High dietary fat, cholesterol linked to increased risk of breast cancer

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Elevated fat and cholesterol levels found in a typical American-style diet play an important role in the growth and spread of breast cancer, say researchers at the Kimmel Cancer Center at Jefferson.

The study, published in the January issue of The American Journal of Pathology, examines the role of fat and cholesterol in breast cancer development using a mouse model. The results show that mice fed a Western diet and predisposed to develop mammary tumors, can develop larger tumors that are faster growing and metastasize more easily, compared to animals eating a control diet.

The research team led by cancer biologist Philippe G. Frank, Ph.D., Assistant Professor in the Department of Stem Cell Biology and Regenerative Medicine at Thomas Jefferson University, was interested in learning about the link between diet and breast cancer. The incidence rate of this cancer is five times higher in Western countries than in other developed countries. Moreover, studies have shown an increase in breast cancer incidence in immigrant populations that relocate from a region with low incidence. "These facts suggest strong environmental influence on breast cancer development," says Dr. Frank.

Dietary fat and cholesterol have been shown to be important risk factors in the development and progression of a number of tumor types, but diet-based studies in humans have reached contradictory conclusions. This has led Dr. Frank to turn to animal models of human cancer to examine links between cholesterol, diet, and cancer.

The research team turned to the PyMT mouse model to determine the role of dietary fat and cholesterol in tumor development. This mouse model is believed to closely parallel the pathogenesis of human breast cancer. PyMT mice were placed on a diet that contained 21.2 percent fat and 0.2 percent cholesterol, reflective of a typical Western diet. A control group of PyMT mice was fed a normal chow that had only 4.5 percent fat and negligible amounts of cholesterol.

The researchers found that tumors began to develop quickly in mice fed the fat/cholesterol-enriched chow. In this group, the number of tumors was almost doubled, and they were 50 percent larger than those observed in mice that ate a normal diet. "The consumption of a Western diet resulted in accelerated tumor onset and increased tumor incidences, multiplicity, and burden, suggesting an important role for dietary cholesterol in tumor formation," Dr. Frank says. There was also a trend towards an increased number of lung metastasis in mice fed the fatty diet, he adds.

To confirm the aggressive nature of the cancer in animals fed a cholesterol-rich diet, the researchers examined the levels of several biomarkers of tumor progression and found a signature of a more advanced cancer stage, compared to tumors that developed in the control group.

The researchers also showed that plasma cholesterol levels in experimental mice that developed tumors were significantly reduced compared to a group of "wild-type" mice – animals with no predisposition to develop tumors – that was also fed a cholesterol-rich diet. "This suggests that tumor formation was responsible for the reduction in blood cholesterol levels observed in our animals," indicates Dr. Frank.

Dr. Frank explains the use of cholesterol in breast tumors this way: "In a neighborhood, if you want to build more houses, you need more bricks. In tumors, cholesterol provides the bricks that are the foundation for further growth, and this cholesterol comes from the blood. A drop in blood cholesterol may signify that some tumors are growing as cholesterol provides support for breast cancer growth."

"These data provide new evidence for an increase in cholesterol utilization by breast tumors and thus provides many new avenues for prevention, screening, and treatment," indicates Dr. Frank. These findings suggest that use of cholesterol-lowering drugs, such as statins, may both protect against breast cancer as well as treat patients carrying tumors. Since researchers also found that blood cholesterol levels dropped significantly as tumors began to develop, the study indicates measuring blood cholesterol levels may also be an effective method of screening cancer development.

This research team also discovered the same association between cholesterol and growth of prostate cancer in mice in a study published in the December issue of The American Journal of Pathology. The results of these two new studies indicate, according to Dr. Frank that, "Cholesterol does indeed seem to be an important factor in the regulation of tumor formation in several cancer types."

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How resveratrol works

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Resveratrol, a compound in grapes, displays antioxidant and other positive properties. In a study published this week, researchers at the UT Health Science Center San Antonio describe a novel way in which resveratrol exerts these beneficial health effects.

Resveratrol stimulates the expression of adiponectin, a hormone derived from cells that manufacture and store fat, the team found. Adiponectin has a wide range of beneficial effects on obesity-related medical complications, said senior author Feng Liu, Ph.D., professor of pharmacology and member of the Barshop Institute of Longevity and Aging Studies at the Health Science Center.

