Being overweight increases the chances of premature death

Global study contradicts a previous finding that being overweight increases longevity

Being overweight increases the chances of premature death, according to a USC researcher.

Although people accept that obesity can shorten a person's life span, scientists have debated whether the weight category between normal and obese is, in fact, a health risk.

Being overweight definitely does not help people live longer, said Jonathan Samet, director of the USC Institute for Global Health. His statement is backed by a four-continent effort involving 239 studies and data from 10.6 million people. The collaborative and comprehensive study -- one of the largest to date -- was published in The Lancet.

The results have important clinical and public health implications, Samet said.

"Physicians should identify being overweight as posing a risk to health," said Samet, one of the study's authors and holder of the Flora L. Thornton Chair in Preventive Medicine at the Keck School of Medicine of USC. "Increasing the risk of dying is a powerful indicator of health. The new results on overweight should be strong motivation for people to return to a healthy weight."

The World Health Organization states that more than 1.9 billion people -- about 39 percent of adults -- are overweight, defined as having a body mass index between 25 and 30. For example, a 5-foot-4 person who weighs 140 pounds has a healthy BMI of 24. Add five pounds and this individual would be considered overweight.

The study analyzed participants who had never smoked, did not have chronic disease and were still alive five years after the research began. The study involved 385,879 deaths in 239 studies.

Overweight and obesity were strongly connected to coronary heart disease, stroke and respiratory disease death, and were moderately linked to cancer mortality. The findings were reflected in Europe, North America and East Asia.

The new finding contradicts a 2013 review article

The new finding on overweight is counter to the results of a prior paper in the Journal of the American Medical Association, which found that being overweight actually adds to one's life span, and "grade 1 obesity" (BMI 30-35) did not increase mortality. The JAMA article was based on a review of 97 studies with 2.9 million participants.

The Lancet study did more than just summarize published results; the data from all 239 studies was analyzed in a standard way.

"Our study was able to reproduce [the JAMA review's] findings when conducting crude analyses with inadequate control of reverse causality, but not when we conducted appropriately strict analyses," the Lancet paper stated.

The WHO states that about 95 million children -- mostly in less developed regions -- are underweight.

Being underweight, according to the study, was associated with substantially higher respiratory disease mortality and somewhat higher death rates from coronary heart disease, stroke and cancer. These findings held true in Asia, Australia, New Zealand, Europe and North America.

Keeping your weight in check

One of the study's limitations, like many other research papers in this arena, is the use of BMI as a surrogate for visceral fat, which is thought to be key in bringing about the negative consequences linked to obesity.

"The health risk associated with obesity is thought to be driven by abdominal fat," Samet said. "BMI is an imperfect measure of fat in someone's belly. There are more gold standard ways to measure fat, but that can't be done for 10.6 billion people."

Using an accepted but imperfect measure, the study was able to find a connection between premature death and being overweight. The proportion of premature deaths that could be avoided with a healthy weight (between BMI 18.5 and 25) is about 1 in 5 in North America, 1 in 6 in Australia and New Zealand, 1 in 7 in Europe and 1 in 20 in East Asia.

In short, like smoking, the health problems associated with underweight, overweight and obesity are substantial but potentially preventable.
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Moderate physical activity linked with 50 percent reduction in cardiovascular death in over-65s

Moderate physical activity is associated with a greater than 50% reduction in cardiovascular death in over-65s, according to research presented at ESC Congress 2016 today.1 The 12 year study in nearly 2500 adults aged 65 to 74 years found that moderate physical activity reduced the risk of an acute cardiovascular event by more than 30%. High levels of physical activity led to greater risk reductions.

"The role of physical activity in preventing cardiovascular disease (CVD) in people of working age is well established," said Professor Riitta Antikainen, professor of geriatrics at the University of Oulu, Finland. "But relatively little is known about the effect of regular physical activity on CVD risk in older people."

The present study assessed the association between leisure time physical activity and CVD risk and mortality in 2456 men and women aged 65 to 74 years who were enrolled into the National FINRISK Study between 1997 and 2007.

Baseline data collection included self-administered questionnaires on physical activity and other health related behaviour, clinical measurements (blood pressure, weight and height), and laboratory measurements including serum cholesterol. Participants were followed up until the end of 2013. Deaths were recorded from the National Causes of Death Register and incident CVD events (coronary heart disease and stroke) were collected from the National Hospital Discharge register.

The researchers classified self-reported physical activity as:

• Low: reading, watching TV or working in the household without much physical activity.
• Moderate: walking, cycling or practising other forms of light exercise (fishing, gardening, hunting) at least four hours per week.
• High: recreational sports (for example running, jogging, skiing, gymnastics, swimming, ball games or heavy gardening) or intense training or sports competitions at least three hours a week.
•  

During a median follow-up of 11.8 years, 197 participants died from CVD and 416 had a first CVD event.

When the researchers assessed the link between physical activity and outcome they adjusted for other cardiovascular risk factors (blood pressure, smoking and cholesterol) and social factors (marital status and education). To minimise reverse causality, where worse health leads to less physical activity, patients with coronary heart disease, heart failure, cancer, or prior stroke at baseline were excluded from the analysis.

The investigators found that moderate and high leisure time physical activity were associated with a 31% and 45% reduced risk of an acute CVD event, respectively (figure 1). Moderate and high leisure time physical activity were associated with a 54% and 66% reduction in CVD mortality.

Professor Antikainen said: "Our study provides further evidence that older adults who are physically active have a lower risk of coronary heart disease, stroke, and death from cardiovascular disease. The protective effect of leisure time physical activity is dose dependent - in other words, the more you do, the better. Activity is protective even if you have other risk factors for cardiovascular disease such as high cholesterol."

She concluded: "Physical exercise may become more challenging with ageing. However, it is important for older people to still get enough safe physical activity to stay healthy after their transition to retirement."

Mediterranean diet associated with lower risk of death in cardiovascular disease patients

The Mediterranean diet is associated with a reduced risk of death in patients with a history of cardiovascular disease, according to results from the observational Moli-sani study presented at ESC Congress 2016 today.1

"The Mediterranean diet is widely recognised as one of the healthier nutrition habits in the world," said Professor Giovanni de Gaetano, head of the Department of Epidemiology and Prevention at the I.R.C.C.S. Neuromed Institute in Pozzilli, Italy. "In fact, many scientific studies have shown that a traditional Mediterranean lifestyle is associated with a lower risk of various chronic diseases and, more importantly, of death from any cause."

"But so far research has focused on the general population, which is mainly composed of healthy people," he added. "What happens to people who have already suffered from cardiovascular disease? Is the Mediterranean diet optimal for them too?"

The answer is yes, according to a study in patients with a history of cardiovascular disease, such as coronary artery disease and stroke. The patients were among the participants enrolled into the Moli-sani project, a prospective epidemiological study that randomly recruited around 25 000 adults living in the Italian region of Molise.2

"Among the participants, we identified 1197 people who reported a history of cardiovascular disease at the time of enrolment into Moli-sani," said Dr Marialaura Bonaccio, lead author of the research.

Food intake was recorded using the European Prospective Investigation into Cancer (EPIC) food frequency questionnaire. Adherence to the Mediterranean diet was appraised with a 9-point Mediterranean diet score (MDS). All-cause death was assessed by linkage with data from the office of vital statistics in Molise.

During a median follow up of 7.3 years there were 208 deaths. A 2-point increase in the MDS was associated with a 21% reduced risk of death after controlling for age, sex, energy intake, egg and potato intake, education, leisure-time physical activity, waist to hip ratio, smoking, hypertension, hypercholesterolaemia, diabetes and cancer at baseline.

When considered as a 3-level categorical variable, the top category (score 6-9) of adherence to the Mediterranean diet was associated with 37% lower risk of death compared to the bottom category (0-3).

Professor de Gaetano said: "We found that among those with a higher adherence to the Mediterranean diet, death from any cause was reduced by 37% in comparison to those who poorly adhered to this dietary regime."

The researchers deepened their investigation by looking at the role played by individual foods that make up Mediterranean diet. "The major contributors to mortality risk reduction were a higher consumption of vegetables, fish, fruits, nuts and monounsaturated fatty acids - that means olive oil," said Dr Bonaccio.

Professor de Gaetano concluded: "These results prompt us to investigate the mechanism(s) through which the Mediterranean diet may protect against death. This was an observational study so we cannot say that the effect is causal. We expect that dietary effects on mediators common to chronic diseases such as inflammation might result in the reduction of mortality from any cause but further research is needed."

Stopping exercise decreases brain blood flow in older adults

We all know that we can quickly lose cardiovascular endurance if we stop exercising for a few weeks, but what impact does the cessation of exercise have on our brains? New research led by University of Maryland School of Public Health researchers examined cerebral blood flow in healthy, physically fit older adults (ages 50-80 years) before and after a 10-day period during which they stopped all exercise. Using MRI brain imaging techniques, they found a significant decrease in blood flow to several brain regions, including the hippocampus, after they stopped their exercise routines.

