Cancer-protective properties of milk

Milk consumption has been linked to improved health, with decreased risks of diabetes, metabolic syndrome, and colon cancer. A group of scientists in Sweden found that lactoferricin4-14 (Lfcin4-14), a milk protein with known health effects, significantly reduces the growth rate of colon cancer cells over time by prolonging the period of the cell cycle before chromosomes are replicated. In a new study, investigators report that treatment with Lfcin4-14 reduced DNA damage in colon cancer cells exposed to ultraviolet (UV) light. Their results are published in the October issue of the Journal of Dairy Science®.

"We previously hypothesized that the prolongation of the cell cycle in colon cancer cells as a result of Lfcin4-14 treatment may give the cells extra time for DNA repair," says one of the lead investigators, Professor Stina Oredsson, of the Department of Biology at the University of Lund, Sweden. "Indeed, UV light-induced damage was decreased in colon cancer cells treated with Lfcin4-14 compared with controls. The differences were small but significant."

Investigators exposed colon cancer cells to UV light that caused DNA damage and then grew the cells in the absence or presence of Lfcin4-14. They evaluated DNA damage using a sensitive technique known as comet assay. After the cells are processed, the cells with DNA damage resemble a comet with a tail, and the intensity of the tail compared to the comet head indicates the number of DNA breaks. UV light exposure resulted in an increase in the number of comets while treatment with Lfcin4-14 reduced the number of comets in UV light-exposed cells.

To understand the mechanism by which Lfcin4-14 reduced DNA damage, investigators evaluated the levels of several proteins involved in cell cycle progression, DNA repair, and cell death. They found an increase in flap endonuclease-1, a protein associated with DNA synthesis; a decrease in b-cell lymphoma 2-associated X protein, which is involved with cell death; and a decrease in the level of -H2AX, indicating more efficient DNA repair. "These changes in expression support our hypothesis that Lfcin4-14 treatment resulted in increased DNA repair," says Dr. Oredsson.

Dr. Oredsson notes that cancer cells, in general, have defects in the DNA repair mechanisms. Thus, Lfcin4-14 may have a greater effect on normal cells than on cancer cells. "Our data suggest that the effects of Lfcin4-14 in prolonging the cell cycle may contribute to the cancer preventive effect of milk. This must be further investigated in different systems," she concludes.

An apple a day might keep the cardiologist away

Eating an apple a day might in fact help keep the cardiologist away, new research suggests.

In a study of healthy, middle-aged adults, consumption of one apple a day for four weeks lowered by 40 percent blood levels of a substance linked to hardening of the arteries.

Taking capsules containing polyphenols, a type of antioxidant found in apples, had a similar, but not as large, effect.

The study, funded by an apple industry group, found that the apples lowered blood levels of oxidized LDL -- low-density lipoprotein, the "bad" cholesterol. When LDL cholesterol interacts with free radicals to become oxidized, the cholesterol is more likely to promote inflammation and can cause tissue damage.

"When LDL becomes oxidized, it takes on a form that begins atherosclerosis, or hardening of the arteries," said lead researcher Robert DiSilvestro, professor of human nutrition at Ohio State University and a researcher at the university's Ohio Agricultural Research and Development Center. "We got a tremendous effect against LDL being oxidized with just one apple a day for four weeks.”

The difference was similar to that found between people with normal coronary arteries versus those with coronary artery disease, he said.

The study is published online in the Journal of Functional Foods and will appear in a future print edition.

DiSilvestro described daily apple consumption as significantly more effective at lowering oxidized LDL than other antioxidants he has studied, including the spice-based compound curcumin, green tea and tomato extract.

“Not all antioxidants are created equal when it comes to this particular effect,” he said.

DiSilvestro first became interested in studying the health effects of eating an apple a day after reading a Turkish study that found such a regimen increased the amount of a specific antioxidant enzyme in the body.

In the end, his team didn't find the same effect on the enzyme, but was surprised at the considerable influence the apples had on oxidized LDL.

