176 – 07 MAR 2014 Compiled by Ralph Turchiano
• Detailed research references and further affiliations on each article are posted at http://www.healthreserachreport.me .
In this issue:
- Abdominal fat accumulation prevented by unsaturated fat
- Study examines acetaminophen use in pregnancy, child behavioral problems
- Vinegar kills tuberculosis and other mycobacteria
- PFC exposure may spark metabolic changes in overweight children
- Psychological side-effects of anti-depressants worse than thought
- Vitamin A may help boost immune system to fight tuberculosis
- Ordinary conditioner removes head lice eggs as effectively as special products
- Suicide in apparently well-functioning young men
- Don’t throw out old, sprouting garlic — it has heart-healthy antioxidants
- Ancient Chinese medicine put through its paces for pancreatic cancer
- Plant extract offers hope for infant motor neuron therapy
- Study shows nearly fivefold increased risk for heart attack after angry outburst
- Screening does not shift breast cancer to earlier stages
- Hop leaves — discarded in beer brewing — have substances that could fight dental diseases
- Calcium and vitamin D improve cholesterol in postmenopausal women
- Study suggests higher levels of omega-3 in diet are associated with better sleep
- Vitamin D increases breast cancer patient survival
Abdominal fat accumulation prevented by unsaturated fat
New research from Uppsala University shows that saturated fat builds more fat and less muscle than polyunsaturated fat. This is the first study on humans to show that the fat composition of food not only influences cholesterol levels in the blood and the risk of cardiovascular disease but also determines where the fat will be stored in the body. The findings have recently been published in the American journal Diabetes.
The study involved 39 young adult men and women of normal weight, who ate 750 extra calories per day for seven weeks. The goal was for them to gain three per cent of their starting weight. The project received considerable attention when it started in 2011, partly because the extra calories were ingested in the form of muffins with high fat content, baked in the lab by Fredrik Rosqvist, a doctoral candidate and first author of the study.
One half of the subjects were random to eat surplus calories from polyunsaturated fat (sunflower oil), while the other half got their surplus calories from saturated fat (palm oil). Both diets contained the same amount of sugar, carbohydrates, fat, and protein; the only difference between muffins was the type of fat.
The increase in body fat and the distribution of fat in the body was measured using a magnetic resonance imaging (MRI scans) before and after the weight gain, as was the muscle mass in the body. Gene activity was measured in the abdominal visceral fat before and after the weight gain with the help of a gene chip that studies several thousand genes at a time.
Despite comparable weight gains between the two diet groups, the surplus consumption of saturated fat caused a markedly greater increase in the amount of fat in the liver and abdomen (especially the fat surrounding the internal organs, visceral fat) in comparison with the surplus consumption of polyunsaturated fat. Moreover the total amount of body fat was greater in the saturated fat group, while, on the other hand, the increase in muscle mass was three times less for those who ate saturated fat compared with those who ate polyunsaturated fat. Thus, gaining weight on excess calories from polyunsaturated fat caused more gain in muscle mass, and less body fat than overeating a similar amount of saturated fat. Since most of us are in positive energy balance, and consequently gain weight slowly but gradually over time, the present results are highly relevant for most Western populations.
“Liver fat and visceral fat seems to contribute to a number of disturbances in metabolism. These findings can therefore be important for individuals with metabolic diseases such as diabetes. If the results regarding increased muscle mass following consumption of polyunsaturated fat can be confirmed in our coming studies, it will potentially be interesting for many elderly people, for whom maintaining muscle mass is of great importance in preventing morbidity”, says Ulf Risérus, associate professor at the Department of Public Health and Caring Science and director of the study.
When it comes to the risk of developing diabetes and cardiovascular diseases, it seems more important where in the body the fat is stored than how much fat the body has. Visceral fat, along with a high proportion of fat in the liver, is closely associated with increased risk for developing type-2 diabetes. These fat depots are therefore important targets for new drugs and dietary strategies. A number of studies have indicated that a higher intake of polyunsaturated fats from plant oils and nuts is associated with a decreased risk of type-2 diabetes, but the reasons for this remain unclear.
The present study proposes a potential explanation for such an association, showing that polyunsaturated fatty acids can affect fat distribution in the body more favorably than saturated fats, probably by regulating increased energy combustion or decreased storage of visceral fat in connection with calorie-rich diets.
The researchers were also able to see that over-consumption of saturated fats seems to be able to “turn on” certain genes in fatty tissue that increase the storage of fat in the abdomen and at the same time hamper insulin regulation. Polyunsaturated fats, instead, can “turn on” genes in visceral fat that in turn are linked to reduced storage of fat and improved sugar metabolism in the body. However, more research is required to understand how this occurs in humans.
The discovery may also be a contributing factor regarding the tendency of some individuals to accumulate fat in the liver and abdomen. The new findings suggest that the fat composition of the diet, in the long term, might play a role in preventing obesity-related disorders, like type-2 diabetes, at an early stage, before overweight develops.
“This is of great interest, as we lack preventive treatments for fatty liver and visceral fat today. The new findings also support international dietary recommendations including the new Nordic nutritional recommendations, which, among other things, recommend replacing some saturated fat from meat, butter, and palm oil, for example, with unsaturated fats from plant oils and fatty fish”, says Ulf Risérus.
The next step is now to find out in greater detail what happens in the body when we eat the respective fats and to study what the effects are in overweight individuals with elevated risk of type-2 diabetes.
