19928JAN2015
CNO Report 199
Release Date 31 JAN 2015
Draft Report Compiled by
Ralph Turchiano
In This Issue:
- Citrus scent inhibits liver cancer
- Common gut microbe might curb MS risk — at least in women
- Fatty acids in fish may shield brain from mercury damage
- Probiotic helps treat diabetes in rats, could lead to human remedy
- Small study shows beetroot juice improves exercise function of COPD patients
- Are medications’ adverse cognitive effects reversible?
- Common pesticide may increase risk of ADHD
- Neuroscience researchers believe in quitting smoking gradually
- ‘Healthy’ fat tissue could be key to reversing type 2 diabetes
- Beer compound could help fend off Alzheimer’s and Parkinson’s diseases
- Obesity and diabetes symptoms in mice improved by reversing brain inflammation
- Added fructose is a principal driver of type 2 diabetes
- Study by CU researcher finds everyday exposure to chemicals could trigger early menopause
- Green tea ingredient may target protein to kill oral cancer cells
Public Release: 19-Jan-2015
Citrus scent inhibits liver cancer
Essential oils occur in plants, protecting them through their antibacterial, antiviral and fungicidal properties. It has been recently discovered that terpenes, the oils’ main components, can also inhibit the growth of different cancer cells, including liver cancer. Their function had not previously been fully understood.
Olfactory receptors not just in the nose
Terpenes can trigger signalling processes in cells by activating olfactory receptors. Those receptors are mainly located in the nose, but they have been proved to occur in all types of human tissue, including skin, prostate and spermatozoa. Carcinogenesis and cancer growth are likewise significantly affected by terpenes, even though it has not been understood which function exactly they fulfil.
Terpene triggers signalling pathway in the cell
In order to find this out, the researchers from Bochum utilised a cellular model of hepatocellular carcinoma, a common liver tumour. They exposed the cells to a subset of terpenes with different concentrations, and monitored their reactions. It emerged that two of the eleven terpenes tested resulted in a significant increase in calcium concentration in the cells: (-)-citronellal and citronellol. During a follow-up analysis, the researchers focused on (-)-citronellal and scanned for a receptor into which the terpene has to fit like a key into a lock. They demonstrated that the decisive olfactory receptor OR1A2 occurs in liver cells and is responsible for detection of the citrus scent and cellular reaction. If the option for producing that receptor had been removed from the cells, they did no longer react to the terpene. The researchers, moreover, succeeded in tracking the signalling pathway which the terpene uses for increasing calcium concentration inside the cells, thus reducing cell growth. “These results are yet another example for the significance of olfactory receptors outside the nose, and they give rise to hope that new drugs with no severe side effects may be developed for cancer therapy.”
Common gut microbe might curb MS risk — at least in women
A common gut microbe might curb the risk of developing multiple sclerosis–at least in women–suggests the largest study of its kind published online in the Journal of Neurology Neurosurgery & Psychiatry.
If confirmed in other studies, this might prove the hygiene hypothesis, the premise of which is that childhood infections help to prime and regulate the immune system and ward off autoimmune and allergic diseases in later life, say the researchers.
The prevalence of multiple sclerosis (MS) has increased worldwide, in tandem with other autoimmune disease, but the reasons behind this rise are unclear. Some studies have suggested a link between early childhood infection and reduced MS risk, but they have all been small.
The researchers therefore tested 550 people with confirmed MS and a comparison group of 299 healthy people, matched for age and sex, for the presence of antibodies to Helicobacter pylori. The tests were done between 2007 and 2011.
- pylori is usually acquired before the age of 2, and lasts for life in the stomach, unless treated. Around half the world’s population is infected with it, most of whom live in the developing world, where hygiene standards and antibiotic prescribing rates tend to be lower than they are in developed countries.
The results showed that the prevalence of the infection was significantly lower in those with MS than in the comparison group, but only among women, in whom it was around 30% lower.
Furthermore, after taking account of influential factors, such as age at diagnosis, year of birth, and duration of symptoms, those women with MS who tested positive for H. pylori seemed to be less disabled by their condition than those who tested negative for the infection.
The reverse was true in men, among whom a positive test result was linked to higher rates of disability.
There was no evidence of any link between the presence of the infection and relapse rate.
There’s no obvious explanation for the gender disparity, which definitely warrants further study, say the researchers. Rates of MS are higher in women than they are in men, with most of the increased prevalence of MS in recent years, occurring in women.
In a linked editorial, Professor Jun-ichi Kira, of the Neurological Institute at Kyushu University, Fukuoka, Japan, points out that the lower disability scores reported by the women with MS who tested positive for H. pylori, suggests that the infection might be protective.