For the study, the researchers recruited nonsmoking healthy adults between the ages of 40 and 60 who had a history of eating apples less than twice a month and who didn't take supplements containing polyphenols or other plant-based concentrates.

In all, 16 participants ate a large Red or Golden Delicious apple purchased at a Columbus-area grocery store daily for four weeks; 17 took capsules containing 194 milligrams of polyphenols a day for four weeks; and 18 took a placebo containing no polyphenols. The researchers found no effect on oxidized LDLs in those taking the placebo.

“We got a tremendous effect against LDL being oxidized with just one apple a day for four weeks.”

"We think the polyphenols account for a lot of the effect from apples, but we did try to isolate just the polyphenols, using about what you'd get from an apple a day," DiSilvestro said. "We found the polyphenol extract did register a measurable effect, but not as strong as the straight apple. That could either be because there are other things in the apple that could contribute to the effect, or, in some cases, these bioactive compounds seem to get absorbed better when they're consumed in foods."

Still, DiSilvestro said polyphenol extracts could be useful in some situations, "perhaps in higher doses than we used in the study, or for people who just never eat apples."

The study also found eating apples had some effects on antioxidants in saliva, which has implications for dental health, DiSilvestro said. He hopes to follow up on that finding in a future study.

Moderate alcohol intake and cancer: the role of under-reporting

A large US cohort study in 129,987 persons suggests that the apparent increased risk of cancer among light-moderate drinkers is substantially due to underreporting of intake.

Although experts agree that heavy consumption of alcohol is related to increased risk of several cancer types, the role of light-to-moderate drinking is less clear, said Dr Arthur Klatsky of Kaiser Permanente Medical Care Program, Oakland, CA, USA. Some studies have suggested there is a connection, while others have found no link.

The results of the new analysis suggest that any apparent relationship between cancer risk and light-to-moderate drinking, meaning up to 2 standard sized drinks per day for men and one for women, may be largely an artifact of under-reporting—that is, lying about drinking amount.

"If some heavy drinkers answer surveys saying that they only drink lightly, the effects of heavy drinking then appear to be related to light-to-moderate intake," Dr Klatsky explained. "Our analysis inferentially supports this factor in our study population and it is probably applicable to most studies, as under-reporting of alcohol consumption is surely prevalent."

"There are plenty of reasons why people need to avoid heavy drinking, but these do not generally apply to light drinking," Dr Klatsky said. "All concerns about the risks of light drinking need to be balanced by the evidence that persons at risk of heart disease benefit from lighter alcohol drinking. This --with plenty of exceptions-- means most persons over 50."

Reduced glaucoma risk in patients who take statins

People who take statins to reduce their risk of cardiovascular disease are less likely to be diagnosed with the most common form of glaucoma, according to a nationwide study of more than 300,000 patients. A University of Michigan School of Medicine research team, directed by Joshua Stein, MD, MS, found that the risk for glaucoma was reduced by eight percent in patients who took statins continuously for two years, compared with patients who did not take statins. The study, the largest to date on the topic, is published in the October issue of Ophthalmology, the journal of the American Academy of Ophthalmology.

Dr. Stein's study was sparked by growing evidence that statin use may protect the optic nerve and retinal nerve fibers, structures that are essential to good vision and are damaged by glaucoma. His team used healthcare claims data for a diverse population of Americans aged 60 and older who took statins to control high blood levels of unhealthy fats, a condition known as hyperlipidemia, between 2001 and 2009, The researchers assessed patients' risk for open-angle glaucoma (OAG). Unlike earlier studies, their analysis adjusted for patients who also had diabetes and/or hypertension to prevent distortion of the results.

Several of the study's findings suggest that statin use may be most important before glaucoma is diagnosed, or in the early stages of the disease. Dr. Stein's research may lead to new preventive treatments that could especially benefit groups at increased risk, including African-Americans, Hispanics and those with a family history of glaucoma.

