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IRA FLATOW, host:

This is TALK OF THE NATION/SCIENCE FRIDAY. I'm Ira Flatow. A bit later in the hour, we'll be talking about mercury in fish, but first, studies in animals as diverse as mice, worms, fish, have shown that when they eat a really low-calorie diet, some major illnesses like heart disease, diabetes, and some cancers, can actually be prevented and the life spans of the animals can be extended. But scientists don't fully understand why this happens and they aren't sure if they'd see the same results in people on such a calorie-restrictive diet. But, now according to a new study in the Journal of the American Medical Association, people in a six-month calorie-restriction diet, showed several improvements in health markers associated with aging. Joining us by phone to talk about the findings of the study and calorie-restriction research is my guest Dr. Eric Ravussin. He's professor at the Pennington Biomedical Research Center in Baton Rouge, Louisiana. Welcome to SCIENCE FRIDAY.

Dr. ERIC RAVUSSIN (Chief, Division of Health and Performance Enhancement; Douglas L. Gordon Chair in Diabetes and Metabolism; Professor, Human Physiology Exercise Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana): Good afternoon, Ira.

FLATOW: Thank you. How stark is it in animals? What kinds of benefits do you see in animals on these calorie-restriction diets?

Dr. RAVUSSIN: I think the most spectacular, at least in rodents, is basically, they live free of cancers. Usually, mice and rats die from cancers, but if you calorie-restrict them like 30, 35, or 40 percent, compared to what they would eat normally, you see them aging longer. I mean, they look younger, even myself, I can see, you know, just the coat of the mice, for example, and especially, they stay free of cancers. And the maximum lifespan, which is basically the tenth upper percentile of those who live the longest, is really extremely expanded.

FLATOW: Hmm. And you have no idea why that is?

Dr. RAVUSSIN: You know, the first observation was made in the ‘30s, 1930, and, of course, there is a lot of research and there are a lot of candidate genes, there are a lot of theories. There are some that we are interested, and we started to test in humans.

FLATOW: Mm hmm. And let's talk about those tests. You can't do exactly the same tests because the lifespan of a mouse is a lot shorter, isn't it?

Dr. RAVUSSIN: Oh, that's true. I mean, you know, even now, there are some studies in monkeys, and monkeys live normally about 25, Rhesus monkeys, 25 to 28 years. And, of course, a study like this is already a 30 or 40 year study. Now, there are monkeys who have been for more than 15 years on calorie-restriction. Now, of course, in human, there is no way, even the NIH, not in the present time, but anyway, could sponsor a study like that. What is done is, really, to look at biomarkers of aging or longevity.

FLATOW: Mm hmm. So, tell us about the study, how you set it up with people and what you found.

Dr. RAVUSSIN: What we did, this first study was really the first one in non-obese humans, because there is a lot of calorie-restriction done, you know, in obese people for weight loss and so on, and those people were non-obese. And the major point of this first study was really to check if we can enroll people in such a study, can we retain them in such a study, and is that safe. Those were the three first goals of the study. But, of course, when you do a study like that which is quite long and costful, you try to put as much science as you can, and we did a lot of assessment on these people. And, ourself here, we enrolled 48 people, we randomized them blindly to four different groups.

FLATOW: Mm hmm. And that was the total number that you had, so you had about 10 or 12 in each group?

Dr. RAVUSSIN: We had 12 in each group. One was a control group. The other one was, you know, what we can expect to do in humans, 25 percent calorie-restriction. We carefully measured in these 48 people, by different means, we measured their energy requirement at baseline. It took us about two to three months. And then, we dropped the energy intake of these people by 25 percent in one group. Another group, we combined exercise and calorie-restriction. We dropped here, the intake, by 12 and a half percent, but also increased the level of physical activity to account for an excess energy expenditure and, therefore, they had the same energy deficit, but half by calorie restriction and half by increased exercise. And the third one was a group that I wanted to test, because there is always this question, can people adhere to such a calorie restriction. And we decided to drop the weight of these people by a low-calorie diet by 15 percent and then ask them to maintain their weight. Of course, if you maintain your weight at a lower weight, you are in the phase of calorie-restriction, because you eat less than what you needed for your original weight.

FLATOW: Mm hmm. And did you get equal results in all three groups?

Dr. RAVUSSIN: Not exactly. I mean, of course, this study, it was a preliminary study to embark on a longer study that we are finishing to design now, and that we hopefully start in September, and we were limited by power, of course, four groups and 12 subjects per group. But, we found differences. For example, there's no question that calorie restriction seems to bring something more than exercise, for example. And it's been shown in rodents. I mean, you can increase the activity of rodents, on average they live longer, but the maximum lifespan is not extended.

