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Forget the Munchies: Can Calorie Restriction Improve Memory?
Abstract & Commentary
By Russell H. Greenfield, MD
Synopsis: Self-reported modest reduction of caloric intake by 30% for a duration of three months improves cognitive function in healthy elderly subjects.
Source: Witte AV, et al. Caloric restriction improves memory in elderly humans. Proc Natl Acad Sci U S A 2009;106:1255-1260; doc: 10.1073/pnas.0808587106.
The authors of this paper designed a prospective interventional trial to study the effects of calorie restriction (CR) or a diet high in unsaturated fatty acids (UFA) on cognition in healthy, normal to overweight elderly people. A total of 50 subjects (29 women) were enrolled in the study with an average age of 60.5 years and an average body mass index (BMI) of 28 kg/m2. At the end of three months, data were evaluable on 49 participants.
At baseline, a routine physical examination, including neurologic examination with Mini-Mental State Examination (score had to be higher than 26 for study participation), was performed. Subjects were then placed into one of three groups based on age, gender, and BMI: CR (caloric intake to be reduced by 30% from previous habits); "UFA enhancement" (increase amount of UFA ingested by 20% compared with previous intake, while keeping total fat intake constant); and control group (no change to eating habits). The active intervention groups received training by nutritionists blinded to the underlying study hypothesis and received phone instruction if needed (the CR group was privy to a small number of extra sessions of instruction). All participants were required to fill out nutrition diaries and were interviewed at intervals by trained dietitians regarding their diets.
The primary outcome measure of interest was the ability to learn and remember new information. Before and after the three-month intervention subjects were tested on memory performance by a trained neuropsychologist. Participants were asked to learn and remember as many words as possible out of a list of 15, and then to recall the words 30 minutes later. The total number of words recalled was called the memory score. Different exams were given at baseline and at three months.
Blood tests were assessed at baseline and at trial's end for a wide variety of measures including fasting peripheral serum insulin and glucose levels, highly specific C-reactive protein (hs-CRP), TNF-alpha, IGF-1, and brain-derived neurotrophic factor (BDNF).
By the end of the trial, subjects in the CR group had experienced both significant weight loss and a decrease in BMI. While all groups increased their proportional intake of UFAs according to dietary records, seafood intake did not change significantly across the groups, and the ratio of UFAs:saturated fat intake improved only in the UFA enhancement group. There were no significant changes in measures of lipid metabolism or waist-to-hip ratio.
There were, however, significant improvements in memory scores in the CR group at the end of the three-month intervention. Subjects in the CR group remembered more words and made fewer mistakes after calorie restriction. In addition, those in the CR group had decreased fasting insulin levels, decreased hs-CRP levels, and trended toward decreased fasting blood glucose levels. When analysis focused solely on those who most closely adhered to the CR diet (weight loss > 1 SD of mean weight loss of the control group, or weight loss > 2 kg, n = 9), a significant inverse association between memory scores and fasting insulin levels became apparent. Again using this focused analysis, the same inverse relationship was found for memory scores and hs-CRP levels. No memory improvements were found for the UFA enhancement and control groups. No association was found for neurotrophic factors and any of the groups' memory scores.
The authors conclude that moderate calorie restriction over three months time improves memory performance in healthy, normal to overweight elderly people. They posit that the mechanisms of action of CR are increased insulin sensitivity and reduced inflammation.
Results of a significant number of animal trials, and some human epidemiologic data, suggest that moderate CR could improve the chances for healthy aging, retained cognitive function, and enhanced longevity. Some studies using animal models of aging and neurodegeneration showed that CR protects against functional decline; other trials, however, were not quite so positive, dampening initial enthusiasm. Still, it is known that obesity in later years is associated with cognitive dysfunction. A few of the micronutrient studies that focused on essential fatty acid intake offered some promise for beneficial effects on the aging brain, especially in the animal models, but results have been contradictory.
The authors of the current trial did a very good job assessing the potential impact of the dietary interventions in question using refreshingly simple methodology. They also, however, investigated multiple laboratory parameters and identified interesting inverse relationships between memory scores and fasting insulin and hs-CRP levels in the CR group. Specifically as relates to insulin, the authors state that lower fasting insulin levels due to CR should create less insulin resistance and higher insulin sensitivity, resulting in improved cortical insulin signaling in the brain and neuronal survival. They propose that insulin and inflammatory changes play roles in cognitive impairment in the elderly.
The study is not without its weaknesses: Dietary changes were self-reported by questionnaire with meals prepared independently at subjects' homes, and although subjects in the CR group did lose weight and have decreased BMI at trial's end, it is likely that protocol adherence was not as strong as reported; simply being enrolled in a study often leads to changes in diet and lifestyle, so the report of no change in exercise activity could likewise be overstated; and subjects in the CR group received more interpersonal attention than did members of the other groups.
The results for UFA enhancement are disappointing but could be related to the relative lack of marine fatty acid intake, insufficient overall UFA intake, or simply non-adherence to the UFA enhancement diet.
Practitioners considering the merits of CR for their middle-aged and older patients would be wise to show caution, as a significant proportion of elderly people are malnourished due to any number of factors including illness, the inability to prepare meals for themselves, changes in taste and dental issues, to name but a few. The data suggesting that CR may be part of a comprehensive healthy aging strategy are intriguing, but, as with any health care intervention, individualization of care is critically important, and we still lack firm guidelines with which to offer recommendations. Stay tuned, thoughclearly there will be more research into the intriguing realm of CR and aging.