Prostate Cancer Symptoms Tips What is prostate cancer symptoms? We have tips about prostate cancer symptoms

Ω

Researchers analyze effects of air pollution, traffic accidents, and physical activity


Even though urban cyclists face hazards such as exposure to car exhaust and the risk of traffic accidents, it’s still far healthier to park the car and get on a bike. The health of the individual cyclists may improve as they drive less and exercise more, and the resulting reduction in exhaust emissions will benefit the entire community, according to a study published online June 30 ahead of print in the peer-reviewed journal Environmental Health Perspectives (EHP).

“The promotion of walking and cycling is a promising way to increase physical activity across the population by integrating it into daily life,” state the study authors. However, they note that if cycling is to be promoted for health reasons, the health benefits of cycling should outweigh the risks. Studies in Denmark, Finland, and China have shown that cycling is healthier than driving, but these studies have not tried to quantify specific health risks and benefits related to cycling, making it difficult to extrapolate results to specific environments and populations.

To develop an integrated assessment of the health risks and benefits of cycling, the researchers analyzed data from international studies on exposure to components of automobile exhaust, traffic fatalities, and benefits of exercise. For their analysis, the authors estimated the health impacts if 500,000 Dutch people aged 18–64 years were to switch from driving to cycling for one round trip of 7.5–15 km each day. They chose to estimate health in terms of mortality (years of life gained or lost) rather than morbidity (illness) because data about mortality tend to be more consistent; for example, minor traffic accidents involving cyclists tend to be far underreported compared with traffic deaths.

The authors found that cycling even short times in traffic can cause significant exposure to components of car exhaust, including ultrafine particles and soot, which can contribute to respiratory and cardiac illness. Cyclists tend to breathe about twice as deeply as drivers during their respective modes of travel, so cyclists inhale a larger dose of pollutants.

Cyclists are also more vulnerable to fatal traffic accidents than drivers, even in The Netherlands, which has a strong cycling culture and infrastructure, including dedicated bike trails. The authors estimated that in The Netherlands, the risk of dying in a traffic accident is four times greater per kilometer traveled for cyclists than for drivers. The risk ratios vary by age, because younger drivers are far more likely to die in traffic accidents than older drivers, so their risk of death might actually decrease if they switch to cycling.

Health benefits from cycling may also vary by the age. For example, older, sedentary adults tend to benefit most from increased exercise. However, benefits of exercise can be substantial for persons of all ages; some researchers estimate that inactive individuals who begin moderate exercise programs can lower their risk of death from all causes by 10% to 50%.

The researchers estimated that in The Netherlands the health benefits of cycling are at least nine times greater than the hazards, with the average person who switches to cycling living 3–14 months longer because of increased physical activity, while potentially losing 0.8–40 days of life due to increased exposure to air pollution and an average of 5–9 days due to fatal traffic accidents. The community health benefits are also greater than the risks to the individual cyclists, primarily because eliminating 500,000 car trips per day would reduce air pollution. In countries like the United Kingdom, which has a higher rate of traffic fatalities among cyclists, the researchers estimated that benefits of cycling would still be seven times greater than the risks.

The health benefits of cycling may be less in some developing countries where cyclists may face higher levels of pollution and higher risks in traffic, according to the researchers. Nevertheless, they state that their results are part of a growing body of research that supports the public health benefits of walking and cycling for transportation.

Authors of the paper were Jeroen Johan de Hartog, Hanna Boogaard, Hans Nijland, and Gerard Hoek. This work was funded by the European Union Sixth Framework Programme through the INTARESE (Integrated Assessment of Health Risks of Environmental Stressors in Europe) project.

•
•

Ω

Men who use statins to lower their cholesterol are 30 percent less likely to see their prostate cancer come back after surgery compared to men who do not use the drugs, according to researchers at Duke University Medical Center. Researchers also found that higher doses of the drugs were associated with lower risk of recurrence.

The findings are published in the journal CANCER.

"The findings add another layer of evidence suggesting that statins may have an important role in slowing the growth and progression of prostate cancer," says Stephen Freedland, M.D., a member of the Duke Prostate Center and the Urology Section at the Durham Veterans Affairs Medical Center, and the senior author of the study. "Previous studies have shown that statins have anti-cancer properties, but it's not entirely clear when it's best to use them – or even how they work."

Researchers examined the records of 1319 men who underwent radical prostatectomy included in the Shared Equal Access Regional Cancer Hospital (SEARCH) database. They found that 18 percent of the men – 236 – were taking statins at the time of surgery.

Researchers followed the patients after surgery to evaluate recurrence rates, measured by slight rises in the PSA levels after surgery, a development known as "biochemcical recurrence." Time to biochemical recurrence is viewed as an important clinical factor because it is correlated with the risk of disease progression and death.

The authors found that 304 men had a rising PSA, including 37 (16 percent) of the statin users and 267 (25 percent) of the non-users. Taking into account various clinical and pathological features that differed between the two groups, the data showed that overall, statin use reduced the risk of biochemical recurrence by 30 percent.

Among men taking statins equivalent to 20 mg of simvastatin a day, the risk of recurrence was reduced 43 percent and among the men taking the equivalent of more than 20 mg of simvastatin a day, the risk of recurrence was reduced 50 percent. Men who took a statin dose the equivalent of less than 20 mg of simvastatin daily saw no benefit.

There were significant differences between those who took the drugs and those who did not. Statin users tended to be white, older and heavier than non-users. They also had lower clinical stages at diagnosis, but higher Gleason scores, a measure of tumor aggressiveness.

"These findings are intriguing, but we do need to approach them with some caution," says Robert Hamilton, M.D., a urologist at the University of Toronto and the lead author of the study. "For example, we don't know the diet, exercise or smoking habits of these men. So it's not entirely clear if the lower risk we detected is related to the statins alone – it could be due to other factors we were not able to measure. We do feel, however, that based on these findings and those from other studies, the time is ripe to perform a well-controlled randomized trial to test whether statins do indeed slow prostate cancer progression."

Ω

A meta-analysis of previously published studies finds no evidence that statins are associated with a reduced risk of death among individuals at risk for but with no history of cardiovascular disease, according to a report in the June 28 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

"Statins are now one of the most widely used drugs for the treatment and prevention of cardiovascular disease both among individuals with established disease and among high-risk healthy individuals who are at elevated risk of incident [new-onset] cardiovascular disease," the authors write as background information in the article. "There is little debate that, compared with placebo, statin therapy among individuals with established coronary heart disease not only prevents complications related to atherosclerosis but also reduces all-cause mortality [death]." However, there is little evidence that statins reduce the risk of dying from any cause in individuals without heart disease. This, along with harms caused by statins in some subgroups, have called into question the benefit of statins in primary prevention (prevention of the development of heart disease).

In the meta-analysis, Kausik K. Ray, M.D., M.Phil., F.A.C.C., F.E.S.C., Sreenivasa Rao Kondapally Seshasai, M.D., M.Phil., and Sebhat Erqou, M.D., M.Phil., Ph.D., of University of Cambridge and Addenbrooke's Hospital, Cambridge, England, and colleagues combined data from 11 studies involving 65,229 participants. A total of 32,623 individuals were assigned to take statins and 32,606 individuals were assigned to take placebo. Some data about participant deaths was obtained from the originally published studies, whereas in other cases, study investigators were contacted for updated information.

Over an average of 3.7 years of follow-up, 2,793 participants died, including 1,447 assigned to take placebo and 1,346 assigned to take statins. This did not represent a statistically significant reduction in the risk of dying associated with statin use.

Low-density lipoprotein (LDL, or "bad" cholesterol) levels were higher among those taking placebo than those taking statins (134 milligrams per deciliter vs. 94 milligrams per deciliter). However, there was no association between risk of death and either LDL levels at the beginning of the study or average reduction in LDL levels.

"Current prevention guidelines endorse statin therapy for subjects at high global risk of incident cardiovascular disease as a means to reduce fatal and non-fatal vascular events," they conclude. The results of the current meta-analysis indicate the need for caution when extending the potential benefits of statins to a wider population. "Due consideration is needed in applying statin therapy in lower-risk primary prevention populations."

Ω

The nitrate content of beetroot juice is the underlying cause of its blood pressure lowering benefits, research from Queen Mary University of London reveals today.

The study, published online in the American Heart Association journal Hypertension, found that blood pressure was lowered within 24hours in people who took nitrate tablets, and people who drank beetroot juice.

The research will be welcome news to people with high blood pressure who might now be able to use a new 'natural' approach to reduce their risk of cardiovascular disease (including stroke and heart attacks) - the world's biggest killer.

Study author Amrita Ahluwalia, Professor of Vascular Biology at Queen Mary's William Harvey Research Institute, said the investigation was able to demonstrate that the nitrate found in beetroot juice was the cause of its beneficial effects upon cardiovascular health by increasing the levels of the gas nitric oxide in the circulation

Professor Ahluwalia said. "We gave inorganic nitrate capsules or beetroot juice to healthy volunteers and compared their blood pressure responses and the biochemical changes occurring in the circulation.

"We showed that beetroot and nitrate capsules are equally effective in lowering blood pressure indicating that it is the nitrate content of beetroot juice that underlies its potential to reduce blood pressure. We also found that only a small amount of juice is needed – just 250ml - to have this effect, and that the higher the blood pressure at the start of the study the greater the decrease caused by the nitrate.

"Our previous study two years ago found that drinking beetroot juice lowered blood pressure; now we know how it works."

The results of the study could pave the way for a natural approach to lowering blood pressure that ultimately may help reduce the currently massive burden of cardiovascular disease on the NHS.

