Light to moderate alcohol leads to good cheer at Danish high-school parties

Contact: Marie Eliasen, M.Sc. mae@niph.dk 45-6550-7777 (Denmark) University of Southern Denmark

Alcoholism: Clinical & Experimental Research

Many people, especially young adults, engage in high-risk drinking because of the belief it will lead to positive mood effects such as cheerfulness.  A new study of the association between blood alcohol content (BAC) and the subjective effects of alcohol like cheerfulness, focus distraction, and sluggishness among students in a real-life setting of high-school parties, has found that cheerfulness increased up to a certain BAC value for girls, and then decreased at higher BACs, while it increased linearly for boys.

Results will be published in the March 2014 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

“A large body of research has shown that the majority of adolescents and young adults report [having] social and enhancement motives for drinking alcohol,” said Marie Eliasen, a research assistant at the University of Southern Denmark as well as corresponding author for the study.  “These motives can include: ‘it makes social gatherings more fun,’ ‘to get in a party mood,’ and ‘because it’s fun.’  Comparing nationalities, social and enhancement motives were especially prevalent in North America and northern and mid-Europe, while for example in Spain, the most frequent motives of drinking among young adults were that they liked the taste and that it was a custom/social habit.”

Eliasen explained that in Denmark, there exist no national or regional restrictions or policies on selling and drinking alcohol at high-school parties; students are allowed to drink and buy alcohol regardless their age as these functions are regarded as private and thus the age limit for purchasing alcohol is not enforced.  “At least since the 1960s and probably also before that, students have bought and drank alcohol at these parties,” she said.  “In the last couple of years, a few Danish high schools have introduced alcohol-free parties, but we do not have any exact statistics.  It is still the norm to serve alcohol at the parties at the majority of Danish high schools.”

Eliasen and her colleagues examined 230 Danish high-school students (151 girls, 79 boys) aged 15 to 20 years who were attending high school parties.  During the parties, the students visited an examination room located near the party in one-hour intervals to have their BAC and levels of cheerfulness, focus distraction, and sluggishness measured.  BACs were measured by means of a breath analyzer, while cheerfulness (on a score from 0-16), focus distraction (score from 0-8), and sluggishness (score from 0-4) were self-reported.

“We found that low to moderate alcohol consumption is associated with increased cheerfulness among adolescents attending high-school parties,” said Eliasen.  “Extensive alcohol consumption leading to high BACs was associated with decreased cheerfulness among girls while this was not found for boys.  However, few boys had very high BACs, which makes it difficult to draw conclusions.  In addition, alcohol consumption increased focus distraction among these students.  Another interesting finding was that the majority of the participating students had low to moderate BACs, indicating that they did not drink as much alcohol as is normally presumed.”

Eliasen noted that the lack of a decrease in cheerfulness at higher BACs among boys may be explained by a higher tolerance to alcohol among boys, compared to the girls, as the boys drank alcohol and binge drank more frequently, and generally had higher weekly alcohol consumption than the girls.  Eliasen underlined that, most likely, cheerfulness will also decrease at high BACs for boys, but as only a few boys had high BACs at the parties, the turning point could not be identified in the study.

“These findings show alcohol’s subjective effects in a real-life setting,” said Eliasen.  “The participants were followed over time, acting as they normally did at a party, including deciding themselves how much to drink.  It is important to incorporate the context in which alcohol is consumed in order to obtain full knowledge about alcohol’s subjective effects, as the context has been shown to have a high impact on the subjective effects of alcohol.”

Eliasen said findings have several implications:  “First, public-health campaigns as well as parental and clinician comments that neglect aspects of cheerfulness associated with alcohol may contradict adolescents’ positive experiences.  Such statements and campaigns might seem untrustworthy, as adolescents actually perceive increased cheerfulness when drinking alcohol up to certain amounts.  Perhaps alcohol prevention strategies targeting adolescents … could instead focus on having fun without an excessive alcohol intake.  Second, our findings of increased focus distraction at high BACs stress the importance of reducing excessive alcohol drinking, as increased focus distraction is strongly associated with higher risks of accidents.  This finding may also work as an argument for parents and clinicians trying to reduce excessive alcohol consumption among adolescents.  Third, the findings of a low to moderate BAC among the majority of the students may be used to challenge the idea that the majority of adolescents drink in excess and thus change adolescents’ own perception of normality, which again may reduce their alcohol consumption.”

