CNO Report 186
Release Date 25 JUL 2014
Draft Report Compiled by
In This Issue:
- Acute glaucoma discovered to be an inflammatory disease
- Pre-diabetes label ‘unhelpful and unnecessary’
- Is it time to lock up those who commit research fraud?
- Fish oil supplements reduce incidence of cognitive decline, may improve memory function
- Potassium supplements may increase survival in patients taking diuretics for heart failure
- Genetic variations may modify cardiovascular benefit of aspirin
- Consuming probiotics for a month helps diminish fat accumulation in the liver, new study says
- How does L-carnitine maintain the normal structure of sciatic nerve in crush injury?
- In alcohol abusers, fish oil may reduce risk of neurodegeneration and ensuing dementia
- Lipoic acid helps restore, synchronize the “biological clock”
- Preventing foodborne illness, naturally — with cinnamon
- Eating probiotics regularly may improve your blood pressure
- Healing the heart with fat
- Iodine may alleviate swelling in retinitis pigmentosa patients’ retinas
- Ginkgo biloba enhances neurogenesis and improves recovery following a stroke in mice
- In asthma, it’s not just what you smell, but what you think you smell
- Rosemary and oregano contain diabetes-fighting compounds
- Melatonin reduces traumatic brain injury-induced oxidative stress
- Exposure to dim light at night may make breast cancers resistant to tamoxifen
- Natural products from plants protect skin during cancer radiotherapy
Acute glaucoma discovered to be an inflammatory disease
Researchers at the University of California, San Diego School of Medicine and Sun Yat-sen University in China have shown that acute glaucoma in mice is largely an inflammatory disease and that high pressure in the eye causes vision loss by setting in motion an inflammatory response similar to that evoked by bacterial infections.
The study, published in this week’s issue of the Proceedings of the National Academy of Sciences, has immediate clinical relevance in treating the tens of millions of people worldwide from what is known as acute closed-angle glaucoma.
“Our research is the first to show an inflammatory mechanism by which high ocular pressure causes vision loss in acute glaucoma patients,” said co-senior author Kang Zhang, MD, PhD and professor of ophthalmology.
The second leading cause of irreversible blindness globally, glaucoma refers to a group of eye diseases associated with elevated intraocular pressure broadly classified as either open-angle or closed-angle. Open-angle is sometimes called the silent thief of sight because of its slow, often overlooked progression. By contrast, acute closed-angle glaucoma often is a painful ophthalmologic emergency in which there is a sudden rise in eye pressure and immediate damage to eyesight.
Less than 10 percent of glaucoma patients in America have the closed-angle form, but in parts of Asia it accounts for almost half of all cases. The higher prevalence of closed-angle glaucoma in Asians and women is believed to be due to a shallower anterior (frontal) eye chamber.
In the study, researchers showed that a rapid, sustained large increase in eye pressure in mice turns on a gene (TLR4) that activates a protein known as caspase-8. This signaling protein in turn triggers the production of inflammatory proteins that normally help mammals fight microbial infections.
“This immune response is a double-edge sword because, while these proteins protect us from infection in a normal situation, they stimulate apoptosis (programmed cell death) in retinal cells in cases of acute glaucoma,” said Zhang, who is also a staff physician at the Veterans Affairs San Diego Healthcare System.
To further confirm the mechanism linking high eye pressure to retinal damage, researchers showed that they could slow retinal cell death in mice with acute glaucoma by suppressing either the TLR4 gene or caspace-8 protein.
The latter is particularly significant because caspace-8 inhibitors are currently in clinical trials for treating cancer and stroke. “By injecting these inhibitors into the eyes of acute glaucoma patients, it may be possible to evaluate and bring them vision-sparing treatments more quickly,” said co-author Robert N. Weinreb, MD, chairman and Distinguished Professor of Ophthalmology.
This study was funded by the National Natural Science Foundation of China.
Pre-diabetes label ‘unhelpful and unnecessary’
Labelling people with moderately high blood sugar as pre-diabetic is a drastically premature measure with no medical value and huge financial and social costs
Labelling people with moderately high blood sugar as pre-diabetic is a drastically premature measure with no medical value and huge financial and social costs, say researchers from UCL and the Mayo Clinic, Minnesota.
The analysis, published in the BMJ, considered whether a diagnosis of pre-diabetes carried any health benefits such as improved diabetes prevention. The authors showed that treatments to reduce blood sugar only delayed the onset of type 2 diabetes by a few years, and found no evidence of long-term health benefits.
Type 2 diabetes is typically diagnosed with a blood test that measures levels of haemoglobin A1c, which indicates average blood sugar level over the last three months. People with an A1c over 6.5% can be diagnosed with diabetes but the latest guidelines from the American Diabetes Association (ADA) define anyone with an A1c between 5.7% and 6.4% as having pre-diabetes.
If the ADA guidelines were adopted worldwide, a third of the UK adult population and more than half of adults in China would be diagnosed with pre-diabetes. The latest study questions the logic of putting a label on such huge sections of the population, as it could create significant burdens on healthcare systems without conferring any health benefits. Previous research has shown that type 2 diabetes treatments can do more harm than good for people with A1c levels around 6.5%, let alone people below this level.
3.2 million people in the UK are currently diagnosed with type 2 diabetes, but approximately 16 million would fall into the ADA’s pre-diabetes category. There is a condition known as impaired glucose tolerance (IGT) that affects around 3.7 million adults in the UK (8%). People with IGT are at high risk of diabetes, but the test is more time-consuming than a simple A1c blood test. There is evidence to suggest that interventions can delay the progression of IGT into diabetes, but the ADA category of pre-diabetes also includes another 12 million people who are at a much lower risk of progressing to diabetes, for whom any benefit from treatment is unknown.
The World Health Organisation (WHO) has stated that “use of ‘pre-diabetes’ is discouraged to avoid any stigma associated with the word diabetes and the fact that many people do not progress to diabetes as the term implies.” Guidance from the UK National Institute for Health and Care Excellence (NICE) broadly aligns with the WHO statement, looking to “move away from describing ‘pre-diabetes’ as a separate condition”. So in the way of official authoritative organisations, ADA is pretty much on its own in using this term. Yet it has caught on heavily in the global scientific literature and because of ethnic differences in A1c levels, it may be an even less valid category in other countries and demographics.