Ω

For people with hypertension, eating dark chocolate can significantly reduce blood pressure. Researchers writing in the open access journal BMC Medicine combined the results of 15 studies into the effects of flavanols, the compounds in chocolate which cause dilation of blood vessels, on blood pressure.

Dr Karin Ried worked with a team of researchers from the University of Adelaide, Australia, to conduct the analysis. She said, "Flavanols have been shown to increase the formation of endothelial nitric oxide, which promotes vasodilation and consequently may lower blood pressure. There have, however, been conflicting results as to the real-life effects of eating chocolate. We've found that consumption can significantly, albeit modestly, reduce blood pressure for people with high blood pressure but not for people with normal blood pressure".

The pressure reduction seen in the combined results for people with hypertension, 5mm Hg systolic, may be clinically relevant – it is comparable to the known effects of 30 daily minutes of physical activity (4-9mm Hg) and could theoretically reduce the risk of a cardiovascular event by about 20% over five years. The researchers are cautious, however, "The practicability of chocolate or cocoa drinks as long-term treatment is questionable", said Dr Ried.

Does chocolate reduce blood pressure? A meta-analysis
Karin Ried, Thomas Sullivan, Peter Fakler, Oliver R Frank and Nigel P Stocks
BMC Medicine 2010, 8:39 doi:10.1186/1741-7015-8-39

Ω

Equation offers different exercise heart rate for women and better predicts heart risk


Women who measure their peak heart rates for exercise will need to do some new math as will physicians giving stress tests to patients.

A new formula based on a large study from Northwestern Medicine provides a more accurate estimate of the peak heart rate a healthy woman should attain during exercise. It also will more accurately predict the risk of heart-related death during a stress test.

"Now we know for the first time what is normal for women, and it's a lower peak heart rate than for men," said Martha Gulati, M.D., assistant professor of medicine and preventive medicine and a cardiologist at Northwestern Medicine. "Using the standard formula, we were more likely to tell women they had a worse prognosis than they actually did."

Gulati is the lead author of a study published June 28 in the journal Circulation.

"Women are not small men," Gulati added. "There is a gender difference in exercise capacity a woman can achieve. Different physiologic responses can occur. " Gulati was the first to define the normal exercise capacity or fitness level for women in a 2005 study.

The old formula -- 220 minus age -- used for almost four decades, is based on studies of men. The new formula for women, based on the new research, is 206 minus 88 percent of age.

At age 50, the original formula gives a peak rate of 170 beats per minute for men and women. The new women's formula gives a maximum heart rate of 162 beats for women. Many men and women use their peak heart rate multiplied by 65 to 85 percent to determine their upper heart rate when exercising.

"Before, many women couldn't meet their target heart rate," Gulati said. "Now, with the new formula, they are actually meeting their age-defined heart rate."

The new formula is trickier to calculate, Gulati acknowledged, but is easily determined with a calculator. She currently is working on an iPhone application for a quick calculation.

The new formula is based on a study of 5,437 healthy women ages 35 and older who participated in the St. James Women Take Heart Project, which began in the Chicago area in 1992.

With the new formula, physicians will more accurately determine if women are having a normal or abnormal response to exercise. "If it's abnormal, that's a marker for a higher risk of death," Gulati said. "Maybe we need to talk about whether you exercise enough and what we need to do to get it into the normal range."

"We need to keep studying women to get data applicable to women," Gulati said. "It's important to not get complacent that we have data on men and assume women must be the same. They're not."

Gulati's senior author on the study was Morton Arnsdorf, M.D., professor emeritus and associate vice chairman of medicine and former section chief of cardiology at the University of Chicago. Arnsdorf died in a motor vehicle accident in June.

"I feel fortunate to have been his student, have him take me under his wing and be my mentor," Gulati said. "He was an amazing mentor." The Women Take Heart Project study had been sitting dormant, and Arnsdorf encouraged her to open it to do more research, Gulati said.

Ω

Researchers at the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC-James) have discovered how a substance that is produced when eating broccoli and Brussels sprouts can block the proliferation of cancer cells.

Compelling evidence indicates that the substance, indole-3-carbinol (I3C), may have anticancer effects and other health benefits, the researchers say. These findings show how I3C affects cancer cells and normal cells.

The laboratory and animal study discovered a connection between I3C and a molecule called Cdc25A, which is essential for cell division and proliferation. The research showed that I3C causes the destruction of that molecule and thereby blocks the growth of breast cancer cells.

The study was published online June 29 in the journal Cancer Prevention Research.

"Cdc25A is present at abnormally high levels in about half of breast cancer cases, and it is associated with a poor prognosis," says study leader Xianghong Zou, assistant professor of pathology at the Ohio State University Medical Center.

The molecule also occurs at abnormally high levels in cancers of the breast, prostate, liver, esophagus, endometrium and colon, and in non-Hodgkin lymphoma, and in other diseases such as Alzheimer's disease, he noted.

"For this reason, a number of anti-Cdc25 agents have been identified, but they have not been successful for cancer prevention or treatment due to concerns about their safety or efficacy," says Zou, who is also a member of the OSUCCC-James Molecular Carcinogenesis and Chemoprevention program.

"I3C can have striking effects on cancer cells," he explains, "and a better understanding of this mechanism may lead to the use of this dietary supplement as an effective and safe strategy for treating a variety of cancers and other human diseases associated with the overexpression of Cdc25A," Zou says.

For this study, Zou and his colleagues exposed three breast cancer cell lines to I3C. These experiments revealed that the substance caused the destruction of Cdc25A. They also pinpointed a specific location on that molecule that made it susceptible to I3C, showing that if that location is altered (because of a gene mutation), I3C no longer causes the molecule's destruction.

Last, the investigators tested the effectiveness of I3C in breast tumors in a mouse model. When the substance was given orally to the mice, it reduced tumor size by up to 65 percent. They also showed that I3C had no affect on breast-cell tumors in which the Cdc25A molecule had a mutation in that key location.

Ω

"A very high dosage of caffeine, most likely achieved via tablets, powder or a concentrated liquid, is feasible and might prove attractive to a number of athletes wishing to improve their athletic performance", explains lead researcher, Dr Rob James.

"A small increase in performance via caffeine could mean the difference between a gold medal in the Olympics and an also-ran", he added.

Caffeine is not currently listed by the World Anti-Doping Agency (WADA) as a banned substance at any concentration in blood or urine samples. Before 2004 WADA did set a specific level over which athletes could be banned, but this restriction was removed.

Muscle activity is divided into maximal, where the muscles are pushed to full capacity such as in sprinting or weight lifting, and sub-maximal, which covers all other activities.

A member of the team, Jason Tallis, tested the effect of caffeine on both the power output and endurance of soleus muscles (lower leg muscle) in mice, under both maximal and sub-maximal activities.

He found that a caffeine dosage of 70 µM enhanced power output by ~6% during both types of activity. This effect in humans is likely to be very similar, according to the researchers.

"70 μM caffeine concentration is the absolute maximum that can normally achieved in the blood plasma of a human, however concentrations of 20-50 μM are not unusual in people with high caffeine intakes", explains Dr James.

Resultant caffeine in blood plasma (70μM maximum) may act at receptors on skeletal muscle causing enhanced force production. Scientists already know that ingestion of caffeine can increase athletic performance by stimulating the central nervous system.

Additionally, 70μM caffeine treatment increased endurance during sub-maximal activity, but significantly reduced endurance during maximal activity.

Ω

A discussion by renowned epidemiologist Kenneth Mukamal has recently been published in the Journal of the American Medical Association, JAMA. It provides a discussion in response to a theoretical question, - if you are a 42 year old male, should you drink alcohol ( in moderation) for your health?

The paper provides an excellent discussion of a theoretical question about drinking and health. It focuses on the potential risks and benefits associated with moderate drinking for a middle-aged male patient. ' Most members of the International Scientific Forum on Alcohol Research (ISFAR) were pleased with the discussion of the topic. It was noted how uncommon it is that such knowledgeable, detailed, and mostly objective data appear in the mainstream medical literature. It was thought to be readable, informative and thoughtful.'

The reason the patient questioned his moderate use of alcohol was based on an encounter with a "specialist" who advised him to consider stopping drinking because alcohol could "accelerate brain shrinkage." While "brain shrinkage" is a radiological term with little known relation with clinical outcomes, most studies suggest less decline in cognitive functioning over time, and lower risk of dementia, among moderate drinkers in comparison with non-drinkers. Such findings are supported by much data from basic science experiments. This illustrates the danger of incomplete information ("a little knowledge") by a member of the medical profession. Mr. Q seems to be very careful (perhaps even a little too careful) in following a healthy lifestyle, including consuming small amounts of alcohol in a reasonable pattern. The ISFAR critique points out a number of topics that were covered incompletely in the paper, including inadequate information on the importance of the pattern of drinking: moderate regular consumption versus binge drinking. Overall, it was believed that the paper provided important information for physicians who may be discussing alcohol consumption with their patients.

###
To read the full critique of this research, please log onto www.alcoholforum4profs.org

reference: Clinical Crossroads: Conferences with patients and doctors. A 42-year-old man considering whether to drink alcohol for his health. Kenneth J. Mukamal, MD, MPH, Discussant. JAMA 2010;303:2065-2073. (doi:10.1001/jama.2010.550)

Ω

Women who are physically active at any point over the life course (teenage, age 30, age 50, late life) have lower risk of cognitive impairment in late-life compared to those who are inactive, but teenage physical activity appears to be most important. This is the key finding of a study of over nine thousand women published today in the Journal of the American Geriatrics Society.