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Alcoholism: Clinical & Experimental Research (ACER) is the official journal of the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism.  Co-authors of the ACER paper, “The Association between Blood Alcohol Content and Cheerfulness, Focus Distraction, and Sluggishness among Young Adults Attending High School Parties,” were:  Morten Hulvej Rod, Morten Grønbæk, and Janne Schurmann Tolstrup of the National Institute of Public Health at the University of Southern Denmark; Trine Flensborg-Madsen of the National Institute of Public Health at the University of Southern Denmark, and the Unit of Medical Psychology in the Department of Public Health at the University of Copenhagen; and Jørgen Holm Petersen of the Section of Biostatistics in the Department of Public Health at the University of Copenhagen.  The study was funded by the Danish Health and Medicine Authority.  This release is supported by the Addiction Technology Transfer Center Network at http://www.ATTCnetwork.org.

1 in 4 has alarmingly few intestinal bacteria

Contact: Oluf Pedersen oluf@sund.ku.dk 45-52-39-56-50 University of Copenhagen

All people have trillions of bacteria living in their intestines. If you place them on a scale, they weigh around 1.5 kg. Previously, a major part of these ‘blind passengers’ were unknown, as they are difficult or impossible to grow in laboratories. But over the past five years, an EU-funded research team, MetaHIT, coordinated by Professor S. Dusko Ehrlich at the INRA Research Centre of Jouy-en-Josas, France and with experts from Europe and China have used advanced DNA analysis and bioinformatics methods to map human intestinal bacteria.

-The genetic analysis of intestinal bacteria from 292 Danes shows that about a quarter of us have up to 40% less gut bacteria genes and correspondingly fewer bacteria than average. Not only has this quarter fewer intestinal bacteria, but they also have reduced bacterial diversity and they harbour more bacteria causing a low-grade inflammation of the body. This is a representative study sample, and the study results can therefore be generalised to people in the Western world, says Oluf Pedersen, Professor and Scientific Director at the Faculty of Health and Medical Sciences, University of Copenhagen.

Oluf Pedersen and Professor Torben Hansen have headed the Danish part of the MetaHIT project, and the findings are reported in the highly recognised scientific journal Nature.

The gut is like a rainforest

Oluf Pedersen compares the human gut and its bacteria with a tropical rainforest. He explains that we need as much diversity as possible, and – as is the case with the natural tropical rainforests – decreasing diversity is a cause for concern. It appears that the richer and more diverse the composition of our intestinal bacteria, the stronger our health. The bacteria produce vital vitamins, mature and strengthen our immune system and communicate with the many nerve cells and hormone-producing cells in the intestinal system. And, not least, the bacteria produce a wealth of bioactive substances which penetrate into the bloodstream and affect our biology in countless ways.

-Our study shows that people having few and less diverse intestinal bacteria are more obese than the rest. They have a preponderance of bacteria which exhibit the potential to cause mild inflammation in the digestive tract and in the entire body, which is reflected in blood samples that reveal a state of chronic inflammation, which we know from other studies to affect metabolism and increase the risk of type 2 diabetes and cardiovascular diseases, says Oluf Pedersen.

-And we also see that if you belong to the group with less intestinal bacteria and have already developed obesity, you will also gain more weight over a number of years. We don’t know what came first, the chicken or the egg, but one thing is certain: it is a vicious circle that poses a health threat, says the researcher.

Take care of your intestinal bacteria

The researchers thus still cannot explain why some people have fewer intestinal bacteria, but the researchers are focusing their attention at dietary components, genetic variation in the human host, exposure to antimicrobial agents during early childhood and the chemistry we encounter daily in the form of preservatives and disinfectants.

A French research team reports a study in the same issue of Nature showing that by maintaining a low-fat diet for just six weeks, a group of overweight individuals with fewer and less diverse intestinal bacteria may, to some extent, increase the growth of intestinal bacteria, both in terms of actual numbers and diversity.

