The Fasting Brain
Mattson's research centers on a possibly more surprising benefit of fasting: its ability to enhance cognition and brain function. He and others have provided abundant animal data showing that fasting-related ketogenic states lead to cellular and molecular adaptions in the brain that confer such benefits as resistance to stress, injury, and disease.
"Another interesting finding is if you take rats or mice and reduce their calorie intake aggressively—a 40%-50% reduction in calories approaching starvation—their heart, liver, gut, and muscles all decrease in size, but the brain remains the same size."
Here, too, we have a compelling evolutionary explanation. Ketones are an exceptional energy source for the brain, more so than the unreliable fluctuations of glucose. It is likely that mammals who excelled at surviving long periods of food deprivation were naturally selected for optimal brain function in that state.
Mattson and colleagues at the National Institute on Aging are currently running a trial in which participants at risk for cognitive impairment owing to age (55-70 years) and metabolic status (body mass index ≥ 30 kg/m2, insulin resistant but nondiabetic) are randomly assigned to receive either the 5:2 diet or control (healthy eating). After 2 months, they are tested for cognition and psychological factors, in addition to undergoing functional MRI on network activity in the brain and spinal taps for brain-derived neurotrophic factor, which animal studies suggest is critical for learning and memory.
"On the basis of what we know about the impact of aging and obesity on cognition and brain function in human subjects and the effects of intermittent fasting on cognition and nerve cell network activity in animal studies, we're predicting that intermittent fasting will improve performance and the cognitive test, and enhance the fidelity of communication between brain regions that are critical for cognition," Mattson said.
In Fasting to Fight Cancer, Timing May Be Everything
Recent clinical research on fasting's role in breast cancer suggests that its positive impact may depend not just on whether people abstain from eating, but also when.
In a 2015 epidemiologic analysis of women participating in the 2009-2010 US National Health and Nutrition Examination Survey, researchers were able to show, for the first time, that longer nighttime fasting duration was significantly associated with improved glycemic regulation, and thereby reduced risk for breast cancer.
In a study the following year, researchers looked at over 2400 patients who were in remission from early-stage breast cancer. In those who self-reported nightly fasting of less than 13 hours, there was a statistically significant 36% increase of the risk for breast cancer recurrence compared with those whose nightly fasting lasted more than 13 hours.
"This finding was the first time that anyone had ever made an association between a clinical outcome of breast cancer occurrence and prolonged nightly fasting," explained Dorothy D. Sears, PhD, associate director of the Center for Circadian Biology, and an associate professor at the University of California, San Diego, who worked on both studies.
According to Sears, there are good reasons why nighttime eating would have negative effects. Although insulin works well in the morning and early afternoon, in the evening it begins to be counteracted by melatonin and growth hormone.
"That's bad, because sugar in the blood causes reaction with proteins and the blood vessels," she said. "Lots of proteins in the body can become glycated, or sugar-coated, which causes a form of irreversible damage."
"Another negative effect of having high glucose and insulin at night or for an extended period in the night is that it can drive the growth of tumors," Sears continued.
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Cite this: Hungry for Health: Fasting's Medical Benefits - Medscape - Jul 12, 2018.