There is growing evidence to suggest that people who are physically active in mid- and late life have lower chance of dementia and more minor forms of cognitive impairment in old age. However, there is a poorer understanding of the importance of early life physical activity and the relative importance of physical activity at different ages. Researchers led by Laura Middleton, PhD, of Sunnybrook Health Sciences Centre, Canada, compared the physical activity at teenage, age 30, age 50, and late life against cognition of 9,344 women from Maryland, Minnesota, Oregon and Pennsylvania to investigate the effectiveness of activity at different life stages.

Of the participants, 15.5%, 29.7%, 28.1%, and 21.1% reported being physically inactive at teenage, at 30 years, at 50 years, and in late life respectively; the increase in cognitive impairment for those who were inactive was between 50% and 100% at each time point. When physical activity measures for all four ages were entered into a single model and adjusted for variables such as age, education, marital status, diabetes, hypertension, depressive symptoms, smoking, and BMI, only teenage physical activity status remained significantly associated with cognitive performance in old age.

"Our study shows that women who are regularly physically active at any age have lower risk of cognitive impairment than those who are inactive but that being physically active at teenage is most important in preventing cognitive impairment," said Middleton.

The researchers also found that women who were physically inactive at teenage but became physically active at age 30 and age 50 had significantly reduced odds of cognitive impairment relative to those who remained physically inactive. In contrast, being physically active at age 30 and age 50 was not significantly associated with rates of cognitive impairment in those women who were already physically active at teenage.

Middleton added, "As a result, to minimize the risk of dementia, physical activity should be encouraged from early life. Not to be without hope, people who were inactive at teenage can reduce their risk of cognitive impairment by becoming active in later life."

The researchers concluded that the mechanisms by which physical activity across the life course is related to late life cognition are likely to be multi-factorial. There is evidence to suggest that physical activity has a positive effect on brain plasticity and cognition and in addition, physical activity reduces the rates and severity of vascular risk factors, such as hypertension, obesity, and type II diabetes, which are each associated with increased risk of cognitive impairment.

"Low physical activity levels in today's youth may mean increased dementia rates in the future. Dementia prevention programs and other health promotion programs encouraging physical activity should target people starting at very young ages, not just in mid- and late life," said Middleton.

Ω

Ω

New research in the FASEB Journal suggests that the polyphenols in virgin olive oil modify the expression of atherosclerosis-related genes, leading to health benefits

Everyone knows olive oil and a Mediterranean diet are associated with a lower risk for cardiovascular disease, but a new research report published in the July 2010 print issue of the FASEB Journal (http://www.fasebj.org) offers a surprising reason why: These foods change how genes associated with atherosclerosis function.

"Knowing which genes can be modulated by diet in a healthy way can help people select healthy diets," said Maria Isabel Covas, D.Pharm., Ph.D., a researcher involved in the work from the Cardiovascular Risk and Nutrition Research Group at the Institut Municipal d'Investigacio Medica in Barcelona, Spain. "It is also a first step for future nutritional therapies with selected foods."

Scientists worked with three groups of healthy volunteers. The first group consumed a traditional Mediterranean diet with virgin olive oil rich in polyphenols. The second group consumed a traditional Mediterranean diet with an olive oil low in polyphenols. The third group followed their habitual diet. After three months, the first group had a down-regulation in the expression of atherosclerosis-related genes in their peripheral blood mononuclear cells. Additionally, the olive oil polyphenols made a significant impact on the expression of genetic changes influencing coronary heart disease. Results also showed that the consumption of virgin olive oil in conjunction with a Mediterranean diet can positively impact lipid and DNA oxidation, insulin resistance, inflammation, carcinogenesis, and tumor suppression.

"This study is ground breaking because it shows that olive oil and a Mediterranean diet affect our bodies in a far more significant way than previously believed," said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal. "Not only does this research offer more support for encouraging people to change their eating habits, it is an important first step toward identifying drug targets that affect how our genes express themselves."

\Ω

Breast cancer is the most common type of cancer in Western countries. Research carried out with animal models demonstrate that a diet rich in fats is directly related to the incidence of cancer. Some types of fats however can play a protective role against the development of these tumours. Such is the case of virgin olive oil, rich in oleic acid, a mono-unsaturated fatty acid, and containing several bioactive compounds such as antioxidants. A moderate and regular intake of virgin olive oil, characteristic of the Mediterranean diet, is associated with low incidences of specific types of cancer, including breast cancer, as well as with having a protective role against coronary diseases and other health problems.

The study carried out by UAB researchers decoded the mechanisms operating within the tumour cell and induced by the intake of olive oil, in comparison to those activated by corn oil, rich in n-6 polyunsaturated fatty acids, which increase the aggressiveness of tumours.

Scientists demonstrated that virgin olive oil is associated with higher incidences of benign breast tumours and at the same time with a decrease in the activity of the p21Ras oncogene, which spurs uncontrolled cell proliferation and stimulates the growth of tumours. In addition, olive oil suppresses the activity of some proteins, such as the AKT, essential for the survival of cells since they prevent apoptosis, the cell's "suicide" programme. Between proliferation and apoptosis in tumour cells, these effects tip the balance towards cell death, thereby slowing the growth of tumours.

Another result obtained by researchers is the protection of DNA in the cell nucleus. Cells from animals fed a diet rich in virgin olive oil contained less DNA lesions than those fed a control diet.

Scientists of the UAB Breast Cancer Study Multidisciplinary Group (GMECM) have spent over twenty years working to determine the effects fats have on breast cancer, and in particular the effects of virgin olive oil. Previous studies of the group revealed the beneficial effects of this component of the human diet on the clinical conduct of mammary tumours and on their histological grade (malignancy). Scientists also described several molecular mechanisms producing these effects and in 2004 the same group was the one to identify the four genes involved in the effects dietary fats have on experimental breast cancer. The mechanism recently discovered was published in the journal Carcinogenesis.

Ω

Scientists are reporting a possible explanation for the symptoms of anxiety and depression that occur in some patients taking the popular statin family of anti-cholesterol drugs, and reported by some individuals on low-cholesterol diets. These symptoms could result from long-term, low levels of cholesterol in the brain, the report suggests. It appears in ACS' weekly journal Biochemistry.

Amitabha Chattopadhyay and colleagues note in the study that statins work by blocking a key enzyme involved in the body's production of cholesterol. Some studies link the drugs to an increased risk of anxiety and depression, but the reasons are unclear. The scientists previously showed that maintaining normal cholesterol levels is important for the function of cell receptors for serotonin, a brain hormone that influences mood and behavior. But the long-term effect of cholesterol depletion on these receptors, which can occur in patients taking anti-cholesterol drugs, is unknown.

The scientists turned to the statin medication mevastatin to find out. In lab tests using human serotonin receptors expressed in animal cells, they showed that long-term use of the drug caused significant changes in the structure and function of serotonin cell receptors. Adding cholesterol to cells treated with mevastatin restored them to normal. The results represent the first report describing the effect of long-term cholesterol depletion on this type of cell receptor and suggest that chronic, low cholesterol levels in the brain might trigger anxiety and depression, the scientists say.

"Chronic Cholesterol Depletion using Statin Impairs the Function and Dynamics of Human Serotonin1A Receptors"

Ω

This is a very brief survey of the latest research. Click on links for more information on the research cited here. My Health Research Report blog also includes additional items, including a recent National Cancer Institute Report on Vitamin D And Cancer Prevention, and an interesting Consumer Reports Health Report.

I am taking less Vitamin D now that I’m out in the sun more, but that’s probably a mistake according to new research – I need to keep up 2000 units a day:

Vitamin D Promotes Mental Agility in Elders

Vitamin D deficiency common across a range of rheumatic conditions

Vitamin D deficiency is highly prevalent in patients with Type 2 diabetes

My consumption of red wine is flagging a bit in the summer – I really, really prefer beer, but I will try to drink more


Lose Weight With Resveratrol?

“The physiological benefits of resveratrol are currently under intensive investigation, with recent work suggesting that it could be a good candidate for the development of obesity therapies.”

Resveratrol Neutralizes Toxicity of Proteins Related to Alzheimer's

Alcohol consumption lowers risk of developing several arthritic conditions

I continue to drink a lot of green tea:

Tea Heart Benefits

“Drinking more than six cups of tea per day was associated with a 36 percent lower risk of heart disease compared to those who drank less than one cup of tea per day. Drinking three to six cups of tea per day was associated with a 45 percent reduced risk of death from heart disease, compared to consumption of less than one cup per day."

Red wine and green tea halt prostate cancer growth

But:

Women who consume large amounts of tea (but not coffee) have increased risk of rheumatoid arthritis

I continue to eat lots of fish and fish oil supplements, which I am cheerful about:

Encouraging Results: Treating Depression With Omega-3

I eat a handful (or a little more of nuts every day:

Pecans provide neurological protection

I try to eat a Mediterranean-style diet:

Mediterranean-style diet improves heart function

I continue to try to limit my salt intake – I’ve switched to no-salt nuts and pretzels, and some canned vegetables:

Nine in 10 U.S. Adults Consume Too Much Sodium

“Most sodium in the American diet comes from processed grains such as pizza and cookies, and meats, including poultry and luncheon meats.”

I continue to avoid foods supplemented with much iron (bad for the heart)

Link between iron overload and macular degeneration

I don't drink coffee but perhaps I should:

Drinking coffee may reduce the risk of diabetes

Coffee may protect against head and neck cancers

I only need to keep a sense of humor for 5 more years:

A Sense of Humor Helps Keep You Healthy Until Retirement Age

"A sense of humor helps to keep people healthy and increases their chances of reaching retirement age. But after the age of 70, the health benefits of humor decrease."


P.S.

