Intermittent Fasting (IF) is high on the list of dietary concepts that have received the most attention over the past decade. It’s become quite popular and gained a substantial following composed not only of hardcore fitness devotees and evolutionary health aficionados, but also of housewives, office workers, and weight watchers who’re looking to level up their health or lose a couple of pounds before the summer. A growing body of research suggests that these voluntary food restrictors not only are on the right
The evolutionary basis of intermittent fasting
IF has been on the rise; however, not everyone is enthusiastic about the prospect of going to work on an empty stomach. The concept has its fair share of detractors, some of which perceive it as being aberrant and dubious. This isn’t particularly surprising, given that the idea behind IF goes against conventional nutritional wisdom, in
What’s often overlooked is that IF is by no means a new or revolutionary concept, which is unfortunately how it’s often presented. On the contrary, it’s one of the most long-lived nutritional practices of all, with roots extending long into our primal past. In reality, if we look at human evolution as a whole, it’s the practise of eating every three-four hours during the day, starting with an early breakfast, that is novel and aberrant, whereas periodic food deprivation is the norm or standard.
This is something a lot of people fail to take into account when they consider the merits of intermittent food restriction. Not everyone though. Some people have employed the evolutionary approach, a foremost example being researcher Mark Mattson, the most highly cited neuroscientist in the world and a leading expert on the health effects of IF. He’s published a number of studies and research papers on the subject, including a recent intriguing article entitled An Evolutionary Perspective on Why Food Overconsumption Impairs Cognition. That paper, in addition to several other related articles (e.g., this one, this one, this one, and this one), put him on my radar.
IF is inherent to the evolutionary approach to health. I’ve talked quite a bit about it here on the site in the past and also shared some of my own experiences with it; however, I haven’t explored the concept
With that said, let’s jump in with the interview…
1. Please tell us a little about yourself. I’m particularly interested in hearing about your research background and motivation for getting involved in neuroscience.
I received a B.S. degree in Zoology from Iowa State University and a Ph.D. in Biology from the University of Iowa where my thesis research project was aimed at understanding the signaling mechanisms involved in the neuroendocrine regulation of molting in crabs. There I gained a broad knowledge of how hormones and neurotransmitters are synthesized in endocrine cells and neurons, and how they elicit responses in their target cells.
My postdoc training was in developmental neurobiology at Colorado State University where I discovered that the neurotransmitter glutamate regulates the outgrowth of dendrites and synapse formation in the developing embryonic rat brain. I focused on a brain region called the hippocampus which plays critical roles in learning and
I established a critical role for calcium influx in the regulation of dendrite outgrowth and synapse
This led to my interest in neuronal degeneration and Alzheimer’s disease. I then spent 11 years building my own independent research program as a Professor of Neuroscience at the University of Kentucky School of Medicine. There my team and I made major inroads towards understanding the reasons why neurons degenerate in Alzheimer’s disease. It was also there that we discovered that intermittent fasting can protect neurons in the brain against dysfunction and degeneration in rat and mouse models of Alzheimer’s and Parkinson’s diseases, and stroke.
I was then recruited to the NIH to build and lead the neuroscience research program at the National Institute on Aging. It was there that we made major advances in understanding how IF affects cells and organ systems in ways that enhance their performance and increase their resistance to injury and disease.
2. How did you first become interested in intermittent fasting?
Aging is the major risk factor for Alzheimer’s and Parkinson’s diseases. Previous studies had shown that daily calorie restriction and every-other-day fasting can greatly increase lifespan in rats and mice. We therefore designed experiments to test the hypothesis that every-other-day fasting could protect neurons and improve functional outcome in animal models of neurodegenerative conditions.
The postdocs in my laboratory found that the IF protects neurons in the hippocampus against epileptic seizures and prevents memory impairment. We further showed that IF protects neurons against damage caused by a stroke. We went on to demonstrate that IF can counteract the disease processes in models of Alzheimer’s and Parkinson’s diseases.
3. Over the most recent decades, a number of studies linking intermittent fasting with a variety of health benefits have come out, some of which were conducted by you and your colleagues. As you see it, what is the most important takeaway message from this body of research?
IF improves general health and brain health by stimulating cells in ways that enhance their ability to prevent and repair damage to their molecules (DNA, protein and membranes). IF improves glucose regulation, promotes utilization of abdominal fat and ketones during the fasting period, and reduces inflammation.
IF improves cardiovascular health as indicated by reduced blood pressure and resting heart rate, improved cardiovascular adaptation to stress and reduced LDL cholesterol and triglyceride levels. IF improves brain health by increasing the number of healthy mitochondria in neurons and by stimulating the production of a neurotrophic protein called BDNF. Others have shown robust suppression of tumor growth in animal models of various types of cancer and clinical trials of IF in cancer patients are in progress.
4. In nature, organisms have to “struggle” to survive and put in quite a bit of effort in order
Our research on IF supports the evolutionary hypothesis that the brain and body function well, perhaps optimally, when the individual is in
It turns out that compared to glucose, ketones are a more efficient fuel for cells and also stimulate cells in ways that enhance their performance. For example, we discovered that the ketone beta-hydroxybutyrate stimulates the production of BDNF in neurons in the brain and the BDNF, in turn, enhances learning and memory by strengthening synapses and promoting the formation of new synapses between neurons
We have also published a paper in which we show that IF enhances endurance in runner mice which involves ketones and stimulation of an increase in the number of mitochondria in muscle cells. We find that these beneficial effects of IF are not immediate, but instead require 2-4 weeks. This is important for people who would like to try IF because they have to become adapted to the new intermittent eating pattern before they experience the benefits on brain and body performance.
