How Ketones Boost Brain and Body Health | Dr Mark Mattson

**Benjamin Hopkins** (0:04)
Dr. Mark Mattson, thank you so much for your time in advance.

**Mark Mattson** (0:07)
It's nice to talk to you, Ben. I'm looking forward to it.

**Benjamin Hopkins** (0:09)
As am I. I have been, so I'm 30 years old now, and I've been experimenting with different forms of fasting for probably maybe since I was 17 So a while in the course of my life now. And I got onto it through a guy called, I should forget his name, but he championed the warrior diet, Uri something in his radio.
Yeah, and that was my first.

**Mark Mattson** (0:30)
He was a, actually I have that book. It's Ori Hoffmeckler.

**Benjamin Hopkins** (0:34)
That's it. Thank you.

**Mark Mattson** (0:35)
Ori Hoffmeckler.

**Benjamin Hopkins** (0:37)
Yes. So he was the first sort of approach into that rabbit hole. And I've been experimenting with various different things ever since. You know, I've done one with a day, I've done sort of five day fast, seven day fast, 24 hour fast, all this kind of stuff. And I'm convinced that the benefits of my own personal experience match the data in the sense of all these amazing things I feel and the data is very compelling. However, my first question to you is, are the benefits of intermittent fasting calorie restriction or are they the presence of ketones? Are they glycation slows? Are they inflammation slows down? Or are they simply a whole myriad of things, some we know, some we don't? How do you attribute what mechanisms are at play when it comes to the benefits?

**Mark Mattson** (1:15)
Well, it's all of those.
Right. So the question of whether the benefits of intermittent fasting can be completely attributed to an overall reduction in calorie intake is an important one. And it's been addressed experimentally first by my lab, actually more than 20 years ago, in studies we did in mice, where we had a strain of mice that when we, most of our animal studies, we actually did every other day complete fasting. So they go 24 hours, no food. Then the next day they have food for 24 hours. When that's initiated, when they're young, they live up to 40% longer. So it's like a huge effect in extending lifespan. But that particular strain of mice, on the days they have food, they eat twice as much as they normally would. So their body weight are not different than the animal's pet ad libitum. And yet, there's extension of lifespan and we found some beneficial effects on the brain. And then the first, now the second human study I was involved with was with Michelle Harvey in England. And actually, Ben, the study that I'm going to mention here led quite directly to the popularization of intermittent fasting, to it becoming a thing on the internet. I'll explain how that happened. Michelle Harvey is, well, she's a PhD, she's a dietician, but she works with women at risk for breast cancer because of their metabolic state. Essentially, metabolic health increases risks for all kinds of cancer, including breast cancer.
And also a lot of these women, they have a mom that had breast cancer and they have the genetic predisposition to breast cancer. So in that study, we randomly assigned 100 women to either what's now called 5-2 intermittent fasting. We didn't call that in the study we published, we called it intermittent energy restriction. And then the other 50 women, we had not just no change in their calorie intake, but we had them eat breakfast, lunch, dinner every day, so spread out. And each meal had about 20 to 25% fewer calories than they were normally taken. And we did this calculation that the weekly calorie intake of both groups would be the same. We did two days a week fasting. And anyway, you do the calculation, it comes out the same. And indeed, over six months, groups of women lost the same amount of weight. And both groups had improvements in a lot of health indicators, insulin sensitivity, belly fat, lipid profile, including triglyceride lowering. And but the women on the 5200 men fasting had a statistically significant and it was quite significant, greater benefit in improving insulin sensitivity. So that, to my knowledge, was the first human study where there's dissociation between, now again, calorie restriction alone had benefits. These are overweight women, they're losing weight, but there was a benefit that went beyond calorie intake. There's a lot of studies coming out now, and these are not from my group, it's from many others. The group in Italy actually has some interesting stuff, Antonio Paoli on exercise and intermittent fasting. Because one question is, for someone who's already has a healthy body weight, relatively low body fat, good metabolic status, blood glucose is fine, et cetera, et cetera.