Both adiponectin and resveratrol display anti-obesity, anti-insulin resistance and anti-aging properties.

“Results from these studies should be of interest to those who are obese, diabetic and growing older,” Dr. Liu said. “The findings should also provide important information on the development of novel therapeutic drugs for the treatment of these diseases.”

The researchers confirmed the finding in cells and animal models. The study is in the Jan. 7 issue of the Journal of Biological Chemistry.

Previous studies

In July 2009 in the journal Nature, the Barshop Institute and collaborators reported that the compound rapamycin extended life in mice. Rapamycin, like resveratrol, is under scrutiny for its beneficial health effects.

In 2010, Dr. Liu and colleagues announced that resveratrol inhibits activity of the mammalian target of rapamycin (mTOR). This discovery was included in the prestigious Faculty of 1000 (F1000), a service that identifies and evaluates the most important articles in biology and medical research publications. The selection process involves a peer-nominated global “faculty” of the world's leading scientists and clinicians who rate the best of the articles they read and explain their importance.

A reviewer said the study, which appeared in the Journal of Biological Chemistry, would open up work in a new area: explaining how resveratrol and rapamycin synergistically achieve their results.

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Regularly drinking green tea could protect against Alzheimer's and other forms of dementia

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Regularly drinking green tea could protect the brain against developing Alzheimer's and other forms of dementia, according to latest research by scientists at Newcastle University.

The study, published in the academic journal Phytomedicine, also suggests this ancient Chinese remedy could play a vital role in protecting the body against cancer.

Led by Dr Ed Okello, the Newcastle team wanted to know if the protective properties of green tea – which have previously been shown to be present in the undigested, freshly brewed form of the drink – were still active once the tea had been digested.

Digestion is a vital process which provides our bodies with the nutrients we need to survive. But, says Dr Okello, it also means that just because the food we put into our mouths is generally accepted to contain health-boosting properties, we can't assume these compounds will ever be absorbed by the body.

"What was really exciting about this study was that we found when green tea is digested by enzymes in the gut, the resulting chemicals are actually more effective against key triggers of Alzheimer's development than the undigested form of the tea," explains Dr Okello, based in the School of Agriculture, Food and Rural Development at Newcastle University.

"In addition to this, we also found the digested compounds had anti-cancer properties, significantly slowing down the growth of the tumour cells which we were using in our experiments."

As part of the research, the Newcastle team worked in collaboration with Dr Gordon McDougall of the Plant Products and Food Quality Group at the Scottish Crop Research Institute in Dundee, who developed technology which simulates the human digestive system.

It is this which made it possible for the team to analyse the protective properties of the products of digestion.

Two compounds are known to play a significant role in the development of Alzheimer's disease – hydrogen peroxide and a protein known as beta-amyloid.

Previous studies have shown that compounds known as polyphenols, present in black and green tea, possess neuroprotective properties, binding with the toxic compounds and protecting the brain cells.

When ingested, the polyphenols are broken down to produce a mix of compounds and it was these the Newcastle team tested in their latest research.

"It's one of the reasons why we have to be so careful when we make claims about the health benefits of various foods and supplements," explains Dr Okello.

"There are certain chemicals we know to be beneficial and we can identify foods which are rich in them but what happens during the digestion process is crucial to whether these foods are actually doing us any good."

Carrying out the experiments in the lab using a tumour cell model, they exposed the cells to varying concentrations of the different toxins and the digested green tea compounds.

Dr Okello explained: "The digested chemicals protected the cells, preventing the toxins from destroying the cells.

"We also saw them affecting the cancer cells, significantly slowing down their growth.

"Green tea has been used in Traditional Chinese medicine for centuries and what we have here provides the scientific evidence why it may be effective against some of the key diseases we face today."

The next step is to discover whether the beneficial compounds are produced during digestion after healthy human volunteers consume tea polyphenols. The team has already received funding from the Biotechnology and Biological Sciences Research Council (BBSRC) to take this forward.

