February 24, 2014

expert reaction to diet, diabetes and dementia

Research in PNAS  found a potential causal link between compounds present in the Western diet and the accumulation of amyloid,  a component of the plaques characteristic of Alzheimer’s disease. The compounds – advanced glycation endproducts (AGEs) -have been previously linked to diabetes and neurodegenerative disease.

Dr Simon Ridley, Head of Research at Alzheimer’s Research UK, the UK’s leading dementia research charity, said:

“Diabetes has previously been linked to an increased risk of dementia, and this small study provides some new insight into some of the possible molecular processes that may link the two conditions. Although these findings add to some earlier evidence linking a decrease in the SIRT1 protein to Alzheimer’s, the most common cause of dementia, it’s important to note that the people in this study did not have dementia. This subject has so far not been well-studied in people, and we don’t yet know whether the amount of AGEs in our diet might affect our risk of dementia.

“This research is at an early stage, and continued investment in research is crucial to understand the significance of results like this. The diseases that cause dementia are complex, and our risk of the condition is likely to be affected by a number of genetic and environmental factors that are not yet fully understood. In the meantime, the best evidence suggests that a balanced diet can help lower the risk of Alzheimer’s, as part of a healthy lifestyle that includes regular exercise, not smoking, and keeping blood pressure and weight in check.”

Dr Doug Brown, Director of Research and Development, Alzheimer’s Society, said:

“We are often told that burgers or fried chicken are bad for us and this study is not the first to link the chemicals in some cooked foods to Alzheimer’s. However, this research adds to our understanding of how they might work and makes a strong case for further research.

“Diets with low levels of the compounds show promising effects in mice and should be further explored as a way to prevent dementia through changes in diet. Of course, we must not forget that the majority of research was conducted in mice and the human element of this study is too small to draw any conclusions.

“Evidence suggests that the best way to reduce your risk of developing dementia is regular exercise, not smoking and following a healthy diet.”

Dr David Llewellyn, Senior Research Fellow in Clinical Epidemiology, University of Exeter Medical School, said:

“Caution should be exercised when considering the possible clinical significance of oral glycotoxins, and this paper does not confirm a causal relationship in humans as the title suggests. Rather it establishes an observational association with decline on a brief measure of cognitive function over a nine month period. Dementia typically develops over many years and they did not assess whether this association lead to a clinically significant increase in dementia risk. We should be mindful that general dietary patterns are already known to be associated with dementia, and other environmental and lifestyle factors may also account for this association. This study therefore highlights the need for further research investigating dietary interventions as a strategy for dementia prevention or treatment.”

Prof Derek Hill, Professor of Medical Imaging Sciences, UCL and CEO of IXICO plc, said:

“There is a great deal of public interest in the way that diet can cause, or prevent, serious diseases in older life. Some of the proposed ‘bad guys’ in the diet are AGEs (advanced glycation end products), which are present in especially high quantities in meat that is cooked by frying or grilling. People with high levels of AGEs seem to have higher risk of developing many of the serious diseases of aging including diabetes, cardiovascular disease and dementia. It is, therefore, important to better understand the link between diets high in AGE, and the development of those diseases. And there is an exciting potential spin-off, which is that if we better understand the cause of those diseases we may be able to use that information to prevent people getting these diseases or develop new treatments.

“Helen Vlassara’s research team has been looking at the link between eating food with a high AGE content and developing the most common type of dementia – Alzheimer’s disease. There are two parts of their study: a controlled experiment on mice, and an observational study on healthy older people.  They found in the mice experiment that the older mice with a high AGE diet developed one of the molecular hallmark of Alzheimer’s disease – amyloid. In the study of people, they found that levels of AGE in the blood are linked with getting the early symptoms of dementia.

“The results are compelling. Because cures for Alzheimer’s disease remain a distant hope, efforts to prevent it are extremely important. But this study should be seen as encouraging further work, rather than as providing definitive answers. It is notoriously difficult to do experiments on mice that properly mimic Alzheimer’s disease in humans. And a study of only 96 healthy older people just isn’t large enough to provide a high degree of confidence that high levels of AGE causes you to develop dementia symptoms more quickly. But it is grounds for optimism – this paper adds to the body of evidence suggesting that using preventative strategies might reduce the prevalence of Alzheimer’s disease and other dementias in society. And that could have very positive impact on us all.”

Prof Tom Dening, Professor of Dementia Research, Institute of Mental Health, University of Nottingham, said:

“We already know that increasing chronological age makes you more at risk of developing dementia, but how about AGE, with capitals? Advanced glycation end products (or AGEs) are proteins or fats that become modified after contact with sugars. They have various unpleasant effects, for example contributing to the risk of vascular complications of diabetes. Scientists have speculated since the 1990s that AGEs may be important in Alzheimer’s disease, which is the most important cause of dementia. 

“This paper adds to the picture. Mice were fed diets with varying levels of a particular AGE, called MG. Those who received higher amounts showed biochemical and brain changes, including higher levels of amyloid (the characteristic marker of Alzheimer’s disease) in their brains. They also showed impairments of learning and memory. Alongside this work, the research team also tested 93 healthy New York volunteers over 9 months and found that their  MG levels was related to more AGE in their diet and that higher MG led to more cognitive decline during the period studied.

“Should we worry about our diet? Yes, there is already plenty of evidence to support healthy eating. Does this paper make us more worried? A bit. Foods high in protein and fat, such as meat, cheese, and egg yolk, are rich in AGEs, and cooking at high temperatures, e.g. frying and barbecues, increases AGEs. Dietary restriction of AGEs can bring about significant reductions. What isn’t yet clear is how much these effects contribute to Alzheimer’s disease compared to other factors, and we don’t know whether dietary restriction of AGEs would be helpful in prevention. The difficulty will be in the length of the research projects you’d have to run in order to show significant effects. In the meantime, crunch those carrots and reach for the brown rice.”

Prof Martin Prince, Professor of Epidemiological Psychiatry, King’s College London’s Institute of Psychiatry, said:

“There is already persuasive evidence from epidemiological research linking diabetes, insulin resistance and obesity in mid-life to an increased risk of developing dementia and Alzheimer’s disease in late-life. This new research makes a link between advanced glycolated end products (AGE) and the development of Alzheimer pathology in mice.

“We need to better understand the underlying mechanisms and dietary implications of the association between obesity and dementia risk in humans, and this research suggests promising avenues for further research.”

‘Oral glycotoxins are a modifiable cause of dementia and the metabolic syndrome in mice and humans’ by Cai, et al. published in Proceedings of the National Academy of Sciences (PNAS) on Monday 24^th February