I recently reported on researching the benefits of alcohol consumption vs. the risks of breast cancer .

However, those risks can be cut by vigorous exercise, taking ibuprofen, and drinking coffee.

Ω

# Is it safe to take vitamin D supplements?

Vitamin D toxicity is more likely to occur from high intakes of dietary supplements than from high intakes of vitamin D-fortified foods. For most children and adults, the tolerable upper intake level (UL) of vitamin D intake from foods and supplements is 25 μg (1,000 IU) per day for those less than 1 year of age and 50 μg (2,000 IU) per day for older individuals (1, 2). The UL is the highest level of daily intake (from all sources combined) that is likely to pose no risk of adverse effects for almost all people.

Excessive vitamin D intake is toxic because it increases calcium levels. Increased calcium levels can lead to calcinosis (the deposit of calcium salts in soft tissues of the body, such as the kidneys, heart, and lungs) and hypercalcemia (high blood levels of calcium). Symptoms of excessive vitamin D intake may include heart rhythm abnormalities; mental status changes, such as confusion; pain; conjunctivitis; anorexia; fever; chills; thirst; vomiting; and weight loss (1, 2, 4).

# Is there a role for vitamin D in reducing cancer risk?

A large number of scientific studies have investigated a possible role for vitamin D in cancer prevention.

* The first results came from epidemiologic studies known as geographic correlation studies. In these studies, an inverse relationship was found between sunlight exposure levels in a given geographic area and the rates of incidence and death for certain cancers in that area. Individuals living in southern latitudes were found to have lower rates of incidence and death for these cancers than those living at northern latitudes. Because sunlight/UV exposure is necessary for the production of vitamin D3, researchers hypothesized that variation in vitamin D levels accounted for the observed relationships.

* Evidence of a possible cancer-protective role for vitamin D has also been found in laboratory studies of the effect of vitamin D treatment on cancer cells in culture. In these studies, vitamin D promoted the differentiation and death (apoptosis) of cancer cells, and it slowed their proliferation.

* Randomized clinical trials designed to investigate the effects of vitamin D intake on bone health have suggested that higher vitamin D intakes may reduce the risk of cancer. One study involved nearly 1,200 healthy postmenopausal women who took daily supplements of calcium (1,400 mg or 1,500 mg) and vitamin D (25 μg vitamin D, or 1,100 IU―a relatively large dose) or a placebo for 4 years. The women who took the supplements had a 60 percent lower overall incidence of cancer (6); however, the study did not include a vitamin D-only group. Moreover, the primary outcome of the study was fracture incidence; it was not designed to measure cancer incidence. This limits the ability to draw conclusions about the effect of vitamin D intake on cancer risk.

* A number of observational studies have investigated whether people with higher vitamin D levels or intake have lower risks of specific cancers, particularly colorectal cancer and breast cancer. Associations of vitamin D with risks of prostate, pancreatic, and other, rarer cancers have also been examined. These studies have yielded inconsistent results, most likely because of the challenges of conducting observational studies of diet (7). Information about dietary intakes is obtained from the participants through the use of food frequency questionnaires, diet records, or interviews in which the participants are asked to recall information about their dietary intakes. Information collected in this manner can be inaccurate. In addition, only recently has a comprehensive food composition database with vitamin D values for the U.S. food supply become available. Other dietary components or energy balance may also modify vitamin D metabolism (8).

Measuring blood levels of 25-hydroxyvitamin D to determine vitamin D status avoids some of the limitations of assessing dietary intake. However, vitamin D levels in the blood vary by race, with the season, and possibly with the activity of genes whose products are involved in vitamin D transport and metabolism. These variations complicate the interpretation of studies that measure the concentration of vitamin D in serum at a single point in time.

Finally, it is difficult to separate the effects of vitamin D and calcium because of the complicated biological interactions between these substances. To fully understand the effect of vitamin D on cancer and other health outcomes, new randomized trials will need to be carried out (9). However, the appropriate dose of vitamin D to use in such trials is still not clear (10).

# Is there evidence that vitamin D can help reduce the risk of colorectal cancer?

Epidemiologic studies of the association between vitamin D and the risk of colorectal cancer have provided some indications that higher levels of intake are associated with a reduced risk. However, the data are inconsistent.

In the American Cancer Society’s Cancer Prevention Study (CPS) II Nutrition Cohort, the diet, medical history, and lifestyle of more than 120,000 men and women were analyzed (11). Men who had the highest intakes of vitamin D through both their diet and supplement use (greater than 13 μg, or 525 IU, per day) had a slightly lower risk of colorectal cancer than men who had the lowest vitamin D intakes. However, this association was not observed among women.

In a pooled analysis of data from 10 cohort studies (including the CPS II cohort), individuals with the highest dietary vitamin D intakes had a slightly lower risk of colorectal cancer than those with the lowest intakes, but the reduction in risk was not statistically significant (12).

In the Women’s Health Initiative randomized trial, healthy postmenopausal women took daily supplements that contained both calcium (1,000 mg) and vitamin D (10 μg, or 400 IU) or a placebo for an average of 7 years. Supplementation did not reduce the incidence of colorectal cancer (13). However, some scientists have raised the possibility that the relatively low level of vitamin D supplementation and the short duration of participant follow-up might account for the negative results.

At least one epidemiologic study has reported an association between vitamin D and reduced mortality from colorectal cancer. Among the 16,818 participants in the Third National Health and Nutrition Examination Survey, those with higher vitamin D blood levels (≥80 nmol/L) had a 72 percent lower risk of colorectal cancer death than those with lower vitamin D blood levels (< 50 nmol/L) (14).

Most colorectal cancers develop from pre-existing colorectal adenomas, and interventions that reduce the risk of adenoma development or recurrence are likely to reduce the risk of colorectal cancer. Several large studies have investigated the association of vitamin D intake or serum status with adenoma risk.

A cohort from the National Cancer Institute (NCI)-sponsored Polyp Prevention Trial (PPT) was evaluated for the association of vitamin D intake with recurrence of colorectal adenomas in individuals who previously had one or more adenomas removed during a qualifying colonoscopy (15). PPT was a multicenter randomized clinical trial to determine the effects of a diet high in fiber, fruits, and vegetables and low in fat on adenoma recurrence. The detailed dietary information obtained during the trial allowed the researchers to investigate the association between additional dietary factors and adenoma recurrence. Total vitamin D intake (that is, from dietary sources and supplements combined) was not associated with a reduced risk of adenoma recurrence (15). However, individuals who used any amount of vitamin D supplements had a lower risk of adenoma recurrence (15).

In another study, the vitamin D intakes of 3,000 people from several Veterans Affairs medical centers were examined to determine whether there was an association between intake and advanced colorectal neoplasia (an outcome that included high-risk adenomas as well as colon cancer) (16). Individuals with the highest vitamin D intakes (more than 16 μg, or 645 IU, per day) had a lower risk of developing advanced neoplasia than those with lower intakes (16).

A pooled analysis of data from these and a number of other observational studies found that higher circulating levels of vitamin D and higher vitamin D intakes were associated with lower risks of colorectal adenoma (17). Inverse associations were seen with both dietary and total vitamin D intake but not with supplemental vitamin D intake. However, the associations with dietary intake were not statistically significant.

Another large, NCI-sponsored randomized, placebo-controlled trial explored the effects of calcium supplementation and blood levels of vitamin D on adenoma recurrence (18). Calcium supplementation reduced the risk of adenoma recurrence only in individuals with vitamin D blood levels above 73 nmol/L. Among individuals with vitamin D levels at or below this level, calcium supplementation was not associated with a reduced risk (18).

# Is there evidence that vitamin D can help reduce breast cancer risk?

Epidemiologic studies of the association between vitamin D and breast cancer risk have had conflicting results. Although several studies have suggested an inverse association between vitamin D intake and the risk of breast cancer, others have shown no association or even a positive association (that is, individuals with higher intakes had higher risks). A meta-analysis of six studies that investigated the relationship between vitamin D intake and breast cancer risk found no association (19). However, most women in these studies had relatively low vitamin D intakes, and, when the analysis was restricted to women with the highest vitamin D intakes (>10 μg, or 400 IU, per day), their breast cancer risks were lower than those of women with the lowest intakes (typically <1.25 μg, or 50 IU, per day) (19).

In the Women’s Health Initiative, calcium plus vitamin D supplementation for an average of 7 years did not reduce the incidence of invasive breast cancer compared with placebo (20).

The association between blood levels of vitamin D and breast cancer risk was examined in a cohort of postmenopausal women who were enrolled in NCI’s Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and from whom blood was drawn at study entry. During the subsequent follow-up period, 1,005 of these women developed breast cancer. When researchers compared the blood vitamin D levels of these women with those of 1,005 similar control women who did not develop breast cancer, they found no association between vitamin D status and risk of breast cancer (21).
# Is there evidence that vitamin D can help reduce prostate cancer risk?

Some geographic correlation studies (see Question 6) have suggested that men exposed to higher levels of sunlight may have a lower risk of prostate cancer. Although some epidemiologic studies have suggested that men with higher vitamin D levels have an increased risk of prostate cancer, most studies have not shown such an association.

In one relatively large study of men diagnosed 1 to 8 years after their blood was drawn, higher vitamin D blood levels were not associated with a lower risk of prostate cancer overall (22). Indeed, there was some evidence that men with higher vitamin D levels had an increased risk for aggressive disease (22).

In another study, the European Prospective Investigation into Cancer and Nutrition (EPIC), blood samples obtained at study entry were examined for 652 men who developed prostate cancer during follow-up and 752 matched control subjects (23). No association was observed between serum vitamin D levels and risk of prostate cancer, either overall or by cancer stage.
# Is there evidence that vitamin D can help reduce pancreatic cancer risk?