-This indicates that you can repair some of the damage to your gut bacteria simply by changing your dietary habits. Our intestinal bacteria are actually to be considered an organ just like our heart and brain, and the presence of health-promoting bacteria must therefore be cared for in the best way possible. Over the next years, we will be gathering more knowledge of how best to do this,” says Oluf Pedersen, whose research team is studying, among other things, the impact of dietary gluten on gut bacteria composition and gut function.

Towards innovative early diagnostics and treatment options

Obesity and type 2 diabetes are not just a result of unfortunate combinations of intestinal bacteria or lack of health-promoting intestinal bacteria, Oluf Pedersen emphasises. There are likely many causal factors at play. But the MetaHit researchers’ contribution opens a new universe in which we begin to understand how gut bacteria in direct contact with the surrounding environment have a decisive impact on our health and risk of disease.

-At present we cannot do anything about our own DNA, individual variation in which also plays a crucial role in susceptibility for lifestyle diseases. But thanks to the new gut microbiota research, we now can start exploring interactions between host genetics and the gut bacteria- related environment which we may be able to change. That is why it is so exciting for us scientist within this research field– the possibilities are huge, says Oluf Pedersen.

-The long-term dream is to map and characterize any naturally occurring gut bacteria that produce appetite-inhibiting bioactive substances and in this way learn to exploit the body’s own medicine to prevent the obesity epidemic and type 2 diabetes, says Oluf Pedersen.

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Factbox 1: Danish researchers involved

Scientists from a number of Danish research institutions and hospitals have participated in the study: Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen;  Lundbeck Foundation Center for Applied Medical Genomics in Personalised Disease Prediction, Prevention and Care (LuCamp); Center for Biological Sequence Analysis, Technical University of Denmark; Hagedorn Research Institute, Gentofte; Department of Systems Biology, Technical University of Denmark; Department of Biology, Faculty of Science, University of Copenhagen; University of Aarhus; University of Aalborg; University of Southern Denmark; Research Centre for Prevention and Health, Glostrup; Hospital of Vejle.

Factbox 2: The scientific article

In the article in Nature, the MetaHit scientists demonstrate that they by testing for just a few different bacteria species – with 98 % accuracy can distinguish between people with healthy intestinal bacteria and those who lack and have unhealthy bacteria. This provides promising opportunities for predicting diseases associated with an unhealthy bacterial composition in the intestines, for example type 2 diabetes and cardiovascular diseases.

Infections increase risk of mood disorders

Contact: Michael Eriksen Benrós benros@ncrr.dk 45-26-25-52-39 Aarhus University

New research shows that every third person who is diagnosed for the first time with a mood disorder has been admitted to hospital with an infection prior to the diagnosis

New research shows that every third person who is diagnosed for the first time with a mood disorder has been admitted to hospital with an infection prior to the diagnosis. The study is the largest of its kind to date to show a clear correlation between infection levels and the risk of developing mood disorders.

Anyone can suffer from an infection, for example in their stomach, urinary tract or skin. It would now appear that their distress does not necessarily end once the infection has been treated. A new PhD project shows that many people subsequently suffer from a mood disorder:

“Our study shows that the risk of developing a mood disorder increases by 62% for patients who have been admitted to hospital with an infection.  In other words, it looks as though the immune system is somehow involved in the development of mood disorders,” says Michael Eriksen Benrós, MD and PhD from Aarhus University and Psychiatric Centre Copenhagen.

He is behind the study together with researchers from Aarhus University and the University of Copenhagen as well as The Johns Hopkins University in the USA.

Three million Danes included

The study is a register study, which has involved following more than 3 million Danes. Between 1977 and 2010, more than 91,000 of these people had hospital contact in connection with a mood disorder.  It transpired that 32% of the patients had previously been admitted with an infectious disease, while 5% had been admitted with an autoimmune disease.

According to Michael Eriksen Benrós, the increased risk of mood disorders can be explained by the fact that infections affect the brain:

“Normally, the brain is protected by the so-called blood-brain barrier (BBB), but in the case of infections and inflammation, new research has shown that the brain can be affected on account of a more permeable BBB.”

“We can see that the brain is affected, whichever type of infection or autoimmune disease it is. Therefore, it is naturally important that more research is conducted into the mechanisms which lie behind the connection between the immune system and mood disorders,” says Michael Eriksen Benrós.   He hopes that knowing more about this connection will help to prevent mood disorders and improve future treatment.

