Archive for May 2009

Vitamin B +folic acid reduces age-related vision loss

Saturday, May 23, 2009

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.
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Vitamin E Can Help Or Hurt You

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.
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Multivitamins Have No Impact

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.”
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Jon’s Health Tips - Glutamine Supplements

Tuesday, May 19, 2009

I am going to start taking L-glutamine. Here’s why:

My father died from complications from ulcer surgery. He was only 65. His father died from a stroke age 65 as well. I am now 64. I will regard every year beyond 65 as a precious gift.

My father suffered from ulcers his whole life. He was often in intense pain. There was no known cure. He ate almost nothing but eggs and dairy products to soothe his stomach, and was very overweight as a result. He suffered a heart attack, which went undiscovered – just more ulcer pain I guess, and contracted diabetes.

Tragically, not long after he passed away, it was discovered that bacteria known as Helicobacter pylori were responsible for stomach ulcers. Since then, antibiotics have become the primary therapy used to combat the H. pylori infection. He could have been easily cured.

But today the bacteria is growing increasingly resistant to antibiotics.

Now a study led by scientists at Beth Israel Deaconess Medical Center (BIDMC) and the Massachusetts Institute of Technology demonstrates that the amino acid glutamine, found in many foods as well as in dietary supplements, may prove beneficial in offsetting gastric damage caused by H. pylori infection. Reported in the May 2009 issue of the Journal of Nutrition., the findings offer the possibility of an alternative to antibiotics for the treatment of stomach ulcers.

"Our findings suggest that extra glutamine in the diet could protect against gastric damage caused by H. pylori," says senior author Susan Hagen, PhD, Associate Director of Research in the Department of Surgery at BIDMC and Associate Professor of Surgery at Harvard Medical School. "Gastric damage develops when the bacteria weakens the stomach's protective mucous coating, damages cells and elicits a robust immune response that is ineffective at ridding the infection." Eventually, she notes, years of infection result in a combination of persistent gastritis, cell damage and an environment conducive to cancer development.

Glutamine is a nonessential amino acid naturally found in certain foods, including beef, chicken, fish, eggs, dairy products and some fruits and vegetables. L-glutamine – the biologically active isomer of glutamine – is widely used as a dietary supplement by body builders to increase muscle mass.

Hagen and her coauthors had previously shown that glutamine protects against cell death from H. pylori-produced ammonia. "Our work demonstrated that the damaging effects of ammonia on gastric cells could be reversed completely by the administration of L-glutamine," explains Hagen. "The amino acid stimulated ammonia detoxification in the stomach – as it does in the liver – so that the effective concentration of ammonia was reduced, thereby blocking cell damage."

She and her coauthors, therefore, hypothesized that a similar mechanism might be at work in the intact stomach infected with H. pylori. To test this hypothesis, the investigators divided 105 mice into two groups, which were fed either a standardized diet (containing 1.9 percent glutamine) or the same diet with supplemental L-glutamine (containing 6.9 percent glutamine) replacing carbohydrates for five percent of the total calories. After two weeks, the mice were subdivided into two more groups, with one group receiving a sham (fake) dose and the other group receiving a real dose containing H. pylori. (This resulted in four separate mouse groups: an uninfected control group; an uninfected glutamine group; an infected control group; and an infected glutamine group.)

The mice were then followed for a 20-week period, during which time samples of blood and stomach tissue were removed. Blood was analyzed for antibodies to specific types of T-helper immune cells, which mediate the body's response to H. pylori infection. Stomach tissues were examined for evidence of damage and cancer progression and also chemically analyzed for cytokines (inflammatory substances) which are produced by T-helper cells.

Their results showed that at six-weeks-post infection, the animals exhibited increased expression of three cytokines – interleukin 4, interleukin 10 and transforming growth factor-alpha mRNA. "These all play an important role in the stomach's ability to protect against damaging effects resulting from other responses to H. pylori infection," explains Hagen.

Of even greater significance, by week 20, the study results showed that, among the H. pylori-infected animals, the mice that were fed the L-glutamine diet exhibited lower levels of inflammation than did the mice that received the standard control diet.

"Because many of the stomach pathologies during H. pylori infection [including cancer progression] are linked to high levels of inflammation, this result provides us with preliminary evidence that glutamine supplementation may be an alternative therapy for reducing the severity of infection," explains Hagen, adding that studies in human subjects will be the next step to determine the relevance of this finding in the clinical setting.

"H. pylori bacteria infect more than half of the world's population and were recently identified as a Group 1 carcinogen by the World Health Organization," she adds. "Approximately 5.5 percent of the entire global cancer burden is attributed to H. pylori infection and, worldwide, over 900,000 new cases of gastric cancer develop each year. The possibility that an inexpensive, easy-to-use treatment could be used to modify the damaging effects of H. pylori infection warrants further study in clinical trials."
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Statins and Lung Fuction

Saturday, May 16, 2009

Statins reduce loss of function, keeping old lungs young - even in smokers

Statins are known to be good for lowering cholesterol and maybe even fighting dementia, and now they have another reported benefit: they appear to slow decline in lung function in the elderly— even in those who smoke. According to researchers in Boston, it may be statins’ anti-inflammatory and antioxidant properties that help achieve this effect.

Their findings were published in the second issue for October in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.

“We hypothesized that statins would have a protective effect on decline in lung function,” wrote Dr. Joel Schwartz, Ph.D., professor of environmental epidemiology at Harvard School of Public Health, a lead researcher on the study, the first to examine the relationships between statins and lung function decline.

“The link between lung function and mortality and the reduced levels of lung function in the elderly indicates the importance of a possibility of reducing the rate of decline,” wrote Dr. Schwartz.

To investigate whether statins had an effect of loss of lung function, the researchers used data from the ongoing and longitudinal Veterans Administration Normative Aging Study, which began in 1963. They analyzed 803 subjects who had had their lung function measured at least twice between January 1995 and June 2005. Both forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were measured. The study subjects also completed questionnaires on pulmonary disorders, smoking and medication usage.

The investigators found that subjects taking statins experienced a markedly slower annual decline in lung function. In FEV1, statin users lost 10.9 ml on average, whereas nonusers lost an average of 23.9 ml each year—more than twice that of the statin group. Similarly, statin users lost an average of 14 ml a year in FVC, whereas nonusers lost an average of 36.2 ml.

To determine whether smoking status modified that effect, the researchers also divided their subjects into four smoking groups: never-smokers, long-ago quitters, recent quitters and current smokers. “Within each smoking group, those not taking statins were estimated to experience faster declines in FEV1 and FVC than those taking statins,” wrote Dr. Schwartz, noting that the size of the effect varied a bit with smoking status.

“Our results suggest (weakly) that long-term quitters and recent quitters may be able to benefit more from statin use than other groups,” Dr. Schwartz wrote.

But because of overlap between groups and the lack of randomization and controls in this study, the researchers point out that further data is needed before any definitive conclusions are drawn. Their findings do, however, support the hypothesis that statins reduce the annual loss of lung function that occurs with age.

The researchers suggest that the observed effect may be attributable to statins’ ability to reduce inflammation and smoking-induced injury in the lung, as well as their capacity to reduce serum levels of C-reactive protein, which relates to systemic inflammation, and to protect against oxidative damage.

The research adds to a growing body of knowledge indicating the positive effects of statin use beyond its cholesterol lowering properties.
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Cancer preventive effect for statins

The commonly used prescription statin drugs may have a protective effect in the prevention of liver cancer and lead to a reduction in the need for gallbladder removals, according to two studies published in Gastroenterology. As millions of Americans use statins each day to help lower their cholesterol and risk of heart disease, researchers are learning of the beneficial effects these drugs may have on gastrointestinal disorders. Gastroenterology is the official journal of the American Gastroenterological Association (AGA) Institute.

Statins Reduce Risk of Liver Cancer

Statin use is associated with a significant reduction in the risk of hepatocellular carcinoma (HCC), or liver cancer, among patients with diabetes, according to a new study in Gastroenterology.

"Our study provides the first indication of a cancer preventive effect for statins specific to HCC," said Hashem B. El-Serag, MD, MPH, of the Baylor College of Medicine and lead author of the study. "While these findings need to be confirmed in future studies, we are hopeful that further research continues to show the beneficial effect of statins for liver cancer prevention in patients with diabetes."

HCC is a highly fatal malignancy that has been increasing in several regions of the world, including the U.S. Experimental as well as indirect human data suggests that statins exert a beneficial action, reducing the progression of HCC.