“Collectively, such an inverse correlation of H. pylori infection with MS in developing countries where MS and allergic disorders have increased, may support the ‘hygiene hypothesis,’ he writes.
“Although why the protective effects of H. pylori against MS were observed only in women remains to be elucidated, but might explain the recent increase in female to male ratio of MS in developed countries,” he adds.
Public Release: 21-Jan-2015
Fatty acids in fish may shield brain from mercury damage
New findings from research in the Seychelles provide further evidence that the benefits of fish consumption on prenatal development may offset the risks associated with mercury exposure. In fact, the new study, which appears today in the American Journal of Clinical Nutrition, suggests that the nutrients found in fish have properties that protect the brain from the potential toxic effects of the chemical.
Three decades of research in the Seychelles have consistently shown that high levels of fish consumption by pregnant mothers – an average of 12 meals per week – do not produce developmental problems in their children. Researchers have previously equated this phenomenon to a kind of biological horse race, with the developmental benefits of nutrients in fish outpacing the possible harmful effects of mercury also found in fish. However, the new research indicates that this relation is far more complex and that compounds present in fish – specifically polyunsaturated fatty acids (PUFA) – may also actively counteract the damage that mercury causes in the brain.
“These findings show no overall association between prenatal exposure to mercury through fish consumption and neurodevelopmental outcomes,” said Edwin van Wijngaarden, Ph.D., and associate professor in the University of Rochester Department of Public Health Sciences and a co-author of the study. “It is also becoming increasingly clear that the benefits of fish consumption may outweigh, or even mask, any potentially adverse effects of mercury.”
“This research provided us the opportunity to study the role of polyunsaturated fatty acids on development and their potential to augment or counteract the toxic properties of mercury,” said Sean Strain, Ph.D., a professor of Human Nutrition at the Ulster University in Northern Ireland and lead author of the study. “The findings indicate that the type of fatty acids a mother consumes during pregnancy may make a difference in terms of their child’s future neurological development.”
The new study comes as the U.S. Food and Drug Administration and international agencies are in the process of revisiting fish consumption advisories to better reflect the health benefits of nutrients found in fish. The FDA’s current guidance – which recommends that pregnant women limit their consumption of certain fish to twice a week – was established because of the known risk of high level mercury exposure on childhood development.
Mercury is found in the environment as a result of both natural and human (e.g. coal plant emissions) activity. Much of it ends up being deposited in the world’s oceans and, as a result, fish harbor the chemical in very small amounts.
This has given rise to concerns that the cumulative impact of prenatal exposure to mercury through fish consumption may have negative health outcomes, despite the fact that that a link between low-level exposure and developmental consequences in children has never been definitively established.
At the same time, fish are rich in a host of beneficial nutrients, including fatty acids, which are essential to brain development, leading to a long-standing exchange among scientists, environmentalists, and policymakers over the risk vs. benefit of fish consumption. This debate has significant consequences for global health, as billions of people across the world rely on fish as their primary source of protein.
The Seychelles Child Development Study – a partnership between the University of Rochester Ulster University, and the Republic of Seychelles Ministry of Health and Education – is one of the longest and largest population studies of its kind. The Seychelles, a cluster of islands in the Indian Ocean, has proven to be the ideal location to examine the potential health impact of persistent low-level mercury exposure. The nation’s 89,000 residents consume fish at a rate 10 times greater than the populations of the U.S. and Europe.
The study published today followed more than 1,500 mothers and their children. At 20 months after birth, the children underwent a battery of tests designed to measure their communication skills, behavior, and motor skills. The researchers also collected hair samples from the mothers at the time of their pregnancy to measure the levels of prenatal mercury exposure.
The researchers found that mercury exposure did not correlate with lower test scores. This finding tracked with the results of previous studies by the group – some of which have followed children in the Seychelles into their 20s – that have also shown no association between fish consumption and subsequent neurological development.
The researchers also measured the PUFA levels present in the pregnant women and found that the children of mothers with higher levels of fatty acids known as n3 – the kind found in fish – performed better on certain tests. Another common form of PUFA, called n6, comes from other meats and cooking oils and is found in greater abundance in the diets of residents of developed countries.
The fatty acids in fish (n3) are known to have anti-inflammatory properties, compared to n6, which can promote inflammation. One of the mechanisms by which mercury inflicts its damage is through oxidation and inflammation and this has led the researchers to speculate that not only does n3 provide more benefit in terms of brain development, but that these compounds may also counteract the negative effects of mercury.
This was reflected in the study’s findings, which showed that the children of mothers with relatively higher levels of n6 did poorer on tests designed to measure motor skills.