The study was conducted at Uppsala University Hospital and Uppsala University in collaboration with the Karolinska Institutet. It was funded by the Swedish Research Council and the Swedish Society of Medicine undertaken within the framework of EXODIAB – Excellence of Diabetes Research in Sweden.
Study examines acetaminophen use in pregnancy, child behavioral problems
Bottom Line: Children of women who used the pain reliever acetaminophen (paracetamol) during pregnancy appear to be at higher risk for attention-deficit/hyperactivity disorder (ADHD)-like behavioral problems and hyperkinetic disorders (HKDs, a severe form of ADHD).
Author: Zeyan Liew, M.P.H., of the University of California, Los Angeles, and colleagues.
Background: Acetaminophen is the most commonly used medication for pain and fever during pregnancy. But some recent studies have suggested that acetaminophen has effects on sex and other hormones, which can in turn affect neurodevelopment and cause behavioral dysfunction.
How the Study Was Conducted: The authors studied 64,322 children and mothers in the Danish National Birth Cohort (1996-2002). Parents reported behavioral problems on a questionnaire, and HKD diagnoses and ADHD medication prescriptions were collected from Danish registries.
Results: More than half of the mothers reported using acetaminophen while pregnant. The use of acetaminophen during pregnancy appeared to be associated with a higher risk of HKD diagnosis, of using ADHD medications or of having ADHD-like behaviors at age 7 years. The risk increased when mothers used acetaminophen in more than one trimester during pregnancy.
Conclusion: “Maternal acetaminophen use during pregnancy is associated with a higher risk for HKDs and ADHD-like behaviors in children. Because the exposure and outcomes are frequent, these results are of public health relevance but further investigations are needed.”
Editorial: An Interesting Observed Association
In a related editorial, Miriam Cooper, M.R.C.Psych, M.Sc., of Cardiff University School of Medicine, Wales, and colleagues write: “An interesting new study in this issue of the journal has found preliminary evidence that prenatal exposure to a drug considered safe in pregnancy (acetaminophen or paracetamol) may be associated with ADHD in childhood.”
“Indeed, causation cannot be inferred from the present observed assocaitions, and Liew et al are right to point out that a replication of their study is needed,” they continue.
“In summary, findings from this study should be interpreted cautiously and should not change practice. However, they underline the importance of not taking a drug’s safety during pregnancy for granted, and they provide a platform from which to conduct further related analyses exploring a potential relationship between acetaminophen use and altered neurodevelopment,” the editorial concludes.
Vinegar kills tuberculosis and other mycobacteria
The active ingredient in vinegar, acetic acid, can effectively kill mycobacteria, even highly drug-resistant Mycobacterium tuberculosis, an international team of researchers from Venezuela, France, and the US reports in mBio®, the online open-access journal of the American Society for Microbiology.
Acetic acid might be used as an inexpensive and non-toxic disinfectant against drug-resistant tuberculosis (TB) bacteria as well as other stubborn, disinfectant-resistant mycobacteria.
Work with drug-resistant tuberculosis bacteria carries serious biohazard risks. Chlorine bleach is often used to disinfect TB cultures and clinical samples, but bleach is toxic and corrosive. Other effective commercial disinfectants can be too expensive for TB labs in the resource-poor countries where the majority of TB occurs.
“Mycobacteria are known to cause tuberculosis and leprosy, but non-TB mycobacteria are common in the environment, even in tap water, and are resistant to commonly used disinfectants. When they contaminate the sites of surgery or cosmetic procedures, they cause serious infections. Innately resistant to most antibiotics, they require months of therapy and can leave deforming scars.” says Howard Takiff, senior author on the study and head of the Laboratory of Molecular Genetics at the Venezuelan Institute of Scientific Investigation (IVIC) in Caracas.
“Many cosmetic procedures are performed outside of hospital settings in developing countries, where effective disinfectants are not available.” Takiff says, “These bacteria are emerging pathogens. How do you get rid of them?”
While investigating the ability of non-TB mycobacteria to resist disinfectants and antibiotics, Takiff’s postdoctoral fellow, Claudia Cortesia stumbled upon vinegar’s ability to kill mycobacteria. Testing a drug that needed to be dissolved in acetic acid, Cortesia found that the control, with acetic acid alone, killed the mycobacteria she wanted to study.
“After Claudia’s initial observation, we tested for the minimal concentrations and exposure times that would kill different mycobacteria,” says Takiff. Since the Venezuelan lab does not work with clinical TB, collaborators Catherine Vilchèze and William Jacobs, Jr. at the Albert Einstein College of Medicine in New York tested TB strains and found that exposure to a 6% solution of acetic acid for 30 minutes effectively kills tuberculosis, even strains resistant to almost all antibiotics.
Said another way, exposure to 6% acetic acid, just slightly more concentrated than supermarket vinegar, for 30 minutes, reduced the numbers of TB mycobacteria from around 100 million to undetectable levels.
During a sabbatical in Laurent Kremer’s laboratory at the University of Montpellier 2 in France, Takiff tested how effective acetic acid was against M. abscessus, one of the most resistant and pathogenic of the non-TB mycobacteria.
M. abscessus required exposure to a stronger 10% acetic acid solution for 30 minutes to be effectively eliminated. The team also tested the activity under biologically ‘dirty’ conditions similar to those encountered in clinical situations, by adding albumin protein and red blood cells to the acetic acid and found it was still effective.