There is conflicting evidence about vitamin D’s relationship to risk of pancreatic cancer. A study of more than 120,000 men and women from the Health Professionals Follow-Up Study and the Nurses’ Health Study showed that participants with higher dietary intake of vitamin D had progressively lower risk of pancreatic cancer, compared with those who had the lowest intake (24). The estimates of vitamin D intake were based on detailed dietary information provided through questionnaires. Participants were followed for 16 years for the incidence of pancreatic cancer, and 365 cases were identified.

In a study of men and women enrolled in the PLCO Screening Trial, no association between vitamin D level and pancreatic cancer risk was observed. The PLCO study examined vitamin D levels in blood from 184 individuals who were diagnosed with pancreatic cancer during nearly 12 years of follow-up and 368 matched cancer-free control subjects (25). In contrast, among Finnish male smokers participating in the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study (26), higher blood levels of vitamin D were associated with an increased risk of pancreatic cancer. More recently, in the NCI Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (see Question 11), men and women with the highest blood vitamin D levels (greater than 100 nmol/L, or 40 ng/mL) had twice the pancreatic cancer risk of men and women whose blood vitamin D levels were in the normal range of 50-75 nmol/L (20-30 ng/mL).
# Is there evidence that vitamin D can help reduce the risk of other rare cancers?

A recent large collaborative effort analyzed data from 10 prospective cohort studies to examine whether vitamin D levels in blood were associated with seven rare cancers (27). The NCI Cohort Consortium Vitamin D Pooling Project of Rarer Cancers included information on blood vitamin D levels and incidence of rare cancers in a subset of more than 12,000 men and women. The researchers matched participants on date and season of blood draw and used other statistical techniques to adjust for seasonal variation in blood vitamin D levels. When the data from the different studies were pooled, there was no overall association between vitamin D level and risk of non-Hodgkin lymphoma or cancers of the endometrium, esophagus, stomach, kidney, or ovary. As described in Question 10, an increased risk of pancreatic cancer was observed in those with the highest blood levels of vitamin D (greater than 100 nmol/L or 40 ng/mL).
# What are the possible mechanisms by which vitamin D may modify cancer risk?

Mechanisms by which vitamin D may modify cancer risk are not fully understood. Laboratory studies have shown that vitamin D promotes cellular differentiation, decreases cancer cell growth, and stimulates apoptosis (28, 29).

Vitamin D acts on cells by binding to the vitamin D receptor (VDR). The VDR is a regulator of gene transcription that is found in the nucleus of cells. Vitamin D-bound VDR binds to the retinoid-X receptor (RXR), and the resulting complex activates the expression of specific genes. Among the many genes regulated by vitamin D are those that produce the proteins calbindin and TPRV6, both of which are involved in the absorption of calcium by intestinal cells (30). Another vitamin D-regulated gene is CYP3A4, whose protein product detoxifies the bile acid lithocholic acid (LCA). LCA is believed to damage the DNA of intestinal cells and may promote colon carcinogenesis. Stimulating the production of a detoxifying enzyme by vitamin D could explain a protective role for vitamin D against colon cancer (31).

Further insight into the mechanisms by which vitamin D might modify cancer risk could come from study of the vitamin D receptor itself. A large number of variant forms of the VDR gene have been identified, some of which are known to alter the structure or function of the VDR protein. Some of these variants have been linked to risk for certain cancers, including prostate, colorectal, breast, bladder, and melanoma (32). The association of VDR variants with cancer risk differs by cancer site and appears to be modified by environmental exposures, such as diet and sun exposure.
# How can people get enough sunlight for vitamin D synthesis while minimizing the risk of skin cancer?

Although people obtain some vitamin D from dietary sources, most vitamin D is made in the body after the skin is exposed to sunlight. Despite the known and potential health benefits of vitamin D, increasing sun exposure increases the risk of skin cancer. In general, most experts believe that people should continue to use sun protection when UV levels are moderate or higher. Some researchers have suggested that brief daily exposure to UV will ensure adequate vitamin D production, but many variables (such as skin color, latitude, and season) can affect the production of vitamin D, and such recommendations have proven controversial. Other experts recommend vitamin D supplementation to avoid the problem of increasing skin cancer risk.

Ω

At a time when consumer interest in health-enhancing foods is high, Agricultural Research Service (ARS)-funded scientists have contributed to a limited but growing body of evidence of a link between vitamin D and cognitive function.

Cognitive function is measured by the level at which the brain is able to manage and use available information for activities of daily life. Alzheimer's disease, the most common form of age-related dementia, affects about 47 percent of adults aged 85 years or older in the United States. Identifying nutritional factors that lower cognitive dysfunction and help preserve independent living provides economic and public health benefits, according to authors.

The study, which was supported by ARS, the National Institutes of Health, and others, was led by epidemiologist Katherine Tucker with the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University in Boston, Mass. Tucker collaborated with HNRCA laboratory directors Irwin Rosenberg, Bess Dawson-Hughes and colleagues.

Metabolic pathways for vitamin D have been found in the hippocampus and cerebellum areas of the brain involved in planning, processing, and forming new memories. This suggests that vitamin D may be implicated in cognitive processes.

The study involved more than 1,000 participants receiving home care. The researchers evaluated associations between measured vitamin D blood concentrations and neuropsychological tests. Elders requiring home care have a higher risk of not getting enough vitamin D because of limited sunlight exposure and other factors.

The participants, ages 65 to 99 years, were grouped by their vitamin D status, which was categorized as deficient, insufficient, or sufficient. Only 35 percent had sufficient vitamin D blood levels. They had better cognitive performance on the tests than those in the deficient and insufficient categories, particularly on measures of "executive performance," such as cognitive flexibility, perceptual complexity, and reasoning. The associations persisted after taking into consideration other variables that could also affect cognitive performance.

The 2009 study appears in the Journals of Gerontology, Series A, Biological Sciences and Medical Sciences.

Ω

ß
The anti-obesity properties of resveratrol have been demonstrated for the first time in a primate. Researchers writing in the open access journal BMC Physiology studied the compound, generated naturally by plants to ward off pathogens, which has received much interest as a dietary supplement for its supposed life-extending effects.

Fabienne Aujard, from the Centre National de la Recherche Scientifique, Paris, France, worked with a team of researchers to investigate the effect of dietary supplementation with resveratrol on the weight, metabolism and energy intake of six mouse lemurs.

She said, "The physiological benefits of resveratrol are currently under intensive investigation, with recent work suggesting that it could be a good candidate for the development of obesity therapies. We've found that lemurs eating a diet supplemented with the compound decreased their energy intake by 13% and increased their resting metabolic rate by 29%."

The researchers demonstrated that a four-week resveratrol supplementation was associated with a decrease in food intake and a reduction in seasonal body-mass gain. The response to resveratrol supplementation also involved significant changes in the animals' body temperatures. According to Dr Aujard, "These results provide novel information on the potential effects of resveratrol on energy metabolism and control of body mass in a primate."

Ω

Majority of sodium comes from most commonly eaten foods

Less than 10 percent of U.S. adults limit their daily sodium intake to recommended levels, according to a new report, "Sodium Intake in Adults – United States, 2005-2006," published today in CDC's Morbidity and Mortality Weekly Report. The report also finds that most sodium in the American diet comes from processed grains such as pizza and cookies, and meats, including poultry and luncheon meats.

According to the report, U.S. adults consume an average of 3,466 milligrams (mg) of sodium per day, more than twice the current recommended limit for most Americans. Grains provide 36.9 percent of this total, followed by dishes containing meat, poultry, and fish (27.9 percent). These two categories combined account for almost two-thirds of the daily sodium intake for Americans.

An estimated 77 percent of dietary sodium comes from processed and restaurant foods. Many of these foods, such as breads and cookies, may not even taste salty. "Sodium has become so pervasive in our food supply that it's difficult for the vast majority of Americans to stay within recommended limits," said Janelle Peralez Gunn, public health analyst with CDC's Division for Heart Disease and Stroke Prevention and lead author of the report. "Public health professionals, together with food manufacturers, retailers and health care providers, must take action now to help support people's efforts to reduce their sodium consumption."

The 2005 Dietary Guidelines for Americans recommends that people consume less than 2,300 mg of sodium per day. Specific groups, including persons with high blood pressure, all middle-aged and older adults and all blacks, should limit intake to 1500 mg per day. These specific groups comprise nearly 70 percent of the U.S. adult population. This study found that only 9.6 percent of all participants met their applicable dietary recommendation, including 5.5 percent of the group limited to 1,500 mg per day and 18.8 percent of the 2,300 mg per day group.

The report examined data for 2005–2006 from the National Health and Nutrition Examination Survey (NHANES), an ongoing study that explores the health and nutritional status of adults and children in the United States. Researchers used information from 24-hour dietary recall and the USDA National Nutrient Database to estimate the daily sodium intake and sources of sodium intake for U.S. adults.

The findings add to a growing body of observational research studies on Americans' excessive sodium consumption. Overconsumption of sodium can have negative health effects, including increasing average levels of blood pressure. One in three U.S. adults has high blood pressure, and an estimated 90 percent of U.S. adults will develop the disease in their lifetime. Blood pressure is a major risk factor for heart disease and stroke, the first and third leading causes of death among adults in the United States.

Ω

The most common – and under-diagnosed – genetic disease in humans just may be a cause of the worst form of macular degeneration, Medical College of Georgia researchers report.