"We know that the hippocampus plays an important role in learning and memory and is one of the first brain regions to shrink in people with Alzheimer's disease," says Dr. J. Carson Smith, associate professor of kinesiology and lead author of the study, which is published in Frontiers in Aging Neuroscience in August 2016. "In rodents, the hippocampus responds to exercise training by increasing the growth of new blood vessels and new neurons, and in older people, exercise can help protect the hippocampus from shrinking. So, it is significant that people who stopped exercising for only 10 days showed a decrease in brain blood flow in brain regions that are important for maintaining brain health."

The study participants were all "master athletes," defined as people between the ages of 50 and 80 (average age was 61) who have at least 15 years history of participating in endurance exercise and who have recently competed in an endurance event. Their exercise regimens must have entailed at least four hours of high intensity endurance training each week. On average, they were running ~36 miles (59 km) each week or the equivalent of a 10K run a day! Not surprisingly, this group had a V02 max above 90% for their age. This is a measure of the maximal rate of oxygen consumption of an individual and reflects their aerobic physical fitness.

Dr. Smith and colleagues measured the velocity of blood flow in brain with an MRI scan while they were still following their regular training routine (at peak fitness) and again after 10 days of no exercise. They found that resting cerebral blood flow significantly decreased in eight brain regions, including the areas of the left and right hippocampus and several regions known to be part of the brain's "default mode network" - a neural network known to deteriorate quickly with a diagnosis of Alzheimer's disease. This information adds to the growing scientific understanding of the impact of physical activity on cognitive health.

"We know that if you are less physically active, you are more likely to have cognitive problems and dementia as you age," says Dr. Smith. "However, we did not find any evidence that cognitive abilities worsened after stopping exercising for just 10 days. But the take home message is simple - if you do stop exercising for 10 days, just as you will quickly lose your cardiovascular fitness, you will also experience a decrease in blood brain flow."

Dr. Smith believes that this could have important implications for brain health in older adults, and points to the need for more research to understand how fast these changes occur, what the long term effects could be, and how fast they could be reversed when exercise is resumed.

Selenium status influence cancer risk

As a nutritional trace element, selenium forms an essential part of our diet. In collaboration with the International Agency for Research on Cancer, researchers from Charité - Universitätsmedizin Berlin have been able to show that high blood selenium levels are associated with a decreased risk of developing liver cancer. In addition to other risk factors, the study also examines in how far selenium levels may influence the development of other types of cancer. Results from this study have been published in the American Journal of Clinical Nutrition.

Selenium (Se) is found in foods like fish, shellfish, meat, milk and eggs; certain South American nuts, such as Brazil nuts, are also good sources of selenium. It is a trace element that occurs naturally in soil and plants, and enters the bodies of humans and animals via the food they ingest. European soil has a rather low selenium concentration, in comparison with other areas of the world, especially in comparison to North America. Deficiencies of varying degrees of severity are common among the general population, and are the reason why German livestock receive selenium supplements in their feed.

While in Europe, neither a selenium-rich diet nor adequate selenium supplementation is associated with adverse effects, selenium deficiency is identified as a risk factor for a range of diseases. "We have been able to show that selenium deficiency is a major risk factor for liver cancer," says Prof. Dr. Lutz Schomburg of the Institute of Experimental Endocrinology, adding: "According to our data, the third of the population with lowest selenium status have a five- to ten-fold increased risk of developing hepatocellular carcinoma - also known as liver cancer."

In this case-control study, the team of European researchers investigated a cohort of 477,000 participants, and selected individuals who had developed hepatocellular carcinoma during a 10-year follow up. Blood samples were also chosen from healthy participants and subsequently analyzed to determine their selenium status. "Our study does not show that selenium supplementation has a direct protective effect against liver cancer. However, it does confirm the importance of a balanced diet, of which selenium forms an integral part," explains Prof. Schomburg. Previous studies had suggested a similar relationship between a person's selenium status and their risk of developing colon cancer, as well as their risk of developing autoimmune thyroid disease.

Breast cancer mortality lower in women who breastfeed

A new study of women 20 years after undergoing surgery for primary breast cancer shows that breastfeeding for longer than 6 months is associated with a better survival rate. Among breast cancer survivors who breastfed for >6 months, both breast cancer mortality and overall mortality risk were less after 20 years, according to the study published in Breastfeeding Medicine, the official journal of the Academy of Breastfeeding Medicine published by Mary Ann Liebert, Inc., publishers. The article is available free on the Breastfeeding Medicine website until September 30, 2016.

In "Breastfeeding Associated with Reduced Mortality in Women with Breast Cancer," Margaretha Lööf-Johanson, MD, Lars Brudin, MD, PhD, and Marie Sundquist, MD, PhD, University of Linkoping, and County Hospital, Kalmar, Sweden, and Carl Edvard Rudebeck, MD, PhD, University of Tromso, Norway, examined the link between lifetime breastfeeding history and both breast cancer-specific and overall survival among women treated for breast cancer who had lived long enough for other causes of death to contribute substantially to mortality.

"This study confirms that the long-term maternal health benefits of breastfeeding are not only preventative in nature, but that it also has the capacity to reduce the severity of breast cancer," says Arthur I. Eidelman, MD, Editor-in-Chief of Breastfeeding Medicine.

Western diet increases Alzheimer's risk

Globally, about 42 million people now have dementia, with Alzheimer's disease as the most common type of dementia. Rates of Alzheimer's disease are rising worldwide. The most important risk factors seem to be linked to diet, especially the consumption of meat, sweets, and high-fat dairy products that characterize a Western Diet. For example, when Japan made the nutrition transition from the traditional Japanese diet to the Western diet, Alzheimer's disease rates rose from 1% in 1985 to 7% in 2008, with rates lagging the nutrition transition by 20-25 years. 

The evidence of these risk factors, which come from ecological and observational studies, also shows that fruits, vegetables, grains, low-fat dairy products, legumes, and fish are associated with reduced risk. "Using Multicountry Ecological and Observational Studies to Determine Dietary Risk Factors for Alzheimer's Disease," a review article from the Journal of the American College of Nutrition presents the data.

In addition to reviewing the journal literature, a new ecological study was conducted using Alzheimer's disease prevalence from 10 countries (Brazil, Chile, Cuba, Egypt, India, Mongolia, Nigeria, Republic of Korea, Sri Lanka, and the United States) along with dietary supply data 5, 10, and 15 years before the prevalence data. Dietary supply of meat or animal products (minus milk) 5 years before Alzheimer's disease prevalence had the highest correlations with Alzheimer's disease prevalence in this study. The study discussed the specific risk each country and region faces for developing Alzheimer's disease based on their associated dietary habits.

Residents of the United States seem to be at particular risk, with each person in the U.S. having about a 4% chance of developing Alzheimer's disease, likely due in part to the Western dietary pattern, which tends to include a large amount of meat consumption. The author, William B. Grant, states, "reducing meat consumption could significantly reduce the risk of Alzheimer's disease as well as of several cancers, diabetes mellitus type 2, stroke, and, likely, chronic kidney disease."

He concludes, "Mounting evidence from ecological and observational studies, as well as studies of mechanisms, indicates that the Western dietary pattern -- especially the large amount of meat in that diet -- is strongly associated with risk of developing Alzheimer's disease and several other chronic diseases. Although the traditional Mediterranean diet is associated with about half the risk for Alzheimer's disease of the Western diet, the traditional diets of countries such as India, Japan, and Nigeria, with very low meat consumption, are associated with an additional 50% reduction in risk of Alzheimer's disease."


 

 

Despite physical ailments, older adults happier

A new study by researchers at University of California, San Diego School of Medicine suggests that the mental health of aging adults sees to get better over time.

"Their improved sense of psychological well-being was linear and substantial," said senior author Dilip Jeste, MD, Distinguished Professor of Psychiatry and Neurosciences and director of the Center on Healthy Aging at UC San Diego. "Participants reported that they felt better about themselves and their lives year upon year, decade after decade."

The findings are published in the August 2016 issue of the Journal of Clinical Psychiatry.

Conversely, Jeste and colleagues noted high levels of perceived stress and symptoms of depression and anxiety among adults in their 20s and 30s participating in the study. "This 'fountain of youth' period is associated with far worse levels of psychological well-being than any other period of adulthood," he said.

Conventional notions of aging have largely described it as an ongoing process of physical and cognitive decline, with little discussion about mental health except in the context of decline. It has been broadly assumed that the mental health of older people mirrors their worsening physical and cognitive function.

But Jeste, who has long studied the phenomenon as the Estelle and Edgar Levi Chair in Aging and director of the Sam and Rose Stein Institute for Research on Aging, both at UC San Diego, said actual research, though limited, produces mixed findings.

"Some investigators have reported a U-shaped curve of well-being across the lifespan, with declines from early adulthood to middle age followed by an improvement in later adulthood. The nadir of mental health in this model occurs during middle age, roughly 45 to 55. However, we did not find such a mid-life dip in well-being."

The reasons for these differences in results aren't obvious. There is measurement variation across studies, with different researchers emphasizing different indicators that, ultimately, produce different conclusions. Nonetheless, the commonality is in finding improved well-being in the second half of life. Jeste emphasized that this study was not restricted to psychological well-being, but included "mental health", which is broader in definition and also includes satisfaction with life, and low levels of perceived stress, anxiety, and depression.