Dr Okello adds: "There are obviously many factors which together have an influence on diseases such as cancer and dementia - a good diet, plenty of exercise and a healthy lifestyle are all important."

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Mediterranean Diet Associated With Slower Rate of Cognitive Decline

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The Mediterranean diet, rich in vegetables, fish, and olive oil and moderate in wine and alcohol, is associated with slower rates of cognitive decline in older adults, according to researchers at Rush University Medical Center.

The results are published in the American Journal of Clinical Nutrition.

Included in the study were 3,759 older residents of the South side of Chicago who are part of the Chicago Healthy Aging Project, an ongoing evaluation of cognitive health in adults over the age of 65. Every three years, the study participants, age 65 and older, underwent a cognitive assessment that tested such things as memory and basic math skills. Participants also filled out a questionnaire on the frequency with which they consumed 139 food items ranging from cereals and olive oil to red meat and alcohol.

The researchers then analyzed how closely each of the study participants adhered to a Mediterranean diet, which includes daily consumption of such foods as fruit, vegetables, legumes, olive oil, fish, potatoes and nonrefined cereals, as well as wine.

Out of a maximum score of 55, which would indicate complete adherence to the Mediterranean diet, the average study participant scored 28. Those with the higher scores were also the individuals whose cognitive tests showed a slower rate of decline, even when other factors that might account for the result, such as education level, were considered.

The researchers also analyzed how closely study participants adhered to the Healthy Eating Index—2005, which is based on the recommendations from the 2005 Dietary Guidelines for Americans. Higher scores indicating closer adherence to this index, which gives less weight to fish, legumes and moderate alcohol intake, did not correspond with differences in rates of cognitive decline.

Christy Tangney, PhD, lead author of the study and associate professor of clinical nutrition at Rush University, said that the results add to other studies showing that a Mediterranean diet reduces the risk of heart disease, certain cancers and diabetes.

“The more we can incorporate vegetables, olive oil, and fish into our diets and moderate wine consumption, the better for our aging brains and bodies,” Tangney said.

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The Effect of Diet on Mental Energy

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The Life Sciences Research Organization, Inc. (LSRO) has published a review article in the December 2010 issue of Nutrition Reviews entitled Do Specific Constituents and Supplements Affect Mental Energy? Review of the Evidence.

The marketplace abounds with claims that various foods, beverages, and dietary supplements increase mental energy. LSRO has undertaken a review of the scientific evidence for more than 35 food ingredients, dietary supplements, dietary constituents, and dietary factors and any measure of mental energy that could support these claims. Mental energy was defined as consisting of mood (transient feelings about the presence of fatigue or energy), motivation (determination and enthusiasm), and cognition (sustained attention and vigilance).

The review article focuses on four dietary constituents/supplements: Ginkgo biloba, ginseng, glucose, and omega-3 polyunsaturated fatty acids (PUFA) to illustrate the current state of the peer-reviewed scientific literature on dietary constituents and mental energy. The strongest evidence, other than that for caffeine, suggests effects of Ginkgo biloba on certain aspects of mood and attention in healthy subjects, as well as associations between omega-3 PUFA and reduced risk of age-related cognitive decline.

Among the key findings of the review are:

_ Until recently, mental energy has been only loosely defined and methods to assess it were not clearly described.

_ For most ingredients and dietary factors fewer than 5 scientific studies address mental energy.

_ Other than caffeine, the strongest evidence suggests Gingko biloba affects mood and attention and omega-3 PUFA may reduce the risk of cognitive decline.

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Consistent exercise = lower risk of colon cancer death

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Consistent exercise is associated with a lower risk of dying from colon cancer, according to a new study led by researchers at the Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis. The study is among the first to show that physical activity can make the disease less deadly.

The Washington University researchers worked with colleagues from the American Cancer Society and examined data from the American Cancer Society Prevention Study II (CPS II) to look at whether changes in physical activity influenced either the incidence of colon cancer diagnosis or the risk of death from the disease.

The CPS II study included more than 150,000 men and women. To determine how exercise affected colon cancer, the researchers compared their levels of physical activity between 1982 and 1997, and linked those activity levels both to the number of colon cancer diagnoses between 1998 and 2005, and to the number of colon cancer deaths that occurred between 1998 and 2006. It turned out that those who exercised consistently for at least 10 years had the lowest risk of colon cancer death.