“It appears that relationship between fish nutrients and mercury may be far more complex than previously appreciated,” said Philip Davidson, Ph.D., the principal investigator of the Seychelles Child Development Study, a professor emeritus at the University of Rochester, and senior author of the study. “These findings indicate that there may be an optimal balance between the different inflammatory properties of fatty acids that promote fetal development and that these mechanisms warrant further study.”
PUBLIC RELEASE: 29-JAN-2015
Probiotic helps treat diabetes in rats, could lead to human remedy
CORNELL UNIVERSITY
ITHACA, N.Y. – Science may be one step closer to treating diabetes with a human probiotic pill, according to new Cornell University research.
In the study, published Jan. 27 in the journal Diabetes, the researchers engineered a strain of lactobacillus, a human probiotic common in the gut, to secrete a Glucagon-like peptide 1 (GLP-1). They then administered it orally to diabetic rats for 90 days and found the rats receiving the engineered probiotic had up to 30 percent lower high blood glucose, a hallmark of diabetes.
The study was a proof of principle, and future work will test higher doses to see if a complete treatment can be achieved, said John March, professor of biological and environmental engineering at Cornell University and the paper’s senior author.
The researchers found that upper intestinal epithelial cells in diabetic rats were converted into cells that acted very much like pancreatic beta cells, which monitor blood glucose levels and secrete insulin as needed to balance glucose levels in healthy individuals.
“The amount of time to reduce glucose levels following a meal is the same as in a normal rat, … and it is matched to the amount of glucose in the blood,” just as it would be with a normal-functioning pancreas, March said. “It’s moving the center of glucose control from the pancreas to the upper intestine.”
Also, though it replaces the insulin capacity in diabetic rats, the researchers found no change in blood glucose levels when administered to healthy rats. “If the rat is managing its glucose, it doesn’t need more insulin,” March said.
This technology was licensed by the BioPancreate, a wholly-owned subsidiary of Cortendo AB, a biopharmaceutical company incorporated in Sweden and based in Radnor, Penn., which is working to get the therapy into production for human use.
Human patients would likely take a pill each morning to help control their diabetes, March said.
Small study shows beetroot juice improves exercise function of COPD patients
The study to investigate the effects of acute beetroot juice ingestion on the exercise capacity of COPD patients shows some promise, but a larger clinical trial is needed to verify results.
The new research, published online ahead of print in the journal Nitric Oxide: Biology and Chemistry, looked at a small group of COPD patients who drank beetroot juice as compared to a placebo drink before exercise.
“The intent of this study was to determine if acute ingestion of beetroot juice, which is rich with nitrates, prior to exercising could improve the exercise capacity of COPD patients,” said Michael Berry, who is the primary investigator and lead author of the study. As chair of Wake Forest’s department of health and exercise science, Berry is interested in the potential benefits of beetroot juice on physical function.
COPD, or chronic obstructive pulmonary disease, makes it difficult for patients to breathe and worsens over time. Patients often complain of shortness of breath with exertion, so tasks like climbing steps can leave them gasping for air. In turn, they tend to limit their activities, become more sedentary, and lose fitness and physical function.
The single-blind, placebo-controlled, cross-over study was primarily funded by Wake Forest University’s Translational Science Center (TSC) with additional funding from the National Institutes of Health grant NR011186. The TSC has conducted research that looks at how nitrite and its biological precursor, nitrate (found in beetroot juice) can be utilized in treatments for a variety of conditions. In a 2010 study, Wake Forest researchers were the first to find a link between consumption of nitrate-rich beet juice and increased blood flow to the brainand the Hartwell Foundation.
Berry said his study findings showed overall that those patients who drank beetroot juice were able to extend their exercise time, and had reduced exercise diastolic and resting systolic blood pressures. This is the first study to demonstrate beneficial effects of dietary nitrite supplementation on exercise performance and blood pressure in patients with COPD, he added.
Researchers recruited 15 COPD patients; 11 white males, one African-American male and three white females. Patients completed four visits. During visit one, they completed baseline pulmonary function testing, filled out health status questionnaires, had a brief medical examination and completed an incremental exercise test on a stationary bicycle to determine their maximal exercise work rate. The second visit one week later consisted of additional pulmonary function and lung volume testing, as well as a familiarization exercise test on an exercise bicycle at 75 percent of the patients’ previously determined maximal work rates.
Berry said this type of exercise test has been used in previous trials with COPD patients examining the effects of pharmaceutical agents on exercise performance and is designed to exhaust the patient in a period of four to 10 minutes.
Participants were assigned to one of two treatments — beetroot juice (visit three) and placebo (visit four) or placebo (visit three) and beetroot juice (visit four). These visits were separated by at least a seven-day break.
