFEA’s scientific review of these methods*, any mitochondrial donor will be crucial to the outcome, namely to the birth of healthy offspring. But I personally do not think that we should get tangled up too much in a debate about whether they constitute a third parent or not. If I had eggs to give, I would be delighted that my mitochondria could help, but they would not convey any character that could be claimed as mine.”

Robert Meadowcroft, Chief Executive of the Muscular Dystrophy Campaign said:

“This research could end the heartbreak of parents passing on these diseases to their children – diseases that can cause devastating symptoms and even death – so it’s imperative that this research is taken forward.

“This technology has been shown to work in the lab so now we must explore it further and move it into clinical trials without delay.

Sharmila Nebhrajani, chief executive of the Association of Medical Research Charities (AMRC) said:

“Right now there are no cures for mitochondrial diseases and no way of helping people avoid passing them on to their children. Research in this area is much needed and AMRC are delighted that the team in Newcastle have funding. If their research is successful it will be vital the health secretary moves quickly to ensure these techniques can be licensed and are available to patients. It is also essential that we all have confidence in the legal and ethical framework around these therapies, and we welcome the Department of Health’s public dialogue as an important step in this process.”

 Dr Geoff Watts, Chair of the Nuffield Council on Bioethics inquiry on mitochondrial donation, said:

“The strong interest in mitochondrial disease research shows that it is an important time to be thinking ahead and taking stock of the ethical questions that could arise. With this in mind the Nuffield Council on Bioethics has launched an open call for evidence to seek people’s views on the ethical issues raised by techniques to prevent the transmission of inherited mitochondrial disorders.

“The techniques we are particularly concerned with involve using healthy mitochondria from a donor egg to replace the mother’s unhealthy mitochondria. If these procedures were permitted for treatment, the resulting child is expected to be free from inherited mitochondrial disorders. However, some people may be concerned about the ethical acceptability of these techniques. At this stage of our investigation we are seeking views from a wide range of people on important ethical questions such as ‘Is it acceptable to make changes in the embryo that will then be inherited by future generations?’

UK Science Media Centre Fact Sheet

Mitochondrial DNA

 Mitochondrial DNA (mtDNA) is DNA contained in the mitochondria in our cells – these are the energy-generating structures commonly referred to as the ‘batteries’ or ‘powerhouses’ of the cells

Mitochondria have their own genome which is separate from that contained within the cell nucleus – this consists of a circular molecule of DNA, containing the genes necessary for mitochondrial formation – the mitochondria The mitochondrial genome contains around 16,500 base pairs (the nuclear genome contains over 3 billion base pairs) and 37 genes (compared to around 23,000 genes in the nuclear genome).

It is thought to have evolved separately from nuclear DNA, when bacteria containing circular DNA became part of the precursors to cells that exist today – this is shown by the observation of similarities between mitochondrial and bacterial genomes.

Mitochondrial DNA is inherited solely through the maternal side (i.e. from the mother).

Mitochondrial diseases

Mitochondrial diseases are a group of disorders caused by damage to the mitochondrial DNA, or to nuclear DNA that contributes to mitochondrial components. A number of these conditions are associated with mitochondrial myopathy, which feature neuromuscular disease symptoms resulting from failure of the mitochondria to function properly.

Examples of mitochondrial diseases include:

•   Neuropathy, Ataxia, and Retinitis Pigmentosa (NARP) – a condition consisting of various symptoms affecting the nervous system, including numbness or pain in the limbs (sensory neuropathy), muscle weakness, and problems with balance and coordination (ataxia) as well as deterioration of light-sensing cells I the retina (retinitis pigmentosa).
•   Leigh syndrome – a progressive degenerative disorder affecting the brain and nervous syndrome which mainly appears in infants during their first year of life.
•   Myoclonic Epilepsy with Ragged Red Fibres (MERRF) – a rare type of progressive epilepsy characterised by ‘ragged red’ muscle fibres.
•   Leber’s hereditary optic atrophy (LHON) — the onset in midlife (average age 30) of painless central visual loss that progresses over a period averaging 4 months, resulting in blindness in both eyes.

They can affect either single or multiple organs, and can appear at any age and with variable frequency. The defects that cause them are transmitted by maternal inheritance, in accordance with the maternal pattern of mtDNA inheritance.

It’s important to note that these are not always clearly distinguishable conditions – there may be various symptoms present than can be attributable to more than one disorder, and careful examination may be required to make a diagnosis.

In most cases, the possibilities of treatment are limited, although there are options for managing the conditions.

Emerging research on mtDNA

Researchers are working on ways to replace damaged mitochondrial DNA in cells as a means of preventing mitochondrial disease being passed on to the next generation. Research in this area is at a stage where treatments could be offered to parents, although it is tightly controlled. It is permitted by the most recent Human Fertilisation and Embryology Act (2008) and is subject to licensing by the Human Fertilisation and Embryology Authority.

The idea is to be able to extract genetic material (nuclear DNA) from the fertilised egg in which the mitochondrial DNA is damaged, and to insert it into another unfertilised egg obtained from a donor in which the mitochondria are undamaged. The DNA is in the form of two pronuclei – one from the egg and one from the sperm that fertilised it – which exist separately before they fuse to form the nucleus with the full set of chromosomes (one set each from mother and father).

The egg is then allowed to develop in vitro with normal mitochondria, as per the (simplified) diagram below.

An alternative emerging technique is maternal spindle transfer, whereby the mother’s nuclear genetic material (the spindle with the chromosomes attached) is transferred from an unfertilised egg into a donor egg which has had its own nuclear material removed; the reconstituted egg is then fertilised with sperm from the patients partner. This is not dissimilar from pronuclear transfer (described above) in that both techniques require donated eggs and involve the transfer of genetic material; but with spindle transfer the extraction of the genetic material takes place prior to fertilisation, whereas pronuclear transfer involves the transfer of the pronuclei after fertilisation has taken place.

