Jon's Health Tips - Reservatrol Pills

Well I’ve done it – I’ve added another pill to my repertoire - Reservatrol Pills. But it’s probably useless according to the expert advice below because it is not enteric coded – but it does meet the other suggestions – it is from Country Life.


Here’s why I have started taking the pill to supplement red wine and other reseveratrol sources – A TV show did it!


Reservatrol Pills - 60 Minutes


"If the promise holds true, I think this has the chance to change healthcare," Dr. Christoph Westphal tells correspondent Morley Safer on 60 Minutes.


Dr. Westphal says we all may soon be taking a drug that just might beat the clock, a simple pill that could delay the inevitable. "Our goal is to prevent and forestall many of the diseases that strike us as we reach 50, 60, and 70. All with one pill."



Asked if he's suggesting that it's some kind of a rejuvenation drug that would turn a 70-year-old into a 35-year-old, Westphal tells Safer, "That might be pretty hard to do. But I think if we're on a train heading one direction, we can slow down that train. I think we can slow down these genes that control the aging process."



That quest to put death on hold began in 2003 when Westphal met David Sinclair, a biochemist at Harvard who was studying the genetic components of aging. "Five years ago I met David. And he had shown that you could extend life span in yeast. That’s pretty exciting," Westphal recalls.



Yeasts are one thing. Human beings are more complicated. So Sinclair focused on a gene present in almost all life forms: the sirtuin gene. It's normally inactive, but when it is active, Sinclair believes it triggers a survival mechanism that extends life.



Convinced that something in nature could activate that gene, Sinclair randomly tested thousands of compounds and got a hit: resveratrol.



"When I Googled this resveratrol, I was shocked to find that red wine was the top hit," Sinclair remembers.



Red wine is brimming with resveratrol. It is found in high concentrations in the skin of the grape, and seems to play a role in protecting it from in ading bacteria and fungi.



Sinclair says he was aware of research into red wine and certain health benefits. "I mean, that's why I almost fell off my chair when the link was made. And I thought that this was a potential explanation for the benefits of red wine."



Convinced they were on the verge of a major scientific breakthrough, Sinclair and Westphal launched Sirtris, a Cambridge, Mass. research company. They, along with a handful of other cutting-edge biotech companies, are developing resveratrol-based drugs that they believe zero-in on the longevity gene.



"The important news here is not that we'd found something in red wine. The important thing is that we passed a milestone where we can now make drugs based on this knowledge and we can potentially slow down aging itself," Sinclair explains. ..



We have a pill that can mimic many of the effects of calorie restriction or exercise," Westphal says.



"So one could be very healthy and obese at the same time," Safer remarks.



"Our goal is healthy individuals, ideally via lifestyle, and if that doesn't work, we believe that we'll have a pill that can mimic that," Westphal replies.



A pill that - in effect - diets for you, a pill that turns on the survival gene.



"What we're trying to do with our drugs here is to put the body in a defensive state to ring the alarm bells and get the body to defend itself instead of dieting to set the alarm off, pop a pill," Sinclair says.



The pill is a highly concentrated form of resveratrol, a virtual vineyard of healthy living. Asked how much red wine one would have to drink to get the kind of resveratrol they are using in their experimental pills, Sinclair says, "Well, the sad news is that you'd need to drink about 1,000 bottles a day of red wine, which I don't recommend."



The pill itself may not extend lifespan but could prevent the diseases of aging, like Alzheimer's, diabetes, heart disease, even cancer. "What we're talking about is activating the body's natural, genetic defenses against diseases. And that's very powerful if we can harness that," Sinclair says. ..



Convinced that they were on the right path, they fast-tracked the drug into human trials on people with untreated diabetes. The results were impressive: it significantly lowered glucose and insulin levels, without the patients changing their diet or taking any other drugs.



"Originally our hope was that you'd be able to prevent diseases of aging. What we ended up seeing is actually you could therapeutically intervene in patients who have diseases of aging. And that was unexpected," Westphal says.



"Yeah, the diabetic patients with high blood sugar, and the molecules bring it down. That's treatment. That's not prevention," Sinclair adds.



Sirtris is now developing what they say is a much more potent synthetic version of resveratrol that will also soon go into human trials, this time on cancer patients.



"I keep on thinking, you know, what used to seem like it was science fiction, I actually believe the biology is right. And if we're right this may be the most important thing that we're going to do in our live," Westphal says.



Possibly. But it is important to remember that nine out of ten drugs that look good in mice ultimately fail in human trials.



Still, the speed and results generated by Sirtris and their resveratrol drugs are unusual, and Sinclair believes these drugs will not only keep people living longer, but will keep them healthy longer. "We're talking about is potentially making a 90-year-old as healthy as a 60-year-old. A 90-year-old can play tennis, and see their great grandkids graduate from college. People will live active, healthy lives and then die quietly in their sleep. And that's really the aim here with these medicines," he says.



Asked if humans are on the edge of maintaining lives into their 100s, Sinclair says, "Well, we certainly passed a corner in terms of the science. And someone's going to achieve it. And if it's not us, it's gonna be someone else."



But the question that most of us want answered is: when do we get this pill?



"I would say five years to be conservative that this'll happen within our lifetimes. I'm fairly certain about that," Sinclair says.



One measure of the potential of this research: Dr. Sinclair and Dr. Westphal’s little start-up company was recently bought by the pharmaceutical giant GlaxoSmithKline for almost three quarters of a billion dollars.



But reservatrol pills are available today. Here’s some advice:



A resveratrol pill should provide 50% trans-resveratrol, the most active form of the nutrient. It should have an enteric coating, so that it makes it to the upper intestine, where it can be readily used by your body.

Here's why those things are important.

There are several types of resveratrol on the market. Some are derived from the skins of red grapes. Others are derived from Japanese knotweed.

The concentration in knotweed is higher than that of other sources. Supplements are sold in liquid, powder and tablet form.

Trans-resveratrol is the most stable form of the nutrient. It is the only one that is useful to the human body.

Liquid and powder supplements are rapidly metabolized into its component parts. They do not increase the levels of trans-resveratrol circulating in the bloodstream.

The same is true of uncoated tablets. So, in order for a resveratrol pill to actually increase the levels of the nutrient in the bloodstream, it must have an enteric coating.

The better companies have websites that fully outline the manufacturing processes and fully disclose the compounds present in the resveratrol pill that they sell. One of the more reputable companies admits that their supplement provides only 20% trans-resveratrol, which requires a higher daily dosage to achieve the same results that one would get with a 50% trans-resveratrol extract.



Resveratrol may protect against radiation exposure



Resveratrol, the natural antioxidant commonly found in red wine and many plants, may offer protection against radiation exposure, according to a study by the University of Pittsburgh School of Medicine. When altered with acetyl, resveratrol administered before radiation exposure proved to protect cells from radiation in mouse models. The results of the research will be presented during the American Society for Therapeutic Radiology and Oncology's (ASTRO) 50th Annual Meeting in Boston.

The study, led by Joel Greenberger, M.D., professor and chairman of the Department of Radiation Oncology at the University of Pittsburgh School of Medicine, is overseen by Pitt's Center for Medical Countermeasures Against Radiation. The center is dedicated to identifying and developing small molecule radiation protectors and mitigators that easily can be accessed and administered in the event of a large-scale radiological or nuclear emergency.

"New, small molecules with radioprotective capacity will be required for treatment in case of radiation spills or even as countermeasures against radiological terrorism," said Dr. Greenberger. "Small molecules which can be easily stored, transported and administered are optimal for this, and so far acetylated resveratrol fits these requirements well."

"Currently there are no drugs on the market that protect against or counteract radiation exposure," he added. "Our goal is to develop treatments for the general population that are effective and non-toxic."

Dr. Greenberger and his team are conducting further studies to determine whether acetylated resveratrol eventually can be translated into clinical use as a radioprotective agent. In 2004, this same team of researchers identified the drug JP4-039, which can be delivered directly to the mitochondria, the energy producing areas of cells. When this occurs, the drug assists the mitochondria in combating radiation-induced cell death.

Jon's Health Tips - Updates #2

Once again, the pace of new health related research reports is overwhelming. Here are updates on alcohol (so distressing that my wife, who has made an effort to have a drink a day, is going on the wagon), tea ( so encouraging I am going to try to drink even more green tea), vitamins and minerals (D and calcium encouraging, E baffling), diet, exercise and apples (all encouraging):



Million women study shows even moderate alcohol consumption associated with increased cancer risk



Low to moderate alcohol consumption among women is associated with a statistically significant increase in cancer risk and may account for nearly 13 percent of the cancers of the breast, liver, rectum, and upper aero-digestive tract combined, according to a report in the February 24 online issue of the Journal of the National Cancer Institute.

With the exception of breast cancer, little has been known about the impact of low to moderate alcohol consumption on cancer risk in women.

To determine the impact of alcohol on overall and site-specific cancer risk, Naomi Allen, D.Phil., of the University of Oxford, U.K., and colleagues examined the association of alcohol consumption and cancer incidence in the Million Women Study, which included 1,280,296 middle-aged women in the United Kingdom. Participants were recruited to the study between 1996 and 2001. Researchers identified cancer cases through the National Health Service Central Registries.

Women in the study who drank alcohol consumed, on average, one drink per day, which is typical in most high-income countries such as the U.K. and the U.S. Very few drank three or more drinks per day. With an average follow-up time of more than 7 years, 68,775 women were diagnosed with cancer.

The risk of any type of cancer increased with increasing alcohol consumption, as did the risk of some specific types of cancer, including cancer of the breast, rectum, and liver. Women who also smoked had an increased risk of cancers of the oral cavity and pharynx, esophagus, and larynx. The type of alcohol consumed--wine versus spirits or other types--did not alter the association between alcohol consumption and cancer risk.

Each additional alcoholic drink regularly consumed per day was associated with 11 additional breast cancers per 1000 women up to age 75; one additional cancer of the oral cavity and pharynx; one additional cancer of the rectum; and an increase of 0.7 each for esophageal, laryngeal, and liver cancers. For these cancers combined, there was an excess of about 15 cancers per 1000 women per drink per day. (The background incidence for these cancers was estimated to be 118 per 1000 women in developed countries.)