All visits were performed at a similar time in the morning and the beetroot juice or placebo juice, about three ounces of each, was ingested two-and-a-half hours before the final two visits. Prune juice was used as the placebo because it contains similar amounts of carbohydrates, sugars and fats, but does not contain any nitrates, Berry said. How long patients exercised during the third and fourth visits was recorded.
Berry said that while the study has its limitations, he is hopeful the data generated will lead to grant funding for a larger study to look at the mechanisms for how nitrates can improve the physical function of COPD patients.
“One of the benefits of exercise is that if you get positive results, you’re more likely to continue doing it. If beetroot juice positively impacts those results, it could motivate COPD patients to continue to be physically active and improve their health,” he said.
Public Release: 26-Jan-2015
Are medications’ adverse cognitive effects reversible?
INDIANAPOLIS — Whether the adverse cognitive effects of medications can be reversed is of significant importance to an aging population, their caregivers and their families, as well as to an overburdened health care system.
In a commentary in JAMA Internal Medicine, Noll Campbell, Pharm.D., and Malaz Boustani, M.D., MPH, of the Regenstrief Institute and the Indiana University Center for Aging Research, probe the possibility of reversing the adverse cognitive effects of medications frequently prescribed to older adults for chronic conditions including depression, anxiety and incontinence and sold over the counter as allergy and sleep aids.
It is not unusual for older adults to take two, three or more drugs that have a negative impact on their brain function. Over the past decade, Drs. Boustani and Campbell and colleagues have conducted several studies that have found associations between exposure to anticholinergic medications, which block acetylcholine, a nervous system neurotransmitter, and the clinical diagnosis of mild cognitive impairment or dementia. Low levels of acetylcholine have long been implicated in patients with dementia.
In a 2013 study, they reported that drugs with strong anticholinergic effects were associated with a clinical diagnosis of cognitive impairment when taken continuously for as few as 60 days over a one-year period. A similar impact was seen with 90 days of continuous use over a year when taking multiple drugs with weak anticholinergic effect.
In “Adverse Cognitive Effects of Medications: Turning Attention to Reversibility” published in the Jan. 26, 2015, issue of JAMA Internal Medicine, Drs. Campbell and Boustani call for further research to determine whether cognitive impairment caused by the adverse effects of medications can be reversed and to establish the safety risks of discontinuing these medications.
Their commentary accompanies a 10-year observational study by Shelly Gray, Pharm.D., M.S., of the University of Washington and colleagues that reports a higher risk of dementia with increasing dose and duration of exposure to medications with strong anticholinergic activities.
“While the Gray study suggests that adverse cognitive effects of medications were permanent, this may represent the use of dementia as the outcome — a non-reversible condition — rather than a diagnosis of mild cognitive impairment which may be reversible in some older adults. Our previous studies have shown a stronger association of these harmful medications with the diagnosis of mild cognitive impairment than with dementia,” Dr. Campbell said.
Common pesticide may increase risk of ADHD
Rutgers study suggests that pregnant women and young children are more susceptible
RUTGERS UNIVERSITY
A commonly used pesticide may alter the development of the brain’s dopamine system — responsible for emotional expression and cognitive function – and increase the risk of attention deficit hyperactivity disorder in children, according to a new Rutgers study.
The research published Wednesday in the Journal of the Federation of American Societies for Experimental Biology (FASEB), by Rutgers scientists and colleagues from Emory University, the University of Rochester Medical Center, and Wake Forest University discovered that mice exposed to the pyrethroid pesticide deltamethrin in utero and through lactation exhibited several features of ADHD, including dysfunctional dopamine signaling in the brain, hyperactivity, working memory, attention deficits and impulsive-like behavior.
These findings provide strong evidence, using data from animal models and humans, that exposure to pyrethroid pesticides, including deltamethrin, may be a risk factor for ADHD, says lead author Jason Richardson, associate professor in the Department and Environmental and Occupational Medicine at Rutgers Robert Wood Johnson Medical School and a member of the Environmental and Occupational Health Sciences Institute (EOHSI).
“Although we can’t change genetic susceptibility to ADHD, there may be modifiable environmental factors, including exposures to pesticides that we should be examining in more detail,” says Richardson.
Attention deficit hyperactivity disorder most often affects children, with an estimated 11 percent of children between the ages of 4-17- about 6.4 million – diagnosed as of 2011. Boys are three to four times more likely to be diagnosed than girls. While early symptoms, including an inability to sit still, pay attention and follow directions, begin between the ages of 3 to 6, diagnosis is usually made after the child starts attending school full time.