Facts

  • 3.56 million Danes born between 1945 and 1996 were followed via the Danish patient registers.
  • Of these, 91,637 had hospital contact in connection with a mood disorder.
  • The study has been financed by the Stanley Medical Foundation and the National Institute of Mental Health in the USA.
  • The findings have just been published in the prestigious international journal JAMA Psychiatry.

 

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Further information

Michael Eriksen Benrós, MD and PhD Aarhus University and the University of Copenhagen Tel.: +45 2625 5239 benros@ncrr.dk

Quantum Teleportation Between Atomic Systems Over Long Distances

There are two glass containers, each containing a cloud of billions of caesium gas atoms. Both glass containers are enclosed in a chamber with a magnetic field. The two glass containers are not connected to each other, but information is teleported from the one glass cloud to the other by means of laser light. (Credit: Image courtesy of University of Copenhagen – Niels Bohr Institute)

June 6, 2013 — Researchers have been able to teleport information from light to light at a quantum level for several years. In 2006, researchers at the Niels Bohr Institute succeeded in teleporting between light and gas atoms. Now the research group has succeeded in teleporting information between two clouds of gas atoms and to carry out the teleportation — not just one or a few times, but successfully every single time.

The results are published in the scientific journal, Nature Physics.

“It is a very important step for quantum information research to have achieved such stable results that every attempt will succeed,” says Eugene Polzik, professor and head of the research center Quantop at the Niels Bohr Institute at the University of Copenhagen.

The experiments are conducted in the laboratories of the research group in the basement under the Niels Bohr Institute. There are two glass containers, each containing a cloud of billions of caesium gas atoms.

The two glass containers are not connected to each other, but information is teleported from the one glass cloud to the other by means of laser light. The light is sent into the first glass container and then that strange quantum phenomenon takes place, the light and gas become entangled. The fact that they are entangled means that they have established a quantum link — they are synchronised.

Both glass containers are enclosed in a chamber with a magnetic field and when the laser light (with a specific wavelength) hits the gas atoms, the outermost electrons in the atoms react -like magnetic needles — by pointing in the same direction. The direction can be up or down, and it is this direction that makes up quantum information, in the same way that regular computer information is made up of the numbers 0 and 1.

The gas now emits photons (light particles) containing quantum information. The light is sent on to the other gas container and the quantum information is now read from the light and registered by a detector. The signal from the detector is sent back to the first container and the direction of the atoms’ electrons are adjusted in relation to the signal. This completes the teleportation from the second to the first container.

New method

The experiments are carried out at room temperature and the gas atoms therefore move at a speed of 200 meters per second in the glass container, so they are constantly bumping into the glass wall and thus lose the information they have just been encoded with. But the research group has developed a solution for this.

“We use a coating of a kind of paraffin on the interior of the glass contains and it causes the gas atoms to not lose their coding, even if they bump into the glass wall,” explains Professor Eugene Polzik. It sounds like an easy solution, but in reality it was complicated to develop the method. Another element of the experiment was to develop the detector that registers the photons. Here the researchers developed a particularly sensitive detector that is very effective at detecting the photons. The experiments therefore works every single time.

But it is one thing to perform tests in a laboratory and quite another to apply it in wider society! In the experiment, the teleportation’s range is ½ meter — hardly impressive in a world where information must be transported around the world in no time.

“The range of ½ meter is entirely due to the size of the laboratory,” explains Eugene Polzik with a big smile and continues — “we could increase the range if we had the space and, in principle, we could teleport information, for example, to a satellite.” The stable results are an important step towards the quantum communication network of the future.

http://www.sciencedaily.com/releases/2013/06/130606140844.htm

 

146th Health Research Report 11 JAN 2013

 

 

In this issue:

1. Foodborne Illness Could Have Sinister Causes : Medications being intentionally added

2. Cholesterol medicine affects energy production in muscles

3. Sublingual immunotherapy shows promise as treatment for peanut allergy

4. Hold the diet soda? Sweetened drinks linked to depression, coffee tied to lower risk

5. Disappearing bacterium may protect against stroke

6. High fiber diet prevents prostate cancer progression

7. High Fructose Corn Syrup Direct Correlation with Autism in the U.S. – Clin Epigenetics. 2012 (Excerpt)

 

