Effects of Intermittent Fasting on Health, Aging, and Disease

This is a review article published by the New England Journal of Medicine on December 26, 2019 and it’s reception has been big! Medics and subscribers to intermittent fasting have been discussing this article, so lets break it down and see what all the fuss is about.

The article introduces the concept of intermittent fasting by highlighting a study done in 1997 which showed that caloric restriction over a lifetime has positive effects on aging and lifespan. It then describes the most commonly studied intermittent fasting regimens and the body’s response to it, and finally, presents and discusses the findings from recent studies that tested intermittent fasting regimens in healthy people, as well as people with chronic illnesses like obesity, diabetes, and hypertension. One of the best part of this article in my opinion is that it concludes that providing practical information on how to prescribe and implement intermittent fasting regimens.

What is Intermittent fasting?

It is a meal timing schedule in which a person fasts (no eating) for a certain number of hours, and then eats for a certain amount of time. In order to understand why eating in a specific and timed method with relatively longer periods of fasting works, we have to go to physiology. The main sources of energy for cells in our bodies are glucose and fatty acids. Fasting allows the body to switch from using glucose to using fatty acids and ketone bodies. When we eat, we use glucose for energy and store the remainder as fat (triglycerides). When we fast, triglycerides are broken down into fatty acids and glycerol for energy. During the fasting state, the liver converts the fatty acids to ketone bodies (which is a huge source of energy, especially for the brain). Typically, blood ketone levels are low, but about 8-12 hours into a fast, the levels in our bodies begin to rise. It’s this timing, the rise in ketone levels, that has dictated the optimal timing for different intermittent fasting regimens. There are three main (most popular) methods of intermittent fasting:

Alternate-day fasting

5:2 intermittent fasting (fasting 2 days each week)

Daily time-restricted fasting (eating period of 6-8 hours a day)

The positive effects of intermittent fasting, according to the article, are not only to do with reduced production of free radicals or weight loss, but because it “elicits evolutionarily conserved, adaptive cellular responses that are integrated between and within organs in a manner that improves glucose regulation, increases stress resistance, and suppresses inflammation”. All of that is to say that intermittent fasting allows us to better utilize different forms of stored glucose, cope with metabolic stress better, and suppress inflammation.

In animal studies, intermittent fasting has positively affected chronic disorders such as diabetes, obesity, some cancers, neurodegenerative brain diseases, and cardiovascular disease.

Intermittent fasting has been shown to improve cell function and ability to stress resistance ability; it stimulates autophagy and mitophagy and inhibits the mTOR pathway (a big player in driving cancer growth). Cells are better able to remove damaged proteins and repair and recycle its components.

Intermittent fasting has been shown to increase lifespan in rats and mice at different degrees, and in non-human primate studies, one study showed positive effect on both health and survival, whereas another study showed no significant reduction in mortality but did show improvement in overall health. The article states that, “in humans, intermittent-fasting interventions ameliorate obesity, insulin resistance, dyslipidemia, hypertension, and inflammation”. A trial describes in the article consisting of about 200 overweight women, divided into two groups, one group had a 25% reduction in their daily caloric intake and the other group did 5:2 intermittent fasting. Both groups of women lost the same amount of weight in the 6-month period but those in the 5:2 intermittent fasting group had, “greater increase in insulin sensitivity and a larger reduction in waist circumference”.

Intermittent fasting has been shown to enhance cognition in spacial memory, associative memory, and working memory. “Alternate-day fasting and daily caloric restriction reverse the adverse effects of obesity, diabetes, and neuroinflammation on spatial learning and memory”.

In regards to cancer, studies have already shown that daily caloric restriction or alternate-day fasting reduces spontaneous tumor growth that is a factor of the normal aging process in rodents. It also suppresses the growth of many types of induced tumors while increasing sensitivity (effectiveness) to chemotherapy and radiation. Mechanism is thought to be via a reduction of signaling in FOXO and NRF2; activation of specific processes via intermittent fasting may convey protection against cancer. There are already on-going studies of intermittent fasting in patient’s with cancers such prostate, breast, ovarian, endometrial, and colorectal cancer. And in Glioblastoma, some case studies suggest that intermittent fasting can suppress tumor growth and extend survival.

My thoughts:

Is intermittent fasting the new way we should all be eating? It very well could be, but that doesn’t mean this is going to be the case. Three meals a day is such a cultural expectation; it is deeply engraved within society and heavily marketed towards consumers. Also, fasting and caloric restriction is hard! The paper points out that “people will experience hunger, irritability, and reduced ability to concentrate during periods of food restriction”, but these side effects usually pass after one month. Intermittent fasting is not a new concept, in fact many cultures and religions are already experts in fasting (Muslims during Ramadan, some Christian sects during lent, Asian spiritual practices etc), but the science and understanding of why it works, is new and the data is exciting. I get concerned when people see a headline for intermittent fasting and weight loss and that becomes the sole motivator. When people become obsessed with counting down time to their next meal and counting their calories, and when mental health and general happiness begins to get affected, it’s time to re-evaluate choices. Intermittent fasting should be looked at not as a short term weight loss goal, but a life-style adaptation with focus on a healthy body, healthier mind, and reducing disease risk and possibly increasing longevity. More studies are on-going and I’m personally looking forward to those focused fighting cancer.