Researchers undertook an epidemiological study in a large cohort of diabetics, whose risk of HCC was higher than average, to characterize the relationship between statin use and HCC and other liver disease. The team examined 1,303 cases and 5,212 controls; the mean age was 72 years. Ninety-nine percent were men and 13 percent were African Americans. A significantly smaller proportion of cases (34.3 percent) had at least one filled prescription for statins than controls (53.1 percent).

The research team found a significant inverse association between having statin prescriptions filled and the risk of developing HCC. There was a trend toward stronger risk reduction with longer and more frequent statin prescriptions. The risk reduction observed with statins ranged between 25 percent and 40 percent. Reduced HCC risk was similar, whether the prescriptions were for simvastatin or any other statin dispensed.

Statins May Reduce Risk of Gallbladder Removal Surgery

The use of statins appears to reduce the risk of cholecystectomy, surgical removal of the gallbladder, in women, according to a new study in Gastroenterology.
Gallstone disease is a common abdominal condition in developed countries and is a major cause of digestive disease leading to hospital admissions. In the U.S., more than 800,000 cholecystectomies are performed each year.

Researchers examined the relationship between statin use and the risk of cholecystectomy in a cohort of U.S. women participating in the prospective Nurses' Health Study. Participants biennially reported their health history, including incidence of gallstone disease and whether they had undergone cholecystectomy.
Researchers conducted a retrospective analysis of statin use through data collected in 2000 to define use from 1994 forward, and a prospective analysis for general lipid-lowering drugs from 1994 to 2004. In the statin analysis, the researchers ascertained 2,479 cases of cholecystectomy during 305,197 person-years of follow-up. The multivariate relative risk for current statin users, compared with nonusers, was 18 percent. In the analysis of general cholesterol-lowering drugs, researchers ascertained 3,420 cases of cholecystectomy during 511,411 person-years of follow-up. Compared with nonusers, the multivariate relative risk for current users of general cholesterol-lowering drugs, mostly statins in this cohort, was 12 percent. Among diabetic women, duration of current statin use was correlated with risk of cholecystectomy. Compared with statin nonuse, the relative risk for current statin use of two or more years was 75 percent.

"Further study, particularly among diabetics, is warranted to evaluate the associations of longer durations of statin use and specific types of statins with risk," said Chung-Jyi Tsai, MD, of the University of Kentucky Medical Center and lead author of the study. "Our results should have implications for additional clinical, epidemiological and mechanistic research."
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Statin Use Benefits Multiple Areas of Urologic Health

New Body of Research Suggests Statin Use Benefits Multiple Areas of Urologic Health


Several new studies presented at the American Urological Association's (AUA) 104th Annual Scientific Meeting suggest that the use of statins--commonly prescribed to lower cholesterol--may benefit men with prostate cancer, erectile dysfunction or lower urinary tract symptoms (LUTS). Several key research studies highlighting these benefits will be presented during a special panel for the media on Monday, April 27 from 9 to 10:30 a.m. during the 104th Annual Scientific Meeting of the American Urological Association (AUA).

The following study findings will be discussed by authors during the panel press conference:

Abstract 576: Is statin use associated with prostate cancer aggressiveness?

Use of statins may be associated with more favorable pathological features at radical prostatectomy, including adverse tumor features and lower risk of positive surgical margins.

Abstract 1598: Statin medication use and the risk of biochemical recurrence following radical prostatectomy: results from the SEARCH database

Statin use may be associated with a reduction in the risk of biochemical recurrence following prostatectomy.

Abstract 574: Associations between statin use and prostate-specific antigen levels and prostate cancer diagnosis

Statin use may be associated with a decreased risk of prostate biopsy, prostate cancer and exceeding age-specific prostate-specific antigen thresholds. Statin use may also prevent the development of prostate cancer.

Abstract 575: Association between statins, obesity and prostate tumor inflammatory infiltrate in men undergoing radical prostatectomy

Statin use was associated with a significant 72 percent reduction in the risk for inflammation within the prostate tumor. Obesity may be associated with increased tumor inflammation, and with more aggressive prostate cancer.

Abstract 925: Statin use and development of erectile dysfunction

Statins may provide the added benefit of reducing a man's risk of developing erectile dysfunction in association with the drug's use in vascular disease.

Abstract 1646: Statin and non-steroidal anti-inflammatory drug use and development of urologic outcomes

The combined use of statins and non-steroidal anti-inflammatory drugs (NSAIDs) may further decrease the risk of developing lower urinary tract symptoms related to benign prostatic hyperplasia.

"These studies add to a growing body of literature supporting the beneficial effects of statins in certain subsets of patients," said J. Brantley Thrasher, MD, an AUA spokesman.
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Aspirin can prevent liver damage

Tuesday, May 12, 2009

Aspirin can prevent liver damage that afflicts millions, Yale study finds


Simple aspirin may prevent liver damage in millions of people suffering from side effects of common drugs, alcohol abuse, and obesity-related liver disease, a new Yale University study suggests.

The study in the January 26 edition of Journal of Clinical Investigation documents that in mice, aspirin reduced mortality caused by an overdose of acetaminophen, best known by the brand name Tylenol. It further showed that a class of molecules known as TLR antagonists, which block receptors known to activate inflammation, have a similar effect as aspirin. Since these agents seem to work by reducing injury-induced inflammation, the results suggest aspirin may help prevent and treat liver damage from a host of non-infectious causes, said Wajahat Mehal, M.D., of the Section of Digestive Diseases and Department of Immunobiology at Yale School of Medicine.

"Many agents such as drugs and alcohol cause liver damage, and we have found two ways to block a central pathway responsible for such liver injury," Mehal said. "Our strategy is to use aspirin on a daily basis to prevent liver injury, but if it occurs, to use TLR antagonists to treat it."

Promising drugs that have failed clinical trials because of liver toxicity might be resurrected if combined with aspirin, Mehal said.

"This offers the exciting possibility of reducing a lot of pain and suffering in patients with liver diseases, using a new and very practical approach," Mehal said.
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Aspirin can reduce risk of Alzheimer's disease

Ibuprofen, aspirin, naproxen may be equally effective at reducing risk of Alzheimer's disease



Different types of non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, naproxen, and aspirin, appear to be equally effective in lowering the risk of Alzheimer’s disease, according to the largest study of its kind published in the May 28, 2008, online issue of Neurology®, the medical journal of the American Academy of Neurology. Experts have debated whether a certain group of NSAIDs that includes ibuprofen may be more beneficial than another group that includes naproxen and aspirin.

Using information from six different studies, researchers examined data on NSAID use in 13,499 people without dementia. Over the course of these six studies, 820 participants developed Alzheimer’s disease.

Researchers found that people who used NSAIDs had 23 percent lower risk of developing Alzheimer’s disease compared to those who never used NSAIDs. The risk reduction did not appear to depend upon the type of NSAID taken.

“This is an interesting finding because it seems to challenge a current theory that the NSAID group which includes ibuprofen may work better in reducing a person’s risk of Alzheimer’s,” said study author Peter P. Zandi, PhD, with Johns Hopkins Bloomberg School of Public Health in Baltimore, MD. “The NSAID group that includes ibuprofen was thought to target a certain type of plaque in the brain found in Alzheimer’s patients. But our results suggest there may be other reasons why these drugs may reduce the risk of Alzheimer’s.”

The study’s lead author Chris Szekely, PhD, with Cedars Sinai Medical Center in Los Angeles, says the discrepancy between studies such as this one and the negative clinical trials of NSAIDs in treatment or prevention of Alzheimer’s need to be further explored.
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Aspirin may reduce or increase blood pressure


Aspirin at night = significant reductions in blood pressure


Data unveiled today at the American Society of Hypertension's Twenty Third Annual Scientific Meeting and Exposition (ASH 2008) revealed for the first time that people with prehypertension who are treated with aspirin may experience significant reductions in blood pressure—but only if they take the pill before bedtime, and not when they wake up in the morning.

People with prehypertension (a blood pressure reading between normal and high; when systolic blood pressure is between 120 and 139 or diastolic blood pressure is between 80 and 89 on multiple readings) are at significant risk of hypertension, or consistently high blood pressure—the biggest risk factor for heart disease and stroke, the two leading causes of death in the Western world.

“This is the first study to reveal that taking aspirin before bedtime as opposed to upon waking in the morning is an effective strategy to lower blood pressure and cost effective way to individualize treatment regimes in pre-hypertensive patients," said lead investigator Prof. Ramón C. Hermida, Director of Bioengineering and Chronobiology at the University of Vigo in Spain. "These findings therefore have vital treatment implications for these at-risk patients throughout the world.”

