Common Dietary Fat and Intestinal Microbes Linked to Heart Disease

Common Dietary Fat and Intestinal Microbes Linked to Heart Disease

  12:22:00 PM    Science Lover

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A new pathway has been discovered that links a common dietary lipid and intestinal microflora with an increased risk of heart disease, according to a Cleveland Clinic study published in the latest issue of Nature.

Baked goods. Lecithin, and its metabolite, choline, are found in many commercial baked goods, dietary supplements, and even children's vitamins, as well as eggs, liver and other meats, cheese and other dairy products, fish and shellfish. (Credit: iStockphoto)

The study shows that people who eat a diet containing a common nutrient found in animal products (such as eggs, liver and other meats, cheese and other dairy products, fish, shellfish) are not predisposed to cardiovascular disease solely on their genetic make-up, but rather, how the micro-organisms that live in our digestive tracts metabolize a specific lipid -- phosphatidyl choline (also called lecithin). Lecithin and its metabolite, choline, are also found in many commercial baked goods, dietary supplements, and even children's vitamins.

The study examined clinical data from 1,875 patients who were referred for cardiac evaluation, as well as plasma samples from mice. When fed to mice, lecithin and choline were converted to a heart disease-forming product by the intestinal microbes, which promoted fatty plaque deposits to form within arteries (atherosclerosis); in humans, higher blood levels of choline and the heart disease forming microorganism products are strongly associated with increased cardiovascular disease risk.

"When two people both eat a similar diet but one gets heart disease and the other doesn't, we currently think the cardiac disease develops because of their genetic differences; but our studies show that is only a part of the equation," said Stanley Hazen, M.D., Ph.D., Staff in Lerner Research Institute's Department of Cell Biology and the Heart and Vascular Institute's Department of Cardiovascular Medicine and Section Head of Preventive Cardiology & Rehabilitation at Cleveland Clinic, and senior author of the study. "Actually, differences in gut flora metabolism of the diet from one person to another appear to have a big effect on whether one develops heart disease. Gut flora is a filter for our largest environmental exposure -- what we eat."



Dr. Hazen added, "Another remarkable finding is that choline -- a natural semi-essential vitamin -- when taken in excess, promoted atherosclerotic heart disease. Over the past few years we have seen a huge increase in the addition of choline into multi-vitamins -- even in those marketed to our children -- yet it is this same substance that our study shows the gut flora can convert into something that has a direct, negative impact on heart disease risk by forming an atherosclerosis-causing by-product."

In studies of more than 2,000 subjects altogether, blood levels of three metabolites of the dietary lipid lecithin were shown to strongly predict risk for cardiovascular disease: choline (a B-complex vitamin), trimethylamine N-oxide (TMAO, a product that requires gut flora to be produced and is derived from the choline group of the lipid) and betaine (a metabolite of choline).

"The studies identify TMAO as a blood test that can be used in subjects to see who is especially at risk for cardiac disease, and in need of more strict dietary intervention to lower their cardiac risk," Dr. Hazen said.

Healthy amounts of choline, betaine and TMAO are found in many fruits, vegetables and fish. These three metabolites are commonly marketed as direct-to-consumer supplements, supposedly offering increased brain health, weight loss and/or muscle growth.

These compounds also are commonly used as feed additives for cattle, poultry or fish because they may make muscle grow faster; whether muscle from such livestock have higher levels of these compounds remains unknown.

"Knowing that gut flora generates a pro-atherosclerotic metabolite from a common dietary lipid opens up new opportunities for improved diagnostics, prevention and treatment of heart disease," Dr. Hazen said. "These studies suggest we can intelligently design a heart healthy yogurt or other form of probiotic for preventing heart disease in the future. It also appears there is a need for considering the risk vs. benefits of some commonly used supplements."

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How Dark Chocolate May Guard Against Brain Injury from Stroke

How Dark Chocolate May Guard Against Brain Injury from Stroke

  1:02:00 AM    Science Lover

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Researchers at Johns Hopkins have discovered that a compound in dark chocolate may protect the brain after a stroke by increasing cellular signals already known to shield nerve cells from damage.

A compound in dark chocolate may protect the brain 
after a stroke by increasing cellular signals already 
known to shield nerve cells from damage, new 
research shows. (Credit: iStockphoto/Lasse Kristensen)

Ninety minutes after feeding mice a single modest dose of epicatechin, a compound found naturally in dark chocolate, the scientists induced an ischemic stroke by essentially cutting off blood supply to the animals' brains. They found that the animals that had preventively ingested the epicatechin suffered significantly less brain damage than the ones that had not been given the compound.

While most treatments against stroke in humans have to be given within a two- to three-hour time window to be effective, epicatechin appeared to limit further neuronal damage when given to mice 3.5 hours after a stroke. Given six hours after a stroke, however, the compound offered no protection to brain cells.