Most epidemiologic studies report lower prevalence of all mental illnesses in older adults, except for dementias. "Some cognitive decline over time is inevitable," said Jeste, "but its effect is clearly not uniform and in many people, not clinically significant -- at least in terms of impacting their sense of well-being and enjoyment of life."

In the latest study, Jeste and colleagues examined the physical health, cognitive function, and other measures of mental health in 1,546 adults, ages 21 to 100 years, living in San Diego County, who were selected using random digit dialing. Participants were almost evenly split by gender, stratified by age decade, with an oversampling of adults over age 75.

The linear nature of the findings was surprising, said Jeste, particularly in magnitude. The oldest cohort had mental health scores significantly better than the youngest cohort, though the former's physical and cognitive function was measurably poorer than the latter's.

The reasons for improved positive mental health in old age are not clear. Some previous research has shown older adults become more adept at coping with stressful changes. They learn, said Jeste, "not to sweat out the little things. And a lot of previously big things become little." However, another important explanation may be increased wisdom with age. A number of studies have shown that older individuals tend to be more skilled at emotional regulation and complex social decision-making. They also experience and retain fewer negative emotions and memories. These are all collective elements of wisdom, as defined by the researchers.

Michael L. Thomas, PhD, first author of the paper and assistant research scientist in psychiatry at UC San Diego School of Medicine, cautioned that "like many other investigations of this type, it was a cross-sectional study, and thus a snapshot of data. Also, there may have been a survivor bias -- i.e., less healthy adults do not survive into old age". Yet, he also pointed out that older adults in this study were physically more disabled than younger ones -- so this was not a sample of super-normal healthy adults.

Jeste expressed concern that the rates of psychological distress and mental illness in younger persons seem to be rising. "Inadequate attention has been paid to mental health issues that continue or get exacerbated post-adolescence. We need to understand mechanisms underlying better mental health in older age in spite of more physical ailments. That would help develop broad-based interventions to promote mental health in all age groups, including youth."

Fish oil pills reverse the effects of a fatty diet

Scientists have found that fish oil supplements can reverse the effects of a high fat diet according to a study published in the Journal of Physiology.

The research from the University of São Paulo shows that giving mice supplement of fish oil prevents or reverses the harmful effects of a high fat diet. This further demonstrates the beneficial properties of fish oil pills, suggesting that they could be effective in preventing obesity and type-2 diabetes in humans.

Fish oil pills are a popular dietary supplement as they have many perceived benefits. A high-fat diet can lead to insulin resistance, weight gain and increased cholesterol, which can lead to obesity and type-2 diabetes. This research reports, for the first time, that consumption of fish oil can prevent and counter the negative effects of a high-fat diet.

The researchers fed mice that had been administered fish oil a high-fat diet for 4 weeks. They then collected and analysed their body fat samples and compared them to mice on a high-fat diet that had not been consuming fish oil. Factors that affect metabolism, fat deposits and insulin resistance were measured.

Professor Maria Isabel Alonso-Vale, Assistant Professor in the Department of Biological Sciences at the Federal University of São Paulo and lead investigator of the study explained, 'Our research suggests that fish oil supplements may be used in addition to other strategies as a preventative measure for insulin resistance and obesity.'

She added, 'However, it is important to note that this research has been performed in mice which may not translate to humans. More research will need to be done so we can have a better understanding of the effect of fish oil in humans.'

Excess weight linked to 8 more cancer types

There's yet another reason to maintain a healthy weight as we age. An international team of researchers has identified eight additional types of cancer linked to excess weight and obesity: stomach, liver, gall bladder, pancreas, ovary, meningioma (a type of brain tumor), thyroid cancer and the blood cancer multiple myeloma.

Limiting weight gain over the decades could help to reduce the risk of these cancers, the data suggest.

The findings, published Aug. 25 in The New England Journal of Medicine, are based on a review of more than 1,000 studies of excess weight and cancer risk analyzed by the World Health Organization's International Agency for Cancer on Research (IARC), based in France.

"The burden of cancer due to being overweight or obese is more extensive than what has been assumed," said cancer prevention expert Graham Colditz, MD, DrPH, at Washington University School of Medicine in St. Louis, who chaired the IARC Working Group. "Many of the newly identified cancers linked to excess weight haven't been on people's radar screens as having a weight component."

The findings could have a significant bearing on the global population. Worldwide, an estimated 640 million adults and 110 million children are obese, including one-third of adults and children in the United States.

In 2002, the same group of cancer researchers found sufficient evidence linking excess weight to higher risks of cancers of the colon, esophagus, kidney, breast and uterus.

"Lifestyle factors such as eating a healthy diet, maintaining a healthy weight and exercising, in addition to not smoking, can have a significant impact on reducing cancer risk," Colditz said. "Public health efforts to combat cancer should focus on these things that people have some control over."

"But losing weight is hard for many people," he added. "Rather than getting discouraged and giving up, those struggling to take off weight could instead focus on avoiding more weight gain."

For most of the cancers on the newly expanded list, the researchers noted a positive dose-response relationship: the higher the body-mass index, or BMI, the greater the cancer risk.

The cancer risks associated with excess weight were similar for men and women and, when data were available, were consistent across geographic regions -- North America, Europe, Asia and the Middle East.

There are many reasons why being overweight or obese can increase cancer risk, the researchers noted. Excess fat leads to an overproduction of estrogen, testosterone and insulin, and promotes inflammation, all of which can drive cancer growth.

"Significant numbers of the U.S. and the world's population are overweight," Colditz said. "This is another wake-up call. It's time to take our health and our diets seriously."

Diets avoiding dry-cooked foods (grilling, frying, or baking ) can protect against diabetes

, say mount sinai researchers
THE MOUNT SINAI HOSPITAL / MOUNT SINAI SCHOOL OF MEDICINE

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Simple changes in how we cook could go a long way towards preventing diabetes, say researchers at the Icahn School of Medicine at Mount Sinai. A new randomized controlled trial, published online July 29 in the journal Diabetologia, found that obese individuals with signs of insulin resistance showed improvement simply by avoiding the intake of advanced glycation endproducts, or AGEs, a byproduct of cooking found most commonly in dry heat-cooked or heat-processed foods.

The study is a follow-up to a 2014 article published in the journal Proceedings of the National Academy of Sciences. In the earlier study, the researchers, led by Helen Vlassara, MD, Professor Emeritus of Geriatrics and Palliative Medicine and Medicine at the Icahn School of Medicine at Mount Sinai, confirmed that high levels of AGEs in the body can cause pre-diabetes characterized by increasing insulin resistance, as well as brain changes similar to Alzheimer's disease. This study focused more on diabetes risk.

"While food AGEs are prevalent, particularly in Western diets, our study showed that avoiding foods high in AGEs could actually reverse the damage that had been done," said Dr. Vlassara. "This can provide us with new clinical approaches to pre-diabetes, potentially helping protect certain at-risk individuals from developing full diabetes and its devastating consequences."

The researchers divided the study participants into two groups of obese individuals - one eating a regular diet, which is typically high in AGEs (Reg-AGE), and one with a diet low in AGEs (L-AGE). Members of the L-AGE group were instructed to avoid grilling, frying, or baking their food, in favor of poaching, stewing, or steaming.

At the beginning and end of the trial, blood and urine samples were analyzed to determine insulin resistance. The two groups showed similar levels of insulin resistance at the beginning; at the end, the L-AGE group showed significantly improved insulin resistance, as well as slightly decreased body weight and lowered levels of AGEs in the body. The Reg-AGE group had higher levels of AGEs and more markers of insulin resistance than during the baseline measurements.

"Elevated serum AGEs in individuals can be used as a marker to diagnose and treat 'at risk' obesity in patients," said Jaime Uribarri, MD, Professor of Medicine (Nephrology) at the Icahn School of Medicine at Mount Sinai, another investigator in the study. "Even without losing a significant amount of weight, a reduced AGE diet can help prevent diabetes in these patients."

The researchers also found a positive effect on six key genes associated with the regulation of oxidant stress and inflammation. Four of these had been found to be suppressed at the baseline blood and urine analysis, but were markedly increased at the end, including anti-inflammatory SIRT1 and adiponectin, as well as the receptor for the removal of AGEs, AGER1, and glyoxalase-1.

Cognitive activity can reduce dementia risk

Are there any ways of preventing or delaying the development of Alzheimer's disease or other forms of age-associated dementia? While several previously published studies have suggested a protective effect for cognitive activities such as reading, playing games or attending cultural events, questions have been raised about whether these studies reveal a real cause-and-effect relationship or if the associations could result from unmeasured factors. To address this question, a Boston-based research team conducted a formal bias analysis and concluded that, while potentially confounding factors might have affected previous studies' results, it is doubtful that such factors totally account for observed associations between cognitive activities and a reduced risk of dementia.

"Our paper lends support to a potential role for late-in-life cognitive activity in prevention of Alzheimer's disease," says Deborah Blacker MD, ScD, director of the Gerontology Research Unit in the Massachusetts General Hospital Department of Psychiatry and senior author of the report in the September issue of the journal Epidemiology. "While it is possible that socioeconomic factors such as educational level might contribute to the association between cognitive activity and reduced risk, any bias introduced by such factors is probably not strong enough to fully account for the observed association."

