Saturday, December 7, 2013
Low levels of vitamin D have been implicated as a potential cause of diseases ranging from cancer to diabetes. Now an extensive review suggests it's really the other way around: Low levels of the "sunshine vitamin" are more likely a consequence -- not a cause -- of illness.
In their review of almost 500 studies, the researchers found conflicting results. Observational studies, which looked back at what people ate or the kinds of supplements they took, showed a link between higher vitamin D levels in the body and better health.
But, in studies where vitamin D was given as an intervention (treatment) to help prevent a particular ailment, it had no effect. The one exception was a decreased death risk in older adults, particularly older women, who were given vitamin D supplements.
"The discrepancy between observational and intervention studies suggests that low [vitamin D] is a marker of ill health," wrote review authors led by Philippe Autier, at the International Prevention Research Institute, in Lyon, France.
Vitamin D is known to play a key role in bone health. Low levels of vitamin D have been found in a number of conditions, including heart disease, autoimmune diseases, diabetes, cancer and Parkinson's disease. These findings may explain why so many Americans are currently taking vitamin D supplements.
It's nicknamed the sunshine vitamin because the body produces vitamin D when exposed to the sun (if someone isn't wearing sunscreen). It's also found in some foods, such as egg yolks and fatty fish, and in foods that have been fortified with vitamin D, such as milk.
The current review, published online Dec. 6 in The Lancet Diabetes & Endocrinology, looked at 290 observational studies. In these studies, blood samples to measure vitamin D levels were taken many years before the outcome of the study occurred. The review also included results of 172 randomized clinical trials of vitamin D. In randomized trials, some people receive a therapy while others do not.
The observational studies showed a potential benefit from vitamin D. For example, vitamin D was associated with a 58 percent reduced risk of cardiovascular events, a 38 percent decreased risk of diabetes and a 34 percent decreased risk of colon cancer in these studies.
But, when the researchers looked to the randomized clinical trials that used vitamin D as a treatment, they failed to find any effect on disease occurrence or severity from raising vitamin D levels.
However, vitamin D did reduce the risk of dying from any cause in older people taking 800 international units a day, according to the review.
Dr. Shaun Jayakar, an internal medicine and geriatric specialist from St. John Hospital and Medical Center in Detroit, said the findings in elderly people "are likely due to a reduction in falls and fractures. Supplementing with vitamin D would lead to stronger bones, which would reduce falls and factures."
Because the majority of interventional trials failed to find any benefit from vitamin D, the review's authors conclude that low vitamin D levels don't lead to ill health, rather they're caused by ill health.
They theorize that inflammation that occurs in many illnesses may be what depletes vitamin D levels.
Dr. Robert Graham, an internist from Lenox Hill Hospital in New York City, said, "This comprehensive review did a really good job at trying to tease out the effects of different study designs, and the findings will be controversial."
He said there are currently five, large ongoing interventional trials that will help to better define vitamin D's role in disease. However, the results of those studies won't be available for a number of years. Until then, he recommended, "Try to achieve homeostasis [equilibrium]. You don't want to get to a low level of vitamin D."
The Institute of Medicine recommends 600 international units of vitamin D for adults, and 800 international units for people over 70.
Both Graham and Jayakar agreed that those are reasonable supplement levels. Jayakar said that for most people, vitamin D supplements are harmless, but added that "it's a pocketbook issue. Almost 50 percent of the population is taking vitamin D supplements. That's a lot of money for something that likely has no benefit," he said.
Jayakar added that this review's findings suggest that low vitamin D levels could be used as a marker -- a sign -- of disease in younger people. "If someone isn't feeling well and they have low vitamin D, maybe we should use that to start searching to see if something else is going wrong," he said.
Wednesday, December 4, 2013
A University of Colorado Cancer Center study published online ahead of print in the journal Nutrition and Cancer describes the laboratory synthesis of the most active component of grape seed extract, B2G2, and shows this synthesized compound induces the cell death known as apoptosis in prostate cancer cells while leaving healthy cells unharmed.