"Although the magnitude of the excess abso¬lute risk associated with one additional drink per day may appear small for some cancer sites, the high prevalence of moderate alco¬hol drinking among women in many populations means that the proportion of cancers attributable to alcohol is an important public health issue," the authors write.

In an accompanying editorial, Michael Lauer M.D., and Paul Sorlie, Ph.D., of the National Heart, Lung, and Blood Institute, in Bethesda, M.D., emphasize that these new results derived from such a large study population should give readers pause. Although previous epidemiological studies have suggested that there is a cardiovascular benefit associated with moderate alcohol consumption, the excess cancer risk identified in the current study may outweigh that benefit. "From a standpoint of cancer risk, the message of this report could not be clearer. There is no level of alcohol consumption that can be considered safe," the editorialists write.



Green, black tea can reduce stroke risk



Drinking at least three cups of green or black tea a day can significantly reduce the risk of stroke, a new UCLA study has found. And the more you drink, the better your odds of staving off a stroke.

The study results, published in the online edition of Stroke: Journal of the American Heart Association, were presented Feb. 19 at the American Heart Association's annual International Stroke Conference in San Diego, Calif.

The UCLA researchers conducted an evidence-based review of all human observational studies on stroke and tea consumption found in the PubMed and Web of Science archives. They found nine studies describing 4,378 strokes among nearly 195,000 individuals, according to lead author Lenore Arab, a professor of medicine in the division of general internal medicine and health services research at the David Geffen School of Medicine at UCLA.

"What we saw was that there was a consistency of effect of appreciable magnitude," said Arab, who is also a professor of biological chemistry. "By drinking three cups of tea a day, the risk of a stroke was reduced by 21 percent. It didn't matter if it was green or black tea."

And extrapolating from the data, the effect appears to be linear, Arab said. For instance, if one drinks three cups a day, the risk falls by 21 percent; follow that with another three cups and the risk drops another 21 percent.

This effect was found in tea made from the plant Camellia sinensis, not from herbal teas.

There are very few known ways to reduce the risk of stroke, Arab said. And developing medications for stroke victims is particularly challenging, given that the drug has to get to the stroke-damaged site quickly because damage occurs so fast. Arab said that by the time a stroke victim gets medical care, it's nearly too late to impede the damage.

"That's why these findings are so exciting," she said. "If we can find a way to prevent the stroke, or prevent the damage, that is simple and not toxic, that would be a great advance."

Though no one is certain which compounds in tea are responsible for this effect, researchers have speculated that the antioxidant epigallocatechin gallate (EGCG) or the amino acid theanine may be what helps. Antioxidants are believed to help prevent coronary artery disease.

"And we do know that theanine is nearly 100-percent absorbed," Arab said. "It gets across the blood-brain barrier and it looks a lot like a molecule that's very similar to glutamate, and glutamate release is associated with stroke.

"It could be that theanine and glutamate compete for the glutamate receptor in the brain," she added.

Although a randomized clinical trial is needed to confirm this effect, the findings suggest that drinking three cups of green or black tea a day could help prevent an ischemic stroke.



Multivitamins Have No Impact on Risk of Cancer Or Heart Disease in Postmenopausal Women

The largest study of its kind concludes that long-term multivitamin use has no impact on the risk of common cancers, cardiovascular disease or overall mortality in postmenopausal women. The results of the Women’s Health Initiative study, led by researchers at Fred Hutchinson Cancer Research Center, were published in the Feb. 9 issue of the Archives of Internal Medicine.

“Dietary supplements are used by more than half of all Americans, who spend more than $20 billion on these products each year. However, scientific data are lacking on the long-term health benefits of supplements,” said lead author Marian L. Neuhouser, Ph.D., an associate member of the Public Health Sciences Division at the Hutchinson Center.

The study focused the effects of multivitamins because they are the most commonly used supplement. “To our surprise, we found that multivitamins did not lower the risk of the most common cancers and also had no impact on heart disease,” she said.

The study assessed multivitamin use among nearly 162,000 women enrolled in the Women’s Health Initiative, one of the largest U.S. prevention studies of its kind designed to address the most common causes of death, disability and impaired quality of life in postmenopausal women. The women were followed for about eight years.

Nearly half of the study participants – 41.5 percent – reported using multivitamins on a regular basis. Multivitamin users were more likely to be white, live in the western United States, have a lower body-mass index, be more physically active and have a college degree or higher as compared to non-users. Multivitamin users also were more likely to drink alcohol and less likely to smoke than non-users, and they reported eating more fruits and vegetables and consuming less fat than non-users.

During the eight-year study period, 9,619 cases of breast, colorectal, endometrial, renal, bladder, stomach, lung or ovarian cancer were reported, as well as 8,751 cardiovascular events and 9,865 deaths. The study found no significant differences in risk of cancer, heart disease or death between the multivitamin users and non-users.

These findings are consistent with most previously published results regarding the lack of health benefits of multivitamins, Neuhouser said, but this study provides definitive evidence. “The Women’s Health Initiative is one of the largest studies ever done on diet and health. Thus, because we have such a large and diverse sample size, including women from 40 sites across the nation, our results can be generalized to a healthy population.” Since the study did not include men, Neuhouser cautions that the results may not apply to them.

So what advice do Neuhouser and colleagues offer to women who want to make sure they’re getting optimal nutrition? “Get nutrients from food,” she said. “Whole foods are better than dietary supplements. Getting a wide variety of fruits, vegetables and whole grains is particularly important.”



Vitamin E may decrease and increase mortality of male smokers with high dietary vitamin C intake



Six-year vitamin E supplementation decreased mortality by 41% in elderly male smokers who had high dietary vitamin C intake, but increased mortality by 19% in middle-aged smokers who had high vitamin C intake, according to a study published in the American Journal of Epidemiology.

Large-scale controlled trials have not found any overall effects of vitamin E supplementation on the mortality of participants. Nevertheless, the effect of vitamin E on respiratory infections has significantly diverged between different population groups suggesting that the effects of vitamin E may not be uniform over all the population.

Dr. Harri Hemila, and Professor Jaakko Kaprio, of the University of Helsinki, Finland, studied whether the effect of vitamin E supplementation on mortality might diverge between different population groups. They analyzed the data of the large randomized trial (Alpha-Tocopherol Beta-Carotene Cancer Prevention Study) which was conducted in Finland between 1985-1993 and included male smokers aged 50-69 years. There were 3571 deaths in 29,133 participants during the 6-year supplementation of 50 mg/day of vitamin E.

Although vitamin E had no overall effect on mortality, its effect was modified by age and dietary vitamin C intake. Vitamin E had no effect on participants who had low dietary vitamin C intake, less than 90 mg/day. However, in those who had high vitamin C intake, over 90 mg/day, the effect of vitamin E diverged so that it increased mortality in young participants (50-62 years), but decreased mortality in old participants (66-69 years).

The US nutritional recommendations, issued by the prestigious Institute of Medicine, consider that vitamin E is safe in doses up to 1000 mg/day. This new study gives further evidence indicating that in some population groups vitamin E may be harmful in a substantially lower dose, 50 mg/day.

The researchers concluded that "in people younger than 65 years, taking vitamin E supplements should be strongly discouraged, until clear evidence emerges that some population groups of younger or middle-aged people benefit". They also concluded that the effect of vitamin E on elderly people should be further investigated.



Vitamin B and folic acid may reduce risk of age-related vision loss



Taking a combination of vitamins B6 and B12 and folic acid appears to decrease the risk of age-related macular degeneration in women, according to a report in the February 23 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Age-related macular degeneration (AMD) is a leading cause of vision loss in older Americans, according to background information in the article. Treatment options exist for those with severe cases of the disease, but the only known prevention method is to avoid smoking. Recent studies have drawn a connection between AMD and blood levels of homocysteine, an amino acid. High levels of homocysteine are associated with dysfunction of the blood vessel lining, whereas treatment with vitamin B6, vitamin B12 and folic acid appears to reduce homocysteine levels and may reverse this blood vessel dysfunction.

William G. Christen, Sc.D., of Brigham and Women's Hospital and Harvard Medical School, Boston, and colleagues conducted a randomized, double-blind clinical trial involving 5,442 women age 40 and older who already had heart disease or at least three risk factors. Of these, 5,205 did not have AMD at the beginning of the study. In April 1998, these women were randomly assigned to take a placebo or a combination of folic acid (2.5 milligrams per day), pyridoxine hydrochloride (vitamin B6, 50 milligrams per day) and cyanocobalamin (vitamin B12, 1 milligram per day). Participants continued the therapy through July 2005 and were tracked for the development of AMD through November 2005.

Over an average of 7.3 years of treatment and follow-up, 137 new cases of AMD were documented, including 70 cases that were visually significant (resulting in a visual acuity of 20/30 or worse). Of these, 55 AMD cases, 26 visually significant, occurred in the 2,607 women in the active treatment group, whereas 82 of the 2,598 women in the placebo group developed AMD, 44 cases of which were visually significant. Women taking the supplements had a 34 percent lower risk of any AMD and a 41 percent lower risk of visually significant AMD. "The beneficial effect of treatment began to emerge at approximately two years of follow-up and persisted throughout the trial," the authors write.

"The trial findings reported herein are the strongest evidence to date in support of a possible beneficial effect of folic acid and B vitamin supplements in AMD prevention," the authors write. Because they apply to the early stages of disease development, they appear to represent the first identified way—other than not smoking—to reduce the risk of AMD in individuals at an average risk. "From a public health perspective, this is particularly important because persons with early AMD are at increased risk of developing advanced AMD, the leading cause of severe, irreversible vision loss in older Americans."

Beyond lowering homocysteine levels, potential mechanisms for the effectiveness of B vitamins and folic acid in preventing AMD include antioxidant effects and improved function of blood vessels in the eye, they note.



Calcium associated with lower risk of cancer in women



Women with higher intake of calcium appear to have a lower risk of cancer overall, and both men and women with high calcium intakes have lower risks of colorectal cancer and other cancers of the digestive system, according to a report in the February 23 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Calcium is known to benefit bone health, according to background information in the article. Because of this, the Institute of Medicine recommends 1,200 milligrams of calcium for adults age 50 and older, and the 2005 dietary guidelines for Americans recommend 3 cups per day of low-fat or fat-free dairy products. Studies of dairy products, calcium intake and cancer have revealed different results for different cancer sites.