Glaucoma affects more than 2.7 million Americans age 40 and older . If untreated, glaucoma causes vision loss or blindness by damaging the eye's optic nerve. The optic nerve sends signals from the retina — a layer of light-sensitive tissue at the back of the eye — to the brain, where these signals are interpreted as the images we see. Only about half of the people who have glaucoma know it, since symptoms are rarely noticed in the early stages and vision loss is very gradual in most cases.

"Statins' apparent ability to reduce glaucoma risk may be due to several factors, including improved blood flow to the optic nerve and retinal nerve cells and enhanced outflow of the aqueous fluid, which may reduce intraocular pressure," said Dr. Stein. "While more research is needed, we hope our results may contribute to saving the sight of thousands who are predisposed to glaucoma."

Dr. Stein cautioned that the study results apply only to patients with hyperlipidemia, and that further study is needed to determine whether statins also protect patients who don't have this diagnosis or have other characteristics that differ from the study population.

ZINC DEFICIENCY LINKED TO AGING, MULTIPLE DISEASES

A new study has outlined for the first time a biological mechanism by which zinc deficiency can develop with age, leading to a decline of the immune system and increased inflammation associated with many health problems, including cancer, heart disease, autoimmune disease and diabetes.

The research was done by scientists in the Linus Pauling Institute at Oregon State University and the OSU College of Public Health and Human Sciences. It suggests that it’s especially important for elderly people to get adequate dietary intake of zinc, since they may need more of it at this life stage when their ability to absorb it is declining.

About 40 percent of elderly Americans and as many as two billion people around the world have diets that are deficient in this important, but often underappreciated micronutrient, experts say.

The study was published in the Journal of Nutritional Biochemistry, based on findings with laboratory animals. It found that zinc transporters were significantly dysregulated in old animals. They showed signs of zinc deficiency and had an enhanced inflammatory response even though their diet supposedly contained adequate amounts of zinc.

When the animals were given about 10 times their dietary requirement for zinc, the biomarkers of inflammation were restored to those of young animals.

“The elderly are the fastest growing population in the U.S. and are highly vulnerable to zinc deficiency,” said Emily Ho, an LPI principal investigator and associate professor in OSU School of Biological and Population Health Sciences. “They don’t consume enough of this nutrient and don’t absorb it very well.”

“We’ve previously shown in both animal and human studies that zinc deficiency can cause DNA damage, and this new work shows how it can help lead to systemic inflammation,” Ho said.

“Some inflammation is normal, a part of immune defense, wound healing and other functions,” she said. “But in excess, it’s been associated with almost every degenerative disease you can think of, including cancer and heart disease. It appears to be a significant factor in the diseases that most people die from.”

As a result of this and what is now know about zinc absorption in the elderly, Ho said that she would recommend all senior citizens take a dietary supplement that includes the full RDA for zinc, which is 11 milligrams a day for men and 8 milligrams for women. Zinc can be obtained in the diet from seafood and meats, but it’s more difficult to absorb from grains and vegetables – a particular concern for vegetarians.

“We found that the mechanisms to transport zinc are disrupted by age-related epigenetic changes,” said Carmen Wong, an OSU research associate and co-author of this study. “This can cause an increase in DNA methylation and histone modifications that are related to disease processes, especially cancer. Immune system cells are also particularly vulnerable to zinc deficiency.”

Research at OSU and elsewhere has shown that zinc is essential to protect against oxidative stress and help repair DNA damage. In zinc deficiency, the risk of which has been shown to increase with age, the body’s ability to repair genetic damage may be decreasing even as the amount of damage is going up.

Medical tests to determine zinc deficiency are rarely done, scientists say, and are not particularly accurate even if they are done. The best approach is to assure adequate intake of the nutrient through diet or supplements, they said, especially in the elderly.

Even though elderly people have less success in absorbing zinc, the official RDA for them is the same as in younger adults. That issue should be examined more closely, Ho said.