“Pre-diabetes is an artificial category with virtually zero clinical relevance,” says lead author John S Yudkin, Emeritus Professor of Medicine at UCL. “There is no proven benefit of giving diabetes treatment drugs to people in this category before they develop diabetes, particularly since many of them would not go on to develop diabetes anyway.
“Sensibly, the WHO and NICE and the International Diabetes Federation do not recognise pre-diabetes at present but I am concerned about the rising influence of the term. It has been used in many scientific papers across the world, and has been applied to a third of adults in the UK and half of those in China. We need to stop looking at this as a clinical problem with pharmaceutical solutions and focus on improving public health. The whole population would benefit from a more healthy diet and more physical activity, so it makes no sense to single out so many people and tell them that they have a disease.”
Previous studies have tested the effectiveness of giving people with IGT a drug called metformin, which is used to lower blood sugar in people with diabetes. The drug reduced the risk of developing diabetes by 31% over 2.8 years, probably by delaying its onset rather than by completely halting its development. But people who go on to develop diabetes are often treated with metformin anyway and there is no evidence of long-term benefits to starting the treatment early.
“The ADA recommends treating pre-diabetes with metformin, but the majority of people would receive absolutely no benefit,” explains Professor Yudkin. “There are significant financial, social and emotional costs involved with labelling and treating people in this way. And a range of newer and more expensive drugs are being explored as treatments for ‘pre-diabetes.’ The main beneficiaries of such recommendations would be the drug manufacturers, whose available market suddenly leaps to include significant swathes of the population. This is particularly true in emerging economies such as China and India, where regulating the healthcare market is a significant challenge.”
“Healthy diet and physical activity remain the best ways to prevent and to tackle diabetes,” says co-author Victor Montori, Professor of Medicine at the Mayo Clinic, Rochester, Minnesota, USA. “Unlike drugs they are associated with incredibly positive effects in other aspects of life. We need to keep making efforts to increase the overall health of the population, by measures involving public policy rather than by labelling large sub-sections of the population as having an illness. This is a not a problem to be solved at the bedside or in the doctor’s surgery, but rather by communities committed to the health of their citizens.”
Is it time to lock up those who commit research fraud?
Head to head: Should research fraud be a crime?
Dr Zulfiqar Bhutta, Robert Harding Chair in global child health and policy and Co-Director of the Centre for Global Child Health at the Hospital for Sick Children, Toronto believes that criminal sanctions are necessary to deter growing research misconduct.
He says the fact that research fraud is common is no longer news, but a review by PubMed in 2012 found that 67% of research article retractions were “attributable to scientific misconduct, including fraud or suspected fraud”.
Dr Bhutta says the consequences of research fraud on human health can be “huge” and that the damage to global vaccination coverage by Andrew Wakefield “has been incalculable”. Wakefield, however, lives a free man, “raking in money from various support groups.” Criminal proceedings after serious research fraud are rare with such practice being dealt with by institutions, he adds.
Although many think this is fair, given that it is hard to differentiate between fraud and incompetence, errors and misunderstanding, he argues that that “deliberate fraud is often prevalent.” Plus, investigations are often expensive, costing between $116,160 and $2,192,620 per case.
Current measures are not enough, he says. “Although many perpetrators of research fraud never return to academic life; others may claw their way back to active research.”
Bhutta concludes that although the costs of fraud are not known, “human, social and economic costs are likely considerable” and that “additional deterrence through punitive measures such as criminal proceedings should be added to the repertoire of measures available.”
He concludes that because consequences can be huge, “it is time to regard such behaviour in the same category as criminal fraud and deal with it accordingly.”
But Dr Julian Crane from the Department of Medicine at the University of Otago in New Zealand, argues that criminalisation would not have any deterrent effect and would undermine trust rather than improve it.
Crane says the former editor of The BMJ Richard Smith recently defined research misconduct as “the gentlemanly phrase for scientific fraud” and asks who “would not have fallen foul of this definition, so are we all fraudsters?”
Smith says research is “terrifyingly common” but only one in every 18,234 published abstracts are retracted because of real or suspected misconduct, which Crane adds “seems refreshingly small”.
Crane appreciates that research misconduct does cause harm, but asks “would inviting the police to investigate more satisfactorily uncover misconduct or prevent harm?”
He believes that it lies with research organisations to reduce opportunities for misconduct and investigate appropriately. He concludes that criminalising research misconduct “is a sad, bad, even mad idea that will only undermine the trust that is an essential component of research and requires good governance not criminal investigators.”
Fish oil supplements reduce incidence of cognitive decline, may improve memory function
Alzheimer’s disease affects more than 5 million each year in the US
PROVIDENCE, R.I. –Rhode Island Hospital researchers have completed a study that found regular use of fish oil supplements (FOS) was associated with a significant reduction in cognitive decline and brain atrophy in older adults. The study examined the relationship between FOS use during the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and indicators of cognitive decline. The findings are published online in advance of print in the journal Alzheimer’s & Dementia.
“At least one person is diagnosed every minute with Alzheimer’s disease (AD) and despite best efforts, we have not yet found a cure for this pervasive and debilitating disease,” said principal investigator Lori Daiello, PharmD, of the Alzheimer’s Disease and Memory Disorders Center at Rhode Island Hospital. “The field is currently engaged in numerous studies to find better treatments for people suffering with AD; however, researching ways to prevent AD or slow cognitive decline in normal aging is of utmost importance.”
In this retrospective study, older adults involved in the ADNI study were assessed with neuropsychological tests and brain magnetic resonance imaging (MRI) every six months. The group included 229 older adults who were cognitively normal; 397 who were diagnosed with mild cognitive impairment; and 193 with AD.
The study found that fish oil supplement use during the study was associated with significantly lower rates of cognitive decline as measured by the Alzheimer’s Disease Assessment Scale (ADAS-cog), and the Mini Mental State Exam (MMSE), but this benefit was observed only for the group of participants without dementia at the time of enrollment.