“There is a real need for less toxic and less expensive disinfectants that can eliminate TB and non-TB mycobacteria, especially in resource-poor countries,” says Takiff. He notes that even a 25% solution of acetic acid is only a minor irritant and around US$100 can buy enough acetic acid to disinfect up to 20 liters of TB cultures or clinical samples.
“For now this is simply an interesting observation. Vinegar has been used for thousands of years as a common disinfectant and we merely extended studies from the early 20th century on acetic acid,” concludes Takiff. “Whether it could be useful in the clinic or mycobacteriology labs for sterilizing medical equipment or disinfecting cultures or clinical specimens remains to be determined.”
PFC exposure may spark metabolic changes in overweight children
Endocrine-disrupting chemical could raise risk of heart disease, diabetes
Washington, DC—Overweight children who were exposed to higher levels of perfluorinated chemicals tended to show early signs of developing the metabolic syndrome, according to a new study published in The Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.
The term metabolic syndrome describes a cluster of risk factors that increase the chances of developing heart disease, stroke and diabetes. The study is the first to find changing metabolic markers in children were associated with exposure to perfluorinated chemicals (PFCs), common industrial chemicals used as stain and water repellants in carpets, furniture and textiles.
“Our results suggest that these chemicals, which linger in the environment for years, could represent an important public health hazard that merits further study,” said one of the study’s authors, Clara Amalie Gade Timmermann, MSC, of the University of Southern Denmark. “Overweight children who were exposed to higher levels of PFCs tended to have higher concentrations of insulin and triglycerides in their blood, and these metabolic changes could signal the beginnings of the metabolic syndrome.”
The cross-sectional study examined PFC exposure and metabolic changes in 499 third-graders. Researchers measured the participants’ body mass index and waist circumference and analyzed blood samples for PFC, insulin, triglyceride and glucose levels. The samples were taken in 1997 as part of the European Youth Heart Study.
The analysis found that overweight children who had higher levels of certain PFCs in their blood were more likely to have higher levels of insulin and triglycerides as well. There was no relationship between PFC exposure and metabolic markers in normal-weight children.
“Although the two types of PFCs we investigated are being phased out due to health concerns, the use of other types of PFCs is on the rise,” Timmermann said. “There is an ongoing need to determine how the entire class of chemicals is affecting children’s health.”
Psychological side-effects of anti-depressants worse than thought
LIVERPOOL, UK – 26 February 2014: A University of Liverpool researcher has shown that thoughts of suicide, sexual difficulties and emotional numbness as a result of anti-depressants may be more widespread than previously thought.
In a survey of 1,829 people who had been prescribed anti-depressants, the researchers found large numbers of people – over half in some cases – reporting on psychological problems due to their medication, which has led to growing concerns about the scale of the problem of over-prescription of these drugs.
Psychologist and lead researcher, Professor John Read from the University’s Institute of Psychology, Health and Society, said: “The medicalisation of sadness and distress has reached bizarre levels. One in ten people in some countries are now prescribed antidepressants each year.
“While the biological side-effects of antidepressants, such as weight gain and nausea, are well documented, the psychological and interpersonal effects have been largely ignored or denied. They appear to be alarmingly common.”
Each person completed an online questionnaire which asked about twenty adverse effects. The study was carried out in New Zealand and all of the participants had been on anti-depressants in the last five years. The survey factored in people’s levels of depression and asked them to report on how they had felt while taking the medication.
Over half of people aged 18 to 25 in the study reported suicidal feelings and in the total sample there were large percentages of people suffering from ‘sexual difficulties’ (62%) and ‘feeling emotionally numb’ (60%). Percentages for other effects included: ‘feeling not like myself’ (52%), ‘reduction in positive feelings’ (42%), ‘caring less about others’ (39%) and ‘withdrawal effects’ (55%). However, 82% reported that the drugs had helped alleviate their depression.
Professor Read concluded: “While the biological side-effects of antidepressants, such as weight gain and nausea, are well documented, psychological and interpersonal issues have been largely ignored or denied. They appear to be alarmingly common.”
“Effects such as feeling emotionally numb and caring less about other people are of major concern. Our study also found that people are not being told about this when prescribed the drugs.
“Our finding that over a third of respondents reported suicidality ‘as a result of taking the antidepressants’ suggests that earlier studies may have underestimated the problem.”
Vitamin A may help boost immune system to fight tuberculosis
Tuberculosis is a major global problem, affecting 2 billion people worldwide and causing an estimated 2 million deaths annually. Western countries are once again tackling the disease, with recent outbreaks in Los Angeles and London.
The rise of drug-resistant TB, called a “ticking time bomb” by the World Health Organization, and the high cost of fighting the disease highlight the need for new approaches to treatment.
In findings published in the March 1 issue of the Journal of Immunology, UCLA researchers investigating the role of nutrients in helping the immune system fight against major infections show that vitamin A may play an important role combating TB.
The UCLA team describes for the first time the mechanism by which vitamin A and a specific gene assist the immune system by reducing the level of cholesterol in cells infected with TB. This is important because cholesterol can be used by TB bacteria for nutrition and other needs, the researchers said.