Yikyung Park, Sc.D., of the National Cancer Institute, Bethesda, Md., and colleagues analyzed data from 293,907 men and 198,903 women who participated in the National Institutes of Health-AARP Diet and Health Study. Participants took a food frequency questionnaire when they enrolled in the study between 1995 and 1996, reporting how much and how often they consumed dairy and a wide variety of other foods and whether they took supplements. Their records were then linked with state cancer registries to identify new cases of cancer through 2003.

Over an average of 7 years of follow-up, 36,965 cancer cases were identified in men and 16,605 in women. Calcium intake was not associated with total cancer in men but was in women—the risk decreased in women with intake of up to 1,300 milligrams per day, after which no further risk reduction was observed.

"In both men and women, dairy food and calcium intakes were inversely associated with cancers of the digestive system," the authors write. The one-fifth of men who consumed the most calcium through food and supplements (about 1,530 milligrams per day) had a 16 percent lower risk of these types of cancer than the one-fifth who consumed the least (526 milligrams per day). For women, those in the top one-fifth of calcium consumption (1,881 milligrams per day) had a 23 percent lower risk than those in the bottom one-fifth (494 milligrams per day). The decreased risk was particularly pronounced for colorectal cancer. Calcium and dairy food intake was not associated with prostate cancer, breast cancer or cancer in any other anatomical system besides the digestive system.

"Dairy food, which is relatively high in potentially anticarcinogenic nutrients such as calcium, vitamin D and conjugated linoleic acid, has been postulated to protect against the development of colorectal and breast cancer," the authors write. Calcium has been shown to reduce abnormal growth and induce normal turnover among cells in the gastrointestinal tract and breast. In addition, it binds to bile and fatty acids, potentially reducing damage to the mucous membrane in the large intestine.

"In conclusion, our findings suggest that calcium intake consistent with current recommendations is associated with a lower risk of total cancer in women and cancers of the digestive system, especially colorectal cancer, in both men and women," the authors write.





Multivitamins Have No Impact on Risk of Cancer Or Heart Disease in Postmenopausal Women

The largest study of its kind concludes that long-term multivitamin use has no impact on the risk of common cancers, cardiovascular disease or overall mortality in postmenopausal women. The results of the Women’s Health Initiative study, led by researchers at Fred Hutchinson Cancer Research Center, were published in the Feb. 9 issue of the Archives of Internal Medicine.

“Dietary supplements are used by more than half of all Americans, who spend more than $20 billion on these products each year. However, scientific data are lacking on the long-term health benefits of supplements,” said lead author Marian L. Neuhouser, Ph.D., an associate member of the Public Health Sciences Division at the Hutchinson Center.

The study focused the effects of multivitamins because they are the most commonly used supplement. “To our surprise, we found that multivitamins did not lower the risk of the most common cancers and also had no impact on heart disease,” she said.

The study assessed multivitamin use among nearly 162,000 women enrolled in the Women’s Health Initiative, one of the largest U.S. prevention studies of its kind designed to address the most common causes of death, disability and impaired quality of life in postmenopausal women. The women were followed for about eight years.

Nearly half of the study participants – 41.5 percent – reported using multivitamins on a regular basis. Multivitamin users were more likely to be white, live in the western United States, have a lower body-mass index, be more physically active and have a college degree or higher as compared to non-users. Multivitamin users also were more likely to drink alcohol and less likely to smoke than non-users, and they reported eating more fruits and vegetables and consuming less fat than non-users.

During the eight-year study period, 9,619 cases of breast, colorectal, endometrial, renal, bladder, stomach, lung or ovarian cancer were reported, as well as 8,751 cardiovascular events and 9,865 deaths. The study found no significant differences in risk of cancer, heart disease or death between the multivitamin users and non-users.

These findings are consistent with most previously published results regarding the lack of health benefits of multivitamins, Neuhouser said, but this study provides definitive evidence. “The Women’s Health Initiative is one of the largest studies ever done on diet and health. Thus, because we have such a large and diverse sample size, including women from 40 sites across the nation, our results can be generalized to a healthy population.” Since the study did not include men, Neuhouser cautions that the results may not apply to them.

So what advice do Neuhouser and colleagues offer to women who want to make sure they’re getting optimal nutrition? “Get nutrients from food,” she said. “Whole foods are better than dietary supplements. Getting a wide variety of fruits, vegetables and whole grains is particularly important.”



Vitamin E may decrease and increase mortality of male smokers with high dietary vitamin C intake



Six-year vitamin E supplementation decreased mortality by 41% in elderly male smokers who had high dietary vitamin C intake, but increased mortality by 19% in middle-aged smokers who had high vitamin C intake, according to a study published in the American Journal of Epidemiology.

Large-scale controlled trials have not found any overall effects of vitamin E supplementation on the mortality of participants. Nevertheless, the effect of vitamin E on respiratory infections has significantly diverged between different population groups suggesting that the effects of vitamin E may not be uniform over all the population.

Dr. Harri Hemila, and Professor Jaakko Kaprio, of the University of Helsinki, Finland, studied whether the effect of vitamin E supplementation on mortality might diverge between different population groups. They analyzed the data of the large randomized trial (Alpha-Tocopherol Beta-Carotene Cancer Prevention Study) which was conducted in Finland between 1985-1993 and included male smokers aged 50-69 years. There were 3571 deaths in 29,133 participants during the 6-year supplementation of 50 mg/day of vitamin E.

Although vitamin E had no overall effect on mortality, its effect was modified by age and dietary vitamin C intake. Vitamin E had no effect on participants who had low dietary vitamin C intake, less than 90 mg/day. However, in those who had high vitamin C intake, over 90 mg/day, the effect of vitamin E diverged so that it increased mortality in young participants (50-62 years), but decreased mortality in old participants (66-69 years).

The US nutritional recommendations, issued by the prestigious Institute of Medicine, consider that vitamin E is safe in doses up to 1000 mg/day. This new study gives further evidence indicating that in some population groups vitamin E may be harmful in a substantially lower dose, 50 mg/day.

The researchers concluded that "in people younger than 65 years, taking vitamin E supplements should be strongly discouraged, until clear evidence emerges that some population groups of younger or middle-aged people benefit". They also concluded that the effect of vitamin E on elderly people should be further investigated.



Vitamin B and folic acid may reduce risk of age-related vision loss



Taking a combination of vitamins B6 and B12 and folic acid appears to decrease the risk of age-related macular degeneration in women, according to a report in the February 23 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Age-related macular degeneration (AMD) is a leading cause of vision loss in older Americans, according to background information in the article. Treatment options exist for those with severe cases of the disease, but the only known prevention method is to avoid smoking. Recent studies have drawn a connection between AMD and blood levels of homocysteine, an amino acid. High levels of homocysteine are associated with dysfunction of the blood vessel lining, whereas treatment with vitamin B6, vitamin B12 and folic acid appears to reduce homocysteine levels and may reverse this blood vessel dysfunction.

William G. Christen, Sc.D., of Brigham and Women's Hospital and Harvard Medical School, Boston, and colleagues conducted a randomized, double-blind clinical trial involving 5,442 women age 40 and older who already had heart disease or at least three risk factors. Of these, 5,205 did not have AMD at the beginning of the study. In April 1998, these women were randomly assigned to take a placebo or a combination of folic acid (2.5 milligrams per day), pyridoxine hydrochloride (vitamin B6, 50 milligrams per day) and cyanocobalamin (vitamin B12, 1 milligram per day). Participants continued the therapy through July 2005 and were tracked for the development of AMD through November 2005.

Over an average of 7.3 years of treatment and follow-up, 137 new cases of AMD were documented, including 70 cases that were visually significant (resulting in a visual acuity of 20/30 or worse). Of these, 55 AMD cases, 26 visually significant, occurred in the 2,607 women in the active treatment group, whereas 82 of the 2,598 women in the placebo group developed AMD, 44 cases of which were visually significant. Women taking the supplements had a 34 percent lower risk of any AMD and a 41 percent lower risk of visually significant AMD. "The beneficial effect of treatment began to emerge at approximately two years of follow-up and persisted throughout the trial," the authors write.

"The trial findings reported herein are the strongest evidence to date in support of a possible beneficial effect of folic acid and B vitamin supplements in AMD prevention," the authors write. Because they apply to the early stages of disease development, they appear to represent the first identified way—other than not smoking—to reduce the risk of AMD in individuals at an average risk. "From a public health perspective, this is particularly important because persons with early AMD are at increased risk of developing advanced AMD, the leading cause of severe, irreversible vision loss in older Americans."

Beyond lowering homocysteine levels, potential mechanisms for the effectiveness of B vitamins and folic acid in preventing AMD include antioxidant effects and improved function of blood vessels in the eye, they note.



Calcium associated with lower risk of cancer in women



Women with higher intake of calcium appear to have a lower risk of cancer overall, and both men and women with high calcium intakes have lower risks of colorectal cancer and other cancers of the digestive system, according to a report in the February 23 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Calcium is known to benefit bone health, according to background information in the article. Because of this, the Institute of Medicine recommends 1,200 milligrams of calcium for adults age 50 and older, and the 2005 dietary guidelines for Americans recommend 3 cups per day of low-fat or fat-free dairy products. Studies of dairy products, calcium intake and cancer have revealed different results for different cancer sites.

Yikyung Park, Sc.D., of the National Cancer Institute, Bethesda, Md., and colleagues analyzed data from 293,907 men and 198,903 women who participated in the National Institutes of Health-AARP Diet and Health Study. Participants took a food frequency questionnaire when they enrolled in the study between 1995 and 1996, reporting how much and how often they consumed dairy and a wide variety of other foods and whether they took supplements. Their records were then linked with state cancer registries to identify new cases of cancer through 2003.

Over an average of 7 years of follow-up, 36,965 cancer cases were identified in men and 16,605 in women. Calcium intake was not associated with total cancer in men but was in women—the risk decreased in women with intake of up to 1,300 milligrams per day, after which no further risk reduction was observed.

"In both men and women, dairy food and calcium intakes were inversely associated with cancers of the digestive system," the authors write. The one-fifth of men who consumed the most calcium through food and supplements (about 1,530 milligrams per day) had a 16 percent lower risk of these types of cancer than the one-fifth who consumed the least (526 milligrams per day). For women, those in the top one-fifth of calcium consumption (1,881 milligrams per day) had a 23 percent lower risk than those in the bottom one-fifth (494 milligrams per day). The decreased risk was particularly pronounced for colorectal cancer. Calcium and dairy food intake was not associated with prostate cancer, breast cancer or cancer in any other anatomical system besides the digestive system.