They are pursuing a link between hemochromatosis, which results in iron overload, and the wet form of macular degeneration, the leading cause of blindness in people 60 and older. They suspect that too much iron, known to wreak cumulative havoc on the body's organs, hastens normal aging of the eyes.

If they are correct, avoiding the most severe consequences of a disease that robs the central vision could be as simple as donating blood a couple times annually to reduce iron levels, said Dr. Vadivel Ganapathy, chairman of the MCG School of Medicine Department of Biochemistry and Molecular Biology.

A $1.5 million grant from the National Eye Institute is enabling the MCG scientists to define the impact of hemochromatosis on the eye's form and function. Support from MCG's Vision Discovery Institute is enabling screening for its causative genetic mutation in the blood of healthy individuals and those with macular degeneration.

"If this is a predisposing risk for macular degeneration, we have a very useful tool for screening patients," said Dr. Julian Nussbaum, a retinal specialist who chairs the School of Medicine's Department of Ophthalmology and co-directs MCG's Vision Discovery Institute. "We can give patients information right off the bat that may help them."

While linking iron overload to eye disease may seem odd, they have in common the result of too much of a good thing. The eyes need light to see and the body needs iron to deliver oxygen but the price of both is increased oxidative stress, Ganapathy said. "You need oxygen and you need iron to make this bad molecule," he said of oxygen radicals that can destroy tissue down to the DNA.

Light alone takes a slow toll on the retina, which converts it into electrical impulses sent to the brain via the optic nerve. This is despite multiple built-in safeguards such as filters in the cornea and lens that protect against the most harmful rays, like ultraviolet light, and a yellow pigment that provides extra protection for the most central point of vision. Retinal pigmented epithelial cells, which nourish sight-enabling cells in the retina, help gobble up and dump any resulting tissue trash into the circulation for elimination. Leftovers show up as fatty, yellow deposits called drusen.

Everyone experiences some age-related vision changes and accumulation of harmless levels of drusen, Nussbaum said.

But when byproducts start accumulating under the retinal pigment epithelium, the risk increases for the wet form of macular degeneration in which fragile new blood vessels grow underneath the retina, leak and cloud vision. The question is why some people's condition worsens.

"We see it in one patient and it may stay that way for 20 years. We see it in another patient and within five years their vision has functionally started to decrease," said Dr. Emory Patterson, an MCG School of Medicine graduate completing his ophthalmology residency at MCG who is helping with the clinical study.

Ganapathy first determined that the eye had the means to tightly regulate iron levels. Most organs don't have their own system rather the small intestine regulates absorption of the iron consumed in foods like beans and tofu.

But Ganapathy found the same genetic mutation that causes hemochromatosis in a back layer of the retina, which comes in contact with the blood. A mutation in this HFE gene impairs a protein that regulates iron absorption. The finding in the mouse eye and human retinal pigmented epithelial cells was published in 2004 in Investigative Ophthalmology and Visual Science.

His lab now has animal models for hemochromatosis as well as juvenile hemochromatosis, which is caused by a different genetic defect and produces much earlier symptoms.

In the retina of the models, he's finding increased expression of vascular endothelial growth factors, or VEGF, that enable new blood vessel growth. This growth is the hallmark of the wet form of macular degeneration. In fact, anti-VEGF therapies are the most potent treatments available.

"I tell patients that caught early, they have a 92 percent chance of stabilizing their vision with anti-VEGF therapy but they only have about a 38 percent chance of improving their vision," Nussbaum said. "But at least we can treat it. I also remind them there is not a cure. It's similar to cancer therapy: we can put them into remission but we don't know if it will come back."

Most people absorb about 10 percent of the iron they consume. Symptoms such as joint pain, fatigue, lack of energy, abdominal pain, loss of sex drive and heart problems indicate excess absorption although many with the condition have no symptoms when diagnosed.

Ω

An organic compound found in red wine – resveratrol – has the ability to neutralize the toxic effects of proteins linked to Alzheimer’s disease, according to research led by Rensselaer Professor Peter M. Tessier. The findings, published in the May 28 edition of the Journal of Biological Chemistry, are a step toward understanding the large-scale death of brain cells seen in certain neurodegenerative diseases.

“We’ve shown how resveratrol has very interesting selectivity to target and neutralize a select set of toxic peptide isoforms,” Tessier said. “Because resveratrol picks out the clumps of peptides that are bad and leaves alone the ones that are benign, it helps us to think about the structural differences between the peptide isoforms.”

Isoforms are different packing arrangements of a particular peptide. Deformations of a particular peptide - the A_1-42 peptide - have been linked to Alzheimer’s disease. Improperly folded peptides have been shown to collect in accumulations called “plaques” within the brain. Those plaques are often found near areas of cell death in diseased brains.

It is not clear that resveratrol is able to cross the blood-brain barrier, Tessier said. However, the molecule has garnered interest in recent years for its potential impact on cancer and aging.

In their research, Tessier and his co-authors generated A_ peptides packed together in five unique isoforms, or “arrangements” (monomer, soluble oligomer, non-toxic oligomer, fibrillar intermediates and amyloid fibrils). In their experiments, three of these arrangements were toxic to human cells, two were not.

Next, the researchers introduced resveratrol.

The resveratrol reacted with the toxic arrangements of the A_1-42 peptide, neutralizing their toxicity.

It did not affect the non-toxic arrangements.

“The surprise is that this molecule can target some of these packing arrangements that are toxic and rearrange them into packing arrangements that are not toxic. For those forms that are non-toxic, it doesn’t change them,” Tessier said.

Intriguingly, Tessier said, one of the toxic arrangements (the soluble oligomer) and one of the non-toxic arrangements (the non-toxic oligomer) were indistinguishable by various methods. And yet the resveratrol only affected the toxic arrangement.

The point, Tessier concludes, is that the seemingly identical non-toxic and toxic arrangements must have some distinguishing feature yet to be discovered, raising questions for future study.

“We have two things that look very similar, but one is toxic and the other isn’t,” Tessier said. “What is it that makes the bad one bad and the good one good?”

Ω

Data on the effects of coffee on cancer risk have been mixed. However, results of a recent study add to the brewing evidence that drinking coffee protects against cancer, this time against head and neck cancer.

Full study results are published online first in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

Using information from a pooled-analysis of nine studies collected by the International Head and Neck Cancer Epidemiology (INHANCE) consortium, participants who were regular coffee drinkers, that is, those who drank an estimated four or more cups a day, compared with those who were non-drinkers, had a 39 percent decreased risk of oral cavity and pharynx cancers combined.

Data on decaffeinated coffee was too sparse for detailed analysis, but indicated no increased risk. Tea intake was not associated with head and neck cancer risk.

The association is more reliable among those who are frequent, regular coffee drinkers, consuming more than four cups of coffee a day.

"Since coffee is so widely used and there is a relatively high incidence and low survival rate of these forms of cancers, our results have important public health implications that need to be further addressed," said lead researcher Mia Hashibe, Ph.D., assistant professor in the department of family and preventive medicine at the University of Utah, Salt Lake City, and a Huntsman Cancer Institute investigator.

"What makes our results so unique is that we had a very large sample size, and since we combined data across many studies, we had more statistical power to detect associations between cancer and coffee," she said.

At the AACR Frontiers in Cancer Prevention Research Conference last December, researchers from Harvard presented data that showed a strong inverse association between coffee consumption and the risk of lethal and advanced prostate cancers — men who drank the most coffee had a 60 percent lower risk of aggressive prostate cancer than men who did not drink any coffee.

More recently, results of another study published in the January issue of Cancer Epidemiology, Biomarkers & Prevention showed a decreased risk of gliomas, or brain tumors, associated with coffee. This association was found among those who drank five or more cups of coffee or tea a day, according the researchers from the Imperial College, London.

Cancer Epidemiology, Biomarkers & Prevention editorial board member Johanna W. Lampe, Ph.D., R.D., believes this current analysis by Hashibe and colleagues provides strong, additional evidence for an association between caffeinated coffee drinking and cancer risk.

"The fact that this was seen for oral and pharyngeal cancers, but not laryngeal cancers, provides some evidence as to a possible specificity of effect," said Lampe, who is a full member and associate division director in the division of public health sciences at Fred Hutchinson Cancer Research Center, Seattle., Wash.

"These findings provide further impetus to pursue research to understand the role of coffee in head and neck cancer prevention," she added. Lampe is not associated with this study.

Additional research is warranted to characterize the importance of timing and duration of exposure and possible mechanisms of action, according to Hashibe.

Ω

Patients who had experienced a heart attack and lowered their blood homocysteine levels with folic acid and vitamin B12 supplementation did not have an associated lower risk of heart attack, coronary death or stroke, according to a study in the June 23/30 issue of JAMA. However, the researchers did find that folic acid supplementation did not increase the risk of cancer, which has been speculated.

Blood homocysteine levels are positively associated with cardiovascular disease, but it is uncertain whether the association is causal, according to background information in the article. A meta-analysis of prospective studies indicated that, after adjustment for known risk factors, a 25 percent lower than usual homocysteine concentration was associated with an 11 percent lower risk of coronary heart disease and 19 percent lower risk of stroke. "Daily supplementation with folic acid typically lowers homocysteine levels by about 25 percent, and the addition of vitamin B12 lowers it by a further 7 percent," the authors write. Other research has suggested supplementation with folic acid may offer a protective effect against stroke.