“Additionally, serial brain imaging conducted during this study showed that the participants with normal cognition who reported taking fish oil supplements demonstrated less brain shrinkage in key neurological areas, compared to those who did not use the supplements,” Daiello said. “Also, the positive findings on cognitive testing and brain MRI were only observed in persons who did not carry the best-studied genetic risk factor for AD, APOE-4. More research is needed, but these findings are promising and highlight the need for future studies to expand the current knowledge of the effects of FOS use on cognitive aging and AD.”
It is estimated that more than 5 million people in the U.S. have Alzheimer’s disease. It is the most common form of dementia and is the sixth leading cause of death in the U.S.
Potassium supplements may increase survival in patients taking diuretics for heart failure
Survival benefit increases with diuretic dosage
PHILADELPHIA—Researchers from the Perelman School of Medicine at the University of Pennsylvania found that patients taking prescription potassium supplements together with loop diuretics for heart failure have better survival rates than patients taking diuretics without the potassium. Moreover, the degree of benefit increases with higher diuretic doses. The team, including senior author Sean Hennessy, PharmD, PhD, associate professor of epidemiology in Penn’s Center for Clinical Epidemiology and Biostatistics (CCEB), report their findings in a study published online July 16 in PLOS ONE.
Loop diuretics—one type of diuretic or “water pill” named after the part of the kidney it acts on—are commonly used in the treatment of heart failure (and associated lower-limb edema or swelling) to help push out extra fluid that can accumulate when the heart is not working properly. But they also flush out needed potassium, causing many doctors, but not all, to prescribe the supplements. However, its survival benefit has never been studied, and because of this lack of evidence, there is controversy about whether potassium should be prescribed to all patients receiving loop diuretics.
In a retrospective study, the researchers examined existing health care data from Medicaid between 1999 and 2007 to study approximately 180,000 new starters of loop diuretics who were prescribed supplemental potassium and an equal number of people who started a loop diuretic without the potassium supplement. The researchers found that in patients receiving at least 40 mg/day of furosemide (one form of loop diuretic), adding supplemental potassium appeared to reduce mortality by 16 percent, a large and statistically significant reduction.
“Our findings provide evidence that adding potassium supplementation may increase survival rates among patients taking loop diuretics,” said the study’s lead author, Charles E. Leonard, PharmD, MSCE, a senior research investigator in the CCEB and senior manager of the Ambulatory Drug Use & Effects Program at Penn. “Nonetheless, because this is the first such study of this question, we hope that others confirm these results in independent studies.”
They also found that in patients receiving less than 40 mg/day of furosemide, potassium appeared to reduce the mortality rate by seven percent, a suggestive but statistically non-significant finding. (The overall mortality rate was about nine percent per year in the population under examination.)
The use of potassium supplementation under investigation was preventive, as opposed to being prescribed to patients who already had measured reductions in potassium. Only patients receiving supplemental potassium in solid, not liquid form, were studied, the latter possibly being indicative of an inability to swallow and therefore a marker for a possibly complicating corollary medical impairment.
Loop diuretics act at the ascending loop of Henle in the kidney and help the body push out extra fluid that could accumulate in the lungs or legs and ankles when the heart is unable to completely pump blood throughout the body. But they may also cause the body to eliminate excessive amounts of potassium, which might be expected to increase mortality from heart arrhythmias. As a precaution therefore, many doctors prescribe potassium supplements to their patients receiving loop diuretics.
These results appear to support the common (but not universal) practice of using potassium together with loop diuretics. Today, nearly 5.8 million Americans suffer from heart failure.
“Using potassium supplementation for patients receiving loop diuretic therapy may be a relatively inexpensive way to save lives,” said Hennessy. “In today’s climate of seeking cost-effective measures to keep patients healthy, this is a therapy that certainly merits additional consideration.”
Genetic variations may modify cardiovascular benefit of aspirin
BOSTON – Aspirin is the gold standard for antiplatelet therapy and a daily low-dose aspirin is widely prescribed for the prevention of cardiovascular disease.
Now, a new study suggests that common genetic variation in the gene for catechol-O-methyltransferase (COMT) may modify the cardiovascular benefit of aspirin, and in some people, may confer slight harm. The findings, led by investigators at Beth Israel Deaconess Medical Center (BIDMC) and Brigham and Women’s Hospital (BWH) appear online in the American Heart Association journal Arteriosclerosis, Thrombosis, and Vascular Biology.
“This is one of the few cases where you can identify a single genetic polymorphism which has a significant interaction with aspirin such that it affects whether or not it protects against cardiovascular disease,” says first author Kathryn Hall, PhD, MPH, an investigator in the Division of General Medicine and Primary Care at BIDMC and Research Fellow at Harvard Medical School.
COMT is a key enzyme in the metabolism of catecholamines, a group of hormones that include epinephrine, norepinephrine, and dopamine. “These hormones are implicated in a broad spectrum of disorders, including hypertension,” explains Hall, “We were initially interested in finding out if the COMT gene affected people’s susceptibility to incident cardiovascular disease such as myocardial infarction or ischemic stroke.” Knowing that aspirin is commonly prescribed for the prevention of incident cardiovascular disease, the investigators also wanted to learn if genetic variation in COMT would influence aspirin’s potential benefit.
To answer these questions, the researchers used data from the Women’s Genome Health Study, a cohort of over 23,000 women who were followed for 10 years in a randomized double-blind, placebo-controlled trial of low-dose aspirin or vitamin E for the primary prevention of incident cardiovascular disease. Their analysis focused on val158met, a common variant in the COMT gene: Individuals who are homozygous for the enzyme’s high-activity valine form, the “val/vals,” have been shown to have lower levels of catecholamines compared to individuals who are homozygous for the enzyme’s low-activity methionine form, the “met/mets,”. The val/met heterozygotes are in between.
“When we examined women in the placebo arm of the trial, we found that the 23 percent of the women who were ‘val/vals’ were naturally protected against incident cardiovascular disease,” explains senior author Daniel I. Chasman, PhD, a genetic epidemiologist in the Division of Preventive Medicine at Brigham and Women’s Hospital and Associate Professor of Medicine at Harvard Medical School. “This finding, which was replicated in two other population-based studies, was in itself of significant interest.” But, he adds, the investigation further revealed the surprising discovery that when the women with the val/val polymorphism were allocated to aspirin, this natural protection was eliminated.