“People who were consistently active over the course of their adulthood had a lower risk of death from colon cancer than those who were sedentary,” says first author Kathleen Y. Wolin, ScD. “People often wonder around the start of a new year whether exercise really will help them stay healthy or whether it’s already too late. It’s never too late to start exercising, but it’s also never too early to start being active. That’s the message we hope people will take away from this study.”

Wolin, assistant professor of surgery in the Division of Public Health Sciences, says the benefits of starting an exercise program include not just preventing colon cancer and death from the disease, but also reduced risk of heart disease, diabetes and other cancers.

She says the greatest benefits seem to accrue in those who have exercised for the largest percentage of their lives. But it isn’t necessary to run marathons or to work out for many hours every day.

“You get enormous ‘bang for the buck,’” she says. “You go for a 30-minute walk every day, and you’re going to reduce your risk of a number of diseases. And in addition, our research has also shown that you feel better, physically and mentally, so you’re able to function better.”

And physical activity even can be beneficial after a cancer diagnosis already has been made.

“There is evidence that being physically active can reduce the risk of recurrence and death following a cancer diagnosis,” Wolin says. “So even those who haven’t been physically active can begin exercising after their diagnosis and see some real benefits as well.”

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Vitamin D deficiencies may = autoimmune lung disease

Study shows vitamin D deficiencies may impact onset of autoimmune lung disease

CINCINNATI—A new study shows that vitamin D deficiency could be linked to the development and severity of certain autoimmune lung diseases.

These findings are being reported in the Jan. 4 edition of the journal Chest.

Brent Kinder, MD, UC Health pulmonologist, director of the Interstitial Lung Disease Center at the University of Cincinnati and lead investigator on the study, says vitamin D deficiencies have been found to affect the development of other autoimmune diseases, like lupus and type 1 diabetes.

"We wanted to see if lack of sufficient vitamin D would also be seen in patients who are diagnosed with an autoimmune interstitial lung disease (ILD) and whether it was associated with reduced lung function," he says.

Some ILD patients first discover they have an undifferentiated connective tissue disease, a chronic inflammatory autoimmune disease that affects multiple organ systems but is not developed enough for physicians to easily recognize and categorize.

Autoimmune diseases occur when the body produces abnormal cells that turn on the body and attack major organs and tissues. Connective tissue diseases include lupus, scleroderma, polymyositis, vasculitis, rheumatoid arthritis and Sjogren's syndrome.

"ILD is a group of diseases that mainly affect the tissues of the lungs instead of the airways, like asthma and emphysema do," says Kinder. "It causes scarring of the lungs, is more difficult to diagnosis and treat than other kinds of lung diseases and is often fatal.

"Since vitamin D deficiency has implications for other manifestations of autoimmune illnesses, we wanted to see it had an effect on the lungs of this patient population."

Researchers evaluated 118 patients from the UC ILD Center database—67 with connective tissue disease-related ILD and 51 with other causes of lung fibrosis—for serum 25-hydroxyvitamin D levels, which indicate levels of vitamin D in the body. Then, they evaluated associations between these serum levels and the patients' conditions.

Overall, those with connective tissue disease-related ILD were more likely to have vitamin D deficiency—52 percent versus 20 percent—and insufficiency—79 percent versus 31 percent—than other forms of ILD.

Among this same group of patients, reduced serum 25-hydroxyvitamin D levels were strongly associated with reduced lung function.

"These findings suggest that there is a high prevalence of vitamin D deficiency in patients with ILD, particularly those with connective tissue disease," Kinder says. "Therefore, vitamin D may have a role in the development of connective tissue disease-related ILD and patients' worsening lung function.

"One of the next steps is to see if supplementation will improve lung function for these patients."

He adds that if these findings are confirmed and vitamin D supplementation is shown to be effective in clinical trials, this may also provide a more natural, inexpensive treatment for the illness.

"Vitamin D is known to be a critical dietary factor for bone and skin health," he says. "Now, we're learning that it could potentially be modified as a treatment to improve ILD as opposed to other, more toxic therapies."

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