Levels of zinc intake above 40 milligrams per day should be avoided, researchers said, because at very high levels they can interfere with absorption of other necessary nutrients, including iron and copper.

Omega-3 Supplements May Slow A Biological Effect of Aging

Taking enough omega-3 fatty acid supplements to change the balance of oils in the diet could slow a key biological process linked to aging, new research suggests.

The study showed that most overweight but healthy middle-aged and older adults who took omega-3 supplements for four months altered a ratio of their fatty acid consumption in a way that helped preserve tiny segments of DNA in their white blood cells.

These segments, called telomeres, are known to shorten over time in many types of cells as a consequence of aging. In the study, lengthening of telomeres in immune system cells was more prevalent in people who substantially improved the ratio of omega-3s to other fatty acids in their diet.

Omega-3 supplementation also reduced oxidative stress, caused by excessive free radicals in the blood, by about 15 percent compared to effects seen in the placebo group.

“The telomere finding is provocative in that it suggests the possibility that a nutritional supplement might actually make a difference in aging,” said Jan Kiecolt-Glaser, professor of psychiatry and psychology at Ohio State and lead author of the study.

In another recent publication from this study, Kiecolt-Glaser and colleagues reported that omega-3 fatty acid supplements lowered inflammation in this same group of adults.

“Inflammation in particular is at the heart of so many health problems. Anything that reduces inflammation has a lot of potentially good spinoffs among older adults,” she said.

Study participants took either 2.5 grams or 1.25 grams of active omega-3 polyunsaturated fatty acids, which are considered “good fats” that, when consumed in proper quantities, are associated with a variety of health benefits. Participants on the placebo took pills containing a mix of oils representing a typical American’s daily intake.

The researchers say this combination of effects suggests that omega-3 supplements could represent a rare single nutritional intervention that has potential to lower the risk for a host of diseases associated with aging, such as coronary heart disease, Type 2 diabetes, arthritis and Alzheimer’s disease.

The study is published online and scheduled for later print publication in the journal Brain, Behavior, and Immunity.

Participants received either the placebo or one of the two different doses of omega-3 fatty acids. The supplements were calibrated to contain a ratio of the two cold-water fish oil fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), of seven to one. Previous research has suggested that EPA has more anti-inflammatory properties than DHA.

In the case of fatty acids, omega-3 supplementation alone doesn’t tell the whole story of how this dietary change can affect health, explained Martha Belury, professor of human nutrition at Ohio State and a co-author of the study. Also important is the ratio of omega-6 fatty acids to omega-3 fatty acids that are present in a person’s blood.

Omega-6 fatty acids come from vegetable oils, and since the 1960s, research has suggested that these oils, too, can help protect the cardiovascular system. However, the typical American diet tends to be heavy on omega-6 fatty acids and comparatively low in omega-3s that are naturally found in cold-water fish such as salmon and tuna. While the ratio of omega-6 to omega-3 fatty acids averages about 15-to-1, researchers tend to agree that for maximum benefit, this ratio should be lowered to 4-to-1, or even 2-to-1.

The long chains – or bigger molecules – that make up EPA and DHA fatty acids are believed to be the secret to their effectiveness, Belury said.

Both groups of participants who took omega-3 supplements showed, on average, lengthening of telomeres compared to overall telomere effects in the placebo group, but the relationship could have been attributed to chance. However, when the researchers analyzed the participants’ omega-6 to omega-3 ratio in relationship to telomere lengthening, a lower ratio was clearly associated with lengthened telomeres.

“The idea we were looking at with the ratio of omega-6 to omega-3 fatty acids was an increase in the denominator to make the ratio smaller. In the United States, we need to focus on the omega-3 part because we don’t get enough of those,” Belury said.

The researchers also measured levels of compounds called F2-isoprostanes to determine levels of oxidative stress, which is linked to a number of conditions that include heart disease and neurodegenerative disorders. Both omega-3 groups together showed an average overall 15 percent reduction in oxidative stress compared to effects seen in the placebo group.