Jane M. Armitage, F.R.C.P., of the University of Oxford, United Kingdom, and colleagues with the Study of the Effectiveness of Additional Reductions In Cholesterol and Homocysteine (SEARCH) trial assessed the effects of lowering homocysteine levels with folic acid plus vitamin B12 in 12,064 survivors of myocardial infarction (heart attack) in secondary care hospitals in the United Kingdom between 1998 and 2008. Patients were randomized to receive either 2 mg. folic acid plus 1 mg. vitamin B12 daily or matching placebos. The primary outcomes measured included first major vascular event, defined as major coronary event (coronary death, heart attack, or coronary revascularization), fatal or nonfatal stroke, or noncoronary revascularization.

Patients who received the study vitamins reduced homocysteine by an average of 3.8 µmol/L (28 percent). During 6.7 years of follow-up, major vascular events occurred in 1,537 of 6,033 participants (25.5 percent) allocated folic acid plus vitamin B12 vs. 1,493 of 6,031 participants (24.8 percent) allocated placebo. "There was no evidence of any benefit beginning to emerge with more prolonged treatment and follow-up," the authors write.

Receipt of study vitamins also was not associated with a significant effect on any stroke (vitamins, 4.5 percent vs. placebo, 4.4 percent); noncoronary revascularizations (vitamins, 3.0 percent vs. placebo, 2.5 percent); or major coronary events (vitamins, 20.4 percent vs. placebo, 19.6 percent). There were no apparent differences in the numbers of deaths attributed to vascular causes or nonvascular causes.

New primary cancers (excluding non-melanoma skin cancer) were diagnosed in 11.2 percent of the participants allocated folic acid plus vitamin B12 vs. 10.6 percent allocated placebo, with this difference not being significant.

"Taken together with the previous homocysteine-lowering trials, the results of SEARCH indicate that folic acid supplementation has no significant adverse effects on cancer or other major health outcomes, even if it also produces no beneficial effects on cardiovascular disease. In addition, these results highlight the importance of focusing on drug treatments (e.g., aspirin, statins, and antihypertensive therapy) and lifestyle changes (in particular, stopping smoking and avoiding excessive weight gain) that are of proven benefit, rather than lowering homocysteine with folic acid-based vitamin supplements, for the prevention of cardiovascular disease," the authors conclude.

Ω

Among women who drank filtered coffee there was an increased risk for early breast cancer (under 49 years old) and a decreased risk for late breast cancer (over 55 years old).

Women who drink Scandinavian boiled coffee, which chemically resembles French press and Turkish/Greek coffee, more than four times a day run a lower risk of developing breast cancer than women who drink coffee less than once a day. This is shown by Lena Nilsson and her associates at Umeå University in an article in the journal Cancer

A major difference between boiled and filtered coffee is that the boiled version contains up to 80 times as much coffee-specific fatty acids. These fatty acids have previously been shown in animal experiments to inhibit the growth of cancer.

By comparing filtered coffee and boiled coffee in the Västerbotten Intervention Project (64,603 participants), researchers at Umeå University have been able to show for the first time that various brewing techniques can lead to different risk patterns for cancer. For total cancer, prostate cancer, colorectal cancer, and many other less common forms of cancer, there was no correlation.

Among women who drank boiled coffee more than four times a day there was a lowered risk of breast cancer compared with women who drank coffee less than once a day. Among women who drank filtered coffee there was an increased risk for early breast cancer (under 49 years old) and a decreased risk for late breast cancer (over 55 years old). Boiled-coffee drinkers, but not filtered-coffee drinkers, also had an increased risk of pancreatic cancer and lung cancer among men.

The study, recently published in the scientific journal Cancer Causes and Control, is the first in the world to compare the consumption of coffee prepared with two brewing techniques in regard to cancer.

Ω

Fructose, a sugar widely used in soft drinks and processed foods, often gets some of the blame for the widespread rise in obesity. Now a laboratory study has found that when fructose is present as children's fat cells mature, it makes more of these cells mature into fat cells in belly fat and less able to respond to insulin in both belly fat and fat located below the skin.

"Our results suggest that high levels of fructose, which may result from eating a diet high in fructose, throughout childhood may lead to an increase in visceral [abdominal] obesity, which is associated with increased cardiometabolic risk," lead author Georgina Coade, a PhD student at the University of Bristol in the U.K., said.

Defined by a large waistline, abdominal obesity raises the risk of heart disease and Type 2 diabetes. The abdominal cavity contains one of two major types of fat in the body: visceral fat. The other type, subcutaneous fat, is found below the surface of the skin.

Although researchers have shown the negative effects of fructose on the fat distribution of rodents, the effects of this sugar on human adipocytes, or fat cells, are not clear, according to Coade. Therefore, she and her fellow researchers studied biopsy specimens of both subcutaneous and visceral fat from 32 healthy-weight children who had not yet gone through puberty.

From the biopsy samples, the investigators obtained preadipocytes -- the precursors to fat cells that have the potential to differentiate, or mature, into fat-containing adipocytes. They then allowed the precursor cells to mature for 14 days in culture media containing normal glucose (the main sugar found in the bloodstream and the principal source of energy in the body), high glucose or high fructose. The researchers assessed cell differentiation by measuring activity of an enzyme (GPDH) and the abundance of the adipocyte fatty acid binding protein, which are both present only in mature fat cells.

Fructose, the research team found, had different effects to that of glucose and caused the fat cells to differentiate more -- that is, to form more mature fat cells -- but only in visceral fat.

For both types of fat cells, maturation in fructose decreased the cells' insulin sensitivity, which is the ability to successfully take up glucose from the bloodstream into fat and muscles. Decreased insulin sensitivity is a characteristic of Type 2 diabetes.

Although prolonged exposure to fructose had a negative effect on insulin sensitivity, when Coade and her co-workers exposed mature fat cells, rather than preadipocytes, to fructose for 48 hours, the cells' insulin sensitivity increased. The reason why is unknown. However, she said, "Fructose alters the behavior of human fat cells if it is present as the fat cells mature. We can maybe compare this [timing] to periods in children when they are making their fat."

Ω

Study highlights:

- Both high and moderate amounts of tea are linked with reduced heart disease deaths.
- Moderate amounts of coffee are linked with reduced heart disease risk.
- Neither coffee nor tea consumption was associated with stroke risk in this Dutch study.

Coffee and tea drinkers may not need to worry about indulging – high and moderate consumption of tea and moderate coffee consumption are linked with reduced heart disease, according to a study published in Arteriosclerosis, Thrombosis, and Vascular Biology: Journal of the American Heart Association.

Researchers in The Netherlands found:

Drinking more than six cups of tea per day was associated with a 36 percent lower risk of heart disease compared to those who drank less than one cup of tea per day.

Drinking three to six cups of tea per day was associated with a 45 percent reduced risk of death from heart disease, compared to consumption of less than one cup per day.

And for coffee they found:

Coffee drinkers with a modest intake, two to four cups per day, had a 20 percent lower risk of heart disease compared to those drinking less than two cups or more than four cups.

Although not considered significant, moderate coffee consumption slightly reduced the risk of heart disease death and deaths from all causes.

Researchers also found that neither coffee nor tea consumption affected stroke risk.

“While previous studies have shown that coffee and tea seem to reduce the risk of heart disease, evidence on stroke risk and the risk of death from heart disease was not conclusive,” said Yvonne T. van der Schouw, Ph.D., study senior author and professor of chronic disease epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands. “Our results found the benefits of drinking coffee and tea occur without increasing risk of stroke or death from all causes.

Van der Schouw and colleagues used a questionnaire to evaluate coffee and tea consumption among 37,514 participants. They followed the participants for 13 years for occurrences of cardiovascular disease and death.

Study limitations included self-reported tea and coffee consumption, and the lack of specific information on the type of tea participants drank. However, black tea accounts for 78 percent of the total tea consumed in The Netherlands and green tea accounts for 4.6 percent. Coffee and tea drinkers have very different health behaviors, researchers note. Many coffee drinkers tend to also smoke and have a less healthy diet compared to tea drinkers.

Researchers suggest that the cardiovascular benefit of drinking tea may be explained by antioxidants. Flavonoids in tea are thought to contribute to reduced risk, but the underlying mechanism is still not known.

Ω

Ω

Association between coffee consumption and RA not found

RomeWomen who drink tea have an increased risk of developing Rheumatoid Arthritis (RA) compared with those who drink none (p=0.04. Further results from the same study showed no correlation between the amount of coffee consumption and RA incidence (p=0.16).

The results of the US based longitudinal cohort study involving 76,643 women showed a positive association of incident RA in tea drinkers with an increasing Hazard Ratio (HR) observed alongside tea consumption (p=0.03). Consuming any amount of tea carried a significant risk of developing RA (HR 1.40 (95%CI 1.01-1.93) p=0.04) and women who drank ≥4 cups of tea per day had an increased risk of developing RA compared to those who drank none (HR 1.78 (95%CI 0.83-3.82)). An analysis of the method of preparation of coffee (filtered vs unfiltered) and presence or lack of caffeine in the beverage did not show any significant associations with RA or Systemic Lupus Erythematosus (SLE, an autoimmune disease in which the immune system harms the body's own healthy cells and tissues) (RA: filtered p=0.08, unfiltered p=0.38, SLE: filtered p=0.74, unfiltered p=0.97). No increase was shown in the risk of developing RA in participants who drank coffee compared to those that did not (RA: HR 1.09 (95%CI 0.77-1.54 p=0.63).

"We set out to determine whether tea or coffee consumption, or the method of preparation of the drinks was associated with an increased risk of RA or SLE – it is surprising that we saw such differences in results between tea and coffee drinkers," said Professor Christopher Collins, Assistant Professor of Medicine, Georgetown University Medical Center, Washington, USA. "This does make us wonder what it is in tea, or in the method of preparation of tea that causes the significant increase in risk of developing RA."