Sylvain Doré, Ph.D., associate professor of anesthesiology and critical care medicine and pharmacology and molecular sciences at the Johns Hopkins University School of Medicine, says his study suggests that epicatechin stimulates two previously well-established pathways known to shield nerve cells in the brain from damage. When the stroke hits, the brain is ready to protect itself because these pathways -- Nrf2 and heme oxygenase 1 -- are activated. In mice that selectively lacked activity in those pathways, the study found, epicatechin had no significant protective effect and their brain cells died after a stroke.

The study now appears online in the Journal of Cerebral Blood Flow and Metabolism.

Eventually, Doré says, he hopes his research into these pathways could lead to insights into limiting acute stroke damage and possibly protecting against chronic neurological degenerative conditions, such as Alzheimer's disease and other age-related cognitive disorders.

The amount of dark chocolate people would need to consume to benefit from its protective effects remains unclear, since Doré has not studied it in clinical trials. People shouldn't take this research as a free pass to go out and consume large amounts of chocolate, which is high in calories and fat. In fact, people should be reminded to eat a healthy diet with a variety of fruits and vegetables.

Scientists have been intrigued by the potential health benefits of epicatechin by studying the Kuna Indians, a remote population living on islands off the coast of Panama. The islands' residents had a low incidence of cardiovascular disease. Scientists who studied them found nothing striking in the genes and realized that when they moved away from Kuna, they were no longer protected from heart problems. Researchers soon discovered the reason was likely environmental: The residents of Kuna regularly drank a very bitter cocoa drink, with a consistency like molasses, instead of coffee or soda. The drink was high in the compound epicatechin, which is a flavanol, a flavanoid-related compound.

But Doré says his research suggests the amount needed could end up being quite small because the suspected beneficial mechanism is indirect. "Epicatechin itself may not be shielding brain cells from free radical damage directly, but instead, epicatechin, and its metabolites, may be prompting the cells to defend themselves," he suggests.

The epicatechin is needed to jump-start the protective pathway that is already present within the cells. "Even a small amount may be sufficient," Doré says.

Not all dark chocolates are created equally, he cautions. Some have more bioactive epicatechin than others.

"The epicatechin found in dark chocolate is extremely sensitive to changes in heat and light" he says. "In the process of making chocolate, you have to make sure you don't destroy it. Only few chocolates have the active ingredient. The fact that it says 'dark chocolate' is not sufficient."

The new study was supported by grants from the National Institutes of Health and the American Heart and Stroke Association.

Other Johns Hopkins researchers on the study include Zahoor A. Shah, Ph.D.; Rung-chi Li, Ph.D.; Abdullah S. Ahmad, Ph.D.; Thomas W. Kensler, Ph.D.; and Shyam Biswal, Ph.D.

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Men and Women Respond Differently to Stress

Men and Women Respond Differently to Stress

  10:50:00 AM    Science Lover

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Age and gender play a major role in how people respond to stress, according to a new study on 20-to-64-year-olds. Published in the journal Psychophysiology, the investigation was led by scientists from the Université de Montréal and the Montreal Heart Institute in collaboration with colleagues from the Université du Québec à Montréal and McGill University.

"Our findings suggest that women who are more defensive are at increased cardiovascular risk, whereas low defensiveness appears to damage the health of older men," says Bianca D'Antono, a professor at the Université de Montréal Department of Psychiatry and a Montreal Heart Institute researcher.

Defensiveness is a trait characterized by avoidance, denial or repression of information perceived as threatening. In women, a strong defensive reaction to judgment from others or a threat to self-esteem will result in high blood pressure and heart rate. Contrarily, older men with low defensive reactions have a higher cardiovascular rates.

The study was conducted on 81 healthy working men and 118 women. According to Dr. Jean-Claude Tardif a Université de Montréal professor and Montreal Heart Institute researcher, the physiological response to stress in women and older men is linked to this desire of maintaining self-esteem and securing social bonds.

"The sense of belonging is a basic human need," says D'Antono. "Our findings suggest that socialization is innate and that belonging to a group contributed to the survival of our ancestors. Today, it is possible that most people view social exclusion as a threat to their existence. A strong defensive reaction is useful to maintain one's self-esteem faced with this potential threat."

As part of the experiment, participants completed four tasks of varying stress levels. The first task involved reading a neutral text on Antarctica's geography before a person of the same sex. The second and third tasks involved role-playing in which participants followed a script where they were sometimes agreeable and sometimes aggressive. The final task involved a non-scripted debate on abortion.

Heart rate and blood pressure were measured during each of these tasks as was the level of cortisol in saliva. Results showed that women and older men had elevated cardiovascular, autonomic and endocrine responses to stress -- all potentially damaging to their health. The research team cautions, however, that more studies are needed to evaluate the long-term effects of defensiveness and its association to stress response patterns in disease development.