"Dairy food, which is relatively high in potentially anticarcinogenic nutrients such as calcium, vitamin D and conjugated linoleic acid, has been postulated to protect against the development of colorectal and breast cancer," the authors write. Calcium has been shown to reduce abnormal growth and induce normal turnover among cells in the gastrointestinal tract and breast. In addition, it binds to bile and fatty acids, potentially reducing damage to the mucous membrane in the large intestine.

"In conclusion, our findings suggest that calcium intake consistent with current recommendations is associated with a lower risk of total cancer in women and cancers of the digestive system, especially colorectal cancer, in both men and women," the authors write.





It's no fish tale: Omega-3 fatty acids prevent medical complications of obesity

New article in the FASEB Journal shows how omega-3 fatty acids protect against liver damage and insulin resistance

According to a recent study published online in The FASEB Journal (http://www.fasebj.org), diets rich in omega-3 fatty acids protect the liver from damage caused by obesity and the insulin resistance it provokes. This research should give doctors and nutritionists valuable information when recommending and formulating weight-loss diets and help explain why some obese patients are more likely to suffer some complications associated with obesity. Omega-3 fatty acids can be found in canola oil and fish.

"Our study shows for the first time that lipids called protectins and resolvins derived from omega-3 fatty acids can actually reduce the instance of liver complications, such as hepatic steatosis and insulin resistance, in obese people," stated Joan Claria, a professor from the University of Barcelona and one of the researchers involved in the work.

The scientists found that two types of lipids in omega-3 fatty acids—protectins and resolvins—were the cause of the protective effect. To reach this conclusion, they studied four groups of mice with an altered gene making them obese and diabetic. One group was given an omega-3-enriched diet and the second group was given a control diet. The third group was given docosahexaenoic acid, and the fourth received only the lipid resolvin. After five weeks, blood serum and liver samples from the test mice were examined. The mice given the omega-3-rich diet exhibited less hepatic inflammation and improved insulin tolerance. This was due to the formation of protectins and resolvins from omega-3 fatty acids.

"Doctors are always looking for simple and easy ways to counter the harmful effects of obesity, and the great thing about this study is that the information can be used at dinner tonight," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "It's not unlikely that eating lots more fish or a simple switch to canola oil will make a difference."





People who exercise lower their risk of colon cancer



An ambitious new study has added considerable weight to the claim that exercise can lower the risk for colon cancer. Researchers at Washington University School of Medicine in St. Louis and Harvard University combined and analyzed several decades worth of data from past studies on how exercise affects colon cancer risk. They found that people who exercised the most were 24 percent less likely to develop the disease than those who exercised the least.

"What's really compelling is that we see the association between exercise and lower colon cancer risk regardless of how physical activity was measured in the studies," says lead study author Kathleen Y. Wolin, Sc.D., a cancer prevention and control expert with the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University. "That indicates that this is a robust association and gives all the more evidence that physical activity is truly protective against colon cancer."

Colorectal cancer is the third most common type of cancer. Each year more than 100,000 people in the United States are diagnosed with colon cancer and about 40,000 are diagnosed with rectal cancer. The study suggests that if the American population became significantly more physically active, up to 24 percent, or more than 24,000, fewer cases of colon cancer would occur each year.

Wolin's report was published Feb. 10, 2009 through advance online publication in the British Journal of Cancer. In the study, she and her colleagues gathered the results from all relevant studies published in English on the effect of physical activity on colon cancer risk.

They eliminated from consideration any studies that combined both colon and rectal cancer because exercise has not been shown to affect rectal cancer risk — including such studies would have led to an underestimation of the effect of exercise on colon cancer risk. In all, they analyzed 52 studies going back as far as 1984, making their analysis the most comprehensive to date.

They found that the protective effect of exercise held for all types of physical activity, whether that activity was recreational, such as jogging, biking or swimming, or job related, such as walking, lifting or digging.

"The beneficial effect of exercise holds across all sorts of activities," says Wolin, also assistant professor of surgery. "And it holds for both men and women. There is an ever-growing body of evidence that the behavior choices we make affect our cancer risk. Physical activity is at the top of the list of ways that you can reduce your risk of colon cancer."

The difference between people who were the most physically active and those who were the least varied from study to study in Wolin's analysis. As an example, in a 2007 study by Wolin and colleagues, women who walked the most realized a 23 percent reduction in their risk of colon cancer. Those highly active women walked briskly for five to six hours each week. By comparison, the women in that study who walked the least walked only a half hour each week.

Exercise improves quality of life in postmenopausal women

Exercise appears to improve quality of life in postmenopausal women regardless of whether they lose weight, according to a report in the February 9 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Physical inactivity is a risk factor for various chronic conditions including diabetes mellitus, heart disease, stroke and several types of cancers, according to background information in the article. Regular physical activity is often reported to improve mood, reduce stress and increase energy levels, all of which are measurements of quality of life. However, these claims are largely derived from studies composed of participants with serious illnesses and have not been confirmed in healthy populations.

Corby K. Martin, Ph.D., of the Pennington Biomedical Research Center and Louisiana State University System, Baton Rouge and colleagues studied the effect of 50 percent, 100 percent and 150 percent of current public health physical activity recommendations on quality of life in 430 sedentary postmenopausal women (average age 57.4). Participants were randomly assigned to a non-exercise control group (n=92) or one of three exercise groups: exercise energy expenditure of 4 kilocalories per kilogram (2.2 pounds) of body weight per week (4-KKW) (n=147), 8-KKW (n=96) or 12-KKW (n=95). A short health survey was used to measure physical and mental aspects of quality of life at the beginning of the study and six months later.

“Adherence to exercise was 95.4 percent, 88.1 percent and 93.7 percent for the 4-, 8- and 12-KKW groups, respectively, and each group spent 73.9, 138.3 and 183.6 minutes per week exercising,” the authors write. The average weight loss in the control, 4-KKW, 8-KKW and 12-KKW groups was 0.94 kilograms (2.07 pounds), 1.34 kilograms (2.95 pounds), 1.86 kilograms (4.10 pounds) and 1.34 kilograms (2.95 pounds), respectively.

“A dose-response effect of exercise on quality of life was noted for all aspects of quality of life except bodily pain,” they note. “In addition, the 4-KKW group had significantly improved general health perception, vitality and mental health compared with the control group. All three exercise groups had significantly improved social functioning compared with the control group.”

“Our results indicate that improved quality of life can be added to the list of exercise benefits and that these improvements are dose dependent and independent of weight loss, at least among people similar to this study’s sample,” the authors conclude. “The exercise doses are easily obtainable and were well tolerated by sedentary women, resulting in confidence that the exercise doses used in this study can be achieved by women in the community.”

Vigorous Exercise May Help Prevent Vision Loss

There's another reason to dust off those running shoes. Vigorous exercise may help prevent vision loss, according to a pair of studies from the U.S. Department of Energy's Lawrence Berkeley National Laboratory. The studies tracked approximately 31,000 runners for more than seven years, and found that running reduced the risk of both cataracts and age-related macular degeneration.

The research, which is among the first to suggest that vigorous exercise may help prevent vision loss, offers hope for people seeking to fend off the onset of eye disease.

"In addition to obtaining regular eye exams, people can take a more active role in preserving their vision," says Paul Williams, an epidemiologist in Berkeley Lab's Life Sciences Division who conducted the research. "The studies suggest that people can perhaps lessen their risk for these diseases by taking part in a fitness regimen that includes vigorous exercise."

A cataract, which is a cloudy opacity of the eye lens, is the leading cause of blindness. More than one-half of people in the U.S. over the age of 65 suffer from some form of cataracts. Age-related macular degeneration, which is damage to the retina, is the leading cause of irreversible vision loss in older white Americans, affecting 28 percent of people aged 75 and older.

The diseases have several known risk factors, such as sunlight exposure and diabetes in the case of cataracts, but few interventions. Now, it appears that vigorous cardiovascular exercise may be one way to derail the diseases.

To conduct the research, Williams analyzed data collected in the National Runners' Health Study, which he established in 1991 to determine the health benefits of running.

In this case, he followed approximately 29,000 male runners and 12,000 female runners for more than seven years. Of these people, 733 men reported being diagnosed with cataracts on a questionnaire filled out at the end of the study. Too few women reported cataracts to track.

Men who ran more than 5.7 miles per day had a 35 percent lower risk of developing cataracts than men who ran less than 1.4 miles per day. The study also analyzed men's 10-kilometer race performances, which is a good indicator of overall fitness. The fittest men boasted one-half the risk of developing cataracts compared to the least-fit men.

A second study found that running appeared to reduce the risk of age-related macular degeneration. In the study, 152 men and women reported being diagnosed with the disease. Compared to people who ran less than 1.2 miles per day, people who averaged between 1.2 and 2.4 miles per day had a 19 percent lower risk for the disease, and people who ran more than 2.4 miles per day had between 42 percent and 54 percent lower risk of the disease.

"These findings are compelling because of the large size of the study, and the fact that we are looking at something that is fairly well defined: vigorous exercise, as opposed to more moderate exercise," says Williams.

Most of the runners in the study exceeded the current public health recommendations for physical activity, which is at least 30 minutes of moderate-intensity activities such as brisk walking five days a week, or smaller doses of more vigorous exercise such as running. It is unclear whether people might also lower their risk for cataracts and age-related macular degeneration by walking.

"We know there are important health benefits to walking, including lowering heart disease risk," says Williams. "It is quite likely that the studies' results might apply to a lesser extent to smaller doses of more moderate exercise."

Williams also adds that further research is needed to explore why there is a link between vigorous exercise and a decreased risk for eye disease.

"We know some of the physiological benefits of exercise, and we know about the physiological background of these diseases, so we need to better understand where there's an overlap," says Williams.

High-Fat Diets Inflame Fat Tissue Around Blood Vessels, Contribute to Heart Disease



A study by researchers at the University of Cincinnati shows that high-fat diets, even if consumed for a short amount of time, can inflame fat tissue surrounding blood vessels, possibly contributing to cardiovascular disease.