“As we continued to look at the effects of drug allocation, we found that val/val women who were randomly assigned to aspirin had more cardiovascular events than the val/vals who were assigned to placebo,” says Chasman. Among the 28 percent of women who were met/met, the opposite was true, and these women had fewer cardiovascular events when assigned to aspirin compared to placebo. The benefit of aspirin compared to placebo allocation for met/mets amounted to reduction of one case of incident cardiovascular disease for 91 treated women over 10 years of study follow-up. By contrast, the harm of aspirin compared to placebo allocation for the val/val women was an increase of one case per 91 treated.
The researchers further found that rates of cardiovascular disease were also reduced in met/met women assigned to vitamin E compared to those assigned to placebo.
The authors stress that the findings will require further research and replication to understand their potential for clinical impact. Nonetheless they note that given that aspirin is preventively prescribed to millions of individuals and the COMT genetic variant is extremely common, this study underscores the potential importance of individualizing therapies based on genetic profiles.
“What this study suggests is that we can be smarter about the groups of patients that would most likely benefit from aspirin,” says study coauthor Joseph Loscalzo, MD, PhD, Chairman of the Department of Medicine and Physician-in-Chief at BWH. “Rather than give aspirin to all patients with risk factors for heart disease, we need to use modern genomics and genetics to identify those individuals for whom aspirin has the greatest benefit and the lowest risk of adverse effects.”
One possible reason for the val/val protection could lie in COMT’s role in the breakdown of epinephrine, the “fight or flight” hormone which is tightly linked to regulation of the cardiovascular system.
“When epinephrine levels rise in response to stress, blood pressure goes up and high blood pressure is a precursor to heart disease,” explains Hall. “One possibility is that val/val individuals have less epinephrine than met/met individuals because their COMT is more efficient at breaking it down. This might help to naturally protect them against cardiovascular disease – that’s our working hypothesis. It’s harder to explain why the effect is modified by aspirin and that’s what we’re in the lab aggressively trying to figure out.”
Consuming probiotics for a month helps diminish fat accumulation in the liver, new study says
Scientists at the University of Granada have made important strides in the fight against the Non-Alcoholic Fatty Liver Disease, which is closely related to obesity and diabetes
Spanish scientists have demonstrated through an experiment on obese rats that the consumption of probiotics during thirty days helps diminish the accumulation of fat in the liver. This new finding, published today by the journal PLOS ONE, is a great step forward on the fight agains the Non-Alcolohic Fatty Liver Disease (NAFLD), which is closely related to obesity and diabetes.
Researchers from the ‘Nutrition Biochemistry: Theurapetic Applications’ group (CTS-461) and the José Mataix Institute for Nutrition and Food Technology at the University of Granada have demonstrated that the administration of three probiotic strains diminishes the accumulation of fat in the liver of obese rats.
The accumulation of fat in the liver is called steatosis and it constitutes the first stage in the NAFLD disease, which is closely related to obesity and diabetes. Given that the prevalence of these two pathologies does not cease to increase, NAFLD has also become a health problem that affects millions of people throughout the world.
Living or dead microorganisms
Probiotics are microorganisms (bacteria or yeasts) with healthy effects upon individuals that consume them in adequate doses. They were traditionally considered to be living microorganisms, but the concept was widened since some dead microorganisms, or even their components, can display probiotic properties.
University of Granada researchers worked with three strains which are custodied at the Collection Nationale de Cultures de Microorganismes (CNCM) of the Pasteur Institute: Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036. During their first experiment, conducted on healthy volunteers, researchers demonstrated that all three of them are perfectly tolerable and safe for human consumption.
In this current study, the strains were administered during thirty days in the diet of Zucker rats. These rats develop obesity due to a mutation in the gene that codifies the receptor or leptine, a homone that transmits a sensation of satiety to the organism. Zucker rats are among the best characterized genetic models.
In their article, the authors describe that the administration of probiotics led to an accumulation of lipids (most of them triacylglycerides) in the liver which was significantly lower than that occurring in rats fed with a placebo.
“This new finding went hand in hand with lower values in proinflamatory molecules (tumor-a necrosis factor, interleukin 6 and liposacarid) in the serum of rats fed with probiotics. These effects were not observed in those
According to these researchers, this liver disease will not be cured with probiotics, but these microorganisms can certainly be used as support therapy in joint use with other treatment.
How does L-carnitine maintain the normal structure of sciatic nerve in crush injury?
Several studies have demonstrated that L-carnitine exhibits neuroprotective effects on injured sciatic nerve of rats with diabetes mellitus. Dr. Ümmü Zeynep Avsar, Faculty of Medicine, Ataturk University, Turkey and his team proposed a hypothesis that L-carnitine exhibits neuroprotective effects on injured sciatic nerve of rats. Rat sciatic nerve was crush injured by a forceps and exhibited degenerative changes. After intragastric administration of 50 and 100 mg/kg L-carnitine for 30 days, axon area, myelin sheath area, axon diameter, myelin sheath diameter, and numerical density of the myelinated axons of injured sciatic nerve were similar to normal, and the function of injured sciatic nerve also improved significantly. These findings suggest that L-carnitine exhibits neuroprotective effects on sciatic nerve crush injury in rats. This paper was published in Neural Regeneration Research (Vol. 9, No. 10, 2014).
In alcohol abusers, fish oil may reduce risk of neurodegeneration and ensuing dementia
MAYWOOD, Ill– Omega-3 fish oil might help protect against alcohol-related neurodamage and the risk of eventual dementia, according to a study published in the journal PLOS ONE.
Many human studies have shown that long-term alcohol abuse causes brain damage and increases the risk of dementia. The new study found that in brain cells exposed to high levels of alcohol, a fish oil compound protected against inflammation and neuronal cell death.
The study was conducted by Michael A. Collins, PhD, Edward J. Neafsey, PhD, and colleagues at Loyola University Chicago Stritch School of Medicine, and collaborators at the University of Kentucky and the National Institute of Alcohol Abuse and Alcoholism (NIAAA).