The purposeful timing of medications in order to enhance beneficial outcomes or to avert adverse effects is known as ‘chronotherapeutics’. Although factors influencing why aspirin has an impact on prehypertensive patients in the evening and not the morning are somewhat unclear, researchers indicate that it could be because aspirin slows down the production of hormones and other substances in the body that cause clotting. Many of those are produced while the body is at rest.

The study, which ran for three months, involved 244 participants (97 men and 138 women of 43.0±13.0 years of age) all of whom had all received diagnoses for prehypertension. Participants were divided into three groups: non pharmacological hygienic-dietary recommendations (HDR): HDR and a 100mg tablet of aspirin (ASA) on awakening or HDR and ASA at bedtime. Blood pressure levels were monitored at 20 minute intervals from 7:00 a.m. to 11:00 p.m. and at 30-min intervals at night for 48 consecutive hours at baseline and after three months of intervention. Physical activity was simultaneously monitored every minute by wrist (actigraphy) to accurately calculate sleeping and waking blood pressure on an individual basis.

The results showed that those who had taken aspirin before they went to bed (at an average time of 11:00 p.m.), decreased their systolic blood pressure by an average of 5.4 mmHg and their diastolic blood pressure by an average of 3.4 mmHg over the three-month study, without any change in heart rate of physical activity compared to baseline values (p<0.001). This blood pressure reduction was similar during active hours (5.6 and 3.7 mmHg reduction in systolic and diastolic BP, p<0.001) and the nocturnal resting span (5.2 and 3.1 mmHg, respectively). Those who took a morning aspirin, usually at about 8:00 a.m., saw no reduction in ambulatory blood pressure at all, nor did participants in the HDR-only group.

“These results show us that we cannot underestimate the impact of the body's circadian rhythms," said Hermida. "The beneficial effects of time-dependent administration of aspirin have, until now, been largely unknown in people with prehypertension. Personalizing treatment according to one's own rhythms gives us a new option to optimize blood pressure control and reduce risk of cardiovascular disease down the line."

Pain relievers associated with increased blood pressure


Use of common pain relievers associated with increased risk of blood pressure in men

Those who took aspirin six or seven days a week had a 26 percent higher risk. The researchers also looked at the total number of pain-relieving pills men took each week, regardless of type. Compared with men who took no pills, those who took 15 or more pills each week had a 48 percent higher risk of hypertension.

All three types of analgesics may inhibit the effects of chemicals that relax the blood vessels, decreasing blood pressure, the authors suggest. Acetaminophen also may impair cell functioning through high levels of oxygen (oxidative stress) or reduce the proper functioning of blood vessel lining.

"These data add further support to the hypothesis that non-narcotic analgesics independently elevate the risk of hypertension," the authors write. "Given their common consumption and the high prevalence of hypertension, our results may have substantial public health implications and suggest that these agents be used with greater caution. The contribution of non-narcotic analgesics to the hypertension disease burden merits further study."
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Aspirin= + Prostate cancer in prevention/treatment?

Common painkillers lower levels of prostate cancer biomarker

But impact on a man's risk for getting prostate cancer is unclear, physicians say

Common painkillers like aspirin and ibuprofen appear to lower a man's PSA level, the blood biomarker widely used by physicians to help gauge whether a man is at risk of prostate cancer.

But the authors of the study, which appears online Sept. 8 in the journal Cancer, caution that men shouldn't take the painkillers in an effort to prevent prostate cancer just yet.

"We showed that men who regularly took certain medications like aspirin and other non-steroidal anti-inflammatory drugs, or NSAIDS, had a lower serum PSA level," said first author Eric A. Singer, M.D., M.A., a urology resident at the University of Rochester Medical Center. "But there's not enough data to say that men who took the medications were less likely to get prostate cancer. This was a limited study, and we do not know how many of those men actually got prostate cancer."

Singer's team studied the records of 1319 men over the age of 40 who took part in the 2001-2002 National Health and Nutrition Examination Survey (NHANES), a health census conducted by the Centers for Disease Control and Prevention. The team looked at the men's use of NSAIDs such as aspirin and ibuprofen, as well as the painkiller acetaminophen, and at their PSA levels. A man's level of PSA, or prostate-specific antigen, is one of many clues that physicians watch to gauge a man's risk of getting prostate cancer.

The team found that men who used NSAIDs regularly had PSA levels about 10 percent lower compared to men who did not. The team made a similar observation with acetaminophen, but the result was not statistically significant due to the lower number of men in the study taking the medication.

While it might be easy to assume that a lowered PSA level automatically translates to a lowered risk of prostate cancer, the authors stress that it's too soon to draw that conclusion.

"While our results are consistent with other research that indicates that certain painkillers may reduce a man's risk of getting prostate cancer, the new findings are preliminary and don't prove a link," said corresponding author Edwin van Wijngaarden, Ph.D., assistant professor in the Department of Community and Preventive Medicine.

Singer said that a man's PSA level can be elevated for reasons unrelated to cancer. Sometimes, for instance, while inflammation is part of a cancer process, sometimes it is not, and so it's possible that a lowered PSA reflects reduced inflammation without affecting a man's risk of prostate cancer. Another possibility is that a PSA level lowered by NSAIDs might artificially mask a man's risk of getting prostate cancer: The medications might lower the PSA, but a man's risk might stay precisely the same.

"These findings underscore the importance for doctors to know what medications their patients are on," said Singer, who is chief Urology resident at the University of Rochester Medical Center. "For instance, there are medications commonly used to treat an enlarged prostate that can result in a decreased PSA, and most physicians know that. Doctors should also be asking about patients' use of NSAIDs such as aspirin and ibuprofen.

"The data is very interesting, but it will take more research to determine how to interpret the findings. In the meantime, this shouldn't change men's behavior or prompt them to take these medications to try to prevent prostate cancer."
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Aspirin in the prevention/treatment of osteoporosis


USC School of Dentistry researchers uncover benefits of aspirin for treating osteoporosis

Drug appears to prevent both improper bone resorption and the death of bone-forming stem cells


Researchers at the University of Southern California, School of Dentistry have uncovered the health benefits of aspirin in the fight against osteoporosis. Forty-four million Americans, 68 percent of whom are women, suffer from the debilitating effects of osteoporosis according to the National Institute of Health. One out of every two women and one in four men over 50 will have an osteoporosis-related fracture in their lifetime.

This latest study identifies aspirin's medicinal role on two fronts. In mice, the drug appears to prevent both improper bone resorption and the death of bone-forming stem cells. The findings are published in PLoS ONE :
http://www.plosone.org/doi/pone.0002615

An aspirin regimen appears to help mice recover from osteoporosis in two useful ways, striking a balance between bone formation and resorption, according to Associate Professor Songtao Shi and Research Associate Takayoshi Yamaza of the USC School of Dentistry's Center for Craniofacial Molecular Biology (CCMB).
The silent disease affects both men and women. In women, bone loss is greatest during the first few years after menopause. Osteoporosis occurs when bone resorption (loss of bone) occurs too quickly or when formation (replacement) occurs to slowly.

According to Shi, the removal of the ovaries and the resulting decrease in estrogen induces osteoporosis in mice, much like the onset of the disease in post-menopausal women. It is commonly thought that T-lymphocytes, a type of immune system cell, play a pivotal part in this process by over-activating osteoclasts, the bone cells that reabsorb bone material from the skeleton. Most current osteoporosis therapies aim to curb overactive osteoclasts.

However, there seems to be another side to the T-lymphocytes', or T-cells', role in osteoporosis, Yamaza says. While the immune cells typically attack disease cells and other foreign entities, the T-cells can mistakenly attack healthy stem cells.

"After infusing the mice with T-cells, the T-cells impaired the function of bone marrow mesenchymal stem cells as well as caused osteoclast numbers to increase," he says.

The bone marrow mesenchymal stem cells, or BMMSC, differentiate to become many different cells including osteoblasts, the cells responsible for bone formation. If this processed is impaired by T-cells, bone formation cannot keep up with bone resorption caused by osteoclasts, and bone mineral density decreases – the hallmark of osteoporosis that leads to skeletal structural deterioration and fractures.

An aspirin regimen has been linked in earlier epidemiological studies to better bone mineral density, but the mechanisms of its interactions in regards to bone health had not yet been studied extensively, Shi said.

"We've shown how aspirin both inhibits bone resorption and promotes osteoblast formation," Shi says.

Another exciting aspect of the aspirin treatment is that the dose administered to the mice in order to increase their bone mineral density is the same as that of a typical human aspirin regimen when adjusted for body weight differences, he adds. While the species difference is still a factor, the results are promising.