These findings will be published in the Feb. 20 edition of the American Heart Association journal Circulation Research.



Neal Weintraub, MD, and colleagues examined adipose tissue—or fat—surrounding the coronary arteries of humans. The researchers found these fat cells to be highly inflamed, suggesting that they could trigger inflammation of the blood vessels, an important component of atherosclerosis.



They also found that the inflammation of fat tissues around the arteries of mice is increased by feeding the animals a high-fat diet for just two weeks.



“This is independent of weight gain or blood lipids—cholesterol levels,” says Weintraub, senior author of the study and chair of the cardiovascular diseases division at UC.



Weintraub says that high fat diets contribute to atherosclerosis—or the hardening of arteries—in a number of ways.



“Elevated blood lipids—or cholesterol levels—can worsen with the intake of high fat diets, and this is known to contribute to atherosclerosis,” he says. “However, many patients who consume high fat diets do not exhibit abnormal lipid profiles but still develop atherosclerosis nonetheless.



“These new findings suggest a direct link between poor dietary habits and inflammation of blood vessels, mediated by the fat cells surrounding the blood vessel wall.”



Weintraub adds that the diet fed to the mouse models was not unlike the diets consumed by many Americans.



“It produced striking abnormalities of the fat tissue surrounding blood vessels in a very short period of time,” he says. “This is a warning to those who say there isn’t a problem because their weight and cholesterol levels are under control. Lipid profiles don’t hold all the answers.



“Bad dietary habits can lead to a number of problems, and this suggests that a high fat diet is detrimental in ways we didn’t previously understand.”



Weintraub says there is no real way to measure the effects of poor dietary habits on fat tissue surrounding blood vessels.



“We don’t know why these cells are so responsive to high-fat diets,” he says. “We must now conduct further experiments to answer these types of questions.”



An apple a day can keep the breast-cancer away

Six studies published in the past year by a Cornell researcher add to growing evidence that an apple a day -- as well as daily helpings of other fruits and vegetables -- can help keep the breast-cancer doctor away.

In one of his recent papers, published in the Journal of Agricultural and Food Chemistry (57:1), Rui Hai Liu, Cornell associate professor of food science and a member of Cornell's Institute for Comparative and Environmental Toxicology, reports that fresh apple extracts significantly inhibited the size of mammary tumors in rats -- and the more extracts they were given, the greater the inhibition.

"We not only observed that the treated animals had fewer tumors, but the tumors were smaller, less malignant and grew more slowly compared with the tumors in the untreated rats," said Liu, pointing out that the study confirmed the findings of his preliminary study in rats published in 2007.

In his latest study, for example, he found that a type of adenocarcinoma -- a highly malignant tumor and the main cause of death of breast-cancer patients, as well as of animals with mammary cancer -- was evident in 81 percent of tumors in the control animals. However, it developed in only 57 percent, 50 percent and 23 percent of the rats fed low, middle and high doses of apple extracts (the equivalent of one, three and six apples a day in humans), respectively, during the 24-week study.

"That reflects potent anti-proliferative [rapid decrease] activity," said Liu.

The studies highlight the important role of phytochemicals, known as phenolics or flavonoids, found in apples and other fruits and vegetables. Of the top 25 fruits consumed in the United States, Liu reported in the same journal (56:18) that apples provide 33 percent of the phenolics that Americans consume annually._In a study of apple peel published in the same journal (56:21), Liu reported on a variety of new phenolic compounds that he discovered that also have "potent antioxidant and anti-proliferative activities" on tumors. And in yet another study in the same journal (56:24), he reported on his discovery of the specific modulation effects that apple extracts have on cell cycle machinery. Recently, Liu's group also reported the finding that apple phytochemicals inhibit an important inflammation pathway (NFkB) in human breast cancer cells.

Breast cancer is the most frequently diagnosed invasive cancer and the second leading cause of cancer deaths in women in the United States, said Liu._"These studies add to the growing evidence that increased consumption of fruits and vegetables, including apples, would provide consumers with more phenolics, which are proving to have important health benefits. I would encourage consumers to eat more and a wide variety of fruits and vegetables daily."

Jon's Health Tips - Mediterranean diet

I try to eat a Mediterranean diet, characterized by high intakes of fish, vegetables, legumes, fruits, cereals and unsaturated fatty acids, low intakes of dairy products, meat and saturated fats and moderate alcohol consumption. Here’s why- with some notes on the kinds of food and cooking I try to avoid first:

“Western” diet increases heart attack risk globally

The typical Western diet — fried foods, salty snacks and meat — accounts for about 30 percent of heart attack risk across the world, according to a study of dietary patterns in 52 countries reported in Circulation: Journal of the American Heart Association.

Researchers identified three dietary patterns in the world:
• Oriental: higher intake of tofu, soy and other sauces;
• Prudent: higher intake of fruits and vegetables; and
• Western: higher intake of fried foods, salty snacks, eggs and meat.

The Prudent diet was associated with a lower heart attack risk than the Oriental, researchers said.

“The objective of this study was to understand the modifiable risk factors of heart attacks at a global level,” said Salim Yusuf, D.Phil., the study’s senior author.

Previous studies have reached similar conclusions about the Prudent and Western diet in the United States and Europe. This study broadens those findings and identifies a unique dietary pattern that researchers labeled “Oriental” (because of a higher content of food items typical of an Oriental diet.) The dietary pattern recommended by the American Heart Association is similar to the Prudent diet described in this study.

“This study indicates that the same relationships that are observed in Western countries exist in different regions of the world,” said Yusuf, professor of medicine at McMaster University and director of the Population Health Research Institute at Hamilton Health Sciences in Ontario, Canada.

Researchers analyzed the INTERHEART study, which documents the association of various risk factors and the risk of heart attack in about 16,000 participants in 52 countries. Here, they analyzed 5,761 heart attack cases and compared them to 10,646 people without known heart disease (controls).

The researchers created a dietary risk score questionnaire for heart attacks patients, based on 19 food groups and adjusted it for dietary preferences for each country. Trained medical personnel interviewed the heart attack patients and the control group. The questionnaires included healthy food items (such as fruits and vegetables) and unhealthy food items (such as fried foods and salty snacks).

“A simple dietary score, which included both good and bad foods with the higher score indicating a worse diet, showed that 30 percent of the risk of heart disease in a population could be related to poor diet,” said Romania Iqbal, Ph.D., lead author of the study.

After adjusting for known risk factors, researchers found:
• People who consumed the Prudent diet of more fruits and vegetables had a 30 percent lower risk of heart attack compared to people who ate little or no fruits and vegetables.
• People who consumed the Western diet had a 35 percent greater risk of having a heart attack compared to people who consumed little or no fried foods and meat.
• The Oriental pattern showed no relationship with heart attack risk.

Researchers said that while some components of the Oriental pattern may be protective, others such as the higher sodium content of soy sauces, may increase cardiovascular risk, neutralizing any relationship.

It’s expensive and time-consuming to establish a large and long-term study examining the relationship of diet and heart attack in every region of the world. So the approach of this study is the only feasible way to examine the relationship to diet and heart disease from multiple populations in a relatively short time at an affordable cost, Yusuf said.

Data from this study helped confirm that changes in dietary intake, including the consumption of more fruits and vegetables, can help reduce the risk of having a heart attack in populations worldwide, he said.

“At the same time, an unhealthy dietary intake, assessed by a simple dietary risk score, accounts for nearly one-third of the world population’s attributable risk,” Yusuf said.

French Fries and Potato Chips Are Dangerous

A new study published in the March 2009 American Journal of Clinical Nutrition by Marek Naruszewicz and colleagues from Poland suggests that acrylamide from foods may increase the risk of heart disease. Acrylamide has been linked previously to nervous system disorders and possibly to cancer. After ingesting large amounts of potato chips providing about 157 micrograms of acrylamide daily for four weeks, the participants had adverse changes in oxidized LDL, inflammatory markers and antioxidants that help the body eliminate acrylamide—all of which may increase the risk of heart disease. Additional research is needed in long-term studies of people consuming typical amounts of acrylamide (averaging about 20 to 30 micrograms).

It is recommended that FDA and the food industry continue to decrease acrylamide in foods by improving food processing technologies. FDA reports that acrylamide is particularly high in potato chips and French fries (http://www.cfsan.fda.gov/~dms/acrydata.html). According to American Society for Nutrition Spokesperson Mary Ann Johnson, PhD: "Consumers can reduce their exposure to acrylamide by limiting their intake of potato chips and French fries, choosing a variety of fruits, vegetables, whole grains, and low fat meat and dairy products, and quitting smoking, which is a major source of acrylamide."

Eating red meat sets up target for disease-causing bacteria

Non-human molecules absorbed by eating red meat increase risk of food poisoning in humans
Offering another reason why eating red meat could be bad for you, an international research team, including University of California, San Diego School of Medicine professor Ajit Varki, M.D., has uncovered the first example of a bacterium that causes food poisoning in humans when it targets a non-human molecule absorbed into the body through red meats such as lamb, pork and beef.

In findings to be published on line October 29th in advance of print in the journal Nature, the scientists discovered that a potent bacterial toxin called subtilase cytotoxin specifically targets human cells that have a non-human, cellular molecule on their surface. The molecule –N-glycolylneuraminic acid (Neu5Gc) – is a type of glycan, or sugar molecule, that humans don't naturally produce.

Subtilase cytotoxin is produced by certain kinds of E. coli bacteria, causing bloody diarrhea and a potentially fatal disease called haemolytic uraemic syndrome (HUS) in humans. Humans usually become infected after eating contaminated red meat, which is why this is also known as "hamburger" disease.

Varki, UC San Diego School of Medicine distinguished professor of medicine and cellular and molecular medicine, and co-director of the UCSD Glycobiology Research and Training Center, previously discovered that humans don't produce Neu5Gc because they lack the gene responsible for its production. Therefore, it was thought that humans should be resistant to the toxin.

"Ironically, humans may set themselves up for an increased risk of illness from this kind of E. coli bacteria present in contaminated red meat or dairy, because these very same products have high-levels of Neu5Gc," Varki explained. "The Neu5Gc molecule is absorbed into the body, making it a target for the toxin produced by E. coli."