Collins and colleagues exposed cultures of adult rat brain cells over several days to concentrations of alcohol equivalent to about four times the legal limit for driving – a concentration seen in chronic alcoholics. These brain cultures were compared with cultures exposed to the same high levels of alcohol, plus a compound found in fish oil called omega-3 docosahexaenoic acid (DHA).
Researchers found there was up to 90 percent less neuroinflammation and neuronal death in the brain cells exposed to alcohol plus DHA than in the cells exposed to alcohol alone.
An earlier meta-analysis by Collins and Neafsey, which pooled the results of about 75 studies, found that moderate social drinking may have the opposite effect of reducing the risk of dementia and/or cognitive impairment during aging. (Moderate drinking is defined as a maximum of two drinks per day for men and 1 drink per day for women.)
It appears that limited amounts of alcohol might, in effect, tend to make brain cells more fit. Alcohol in moderate amounts stresses cells and thus toughens them up to cope with major stresses and insults down the road that could cause dementia. But too much alcohol overwhelms the cells, leading to neuroinflammation and cell death.
Further studies are needed to confirm whether fish oil protects against alcohol-related cognitive injury and dementia in adult rodent models. “Fish oil has the potential of helping preserve brain integrity in chronic alcohol abusers,” Collins said. “At the very least, it is unlikely that it would hurt them.”
But Collins added that the best way for an alcohol abuser to protect the brain is to cut back to low or moderate amounts or quit entirely. “We don’t want people to think it is okay to take a few fish oil capsules and then continue to go on abusing alcohol,” he said.
Lipoic acid helps restore, synchronize the “biological clock”
CORVALLIS, Ore. – Researchers have discovered a possible explanation for the surprisingly large range of biological effects that are linked to a micronutrient called lipoic acid: It appears to reset and synchronize circadian rhythms, or the “biological clock” found in most life forms.
The ability of lipoic acid to help restore a more normal circadian rhythm to aging animals could explain its apparent value in so many important biological functions, ranging from stress resistance to cardiac function, hormonal balance, muscle performance, glucose metabolism and the aging process.
The findings were made by biochemists from the Linus Pauling Institute at Oregon State University, and published in Biochemical and Biophysical Research Communications, a professional journal. The research was supported by the National Institutes of Health, through the National Center for Complementary and Alternative Medicine.
Lipoic acid has been the focus in recent years of increasing research by scientists around the world, who continue to find previously unknown effects of this micronutrient. As an antioxidant and compound essential for aerobic metabolism, it’s found at higher levels in organ meats and leafy vegetables such as spinach and broccoli.
“This could be a breakthrough in our understanding of why lipoic acid is so important and how it functions,” said Tory Hagen, the Helen P. Rumbel Professor for Healthy Aging Research in the Linus Pauling Institute, and a professor of biochemistry and biophysics in the OSU College of Science.
“Circadian rhythms are day-night cycles that affect the daily ebb and flow of critical biological processes,” Hagen said. “The more we improve our understanding of them, the more we find them involved in so many aspects of life.”
Almost one-third of all genes are influenced by circadian rhythms, and when out of balance they can play roles in cancer, heart disease, inflammation, hormonal imbalance and many other areas, the OSU researchers said.
Of particular importance is the dysfunction of circadian rhythms with age.
“In old animals, including elderly humans, it’s well-known that circadian rhythms break down and certain enzymes don’t function as efficiently, or as well as they should,” said Dove Keith, a research associate in the Linus Pauling Institute and lead author on this study.
“This is very important, and probably deserves a great deal more study than it is getting,” Keith said. “If lipoic acid offers a way to help synchronize and restore circadian rhythms, it could be quite significant.”
In this case the scientists studied the “circadian clock” of the liver. Lipid metabolism by the liver is relevant to normal energy use, metabolism, and when dysfunctional can help contribute to the “metabolic syndrome” that puts millions of people at higher risk of heart disease, diabetes and cancer.
Researchers fed laboratory animals higher levels of lipoic acid than might be attained in a normal diet, while monitoring proteins known to be affected by disruption of the circadian clock in older animals.
They found that lipoic acid helped remediate some of the liver dysfunction that’s often common in old age, and significantly improved the function of their circadian rhythms.
In previous research, scientists found that the amount of lipoic acid that could aid liver and normal lipid function was the equivalent of about 600 milligrams daily for a 150-pound human, more than could normally be obtained through the diet.
A primary goal of research in the Linus Pauling Institute and the OSU Center for Healthy Aging Research is to promote what scientists call “healthspan” – not just the ability to live a long life, but to have comparatively good health and normal activities during almost all of one’s life. Research on lipoic acid, at OSU and elsewhere, suggests it has value toward that goal.
Continued research will explore this process and its role in circadian function, whether it can be sustained, and optimal intake levels that might be needed to improve health.
Preventing foodborne illness, naturally — with cinnamon
Essential oil kills several strains of E. coli
PULLMAN, Wash. – Seeking ways to prevent some of the most serious foodborne illnesses caused by pathogenic bacteria, two Washington State University scientists have found promise in an ancient but common cooking spice: cinnamon.
Recent findings published in Food Control journal online suggest Cinnamomum cassia oil can work effectively as a natural antibacterial agent in the food industry. The study results add to a body of knowledge that will help improve food safety and reduce or eliminate cases of food poisoning and related deaths.
In the study, the essential oil killed several strains of Shiga toxin-producing Escherichia coli (E. coli), known to the U.S. Centers for Disease Control and Prevention as “non-O157 STEC.” The study looked at the top six strains of non-O157 STEC, said co-author Lina Sheng, a graduate student in the School of Food Science.
The cinnamon cassia oil is effective in low concentrations, she said – about 10 drops diluted in a liter of water killed the bacteria within 24 hours.
Demand for natural food additives
Rising health concerns about chemical additives have strengthened demand for natural food additives, said co-author Meijun Zhu, an assistant professor in the School of Food Science.
“Our focus is on exploring plant-derived natural food bioactive compounds as antimicrobials to control foodborne pathogens, in order to ensure safety of fresh produce,” she said.
Sheng said about 110,000 cases of illness are caused annually by non-O157 STEC.
The U.S. Department of Agriculture Food Safety and Inspection Service has a “zero tolerance” policy for the CDC top six non-O157 STECs in raw ground beef and trimmings, indicating any raw non-intact beef products containing these pathogens will be considered adulterated. This has led Zhu and Sheng to include the beef industry in the large-scale application of their findings on cinnamon.