 

 

Foodborne Illness Could Have Sinister Causes : Medications being intentionally added

Observation Article: Foodborne Illness Could Have Sinister Causes

Doctors should consider the intentional addition of medicine to food as a potential cause of foodborne disease outbreaks. The World Health Organization suggests possible sources of foodborne disease outbreaks are pathogenic bacteria, viruses, protozoa, parasitic worms, natural toxins, and chemicals, but not medicines. A 2010 foodborne disease outbreak in Beijing, China was a result of clonidine, a medication used to treat hypertension and ADHD, being intentionally added to lunch ingredients. Eighty travelers who had just finished lunch in a Beijing restaurant began to feel faint. Within a few hours they developed dizziness, weakness, lethargy, dry mouth, and nausea, among other troublesome symptoms. At a nearby hospital, the travelers were treated for low blood pressure and low heart rate. With no response to treatment, the patients were referred for a screening for common toxins and drugs. The screening found clonidine in the patients’ systems. The patients were treated for clonidine poisoning and symptoms resolved in all patients within 48 hours. After six days, all patients had been discharged from the hospital and at one year no patients had residual symptoms. An investigation found that two persons put clonidine into the starch used to make certain dishes (the kitchen staff would not notice the addition because starch and clonidine are both white, odorless powders) to gain a competitive advantage for a nearby restaurant.

Cholesterol medicine affects energy production in muscles

Painful side effects

Up to 75 per cent of patients who take statins to treat elevated cholesterol levels may suffer from muscle pain. Scientists at the Center for Healthy Aging at the University of Copenhagen have now identified a possible mechanism underlying this unfortunate side effect. The results have just been published in the well-reputed Journal of American College of Cardiology.

Statin is a class of drugs which are used to treat high levels of blood cholesterol by way of inhibiting the liver’s ability to produce cholesterol. Statins are the most potent drugs on the market for lowering low-density cholesterol (LDL). At present 600,000 Danes with elevated cholesterol levels take statins daily. 30-40 per cent of the older Danish population (ages 65+) are currently undergoing treatment.

From 30-40% of the older Danish population (ages 65+) are currently undergoing treatment with statins.

“A well-known side effect of statin therapy is muscle pain. Up to 75 per cent of the physically active patients undergoing treatment for high cholesterol experience pain. This may keep people away from either taking their medicine or from taking exercise – both of which are bad choices,” says Professor Flemming Dela from the Center for Healthy Aging at the University of Copenhagen. He continues:

“We have now shown that statin treatment affects the energy production in muscles. We are working on the assumption that this can be the direct cause of muscle weakness and pain in thepatients.”

Scientists also showed that the patients examined who were being treated with statins had low levels of the key protein Q10. Q10 depletion and ensuing lower energy production in the muscles could be the biological cause of the muscle pain that is a problem for many patients.

Side effects of statin therapy

About 40 per cent of the patients being treated with statins in Denmark are in so-called ’mono therapy’ and thus are prescribed only this one drug. Presumably these are people who ‘only’ have high cholesterol and no other risk factors that could influence heart health:

“The effect of statins is marginal for these patients – in a previous published Cochrane analysis only 0.5% reduction in all-cause mortality was detected, indicating that for every 200 patients taking statins daily for five years, one death would be prevented. This patient group is obviously interesting in light of the side effects of statin therapy,” comments Professor Flemming Dela.

The media influence patients

“The new study is the basis for a large planned research project, where we will focus broadly on patients undergoing statin treatment. We will look at statin consumption from a medical point of view, and will also investigate the media’s influence on patients’ acceptance or rejection of statins as a treatment option. Many contradictory views find their way into the public forum, and it can be difficult for patients to distinguish between fact and fiction,” continues Professor Flemming Dela.

Scientists will also be looking at how home-monitoring of cholesterol levels influences patients – for example, does it make patients feel more or less secure when they take responsibility for their own health in this manner? The Center for Healthy Aging is currently seeking funding for the research project.

See scientific article Simvastatin Effects on Skeletal Muscle in Journal of American College of Cardiology.