Importantly, in this study, the male mice were affected more than the female mice, similar to what is observed in children with ADHD. The ADHD-like behaviors persisted in the mice through adulthood, even though the pesticide, considered to be less toxic and used on golf courses, in the home, and on gardens, lawns and vegetable crops, was no longer detected in their system.
There is strong scientific evidence that genetics plays a role in susceptibility to the disorder, but no specific gene has been found that causes ADHD and scientists believe that environmental factors may also contribute to the development of the behavioral condition.
Using data from the Centers for Disease Control, National Health and Nutrition Examination Survey (NHANES) the study analyzed health care questionnaires and urine samples of 2,123 children and adolescents. Researchers asked parents whether a physician had ever diagnosed their child with ADHD and cross-referenced each child’s prescription drug history to determine if any of the most common ADHD medications had been prescribed. Children with higher pyrethroid pesticide metabolite levels in their urine were more than twice as likely to be diagnosed with ADHD.
Young children and pregnant women may be more susceptible to pesticide exposure because their bodies do not metabolize the chemicals as quickly. This is why, Richardson says, human studies need to be conducted to determine how exposure affects the developing fetus and young children.
“We need to make sure these pesticides are being used correctly and not unduly expose those who may be at a higher risk,” Richardson says.
Neuroscience researchers believe in quitting smoking gradually
University of Copenhagen – The Faculty of Health and Medical Sciences
Smoking is harmful in almost every respect. Cancer, stroke, and other cardiovascular diseases are just a small part of a well-documented portfolio of serious consequences of smoking. Nicotine is what makes smoking addictive, but new Danish research suggests that smoking initially increases brain activity. However, the brain tissue quickly adapts and the effect will disappear. On the other hand, according to brain scans, the brain’s oxygen uptake and blood flow decreases by up to 17% immediately after people stop smoking:
Regular smokers experience an almost dementia-like condition in the early hours after quitting, as suggested by brain scans. This can be quite an unpleasant experience, and is probably one of the reasons why it can be very difficult to quit smoking once and for all. Smokers drift back into abuse, perhaps not to obtain a pleasant effect – that ship has sailed – but simply because the withdrawal symptoms are unbearable, says Professor Albert Gjedde, neuroscience researcher at the Department of Neuroscience and Pharmacology, University of Copenhagen.
Together with Associate Professor Manouchehr Seyedi Vafaee from the same department and other scientists, Albert Gjedde is behind the new findings published in the Journal of Cerebral Blood Flow & Metabolism.
The researchers compare the nicotine in tobacco smoke with other pharmacologically active substances:
After a period of time, many users of medicine will no longer experience an effect from treatment – for example with antidepressants. However, the consequences of discontinuing treatment could still be overwhelming if the withdrawal symptoms are very unpleasant, says Albert Gjedde.
Habitual smokers seemingly need to continue smoking just to keep their brain functioning normally. With time, they may become less dependent on smoking, but the researchers still do not know how long it takes before the brain of a former smoker has regained its normal energy consumption and blood flow:
We assume that it takes weeks or months, but we do not know for sure. The new findings suggest that it may be a good idea to stop smoking gradually – simply to avoid the worst withdrawal symptoms that make it so difficult to stick to the otherwise very sensible decision to stop smoking, says Albert Gjedde. He emphasises that there are still many blind spots in relation to researching the brains of smokers.
Public Release: 27-Jan-2015
‘Healthy’ fat tissue could be key to reversing type 2 diabetes
Walter and Eliza Hall Institute
Preventing inflammation in obese fat tissue may hold the key to preventing or even reversing type 2 diabetes, new research has found.
Researchers from Melbourne’s Walter and Eliza Hall Institute, with colleagues from the RIKEN Institute, Japan, found they could ‘reverse’ type 2 diabetes in laboratory models by dampening the inflammatory response in fat tissue.
Dr Ajith Vasanthakumar, Dr Axel Kallies and colleagues from the institute discovered that specialised immune cells, called regulatory T cells (Tregs), played a key role in controlling inflammation in fat tissue and maintaining insulin sensitivity. The findings were published in the journal Nature Immunology.
More than 850,000 Australians are estimated to have type 2 diabetes, which is the most common type of diabetes, and its prevalence is rising. The disease is strongly linked with ‘lifestyle’ factors, such as being overweight or having high blood pressure. Long-term complications of type 2 diabetes include kidney, eye and heart disease, and there is no cure.
People with type 2 diabetes have reduced sensitivity to insulin, a hormone that normally triggers uptake of glucose by cells, and their cells no longer respond to insulin appropriately. This decrease in insulin sensitivity is thought to be a result of long-term, low-level inflammation of fat tissue in people who are obese.