In the Nature study, the researchers discovered that sites where the Neu5Gc has been incorporated into the human body coincide with toxin binding. "When the toxin binds to the non-human Neu5Gc receptors, it can result in serious food-poisoning and other symptoms in humans," said Varki. The research emphasizes the need for people to eat only well-cook meat or pasteurized dairy products, processes that destroy contaminating bacteria.

Five years ago, Varki and his colleagues at the UC San Diego School of Medicine published a paper in the Proceedings of the National Academy of Sciences describing how Neu5Gc is absorbed into human tissues – including the surface of cells lining the intestines and blood vessels – as a result of eating red meat and milk products. At the time, the researchers also showed that this foreign molecule generates an immune response that could potentially lead to inflammation in human tissues. The UC San Diego study was the first to investigate human dietary absorption of the Neu5Gc glycans which, while not produced in humans, does occur naturally in red meats. Levels are very low or undetectable in fruits, vegetables, eggs, poultry and fish. The researchers proved that people who ingest Neu5Gc incorporate some of it into their tissues, and demonstrated that many generated an immune response against the molecule, conjecturing that a lifetime of gradual incorporation of this glycan "invader" could result in disease.


Fried, Broiled, Grilled Foods = Bad Health

Study shows food preparation may play a bigger role in chronic disease than was previously thought_

How your food is cooked may be as important to your health as the food itself. Researchers now know more about a new class of toxins that might soon become as important a risk factor for heart disease and metabolic disorders as trans fats.

This class of toxins, called advanced glycation end products (AGEs), are absorbed into the body through the consumption of grilled, fried, or broiled animal products, such as meats and cheeses. AGEs, which are also produced when food products are sterilized and pasteurized, have been linked to inflammation, insulin resistance, diabetes, vascular and kidney disease, and Alzheimer’s disease.

A new study at Mount Sinai School of Medicine reveals that AGE levels are elevated in the blood of healthy people, and even more so in older individuals than in younger people. Of particular interest was the finding that a major determinant of the blood levels of AGEs is the amount of AGEs in the diet, not dietary calories, sugar, or fat. The study, which was done in collaboration with, and supported by, the National Institute on Aging (NIA), is published in the April issue of the Journal of Gerontology: Medical Sciences.

"AGEs are quite deceptive, since they also give our food desirable tastes and smells," says Helen Vlassara, MD, senior study author, Director of the Division of Experimental Diabetes and Aging, and Professor of Medicine and Geriatrics at Mount Sinai School of Medicine. "So, consuming high amounts of grilled, broiled, or fried food means consuming significant amounts of AGEs, and AGEs in excess are toxic. People should be given information about their AGE intake and be advised to consider their intake in the same way they would think about their trans fats and salt intake. They should be warned about their AGE levels the way they are about their cholesterol levels or cigarette smoking."_

Inflammation and oxidative stress are more common in older age, so the goal of the study was to assess whether AGEs played a significant role in age-related inflammation and oxidative stress by measuring AGE levels in both young and older individuals. The study involved 172 healthy men and women who were divided into two age groups—those between the ages of 18 and 45 and those between the ages of 60 and 80. Dr. Vlassara and her team also wanted to assess whether AGE levels correlated with dietary intake. To do this, her team recorded the patient’s body weight, body fat, three-day dietary information, and collected blood samples to measure biomarkers of inflammation, such as C-reactive protein (CRP). Blood samples were used to test for two common AGEs, called carboxymethyllysine (CML) and methylglyoxal (MG), which latch on to proteins and fats.

The blood tests showed that AGE levels were 35 percent higher in individuals age 65 and older compared with those younger than age 45. The study also showed that in all of the participants, the higher the consumption of foods rich in AGEs, the higher the blood levels of AGEs, and higher the levels of CRP and other markers of inflammation.

Much to the researchers’ surprise, the study also showed that AGE levels could be very high in young healthy people. In fact, high AGE levels found in some healthy adults in this study were on par with AGE levels observed in diabetic patients in their earlier studies. The fact that healthy adults had levels similar to those seen in diabetic patients may suggest that early and prolonged exposure to these substances in the diet could accelerate the onset of diseases. Dr. Vlassara notes that the availability and consumption of AGE-rich foods is high and correlates with rising rates of diabetes and heart disease.

"Excessive intake of fried, broiled, and grilled foods can overload the body’s natural capacity to remove AGEs," Dr. Vlassara notes, "so they accumulate in our tissues, and take over the body’s own built-in defenses, pushing them toward a state of inflammation. Over time, this can precipitate disease or early aging." Once AGEs enter the body, it becomes more difficult to get them out, especially as people age. Older people have a reduced capacity for removing AGEs from the body, the researchers explain, most likely because kidney function slows down as the body ages.

As Dr. Vlassara cautions, "although the accumulation of AGEs pose an immediate and significant health threat to the older adult population, they are also an invisible, lingering danger especially for younger people and this needs to be addressed. AGE levels should be shown on nutrition labels so everyone is aware of them when buying or preparing meals – and our studies explain why."

A Simple Solution: Steam, Boil, Stew

Despite the ubiquity of AGEs, Dr. Vlassara and her team offer simple, safe, and economic solutions that echo the recommendations given concerning trans fats—watch what you eat. New methods of cooking to reduce AGE intake, particularly steaming, boiling or making stews, can make a difference. "Keeping the heat down and maintaining the water content in food reduces AGE levels," Dr. Vlassara says. A 50 percent reduction in AGE intake could have a significant and positive impact on overall health and may even help extend one’s lifespan, according to Dr. Vlassara. In other studies, the team has found that cutting AGE intake in half, but maintaining a diet comprised of the same calories and fat, increased the lifespan of animals when compared with animals fed their usual diet.

At the moment, changing one’s approaches to cooking is the only defense against excessive AGE consumption. There is no routine clinical test to inform individuals of their blood or dietary AGE levels nor established treatment to reduce high AGE blood levels. "The concept that food-related AGE intake is harmful is new to the general public," says Dr. Vlassara, "and scientists are now seeing how AGE intake fits with the current trends of disease epidemics. Hopefully, these wake-up signals, together with other gathering evidence at the cellular and molecular level, will accelerate our efforts to develop effective measures against excessive dietary AGEs. This issue, however, should be dealt with as an important health hazard now, rather than later."


Tips for Safer Grilling

Ruining a piece of meat isn’t the only thing you need to worry about if you’re cooking at high temperatures. High heat can also produce chemicals with cancer-causing properties, reports the June 2007 issue of the Harvard Health Letter.

When meat is cooked at high temperatures, amino acids react with creatine to form heterocyclic amines, which are thought to cause cancer. That’s why cooking meat by grilling, frying, or broiling is the problem. Grilling is double trouble because it also exposes meat to cancer-causing chemicals contained in the smoke that rises from burning coals and any drips of fat that cause flare-ups. How long the meat is cooked is also a factor in heterocyclic amine formation; longer cooking time means more heterocyclic amines. Depending on the temperature at which it’s cooked, meat roasted or baked in the oven may contain some heterocyclic amines, but it’s likely to be considerably less than in grilled, fried, or broiled meat.

Marinating meat is often suggested as one way to cut down on the formation of heterocyclic amines, but the evidence that marinating helps is mixed. The Harvard Health Letter suggests some other tips that may make grilled meat safer to eat:

• Cook smaller pieces: They cook more quickly and at lower temperatures.
• Choose leaner meat: Less fat should reduce flames and therefore smoke.
• Precook in the microwave: Doing so for two minutes may decrease heterocyclic amines by 90%, according to some research.
• Flip frequently: That way, neither side has time to absorb or lose too much heat.

Boiling Vegetables Ruins Benefits

Researchers at the University of Warwick have found that the standard British cooking habit of boiling vegetables severely damages the anticancer properties of many Brassica vegetables such as broccoli, Brussel sprouts, cauliflower and green cabbage.

Past studies have shown that consumption of Brassica vegetables decreases the risk of cancer. This is because of the high concentration in Brassicas of substances known as glucosinolates which are metabolized to cancer preventive substances known as isothiocyanates. However before this research it was not known how the glucosinolates and isothiocyanates were influenced by storage and cooking of Brassica vegetables.

The researchers, Prof Paul Thornalley from Warwick Medical School at the University of Warwick and Dr Lijiang Song from the University of Warwick’s Department of Chemistry bought Brassica vegetables, (broccoli, Brussel sprouts, cauliflower and green cabbage) from a local store and transported them to the laboratory within 30 minutes of purchasing. The effect of cooking on the glucosinolate content of vegetables was then studied by investigating the effects of cooking by boiling, steaming, microwave cooking and stir-fry.

Boiling appeared to have a serious impact on the retention of those important glucosinolate within the vegetables. The loss of total glucosinolate content after boiling for 30 minutes was: broccoli 77%, Brussel sprouts 58%, cauliflower 75% and green cabbage 65%.

The effects of other cooking methods were investigated: steaming for 0–20 min, microwave cooking for 0–3 min and stir-fry cooking for 0–5 min. All three methods gave no significant loss of total glucosinolate analyte contents over these cooking periods._

Domestic storage of the vegetables at ambient temperature and in a domestic refrigerator showed no significant difference with only minor loss of glucosinolate levels over 7 days._

However the researchers found that storage of fresh vegetables at much lower temperatures such as _85 °C (much higher than for storage in a refrigerator at 4–8 °C) may cause significant loss of glucosinolates up to 33% by fracture of vegetable material during thawing._

The researchers found that preparation of Brassica vegetables had caused only minor reductions in glucosinolate except when they were shredded finely which showed a marked decline of glucosinolate levels with a loss of up to 75% over 6 hours after shredding._

Professor Thornalley said: "If you want to get the maximum benefit from your five portions-a-day vegetable consumption, if you are cooking your vegetables boiling is out. You need to consider stir frying, steaming or micro-waving them."


Mediterranean Diet Associated with Lower Risk of Cognitive Impairment

Eating a Mediterranean diet appears to be associated with less risk of mild cognitive impairment—a stage between normal aging and dementia—or of transitioning from mild cognitive impairment into Alzheimer’s disease, according to a report in the February issue of Archives of Neurology, one of the JAMA/Archives journals.