About 600 New Zealand women — and potentially as many as 1000 to 2000 — prescribed a synthetic estrogen decades ago, may have daughters facing the same issues as 53 American women who have gone to court in Boston to sue drug companies who made and promoted the drug.

Professor Charlotte Paul

A study in the New England Journal of Medicine last year indicated an increased risk of 12 medical conditions for  women who were exposed in the womb to diethylstilbestrol (DES). In many cases it was was prescribed in the mistaken belief it could reduce pregnancy complications.

Researchers at the National Cancer Institute (US) and other medical centers followed 4600 women who were exposed to DES before it was discontinued in 1971 found that these “exposed” daughters were twice as likely to be infertile and at five times the risk as of having a preterm delivery, compared with women not exposed in the womb. The daughters also had 40 times the risk of developing a rare cancer of the vagina among young women, called clear cell adenocarcinoma (CCA), and nearly double the risk of breast cancer, the researchers said. DES was known as Stilboestrol when it was given to NZ women.

The USA court case,  in Boston is believed to be the first major litigation alleging a link between DES and breast cancer in “DES daughters” over the age of 40, and the  women’s lawyers say their case is supported by last year’s study  that suggests that breast cancer risk is nearly doubled in DES daughters over this  age.

In New Zealand, Professor Charlotte Paul wrote a paper in 2006 which said  that the longterm adverse effects of Stilboestrol prescribed for pregnant women in New Zealand  were still being clarified. She  said DES was used as a post-coital contraceptive in NZ and was given to women to suppress lactation. It was prescribed to some pregnant women in the 1960s, though the main use was in the 1940s and 1950s.  She was not aware of anyone prescribed it during pregnancy after 1971.

Professor Paul,  Professor of Preventive and Social Medicine, at Otago University — a member of National Ethics Advisory Committee (NEAC)  from 2002 to 2008 and was a medical advisor to the Cartwright Inquiry —   responded to questions from the SMC as the Boston case got underway:

What estimate would you make for the numbers of women in NZ who were exposed (directly or in the womb), and what proportion of those likely suffered from health effects linked to the exposure?  

“We estimated 600 exposed women in 1984 and considered that a major underestimate. It may be 1000 to 2000. It is a guess now. The mothers have an increased risk of breast cancer, the daughters of CCA and breast cancer, and very commonly structural abnormalities of the reproductive tract and hence difficulty with childbearing. The sons have some reproductive tract abnormalities”.

Why do you think there has never been a systematic attempt to identify exposed women in New Zealand?

“The first work my colleagues and I did was in 1983 when we approached obstetricians and gynaecologists to ask about their use of DES in New Zealand. The results were published as a letter to the NZMJ in 1984 (interesting a longer paper reporting the results was rejected by three medical journals). And we got the sense that publicity for this episode was not actively sought (indeed the opposite) by doctors.  I approached the Department of Health about publicising the issue for women after the study was done. The Department did a small survey of general practitioners to gauge GP prescribing and mentioned DES in a clinical services letter in 1989. I persuaded them to fund a pamphlet on DES for exposed mothers, daughters and sons which was published in 1994 and sent to all general practitioners. Following the release of that pamphlet there was a TV programme about DES and subsequently I received many letters from women. For most of them, when they enquired about their records, they were unavailable.
“I remember discussion about a register in the 1980s but the Department of Health were not keen and most of the records were already unavailable.  The current regulations require health records to be held for only 10 years after the last consultation. These regulations date from 1996 and submissions recommending a longer time were unsuccessful. I think some DHBs do keep mother/infant records for longer”.

To what extent has the fact that women who were not exposed to DES had a second peak in the incidence of CCA around age 70 been reflected in the exposed population?

“There has been no information published yet to definitely suggest a second peak [in exposed women]. The Herbst Registry in Chicago stated in 2007:  ‘The Registry, as of December 2007, has accessioned approximately 760 cases of clear cell adenocarcinoma (CCA)….  The initial age-incidence curve showed a peak between ages 15-25 years among the DES-exposed.  Currently cases up to age 55 have been accessioned and there is a suggestion of a possible increase in frequency among DES-exposed beginning to appear in those over 40 years of age’.”

What is the current understanding of the cumulative excess risk for CCA in women exposed to DES while in the womb?

“The cumulative excess risk for CCA would be the same as the cumulative risk of CCA, as the cancer is so rare (30 to 40 times less) in unexposed (women). The cumulative risk is in the order of 1 in 1000 to age 40 years”

What are the implications for sons exposed to DES in the womb?

“Some studies have suggested an increased risk of testicular cancer in sons, but this is not confirmed. The latest study to assess risk of testicular cancer  in a combined cohort analysis of four cohorts of men was published in 2001. The authors found an elevation in risk of testicular cancer, relative risk for exposed versus unexposed men was 3.05 but the 95% confidence interval included 1.0 (0.65 – 22.0), so this could have been a chance finding. Indeed there were only 6 cases in the exposed group and 2 in the unexposed. The combined cohort is too small for robust assessment of risk.

Your 2006 paper mentioned grandchildren of DES-exposed women may also have a potential for DES-linked cancers: has there been any indication of possible health effects on  DES granddaughters?

“The concern about grandchildren is based on animal models.  It is suggested to be an epigenetic effect. A recent study of birth defects in the third generation did find an excess overall among daughters and a significant increase in heart defects. As these were self reported (by parents) reporting bias was considered a possibility”.