"When we gave a large amount of aspirin to the mouse by injection, it did not work," Shi says, "but when we gave a low dose in the mice's water for a long period of time, similar to a human dosage, the bone mineral density increased."

Shi and Yamaza hope that their work will translate into new clinical strategies for osteoporosis.

"We have opened a door," Shi says. "We hope other scientists can confirm what we've found and move the treatment forward."

The use of aspirin offers hope to patients and doctors searching for a potential alternative to bisphophonates currently being used as a means of prevention and treatment for osteoporosis. This latest study opens up the possibility that aspirin some day will not only be prescribed to ward off heart disease but also osteoporosis.
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Aspirin may prevent atherosclerosis

Aspirin has become one of the most widely used medications in the world, owing to its ability to reduce pain, fevers, inflammation, and blood clotting. In animal studies, aspirin has also been shown to prevent atherosclerosis, though none of its known mechanisms of action would seem to account for this. In a new study, though, researchers have uncovered the mechanism that may explain aspirin's ability to prevent arterial plaque buildup.

Using cell culture and mouse models, Sampath Parthasarathy and colleagues observed that aspirin –specifically its active byproduct salicylate– can greatly increase the expression of two proteins: paraoxonase 1 (PON1) and apolipoprotein A1 (ApoA1); in the mouse studies, low dose aspirin supplements could increase PON1 and ApoA1 levels by 7- and 12- fold, respectively.

Both of these proteins are beneficial components of the HDL complex, the "good cholesterol" that helps prevent atherosclerosis; ApoA1 removes bad cholesterol from the bloodstream while PON1 is an antioxidant that breaks down toxic lipid peroxides.

The researchers also noted that the heightened expression of PON1 was accompanied by an increase in a receptor called AHR (aryl hydrocarbon receptor); this was intriguing as a chemical known to attach to AHR is resveratrol, the "heart healthy" component of red wine.
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Aspirin offers lowers risk of asthma


Low-dose aspirin offers lower chance of asthma




In a large, randomized, placebo-controlled study of 22,071 healthy male physicians, taking a low-dose of aspirin every other day lowered the risk of receiving an initial asthma diagnosis by 22 percent._

These findings, based on data from the double-blind Physicians' Health Study, appear in the second issue for January 2007 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

Tobias Kurth, M.D., Sc.D., of the Division of Aging at Brigham and Women's Hospital in Massachusetts, and five associates studied physicians, ages 40 to 84, over a period of 4.9 years. Among the 11,037 individuals who took aspirin, 113 new cases of asthma were diagnosed, as contrasted to 145 in the placebo group.

Asthma is a chronic inflammatory disease that causes potentially reversible obstructive lung problems. Breathing difficulties from asthma usually occur during "attacks," which involve narrowing of the airways, swelling of the lining, tightening of respiratory muscles and an increased secretion of mucus. In 2004, more than 20 million Americans were estimated to have asthma.

"Aspirin reduced the risk by 22 percent of newly-diagnosed adult-onset asthma," said Dr. Kurth. "These results suggest that aspirin may reduce the development of asthma in adults. They do not imply that aspirin improves symptoms in patients with asthma."

"Indeed, asthma can cause severe bronchospasm in some patients who have asthma," he continued. "Because asthma was not the primary endpoint of the U. S. Public Health Service study, additional randomized trials would be helpful to confirm the apparent reduction in asthma incidence caused by aspirin."_

The Physicians Health Study, which began in 1982, was terminated after 4.9 years when results showed a 44-percent reduction in the risk of a first heart attack among those randomly assigned to aspirin._

"Physicians could self-report an asthma diagnosis on questionnaires at baseline, at six months and annually thereafter," said Dr. Kurth. "Asthma was not the original deductive endpoint of the trial."

According to the authors, the 22-percent lower risk of newly-diagnosed asthma among those assigned to the low-dose aspirin group was not affected by participant characteristics like smoking, body mass index or age.

They noted that aspirin-intolerant asthma, a problem in which aspirin exacerbates the disease, affects only a small minority of asthma patients. In three large population-based studies, that difficulty affected only four to 11 percent of the groups. In children, however, the proportion affected by aspirin intolerant asthma was significantly smaller.
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Aspirin Saves Heart Attack Victims

Aspirin saves lives of cancer patients suffering heart attacks, despite fears of bleeding


Many cancer patients who have heart attacks often are not treated with life saving aspirin given the belief in the medical community that they could experience lethal bleeding. Researchers at The University of Texas M. D. Anderson Cancer Center, however, say that notion is now proven wrong and that without aspirin, the majority of these patients will die.__

Researchers say that their study, to be published in the February 1, 2007 issue of the journal Cancer and now available online, turns common medical assumptions upside down and will likely change medical practice for cancer patients. Because aspirin can thin blood and cancer patients experience low platelet counts and abnormal clotting, physicians view aspirin as a relative contraindication. Given that blood platelets are responsible for the clotting process, physicians do not eagerly prescribe aspirin as a standard treatment.

In this study, however, the investigators found that 9 of 10 cancer patients with thrombocytopenia (low platelet count) who were experiencing a heart attack and who did not receive aspirin died, whereas only one patient died in a group of 17 similar cancer patients who received aspirin. They also found aspirin helps cancer patients with normal platelet count survive heart attacks, just as it does for people without cancer._

"The notion that heart attacks in patients with low platelets should be treated with clot-dissolving aspirin defies logic, that is unless you suspect that the cancer is interfering with platelet function," says the study's senior investigator and author, Jean-Bernard Durand, M.D., assistant professor in the Department of Cardiology at M. D. Anderson Cancer Center.

"We believe tumors may be releasing chemicals that allow the cancer to form new blood supplies which makes blood more susceptible to forming clots." Durand, a heart failure specialist, says. "There appears to be a platelet paradox suggesting that cancer may affect the mechanism of the way that blood clots, and from this analysis, we have found that the single most important predictor of survival in these patients is whether or not they received aspirin." Durand says more research is needed to better understand this contraindication.

According to the World Health Organization there are approximately 10 million cancer patients worldwide, of which 1.5 million may develop blood clots during their cancer treatment and, as such, are at a much higher risk of dying from heart disease if not treated properly. "Now that we have this study, it would be a travesty if you survive treatment for cancer only to die of a heart attack soon thereafter," Durand says.

According to Durand, no guidelines currently exist for treatment of heart attacks in patients with cancer. He says that physicians are especially perplexed about what to do for cancer patients with thrombosis (blood clots), a condition that affects about 15 percent of all cancer patients and can be due to the use of chemotherapy or the presence of cancer._

Durand came to M. D. Anderson in 2000 to start the Cardiomyopathy Services, which is believed to be the only program in the world specifically designed to look at cardiovascular complications caused by chemotherapy treatment. He is also the co-founder of CONQUER (Cardiology Oncology International Quest to Educate and Research Heart Failure in Cancer), a newly created organization with goals of increasing the success of chemotherapy by reducing cardiovascular disease as a barrier and long term risk.

He and anesthesiologist Mona Sarkiss, M.D., Ph.D., made the observation that patients with thrombocytopenia who suffered a heart attack and were being treated in the intensive care unit at M. D. Anderson tended to die more often when they were not given aspirin. However, they noted that some of the patients given aspirin and/or beta-blockers had "great" clinical outcomes. "Because no practice guidelines exist, physicians were treating their patients with great variability and the disparity was obvious," Durand says.

Sarkiss, who is the study's lead author, Durand, and a team of researchers which included investigators from Baylor College of Medicine and Duke University Medical Center, conducted a retrospective analysis of cancer patients treated for heart attacks at M. D. Anderson Cancer Center in 2001. These 70 patients were divided into two groups based on their platelet counts, and data was collected on the use of aspirin, bleeding complications, and survival.

They found that heart attack patients with low platelets who did not receive aspirin had a seven-day survival rate of 6 percent, compared with 90 percent survival in those who received aspirin. Dr. Durand notes that there were no severe bleeding complications in patients who used aspirin. Conversely, patients with low platelet counts who formed a blood clot and were not exposed to aspirin died.

The beneficial effect of aspirin also was seen in patients with normal platelet counts. Seven-day survival was 88 percent in aspirin-treated patients as compared to 45 percent in patients who did not receive aspirin, the researchers found.

Durand observed that these deaths rates are abnormally high. "In the non-cancer patient with acute coronary syndrome anywhere in the United States, an expected seven-day mortality is less than 1 percent," he says.