“Among behavioral traits, diet may play an important role in the cause and prevention of Alzheimer’s disease,” the authors write as background information in the article. Previous studies have shown a lower risk for Alzheimer’s disease among those who eat a Mediterranean diet, characterized by high intakes of fish, vegetables, legumes, fruits, cereals and unsaturated fatty acids, low intakes of dairy products, meat and saturated fats and moderate alcohol consumption.

Nikolaos Scarmeas, M.D., and colleagues at Columbia University Medical Center, New York, calculated a score for adherence to the Mediterranean diet among 1,393 individuals with no cognitive problems and 482 patients with mild cognitive impairment. Participants were originally examined, interviewed, screened for cognitive impairments and asked to complete a food frequency questionnaire between 1992 and 1999.

Over an average of 4.5 years of follow-up, 275 of the 1,393 who did not have mild cognitive impairment developed the condition. Compared with the one-third who had the lowest scores for Mediterranean diet adherence, the one-third with the highest scores for Mediterranean diet adherence had a 28 percent lower risk of developing mild cognitive impairment and the one-third in the middle group for Mediterranean diet adherence had a 17 percent lower risk.

Among the 482 with mild cognitive impairment at the beginning of the study, 106 developed Alzheimer’s disease over an average 4.3 years of follow-up. Adhering to the Mediterranean diet also was associated with a lower risk for this transition. The one-third of participants with the highest scores for Mediterranean diet adherence had 48 percent less risk and those in the middle one-third of Mediterranean diet adherence had 45 percent less risk than the one-third with the lowest scores.
The Mediterranean diet may improve cholesterol levels, blood sugar levels and blood vessel health overall, or reduce inflammation, all of which have been associated with mild cognitive impairment. Individual food components of the diet also may have an influence on cognitive risk. “For example, potentially beneficial effects for mild cognitive impairment or mild cognitive impairment conversion to Alzheimer’s disease have been reported for alcohol, fish, polyunsaturated fatty acids (also for age-related cognitive decline) and lower levels of saturated fatty acids,” they write.

Mediterranean Diet May Help Prevent Prostate Cancer

We recently reviewed evidence relating diet and prostate cancer, suggesting that a traditional Cretan Mediterranean style diet based on a variety of plant foods (fruits, vegetables, wholegrain cereals, nuts and legumes), olive oil as the main source of fat, low intake of red meat, moderate to low intake of dairy foods, moderate to high intake of fish and moderate intake of wine, mostly consumed with meals, may be helpful in reducing prostate cancer risk.

Importantly, the Mediterranean diet has other health benefits that further support its widespread adoption. A recent meta-analysis of prospective cohort studies using an a priori score to assess adherence to a Mediterranean diet found that stronger adherence was associated with reduced all cause, cardiovascular and cancer mortality, as well as decreased incidence of Parkinson’s and Alzheimer’s diseases (1).

Two intervention studies have supported the benefits of a Mediterranean style diet on metabolic risk factors (2) (3). In a Spanish study, men and women with elevated levels of cardiovascular risk factors were randomized to either of two “Mediterranean” diets and provided with either olive oil or nuts, or to a control low fat diet. After 3 months the Mediterranean diet groups had lower mean plasma glucose, systolic blood pressure and total/HDL cholesterol ratio than the control group (2). Italian adults with the Metabolic Syndrome were randomized to a “Mediterranean” diet or a “prudent” diet, both with similar macronutrient composition. The “Mediterranean” diet was associated with greater improvements in markers of vascular risk and endothelial function than the control group (3). It should be noted however that in both studies the “Mediterranean” diet groups received more nutrition education than the control groups.

The Lyon Heart Study demonstrated that a modified Cretan diet low in butter and meats, and high in fish, fruits and enriched with _-linolenic acid from canola oil was more effective than a ‘prudent’ diet in the secondary prevention of coronary events and overall mortality (4). We have also shown that a Cretan style diet reduced HbA1c from a mean of 7.1% (95% CI: 6.5-7.7) to 6.8% (95% CI: 6.3-7.3) (p=0.012), in people with type 2 diabetes (unpublished data).

Simopoulos (5) notes that the traditional Greek diet resembles the Paleolithic diet in terms of fibre, antioxidants, saturated and monounsaturated fat, thus is consistent with human evolution. While traditional diets must reflect the regionally available foods, the characteristics of the traditional Greek diet can be applied in many countries, notwithstanding the likely effect of environment and growing methods on the nutrient composition of plant and animal foods. The evidence suggests that a traditional Greek or Cretan style diet is consistent with what humans have evolved to consume and may protect against common chronic diseases, including prostate cancer.

References:
1. Sofi F, Cesari F, Abbate R, Gensini GF, Casini A. Adherence to Mediterranean diet and health status: meta-analysis. Bmj 2008;337:a1344._2. Estruch R, Martinez-Gonzalez MA, Corella D, et al. Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial. Ann Intern Med 2006;145:1-11._3. Esposito K, Marfella R, Ciotola M, et al. Effect of a Mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial. J Am Med Assoc 2004;292:1440-6._4. de Lorgeril M, Salen P. Modified Cretan Mediterranean diet in the prevention of coronary heart disease and cancer. In: Simopoulos AP, Visioli F, eds. Mediterranean Diets. World Review Nutr Diet. Basel: Karger, 2000:1-23._5. Simopoulos AP. The traditional diet of Greece and cancer. Eur J Cancer Prev 2004;13:219-30.

Mediterranean diet wards off childhood respiratory allergies

Protective effect of fruits, vegetables and the Mediterranean diet on asthma and allergies among children in Crete.
"Mediterranean" diet rich in fruits, vegetables and nuts protects against allergic rhinitis and asthma symptoms, suggests research published ahead of print in Thorax.

The researchers assessed the dietary habits, respiratory symptoms, and allergic reactions of almost 700 children living in four rural areas on the Greek island of Crete.

The children were all aged between 7 and 18 years of age.

Skin allergies are relatively common in Crete, but respiratory allergies, such as asthma and allergic rhinitis are relatively rare.
Parents completed detailed questionnaires on their children's allergic and respiratory symptoms and dietary habits.

Whether the children ate a "Mediterranean" diet was measured against a set of 12 foodstuffs, including fruits, vegetables, whole-grains, legumes, nuts, and olive oil.

Eight out of 10 children ate fresh fruit, and over two thirds of them ate fresh vegetables, at least twice a day.

The effect of diet was strongest on allergic rhinitis, but it also afforded protection against asthma symptoms and skin allergy.
Children who ate nuts at least three times a week were less likely to wheeze.

Nuts are a rich source of vitamin E, the body's primary defence against cellular damage caused by free radicals. And they contain high levels of magnesium, which other research suggests, may protect against asthma and boost lung power.

And a daily diet of oranges, apples, and tomatoes also protected against wheezing and allergic rhinitis.

Grapes in particular seemed to protect against current and previous wheezing and allergic rhinitis, even after adjusting for other potentially influential factors.
Red grape skin contains high levels of antioxidants as well as resveratrol, a potent polyphenol, known to curb inflammatory activity, say the authors.
But high consumption of margarine doubled the chances of asthma and allergic rhinitis, the findings showed.

Adherence to the Mediterranean food pattern helps

Adherence to the Mediterranean food pattern predicts the prevalence of hypertension, hypercholesterolemia, diabetes and obesity, among healthy adults.

A diet score (range 0–55) has been developed that assesses adherence to the Mediterranean diet. For the consumption of items presumed to be close to Mediterranean dietary pattern (non-refined cereals, fruits, vegetables, legumes, olive oil, fish and potatoes) scores 0 to 5 for never, rare, frequent, very frequent, weekly and daily consumption were assigned, while for the consumption of foods presumed to be away from this pattern (red meat and products, poultry and full fat dairy products) scores on a reverse scale were assigned.

The Mediterranean diet was a strong predictor of non-occurence of these diseases.

Mediterranean Diet Halves Risk of Lung Disease

A Mediterranean diet halves the chances of developing progressive inflammatory lung disease (COPD), reveals a large study, published ahead of print in Thorax.

COPD (chronic obstructive pulmonary disease) is an umbrella term for chronic progressive lung disease, such as emphysema and bronchitis. It is expected to become the third leading cause of death worldwide by 2020, with cigarette smoking the primary factor in its development.

The researchers tracked the health of almost 43,000 men, who were already part of the US Health Professionals Follow up Study. This began in 1986 and involved more than 50,000 US health care professionals aged between 40 and 75, who were surveyed every two years.

They were asked questions about lifestyle, including smoking and exercise, diet and medical history. Dietary intake was assessed in detail every four years.

Eating patterns fell into two distinct categories: those who ate a diet rich in fruit, vegetables, whole grains and fish (Mediterranean diet); and those who ate a diet rich in processed foods, refined sugars, and cured and red meats (Western diet).
Between 1986 and 1998, 111 cases of COPD were newly diagnosed.

The Mediterranean diet was associated with a 50% lower risk of developing COPD than the Western diet, even after adjusting for age, smoking, and other risk factors.

And men who ate a predominantly Western diet were more than four times as likely to develop COPD, even after taking account of other influential factors.

The higher the compliance with a Mediterranean diet, the lower was the risk of developing COPD over the 12 year period.
Conversely, the higher the compliance with the Western diet, the higher was the risk of developing COPD.

Mediterranean diet and physical activity each associated with lower death rate over 5 years

Eating a Mediterranean diet and following national recommendations for physical activity are each associated with a reduced risk of death over a five-year period, according to two reports in the December 10/24 issue of Archives of Internal Medicine, one of the JAMA/Archives journals. Both studies use data from the National Institutes of Health-AARP Diet and Health Study, which began when questionnaires were returned from 566,407 AARP members age 50 to 71 in six states between 1995 and 1996.

In one study, Panagiota N. Mitrou, Ph.D., then of the National Cancer Institute, Bethesda, Md., and now of the University of Cambridge, England, and colleagues used a nine-point scale to assess conformity with the Mediterranean diet in 380,296 of the participants (214,284 men and 166,012 women) with no history of chronic disease. Components of the diet included vegetables, legumes, fruits, nuts, whole grains, fish, ratio of monounsaturated fats, alcohol and meat. During five years of follow-up, 12,105 participants died, including 5,985 from cancer and 3,451 from cardiovascular disease. Those with higher Mediterranean diet scores were less likely to die of any cause or of cancer or heart disease.

