Fasting: a Natural Nootropic?

Periods of deliberate fasting with restriction of solid food intake are practiced worldwide, mostly based on traditional, cultural or religious reasons. There is large empirical and observational evidence that medically supervised modified fasting (the fasting cure, 200-500 kcal nutritional intake per day) with periods of 7-21 days is efficacious in the treatment of rheumatic diseases, chronic pain syndromes, hypertension, and metabolic syndrome[1].  Various identified mechanisms of fasting point to its potential health-promoting effects, e.g., fasting-induced neuroendocrine activation and hormetic stress response, increased production of neurotrophic factors, reduced mitochondrial oxidative stress, general decrease of signals associated with aging, and promotion of autophagy.

In this study, mice on intermittent fasting had better learning and memory, thicker CA1 pyramidal cell layer, higher expression of drebrin -a dendritic protein- and lower oxidative stress than mice that had free access to regular diet (control mice). In contrast, mice fed with high fat diet was obese and with hyperlipidemia. They also had poorer exercise tolerance. However, these obese mice did not present significant learning and memory impairment or changes in brain structures or oxidative stress compared with control mice. These results suggest that intermittent fasting improves brain functions and structures and that high fat diet feeding started early in life does not cause significant changes in brain functions and structures in obese middle-aged animals.

Other studies point out at the many potential beneficial effects of dietary restriction on brain function as well as delaying the onset of neurological diseases. In this investigation, the effect of late-onset short-term intermittent fasting dietary restriction regimen was studied on motor coordination and cognitive ability of ageing male rats. Results suggested that even late-onset short-term fasting regimen have the potential to retard age-associated detrimental effects, such as cognitive and motor performance as well as oxidative molecular damage to proteins. Thus, intermittent fasting attenuates lipopolysaccharide-induced neuroinflammation and memory impairment, inducing adaptive responses in the brain and periphery that can suppress inflammation and preserve cognitive function in an animal model of systemic bacterial infection.

Isolated studies?

A systematic review of the published literature through January 2015 was performed by using sensitive search strategies to identify randomized controlled clinical trials that evaluated the effects of fasting on either clinically relevant surrogate outcomes (e.g., weight, cholesterol) or actual clinical event endpoints [e.g., diabetes, coronary artery disease] and any other studies that evaluated the effects of fasting on clinical event outcomes.

Three randomized controlled clinical trials of fasting in humans were identified, and the results were published in 5 articles, all of which evaluated the effects of fasting on surrogate outcomes. Improvements in weight and other risk-related outcomes were found in the 3 trials. Two observational clinical outcomes studies in humans were found in which fasting was associated with a lower prevalence of diabetes diagnosis. No randomized controlled trials of fasting for clinical outcomes were identified.

Clinical research studies of fasting with robust designs and high levels of clinical evidence are sparse in the literature. Whereas the few randomized controlled trials and observational clinical outcomes studies support the existence of a health benefit from fasting, substantial further research in humans is needed before the use of fasting as a health intervention can be recommended.