There were parallel findings for those patients in either group who were treated with beta-blockers, which block the heart's use of adrenalin. The protective effect was not as strong as seen with aspirin, but was still life saving._

In those patients with a normal platelet count, 91 percent survived seven days when treated with beta-blockers, whereas 36 percent survived if they were not treated with the agent. In the thrombocytopenic group, 73 percent survived seven days when treated with beta-blockers, whereas only 13 percent survived if they were not treated.
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Aspirin may reduce risk of breast cancer

Aspirin may reduce risk of common type of breast cancer



Taking aspirin on a daily basis may lower women’s risk of a particular type of breast cancer, according to results published in BioMed Central’s open access journal Breast Cancer Research. In this large study, aspirin use was linked to a small reduction in estrogen receptor-positive breast cancers. However, unlike in some previous research, aspirin and related painkillers were not found to reduce the total risk of breast cancer.

Around 75% of breast cancers are estrogen receptor-positive (ER+), which means the cancer cells have receptors for the female hormone estrogen on their surface. Estrogen helps the cancer cells grow, so drugs that block the action of estrogen are often used to treat ER+ cancer.

It is feasible, in theory, that aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) could lower the total risk of breast cancer. They block an enzyme called cyclooxygenase, an activity that could disrupt breast cancer development in a number of ways – for example, by reducing the amount of estrogen produced in the body.

A US research team, led by Gretchen Gierach, studied over 127,000 women enrolled in the National Institutes of Health–AARP Diet and Health Study, which was designed to explore the possible links between diet, health-related behaviours and cancer in older people in the USA. For the current research, the participants were women aged 51–72 with no history of cancer.

Unlike other NSAIDs, aspirin has irreversible effects on cyclooxygenase (COX) enzymes, so the study authors looked for differences in cancer development according to whether women used aspirin or another kind of NSAID.

NSAID use was not linked to total risk of breast cancer in this study. However, when the team considered different cancer subtypes and specific types of NSAIDs, they found that daily aspirin use was associated with a small reduction (16%) in the risk of ER+ breast cancer. A similar link was not seen in cases of ER- breast cancer.

Gierach concludes: “In summary, our results do not support an important influence of NSAIDs on total breast cancer risk. Daily aspirin use, however, appeared to offer some protection for ER+ breast cancer in this population … Our results provide support for further evaluating relationships in prospective studies with well-defined measures of NSAID use by NSAID type … and by ER status.”
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Aspirin can reduce colorectal cancer risk

Three recent studies confirm that aspirin can reduce colorectal cancer risk:

Aspirin can reduce colorectal cancer risk

A study of Medicare patients with osteoarthritis provides additional evidence that non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin reduce the risk of colorectal cancer. Earlier investigations of the drugs’ impact on tumor development could not rule out the possibility that an observed protective effect was caused by other preventive health care measures. The current study, led by a Massachusetts General Hospital (MGH) physician, appears in the August 2007 Journal of General Internal Medicine.

“This is good news for people who take NSAIDs regularly for osteoarthritis,” says Elizabeth Lamont, MD, MS, of the MGH Cancer Center, the study’s lead author. “Although patients face risks such as bleeding or kidney damage from this therapy, they probably are at a lower risk of developing colorectal cancer.” Because of the risks posed by the dosage used to treat osteoarthritis, she and her co-authors stress that currently available NSAIDs should not be used solely to prevent cancer.

Earlier randomized trials clearly showed that NSAID treatment can prevent the development of precancerous colorectal polyps, but whether or not such therapy also reduces the risk of invasive colorectal cancer has not yet been confirmed. Those trials used relatively low doses of aspirin and showed no significant differences in colorectal cancer rates between the aspirin and placebo groups. While many observational studies have shown a protective effect of NSAIDs against colorectal cancer, interpretation of some of those results may have been clouded by other healthy behaviors of the participants.

Benefits of aspirin to prevent colon cancer


A colon cancer researcher at the Ireland Cancer Center of University Hospitals Case Medical Center (UHCMC) has laid out the roadmap for how medical science should employ aspirin and new aspirin-like drugs for use in preventing colon cancer in certain high-risk individuals.

In today's New England Journal of Medicine, Sanford Markowitz, MD, PhD, writes an editorial accompanying research from Dr. Charles Fuchs' team at Harvard Medical School that lays out the hypothesized mechanism by which the use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs), also called COX-2 inhibitors, act to decrease the risk of developing colon cancer.

"The compelling evidence that chronic use of aspirin or certain NSAIDS can substantially lower the risk of colon cancer has important implications, especially because colon cancer is the second leading cause of cancer death," writes Dr. Markowitz, the Francis Wragg Ingalls Professor of Cancer Genetics at UHCMC and Case Western Reserve University School of Medicine.

In the Journal article, the Harvard researchers' findings demonstrated that two-thirds of colon cancers have high levels of expression of the COX-2 enzyme, which is blocked by aspirin. Individuals who regularly used aspirin over a course of several years demonstrated a 36% decrease in the risk of developing one of these high COX-2 expressing colon cancers. These results again demonstrated that drugs that block COX-2 can decrease the risk of colon cancer, and demonstrated that such drugs specifically target those individuals whose tumor development is encouraged by the action of the COX-2 enzyme._

Dr. Markowitz' accompanying editorial maps out those studies which will be required to determine the potential use of aspirin in prevention of colon cancer and to determine which individuals might benefit most from taking aspirin or aspirin-like drugs (NSAIDS) such as ibuprofen and Celebrex. Finally, the editorial outlines potential targets for development of drugs that might provide similar protection as aspirin or COX-2 inhibitor drugs for developing colon cancer but with a lesser risk of adverse side effects.

"Interventional trials have shown a decreased risk of the development of colon cancer in high-risk subjects who were given aspirin or COX-2 selective NSAID inhibitors and observational trials have associated a decreased risk of colon cancer with aspirin use," writes Dr. Markowitz in the editorial. "The researchers' findings provide powerful support for the role of COX-2 as a key mediator in the development of colon cancer and now pose questions about the biologic basis and clinical applications of discovering differences that express high or low levels of COX-2."

Dr. Markowitz has done seminal research in the field of colon cancer genetics and prevention. Among his numerous research articles, he published a study on the findings of a new "Celebrex-like" gene that suppresses the grown of colon cancer in the July 2006 issue of Proceedings of the National Academy of Sciences. Dr. Markowitz likens the gene, called 15-PGDH, to a naturally occurring Cox-2 inhibitor such as Celebrex. These findings may lead to the development of a new drug for colon cancer prevention.

"Sandy and his research team have made great strides in colon cancer prevention," says Stanton Gerson, MD, Director of the Ireland Cancer Center at University Hospitals Case Medical Center as well as the Case Comprehensive Cancer Center. "This editorial and all of his proceeding work may have great impact on individuals at high risk for developing this deadly disease."

Regular, long-term aspirin use reduces risk of colorectal cancer

Patients need to talk to their doctor to discuss risks vs. benefits

The use of regular, long-term aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) reduces the risk associated with colorectal cancer, according to a study published in Gastroenterology, the official journal of the American Gastroenterological Association (AGA) Institute. However, the use of aspirin for chemoprevention of colorectal cancer may require using the drug at doses that are higher than recommended over a long period of time, which may cause serious side effects including gastrointestinal bleeding.

“While the results of our study show that aspirin should not currently be recommended for the chemoprevention of colorectal cancer in a healthy population, there is a need for further studies to help identify for which patients the potential benefits outweigh the risks,” according to Andrew T. Chan, MD, MPH, Massachusetts General Hospital and lead author of the study. “We also need to improve our understanding of how aspirin works to prevent and inhibit the formation of colorectal cancer.”

Study participants were enrolled in the Health Professionals Follow-up Study, a large prospective cohort study which has provided detailed and updated information on aspirin use.

Researchers found that men who used aspirin regularly experienced a significantly lower risk of colorectal cancer, including distal colon cancer, proximal colon cancer and rectal cancer, even after controlling for other risk factors. The reduction in risk was seen in both early (stage I/II) and advanced (stage III/IV) colorectal cancers. There were 975 documented cases of colorectal cancer over 761,757 person-years, among the 47,636 eligible men. Participants who reported regular aspirin use, equal to or more than twice a week, were older, more likely to have smoked, used multivitamins and folate, and consumed slightly more alcohol.

In an average-risk population of men, results showed that the benefit of aspirin was not apparent until after more than five years of use. The greatest reduction in risk was observed at cumulative doses of more than 14 standard tablets (325 mg) per week, which is higher than normally recommended. The benefit of aspirin use appears to diminish less than four years after stopping use and is not evident after four to five years of discontinued use.