“If we can reduce the amount of cholesterol in a cell infected with tuberculosis, we may be able to aid the immune system in better responding to the infection,” said senior author Philip Liu, an assistant professor of medicine in the divisions of dermatology and orthopedic surgery at UCLA’s David Geffen School of Medicine and Orthopaedic Hospital Research Center. “Understanding how nutrients like vitamin A are utilized by our immune system to fight infections may provide new treatment approaches.”
Although vitamin A circulates in the body in an inactive form known as retinol, it’s the active form of the nutrient — all-trans reinoic acid — that is responsible for activating the immune system.
To investigate the role of this active form of vitamin A in immune defense, the UCLA team first compared its effects on cells to the effects of a similar nutrient, vitamin D, which the group had previously studied. The researchers thought the two vitamins might use the same mechanism to aid the immune system, but this wasn’t the case. They found that when the vitamins were added to human blood cells infected with tuberculosis, only vitamin A decreased the cells’ cholesterol levels.
The researchers also discovered that the action of vitamin A was dependent on the expression of a gene called NPC2. Further experiments in the lab showed that even if an infected blood cell was stimulated with vitamin A, it would not be able to fight the tuberculosis bacteria if the cell couldn’t express the NPC2 gene.
“We were very surprised that this particular gene was involved, since it has traditionally been associated with cholesterol transport and not immune defense,” said co-first author Elliot Kim, who was a research technician in Liu’s lab at the time of the study and is currently a graduate student in the department of microbiology, immunology and molecular genetics at the Geffen School.
However, once the team took a closer look at the actions taking place in the cells, it made sense.
Cholesterol is stored in lysosomes, compartments in a cell that also play an integral role in fighting infections. If the lysomome is full of cholesterol, it supplies the bacteria with needed nutrition instead of killing it.
Vitamin A induces the cell to express NPC2, which helps the cell effectively remove cholesterol from the lysosomes so the bacteria can’t access it. This allows the lysomomes to once again become effective in killing the bacteria.
When activated correctly, lysomomes fuse with the area of the cell containing the bacteria and dump antimicrobial material onto the bacteria to kill it, similar to a helicopter dropping water and retardant on a forest fire.
“The cells need vitamin A to trigger this defense process and NPC2 to carry it out,” said co-first author Matthew Wheelwright, a medical and doctoral student at the University of Minnesota who was an undergraduate research assistant in Liu’s lab when the research was conducted. “We may be able to target these pathways that regulate cholesterol within a cell to help the immune system respond to infection.”
The next stage of research will focus on better understanding how the immune system takes retinol, the inactive form of vitamin A, and creates all-trans retinoic acid, the form of the nutrient that can activate the infected cells against the tuberculosis bacteria.
The UCLA team notes that this is an early study and that more research needs to be done before recommending vitamin A supplementation to combat tuberculosis or other infections.
Ordinary conditioner removes head lice eggs as effectively as special products
Eggs from head lice, also called nits, are incredibly difficult to remove. Female lice lay eggs directly onto strands of hair, and they cement them in place with a glue-like substance, making them hard to get rid of. In fact, the eggs are glued down so strongly that they will stay in place even after hair has been treated with pediculicides — substances used to kill lice.
Some shampoos and conditioners that contain chemicals or special oils are marketed as nit-removal products. However, new research just published in the Journal of Medical Entomology shows that ordinary hair conditioner is just as effective.
In an article called “Efficacy of Products to Remove Eggs of Pediculus humanus capitis (Phthiraptera: Pediculidae) From the Human Hair,” (DOI: http://dx.doi.org/10.1603/ME13106) scientists from Belgium gathered 605 hairs from six different children. Each hair had a single nit attached to it. Approximately 14% of the eggshells contained a dead egg, whereas the rest were empty.
They then tried to remove the eggs and tested the amount of force needed to do so. They found that nits on the hairs that were left completely untreated were the most difficult to remove. Eggs on hairs that had been soaked in deionized water were much easier to remove, as were the eggs on hairs that had been treated with ordinary hair conditioner and with products specifically marketed for the purpose of nit removal.
However, they found no significant differences between the ordinary conditioners and the special nit-removal products. In all cases, less force was required to remove the nits after the hair had been treated, but the effectiveness of the products was essentially the same.
“There were no significant differences in measured forces between the ordinary conditioner and the commercial nit removal product,” the authors write. “The commercial nit removal products tested in the current study do not seem to have an additional effect.”
The authors hypothesize that the deionized water was effective because it acts as a lubricant, so less friction is needed to remove the nits from the hairs. The same goes for the conditioners.
“Treatment with conditioner reduces the coefficient of friction of undamaged and damaged hair,” they write. “As a consequence, conditioners will facilitate nit removal.”
Suicide in apparently well-functioning young men
Suicide among young men is a major public health concern in many countries, despite great efforts to find effective prevention strategies. By interviewing close relatives and friends of apparently well-functioning young men who unexpectedly took their own life, Norwegian researchers found there had been no signs of serious mental disorder. This contradicts previous research which suggests that depression or other mental illness is an important risk factor in suicide.
In Norway, there is still scant scientific evidence of effective prevention strategies, and suicide rates among young men remain high. Most studies of suicide are based on clinical populations, and the detection and treatment of mental disorder is the main focus in suicide prevention strategies in many countries.
Researchers at the Norwegian Institute of Public Health interviewed close relatives and friends of ten young men who, in spite of accomplishments and successes, had unexpectedly taken their own lives in young adulthood about how they knew the deceased and understood the suicide.