Blacker and her colleagues from Harvard T.H. Chan School of Public Health maintain a database on the Alzheimer's Research Forum website cataloging evidence from observational studies and some clinical trials about known and proposed risk and protective factors for the devastating neurologic disorder. The current paper was developed from the database's systematic review of studies examining the impact of cognitive activity, conducted by lead author Guatam Sajeev, ScD, as part of his Harvard Chan school dissertation.

The research team analyzed 12 peer-reviewed epidemiologic studies that examined the relationship between late-in-life cognitive activities and the incidence of Alzheimer's disease or other forms of dementia. The studies were selected on the basis of prespecified criteria for the AlzRisk database, included almost 14,000 individual participants and consistently showed a benefit, sometimes substantial, for cognitive activity.

Since any observational studies are likely to be confounded by unmeasured factors - such as participants' socioeconomic level or the presence of conditions like depression - the researchers also conducted a bias analysis designed to evaluate how much such factors might influence reported associations between the amount of cognitive activity and dementia risk. This analysis indicated that bias due to unmeasured factors was unlikely to account for all of the association because the impact of such factors is likely to be considerably smaller than the observed effect.

The group also investigated the possible role of reverse causation - whether a reduction in cognitive activity among those already in the long phase of cognitive decline that precedes Alzheimer's dementia might have led to an apparent rather than a real causal relationship. The findings of that analysis could not rule out the possibility that reverse causation contributed substantially to the observed associations, but analyses restricted to studies with longer term follow-up might be better able to address this question, the authors note.

"Ultimately, clinical trials with long-term follow-up are the surest way to definitively address reverse causation," says co-author and AlzRisk co-director Jennifer Weuve, MPH, ScD, of Boston University School of Public Health. "Trials could also confront the vexing question of whether training to improve specific cognitive skills has benefits that extend into everyday functions. But not every question about cognitive activity is well-suited for a trial. To fill those gaps, innovations in epidemiology, such as the analytic techniques used in this study, should help us get even greater insights from available observational data."

Blacker adds, "Cognitive activity looks like it may offer some modest protection, and based on our bias analysis, I am somewhat less skeptical than I was previously. But remember that any impact will be relative, not absolute. I typically advise people to engage in cognitive activities that they find interesting and enjoyable for their own sake. There is no evidence that one kind of activity is better than another, so I would advise against spending money on programs claiming to protect against dementia."

Diet, exercise, work equally to protect heart health

Which works better to improve the cardiovascular health of those who are overweight - dieting, exercise or a combination of both? A Saint Louis University study finds it doesn't matter which strategy you choose - it's the resulting weight loss that is the protective secret sauce.

"For men and women with excess body weight, modest weight loss provides powerful protection against cardiovascular disease, regardless of whether weight loss is achieved by using exercise, a healthy low-calorie diet, or both," said Edward Weiss, Ph.D., associate professor of nutrition and dietetics at Saint Louis University and the lead author of the article.

His findings were published in an early issue of the American Journal of Clinical Nutrition.

For the research, Weiss and his team divided 52 overweight, middle-aged men and women into three groups - those who dieted, exercised or did both - and charged them with losing about 7 percent of their body weight during a 12-14 week period. Those who exclusively dieted or exercised were told to decrease their food intake by 20 percent or increase their activity levels by 20 percent. Those who did both were told to eat 10 percent less and move 10 percent more.

The researchers analyzed how the changes affected indicators of cardiovascular health, such as blood pressure, heart rate and other markers for heart disease and stroke, like high "bad" cholesterol levels.

They found the three strategies were equally effective in improving cardiovascular health, and were expected to reduce a person's lifetime risk of developing cardiovascular disease 10 percent - from 46 percent to 36 percent.

While dieting and exercising was no better than dieting or exercising alone, as Weiss sees it, his research doesn't give people who have lost weight to improve their heart health license to eat high calorie junk food or have a sedentary lifestyle. He advocates a combination of healthy eating and exercise as his preferred roadmap to heart health.

"Because our previous research and that of others indicates that exercise and diet each provide their own unique health benefits beyond those that were evaluated in the current study, it is important to recognize that both diet and exercise are important for health and longevity," Weiss said.

"While our study did not find additive benefits of calorie restriction and exercise on traditional risk factors for cardiovascular disease, much of the actual risk of developing cardiovascular disease cannot be accounted for by traditional risk factors. Therefore, our findings don't preclude the possibility that dieting and exercise have additive effects for reducing the likelihood of developing cardiovascular disease. Furthermore, an inactive lifestyle itself is a risk factor for cardiovascular disease, although the physiologic mechanisms for this effect are unknown."

Guarana found to have higher antioxidant potential than green tea

The millions of people who consume green tea all over the world benefit from the catechins it contains. Catechins are a class of chemical compounds with anti-oxidant and anti-inflammatory properties, among other healthy ingredients. Researchers at the University of São Paulo's Public Health School (FSP-USP) have discovered that guarana (Paullinia cupana) is a worthy competitor, at least as far as catechins are concerned: the seeds of the tropical shrub, used in fizzy drinks that are among the most popular in Brazil, as well as in over-the-counter supplements, contain more than ten times the amount of catechins found in green tea.

A clinical trial with healthy human volunteers has demonstrated that guarana is a rich source of catechins, which, when properly absorbed, reduce the oxidative stress associated with the development of neurodegenerative and cardiovascular disorders, as well as diabetes, cancer, inflammation and premature aging due to cell death, among other conditions harmful to health and wellbeing.

"Guarana has always been seen above all as a stimulant, especially by the international scientific community, because of its high caffeine content. We also found few Brazilian scientific studies that seek to identify other biological effects of guarana," said Lina Yonekura, the principal investigator for this research and currently an assistant professor at Kagawa University's School of Agriculture in Japan. "This pioneering assessment of the absorption and biological effects of its catechins in human volunteers should foster interest in guarana as a functional food on the part of scientists, the market, and society in general."

The paper with the results of the study is featured on the cover of the latest issue of Food & Function, published by the Royal Society of Chemistry in the United Kingdom as one of the "Hot Articles in Food & Function 2016.

The month-long study was conducted in two stages. After selecting volunteers who were healthy but slightly overweight and with a moderately elevated risk of cardiovascular disease, the researchers measured baseline parameters on the first day and evaluated the same items again on day 15 after a the implementation of a controlled diet.

The participants were then asked to take guarana at home every morning before breakfast for the next fortnight. They were given bottles containing guarana seed powder and instructed to prepare a daily drink with the contents of one bottle (3 g of guarana powder) in 300 mL of water.

This procedure ensured that each participant acted as his or her own control. The researchers compared the same volunteers' blood tests at different times to avoid the influence of variability between individuals. The acute effect of guarana was measured one hour after the participants drank the solution on day 1 and day 15. The prolonged effect was assessed after overnight fasting on the same days.

The researchers assessed the extent to which guarana affected oxidative stress markers during the two-week intervention period. They also performed a detailed study to evaluate the subjects' absorption of catechins and their metabolites, as they had found no information in the scientific literature on the bioavailability of these compounds in guarana.

The oxidative stress markers included oxidation of low-density lipoprotein (LDL), popularly known as bad cholesterol. LDL is essential to an organism's proper functioning because it is the main particle that carries cholesterol to cells. Cholesterol is a structural component of all cell membranes and is used to manufacture steroid hormones (estrogen and testosterone). When oxidized, however, LDL causes atherosclerosis and increases the risk of cardiovascular disease. The tests performed by Yonekura's team showed an increase in oxidation resistance of the LDL in the blood samples taken from the volunteers after they drank guarana.

They also performed a comet assay, also called single cell gel electrophoresis (SCGE), a technique for quantifying and analyzing DNA damage in individual cells due to various factors, including oxidative stress. In this case, lymphocyte DNA in blood samples taken one hour after guarana intake was less damaged than expected when submitted to an oxidizing environment, indicating the presence of anti-oxidant substances or enhanced performance of the lymphocytes' enzymatic anti-oxidant system.

"All these markers depend on the presence of catechins in the bloodstream," Yonekura said. "The improvement in the parameters we assessed was associated with a rise in the concentration of plasma catechins after guarana intake, showing that guarana was indeed responsible for this effect."

Moreover, she went on, the guarana catechins strengthened the cells' native anti-oxidant enzymes, especially glutathione peroxidase, catalase, and superoxide dismutase, which combine to convert superoxide into peroxide and finally into water, protecting cells from the oxidative damage caused by their own metabolism of outside factors.

The tests showed increased glutathione peroxidase and catalase activity both shortly after guarana ingestion and on the following day.

"These results are exciting, suggesting that the bioavailability of guarana catechins is equal to or greater than that of green tea, cocoa and chocolate catechins," Yonekura said. "In fact, their bioavailability was sufficient to have a positive effect on plasma anti-oxidant activity, protect erythrocyte DNA, reduce plasma lipid oxidation, and increase anti-oxidant enzyme activity. We hope the results lead to heightened interest in guarana as the species is native to the Amazon, and Brazil is practically the only country that produces it on a commercial scale."