The Health Professionals Follow-up Study has been conducted on 51,529 U.S. male dentists, optometrists, osteopaths, podiatrists, pharmacists and veterinarians, who returned a mailed health questionnaire in 1986. The questionnaire included questions about diet, aspirin use and medical diagnoses, including cancer. The biennial questionnaires ask for updated information including cancer diagnoses and aspirin use. The participants were between 40 and 75 years of age when the study began.

This year an estimated 147,000 Americans will be diagnosed with colorectal cancer and 56,500 will die from this disease, with an approximate 1-in-18 lifetime probability of developing colorectal cancer.
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Aspirin Fights Cancer

Aspirin Fights Cancer


Long-term use of adult-strength aspirin linked to a moderate decreased cancer risk_

A daily dose of adult-strength aspirin may modestly reduce cancer risk in populations with high rates of colorectal, prostate, and breast cancer if taken for at least five years.

The Women's Health Study trial recently reported that long-term use of low-dose aspirin (about 100mg every other day) does not reduce a woman's cancer risk, but it did not examine whether high doses of aspirin have an effect on cancer risk.

Eric Jacobs, Ph.D., of the American Cancer Society in Atlanta, and colleagues looked for associations between long-term daily aspirin use (at least 325mg/day) and cancer incidence in a group of nearly 70,000 men and 76,000 women. Aspirin use was determined by a questionnaire.

During the 12 year follow-up, nearly 18,000 men and women in the study were diagnosed with cancer. The researchers found that daily use of adult-strength aspirin for at least five years was associated with an approximately 15 percent relative reduction in overall cancer risk, though the decrease was not statistically significant in women. Additionally, aspirin use was associated with a 20 percent reduced risk of prostate cancer and a 30 percent reduced risk of colorectal cancer in men and women, compared to people who didn't take aspirin. There was no effect on risk in other cancers examined—lung cancer, bladder cancer, melanoma, leukemia, non-Hodgkins lymphoma, pancreatic cancer, and kidney cancer. Aspirin use for less than five years was not associated with decreased cancer risk.

"Our results do not have immediate clinical implications. Confirmation from randomized trials is necessary before a reduction in cancer risk could be considered a benefit of using adult-strength aspirin. Our results indicate that a randomized trial examining the effect of aspirin on cancer incidence would need to be both large and long term, probably lasting a minimum of 10 years. More evidence is needed before any such trial can be justified," the authors write.

In an accompanying editorial, Maria Elena Martinez, Ph.D., of the Arizona Cancer Center in Tucson, and E. Robert Greenberg, M.D., of the Fred Hutchinson Cancer Center in Seattle, write that, for the average person, the side effects of daily long-term aspirin use, such as intestinal bleeding or stroke, might outweigh the its benefits of cancer prevention. "However, if aspirin were shown to truly prevent a multitude of common cancers, there might be clinical situations in which daily adult-strength aspirin would be indicated," the authors write.
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Aspirin not as good for women as for men

Long-term aspirin = reduced risk of dying in women?

Long-term aspirin use associated with reduced risk of dying in women_

Women who take low to moderate doses of aspirin have a reduced risk of death from any cause, and especially heart disease–related deaths, according to a report in the March 26 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Some studies have provided evidence that aspirin may reduce the risk of heart disease and some types of cancer, the two leading causes of death in U.S. women, according to background information in the article. However, it is unclear whether aspirin reduces the risk of death overall for women.

Andrew T. Chan, M.D., M.P.H., Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues examined the association between aspirin use and death in 79,439 women enrolled in the Nurses’ Health Study, a large group of female nurses who have been followed since 1976. Beginning in 1980 and again every two years through 2004, the women were asked if they used aspirin regularly and if so, how many tablets they typically took per week. At the beginning of the study, the women had no history of cardiovascular disease or cancer.

A total of 45,305 women did not use aspirin; 29,132 took low to moderate doses (one to 14 standard 325-milligram tablets of aspirin per week); and 5,002 took more than 14 tablets per week. By June 1, 2004, 9,477 of the women had died, 1,991 of heart disease and 4,469 of cancer. Women who reported using aspirin currently had a 25 percent lower risk of death from any cause than women who never used aspirin regularly. The association was stronger for death from cardiovascular disease (women who used aspirin had a 38 percent lower risk) than for death from cancer (women who used aspirin had a 12 percent lower risk).

"Use of aspirin for one to five years was associated with significant reductions in cardiovascular mortality," the authors write. "In contrast, a significant reduction in risk of cancer deaths was not observed until after 10 years of aspirin use. The benefit associated with aspirin was confined to low and moderate doses and was significantly greater in older participants and those with more cardiac risk factors."

There are several mechanisms by which aspirin could reduce the risk of death, the authors note. "Aspirin therapy may influence cardiovascular disease and cancer through its effect on common pathogenic pathways such as inflammation, insulin resistance, oxidative stress [damage to the cells caused by oxygen exposure] and cyclooxygenase (COX) enzyme activity," also linked to inflammation, they write.

Because the study looked at women who made the decision themselves whether or not to take aspirin, as opposed to a clinical trial where women are randomly assigned to aspirin or a placebo, the results do not suggest that all women should take aspirin. "Nevertheless, these data support a need for continued investigation of the use of aspirin for chronic disease prevention," the authors conclude._

These findings differ from the results of other studies regarding the benefits of aspirin use in healthy women, leaving confusion about aspirin’s role, writes John A. Baron, M.D., Dartmouth Medical School, Lebanon, N.H., in an accompanying editorial._

Dr. Baron points out that in the Women’s Health Study, researchers followed almost 40,000 women for 11 years and did not find any reduced risk of cardiovascular or other death associated with aspirin therapy, in contrast to the dramatic risk reduction seen in the Nurses’ Health Study. "Is aspirin really that good or is there some other explanation for the findings that differ so much from those of the WHS and other primary prevention trials?" he writes.

"The difference between the NHS and the aggregated data from the WHS and other trials is too large to be explained by potential weaknesses in the randomized studies," Dr. Baron writes. "At the same time, one has to consider that the observational NHS may not have been able to deal with the differences between aspirin users and non-users."

"Therefore, these new findings by Chan et al cannot overcome the accumulated evidence that aspirin is not particularly effective for the primary prevention of death from cardiovascular disease in women," he concludes.

A new study shows that aspirin therapy for coronary artery disease is four times more likely to be ineffective in women compared to men with the same medical history.

Historically, studies have shown that aspirin therapy is less effective in women than in men, but it has remained unclear how much less effective and whether this affects patient outcomes, said Michael Dorsch, clinical pharmacist and adjunct clinical instructor at the University of Michigan College of Pharmacy.

Dorsch is the lead author of the paper, "Aspirin Resistance in Patients with Stable Coronary Artery Disease," which appears online today in the Annals of Pharmacotherapy.

Originally, Dorsch and his team set out to determine if patients with a history of heart attacks were more apt to be aspirin resistant than those with coronary artery disease but no history of heart attack. They found that gender and not medical history was a predictor for aspirin resistance, Dorsch said. The results surprised him.

"I was surprised by how big of a difference it was for females," said Dorsch, who has appointments at the U-M Health System and the U-M College of Pharmacy, and started the study as a resident at the University of North Carolina. "This is another piece of information that affirms we need more studies in women."

Aspirin therapy is a cornerstone in managing heart disease because it inhibits blood clotting. Aspirin therapy can reduce the risk of a nonfatal heart attack or stroke by about 23 percent, and an estimated 20 million men and women take a low dose of aspirin (81-325 mg daily) to control heart disease. But despite its effectiveness, there is evidence that aspirin is less effective in some patients, and researchers don't really know why. This can be frightening because most doctors do not check for aspirin resistance before prescribing aspirin therapy and therefore presume it's working in the patient when it may not be, he said.

There isn't enough evidence to show if people who are aspirin resistant can simply take larger doses, but Dorsch warns that people taking aspirin on the advice of a doctor shouldn't stop therapy on account of these results.

Not only did the study quantify how much more effective aspirin therapy is for men than for women, it is also the first study that Dorsch knows of to measure aspirin resistance in men and women with stable coronary artery disease. Previous studies have looked at the impact of aspirin therapy on people who have had a heart attack.

For the study, researchers randomly selected 100 patients who were visiting their cardiologist for a regularly scheduled appointment. All had coronary artery disease but only half had a history of heart attack. Researchers used a device called VerifyNow Aspirin Assay to test the percentage of platelet reactivity after blood samples were exposed to a chemical that causes clotting.

Aspirin works by causing platelet inhibition in the blood, which means that platelets cannot stick together and this slows the formation of blood clots that cause a heart attack or stroke.

