Intermittent fasting health benefits are misunderstood, and this is primarily because the concept has been hijacked by new fad diets like the 5:2 diet plan. The problem with these fads is that they encourage binging on non-fasting days and target only one of the intermittent fasting benefits: weight loss. However, when we examine how longevity and intermittent fasting are related, it becomes clear why binging on non-fasting days is counterproductive to good health.
Calorie Restriction Diet vs Intermittent Fasting Benefits
The calorie restriction diet, has been shown to extend life in many species, but scientists are divided on what factors should be attributed the credit for life extension. What we do observe is that calorie restriction improves insulin sensitivity – and by extent, all types of metabolic dysfunction related to chronically elevated insulin levels; it reduces oxidative stress; it improves the immune system; it suppresses cancer growth; it increases cognitive performance and provides protection against neurodegenerative disorders.
In experiments on mice, scientists have managed to exceed the beneficial effects of a calorie restriction diet without reducing the overall food intake. They did so by maintaining the mice on an intermittent fasting regimen. The results contradicted the traditional “calories in, calories out” theory of metabolism. In fact, the weight reduction exceeded that of the calorie restriction diet. With the same calorie intake, the mice had reduced serum glucose, lower insulin levels, and neurons that appeared more resistant to excitotoxic stress.
With similar results as the calorie restriction diet, other studies have reported that intermittent fasting results in increased lifespans in many species. The same theories are proposed as calorie restrictive diets. Insulin sensitivity is improved, and consequently the reduction in the incidence metabolic syndrome. In a fasting state, the body produces antioxidant enzymes that help cells cope with oxidative stress.
History of Fasting
Archaeological data indicate that the population in Europe remained in a positive quasi-stationary state with a mean of 4,400 to 5,900 inhabitants between the Aurignacian period 40,000 years ago and the Glacial Maximum 20,000 years ago. Even when allowing for statistical error, we can say that with 95% confidence that the population of Europe remained between 1,700 and 37,700 during this period.
The question is, with such scarcity of food, how did homo sapiens manage to maintain a stable population for 20,000 years? From an evolutionary perspective, our biological ability to withstand famine and food scarcity is one of the main reasons homo sapiens have managed to survive the last ice age’s Glacial Maximum period, when ice sheets were at their maximum.
Simply put, evolution has created in homo sapiens a physiology built for the feast and famine pattern of energy intake. In the grand scheme, the 3 meals per day is the exception and not the rule.
Lower Metabolic State
Intermittent fasting, like the calorie restriction diet, lowers the metabolic rate by promoting more efficient glucose catabolism through cellular respiration. When glucose levels reach levels too low for the brain, cells transition to metabolizing fatty acids. Neural cells are not permeable to fats, but evolution allowed humans to utilize ketones – which are produced from the body’s fat stores – as fuel for the brain when glucose levels are low. In a healthy human, the liver synthesizes glucose and produces ketone bodies when they are needed.
Increased Insulin-Like Growth Factor Hormone
Perhaps the most striking difference between the calorie restriction diet and intermittent fasting is the effect on insulin-like growth factor 1 (IGF-1). Under intermittent fasting, IGF-1 is increased markedly, while in calorie restriction diets they were decreased. While genetics, exercise and age have an impact on the levels of IGF-1, diet can play a part. When increased lifespan is the objective function, a diet reducing IGF-1 is not optimal.
IGF-1 is similar to insulin, and it plays a vital role in cell growth. It hits a key pathway to cell growth and proliferation through anabolic processes. This pathway is regulated by phosphatidylinositol-3 kinase and the mammalian target of rapamycin complex 1 – otherwise known as the mTORC1. It promotes protein synthesis and plays a role in regulating adenosine triphosphate (ATP), the source of all energy at the cellular level.
Inhibition of mTORC1 lowers mitochondrial membrane potential. The lower metabolic state comes with reduced oxygen consumption and lower cellular ATP levels. Catabolic processes increase with mTORC1 inhibition, which increases autophagy – the consumption of the body’s own tissue. Therefore, it would be a challenge to maintain muscle mass on a prolonged calorie restriction diet.
In experiments involving the injection of the hormone into calorie restricted mice with cancer, the IGF-1 supplementation was correlated with tumor growth. However, intermittent fasting seems to work through other channels to prevent and restrict cancer growth. This could be as a consequence of the lower glucose levels that feed cancer. The mechanisms involved are still speculative at best, but fasting is already being applied alongside the standard cancer treatments.
Effects of Aging on Brain Function
As humans age, their brains suffer the cumulative effects of oxidative and metabolic stress in the form of modified proteins, lipids, DNA and RNA. Modifications to these essential molecules contribute to degenerative neural disorders such as dementia, dysautonomia, Huntington’s, Alzheimer’s and Parkinson’s disease.
Studies on intermittent fasting suggest that it has neuroprotective effects against neurodegenerative disorders. This is partially related to the increase in IGF-1 levels, but it is also related to the increase in ketone bodies, which replace glucose as the primary fuel for the brain. Ketosis – a metabolic state in which the body switches to fatty acids as its primary fuel – is known to provide protection against neurological disorders. One of those ketone bodies is beta hydroxybutyrate, which protects neurons in patients with Alzheimer’s and Parkinson’s disease.
Inflammation and Aging
Aging creates a feedback loop in which the body’s immune system is activated in response to injury from free radicals and other age-related dysfunction. The immune system attacks the offending cells and causes an inflammatory response. Inflammatory cytokines may be responsible for the neurdegeneration that is alleviated with intermittent fasting. Due to the lower metabolic state, production of free radicals is also reduced along with inflammation.
Anson RM, Guo Z, de Cabo R, Iyun T, Rios M, Hagepanos A, et al. Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake. Proc. Natl. Acad. Sci. U.S.A. 2003;100:6216–6220.
Jean-Pierre Bocquet-Appel; et al. (2005). “Estimates of Upper Palaeolithic meta-population size in Europe from archaeological data” (PDF). Journal of Archaeological Science. 32: 1656–1668. doi:10.1016/j.jas.2005.05.006.