“We’ve shown similar anti-cancer activity in the past with grape seed extract (GSE), but now we know B2G2 is its most biologically active ingredient which can be synthesized in quantities that will allow us to study the detailed death mechanism in cancer cells,” says Alpna Tyagi, PhD, of the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences. Tyagi works in the lab of CU Cancer Center investigator and Skaggs School of Pharmacy faculty member, Chapla Agarwal, PhD.
The group has spent more than a decade demonstrating the anti-cancer activity of GSE in controlled, laboratory conditions. For example, previous studies have shown the GSE effectiveness against cancer cells and have also shown its mechanism of action. “But until recently, we didn’t know which constituent of GSE created this effect. This naturally occurring compound, GSE, is a complex mixture of polyphenols and also so far it has been unclear about the biologically active constituents of GSE against cancer cells,” Tyagi says.
Eventually the group pinpointed B2G2 as the most active compound, but, “it’s expensive and it takes a long time to isolate B2G2 from grape seed extract,” Tyagi says.
This expense related to the isolation of B2G2 has limited the group’s further exploration. So instead of purifying B2G2 from GSE, the group decided to synthesize it in the lab. The current study reports the success of this effort, including the ability to synthesize gram-quantity of B2G2 reasonably quickly and inexpensively.
In the paper’s second half, the group shows anti-cancer activity of synthesized B2G2 similar in mechanism and degree to overall GSE effectiveness.
“Our goal all along has been a clinical trial of the biologically active compounds from GSE against human cancer. But it’s difficult to earn FDA approval for a trial in which we don’t know the mechanisms and possible effects of all active components. Therefore, isolating and synthesizing B2G2 is an important step because now we have the ability to conduct more experiments with the pure compound. Ongoing work in the lab further increases our understanding of B2G2′s mechanism of action that will help for the preclinical and clinical studies in the future,” Tyagi says.
Tuesday, December 3, 2013
People who exercise regularly are better at creative thinking. This is the outcome of research by Leiden cognitive psychologist Lorenza Colato. She published an article on this subject in the scientific magazine Frontiers in Human Neuroscience.
Taking a stroll
We know that authors like Søren Kierkegaard, Henry James en Thomas Mann used to take a stroll before they sat down behind their writing desk. Apparently, this helped them to get new ideas and insights. But is it possible to prove scientifically that physical exercise makes creative thinking easier?
Divergent and convergent
To find this out, Colzato investigated whether regular exercise may promote the two main ingredients of creativity: divergent thinking and convergent thinking. Divergent thinking means to think up as many solutions as possible for a certain problem. Convergent thinking leads to one single correct solution for a given problem.
The psychologist gave thinking tasks to two groups of test persons: people who do physical exercise at least four times a week -- i.e. cycling -- and people who do not exercise on a regular basis. The first assignment was a so-called alternate uses test, in which the participants had to note down all the possible uses for a pen. This was followed by a remote associates task: the test persons were presented with three non-related words, like 'time', 'hair' and 'stretch', and had to come up with the common link, which in this case was 'long'.
Healthy body = sound mind
On the remote associates task, people from the group of frequent exercisers appeared to outperform those who did not exercise regularly. Colzato: 'We think that phsysical movement is good for the ability to think flexibly, but only if the body is used to being active. Otherwise a large part of the energy intended for creative thinking goes to the movement itself.' Colzato believes that these results support the famous classical idea of a 'sound mind in a healthy body': 'Exercising on a regular basis may thus act as a cognitive enhancer promoting creativity in inexpensive and healthy ways.'
Monday, December 2, 2013
A new study led by University of Kentucky researchers suggests that a diet low in vitamin D causes damage to the brain.
In addition to being essential for maintaining bone health, newer evidence shows that vitamin D serves important roles in other organs and tissue, including the brain. Published in Free Radical Biology and Medicine, the UK study showed that middle-aged rats that were fed a diet low in vitamin D for several months developed free radical damage to the brain, and many different brain proteins were damaged as identified by redox proteomics. These rats also showed a significant decrease in cognitive performance on tests of learning and memory.
"Given that vitamin D deficiency is especially widespread among the elderly, we investigated how during aging from middle-age to old-age how low vitamin D affected the oxidative status of the brain," said lead author on the paper Allan Butterfield, professor in the UK Department of Chemistry, director of the Center of Membrane Sciences, faculty of Sanders-Brown Center on Aging, and director of the Free Radical Biology in Cancer Core of the Markey Cancer Center. “Adequate vitamin D serum levels are necessary to prevent free radical damage in brain and subsequent deleterious consequences."