"This does happen in women, but it doesn't happen in as many women and it's not as effective," Dorsch said. The testing device uses an optical sensor to "see" what percentage of the platelets in the blood sample clump together. Anything less than 40 percent platelet inhibition is considered aspirin resistant.

"We really don't know the mechanism," Dorsch said. "It could be that women have a more active platelet system in the body so it's less likely that platelet action would be inhibited."

In the future, researchers hope to look at aspirin therapy outcomes in women only and see if those outcomes can be changed. The majority of testing for aspirin therapy has been on men, so not much is known about how women respond.

"Heart disease is the number one killer of women in the United States. Future research should be aimed at finding out the cause of this increase in aspirin resistance and the effect on outcomes in women with heart disease." Dorsch said.
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Coated Aspirin As Bad on Stomach as Plain Aspirin

Some people take aspirin without ever having a problem with their stomach. Others develop low-grade stomach pain or get an ulcer. A few develop gastrointestinal bleeding severe enough to require a transfusion. But coated or buffered aspirin doesn’t do much to help.

Coated aspirin, also called enteric-coated aspirin, is the pharmaceutical industry’s attempt to limit the drug’s effect on the stomach. It’s a great idea: Cover aspirin with a coating designed to withstand stomach acids so it sails through the stomach untouched and dissolves in the more neutral small intestine. Keeping aspirin intact for as long as possible might mean it won’t damage the lining of the stomach. Yet studies show that coasted aspirin has virtually the same effect on the stomach as plain, uncoated aspirin.

The Harvard Heart Letter notes that aspirin doesn’t have to be in contact with stomach cells to harm them. Even when the pill dissolves in the intestines, the medicine gets into the bloodstream and is carried to all parts of the body—including the cells lining the stomach. Once there, it blocks the COX-1 enzyme. Stomach cells need COX-1 in order to churn out compounds that protect them from the powerful acids that digest food.

Of course, we’re all different, and coated aspirin may work for some people. But be advised that coating doesn’t guarantee problem-free aspirin use.
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U.S. Preventive Services Task Force: Aspirin

Monday, May 11, 2009

Risks of Using Aspirin to Prevent Heart Attack Or Stroke Differ by Gender and Age

Patients and clinicians should consider risk factors-- including age, gender, diabetes, blood pressure, cholesterol levels, smoking and risk of gastrointestinal bleeding-- before deciding whether to use aspirin to prevent heart attacks or strokes, according to new recommendations from the U.S. Preventive Services Task Force. These recommendations do not apply to people who have already had a heart attack or stroke.
The recommendations are published in the March 17 issue of the Annals of Internal Medicine. The Task Force reviewed new evidence from the National Institutes of Health’s Women’s Health Study published since the last Task Force review of this topic in 2002, including a recent meta-analysis of the risks and benefits of aspirin and found aspirin may have different benefits and harms in men and women. The Task Force found good evidence that aspirin decreases first heart attacks in men and first strokes in women.

The more risk factors people have, the more likely they are to benefit from aspirin. The Task Force recommends that men between the ages of 45 and 79 should use aspirin to reduce their risk for heart attacks when the benefits outweigh the harms for potential gastrointestinal bleeding. Women between the ages of 55 and 79 should use aspirin to reduce their risk for ischemic stroke when the benefits outweigh the harms for potential gastrointestinal bleeding. Ischemic strokes occur as a result of an obstruction within a blood vessel supplying blood to the brain and are potentially prevented by aspirin use. The risk of gastrointestinal bleeding with and without aspirin use increases with age and is twice as high in men as in women. Other risk factors for gastrointestinal bleeding include upper gastrointestinal tract pain, gastrointestinal ulcers, and using non-steroidal anti-inflammatory drugs.

The Task Force recommended against using aspirin to prevent either strokes or heart disease in men under 45 or women under age 55 because heart attacks are less likely to occur in men younger than 45 and ischemic strokes are less likely to occur in women younger than 55, and because limited evidence exists in these age groups.

People age 80 and older could benefit more than younger people from aspirin because of their higher risk of cardiovascular disease, but the harms are also greater because the risk of gastrointestinal bleeding increases with age. The Task Force could not find clear evidence that the benefits of using aspirin outweigh the risks in people 80 years or older.

“The decision about whether the benefits of taking aspirin outweigh the harms is an individual one. Patients should work with their clinicians to look at their risk factors and decide if taking aspirin to lower their risk for heart attacks or strokes outweighs the potential risk of gastrointestinal bleeding,” said Task Force Chair Ned Calonge, M.D., who is also chief medical officer and state epidemiologist for the Colorado Department of Public Health and Information.

Cardiovascular disease is the leading cause of death in the United States. It is the underlying or contributing cause in approximately 58 percent of all deaths. In 2003, 1 in every 3 adults had some type of cardiovascular disease. In adults over the age of 40, the risk of developing cardiovascular disease is 2 in 3 for men and more than 1 in 2 for women.

The Task Force could not find evidence about what the optimum dose of aspirin is to prevent heart attacks or strokes. Evidence shows benefits at a range of doses, and the risk of gastrointestinal bleeding may increase with the dose. A dose as low as 75 mg seems as effective as higher doses. Taking aspirin increases a person’s chances of gastrointestinal bleeding, the sudden loss of blood or perforation of the digestive tract that can lead to hospitalization or death. Taking aspirin also increases the chance of a hemorrhagic stroke, or bleeding in the brain, which is different than the ischemic stroke that aspirin can prevent.

In 2002, the Task Force strongly recommended that clinicians discuss aspirin use with adults at increased risk for coronary heart disease and that discussions with patients should address both the potential benefits and potential harms of aspirin therapy. The new recommendation provides more specific guidance about benefits and harms to specific age groups and gender-specific benefits and provides clinicians with information on how to estimate an individual’s risks for heart disease or stroke.

The U.S. Preventive Services Task Force is an independent panel of experts in prevention and primary care. The Task Force conducts rigorous, impartial assessments of the scientific evidence for the effectiveness of a broad range of clinical preventive services, including screening, counseling and preventive medications. Its recommendations are considered the gold standard for clinical preventive services.

Summary of Recommendations
• The USPSTF recommends the use of aspirin for men age 45 to 79 years when the potential benefit due to a reduction in myocardial infarctions outweighs the potential harm due to an increase in gastrointestinal hemorrhage.
• The USPSTF recommends the use of aspirin for women age 55 to 79 years when the potential benefit of a reduction in ischemic strokes outweighs the potential harm of an increase in gastrointestinal hemorrhage.
• The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of aspirin for cardiovascular disease prevention in men and women 80 years or older._
• The USPSTF recommends against the use of aspirin for stroke prevention in women younger than 55 years and for myocardial infarction prevention in men younger than 45 years. _
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Mediterranean diet = lower heart disease

Saturday, May 9, 2009

A review of previously published studies suggests that vegetable and nut intake and a Mediterranean dietary pattern appear to be associated with a lower risk for heart disease, according to a report published in the April 13 issue of Archives of Internal Medicine, one of the JAMA/Archives journals. However, intake of trans-fatty acids and foods with a high glycemic index may be harmful to heart health.

"The relationship between dietary factors and coronary heart disease has been a major focus of health research for almost half a century," the authors write as background information in the article. Although "a wealth of literature" has been published on the topic, "the strength of the evidence supporting valid associations has not been evaluated systematically in a single investigation."

Andrew Mente, Ph.D., of the Population Health Research Institute, and colleagues conducted a systematic search for articles investigating dietary factors in relation to heart disease published between 1950 and June 2007. A total of 146 prospective cohort studies (looking back on the habits of a particular group of individuals) and 43 randomized controlled trials (where participants are randomly assigned to a dietary intervention or a control group) were identified and included in the systematic review.

When the researchers pooled the study results and applied a predefined algorithm, "we identified strong evidence of a causal relationship for protective factors, including intake of vegetables, nuts and monounsaturated fatty acids and Mediterranean, prudent and high-quality dietary patterns, and harmful factors, including intake of trans–fatty acids and foods with a high glycemic index or load and a western dietary pattern," they write. "Among these dietary exposures, however, only a Mediterranean dietary pattern has been studied in randomized controlled trials and significantly associated with coronary heart disease."

In addition, modest relationships were found supporting a causal relationship between intake of several other foods and vitamins and heart disease risk, including fish, omega-3 fatty acids from marine sources, folate, whole grains, alcohol, fruits, fiber and dietary vitamins E and C and beta carotene. Weak evidence also supported causal relationships between vitamin E and ascorbic acid supplements, saturated and polyunsaturated fatty acids and total fats, alpha-linoleic acid, meat, eggs and milk.