5. In your papers on intermittent challenges, you present evidence suggesting that intermittent fasting may help negate several disease processes. What diseases are particularly relevant in this respect?
Obesity, diabetes, cardiovascular disease and stroke, epilepsy, Alzheimer’s and Parkinson’s diseases, and cancers.
6. A large part of the reason why intermittent fasting has become so popular is that it has long been touted as being effective for weight loss. Is this reputation well-deserved? In as few words as possible, what’s your interpretation of the science pertaining to intermittent fasting and fat loss?
Yes, IF is effective for weight loss if the person can make it long-term/lifelong eating pattern, and if the person avoids unhealthy foods (i.e. sugar, fructose and saturated fats). The reason for its effectiveness is well-established. People who eat three meals plus snacks spread out through the day may never deplete liver glucose stores and so do not utilize (“burn”) fat. People who have an IF eating pattern burn fat towards the end of the fasting period.
7. There are many possible ways to implement the principles you discuss in your research papers on intermittent fasting into one’s daily life. A popular approach is to fast for 14-18 hours every day, often skipping breakfast, and then eating during a 6-10 hour eating window. However, many other strategies exist, some of which include alternate day fasting or a more unplanned, irregular way of eating. Do you have any thoughts about this aspect of intermittent fasting? Do you favor a particular regimen over others in some instances? What would you recommend to the average Joe or Jen who’s looking to stay fit and healthy?
I would recommend restricting the time window during which one eats each day to 6-8 hours (fasting for 16-18 hours) every day. For
However, our studies with Dr. Michelle Harvie have shown that eating only 500-600 calories (one
8. Intermittent fasting, while certainly being something that people who are looking to enhance their health and well-being should consider incorporating into their lives, is obviously not a panacea. Nor would it be expected to work equally well for everyone. Different subgroups of people would be expected to differ with respects to how they respond to intermittent food abstention. Some people, such as severely sick individuals, bodybuilders, and athletes, for example, have special nutritional requirements. Furthermore, men and women are dissimilar with respects to their physiological design and have historically had different roles and responsibilities. In hunter-gatherer societies, there’s a division of labor, with men doing most of the running and hunting, while women typically stay closer to camp, where they care for the young and collect tubers, berries, and/or fruit, among other things. This would be expected to cause inter-gender differences in adaptations and responses to endurance activity and fasting. Do you have any thoughts about this? I’ve seen it suggested that intermittent fasting may be more prudent for men than for women. As you see it, is this supported by the research? Is there any evidence to suggest that men and women respond differently to intermittent fasting?
This is an important question for which we do not as yet have a definitive answer. IF counteracts aging and extends lifespan in both male and female mice. Both male and female monkeys also benefited from caloric restriction/daily fasting. Our human studies in overweight women and women with asthma have shown that they benefit from IF.
We do not know whether IF is “better” for
9. In your research papers, you’ve talked about other “intermittent challenges” besides intermittent fasting, including exposure to dietary phytochemicals and exercise. Could you briefly talk about some of these challenges/stresses and how they affect our health? If you could relate your answers to our evolutionary journey, then that would be spectacular. I’m particularly interested in hearing about things that generally don’t get much attention/things that most people don’t know much about.
I have proposed that the reason vegetables and fruits are good for health is that they contain chemicals that function to prevent insects, herbivores
However, it was advantageous for herbivores and humans to be able to consume these plant parts because they are a source of energy and other nutrients. And so our cells evolved to respond to these chemicals in ways that protect the cells against the potentially noxious effects of the chemicals.
Indeed, sulforaphane stimulates the production of antioxidant enzymes in cells, and
10. How would you go about implementing the things you discuss in your research on hormesis and intermittent cellular stress into health care and medical training and
Incorporate education of medical students and physicians on the basic science of IF – how it affects energy metabolism, the role of ketones, the adaptive stress responses, etc. This training should include the emerging clinical applications of IF in patients with obesity, diabetes, cardiovascular disease or cancers.
Health insurance should cover outpatient and inpatient programs in which patients can be “coached” on how to change their eating
Employers should encourage healthy lifestyles in their employees and accommodate IF eating patterns be allowing employees to, for example, arrive and begin work one hour earlier than usual, and then allow the employees a 90 minute period midday when they can exercise and then eat. The “dark forces” of the processed food (including the breakfast food) industries and the pharmaceutical industries that encourage unhealthy food consumption and lifestyles should be reigned-in by government-enforced limitations on advertisements.
More from Mark Mattson
Selected books
Mark Mattson has contributed to and edited a number of books. Below are some of the ones that touch on topics related to intermittent fasting and hormesis.
Selected publications
- An Evolutionary Perspective on Why Food Overconsumption Impairs Cognition
- Hallmarks of Brain Aging: Adaptive and Pathological Modification by
Metabolic States - Flipping the Metabolic Switch: Understanding and Applying Health Benefits of Fasting
- Intermittent metabolic switching, neuroplasticity and brain health
- Impact of intermittent fasting on health and disease processes
- How
does hormesis impact biology, toxicology, and medicine? - Challenging Oneself Intermittently to Improve Health
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