Contact:

Professor Flemming Dela Phone: +45 35 32 74 25

Sublingual immunotherapy shows promise as treatment for peanut allergy

CHAPEL HILL, N.C. – Peanuts are one of the most common triggers of severe food-induced allergic reactions, which can be fatal, and the prevalence of peanut allergy is increasing. However, there is currently no clinical treatment available for peanut allergy other than strict dietary elimination and, in cases of accidental ingestion, injections of epinephrine.

But a new multicenter clinical trial shows promise for sublingual immunotherapy (SLIT), a treatment in which patients are given daily doses, in gradually increasing amounts, of a liquid containing peanut powder. The patients first hold the liquid under the tongue for 2 minutes and then swallow it.

The two lead authors of the study, published in the January 2013 issue of the Journal of Allergy and Clinical Immunology, are David M. Fleischer, MD, of National Jewish Health in Denver, Colo., and Wesley Burks, MD, Curnen Distinguished Professor and Chair of the Department of Pediatrics in the University of North Carolina School of Medicine.

“These results are encouraging,” Burks said. “The immune response was stronger than we thought it might be, and the side effects of this treatment were relatively small. However, the magnitude of the therapeutic effect was somewhat less than we had anticipated. That’s an issue we plan to address in future studies.”

In the study, 40 people with peanut allergy, ages 12 to 37 years, were randomized to receive daily peanut or placebo SLIT. All were given a baseline oral food challenge of up to 2 grams of peanut powder to test how much peanut powder they could consume without symptoms.

After 44 weeks, all were given a second oral food challenge. Those who were able to consume either 5 grams, or at least 10-fold more peanut powder than their baseline amount, were considered to be responders (i.e., desensitized to peanut). At 44 weeks, 70 percent of those who received peanut SLIT were responders, compared to 15 percent of those receiving placebo. Among the peanut-SLIT responders, the median amount of peanut powder they could successfully consume increased from 3.5 to 496 milligrams. After 68 weeks, that amount increased significantly, to 996 milligrams.

Of 10,855 peanut doses given through week 44 of the study, 63.1 percent were symptom-free. When oral/pharyngeal symptoms were excluded from the analysis, 95.2 percent of doses were symptom-free.

The study concluded that peanut SLIT safely induced desensitization in a majority of participants compared to placebo, and that longer duration of therapy led to significant increases in the amount of peanut powder people could safely consume.

However, Burks cautions, this is not a treatment that people should try on their own. For now it’s a treatment that should only be given by medical professionals in a carefully monitored clinical trial, he said.

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Study participants were recruited from five U.S. sites: New York, N.Y.; Baltimore, Md.; Little Rock, Ark.; Denver, Colo.; and Durham, N.C. Study co-authors include researchers from the University of Arkansas for Medical Sciences and Arkansas Children’s Hospital, Johns Hopkins University School of Medicine, Mount Sinai School of Medicine, the EMMES Corp. in Rockville, Md., and the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH).

The study was funded by grants from the NIAID and the NIH’s National Center for Research Resources.

Hold the diet soda? Sweetened drinks linked to depression, coffee tied to lower risk

SAN DIEGO – New research suggests that drinking sweetened beverages, especially diet drinks, is associated with an increased risk of depression in adults while drinking coffee was tied to a slightly lower risk. The study was released today and will be presented at the American Academy of Neurology’s 65th Annual Meeting in San Diego, March 16 to 23, 2013.

“Sweetened beverages, coffee and tea are commonly consumed worldwide and have important physical—and may have important mental—health consequences,” said study author Honglei Chen, MD, PhD, with the National Institutes of Health in Research Triangle Park in North Carolina and a member of the American Academy of Neurology.

The study involved 263,925 people between the ages of 50 and 71 at enrollment. From 1995 to 1996, consumption of drinks such as soda, tea, fruit punch and coffee was evaluated. About 10 years later, researchers asked the participants whether they had been diagnosed with depression since the year 2000. A total of 11,311 depression diagnoses were made.

People who drank more than four cans or cups per day of soda were 30 percent more likely to develop depression than those who drank no soda. Those who drank four cans of fruit punch per day were about 38 percent more likely to develop depression than those who did not drink sweetened drinks. People who drank four cups of coffee per day were about 10 percent less likely to develop depression than those who drank no coffee. The risk appeared to be greater for people who drank diet than regular soda, diet than regular fruit punches and for diet than regular iced tea.