Fruit and vegetable intake and head and neck cancer

Fruit and vegetable intake and head and neck cancer in a large United States prospective cohort study: Abstract 849
A new study among AARP members shows that just one additional serving of fruit and vegetables per day may lower your risk of head and neck cancer, but the data suggest that you may not want to stop at just one, according to researchers from the National Cancer Institute.

A large prospective study of 500,000 men and women aged 50 and older has found that those who ate more fruit and vegetables had a reduced risk of head and neck cancer. Head and neck cancer is the sixth leading cause of cancer-related mortality worldwide, resulting in more than 350,000 deaths annually.

"Identifying protective factors for head and neck cancer is particularly important as it has a high mortality rate," said Neal Freedman, Ph.D., cancer prevention fellow at the National Cancer Institute.

At the beginning of the study, participants reported their typical dietary habits on a food frequency questionnaire. Freedman and his colleagues followed participants for five years and recorded all diagnoses of head and neck cancer cases during this time.

In their findings, the researchers report that participants who ate six servings of fruit and vegetables per day per 1000 calories had 29 percent less risk for head and neck cancer than did participants who consumed one and a half servings per 1000 calories per day. Typically, adults consume approximately 2000 calories per day. One serving equals approximately one medium sized fresh fruit, one half cup of cut fruit, six ounces fruit juice, one cup leafy vegetables, or one half cup of other vegetables.

"Increasing consumption by just one serving of fruit or vegetables per 1000 calories per day was associated with a six percent reduction in head and neck cancer risk," Freedman said.

According to Freedman, people who ate a lot of fruit also tended to eat a lot of vegetables, and vice versa. To measure these two types of foods independently, the researchers included both fruit and vegetable intake in the statistical models, a common statistical approach. This allowed them to compare participants with different levels of fruit consumption while holding constant the level of vegetable intake and vice versa. When examining fruit and vegetable intake simultaneously, the protective association with vegetables seemed to be stronger than the association with fruits.

"Although we cannot absolutely rule out a cancer preventive role for other lifestyle factors that go along with eating more fruits and vegetables, our results are consistent with those from previous studies," Freedman said. "Our study suggests that fruit and vegetable consumption may protect against head and neck cancer and adds support to current dietary recommendations to increase fruit and vegetable consumption."

Flavonols and pancreatic cancer risk

A study of food consumption in 183,518 residents of California and Hawaii has found that a diet high in flavonols might help reduce pancreatic cancer risk, especially in smokers. These compounds are generally ubiquitous in plant-based foods, but are found in highest concentrations in onions, apples, berries, kale and broccoli.

People who ate the largest amounts of flavonols had a 23 percent reduced risk of developing pancreatic cancer compared to those who ate the least, according to a research team led by Laurence Kolonel, M.D., Ph.D., at the Cancer Research Center of Hawaii.

Smokers gained the most benefit. Those who ate the most flavonols reduced their risk of developing pancreatic cancer by 59 percent, compared to those who ate the least, says the study’s lead author, Ute Nöthlings, DrPH, who conducted the study as a postdoctoral fellow in Hawaii and is now a researcher at the German Institute of Human Nutrition Potsdam-Rehbruecke.

‘The effect was largest in smokers, presumably because they are at increased pancreatic cancer risk already," said Nöthlings. Smoking is the only established risk factor for pancreatic cancer, and "short of stopping tobacco use, it has been difficult to consistently show lifestyle factors that might help protect against this deadly cancer," she says.

As part of a larger research project known as The Multiethnic Cohort Study, Kolonel and Nöthlings followed the participants for an average of eight years after they filled out a comprehensive food questionnaire.

Although Nöthlings says the study has a large statistical power because of the large number of pancreatic cancer cases (529) that occurred in the study population, she says that this one study cannot firmly answer the question of whether flavonols can prevent development of pancreatic cancer. "Further epidemiological studies in other populations and geographic regions are needed to confirm our findings," she said.

The study also is the first to examine prospectively specific classes of flavonols and pancreatic cancer risk.

The researchers looked at consumption of three flavonols: quercetin, which is most abundant in onions and apples; kaempferol, found in spinach and some cabbages; and myricetin, found mostly in red onions and berries.

Of the three individual flavonols, kaempferol was associated with the largest risk reduction (22 percent) across all participants. When the researchers divided intake into quartiles, and then compared highest intake to lowest, all the three classes of flavonols were associated with a significant trend toward reduced pancreatic cancer risk in current smokers, but not in never or former smokers. The interaction with smoking status was statistically significant for total flavonols, quercetin and kaempferol.

The researchers say their study did not examine the biological mechanisms by which these flavonols could exert a protective effect against pancreatic cancer. "But anti-carcinogenic effects of flavonoids in general have been attributed to the ability of these constituents to inhibit cell cycle, cell proliferation and oxidative stress, and to induce detoxification enzymes and apoptosis," Nöthlings said.

Studies Force New View on Biology, Nutritional Action of Flavonoids

Flavonoids, a group of compounds found in fruits and vegetables that had been thought to be nutritionally important for their antioxidant activity, actually have little or no value in that role, according to an analysis by scientists in the Linus Pauling Institute at Oregon State University.

However, these same compounds may indeed benefit human health, but for reasons that are quite different – the body sees them as foreign compounds, researchers say, and through different mechanisms, they could play a role in preventing cancer or heart disease.

Based on this new view of how flavonoids work, a relatively modest intake of them – the amount you might find in a healthy diet with five to nine servings of fruits and vegetables – is sufficient. Large doses taken via dietary supplements might do no additional good; an apple a day may still be the best bet.

A research survey, and updated analysis of how flavonoids work and function in the human body, were recently published in Free Radical Biology and Medicine, a professional journal.

“What we now know is that flavonoids are highly metabolized, which alters their chemical structure and diminishes their ability to function as an antioxidant,” said Balz Frei, professor and director of the Linus Pauling Institute. “The body sees them as foreign compounds and modifies them for rapid excretion in the urine and bile.”

Flavonoids are polyphenolic compounds with some common characteristics that are widely found in fruits and vegetables and often give them their color – they make lemons yellow and certain apples red. They are also found in some other foods, such as coffee, tea, wine, beer and chocolate, and studies in recent years had indicated that they had strong antioxidant activity – and because of that, they might be important to biological function and health.

“If you measure the activity of flavonoids in a test tube, they are indeed strong antioxidants,” Frei said. “Based on laboratory tests of their ability to scavenge free radicals, it appears they have 3-5 times more antioxidant capacity than vitamins C or E. But with flavonoids in particular, what goes on in a test tube is not what’s happening in the human body.”

Research has now proven that flavonoids are poorly absorbed by the body, usually less than five percent, and most of what does get absorbed into the blood stream is rapidly metabolized in the intestines and liver and excreted from the body. By contrast, vitamin C is absorbed 100 percent by the body up to a certain level. And vitamin C accumulates in cells where it is 1,000 to 3,000 times more active as an antioxidant than flavonoids.

The large increase in total antioxidant capacity of blood observed after the consumption of flavonoid-rich foods is not caused by the flavonoids themselves, Frei said, but most likely is the result of increased uric acid levels.

But just because flavonoids have been found to be ineffectual as antioxidants in the human body does not mean they are without value, Frei said. They appear to strongly influence cell signaling pathways and gene expression, with relevance to both cancer and heart disease.

“We can now follow the activity of flavonoids in the body, and one thing that is clear is that the body sees them as foreign compounds and is trying to get rid of them,” Frei said. “But this process of gearing up to get rid of unwanted compounds is inducing so-called Phase II enzymes that also help eliminate mutagens and carcinogens, and therefore may be of value in cancer prevention.

“Flavonoids could also induce mechanisms that help kill cancer cells and inhibit tumor invasion,” Frei added.

It also appears that flavonoids increase the activation of existing nitric oxide synthase, which has the effect of keeping blood vessels healthy and relaxed, preventing inflammation, and lowering blood pressure – all key goals in prevention of heart disease.

Both of these protective mechanisms could be long-lasting compared to antioxidants, which are more readily used up during their free radical scavenging activity and require constant replenishment through diet, scientists say.

However, Frei said, it’s also true that such mechanisms require only relatively small amounts of flavonoids to trigger them – conceptually, it’s a little like a vaccine in which only a very small amount of an offending substance is required to trigger a much larger metabolic response. Because of this, there would be no benefit – and possibly some risk – to taking dietary supplements that might inject large amounts of substances the body essentially sees as undesirable foreign compounds.

Numerous studies in the United States and Europe have documented a relationship between adequate dietary intake of flavonoid-rich foods, mostly fruits and vegetables, and protection against heart disease, cancer and neurodegenerative disease, Frei said.

FRESH VEGETABLES, FRUITS REDUCE DIABETES RISK

Eating just one more serving of green leafy vegetables or three more servings of fruit a day reduces the risk of developing Type II diabetes, according to results of data analysis performed by researchers in the Tulane School of Public Health and Tropical Medicine and the Harvard School of Public Health. The research team also found that one serving of fruit juice a day increased the risk of Type II diabetes in women.

Tulane epidemiologist Dr. Lydia Bazzano says, “Based on the results of our study, people who have risk factors for diabetes may find it helpful to fill up on leafy greens like lettuces, kale and spinach and whole fruits, like apples, bananas, oranges and watermelon rather than drink fruit juices, which deliver a big sugar load in a liquid form that gets absorbed rapidly.”

Bazzano, an assistant professor of epidemiology, cautioned that since this is one of the first studies to separate fruit juice consumption from fruits as a whole, the association between juice and diabetes must be confirmed by additional research.

She and her team analyzed 18 years worth of diet and health data from 71,346 nurses who participated in the Nurses’ Health Study from 1984 to 2002. The women were all between 38 and 63 years old and diabetes-free when the study began. Approximately 7 percent of the participants developed diabetes over the course of the study.

The researchers determined that the association between fruit and green leafy vegetable consumption and lowered diabetes risk remained after other factors, such as family history, cigarette smoking and weight, were analyzed. However, they found that women who ate more fruits and green leafy vegetables also were likely to be older, non-smokers and more physically active.

In addition to emphasizing the importance of eating whole fruits and green leafy vegetables to prevent diabetes, the team also recommends replacing refined grains and white potatoes with whole fruit or green leafy vegetable servings. White flours and potatoes have been associated with an increased risk of diabetes.

 
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