Dr Vasanthakumar said Tregs acted as the guardians of the immune system, preventing the immune response from getting out-of-hand and attacking the body’s own tissues. “When Treg numbers are reduced, inflammatory diseases such as diabetes and rheumatoid arthritis can occur,” he said.
Recent studies have shown that fat tissue has its own unique type of Tregs, which disappear from fat tissue during obesity. “The fat tissue of obese people has lower numbers of Tregs than the fat tissue of people in a healthy weight range,” Dr Vasanthakumar said. “Without Tregs, inflammation-causing cell levels increase, and this rise in inflammation can lead to insulin resistance and high blood glucose levels, a classic hallmark of type 2 diabetes.”
The research team discovered a key hormone called IL-33 (interleukin-33) was able to selectively boost Treg populations in fat tissue, effectively halting the development of type 2 diabetes, or even reversing the disease in preclinical models.
“Treating fat tissues with IL-33 restored normal Treg cell levels, which reduced inflammation and decreased blood glucose levels,” Dr Vasanthakumar said. “Treatments that mimic IL-33 could have the potential to reduce obesity-related inflammation and type 2 diabetes.”
Dr Kallies said the research underscored the importance of ‘healthy’ fat tissue in maintaining a healthy body. “We can no longer think of fat tissue simply as energy storage,” Dr Kallies said.
“Fat tissue is increasingly being recognised as a crucial organ that releases hormones and regulates development. Keeping our fat tissue healthy is important for our general wellbeing, and our research highlights the important role it plays in preventing disease.”
Public Release: 28-Jan-2015
Beer compound could help fend off Alzheimer’s and Parkinson’s diseases
The health-promoting perks of wine have attracted the spotlight recently, leaving beer in the shadows. But scientists are discovering new ways in which the latter could be a more healthful beverage than once thought. They’re now reporting in ACS’ Journal of Agricultural and Food Chemistry that a compound from hops could protect brain cells from damage — and potentially slow the development of disorders such as Alzheimer’s and Parkinson’s diseases.
Jianguo Fang and colleagues note that mounting evidence suggests that oxidative damage to neuronal cells contributes to the development of diseases that originate in the brain. If scientists could find a way to guard these cells from this type of damage, they might be able to help prevent or slow down Alzheimer’s disease, Parkinson’s disease and other neurodegenerative conditions. One compound found in hops, called xanthohumol, has gotten the attention of researchers for its potential benefits, including antioxidation, cardiovascular protection and anticancer properties.
Fang’s team decided to test xanthohumol’s effects on brain cells.
In lab tests, the researchers found that the compound could protect neuronal cells and potentially help slow the development of brain disorders. The scientists conclude xanthohumol could be a good candidate for fighting such conditions.
Public Release: 28-Jan-2015
Obesity and diabetes symptoms in mice improved by reversing brain inflammation
UNIVERSITY OF OTAGO
Using an antioxidant to reverse inflammation in the brain caused by a high-fat diet greatly improves symptoms related to obesity and type II diabetes, a new study from New Zealand’s University of Otago suggests.
The research, which appears in the leading international journal Diabetes, was led by Dr Alex Tups of the University’s Centre for Neuroendocrinology and Department of Physiology.
Dr Tups and an international team investigated whether directly stopping inflammatory processes in the brain’s hypothalamus could help lower blood sugar levels and reduce insulin resistance.
In their research the team blocked a particular inflammatory signalling pathway (IKKβ/NF-κB) in the brains of obese mice. The researchers studied both mice that were obese due to a deficiency in the satiety hormone leptin and others due to a high-fat diet.
The scientists administered butein to the mice to block the signalling pathway, which is involved in the body’s inflammatory immune responses. Butein is a flavonoid derived from plants traditionally used in Chinese herbal medicine.
Dr Tups says the team found that administering butein either directly into the brain or orally greatly improved glucose tolerance and brain insulin signalling in both types of obese mice.
“We also showed that this profound effect was dose-dependent with better glucose tolerance achieved through higher doses of butein,” Dr Tups says.
The improved glucose tolerance of high-fat diet mice treated with the antioxidant was such that no difference was noticeable between them and low fat-diet mice that had not received butein.
To confirm that activation of the IKKβ/NF-κB pathway plays a central role in metabolic obesity symptoms, the researchers also used a gene therapy technique to inhibit it in neurons in the hypothalamus.
This gene therapy resulted in high-fat diet mice having a reduced body weight, building up less fat, expending more energy, and showing evidence of improved leptin-signalling.
Dr Tups says the study adds to growing body of evidence that a diet high in saturated fats activates a cascade of inflammatory processes in the brain which impair leptin and insulin signalling, leading to obesity and type II diabetes.
“Our findings strongly support this idea and we also show that reversing this inflammation promotes a return towards normal metabolic functioning,” he says.