The main finding suggests that developmentally, these young men appeared to have compensated for their lack of self-worth by exaggerating the importance of success, thus developing a fragile, achievement-based self-esteem in adulthood which left them vulnerable in the face of rejection and perception of failure.
No signs of mental illness
“Contrary to previous research suggesting that mental illness – in particular depression – in the period prior to death is an important risk factor for suicide, few of the informants in our study mentioned depression or other mental illnesses in their narratives”, says researcher Mette Lyberg Rasmussen, the first author of the recently published study.
Vulnerable to rejection and failure
“The study’s main findings uncover a particular vulnerability to feeling rejected and to not having succeeded in achieving their goals,” explains Rasmussen.
“In these situations there is a strong sense of shame and of being trapped in anger. This develops into unbearable thoughts that the vulnerable person cannot regulate or manage, and leads to a feeling of a life not worth living. The former strategy, which involved compensation with continual increased efforts, does not work anymore, and suicide becomes a way out of a situation of unbearable psychological pain,” says Rasmussen.
The study is based on a unique qualitative data set, consisting of 61 in-depth interviews and 6 suicide notes related to 10 suicides among young men (18 and 30 years) with no prior psychiatric treatment and no previous suicide attempts. For every suicide, Rasmussen and her co-authors analysed in-depth interviews with mothers, fathers/father figures, male friends, siblings and (ex-)-girlfriends about how each one of them experienced the deceased and his suicide in all its complexity.
Don’t throw out old, sprouting garlic — it has heart-healthy antioxidants
“Sprouted” garlic — old garlic bulbs with bright green shoots emerging from the cloves — is considered to be past its prime and usually ends up in the garbage can. But scientists are reporting in ACS’ Journal of Agricultural and Food Chemistry that this type of garlic has even more heart-healthy antioxidant activity than its fresher counterparts.
Jong-Sang Kim and colleagues note that people have used garlic for medicinal purposes for thousands of years. Today, people still celebrate its healthful benefits. Eating garlic or taking garlic supplements is touted as a natural way to reduce cholesterol levels, blood pressure and heart disease risk. It even may boost the immune system and help fight cancer. But those benefits are for fresh, raw garlic. Sprouted garlic has received much less attention. When seedlings grow into green plants, they make many new compounds, including those that protect the young plant against pathogens. Kim’s group reasoned that the same thing might be happening when green shoots grow from old heads of garlic. Other studies have shown that sprouted beans and grains have increased antioxidant activity, so the team set out to see if the same is true for garlic.
They found that garlic sprouted for five days had higher antioxidant activity than fresher, younger bulbs, and it had different metabolites, suggesting that it also makes different substances. Extracts from this garlic even protected cells in a laboratory dish from certain types of damage. “Therefore, sprouting may be a useful way to improve the antioxidant potential of garlic,” they conclude.
Ancient Chinese medicine put through its paces for pancreatic cancer
SAN ANTONIO (March 3, 2014) – The bark of the Amur cork tree (Phellodendron amurense) has traveled a centuries-long road with the healing arts. Now it is being put through its paces by science in the fight against pancreatic cancer, with the potential to make inroads against several more.
UT Health Science Center researcher A. Pratap Kumar was already exploring the cork tree extract’s promise in treating prostate cancer when his team found that deadly pancreatic cancers share some similar development pathways with prostate tumors.
In a paper published today in the journal Clinical Cancer Research, the researchers show that the extract blocks those pathways and inhibits the scarring that thwarts anti-cancer drugs. Dr. Jingjing Gong, currently pursuing post-doctoral studies at Yale University, conducted the study as a graduate student in Dr Kumar’s laboratory in the Department of Pharmacology.
“Fibrosis is a process of uncontrolled scarring around the tumor gland,” said Dr. Kumar, a professor of urology in the School of Medicine at the Health Science Center and the study’s principal investigator. “Once you have fibrotic tissue, the drugs cannot get into the cancer.”
Liver and kidney tumors also develop fibrosis and the resulting resistance to drugs, he said, and there are no drugs currently targeting that pathway in those cancers.
The two pathways, or proteins, that contribute to fibrosis in those tumors also encourage Cox-2, an enzyme that causes inflammation, and the cork tree extract appears to suppress that as well, Dr. Kumar said. The complex interrelationship of these substances is “the million-dollar question,” he said, and solving that question is one of the next steps in his research.
The potential of natural substances to treat and cure disease has great appeal, but the advantage of cork tree extract, available as a dietary supplement in capsule form, is that it already has been established as safe for use in patients. In a promising prostate cancer clinical study of 24 patients that Dr. Kumar helped spearhead, all the patients tolerated the treatment well, he said. Now researchers are analyzing the results, he said, and with more funding they plan to expand the study to a much larger group of patients.
The dietary supplement is marketed as Nexrutine by Next Pharmaceuticals of Salinas, Calif., which provided a supply of the compound for the studies.
Plant extract offers hope for infant motor neuron therapy
A chemical found in plants could reduce the symptoms of a rare muscle disease that leaves children with little or no control of their movements.
Scientists have found that a plant pigment called quercetin – found in some fruits, vegetables, herbs and grains – could help to prevent the damage to nerves associated with the childhood form of motor neuron disease.