This study was supported by the Canadian Institutes of Health Research and the Fonds de la recherche en santé du Québec.

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'Biological Clock' Could Be a Key to Better Health, Longer Life

'Biological Clock' Could Be a Key to Better Health, Longer Life

  12:45:00 AM    Science Lover

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If you aren't getting a good, consistent and regular night's sleep, a new study suggests it could reduce your ability to handle oxidative stress, cause impacts to your health, increase motor and neurological deterioration, speed aging and ultimately cut short your life.

 

That is, if your "biological clock" genes work the same way as those of a fruit fly. And they probably do.

In research published in the journal Aging, scientists from Oregon State University outline for the first time how a key gene that helps control circadian rhythms can improve the health of aging fruit flies if it is intact, but can result in significant health impacts, up to and including earlier death, if it is absent.

Of particular interest, the research found, was that young fruit flies without this gene were able to handle some stress, but middle-aged and older flies were not.

"We're beginning to identify some of the underlying mechanisms that may help explain why organisms age," said Natraj Krishnan, a research associate in the OSU Department of Zoology. "This study suggests that young individuals may be able to handle certain stresses, but the same insults at an older age cause genetic damage and appear to lead to health problems and earlier death. And it's linked to biological clocks."

It's not completely clear how closely the effects of genetic damage in fruit flies correlate to humans and other animals, Krishnan said, but "the genes themselves, their molecular mechanisms and function is essentially the same, conserved through many millions of years of evolution." The "period" gene in fruit flies, for instance, is also found and expressed in almost every cell in the human body.

This research examined that gene, which is one of four primary genes that help control the biological clock in many animals -- the rhythms that are related to the cycle of day and night, and can be disrupted by anything from inadequate sleep to jet lag or working the swing shift. The study used some normal fruit flies and other mutant flies in which the "period" gene was absent.

The work was done under the leadership of Jadwiga Giebultowicz, an OSU professor of zoology, in collaboration with Dr. Doris Kretzschmar from the Oregon Health and Sciences University. The research was supported by the National Institutes of Health and the Oregon Partnership for Alzheimer's Research.

In control studies, the mutant flies with no functional "period" gene lived just about as long as normal flies, unless they were stressed. In experiments, researchers caused a mild metabolic stress -- an elevated level of reactive oxygen species for 24 hours -- to the flies at various times, which corresponded to their youth, middle age and old age. There was no significant change in the young flies. But in middle-age and older flies, significant damage began to occur.

Mutant flies lost some of their motor ability to climb, and morphologic examinations of their brains showed higher levels of neuronal degeneration, similar to neurodegenerative diseases such as Alzheimer's disease in humans. When exposed to a single stressful event in "middle age," the mutant flies had a 12 percent shorter lifespan than normal flies exposed to the same stress. And when exposed to a single stress in old age, their lifespan was 20 percent shorter.

The study concluded that expression of the "period" gene naturally declines with age. If the same is true for humans, that could help explain why people may lose some of their ability to handle oxidative and other stresses at a time of their life when they need it most.

The scientists theorized that the "period" gene is regulating pathways involved in removal of oxidative damage, and those without this function experienced the symptoms of aging more quickly. This could ultimately have impacts on everything from neurological damage to heart disease and cancer.

"What's worth noting, of course, is that every animal species, unless they are in a protected laboratory, experiences stressful events," Krishnan said. "That's part of a normal life. The metabolic challenge we presented to these fruit flies was only a moderate stress. But even so, it appeared to later cause motor and neuronal degeneration and an earlier death in the mutant flies, due to faster buildup of cellular damage."

Further research will explore ways in which biological clocks might be "re-vitalized."

"Understanding these mechanisms will help to determine in the future whether strong circadian clocks add water to the fountain of youth," the researchers wrote in their conclusion.

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New 'Nanoburrs' Could Help Fight Heart Disease

New 'Nanoburrs' Could Help Fight Heart Disease

  1:03:00 AM    Science Lover

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Building on their previous work delivering cancer drugs with nanoparticles, MIT and Harvard researchers have turned their attention to cardiovascular disease, designing new particles that can cling to damaged artery walls and slowly release medicine.

Researchers have built targeted nanoparticles that can cling to artery walls and slowly release medicine, an advance that potentially provides an alternative to drug-releasing stents in some patients with cardiovascular disease. (Credit: Image courtesy of Massachusetts Institute of Technology)

The particles, dubbed "nanoburrs," are coated with tiny protein fragments that allow them to stick to damaged arterial walls. Once stuck, they can release drugs such paclitaxel, which inhibits cell division and helps prevent growth of scar tissue that can clog arteries.

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