When the scientists revisited their earlier inflammation findings, they also found that decreases in an inflammatory marker in the blood called interleukin-6 (IL-6) were associated with telomere lengthening. In their earlier paper on omega-3s and inflammation, they reported that omega-3 supplements lowered IL-6 by 10 to 12 percent, depending on the dose. By comparison, those taking a placebo saw an overall 36 percent increase in IL-6 by the end of the study.

“This finding strongly suggests that inflammation is what’s driving the changes in the telomeres,” Kiecolt-Glaser said.

Telomeres are a hot topic in science, and their tendency to shorten is associated with such age-related problems as heart disease and early mortality. These short fragments of DNA act as caps at the end of chromosomes, and can be likened to the protective plastic at the end of a shoelace.

“Anything that reduces inflammation has a lot of potentially good spinoffs among older adults.”

“If that plastic comes off, the shoelace unravels and it doesn’t work anymore,” said study co-author Ron Glaser, professor of molecular virology, immunology and medical genetics and director of the Institute for Behavioral Medicine Research (IBMR) at Ohio State. “In the same way, every time a cell divides, it loses a little bit of its DNA at the ends, and over time, that can cause significant problems.”

Kiecolt-Glaser noted that this population was disease-free and reported very little stress. The study included 106 adults, average age 51 years, who were either overweight or obese and lived sedentary lives. The researchers excluded people taking medications to control mood, cholesterol and blood pressure as well as vegetarians, patients with diabetes, smokers, those routinely taking fish oil, people who got more than two hours of vigorous exercise each week and those whose body mass index was either below 22.5 or above 40.

“People who are less healthy than this group, and especially those who experience chronic stress, may gain even more benefits from omega-3 supplementation,” she said.

Gum Disease Bacteria Linked To Pancreatic Cancer Risk

The British Dental Health Foundation believes new scientific research presented is a further indication of a possible link between pancreatic cancer and gum disease.

The latest research, presented in the journal Gut, found one of the bacterium key in the development of gum disease was associated with a two-fold increase in risk for pancreatic cancer. The study also discovered those with non-harmful oral bacteria had a 45 per cent lower risk of pancreatic cancer.

Although researchers cannot confirm whether gum disease contributes towards a higher risk of developing pancreatic cancer, the research is a further indication of a potential link between the two diseases.

Previous research has also drawn an association between bacteria responsible for gum disease and pancreatic cancer, although in both cases it remains unclear whether the presence of particular types of bacteria are a cause or effect of pancreatic cancer.

The paper's corresponding author Dominique Michaud, epidemiologist at Brown University, commented: "This is not an established risk factor. But I feel more confident that something is going on. It's something we need to understand better."

Co-lead author Jacques Izard, of the Forsyth Institute and Harvard University concurred. He said: "We need to further investigate the importance of bacteria in pancreatic cancer beyond the associated risk."

Pancreatic cancer accounted for 7,901 deaths in 20104, while only four per cent of people in England survived the disease for more than five years. Given these statistics, Chief Executive of the British Dental Health Foundation, Dr Nigel Carter OBE, believes any link between the two diseases should provide a timely reminder about the importance of good oral health.

Dr Carter said: "This research provides further ammunition to the growing belief these two diseases could be related.

"There is no escaping the fact poor oral health has some role to play, as a number of studies are now starting to show. What we must remember is oral health is relatively simple to maintain. The Foundation's three key messages - brushing your teeth for two minutes twice a day using a fluoride toothpaste, cutting down on how often you have sugary foods and drinks and visiting the dentist regularly, as often as they recommend - are a great starting point for maintaining good oral health.

"If you have swollen gums that bleed regularly when brushing, bad breath, loose teeth or regular mouth infections appear, it is likely you have gum disease. If any of these symptoms persist, your dentist may be able to help you."