Their findings could pave the way for new treatments for spinal muscular atrophy (SMA) – also known as floppy baby syndrome – which is a leading genetic cause of death in children.
The team has found that the build-up of a specific molecule inside cells – called beta-catenin – is responsible for some of the symptoms associated with the condition.
In tests on zebrafish, flies and mice, scientists found that treating the disease with purified quercetin – which targets beta-catenin – led to a significant improvement in the health of nerve and muscle cells.
Quercetin did not prevent all of the symptoms associated with the disorder but researchers hope that it could offer a useful treatment option in the early stages of disease.
They now hope to create better versions of the chemical that are more effective than naturally-occurring quercetin.
SMA is caused by a mutation in a gene that is vital for the survival of nerve cells that connect the brain and spinal cord to the muscles, known as motor neurons. Until now, it was not known how the mutation damages these cells and causes disease.
The study reveals that the mutated gene affects a key housekeeping process that is required for removing unwanted molecules from cells in the body. When this process doesn’t work properly, molecules can build-up and cause problems inside the cells.
Children with SMA experience progressive muscle wastage and loss of mobility and control of their movements. The disorder is often referred to as ‘floppy baby syndrome’ because of the weakness that it creates.
It affects one in 6000 babies and around half of children with the most severe form will die before the age of two.
The study is published today in the Journal of Clinical Investigation.
Professor Tom Gillingwater from the University of Edinburgh, who led the study, said: “This is an important step that could one day improve quality of life for the babies affected by this condition and their families. There is currently no cure for this kind of neuromuscular disorder so new treatments that can tackle the progression of disease are urgently needed.”
Study shows nearly fivefold increased risk for heart attack after angry outburst
Highlights need for medical and behavioral interventions
BOSTON – Call it what you will – getting red in the face, hot under the collar, losing your cool, blowing your top – we all experience anger. And while we know that anger is a normal, sometimes even beneficial emotion, we’re also aware of the often harmful connection between anger and health. New research from Beth Israel Deaconess Medical shows an even more compelling reason to think about getting anger in check – a nearly fivefold increase in risk for heart attack in the two hours following outbursts of anger.
“There has been a lot of research on anger; we already know it can be unhealthy, but we wanted to quantify the risk, not just for heart attack, but for other potentially lethal cardiovascular events as well,” says lead author Elizabeth Mostofsky, MPH, ScD, a post-doctoral fellow in the cardiovascular epidemiological unit at BIDMC and an instructor at the Harvard School of Public Health. “The hope is this might help patients think about how they manage anger in their everyday lives and prompt physicians to discuss medications and psychosocial supports with their patients for whom anger is an issue, especially patients with known cardiovascular risk factors.”
In the study published Tuesday in the European Heart Journal, Mostofsky and colleagues performed a systematic review of studies published between 1966 and 2013. They identified nine case crossover studies where patients who had experienced cardiovascular events answered questions about anger. They were asked about their level of anger immediately prior to the cardiovascular event with anger at other times, using terms like very angry, furious or enraged.
The researchers found that despite differences between the studies, there was “consistent evidence of a higher risk of cardiovascular events immediately following outbursts of anger.”
The study results showed that the risk of heart attack or acute coronary syndrome – the symptoms like chest pain, shortness of breath or sweating related to a blocked artery – was 4.7 times higher in the two hours following an angry outburst than at any other time. And the risk for stroke caused by a blocked artery in the brain was 3.6 times higher than at other times. One of the studies included in the review indicated a 6.3 fold increased risk for brain aneurysm in the hour following an outburst of anger compared with other times.
Mostofsky and colleagues also examined two studies that looked at arrhythmia and anger. Analysis of these studies showed that patients with implanted cardiac defibrillators (ICD) were nearly twice as likely to experience an abnormal heart rate requiring a shock from the ICD in the 15 minutes following an angry outburst than at other times.
“It’s important to bear in mind that while these results show a significantly higher risk of a cardiovascular event associated with an angry outburst, the overall risk for people without other risk factors like smoking or high blood pressure is relatively small,” says senior author Murray Mittleman, MD, DrPH, a physician in the CardioVascular Institute at Beth Israel Deaconess Medical Center, an Associate Professor of Medicine at Harvard Medical School and director of BIDMC’s cardiovascular epidemiological research program. “However, we should be concerned about the occurrence of angry outbursts with our higher risk patients and our patients who have frequent outbursts of anger.”
While it’s possible that medications and other interventions that may lower the frequency of angry outbursts or the risk associated with anger, Mostofsky says “more research including clinical trials are needed to identify which drugs or behavioral therapies will be most effective.”
Screening does not shift breast cancer to earlier stages
New research from Aarhus University suggests that screening for breast cancer results in increased diagnoses of early stage cancer — but without a similarly sized decrease in the more serious and aggressive cases
Screening for breast cancer appeared to have a very limited effect on the occurrence of serious and aggressive cancer cases. On the other hand, it appeared to detect many more early cancer cases, cases which would otherwise never have developed – but which are treated due to screening.
This is the conclusion of a study from Aarhus University, Denmark, that has just been published in the European Journal of Public Health based on data from all women over the age of 20 in Norway (approx. 1.8 million in 2010).
Looks at the various stages of cancer
The new element is that the researchers look at the severity of the diagnosis, which is divided into four stages: From the very early stages of cancer which is completely local up to the very serious cases where the cancer has already spread.