Previously, low levels of vitamin D have been associated with Alzheimer's disease, and it's also been linked to the development of certain cancers and heart disease. In both the developed world and in areas of economic hardship where food intake is not always the most nutritious, vitamin D levels in humans are often low, particularly in the elderly population. Butterfield recommends persons consult their physicians to have their vitamin D levels determined, and if low that they eat foods rich in vitamin D, take vitamin D supplements, and/or get at least 10-15 minutes of sun exposure each day to ensure that vitamin D levels are normalized and remain so to help protect the brain.
Researchers at Boston University School of Medicine (BUSM) have found further evidence that exercise may be beneficial for brain health and cognition. The findings, which are currently available online in Behavioural Brain Research, suggest that certain hormones, which are increased during exercise, may help improve memory.
Hormones called growth factors are thought to mediate the relationship between exercise and brain health. The hippocampus, a region of the brain crucial for learning and memory, is thought to be uniquely affected by these hormones.
The growth factors brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor-1 (IGF-1), have been implicated in the link between exercise and hippocampal function. BDNF, for example, acts on the nervous system to help regulate communication between existing brain cells (neurons) and stimulate the growth and maturation of new hippocampal neurons and blood vessels.
In this study, the researchers recruited healthy young adults, in whom they measured blood hormone levels together with performance on a recognition memory task and aerobic fitness. The researchers were thus able to correlate the blood hormone levels with aerobic fitness, and subsequently whether there was any effect on memory function.
According to the researchers, BDNF and aerobic fitness predicted memory in an interactive manner, suggesting that at low fitness BDNF levels negatively predicted expected memory accuracy. Conversely, at high fitness resting BDNF levels positively predicted recognition memory. There also was a strong association between IGF-1 and aerobic fitness; however there was no complementary link between IGF-1 and memory function.
"We will be continuing this line of research by testing if memory improves following an exercise training program in both young and geriatric adults, and by adding brain imaging techniques," explained Karin Schon, PhD, assistant professor of anatomy and neurobiology at BUSM, who served as the study's principal investigator.
More than half of older adults in the United States – an estimated 18.7 million people – have experienced bothersome pain in the previous month, impairing their physical function and underscoring the need for public health action on pain. Many of those interviewed by investigators for a study published in the current issue of PAIN® reported pain in multiple areas.
The interviews, which included assessments of cognitive and physical performance, were completed by trained survey research staff in the homes of study participants living in the community or in residential care facilities, such as retirement or assisted-living communities. "Pain is common in older adults and one of the major reasons why we start slowing down as we age," says lead investigator Kushang V. Patel, PhD, MPH, of the Center for Pain Research on Impact, Measurement, and Effectiveness in the Department of Anesthesiology and Pain Medicine at the University of Washington.
The researchers gained several insights from the new study:
- Bothersome pain afflicts half of community-dwelling older adults in the United States.
- The majority of older adults with pain reported having pain in multiple locations, such as in the back, hips, and knees.
- The percentage of people with pain did not differ by age, even when researchers accounted for dementia and cognitive performance.
- Pain was strongly associated with decreased physical capacity. Older adults with pain, particularly those with pain in multiple locations, had weaker muscle strength, slower walking speed, and poorer overall function than those without pain.
The researchers analyzed data from the National Health and Aging Trends Study (NHATS), which was designed to investigate multiple aspects of functioning in later life and is funded by the U.S. National Institute on Aging, part of the National Institutes of Health. Investigators conducted in-person interviews with 7,601 adults ages 65 years and older who were enrolled in the NHATS in 2011. All were Medicare beneficiaries.
The overall prevalence of bothersome pain in the last month in the study group was 52.9%. Pain did not vary across age groups, and this pattern remained unchanged when accounting for cognitive performance, dementia, proxy responses, and residential-care living status. Pain prevalence was higher in women and in older adults with obesity, musculoskeletal conditions, and depressive symptoms. The majority (74.9%) of older adults with pain reported multiple sites of pain.
