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http://www.docguide.com/news/content.nsf/news/8525697700573E18852570F4006CD182

Caloric Restriction Appears to Prevent Primary Aging in the Heart

ST. LOUIS, WA -- January 12, 2006 -- Eating a very low-calorie yet

nutritionally balanced diet is good for your heart. Studying heart

function in members of an organization called the Caloric Restriction

Society, investigators at Washington University School of Medicine in

St. Louis found that their hearts functioned like the hearts of much

younger people.

The researchers report their findings in the Jan. 17 issue of the

Journal of the American College of Cardiology.

Ultrasound examinations showed that the hearts of people on caloric

restriction appeared more elastic than those of age- and

gender-matched control subjects. Their hearts were able to relax

between beats in a way similar to the hearts in younger people.

" This is the first study to demonstrate that long-term calorie

restriction with optimal nutrition has cardiac-specific effects that

ameliorate age-associated declines in heart function, " says principal

investigator Luigi Fontana, MD, PhD, assistant professor of medicine

at Washington University in St. Louis and an investigator at the

Istituto Superiore di Sanita, Rome, Italy.

Research on mice and rats has shown that stringent and consistent

caloric restriction increases the animals' maximum lifespan by about

30% and protects them against atherosclerosis and cancer, but human

study has been difficult because the caloric restriction lifestyle

requires a strict diet regimen, both to keep the total number of

calories low and to insure that people consume the proper balance of

nutrients.

The researchers studied 25 calorie-restricted individuals who had

voluntarily been consuming a very low-calorie diet for an average of

six years (consuming about 1,400 to 2,000 calories per day). They

ranged in age from 41 to 65. The study compared their heart function

to 25 age- and gender-matched individuals who ate a typical Western

diet (about 2,000 to 3,000 calories per day).

In Western countries, heart attacks and strokes are responsible for

about 40% of all deaths. Cancer causes about another 30%. According to

Dr. Fontana, deaths in both groups can be attributed to what

scientists call secondary aging. That's the term used to characterize

health problems that result from conditions such as high cholesterol,

diabetes, high blood pressure and other preventable conditions that

contribute to premature death. A healthy diet and regular exercise can

reduce risks from secondary aging. But this study suggests calorie

restriction with optimal nutrition can do even more.

Normal aging causes a decline in cardiac performance. Before it pumps

blood to the rest of the body, the heart's left ventricle fills with

blood in a two-phase process. The first phase, which fills the

ventricle in healthy hearts to about 80% capacity, is a passive,

suction-mediated mechanism called early ventricular filling. The

second phase is more active because the heart's atrium contracts to

completely fill the ventricle with blood. As we get older, less blood

gathers during the passive, diastolic phase, so the atrium has to work

harder to increase the amount of blood it forces into the ventricle.

" This decline in diastolic function is a marker of primary aging, " Dr.

Fontana says. " Diastolic function declines in most people as they get

older, but in this study we found that diastolic function in

calorie-restricted people resembled diastolic function in individuals

about 15 years younger. " It may even be possible that eating a very

low-calorie, nutrient dense diet reverses declines in diastolic

function. People in the study averaged only six years on the diet, but

their hearts looked 15 years younger. So Dr. Fontana says it's

possible that the diet has a rejuvenating effect.

He notes that most study subjects had parents, grandparents or

siblings who suffered heart attacks or strokes, making it unlikely

that their genetic makeup is a contributor to the unusual healthiness

of their hearts. In the case of one subject, both parents and younger

brother currently take medication for high blood pressure and high

cholesterol. Some subjects actually took medicine for high blood

pressure themselves before they started on caloric restriction.

Dr. Fontana and colleagues previously have found that people on the

very low-calorie diet have low blood levels of cholesterol and

triglycerides, blood pressure scores equivalent to those of much

younger individuals, a lower risk of developing diabetes and reduced

body fat. These markers indicate less secondary aging.

In this study, Dr. Fontana's team found that markers of inflammation

indicative of primary aging were much lower in the caloric restriction

group. Their serum levels of a pro-inflammatory molecule called tumor

necrosis factor-alpha (TNFa) were significantly lower. They also had

less C-reactive protein (CRP).

In addition, they had lower amounts of a substance called transforming

growth factor-beta (TGFb), a molecule that both helps reverse

inflammation and activates cells called fibroblasts to produce

collagen. If, for example, you cut yourself, your body will work to

repair the damage by activating fibroblasts to produce collagen and

make scar tissue to heal the wound.

Dr. Fontana says the low levels of TNFa, CRP and TGFb, combined with

evidence of " younger " hearts in people on caloric restriction, has led

his research team to hypothesize that inflammation may play a key role

in the aging process.

" Our hypothesis is that low-grade, chronic inflammation is mediating

primary aging, " he says. " It's not the only factor, of course -- aging

is a complex process. But we found less inflammation in these people

-- less TNFa, C-reactive protein and TGFb -- as well as a more

flexible ventricle in their hearts. "

Overweight and obese people also tend to have higher levels of

inflammation than lean people. In this study, those on caloric

restriction had about 7% total body fat. The control group had about

25% body fat.

" It's very clear from these studies that caloric restriction has a

powerful, protective effect against diseases associated with aging, "

says co-investigator O. Holloszy, MD, professor of medicine. " We

don't know how long each individual will end up living, but they

certainly have a longer life expectancy than average because they're

most likely not going to die from a heart attack, stroke or diabetes.

And if, in fact, their hearts are aging more slowly, it's conceivable

they'll live for a very long time. "

Members of the Caloric Restriction Optimal Nutrition Society try to

consume between 10 and 25% fewer calories than average Americans while

still maintaining proper nutrition. Dr. Fontana says that's a very

important point. People on this type of diet don't simply consume less

food.

" Caloric restriction does not mean eating half a hamburger and half a

pack of French fries and drinking half of a sugary beverage, " he says.

" These people have very good nutrition. They eliminate calories by

eating nutrient-dense foods. "

He says caloric restriction tends to resemble a traditional

Mediterranean diet, which includes a wide variety of vegetables, olive

oil, beans, whole grains, fish and fruit. The diet avoids refined and

processed foods, soft drinks, desserts, white bread and other sources

of so-called " empty " calories.

But Dr. Fontana and Dr. Holloszy don't believe that caloric

restriction is for everyone. Instead, they recommend a moderate

reduction in calories, combined with moderate, regular exercise.

" If you change the quality of your diet by increasing the servings of

nutrient-dense food and reducing -- actually, it would be better to

slowly eliminate -- all of the servings of 'empty' calorie foods, you

improve your chances of living a healthier and longer life, " Dr.

Fontana says.

This research was supported by was supported by the National Heart,

Lung and Blood Institute and the National Institute of Diabetes and

Digestive and Kidney Diseases of the National Institutes of Health;

the Whitaker Foundation; the American Heart Association; and the Alan

A and Edith L. Wolff Charitable Trust.

REFERENCE:

Meyer TE, Kovacs SJ, Ehsani AA, Klein S, Holloszy JO, Dr. Fontana L.

Long-term caloric restriction ameliorates the decline in diastolic

function in humans. Journal of the American College of Cardiology,

vol. 47:2, pp. 398-402, Jan. 17, 2006.

SOURCE: Washington University School of Medicine

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