Citrus fruits could help prevent obesity-related heart disease, liver disease, diabetes

Oranges and other citrus fruits are good for you -- they contain plenty of vitamins and substances, such as antioxidants, that can help keep you healthy. Now a group of researchers reports that these fruits also help prevent harmful effects of obesity in mice fed a Western-style, high-fat diet.

The researchers are presenting their work today at the 252nd National Meeting & Exposition of the American Chemical Society (ACS). ACS, the world's largest scientific society, is holding the meeting here through Thursday. It features more than 9,000 presentations on a wide range of science topics.

"Our results indicate that in the future we can use citrus flavanones, a class of antioxidants, to prevent or delay chronic diseases caused by obesity in humans," says Paula S. Ferreira, a graduate student with the research team.

More than one-third of all adults in the U.S. are obese, according to the U.S. Centers for Disease Control and Prevention. Being obese increases the risk of developing heart disease, liver disease and diabetes, most likely because of oxidative stress and inflammation, Ferreira says. When humans consume a high-fat diet, they accumulate fat in their bodies. Fat cells produce excessive reactive oxygen species, which can damage cells in a process called oxidative stress. The body can usually fight off the molecules with antioxidants. But obese patients have very enlarged fat cells, which can lead to even higher levels of reactive oxygen species that overwhelm the body's ability to counteract them.

Citrus fruits contain large amounts of antioxidants, a class of which are called flavanones. Previous studies linked citrus flavanones to lowering oxidative stress in vitro and in animal models. These researchers wanted to observe the effects of citrus flavanones for the first time on mice with no genetic modifications and that were fed a high-fat diet.

The team, at Universidade Estadual Paulista (UNESP) in Brazil, conducted an experiment with 50 mice, treating them with flavanones found in oranges, limes and lemons. The flavanones they focused on were hesperidin, eriocitrin and eriodictyol. For one month, researchers gave groups either a standard diet, a high-fat diet, a high-fat diet plus hesperidin, a high-fat diet plus eriocitrin or a high-fat diet plus eriodictyol.

The high-fat diet without the flavanones increased the levels of cell-damage markers called thiobarbituric acid reactive substances (TBARS) by 80 percent in the blood and 57 percent in the liver compared to mice on a standard diet. But hesperidin, eriocitrin and eriodictyol decreased the TBARS levels in the liver by 50 percent, 57 percent and 64 percent, respectively, compared with mice fed a high-fat diet but not given flavanones. Eriocitrin and eriodictyol also reduced TBARS levels in the blood by 48 percent and 47 percent, respectively, in these mice. In addition, mice treated with hesperidin and eriodictyol had reduced fat accumulation and damage in the liver.

"Our studies did not show any weight loss due to the citrus flavanones," says Thais B. Cesar, Ph.D., who leads the team. "However, even without helping the mice lose weight, they made them healthier with lower oxidative stress, less liver damage, lower blood lipids and lower blood glucose."

Ferreira adds, "This study also suggests that consuming citrus fruits probably could have beneficial effects for people who are not obese, but have diets rich in fats, putting them at risk of developing cardiovascular disease, insulin resistance and abdominal obesity."

Relationships with family members, but not friends, decrease likelihood of death

For older adults, having more or closer family members in one's social network decreases his or her likelihood of death, but having a larger or closer group of friends does not, finds a new study that will be presented at the 111th Annual Meeting of the American Sociological Association (ASA).

"We found that older individuals who had more family in their network, as well as older people who were closer with their family were less likely to die," said James Iveniuk, the lead author of the study and a post-doctoral researcher at the University of Toronto's Dalla Lana School of Public Health. "No such associations were observed for number of or closeness to friends."

Titled, "Social Relationships and Mortality in Older Adulthood," the study used nationally representative data from the 2005/2006 and 2010/2011 survey waves of the National Social Life, Health, and Aging Project (NSHAP), to investigate which aspects of social networks are most important for postponing mortality. Mortality of wave one respondents, who were 57 to 85-years old, was assessed at wave two.

In the first wave, these older adults were asked to list up to five of their closest confidants, describe in detail the nature of each relationship, and indicate how close they felt to each person. Excluding spouses, the average number of close confidants named was 2.91, and most older adults perceived high levels of support from their social contacts. Additionally, most respondents were married, in good physical health, and reported not being very lonely.

Iveniuk and co-author L. Philip Schumm, a senior biostatician at the University of Chicago, found that older adults who reported feeling "extremely close" on average to the non-spousal family members they listed as among their closest confidants had about a six percent risk of mortality within the next five years, compared to approximately a 14 percent risk of mortality among those who reported feeling "not very close" to the family members they listed.

Furthermore, the study found that respondents who listed more non-spousal family members in their network -- irrespective of closeness -- had lower odds of death compared to those who listed fewer family members. "Regardless of the emotional content of a connection, simply having a social relationship with another person may have benefits for longevity," Iveniuk said.

Iveniuk said he was surprised that feeling closer to one's family members and having more relatives as confidants decreased the risk of death for older adults, but that the same was not true of relationships with friends.

"Because you can choose your friends, you might, therefore, expect that relationships with friends would be more important for mortality, since you might be better able to customize your friend network to meet your specific needs," Iveniuk said. "But that account isn't supported by the data -- it is the people who in some sense you cannot choose, and who also have little choice about choosing you, who seem to provide the greatest benefit to longevity."

Besides comparing friendships to relationships with family members, the study examined the characteristics of social networks in general and their association with mortality. The four factors most consistently associated with reduced mortality risk were being married, larger network size, greater participation in social organizations, and feeling closer to one's confidants, which all mattered to about the same degree. Factors found to be less important included time with confidants, access to social support, and feelings of loneliness.

"I expected the association between participation in social organizations and mortality to diminish in size considerably once we controlled for other aspects of peoples' social worlds, but that didn't happen," Iveniuk said.

Interestingly, marriage was found to have positive effects on longevity, regardless of marital quality. "We observed no association between measures of support from the spouse and mortality, indicating that the presence of a marital bond may be more important for longevity than certain aspects of the bond itself," Iveniuk said.

Generally, Iveniuk said his findings underscore the substantial importance of familial relationships for longevity. "Going back to the very first sociological theorists, many different thinkers have noted that there is some kind of special significance that people attribute to family ties, leading people to stay close to and support people who wouldn't necessarily be individuals that they would associate with if they had the choice," Iveniuk said.

How often should you have a mammogram? Breast density and risk can inform decision

Women between the ages of 50 and 74 may benefit from more or less frequent mammography screening than is generally recommended, depending on breast density and risk. For average-risk women with lower breast density, which comprises a large proportion of the population, triennial screening offers about the same or better balance of benefits and harms as biennial screening and is also cost-effective. Higher-risk women with dense breasts may fare better with annual screening. Findings from a collaborative modeling study are published in Annals of Internal Medicine.

Accepted clinical guidelines recommend biennial mammography screening for women aged 50 to 74. These recommendations also advocate shared decision making regarding screening frequency that takes into consideration an individual woman's preferences, risk level, and breast density. However, there is limited data available to guide clinicians and women in making these decisions.

Researchers from the Cancer Intervention and Surveillance Modeling Network, collaborating with the Breast Cancer Surveillance Consortium (BCSC), used three well-established models to evaluate outcomes using various screening intervals for digital mammography among subgroups of women based on age, risk, and breast density. The outcomes were projected for women 50 or older who were deciding whether to initiate (or continue) biennial screening until age 74 or to have annual or triennial screening.

The models showed that average-risk women with lower breast density could safely and effectively extend their screening interval to once every three years, which could reduce false-positives, biopsies, and overdiagnosis with minimal effect on breast cancer deaths averted. Women at higher risk for breast cancer and with dense breasts would reap greater benefit from annual screening. The authors suggest that these findings could be useful for guiding shared decision making and tailoring screening intervals.

Soluble corn fiber can help young women build bone, and older women preserve bone

Supplementing with soluble corn fiber at two critical times in a woman's life - adolescence and post-menopause - can help build and retain calcium in bone, according to new research from Purdue University.

"We are looking deeper in the gut to build healthy bone in girls and help older women retain strong bones during an age when they are susceptible to fractures," said Connie Weaver, distinguished professor and head of nutrition science. "Soluble corn fiber, a prebiotic, helps the body better utilize calcium during both adolescence and post-menopause. The gut microbiome is the new frontier in health."

The post-menopause findings are published in the American Journal of Clinical Nutrition, and the adolescent findings are published in Journal of Nutrition. The studies are funded by Tate & Lyle Ingredients America LLC. Weaver serves on the scientific advisory board for Pharmative LLC.

A prebiotic fiber passes through the gut for the microbes in the lower gut to digest. Here is where Weaver found that soluble corn fiber is broken down into short chain fatty acids to aid in bone health.

In the post-menopausal study, calcium retention was measured in 14 women by using an isotope to measure the excretion of 41Ca to measure bone loss. The women consumed 0 grams, 10 grams or 20 grams of this nondigestible carbohydrate each day for 50 days. Bone calcium retention was improved by 4.8 percent and 7 percent for those who consumed 10 grams and 20 grams, respectively. These amounts of soluble corn fiber would be found in supplement form.