FLATOW: Mm hmm. And so, tell us what kinds of results you got for these trials with people.

Dr. RAVUSSIN: I think the most striking result -- I mean, there are two kinds of results. One was to look at what I said, called biomarkers of aging. You know, it can be the color of your hair, or your number of wrinkles, and so on. But there are some solid biomarkers of longevity, and those are a low insulin level, a low core temperature, or your body temperature, and an increased, what we call, DHEAS, which is a hormone secreted by the adrenal gland. And we looked at these three factors and we found that two of them were modified by calorie restrictions and the two were, your fasting insulin, independent of your weight loss, tended to decrease, and it's been shown in the Baltimore Longitudinal Aging Study to confer, you know, longer life. And, also, that the core temperature was decreased. And these two have been shown to be solid biomarkers of longevity.

FLATOW: Mm hmm.

Dr. RAVUSSIN: Now, the second major question was one of the theory of aging which is, one of the most accepted, but this is only one among many, is that all the aging process at the cellular level is caused by what we call free radicals, or in scientific term, reactive oxygen species. And we found that our marker, again, a damage, was reduced. In other words, there was a lower damage to your building blocks, I mean, I'm sorry, your genetic information in your DNA as a result of this six months of calorie restrictions, which I think is an important finding.

FLATOW: You know, we have heard over the years, the theory that longevity also has to do with the telomeres, the little tips on the ends of the DNA there.

Dr. RAVUSSIN: Yes.

FLATOW: Could you study that too to see if there was a, you know, a change in that?

Dr. RAVUSSIN: No, we didn't in this study. We have DNA, and we could do that, and we have talked about doing that, but in the papers that we published, we didn't do that. But, you know, the length of the telomere is really a function of how many times your cell divides. And, of course, I mean all the cells have been dividing more times. I mean, in older people, and have shorter telomere. But we didn't look at that so far.

FLATOW: 1-800-989-8255 is our number. We're talking with Dr. Eric Ravussin about his study with people and the caloric intake. What will you do now? You say you're trying to put together a longer study. What would you do differently, or how would you just scale this up and do the same thing?

Dr. RAVUSSIN: Yeah. I mean, like I said here, we had three different groups and we were interested in a combination of exercise and calorie restriction. We were interested in this lower energy intake. But now we have chosen one strategy, which is 25 percent of calorie restriction in many more people. And here we will work three sides together, one group in Boston, one group in St. Louis, and our self in Baton Rouge, and enroll approximately 250 people. Means it's the longest study, two years of intervention. It's a larger study, more people. We will randomize them either to this 25 percent calorie restriction, two third of them, and one third of them will serve as control. Because, I mean, a randomized trial always need a controlled group to compare with.

FLATOW: What kind of calorie restriction are we talking about? Is it dramatic? I mean, what is the diet the people ate? I mean was it something they could stay on, or was it like eating twigs, and like that?

Dr. RAVUSSIN: No. I mean of course, we had an outstanding psychology group as well dietary group for these studies. And you can design diets which will not cause hunger at 25 percent calorie restriction. And the trick, of course, is always to decrease the fat. You know, the calorie density is higher for fat, and therefore, the volume for the same number of calories is smaller. If you decrease the fat content, you increase the volume, having the same number of calories or less.

FLATOW: How many calories did the group one have, for example?

Dr. RAVUSSIN: I'm sorry?

FLATOW: How many calories was that 25 percent? How many calories total did that add up to?

Dr. RAVUSSIN: Let's say... it depends, you know. We had females and males. And for the males, maybe the baseline was, I don't have these numbers in front of me, but was about 2800 calories. Now you talk 25 percent of that, it's 560 plus 14, it's about 700 calories less than what they usually eat. That's not drastic.

FLATOW: Right.

Dr. RAVUSSIN: And these people were hungry in the first phase for, you know, four to six weeks. But they really got used to that. And one of the secret of this diet is there is a calorie restriction group and they are very, very emphasizing that there is a nutrition, an optimal nutrition in these diets. In other words, all the essential, you know, nutrients, as well as vitamins and all that, present in the diet and this is very important.

FLATOW: Dr. Ravussin, I want to thank you for taking time to be with us. Dr. Ravussin, professor at the Pennington Biomedical Research Center in Baton Rouge, Louisiana. We're going to take a break. We'll be right back, switch gears, talk more about mercury in food, so stay with us. I'm Ira Flatow. This is TALK OF THE NATION SCIENCE FRIDAY from NPR News.

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