"The modest or weak evidence of these dietary exposures is mostly consistent with the findings of randomized controlled trials, although randomized controlled trials have yet to be conducted for several factors," the authors write. "Taken together, these findings support a causal relationship between only a few dietary exposures and coronary heart disease, whereas the evidence for most individual nutrients or foods is too modest to be conclusive."

"Although investigations of dietary components may help to shed light on mechanisms behind the benefits of dietary patterns, it is unlikely that modifying the intake of a few nutrients or foods would substantially influence coronary outcomes," they conclude. "Our findings support the strategy of investigating dietary patterns in cohort studies and randomized controlled trials for common and complex chronic diseases such as coronary heart disease."



Low glycemic breakfast may increase benefits of working out



The benefits of physical activity and a balanced diet are well documented and form the basis of many public health recommendations. This is because each of these factors can independently influence risks for many chronic diseases such as obesity, type 2 diabetes, and some forms of cancer. Some research also suggests that exercise and diet interact to influence health. For instance, exercising after short-term fasting (such as before breakfast) may increase the amount of fat burned. Similarly, consumption of a meal eliciting a low blood glucose response prior to exercise may also boost the use of body fat (instead of glucose). However, most of these studies have used either trained athletes or recreational exercisers, and none has looked at effects of the type of pre-exercise meal on metabolism during and after exercise. To better understand the effects of pre-exercise meal composition on fat metabolism in more typical (sedentary) individuals, a group of researchers headed by Dr. Emma Stevenson at the University of Nottingham conducted a controlled human intervention trial. The results of their study are published in the May 2009 issue of The Journal of Nutrition.

As expected, blood glucose concentrations were higher after the HGI than the LGI meals and had returned to baseline levels by the time exercise was commenced, after which they were not influenced by breakfast type. Plasma free fatty acids (FFA; a marker for adipose oxidation) fell after consumption of both HGI and LGI breakfasts, but began to rise at ~2 h post-breakfast in the LGI (but not HGI) treatment. Exercise caused a rapid increase in FFA in both groups, but this was higher in the LGI trial compared to the HGI trial (P < 0.001). Circulating concentrations of FFA were not different between treatments following lunch. Overall, fat oxidation was higher in the LGI treatment than in the HGI treatment (P < 0.05) during the post-breakfast and exercise periods. Following lunch, fullness scores were higher in the LGI trial than in the HGI trial (P < 0.05). The authors concluded that consuming a LGI breakfast increases fat oxidation during subsequent exercise and improved satiety during recovery in sedentary females. As such, individuals trying to shed fat may consider choosing LGI foods eaten prior to when they exercise.





Dietary acrylamide not associated with increased lung cancer risk in men



Dietary acrylamide was not associated with an increased risk of lung cancer, according to data from a large prospective case-cohort study in the April 28 online issue of the Journal of the National Cancer Institute.

Acrylamide is formed in some starchy foods, such as potato chips and French fries, during high-temperature cooking. Epidemiological studies have found a positive association between dietary acrylamide intake and the risk of endometrial, ovarian, renal cell, and estrogen-receptor positive breast cancers.

To investigate whether dietary acrylamide intake is associated with lung cancer risk, Janneke G. F. Hogervorst, M.Sc., of Maastricht University in the Netherlands, and colleagues conducted a case-cohort study among 58,279 men and 62,573 women in the Netherlands Cohort Study on Diet and Cancer. Intake of acrylamide was estimated based on food-frequency questionnaires completed upon enrollment in the study.

After a follow-up of 13 years, 1,600 men and 295 women were diagnosed with lung cancer. When the investigators divided participants into five groups based on dietary acrylamide intake, they found no statistically significant difference in lung cancer incidence in men who consumed the highest and lowest amounts of acrylamide-containing foods. By contrast, the researchers found that women who ate the most acrylamide-containing foods had a statistically significant lower incidence of lung cancer compared with those in the group who consumed the least acrylamide-containing foods. All analyses were adjusted for smoking.

"Acrylamide intake was not associated with lung cancer risk in men but was inversely associated in women… This finding suggests that acrylamide is involved in human carcinogenesis through pathways other than genotoxicity," the authors write. They hypothesize that acrylamide may affect hormonal balances, which might explain how it could be associated with a reduction in lung cancer risk but an increase in risk of endometrial and ovarian malignancies.

In an accompanying editorial, Lorelei A. Mucci, ScD. and Hans-Olov Adami, M.D., Ph.D., of the Harvard School of Public Health in Boston, review past studies of dietary acrylamide and cancer, as well as the initial discovery of acrylamide in foods. They note that several studies have found a positive association between dietary acrylamide and some types of cancer. The editorialists also express caution about concluding that dietary acrylamide may have a protective effect in women with respect to lung cancer risk, pointing out the potential for false-positive associations.

"In our view, speculation about the potential mechanisms of the protective effect of acrylamide on lung cancer among women should await confirmation of the association in additional studies," the editorialists conclude. "Perhaps the safer conclusion we can make from the Netherlands study is that the findings do not support a positive association between acrylamide intake from diet and risk of lung cancer."
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White Tea Helps Weight Loss

Thursday, May 7, 2009

White tea -- the solution to the obesity epidemic?



Possible anti-obesity effects of white tea have been demonstrated in a series of experiments on human fat cells (adipocytes). Researchers writing in BioMed Central's open access journal Nutrition and Metabolism have shown that an extract of the herbal brew effectively inhibits the generation of new adipocytes and stimulates fat mobilization from mature fat cells.

Marc Winnefeld led a team of researchers from Beiersdorf AG, Germany, who studied the biological effects of an extract of white tea – the least processed version of the tea plant Camellia sinensis. He said, "In the industrialized countries, the rising incidence of obesity-associated disorders including cardiovascular diseases and diabetes constitutes a growing problem. We've shown that white tea may be an ideal natural source of slimming substances".

After treating lab-cultured human pre-adipocytes with the tea extract, the authors found that fat incorporation during the genesis of new adipocytes was reduced. According to Winnefeld, "The extract solution induced a decrease in the expression of genes associated with the growth of new fat cells, while also prompting existing adipocytes to break down the fat they contain".

White tea is made from the buds and first leaves of the plant used to make green tea and the black tea most commonly drunk in Western countries. It is less processed than the other teas and contains more of the ingredients thought to be active on human cells, such as methylxanthines (like caffeine) and epigallocatechin-3-gallate (EGCG) – which the authors believe to be responsible for many of the anti-adipogenic effects demonstrated in their study.


Article: White Tea extract induces lipolytic activity and inhibits adipogenesis in human subcutaneous (pre)-adipocytes _Jörn Söhle, Anja Knott, Ursula Holtzmann, Ralf Siegner, Elke Grönniger, Andreas Schepky, Stefan Gallinat, Horst Wenck, Franz Stäb and Marc Winnefeld _Nutrition & Metabolism article available at the journal website: http://www.nutritionandmetabolism.com/
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Wine may boost life expectancy by 5 years

Half a glass of wine a day may boost life expectancy by 5 years

Long-term wine consumption is related to cardiovascular mortality and life expectancy independently of moderate alcohol intake

Drinking up to half a glass of wine a day may boost life expectancy by five years—at least in men—suggests research published ahead of print in the Journal of Epidemiology and Community Health.

The Dutch authors base their findings on a total of 1,373 randomly selected men whose cardiovascular health and life expectancy at age 50 were repeatedly monitored between 1960 and 2000.

The researchers looked into how much alcohol the men drank, what type it was, and over what period, in a bid to assess whether this had any impact on the risks of their dying from cardiovascular disease, cerebrovascular disease, and from all causes.

They also tracked weight and diet, whether the men smoked, and for how long, and checked for the presence of serious illness.

During the 40 years of monitoring, 1,130 of the men died. Over half the deaths were caused by cardiovascular disease.

The proportion of men who drank alcohol almost doubled from 45% in 1960 to 86% in 2000, with the proportion of those drinking wine soaring from 2% to 44% during that period.

The researchers found that light long term alcohol consumption of all types—up to 20 g a day— extended life by around two extra years compared with no alcohol at all. Extended life expectancy was slightly less for those who drank more than 20 g.

And men who drank only wine, and less than half a glass of it a day, lived around 2.5 years longer than those who drank beer and spirits, and almost five years longer than those who drank no alcohol at all.

Drinking wine was strongly associated with a lower risk of dying from coronary heart disease, cerebrovascular disease, and death from all causes.

These results held true, irrespective of socioeconomic status, dietary and other lifestyle habits, factors long thought to influence the association between wine drinking and better health.
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