The research suggests that butein and other natural compounds that block inflammation in the brain should be vigorously investigated as novel anti-diabetic treatments, he says.
PUBLIC RELEASE: 29-JAN-2015
Added fructose is a principal driver of type 2 diabetes
Clinical experts reporting in Mayo Clinic Proceedings urge drastic reductions in the consumption of foods and beverages containing added sugars, particularly added fructose
Rochester, MN, January 29, 2015 – Recent studies have shown that added sugars, particularly those containing fructose, are a principal driver of diabetes and pre-diabetes, even more so than other carbohydrates. Clinical experts writing in Mayo Clinic Proceedings challenge current dietary guidelines that allow up to 25% of total daily calories as added sugars, and propose drastic reductions in the amount of added sugar, and especially added fructose, people consume.
Worldwide, approximately one in ten adults has type 2 diabetes, with the number of individuals afflicted by the disease across the globe more than doubling from 153 million in 1980 to 347 million in 2008. In the United States, 29 million adults (one in eleven) have type 2 diabetes and another 86 million (more than one in three) have pre-diabetes.
“At current levels, added-sugar consumption, and added-fructose consumption in particular, are fueling a worsening epidemic of type 2 diabetes,” said lead author James J. DiNicolantonio, PharmD, a cardiovascular research scientist at Saint Luke’s Mid America Heart Institute, Kansas City, MO. “Approximately 40% of U.S. adults already have some degree of insulin resistance with projections that nearly the same percentage will eventually develop frank diabetes.”
The net result of excess consumption of added fructose is derangement of both overall metabolism and global insulin resistance say the authors. Other dietary sugars not containing fructose seem to be less detrimental in these respects. Indeed, several clinical trials have shown that compared to glucose or starch, isocaloric exchange with fructose or sucrose leads to increases in fasting insulin, fasting glucose, and the insulin/glucose responses to a sucrose load. “This suggests that sucrose (in particular the fructose component) is more harmful compared to other carbohydrates,” added Dr. DiNicolantonio. Dr. DiNicolantonio and his co-authors, James H O’Keefe, MD, Saint Luke’s Mid America Heart Institute, Kansas City, MO, and Sean C. Lucan, MD, MPH, MS, a family physician at Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, examined animal experiments and human studies to come to their conclusions.
Data from recent trials suggest that replacing glucose-only starch with fructose-containing table sugar (sucrose) results in significant adverse metabolic effects. Adverse effects are broader with increasing baseline insulin resistance and more profound with greater proportions of added fructose in the diet.
The totality of the evidence is compelling to suggest that added sugar, and especially added fructose (usually in the form of high-fructose corn syrup and table sugar), are a serious and growing public health problem, according to the authors.
The 2010 Dietary Guidelines for Americans say it is acceptable for some people to consume up to 19% of calories from added sugars, and the Institute of Medicine permits up to 25% of total calories from added sugars. In contrast, the World Health Organization recommends that added sugars should make up no more than 10% of an entire day’s caloric intake, with a proposal to lower this level to 5% or less for optimal health. Such levels would be more in line with what the authors would recommend and similarly restrictive to existing American Heart Association (AHA) recommendations–to consume no more than six teaspoons (24 grams) of sugar per day for women and no more than nine teaspoons (36 grams) of sugar per day for men.
While fructose is found naturally in some whole foods like fruits and vegetables, consuming these foods poses no problem for human health. Indeed, consuming fruits and vegetables is likely protective against diabetes and broader cardiometabolic dysfunction, explained DiNicolantonio and colleagues. The authors propose that dietary guidelines should be modified to encourage individuals to replace processed foods, laden with added sugars and fructose, with whole foods like fruits and vegetables. “Most existing guidelines fall short of this mark at the potential cost of worsening rates of diabetes and related cardiovascular and other consequences,” they wrote.
The authors also think there should be incentives for industry to add less sugars, especially fructose-containing varieties, to food-and-beverage products. And they conclude that at “an individual level, limiting consumption of foods and beverages that contain added sugars, particularly added fructose, may be one of the single most effective strategies for ensuring one’s robust future health.”
Public Release: 28-Jan-2015
Study by CU researcher finds everyday exposure to chemicals could trigger early menopause
University of Colorado Denver
AURORA, Colo. (January 28, 2015) – Women who are exposed to certain chemicals are more likely to experience menopause at a younger age, according to a newly published study by a researcher from the University of Colorado School of Medicine at the Anschutz Medical Campus.
The study, published in the journal PLOS ONE, reports that women exposed to certain chemicals experienced menopause 1.9 years to 3.8 years earlier than women with lower levels of the same chemicals. Women exposed to these same chemicals were up to six times more likely to be menopausal than non-exposed women.