The researchers examined the stage distribution of breast cancer diagnosed before the introduction of screening, during the introduction and after the scheme was fully implemented.
“The idea of screening is that the cancer should be detected as early as possible so that the woman can be treated and cured. So when you introduce screening women should be, as it were, transferred from having cancer in advanced stages to having cancer in an early stage. That is, if the screening works according to plan,” says Associate Professor, PhD Henrik Støvring, Aarhus University, who is the key researcher behind the project together with BSc Mette Lise Lousdal.
rimarily discovers indolent cancer
The researchers examined how the distribution of the four stages of cancer developed from 1987 to 2010: “We can see that since screening was introduced in Norway, the rate of discovery of breast cancer in the early stage among women aged 50-69 has almost doubled – while there has been virtually no change in the number of advanced stages. This suggests that screening primarily detects more cases of indolent cancer, which if there had been no screening, the woman would have died with – and not died of,” says Henrik Støvring.
He adds that the screening may still have had a beneficial effect on mortality – this aspect was not examined by the study.
“But if that was the case then there should indeed be an increase of the early stages, but there ought to be an almost equally sized decline in the late stages as well. And this we did not find,” he says.
The next step in the research project will be to analyse similar figures from Denmark.
Hop leaves — discarded in beer brewing — have substances that could fight dental diseases
Beer drinkers know that hops are what gives the drink its bitterness and aroma. Recently, scientists reported that the part of hops that isn’t used for making beer contains healthful antioxidants and could be used to battle cavities and gum disease. In a new study in ACS’ Journal of Agricultural and Food Chemistry, they say that they’ve identified some of the substances that could be responsible for these healthful effects.
Yoshihisa Tanaka and colleagues note that their earlier research found that antioxidant polyphenols, contained in the hop leaves (called bracts) could help fight cavities and gum disease. Extracts from bracts stopped the bacteria responsible for these dental conditions from being able to stick to surfaces and prevented the release of some bacterial toxins. Every year, farmers harvest about 2,300 tons of hops in the United States, but the bracts are not used for making beer and are discarded. Thus, there is potentially a large amount of bracts that could be repurposed for dental applications. But very few of the potentially hundreds of compounds in the bracts have been reported. Tanaka’s group decided to investigate what substances in these leaves might cause those healthful effects.
Using a laboratory technique called chromatography, they found three new compounds, one already-known compound that was identified for the first time in plants and 20 already-known compounds that were found for the first time in hops. The bracts also contained substantial amounts of proanthocyanidins, which are healthful antioxidants.
Calcium and vitamin D improve cholesterol in postmenopausal women
Study ties effect to raising vitamin D levels
CLEVELAND, Ohio (March 5, 2014)—Calcium and vitamin D supplements after menopause can improve women’s cholesterol profiles. And much of that effect is tied to raising vitamin D levels, finds a new study from the Women’s Health Initiative (WHI) just published online in Menopause, the journal of The North American Menopause Society (NAMS).
Whether calcium or vitamin D can indeed improve cholesterol levels has been debated. And studies of women taking the combination could not separate the effects of calcium from those of vitamin D on cholesterol. But this study, led by NAMS Board of Trustees member Peter F. Schnatz, DO, NCMP, is helping to settle those questions because it looked both at how a calcium and vitamin D supplement changed cholesterol levels and how it affected blood levels of vitamin D in postmenopausal women.
Daily, the women in the WHI CaD trial took either a supplement containing 1,000 mg of calcium and 400 IU of vitamin D3 or a placebo. This analysis looked at the relationship between taking supplements and levels of vitamin D and cholesterol in some 600 of the women who had both their cholesterol levels and their vitamin D levels measured.
The women who took the supplement were more than twice as likely to have vitamin D levels of at least 30 ng/mL (normal according to the Institute of Medicine) as were the women who took the placebo. Supplement users also had low-density lipoprotein (LDL—the “bad” cholesterol) levels that were between 4 and 5 points lower. The investigators discovered, in addition, that among supplement users, those with higher blood levels of vitamin D had higher levels of high-density lipoprotein (HDL—the “good” cholesterol) and lower levels of triglycerides (although for triglycerides to be lower, blood levels of vitamin D had to reach a threshold of about 15 ng/mL).
Taking the calcium and vitamin D supplements was especially helpful in raising vitamin D levels in women who were older, women who had a low intake, and women who had levels first measured in the winter—what you might expect. But lifestyle also made a difference. The supplements also did more to raise vitamin D levels in women who did not smoke and who drank less alcohol.
Whether these positive effects of supplemental calcium and vitamin D on cholesterol will translate into benefits such as lower rates of cardiovascular disease for women after menopause remains to be seen, but these results, said the authors, are a good reminder that women at higher risk for vitamin D deficiency should consider taking calcium and vitamin D.
“The results of this study should inspire even more women to be conscientious about their calcium and vitamin D intake—a simple and safe way to improve health. One action can lead to multiple benefits!” says NAMS Executive Director Margery Gass, MD.
The study, “Calcium/vitamin D supplementation, serum 25-hydroxyvitamin D concentrations, and cholesterol profiles in the Women’s Health Initiative calcium/vitamin D randomized trial,” will be published in the August 2014 print edition of Menopause.