“The oil can be incorporated into films and coatings for packaging both meat and fresh produce,” Sheng said. “It can also be added into the washing step of meat, fruits or vegetables to eliminate microorganisms.”
Cassia cinnamon is produced primarily in Indonesia and has a stronger smell than the other common cinnamon variety, Ceylon.
In addition to Cinnamomum cassia oil, Sheng plans to take a look at another natural source to kill bacteria. She and her coworkers will study the potential of dandelions to inhibit bacteria related to bovine mastitis, an infection in the mammary glands of dairy cows.
Eating probiotics regularly may improve your blood pressure
American Heart Association Rapid Access Journal Report
Eating probiotics regularly may modestly improve your blood pressure, according to new research in the American Heart Association journal Hypertension.
Probiotics are live microorganisms (naturally occurring bacteria in the gut) thought to have beneficial effects; common sources are yogurt or dietary supplements.
“The small collection of studies we looked at suggest regular consumption of probiotics can be part of a healthy lifestyle to help reduce high blood pressure, as well as maintain healthy blood pressure levels,” said Jing Sun, Ph.D., lead author and senior lecturer at the Griffith Health Institute and School of Medicine, Griffith University, Gold Coast, Queensland, Australia. “This includes probiotics in yogurt, fermented and sour milk and cheese, and probiotic supplements.”
Analyzing results of nine high-quality studies examining blood pressure and probiotic consumption in 543 adults with normal and elevated blood pressure, researchers found:
- Probiotic consumption lowered systolic blood pressure (the top number) by an average 3.56 millimeters of mercury (mm Hg) and diastolic blood pressure (the lower number) by an average 2.38 mm Hg, compared to adults who didn’t consume probiotics.
- The positive effects from probiotics on diastolic blood pressure were greatest in people whose blood pressure was equal to or greater than 130/85, which is considered elevated.
- Consuming probiotics for less than eight weeks didn’t lower systolic or diastolic blood pressure.
- Probiotic consumption with a daily bacteria volume of 109-10 12 colony-forming units (CFU) may improve blood pressure. Consumption with less than 109 CFU didn’t lower blood pressure. CFU is the amount of bacteria or the dose of probiotics in a product.
- Probiotics with multiple bacteria lowered blood pressure more than those with a single bacteria.
“We believe probiotics might help lower blood pressure by having other positive effects on health, including improving total cholesterol and low-density lipoprotein, or LDL, cholesterol; reducing blood glucose and insulin resistance; and by helping to regulate the hormone system that regulates blood pressure and fluid balance,” Sun said.
“The studies looking at probiotics and blood pressure tend to be small,” Sun said. “Moreover, two studies had a short duration of three to four weeks of probiotic consumption, which might have affected the overall results of the analysis.
Additional studies are needed before doctors can confidently recommend probiotics for high blood pressure control and prevention, she said.
Healing the heart with fat
Too much dietary fat is bad for the heart, but the right kind of fat keeps the heart healthy, according to a paper published in The Journal of Experimental Medicine.
Unsaturated dietary fatty acids, such as eicosapentaenoic acid (EPA), are known to protect against cardiovascular diseases. However, the mechanism and the specific fat metabolites responsible for this protection were unknown.
A group of Japanese scientists now show that mice engineered to produce their own EPA are protected against heart disease and have improved cardiac function. One particular EPA metabolite, called 18-hydroxyeicosapentaenoic acid (18-HEPE), was required for this protection. 18-HEPE was produced by immune cells called macrophages, which dampened inflammation and fibrosis in the heart. Treatment with 18-HEPE confirmed its heart-protective effects.
A diet enriched in 18-HEPE might thus help prevent heart failure in patients with cardiovascular diseases.
Iodine may alleviate swelling in retinitis pigmentosa patients’ retinas
Findings online in JAMA Ophthalmology
Boston – Cystoid macular edema (CME) is a common complication of retinitis pigmentosa (RP), a family of retinal diseases in which patients typically lose night and side vision first and then develop impaired central vision. CME can also decrease central vision. Current treatments for CME in RP are not always effective and can lead to adverse results.
Researchers from the Massachusetts Eye and Ear, Harvard Medical School, and Boston University School of Medicine tested whether the extent of retinal swelling due to CME was inversely related to dietary iodine intake in patients with RP and found that it was. This finding raises the possibility that an iodine supplement could help limit or reduce central foveal swelling in RP patients with CME. Their results are presented online in the July issue of JAMA Ophthalmology.
Past research performed on a previous population showed an inverse association between the presence of CME and reported iodine supplementation in RP patients. This finding and physiology research by others pointed to iodine as being worth investigating further. In the present experiment, the researchers performed a cross-sectional observational study of 212 nonsmoking patients 18 to 69 years of age who were referred to Mass. Eye and Ear for RP with visual acuity of no worse than 20/200 in at least one eye. They used optical coherence tomography to measure central foveal swelling due to CME in the patients. Total dietary intake of iodine was estimated from multiple (preferably, 10) spot urine samples collected at home.
The investigators found that the magnitude of central foveal swelling due to CME was inversely related to urinary iodine concentration when emphasizing data with more reproducible urinary iodine concentrations (p<.001) — patients with the lowest urinary iodine levels tended to have retinas with the most swelling.
“Additional study is required to determine whether an iodine supplement can limit or reduce the extent of CME in patients with RP,” said Michael A. Sandberg, Ph.D., lead author of the study and senior scientist in the Berman-Gund Laboratory for the Study of Retinal Degenerations at Massachusetts Eye and Ear and Associate Professor of Ophthalmology at Harvard Medical School.
Ginkgo biloba enhances neurogenesis and improves recovery following a stroke in mice
Led by Dr. Zahoor A. Shah, Dr. Shadia E. Nada and Jatin Tulsulkar (graduate student), researchers at the University of Toledo, Toledo, OH, have discovered that mice treated with Ginkgo biloba 4 hours after inducing experimental stroke and then daily for seven days had improved recovery and less brain damage than the control mice. It was also observed that Ginkgo biloba treated mice had enhanced neurogenesis, partly due to the increased protein expression of hemeoxygenase 1, an antioxidant gene that also has a role in neurogenesis. Pertinently, mice lacking the hemeoxygenase 1 gene were observed to have reduced neurogenesis after stroke.