"If projected out for a year, this would equal and counter the average rate of bone loss in a post-menopausal woman," said Weaver, an expert in mineral bioavailability, calcium metabolism, botanicals and bone health.

The calcium 41 technology, an isotope measure to trace calcium deposits through accelerator mass spectrometry in the Purdue Rare Isotope Measurement Laboratory (PRIME Lab), can measure atomic quantities. In the adolescent study, 44Ca and 43Ca were used.

Thirty-one girls either consumed 0 grams, 10 grams or 20 grams of soluble corn fiber carbohydrate each day for three weeks while maintaining their regular diets. Both 10 grams and 20 grams led to improved calcium absorption by 12 percent for female adolescents, which would build 1.8 percent more skeleton a year.

In both studies, gastrointestinal symptoms were minimal and the same for the control groups, as well as in those who consumed soluble corn fiber.

"Most studies looking at benefits from soluble corn fiber are trying to solve digestion problems, and we are the first to determine that this relationship of feeding certain kind of fiber can alter the gut microbiome in ways that can enhance health," Weaver said. "We found this prebiotic can help healthy people use minerals better to support bone health."

Calcium is considered a shortfall nutrient, and few people meet the recommended intake of 1,300 milligrams of calcium for healthy bone mass.

"The finding doesn't mean we should diminish our recommendation to drink milk and follow a well-balanced diet. This is a strategy to better utilize your minerals for those not consuming the whole recommendation of dairy," Weaver said. "Calcium alone suppresses bone loss, but it doesn't enhance bone formation. These fibers enhance bone formation, so they are doing something more than enhancing calcium absorption."

Weaver's team is looking into the mechanisms of how soluble corn fiber boosts calcium absorption and retention, as well as if the prebiotic fiber benefits the body in other ways.

Diet and exercise can reduce protein build-ups linked to Alzheimer's

A study by researchers at UCLA's Semel Institute for Neuroscience and Human Behavior has found that a healthy diet, regular physical activity and a normal body mass index can reduce the incidence of protein build-ups that are associated with the onset of Alzheimer's disease.

In the study, 44 adults ranging in age from 40 to 85 (mean age: 62.6) with mild memory changes but no dementia underwent an experimental type of PET scan to measure the level of plaque and tangles in the brain. Researchers also collected information on participants' body mass index, levels of physical activity, diet and other lifestyle factors. Plaque, deposits of a toxic protein called beta-amyloid in the spaces between nerve cells in the brain; and tangles, knotted threads of the tau protein found within brain cells, are considered the key indicators of Alzheimer's.

The study found that each one of several lifestyle factors -- a healthy body mass index, physical activity and a Mediterranean diet -- were linked to lower levels of plaques and tangles on the brain scans. (The Mediterranean diet is rich in fruits, vegetables, legumes, cereals and fish and low in meat and dairy, and characterized by a high ratio of monounsaturated to saturated fats, and mild to moderate alcohol consumption.)

"The fact that we could detect this influence of lifestyle at a molecular level before the beginning of serious memory problems surprised us," said Dr. David Merrill, the lead author of the study, which appears in the September issue of the American Journal of Geriatric Psychiatry.

Earlier studies have linked a healthy lifestyle to delays in the onset of Alzheimer's. However, the new study is the first to demonstrate how lifestyle factors directly influence abnormal proteins in people with subtle memory loss who have not yet been diagnosed with dementia, Merrill said. Healthy lifestyle factors also have been shown to be related to reduced shrinking of the brain and lower rates of atrophy in people with Alzheimer's.

Older age is the No. 1 non-modifiable risk factor for Alzheimer's disease, which affects an estimated 5.2 million people in the United States and results in more than $200 billion in health care costs annually.

"The study reinforces the importance of living a healthy life to prevent Alzheimer's, even before the development of clinically significant dementia," Merrill said. "This work lends key insight not only into the ability of patients to prevent Alzheimer's disease, but also physicians' ability to detect and image these changes."

The next step in the research will be to combine imaging with intervention studies of diet, exercise and other modifiable lifestyle factors, such as stress and cognitive health, Merrill said.

Merrill sees patients with cognitive problems, particularly memory loss, at the UCLA Psychiatry Cognitive Health Clinic and Research Program.

Calcium supplements linked to dementia risk in women with certain health conditions

According to a new study, calcium supplements may be associated with an increased risk of dementia in older women who have had a stroke or other signs of cerebrovascular disease. The research is published in the August 17, 2016, online issue of Neurology®, the medical journal of the American Academy of Neurology.

Cerebrovascular disease is a group of disorders that affect blood flow in the brain. These diseases, including stroke, are the fifth leading cause of death in the United States and increase the risk of developing dementia.

"Osteoporosis is a common problem in the elderly. Because calcium deficiency contributes to osteoporosis, daily calcium intake of 1000 to 1200 mg is recommended. Getting this recommended amount through diet alone can be difficult, so calcium supplements are widely used," said study author Silke Kern, MD, PhD with the University of Gothenburg in Sweden. "Recently, however, the use of supplements and their effect on health has been questioned."

The study involved 700 dementia-free women between the ages of 70 and 92 who were followed for five years. Participants took a variety of tests at the beginning and end of the study, including tests of memory and thinking skills. A CT brain scan was performed in 447 participants at the start of the study.

Scientists also looked at the use of calcium supplements in the participants and whether they were diagnosed with dementia over the course of the study. A total of 98 women were taking calcium supplements at the start of the study and 54 women had already experienced a stroke. During the study, 54 more women had strokes, and 59 women developed dementia. Among the women who had CT scans, 71 percent had lesions on their brains' white matter, which is a marker for cerebrovascular disease.

The study found that the women who were treated with calcium supplements were twice as likely to develop dementia than women who did not take supplements. But when the researchers further analyzed the data, they found that the increased risk was only among women with cerebrovascular disease. Women with a history of stroke who took supplements had a nearly seven times increased risk of developing dementia than women with a history of stroke who did not take calcium supplements. Women with white matter lesions who took supplements were three times as likely to develop dementia as women who had white matter lesions and did not take supplements. Women without a history of stroke or women without white matter lesions had no increased risk when taking calcium supplements.

Overall, 14 out of 98 women who took supplements developed dementia, or 14 percent, compared to 45 out of 602 women who did not take supplements, or 8 percent. A total of six out of 15 women with a history of stroke who took supplements developed dementia, compared to 12 out of 93 women with a history of stroke who did not take supplements. Among the women with no history of stroke, 18 out of 83 who took supplements developed dementia, compared to 33 out of the 509 who did not take supplements.

"It is important to note that our study is observational, so we cannot assume that calcium supplements cause dementia," said Kern. The author also noted that the study was small and results cannot be generalized to the overall population, and additional studies are needed to confirm the findings.

Kern noted that calcium from food affects the body differently than calcium from supplements and appears to be safe or even protective against vascular problems.

Unhealthy diet during pregnancy could be linked to ADHD

New research led by scientists from King's College London and the University of Bristol has found that a high-fat, high-sugar diet during pregnancy may be linked to symptoms of ADHD in children who show conduct problems early in life.

Published today in the Journal of Child Psychology and Psychiatry, this study is the first to indicate that epigenetic changes evident at birth may explain the link between unhealthy diet, conduct problems and ADHD.

Early onset conduct problems (e.g. lying, fighting) and attention-deficit/hyperactivity disorder (ADHD) are the leading causes of child mental health referral in the UK. These two disorders tend to occur in tandem (more than 40 per cent of children with a diagnosis of conduct disorder also have a diagnosis of ADHD) and can also be traced back to very similar prenatal experiences such as maternal distress or poor nutrition.

In this new study of participants from the Bristol-based 'Children of the 90s' cohort, 83 children with early-onset conduct problems were compared with 81 children who had low levels of conduct problems. The researchers assessed how the mothers' nutrition affected epigenetic changes (or DNA methylation) of IGF2, a gene involved in fetal development and the brain development of areas implicated in ADHD - the cerebellum and hippocampus. Notably, DNA methylation of IGF2 had previously been found in children of mothers who were exposed to famine in the Netherlands during World War II.

The researchers from King's and Bristol found that poor prenatal nutrition, comprising high fat and sugar diets of processed food and confectionary, was associated with higher IGF2 methylation in children with early onset conduct problems and those with low conduct problems.

Higher IGF2 methylation was also associated with higher ADHD symptoms between the ages of 7 and 13, but only for children who showed an early onset of conduct problems.

Dr Edward Barker from King's College London said: 'Our finding that poor prenatal nutrition was associated with higher IGF2 methylation highlights the critical importance of a healthy diet during pregnancy.

'These results suggest that promoting a healthy prenatal diet may ultimately lower ADHD symptoms and conduct problems in children. This is encouraging given that nutritional and epigenetic risk factors can be altered.'

Dr Barker added: 'We now need to examine more specific types of nutrition. For example, the types of fats such as omega 3 fatty acids, from fish, walnuts and chicken are extremely important for neural development.

'We already know that nutritional supplements for children can lead to lower ADHD and conduct problems, so it will be important for future research to examine the role of epigenetic changes in this process.'

