#160 Calorie Restriction VS Intermittent Fasting with Mark Mattson PhD

Mark Mattson (0:00)

So, it turns out, seeing that many, perhaps all of the calorie restriction studies in rats and mice, in which lifespan was extended, are also intermittent fasting studies. So, the way it's done is, all of the food is given to the animal, the rat at the same time, just all at once.

And when they're calorie restricted, it turns out they eat all of that food within four to six hours. So, they're actually fasting for up to 20 hours each day. No one looked at that. They just give the animals the food all at once, and say this is calorie restriction, and didn't really think about the fact that they're eating all their food in a short time period, and they're actually fasting each day.

Siim Land (0:58)

Body Mind Empowerment.

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Mark Mattson (1:07)

Control your mind.

Siim Land (1:10)

Welcome to the Body Mind Empowerment Podcast. I'm your host Siim Land, and our guest today is Mark Mattson. Mark is a professor of neuroscience at John Hopkins University, and he's known for his research on individual fasting. The National Institute of Health considers him one of the world's top experts on the potential cognitive and physical health benefits of individual fasting.

Mark, welcome to the show.

Mark Mattson (1:31)

It's nice to talk to you, Siim.

Siim Land (1:36)

I think you're one of the first people who started researching individual fasting as comprehensive as you did. So can you tell us a little bit about your background as a scientist and how you got into fasting?

Mark Mattson (1:53)

Yeah. As you indicated, I'm a neuroscientist. And originally, most of our work was aimed at understanding how nerve cell circuits form during development of the brain. What are the signaling pathways? And we were discovering that neurotransmitters regulate the growth of axons and dendrites and the formation of synapses. And then one of the neurotransmitters, actually the main excitatory neurotransmitter in the brain is called glutamate. It's an amino acid neurotransmitter.

Turns out that in epilepsy, and we think also to some extent in neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, and even in acute brain insult such as stroke, there's an over-excitation of neurons. Glutamate is still activating its excitatory receptors under conditions where the nerve cells don't have enough energy or otherwise compromised. And so this is called excitotoxicity.

And we did a lot of work trying to understand what leads to the degeneration of neurons in this excitotoxicity process and found there's a major role for calcium.

And we got interested in death of nerve cells then. And then I kind of switched a little bit, but not really completely switched to studying brain aging and neurodegenerative disorders with the notion being that if we can understand what goes wrong, that leads to dysregulation of calcium in neurons, then maybe we can protect the neurons during aging. And then in the 1990s, when I was a professor at the University of Kentucky, we asked a simple question, can a manipulation that increases lifespan of rats or mice modify the disease process and experimental models of Alzheimer's, Parkinson's and stroke? And we settled on an intermittent fasting regimen in which the rats or mice fast for 24 hours every other day. So 24 hours, no food. The next day they have food 24 hours. Keep repeating that. If that started when the animals are young, they live up to 50% longer than they normally would.

And so what we do is we just take rats or mice and divide them into two groups. One group would be on every other day fasting. The control group would have food every day. And then we would subject the animals to conditions that we think are occurring in Alzheimer's, Parkinson's and stroke.

Sometimes it involved neurotoxins. Sometimes it involved genetic models in which, for example, in the Alzheimer's disease models, the mice accumulate amyloid in their brain and they have cognitive impairment. In the Parkinson's models, the animals have degeneration of the dopamine-producing neurons and then they therefore have difficulty in controlling their body movements. And then stroke, we just occlude an artery in the brain transiently, so kind of like a clot forming and then resolving and we get reliable damage to the brain. In all of these models, the animals on intermittent fasting had better outcomes. They had functional outcomes, their cognition was better in the Alzheimer's model, their motor control was better in the Parkinson's model and the stroke model. And then when we looked at the brains, there was less degeneration of neurons. So that was really our first studies on intermittent fasting in animals. And then from there, we just took off looking at molecular and cellular mechanisms that might explain these, what turned out to be quite dramatic neuroprotective effects of intermittent fasting.