Caloric Restrictions and Brain Function

  • Chronic imbalance between energy intake and energy use leads to chronic metabolic disease.  Metabolic disease is the leading cause of death in Western society.  In the heart and circulation this leads to high blood pressure, atherosclerosis and its consequences: heart attack and stroke.  In the immune system we find increased risk for cancer.  In the brain we see degenerative brain disease.  Cognitive decline (Alzheimer's disease and other chronic dementias) is epidemic in our society. The ageing of the population puts increasing numbers of people at risk for dementia. This is a personal catastrophe for many of the elderly and places an enormous burden on the rest of society.

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    There is abundant data demonstrating that treatment of hypertension prevents cognitive decline in the elderly.  This is partly due to prevention of stroke (an important cause of dementia) and partly associated with reduction of cognitive decline.  Lifestyle change has also been advocated but the data is not as conclusive. 

     

    Caloric restriction has been studied for decades as a therapeutic strategy.  In all species in which it has been studies, caloric restriction prolongs lifespan.  This is true in simple organisms such as fruit flies and worms and in higher mammals including humans.  In animals much of the benefit seems to be associated with reduction of insulin signaling.  Caloric restriction also has an anti-inflammatory effect.  Thin people live longer.  A recent study of long lived Okinawans demonstrated an important role for caloric restriction in their longevity. 

     

    Lifestyle change is of course an important part of treatment of high blood pressure.

    What about caloric restriction and prevention of cognitive decline in the elderly?  In animal models of neurodegenerative disease and aging, restricting caloric intake protects brain cells and ameliorated functional decline.  Several recent intervention studies in humans have shown improvement in brain function in elderly persons with cognitive decline.  In some of these studies caloric restriction seemed to provide the greatest benefit.  In some others substitution of dietary fat with unsaturated fatty acids or omega-3 fatty acids (fish oils) was also beneficial.

     

    Last week A.V. Witte and his associates at the University of Munster in Germany published the results of their research on caloric restriction and dietary modification with unsaturated fatty acids.  Their studies, published in the Proceedings of the National Academy of Sciences, extended the results of previous studies reviewed above and extended our understanding of the role of caloric restriction in prevention of cognitive decline in the elderly.

     

    Witte etal studied three groups of patients: one group ate a diet restricted by 30% in total calories, and a second a diet not calorie restricted but enhanced in unsaturated fat.  A third group served as a control.  All the patients underwent standardized memory tests at baseline and after three months.  Most of the patients were overweight.  Not surprising the first group lost weight and body mass index.  They also had reduced insulin levels and reduced levels of inflammatory markers.  After three months the calorie restricted group performed significantly better in the memory testing than either the UFA group or the control group.  This was correlated with reduced insulin levels and lower levels of inflammatory markers.  The patients most compliant with the diet did best on the memory testing.

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    This study suggests a role for caloric restriction in prevention of dementia in the elderly.  It also supports the concept that lifestyle associated metabolic disease contributes to neurodegenerative disease and more importantly that it can be modified by lifestyle change. 

     

Published On: February 11, 2009