Besides prevention, improving recovery following a stroke should become the prime focus of current stroke research. We now know that neurogenesis is not only an ongoing process in adults, but can also be induced by pathological conditions like traumatic brain injury and ischemic stroke, and strategies that promote endogenous neurogenesis as part of repair and regeneration process should be prioritized. Neurogenesis in the adult brain involves not only the proliferation and migration of precursor cells known as stem cells/neural progenitor cells (NSCs) but also their functional integration into the neural network. Ischemia, though a potent inducer of proliferation and migration of NSCs, does not provide an environment conducive to their survival, differentiation and integration, and creating an environment with exogenous drugs is paramount to improving the number of NSCs that can result in improved brain repair and regeneration.
The study, first reported in Molecular Neurobiology (Vol. 49, 2014) and then reviewed in Neural Regeneration Research (Vol. 9, No.11, 2014), confirmed that Ginkgo biloba, in addition to its antioxidant, neuritogenic and angiogenic properties, provides a conducive environment for the survival and functional integration of NSCs into neural system.
“Controversies and other ethical issues related to stem cell therapies make drug-induced enhanced neurogenesis a promising treatment strategy,” stressed senior author Zahoor A. Shah. “Besides one documented clinical trial recommending the use of Ginkgo biloba after ischemic stroke, further high quality and large-scale randomized controlled trials are warranted to test its efficacy in stroke recovery” he said.
In asthma, it’s not just what you smell, but what you think you smell
Cognitive expectations about odor safety related to airway inflammation
PHILADELPHIA (July 22, 2014) – New research from the Monell Center reveals that simply believing that an odor is potentially harmful can increase airway inflammation in asthmatics for at least 24 hours following exposure. The findings highlight the role that expectations can play in health-related outcomes.
“Asthmatics often are anxious about scents and fragrances. When we expect that an odor is harmful, our bodies react as if that odor is indeed harmful,” said study lead author Cristina Jaén, PhD, a Monell physiologist. “Both patients and care providers need to understand how expectations about odors can influence symptoms of the disease.”
Asthma is a chronic inflammatory disorder of the lungs. According to the National Institutes of Health, over 25 million Americans have the disease, which can interfere with quality of life. The airways of asthmatics are sensitive to ‘triggers’ that further inflame and constrict the airways, making it difficult to breathe. There are many different types of triggers, including pollen, dust, irritating chemicals, and allergens. Strong emotions and stress also can act to trigger asthma symptoms.
Because asthma has no cure, it is important for individuals with the disease to understand how to manage their symptoms to help prevent severe asthma attacks.
Many health organizations list scents and fragrances as asthma triggers, leading patients to become anxious when exposed to environmental odors. The current research was conducted to determine whether odor-triggered asthma symptoms can be elicited or worsened by associated negative expectations.
In the study, published online ahead of print in the Journal of Psychosomatic Research, 17 individuals characterized as moderate asthmatics were exposed to the odor phenylethyl alcohol (PEA) for 15 minutes. Often described as rose-smelling, PEA is regarded as a ‘pure’ odorant with no associated physiological irritant qualities.
Eight subjects were told that the odor had potential therapeutic properties, while nine were told that it potentially could cause mild respiratory problems.
During odor presentation, the subjects rated the odor’s sensory properties, including intensity, irritancy, and annoyance. Measures of lung function and airway inflammation were collected before and immediately after exposure and again at two hours and 24 hours post-exposure.
Subjects’ beliefs about the odor, specifically whether it was potentially harmful (asthma-triggering) or therapeutic, influenced both their psychological and physiological responses to odor exposure.
Individuals who were told that the odor was potentially harmful rated it as more irritating and annoying as compared to those who thought it might be therapeutic.
In addition, airway inflammation increased immediately following odor exposure in subjects who believed the odor might be harmful and remained elevated 24 hours later.
“Introducing a negative bias led to a rapid change in airway inflammation,” said senior author Pamela Dalton, PhD, a cognitive psychologist at Monell. “What really surprised us was that this response lasted for over 24 hours. The increased inflammation during this period likely makes asthmatics more sensitive to other triggers.”
There was no increase of inflammation when the odor was characterized as therapeutic, even in individuals who described themselves as sensitive to perfumes and other odors.
The findings suggest that some fragrance effects on asthma symptoms may be related to the expectation of harm as opposed to chemical properties of the odor.
“It’s not just what you smell, but also what you think you smell,” said Jaén.
Looking forward, the researchers want to identify the biological mechanisms that connect expectations to airway inflammation. They also intend to explore whether a reverse phenomenon also exists. Dalton asks, “Can we improve health outcomes by reducing concern or fear in a disease where emotional arousal is counter-productive?”
Rosemary and oregano contain diabetes-fighting compounds
The popular culinary herbs oregano and rosemary are packed with healthful compounds, and now lab tests show they could work in much the same way as prescription anti-diabetic medication, scientists report. In their new study published in ACS’ Journal of Agricultural and Food Chemistry, they found that how the herbs are grown makes a difference, and they also identified which compounds contribute the most to this promising trait.
Elvira Gonzalez de Mejia and colleagues point out that in 2012, type-2 diabetes affected more than 8 percent of Americans and cost the country $175 billion. Some people can manage the disease with exercise and changes to their diet, and others take medication. But not everyone can stick to a new lifestyle or afford the prescription drugs necessary to keep their blood-sugar level in check. Recent research has shown that herbs could provide a natural way to help lower glucose in blood. So Gonzalez de Mejia’s team decided to take a closer look.
They tested four different herbs, either greenhouse-grown or dried commercial versions, for their ability to interfere with a diabetes-related enzyme, which is also a target of a prescription drug for the disease.
They found that greenhouse herbs contained more polyphenols and flavonoids compared to the equivalent commercial herbs. But this didn’t affect the concentration required to inhibit the enzyme. Commercial extracts of Greek oregano, Mexican oregano and rosemary were better inhibitors of the enzyme, required to reduce risk of type-2 diabetes, than greenhouse-grown herbs. The researchers say more studies are needed to understand the role of these compounds in reducing the risk of type-2 diabetes in humans.