Study suggests higher levels of omega-3 in diet are associated with better sleep
A randomized placebo-controlled study by the University of Oxford
A randomised placebo-controlled study by the University of Oxford suggests that higher levels of omega-3 DHA, the group of long-chain fatty acids found in algae and seafood, are associated with better sleep. The researchers explored whether 16 weeks of daily 600 mg supplements of algal sources would improve the sleep of 362 children. The children who took part in the study were not selected for sleep problems, but were all struggling readers at a mainstream primary school. At the outset, the parents filled in a child sleep questionnaire, which revealed that four in ten of the children in the study suffered from regular sleep disturbances. Of the children rated as having poor sleep, the researchers fitted wrist sensors to 43 of them to monitor their movements in bed over five nights. This exploratory pilot study showed that the children on a course of daily supplements of omega-3 had nearly one hour (58 minutes) more sleep and seven fewer waking episodes per night compared with the children taking the corn or soybean placebo. The findings are due to be published in the Journal of Sleep Research.
The two-phased study looked at sleep in 362 healthy 7-9 year old UK school children in relation to the levels of omega-3 and omega-6 long-chain polyunsaturated fatty acids (LC-PUFA) found in fingerstick blood samples. Previous research has suggested links between poor sleep and low blood omega-3 LC-PUFA in infants and in children and adults with behaviour or learning difficulties. However, this is the first study to investigate possible links between sleep and fatty acid status in healthy children.
At the start of the study, parents and carers were asked to rate their child’s sleep habits over a typical week (using a three-point scale). Their responses to the well-validated Child Sleep Habits Questionnaire indicated that 40 percent of the children had clinical-level sleep problems, such as resistance to bedtime, anxiety about sleep and constant waking in the course of the night.
The study finds that higher blood levels of the long-chain omega-3 DHA (the main omega-3 fatty acid found in the brain) are significantly associated with better sleep, including less bedtime resistance, parasomnias and total sleep disturbance. It adds that higher ratios of DHA in relation to the long-chain omega-6 fatty acid AA (arachidonic acid) are also associated with fewer sleep problems.
Lead author Professor Paul Montgomery of Oxford University said: ‘To find clinical level sleep problems in four in ten of this general population sample is a cause for concern. Various substances made within the body from omega-3 and omega-6 fatty acids have long been known to play key roles in the regulation of sleep. For example, lower ratios of DHA have been linked with lower levels of melatonin, and that would fit with our finding that sleep problems are greater in children with lower levels of DHA in their blood.’
Co-investigator Dr Alex Richardson of Oxford University said: ‘Previous studies we have published showed that blood levels of omega-3 DHA in this general population sample of 7-9 year olds were alarmingly low overall, and this could be directly related to the children’s behaviour and learning. Poor sleep could well help to explain some of those associations.
‘Further research is needed given the small number of children involved in the pilot study. Larger studies using objective sleep measures, such as further actigraphy using wrist sensors, are clearly warranted. However, this randomised controlled trial does suggest that children’s sleep can be improved by DHA supplements and indicates yet another benefit of higher levels of omega-3 in the diet.’
Vitamin D increases breast cancer patient survival
Breast cancer patients with high levels of vitamin D in their blood are twice as likely to survive the disease as women with low levels of this nutrient, report University of California, San Diego School of Medicine researchers in the March issue of Anticancer Research.
In previous studies, Cedric F. Garland, DrPH, professor in the Department of Family and Preventive Medicine, showed that low vitamin D levels were linked to a high risk of premenopausal breast cancer. That finding, he said, prompted him to question the relationship between 25-hydroxyvitamin D — a metabolite produced by the body from the ingestion of vitamin D — and breast cancer survival rates.
Garland and colleagues performed a statistical analysis of five studies of 25-hydroxyvitamin D obtained at the time of patient diagnosis and their follow-up for an average of nine years. Combined, the studies included 4,443 breast cancer patients.
“Vitamin D metabolites increase communication between cells by switching on a protein that blocks aggressive cell division,” said Garland. “As long as vitamin D receptors are present tumor growth is prevented and kept from expanding its blood supply. Vitamin D receptors are not lost until a tumor is very advanced. This is the reason for better survival in patients whose vitamin D blood levels are high.”
Women in the high serum group had an average level of 30 nanograms per milliliter (ng/ml) of 25-hydroxyvitamin D in their blood. The low group averaged 17 ng/ml. The average level in patients with breast cancer in the United States is 17 ng/ml.
“The study has implications for including vitamin D as an adjuvant to conventional breast cancer therapy,” said co-author Heather Hofflich, DO, UC San Diego associate professor in the Department of Medicine.
Garland recommended randomized controlled clinical trials to confirm the findings but suggested physicians consider adding vitamin D into a breast cancer patient’s standard care now and then closely monitor the patient.
“There is no compelling reason to wait for further studies to incorporate vitamin D supplements into standard care regimens since a safe dose of vitamin D needed to achieve high serum levels above 30 nanograms per milliliter has already been established,” said Garland.
A 2011 meta-analysis by Garland and colleagues estimated that a serum level of 50 ng/ml is associated with 50 percent lower risk of breast cancer. While there are some variations in absorption, those who consume 4,000 International Units (IU) per day of vitamin D from food or a supplement normally would reach a serum level of 50 ng/ml. Garland urged patients to ask their health care provider to measure their levels before substantially increasing vitamin D intake.
According to the National Institutes of Health, the current recommended daily allowance for vitamin D is 600 IU for adults and 800 IU for people over 70 years old.
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