Natalia Grindler, MD, an instructor and fellow in the Department of Obstetrics and Gynecology, and her fellow authors reviewed data collected by the National Health and Nutrition Examination Survey between 1999 and 2008, covering 31,575 women. The survey, administered by the Centers for Disease Control and Prevention, covers a cross section of the U.S. population.
The researchers evaluated the levels of 111 potential chemicals present in the women surveyed and found that 15 of those chemicals, which are used in cosmetics, plastics and household cleaners, could be causing women to go through menopause early. The chemicals associated with cases of early menopause included phthalates, polychlorinated biphenyls, surfactants and organophosphate pesticides.
“Our study shows there is a clinically significant association between levels of these chemicals and the age at menopause in a large cross section of U.S. women,” Grindler said. “Early menopause is not the only negative health impact. Any early decline in ovarian function could increase rates of infertility and lead to earlier development of cardiovascular disease, osteoporosis and other medical problems among women.”
Avoiding exposure to products with these chemicals is nearly impossible, so a greater understanding of how these chemicals affect reproductive health and interact with genetic predispositions and environmental factors is needed, Grindler said.
“We support the use of an approach that captures lifestyle, behavior and other exposures from conception onward,” Grindler said. “The health of future generations is at risk and without further research in this area those born today could be affected in decades to come.”
Public Release: 28-Jan-2015
Green tea ingredient may target protein to kill oral cancer cells
A compound found in green tea may trigger a cycle that kills oral cancer cells while leaving healthy cells alone, according to Penn State food scientists. The research could lead to treatments for oral cancer, as well as other types of cancer.
Earlier studies had shown that epigallocatechin-3-gallate — EGCG — a compound found in green tea, killed oral cancer cells without harming normal cells, but researchers did not understand the reasons for its ability to target the cancer cells, said Joshua Lambert, associate professor of food science and co-director of Penn State’s Center for Plant and Mushroom Foods for Health. The current study shows that EGCG may trigger a process in the mitochondria that leads to cell death.
“EGCG is doing something to damage the mitochondria and that mitochondrial damage sets up a cycle causing more damage and it spirals out, until the cell undergoes programmed cell death,” said Lambert. “It looks like EGCG causes the formation of reactive oxygen species in cancer cells, which damages the mitochondria, and the mitochondria responds by making more reactive oxygen species.”
As this mitochondrial demise continues, the cancer cell also reduces the expression of anti-oxidant genes, further lowering its defenses.
“So, it’s turning off its mechanism of protection at the same time that EGCG is causing this oxidative stress,” Lambert added.
The EGCG did not cause this reaction in normal cells. In fact, it appeared to increase the protective capabilities of the cell, according to the researchers, who report their findings in the online issue of Molecular Nutrition and Food Research.
The researchers studied normal human oral cells side-by-side with human oral cancer cells to determine how EGCG was affecting cancer cells differently than normal cells. They grew the normal and cancer cells on petri dishes and then exposed them to EGCG, the major polyphenol found in green tea, at concentrations typically found in the saliva after chewing green-tea chewing gum. At various times, the researchers would collect the cells and check for oxidative stress and signs of antioxidant response.
“We also took a lot of pictures, so we could use fluorescent dyes that measure mitochondrial function and oxidative stress and actually see these things develop,” said Lambert, who worked with Jong-Yung Park, a research technician and Ling Tao, a doctoral candidate in food science.
The researchers said that a protein called sirtuin 3 — SIRT3 — is critical to the process.
“It plays an important role in mitochondrial function and in anti-oxidant response in lots of tissues in the body, so the idea that EGCG might selectively affect the activity of sirtuin 3 in cancer cells — to turn it off — and in normal cells — to turn it on — is probably applicable in multiple kinds of cancers,” Lambert said.
The study builds on earlier research on how EGCG affected oral cancer, a disease that is expected to kill more than 8,000 people in the United States this year.
“We’ve published one paper previously just looking at the effect of these green tea polyphenols on oral cancer cells in cultures, and there have been other papers published using oral cancer cells and at least a couple of animal model studies that have looked at oral cancer and prevention of oral cancer,” said Lambert.
He said the next step would be to study the mechanism in animals. If those tests and human trials are successful, the researchers then hope to create anti-cancer treatments that are as effective as current treatments without the harmful side effects.
“The problem with a lot of chemotherapy drugs — especially early chemotherapy drugs — is that they really just target rapidly dividing cells, so cancer divides rapidly, but so do cells in your hair follicles and cells in your intestines, so you have a lot of side effects,” said Lambert. “But you don’t see these sorts of side effects with green tea consumption.”