Melatonin reduces traumatic brain injury-induced oxidative stress
Traumatic brain injury can cause post-traumatic neurodegenerations with an increase in reactive oxygen species and reactive oxygen species-mediated lipid peroxidation. Melatonin, a non-enzymatic antioxidant and neuroprotective agent, has been shown to counteract oxidative stress-induced pathophysiologic conditions like cerebral ischemia/reperfusion injury, neuronal excitotoxicity and chronic inflammation. Therefore, the research team at the Neuroscience Research Center, University of Suleyman Demire, led by Prof. Mustafa Nazıroğlu, aimed to evaluate whether there would be a protective effect of melatonin on oxidative stress and enzymatic and non-enzymatic antioxidant levels in traumatic brain injury rats. Their study released in the Neural Regeneration Research (Vol. 9, No. 11, 2014) have revealed that the cerebral cortex β-carotene, vitamin C, vitamin E, reduced glutathione, and erythrocyte reduced glutathione levels, and plasma vitamin C level were decreased by traumatic brain injury whereas they were increased following melatonin treatment. In conclusion, melatonin seems to have protective effects on traumatic brain injury-induced cerebral cortex and blood toxicity by inhibiting free radical formation and supporting antioxidant vitamin redox system.
Natural products from plants protect skin during cancer radiotherapy
Radiotherapy for cancer involves exposing the patient or their tumor more directly to ionizing radiation, such as gamma rays or X-rays. The radiation damages the cancer cells irreparably. Unfortunately, such radiation is also harmful to healthy tissue, particularly the skin over the site of the tumor, which is then at risk of hair loss, dermatological problems and even skin cancer. As such finding ways to protect the overlying skin are keenly sought.
Writing in the International Journal of Low Radiation, Faruck Lukmanul Hakkim of the University of Nizwa, Oman and Nagasaki University, Nagasaki, Japan, and colleagues there and at Macquarie University, New South Wales, Australia, Bharathiar University, India and Konkuk University, South Korea, explain how three ubiquitous and well-studied natural products derived from plants can protect the skin against gamma radiation during radiotherapy.
Hakkim and colleagues discuss the benefits of the organic, antioxidant compounds caffeic acid (CA), rosmarinic acid (RA) and trans-cinnamic acid (TCA) used at non-toxic concentrations. They tested the radio protective effect of these compounds against gamma-radiation in terms of reducing levels of reactive oxygen species generated in skin cells by clinical relevance dose of gamma ray in the laboratory and in terms of the damage to the genetic material DNA, specifically double strand breaks in laboratory samples of human skin cells (keratinocytes). They found that treating the human skin cells with CA, RA and TCA can protected the cells by 40, 20 and 15 percent respectively from gamma ray toxicity. They suggest that the protective effect arises because the compounds mop up the reactive oxygen species and chemically deactivate them as well as enhancing the body’s natural DNA repair mechanisms.
The team suggests that these compounds might best be used as skin protectants during combination chemo- and radio-therapy. Further work is under way to investigate the clinical potential of mixtures of the three natural products.
Exposure to dim light at night may make breast cancers resistant to tamoxifen
Animal study shows suppressed production of melatonin
PHILADELPHIA — For rats bearing human breast tumors, exposure to dim light at night made the tumors resistant to the breast cancer drug tamoxifen, according to data published in Cancer Research, a journal of the American Association for Cancer Research. The negative effects of dim light exposure on tamoxifen treatment were overcome by giving rats a melatonin supplement during the night.
“Resistance to tamoxifen is a growing problem among patients with hormone receptor-positive breast cancer,” said Steven M. Hill, PhD, professor of structural and cellular biology and the Edmond and Lily Safra chair for breast cancer research at Tulane University School of Medicine in New Orleans. “Our data, although they were generated in rats, have potential implications for the large number of patients with breast cancer who are being treated with tamoxifen, because they suggest that nighttime exposure to light, even dim light, could cause their tumors to become resistant to the drug by suppressing melatonin production.
“Our study does not identify how much light exposure is needed to suppress nighttime melatonin production, and potentially drive tamoxifen resistance in humans, but we think that it could be as a little as the amount of light that comes in the bedroom window from a street light,” continued Hill, who is also director of the Tulane Center for Circadian Biology. “We are working toward conducting the studies that will answer this question.
“Although melatonin supplements are readily available over the counter at most drug and health-food stores, our research is not at a point where we can make a general recommendation that breast cancer patients taking tamoxifen should go out and buy melatonin,” Hill added. “Melatonin is produced by our bodies at a very specific time of day, exclusively during darkness at night, and taking melatonin supplements at the wrong time of day would potentially disrupt the circadian system, particularly the natural melatonin cycle, which may, in itself, paradoxically impair breast cancer responsiveness to tamoxifen.”
For the study, Hill and colleagues analyzed rats living in either normal light/dark conditions, with 12 hours of light followed by 12 hours of complete darkness, or conditions in which there were 12 hours of normal light followed by 12 hours of dim light. Melatonin levels in the blood of rats living in normal light/dark conditions rose during the dark period before decreasing again during the light period. In rats living in the dim night light conditions, melatonin levels remained low throughout the light/dark cycle.
Tumor growth in rats living in the dim night light conditions was 2.6-fold faster compared with tumor growth in rats living in normal light/dark conditions. In addition, tumors in rats living in dim night light conditions were completely resistant to tamoxifen, whereas tumors in rats living in normal light/dark conditions regressed significantly. If rats living in dim night light conditions were given a nighttime melatonin supplement, their tumors regressed.
“These data suggest that, in the not-too distant-future, it may be possible to combine melatonin and tamoxifen,” said Hill. “However, before this is done we would need to identify the optimal times of day to give the two because if the timing between the two is off, the advantage of giving them in combination may be lost. This brings up another important point: Our levels of melatonin are not determined by sleep, as many people think. It is actually the darkness that is important. During the night, if you sleep in a brightly lit room, your melatonin levels may be inhibited; however, if you are in the dark but cannot sleep, your melatonin levels will rise normally.”
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