Several measures of physical capacity, including muscle strength and lower-extremity physical performance, were associated with pain and multisite pain. For example, self-reported inability to walk three blocks was 72% higher in participants with pain than without pain. Participants with one, two, three, and four or more sites were 41%, 57%, 81%, and 105% more likely to report inability to walk three blocks, respectively, than older adults without pain.
"Considering that pain is often poorly managed in the geriatric population, our findings underscore the need for public health action, including additional epidemiologic research and the development and translation of interventions aimed at improving pain and function in older adults," Patel concludes.
Population aging is occurring in nearly every country of the world. Not only are the number and proportion of older adults increasing globally, but the older adult population itself is getting older as well. Gains in life expectancy at older ages have fueled the rapid growth of the oldest-old segment of the population, although it is unclear whether improvements in functional status of older adults have kept pace. Since disability in late life is a major predictor of medical and social service needs, investigating risk factors for functional decline is a major public health priority. Today's published study in PAIN® by Patel and colleagues clearly identifies the high burden of pain in the older adult population.
Friday, November 29, 2013
A byproduct of cholesterol functions like the hormone estrogen to fuel the growth and spread of the most common types of breast cancers, researchers at the Duke Cancer Institute report.
The researchers also found that anti-cholesterol drugs such as statins appear to diminish the effect of this estrogen-like molecule.
Published in the Nov. 29, 2013, edition of the journal Science, the findings are early, using mouse models and tumor cells. But the research for the first time explains the link between high cholesterol and breast cancer, especially in post-menopausal women, and suggests that dietary changes or therapies to reduce cholesterol may also offer a simple, accessible way to reduce breast cancer risk.
"A lot of studies have shown a connection between obesity and breast cancer, and specifically that elevated cholesterol is associated with breast cancer risk, but no mechanism has been identified," said senior author Donald McDonnell, Ph.D., chair of the Department of Pharmacology and Cancer Biology at Duke. "What we have now found is a molecule – not cholesterol itself, but an abundant metabolite of cholesterol – called 27HC that mimics the hormone estrogen and can independently drive the growth of breast cancer."
The hormone estrogen feeds an estimated 75 percent of all breast cancers. In a key earlier finding from McDonnell's lab, researchers determined that 27-hydroxycholesterol – or 27HC – behaved similarly to estrogen in animals.
For their current work, the researchers set out to determine whether this estrogen activity was sufficient on its own to promote breast cancer growth and metastasis, and whether controlling it would have a converse effect.
Using mouse models that are highly predictive of what occurs in humans, McDonnell and colleagues demonstrated the direct involvement of 27HC in breast tumor growth, as well as the aggressiveness of the cancer to spread to other organs. They also noted that the activity of this cholesterol metabolite was inhibited when the animals were treated with antiestrogens or when supplementation of 27HC was stopped.
The studies were substantiated using human breast cancer tissue. An additional finding in the human tissue showed a direct correlation between the aggressiveness of the tumor and an abundance of the enzyme that makes the 27HC molecule. They also noted that 27HC could be made in other places in the body and transported to the tumor.
"The worse the tumors, the more they have of the enzyme," said lead author Erik Nelson, Ph.D., a post-doctoral associate at Duke. Nelson said gene expression studies revealed a potential association between 27HC exposure and the development of resistance to the antiestrogen tamoxifen. Their data also highlights how increased 27HC may reduce the effectiveness of aromatase inhibitors, which are among the most commonly used breast cancer therapeutics.
"This is a very significant finding," McDonnell said. "Human breast tumors, because they express this enzyme to make 27HC, are making an estrogen-like molecule that can promote the growth of the tumor. In essence, the tumors have developed a mechanism to use a different source of fuel."
McDonnell said the findings suggest there may be a simple way to reduce the risk of breast cancer by keeping cholesterol in check, either with statins or a healthy diet. Additionally, for women who have breast cancer and high cholesterol, taking statins may delay or prevent resistance to endocrine therapies such as tamoxifen or aromatase inhibitors.
The next steps for research include clinical studies to verify those potential outcomes, as well as studies to determine if 27HC plays a role in other cancers, McDonnell said.