Data on women aged 50-79 were taken from the Women's Health Initiative Observational Study database (a major 15-year research program to address the most common causes of death, disability and poor quality of life in postmenopausal women) where participants completed a self-administered questionnaire providing information on daily consumption of coffee and tea.

The relationships between drinking tea and coffee and the risk of RA or SLE were assessed in age-adjusted models and in multivariate Cox proportional hazard models (a statustical approach to estimating survival data). At three years follow up, the diagnosis of incident RA was determined using self-reporting and respondent's feedback on use of disease modifying anti-rheumatic drugs (DMARDS). The variables studied in the RA population were also investigated in women with SLE, but no significant associations were found.

"These are very interesting findings and we hope that additional research will investigate this topic further. We do assert the need for caution in the interpretation of these findings as no strong causation effect has been confirmed, and encourage patients with rheumatic diseases to consult their physician before making any significant changes to their diet or caffeine intake" said Professor Paul Emery, President of EULAR and arc Professor of Rheumatology, Leeds Institute of Molecular Medicine, University of Leeds, UK

Ω




Recommended supplementation is not sufficient to normalise vitamin D levels in RA and osteoporosis patients


Two separate studies have shown that vitamin D deficiency is common in patients with a range of rheumatic diseases, with over half of all patients having below the 'normal' healthy levels of vitamin D (48-145 nmol/L) in their bodies. A further study assessing response to vitamin D supplementation found that taking the recommended daily dose did not normalise vitamin D levels in rheumatic disease patients.

A UK study1 of 180 patients aimed to assess mean levels of vitamin D in patients with inflammatory joint diseases, osteoarthritis and myalgia (muscle pain that, when experienced long term may be associated with nutritional deficiency). Data on vitamin D levels were gathered and results showed that 58% of individuals with a rheumatic condition had levels below that clinically considered to be 'sufficient' in healthy subjects (48-145 nmol/L).

An Italian study2 of 1,191 RA patients aimed to determine a correlation between vitamin D deficiency and several different clinical measures of disease activity. Researchers found that, regardless of supplementation, levels of 25-hydroxyvitamin D (25(OH)D), (a standard clinical measure of vitamin D in the blood), were lower than healthy levels (<50 nmol/L) in 85% of the patients not taking a vitamin D supplement and in 60% of those taking 800 IU or more vitamin D daily as a supplement. In non-supplemented patients levels of 25(OH)D significantly correlated with three measures of disease activity - the Health Assessment Questionnaire Disability Index, (p=0.000) the Mobility Activities of Daily Living Score (p=0.000) and the Number of Swollen Joints count (p=0.000).

"We have seen in studies that vitamin D deficiency is common in patients with a range of rheumatic diseases, and our results have confirmed this using several clinically accepted measures of disease activity," said Dr. L. Idolazzi, of the Rheumatology Unit, University of Verona, Italy. "What we need to see now is a range of long term studies, which examine the clinical response of patients to vitamin D supplementation."

Furthermore, a third study undertaken in Italy3 aimed to evaluate the affect of vitamin D supplementation in patients with inflammatory autoimmune disease (IAD) and non-inflammatory autoimmune disease (NIAD). Following supplementation, only 29% patients reached vitamin D levels greater than the level clinically considered to be 'sufficient' in healthy subjects, with no significant differences in vitamin D levels observed between the IAD and NIAD groups.

"Whilst it is well known that hypovitaminosis D is often seen in patients with inflammatory autoimmune diseases, the effects of supplementation have not been fully investigated in this setting," said Dr. Pier Paolo Sainaghi of the Immuno-Rheumatology Clinic, A. Avogadro University of Eastern Piedmont, Novara, Italy and author of the third study. "The results of our study show that daily 800-1,000 IU supplementation is not sufficient to normalise vitamin D levels in patients with rheumatologic or bone conditions. What is unclear is whether a higher dose would be more effective."

Study designs and key statistics

The UK study1 involved patients with a diagnosis of rheumatoid arthritis (RA), osteoporosis, or unexplained muscle pain, (total n=90, 30 from each group). These patients were matched with a control group of patients presenting with chronic back pain for a minimum of 6 months (n=90). The RA patient group registered median levels of vitamin D of 36 nmol/L (range 16-85 nmol/L, p=0.045) and in osteoporosis patients, these levels were slightly lower with a median value of 31 nmol/L (range 7-82 nmol/L, p=0.005). Patients with unexplained muscle pain had equally low median levels of vitamin D at 31 nmol/l (range 11-79 nmol/L, p= 0.008).

In the first Italian study2 of 1,191 patients (85% women) from 22 rheumatology centres, researchers measured levels of 25(OH)D, alongside paramaters of disease activity, calcium intake, sun exposure and bone mineral density. The association found by researchers between disease activity scores and vitamin D levels remained statistically significant when adjusted for both sun exposure and body mass index (BMI), both known risk factors for vitamin D deficiency. Significantly lower 25(OH)D levels were found in patients with active disease compared with those in disease remission (mean level 21.8 nmol/L 25(OH)D vs. 23.6 nmol/L respectively, p=0.057), and in those who were not responding to treatment compared to patients with a good response to treatment (20.5 nmol/L vs. 23.4 nmol/L p=0.020).

In the third Italian study3, 100 patients (43 with IAD and 57 with NIAD) received daily supplementation of 800-1000 IU of cholecalciferol (a form of vitamin D often used to fortify foods) over the course of six months. Abstract Numbers: FRI0509, SAT0093, SAT0506

Vitamin D deficiency is highly prevalent in patients with Type 2 diabetes and may be associated with poor blood sugar control, according to a new study. The results will be presented Saturday at The Endocrine Society's 92nd Annual Meeting in San Diego.

"This finding supports an active role of vitamin D in the development of Type 2 diabetes," said study co-author Esther Krug, MD, an assistant professor of medicine at The Johns Hopkins University School of Medicine and an endocrinologist at Sinai Hospital, Baltimore.

Krug and her colleagues reviewed the medical charts of 124 patients with Type 2 diabetes who came to an endocrine outpatient clinic for specialty care from 2003 to 2008. Patients' age ranged from 36 to 89 years. All patients had a single measurement of their serum 25-hydroxyvitamin D levels as part of their evaluation at the clinic. The researchers divided the patients into quartiles based on vitamin D level.

Despite receiving regular primary care visits before referral to the endocrine clinic, 91 percent of patients had either vitamin D deficiency (defined as a level below 15 nanograms per deciliter, or ng/dL) or insufficiency (15 to 31 ng/dL), the authors reported. Only about 6 percent of patients were taking vitamin D supplements at their first visit.

Additionally, the investigators found an inverse relationship between the patients' blood levels of vitamin D and their hemoglobin A1c value, a measure of blood sugar control over the past several months. Lower vitamin D levels were discovered in patients with higher average blood sugars as measured by HbA1c, Krug said. Compared with whites, blacks had a higher average A1c and lower average vitamin D level.

"Since primary care providers diagnose and treat most patients with Type 2 diabetes, screening and vitamin D supplementation as part of routine primary care may improve health outcomes of this highly prevalent condition," she said.

Ω

A diet rich in natural antioxidants improves insulin sensitivity in insulin-resistant obese adults and enhances the effect of the insulin-sensitizing drug metformin, a preliminary study from Italy finds. The results will be presented Monday at The Endocrine Society's 92nd Annual Meeting in San Diego.

"The beneficial effects of antioxidants are known, but we have revealed for the first time one of their biological bases of action—improving hormonal action in obese subjects with the metabolic syndrome," said principal author Antonio Mancini, MD, an endocrinology researcher at Catholic University of the Sacred Heart in Rome.

The metabolic syndrome is a cluster of metabolic risk factors for developing diabetes, heart disease and stroke. People with this syndrome cannot efficiently use insulin, the hormone that regulates glucose (sugar) in the blood.

Some evidence exists that oxidative stress may play a role in the metabolic syndrome, according to Mancini. Oxidative stress, a biochemical mechanism which can lead to damage to blood particles and to cells, results from an imbalance between an excessive amount of oxidants and decreased antioxidant defenses. Oxidative stress also plays a part in aging.

Antioxidants, which are found naturally in fruits, vegetables, legumes and nuts, include vitamins E and C, selenium and carotenoids, such as beta-carotene. Past research shows that antioxidants can prevent oxidative damage to cells and in some cases also help repair damage.

Mancini and his colleagues studied the effects of dietary antioxidants on insulin resistance, with partial financial support from MIUR, the Italian Department for University and Research. The study included 16 men and 13 women, ages 18 to 66 years, who were obese and insulin-resistant, but were not yet diabetic.

The researchers randomly assigned the subjects to one of four treatment groups. All groups ate a low-calorie, Mediterranean-type diet averaging 1,500 calories daily, containing only 25 percent from protein foods, with the rest made up of low-glycemic-index carbohydrates (carbs that do not raise blood sugar levels quickly or greatly, such as whole grains). Group A only ate this kind of diet, and group B ate the same diet plus took the drug metformin. For groups C and D, the researchers prescribed a diet enriched in antioxidant, with a calculated intake, 800 to 1,000 milligrams a day, coming from fruits and vegetables, but group D also took metformin.

Despite similar weight loss in all the groups, only the two groups receiving the antioxidant diet (groups C and D) had a significant decrease in insulin resistance, the authors reported. Group D had the best improvement in insulin resistance on some measures of insulin response to an oral glucose tolerance test, according to the abstract.

Subjects reported no adverse effects from the antioxidant diet, Mancini said. When asked about the risk of adding more antioxidants to a diet, he stated, "We think that a total antioxidant level of 800 to 1,000 milligrams a day is safe and probably not close to the maximum tolerable level."