Polyunsaturated fat in adipose tissue linked to lower mortality

In a study from Uppsala University, published in the American journal JAMA Cardiology, the fatty acid linoleic acid (Omega 6) in subcutaneous adipose tissue was linked to lower mortality among older men followed over a 15-year period.

A high proportion of linoleic acid in adipose tissue largely reflects a high intake of various vegetable oils, as this study also demonstrated. The findings may further indicate that an excessively low intake of polyunsaturated fatty acids increases the risk of (premature) death. However, no clear correlation could be established with mortality from cardiovascular disease. This study is the largest yet conducted examining the association between specific fatty acids in adipose tissue and the intake of these fatty acids. The study is also the largest forward-looking study to have analysed the associations between fatty acids in adipose tissue, cardiovascular disease, and mortality from all causes.

The question of what type of fat food should contain has been hotly debated. According to current dietary guidelines, food should contain a relatively high proportion of unsaturated ¬- including 'polyunsaturated' - fatty acids. One difficulty in dietary studies is finding a reliable method of measuring dietary intake, particularly over an extended period. Measuring the fatty acid composition of adipose tissue can therefore make a valuable contribution to our knowledge about the association between diet and disease. The composition of adipose tissue provides an objective reflection of the average fat intake in recent years, particularly of fatty acids that the body cannot produce itself, such as the Omega 6 fatty acid linoleic acid derived from vegetable sources. Linoleic acid occurs in sunflower, rapeseed and other vegetable oils, in soft table and cooking fats (margarine), nuts and seeds.

In the population-based study ULSAM (Uppsala Longitudinal Study of Adult Men), adipose tissue biopsy specimens and blood samples were taken from 853 men at the age of 71 years. At about the same time, the men in the study were asked to fill in a food diary over a period of seven days. Many of the men underestimated their intake of energy and fat. Disregarding the men who reported most inadequately, a clear correlation was evident between the proportion of linoleic acid in adipose tissue and the food diaries. Somewhat weaker correlations were observed between fatty acids in the blood and reported intake, while strong correlations were observed between adipose tissue and blood for most fatty acids. Overall, the findings indicate that the proportion of polyunsaturated fatty acids in adipose tissue reflects the individual's intake of these fatty acids over the long term, and this appears to be particularly true of linoleic acid, which is the most common polyunsaturated fatty acid. With regard to Omega 3 fats, however, this study showed no clear association with a risk of cardiovascular disease or mortality.

After taking statistical account of a number of known risk factors for cardiovascular disease, no clear correlations with cardiovascular disease were observed for any fatty acid (251 deaths during a 15-year follow-up period). However, for total mortality (605 deaths) a correlation was seen, with a higher proportion of linoleic acid in adipose tissue being associated with a ten per cent lower risk of death. Linoleic acid is known to reduce the content of bad cholesterol in the blood, but the study cannot answer the question of whether this is the explanation for the association with reduced mortality.

The study is unique in measuring various fatty acids in adipose tissue among a large population of older men, followed over an extended period of time.

'Even though the study cannot prove any causal connection, the findings nevertheless support current dietary advice to replace some hard fats in the diet - namely, those with a high proportion of saturated fatty acids - with softer fats, e.g. vegetable oils with a high proportion of unsaturated fatty acids,' says David Iggman, a physician and researcher at the Clinical Nutrition and Metabolism Unit at Uppsala University.

Exercise does more good if you believe it will

Everyone knows exercise is supposed to be good for your health, but is the belief that exercise will have a positive effect more important for our well-being than the exercise itself? The psychologist Hendrik Mothes from the University of Freiburg's Department of Sport Science and his team have conducted a study demonstrating that test subjects derive more psychological as well as neurophysiological benefits from exercise if they already have positive mindsets about sports. Moreover, the team provided evidence that test subjects can be positively or negatively influenced in this regard before engaging in the exercise. The study was published in the Journal of Behavioral Medicine.

The researchers invited 76 men and women aged between 18 and 32 years to their research laboratory, where they had to exercise for 30 minutes on a bicycle ergometer. Beforehand, the test subjects were separated into different groups and shown one of several short films that either praised the positive effects of cycling on health or not. In addition, the researchers asked the test subjects whether they had already believed in the positive effects of physical activity before beginning the study. The participants filled out questionnaires asking them about their well-being and their mood before and after the exercise. Moreover, the researchers measured the participants' brain activity with an electroencephalogram (EEG).

"The results demonstrate that our belief in how much we will benefit from physical activity has a considerable effect on our well-being in the manner of a self-fulfilling prophecy," sums up Mothes. The results provide evidence for a placebo effect during exercise: Test subjects who already believed the physical activity would have positive effects before participating in the study enjoyed the exercise more, improved their mood more, and reduced their anxiety more than less optimistic test subjects. In addition, the study revealed a neurophysiological difference between the test subjects: According to the measurements of brain activity, the participants with greater expectations before the beginning of the study and those who had seen a film about the health benefits of cycling beforehand were more relaxed on a neuronal level.

The results likely also apply to other endurance sports like jogging, swimming, or cross-country skiing, reports Mothes. "Beliefs and expectations could possibly have long-term consequences, for instance on our motivation to engage in sports. They can be a determining factor on whether we can rouse ourselves to go jogging again next time or decide instead to stay at home on the couch." The psychologist is now working on his next project. He aims to study further effects of mindsets and investigate the question of whether and how they influence the experience of exertion during physical activity.

High and low levels of 'good cholesterol' may cause premature death

Commonly touted as "good cholesterol" for helping to reduce risk of stroke and heart attack, both high and low levels of high-density lipoprotein (HDL) cholesterol may increase a person's risk of premature death, according to new research at Washington University School of Medicine in St. Louis and Veterans Affairs St. Louis Health Care System.

Conversely, intermediate HDL cholesterol levels may increase longevity, according to the research.

The large-scale epidemiological study is published Aug. 11 in the Clinical Journal of the American Society of Nephrology.
"The findings surprised us," said Ziyad Al-Aly, MD, an assistant professor of medicine at Washington University and the study's senior author. "Previously it was thought that raised levels of the good cholesterol were beneficial. The relationship between increased levels of HDL cholesterol and early death is unexpected and not fully clear yet. This will require further study."

Cholesterol is a fatty substance found in blood that can narrow and block heart vessels, causing cardiovascular disease and stroke. For years, HDL cholesterol has been credited with helping to remove plaque-building "bad cholesterol" from arteries.

For this study, researchers studied kidney function and HDL cholesterol levels in more than 1.7 million male veterans from October 2003 through September 2004. Researchers then followed participants until September 2013.

Patients with kidney disease frequently have lower levels of HDL cholesterol, which might explain their increased risk of early death; however, the association between elevated HDL cholesterol levels and premature death in these patients has been unclear. In the current study, the researchers showed that both high and low HDL cholesterol levels were associated with an increased risk of dying among study participants with all levels of kidney function.

"The findings may explain why clinical trials aimed at increasing HDL cholesterol levels failed to show improved outcomes," said Al-Aly, who also is the VA's associate chief of staff for research and education and co-director of the VA's Clinical Epidemiology Center in St. Louis.

Such findings regarding HDL cholesterol and premature death have not been reported in other large epidemiologic studies that have advanced understanding of the relationship between cholesterol parameters and clinical outcomes, Al-Aly said.

"However, the previous studies are limited in that the number of patients in those cohorts is relatively small compared with what a big data approach enabled us to see in our new research," he said. "Big data allow a more nuanced examination of the relationship between HDL cholesterol and risk of death across the full spectrum of HDL cholesterol levels."

Research data showed a relationship between HDL cholesterol levels and mortality as a U-shaped curve with the risk of death increased at both ends of the spectrum. "Too low and too high are both associated with higher risk of death," Al-Aly said.

Whether maintaining intermediate HDL cholesterol levels may increase longevity will need to be explored in future studies, Al-Aly said.

"A large database is critical in allowing us to research and challenge prior knowledge in our continuing efforts to create a better understanding of HDL cholesterol levels and risk of death," he said.

The longer our parents lived, the longer we are likely to live ourselves

The longer our parents lived, the longer we are likely to live ourselves, and the more likely we are to stay healthy in our sixties and seventies. Having longer-lived parents means we have with much lower rates of a range of heart conditions and some cancers.

The major study, funded by the Medical Research Council and involving almost 190,000 participants in the UK Biobank, is the largest of its kind. It found that our chances of survival increased by 17 per cent for each decade that at least one parent lives beyond the age of 70.

The study, published today in the Journal of the American College of Cardiology, was led by the University of Exeter and involved an international team of academics from the University of Cambridge (UK), UConn Center on Aging at UConn Health in Connecticut, USA, the French National Institute of Health, and the Indian Institute of Public Health. It found evidence showing for the first time that knowing the age at which your parents died could help predict your risk not only of heart disease, but many aspects of heart and circulatory health.

The researchers used data on the health of 186,000 middle-aged offspring, aged 55 to 73 years, followed over a period of up to eight years. The team found that those with longer lived parents had lower incidence of multiple circulatory conditions including heart disease, heart failure, stroke, high blood pressure, high cholesterol levels and atrial fibrillation. For example, the risk of death from heart disease was 20% lower for each decade that at least one parent lived beyond the age of 70 years. In addition, those with longer lived parents also had reduced risk of cancer; 7% reduced likelihood of cancer in the follow-up per longer-lived parent.

Although factors such as smoking, high alcohol consumption, low physical activity and obesity were important, the lifespan of our parents was still predictive of disease onset after accounting for these risks.

Dr Janice Atkins, a Research Fellow in the Epidemiology and Public Health group at the University of Exeter Medical School and lead author on the paper, said: "To our knowledge, this is the largest study to show that the longer your parents live, the more likely you are to remain healthy in your sixties and seventies. Asking about parents' longevity could help us predict our likelihood of ageing well and developing conditions such as heart disease, in order to identify patients at higher or lower risk in time to treat them appropriately."

The study built on previous findings published by the University of Exeter Medical School researchers earlier this year, which established a genetic link between parents' longevity and heart disease risk. That paper, published in the journal Aging, studied 75,000 participants in the UK Biobank, and found that offspring of longer-lived parents were more likely to have protective variants of genes liked to coronary artery disease, systolic blood pressure, body mass index, cholesterol and triglyceride levels, type 1 diabetes, inflammatory bowel disease and Alzheimer's disease.

Dr Luke Pilling, lead author of the second study, said: "This work helps us identify genetic variations explaining the better health of people with longer-lived parents. We prominently found genetic factors linked to blood pressure, cholesterol levels and smoking, which underlines how important these avoidable and treatable risks are. However, we also found novel genetic factors, which could provide new clues to help us understand why having longer-lived parents has health benefits."

Professor David Melzer, who leads the research programme, said: "It's been unclear why some older people develop heart conditions in their sixties while others only develop these conditions much later in life or even avoid them completely. Our research tells us that, while avoiding the well-known risk factors such as smoking is very important, there are also other factors inherited from parents. As we understand these parental factors better, we should be able to help more people to age well."

Professor George Kuchel, study co-author and Director of the UConn Center on Aging also noted: "This study provides additional fuel to really bolster research efforts by us and others in Geroscience, a field that seeks to understand relationships between the biology of aging and age-related diseases. Aging is the most important risk factor for common chronic conditions such as heart disease, Alzheimer's and cancer, which are likely to share pathways with aging and therefore interventions designed to slow biological aging processes may also delay the onset of disease and disability, thus expanding years of healthy and independent lives for our seniors."

Sedentary time may raise heart disease risk -- sit less, move more

Being sedentary is not just a lack of exercise, it is a potentially independent risk factor for heart disease and stroke, according to a science advisory from the American Heart Association.

"Regardless of how much physical activity someone gets, prolonged sedentary time could negatively impact the health of your heart and blood vessels," said Deborah Rohm Young, Ph.D., director of behavioral research at Kaiser Permanente Southern California in Pasadena and chair of the new scientific statement published in the American Heart Association journal Circulation.

According to the statement, sedentary behavior may be associated with an increased risk of developing diabetes, cardiovascular disease, impaired insulin sensitivity (linked to diabetes) and an overall higher risk of death from any cause.

"There are many important factors we don't understand about sedentary time yet. The types of studies available identify trends but don't prove cause and effect," said Young. "We don't have information about how much sedentary behavior is bad for health--the best advice at this time is to 'sit less and move more.'"

The authors also recommend that Americans strive for 30 minutes or so of moderate to vigorous physical activity per day to achieve the American Heart Association's weekly recommendation of 150 minutes of moderate exercise or 75 minutes of vigorous exercise. Instead of lumping all the exercise into one or two days, the goal is to encourage more consistent activity, Young said.

However, the authors found that moderate to vigorous physical activity does not cancel out the impact of sedentary time. Even physically active people who spend a lot of their time being sedentary appear to have increased risk.

Sedentary behaviors include sitting, reclining, or laying down while awake as well as reading, watching television or working on the computer. These "inactive activities" mean energy expenditure is less than or equal to 1.5 metabolic equivalents, or METs.

Light housework or slow, leisurely walking uses about 2.5 METs, moderate to vigorous physical activity usually requires 3.0 or more METs.

"Based on existing evidence, we found that U.S. adults are sedentary for about six to eight hours a day," Young said. "Adults 60 years and older spend between 8.5 - 9.6 hours a day in sedentary time."

Another issue, according to Young, is that it's not clear whether people should replace prolonged sedentary behavior with simple movement or moderate to vigorous physical activity.

"There's a lot of research that we need to do," Young said. "This statement is important because it starts the ball rolling and suggests sedentary behavior may play an important role in heart health and more. But, it's too early to make conclusive recommendations other than to encourage Americans to 'sit less, move more.'"

DASH diet may help prevent gout flares

New research indicates that a healthy diet can effectively lower blood levels of uric acid, a known trigger of gout. The findings are published in Arthritis & Rheumatology, a journal of the American College of Rheumatology (ACR).

Elevated uric acid in the blood plays a key role in gout, an extremely painful form of arthritis that results in profound disability and healthcare expenses. Diet has long been identified as an important determinant of blood uric acid levels, but there is virtually no clinical trial evidence to inform food choice by physicians and patients.

Stephen Juraschek, MD, PhD, of the Johns Hopkins University School of Medicine, and his colleagues looked at the potential of the Dietary Approaches To Stop Hypertension (DASH) diet, a diet with well-established benefits for lowering blood pressure, for lowering uric acid. The DASH diet emphasizes fruits, vegetables, and low-fat dairy foods and reduced consumption of saturated fat, total fat, and cholesterol. It also contains whole grains, lean meats, fish, nuts, and beans.

The investigators assessed a randomized, crossover feeding trial in 103 adults with pre- or stage 1 hypertension. Participants were randomly assigned to receive either the DASH diet or a control diet (typical of the average American diet) and were further fed low, medium, and high sodium levels for 30 days, each in random order.

The DASH diet lowered uric acid on average by 0.35 mg/dL. In individuals with uric acid levels >7 mg/dL however, which is common among patients with gout, the DASH diet lowered uric acid by >1 mg/dL. While the researchers hypothesized that reducing sodium intake would lower uric acid levels, they found that the opposite was true: higher sodium intake (which was about equal to the average sodium consumed in a typical American diet) decreased uric acid levels compared with low sodium intake. The mechanism by which increased sodium intake decreases uric acid is unclear.

The findings suggest that the DASH diet may represent an effective, non-pharmacologic approach to prevent flares in patients with gout. "Physicians may now confidently recommend the DASH diet to patients with gout in order to lower uric acid levels," said Dr. Juraschek. "Our findings also show how sodium, or salt, can alter uric acid levels, which provides important insights in further understanding dietary triggers of gout flares."

Acetaminophen use when pregnant associated with kids' behavioral problems

Using the common pain-relieving medication acetaminophen during pregnancy was associated with increased risk for multiple behavioral problems in children, according to an article published online by JAMA Pediatrics.

Acetaminophen is generally considered safe in pregnancy and is used by a many pregnant women for pain and fever.

Evie Stergiakouli, Ph.D., of the University of Bristol, United Kingdom, and coauthors analyzed data for 7,796 mothers enrolled in the Avon Longitudinal Study of Parents and Children between 1991 and 1992 along with their children and partners. The authors examined associations between behavioral problems in children and their mothers' prenatal and postnatal acetaminophen use, as well as acetaminophen use by their partners.

Questionnaires assessed acetaminophen use at 18 and 32 weeks during pregnancy and when children were 5 years old. Behavioral problems in children reported by mothers were assessed by questionnaire when children were 7 years old.

At 18 weeks of pregnancy, 4,415 mothers (53 percent) reported using acetaminophen and 3,381 mothers (42 percent) reported using acetaminophen at 32 weeks. There were 6,916 mothers (89 percent) and 3,454 partners (84 percent) who used acetaminophen postnatally. The study reports 5 percent of children had behavioral problems.

Study results suggest prenatal use of acetaminophen by mothers at 18 and 32 weeks of pregnancy was associated with increased risk of conduct problems and hyperactivity symptoms in children, and maternal acetaminophen use at 32 weeks of pregnancy also was associated with higher risk for emotional symptoms and total difficulties in children.

Postnatal maternal acetaminophen use and acetaminophen use by partners were not associated with behavioral problems. Because the associations were not observed in these instances, the authors suggest that this may indicate that behavioral difficulties in children might not be explained by unmeasured behavioral or social factors linked to acetaminophen use.

Study limitations include a lack of information on dosage or duration of acetaminophen use.

"Children exposed to acetaminophen use prenatally are at increased risk of multiple behavioral difficulties. ... Our findings suggest that the association between acetaminophen use during pregnancy and offspring behavioral problems in childhood may be due to an intrauterine mechanism. Further studies are required to elucidate mechanisms behind this association as well as to test alternatives to a causal explanation. Given the widespread use of acetaminophen among pregnant women, this can have important implications on public health advice," the authors write.

But the authors also caution: "However, the risk of not treating fever or pain during pregnancy should be carefully weighed against any potential harm of acetaminophen to the offspring."