“Our research suggests that cutting out or down on sweetened diet drinks or replacing them with unsweetened coffee may naturally help lower your depression risk,” said Chen. “More research is needed to confirm these findings, and people with depression should continue to take depression medications prescribed by their doctors.”

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The study was supported by the National Institutes of Health, the National Institute of Environmental Health Sciences and the National Cancer Institute.

Learn more about depression, which commonly affects people with brain diseases, at http://www.aan.com/patients.

The American Academy of Neurology, an association of more than 25,000 neurologists and neuroscience professionals, is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer’s disease, stroke, migraine, multiple sclerosis, brain injury, Parkinson’s disease and epilepsy.

For more information about the American Academy of Neurology, visit http://www.aan.com or find us on Facebook, Twitter, Google+ and YouTube.

Media Contacts:

Rachel Seroka, rseroka@aan.com, (612) 928-6129

Angela Babb, APR, ababb@aan.com, (612) 928-6102

Disappearing bacterium may protect against stroke

H. pylori isn’t a major cause of death and may protect against stroke and some cancers

New York (January 9, 2013) — A new study by NYU School of Medicine researchers reveals that an especially virulent strain of the gut bacterium Helicobacter pylori (H. pylori) isn’t implicated in the overall death rate of the U.S. population, and may even protect against stroke and some cancers. The findings, based a nationwide health survey of nearly 10,000 individuals over a period of some 12 years, are published online, January 9, in the journal Gut.

Those individuals carrying the most virulent strain of H. pylori, the study found, had a 55 percent reduced risk of deaths from stroke compared with their counterparts who were not infected with H. pylori. Participants with the most virulent strain also had a 45 percent reduced risk of death from lung cancer.

These surprising findings emerged from an analysis by Yu Chen, PhD, MPH, associate professor of population health and environmental medicine, and Martin J. Blaser, MD, professor of internal medicine and professor of microbiology, of individuals who participated in a national survey designed to assess the health and nutritional status of adults and children in the United States. Previous studies by Dr. Blaser have confirmed the bacterium’s link to gastric diseases ranging from gastritis to stomach cancer. He and Dr. Chen have more recently shown that H. pylori may protect against childhood asthma. The most virulent H. pylori strains have a gene called cagA.

“The significance of this study is that this is a prospective cohort of participants representative of the U.S. population with a long follow-up,” says Dr. Chen. “We studied both the overall H. pylori as well as cagA strain of H. pylori, which is more interactive with the human body. We found that H. pylori is not related to the risk of death from all causes, despite it being related to increased risk of death from gastric cancer.”

“This finding confirms earlier work, however, that gastric cancers are now uncommon in the United States,” says Dr. Chen. “We also found that H. pylori was related to a reduced risk of stroke and lung cancer, and these effects were stronger for the cagA strain, suggesting its mixed role in human health,” she says.

H. pylori, an ancient bacterium, lives in the mucous layer lining the stomach where, until recently, it survived for decades. More than half of the world’s population harbor H. pylori in their upper gastrointestinal tract. Mainly transmitted in families, the bacterium is usually acquired before age 10. In developing countries H. pylori is still prevalent, but is vanishing in the developed world thanks to better sanitation and widespread use of antibiotics.

To better understand the relationship between H. pylori and the overall death rate, or all-cause mortality, the researchers analyzed data from 9,895 participants in the National Health and Nutrition Surveys (NHANES III), enrolled from 1988 to 1994. Test results for H. pylori and cagA were available on 7,384 subjects at the time of enrollment, and participants were followed until 2000.

There was no association of either H. pylori-positivity or cagA-positivity with all-cause mortality in the population, the researchers found. Participants with and without H. pylori experienced a similar risk of death from all causes. Consistent with past reports, a strong association was observed between H. pylori and gastric cancer mortality, according to the study. Individuals who were H. pylori positive were 40 times more likely to die from gastric cancer. The study also found that participants with cagA-positivity had a 55 percent reduced risk of deaths from stroke compared with their counterparts who were H. pylori negative/ cagA-negative. Participants with cagA-positivity also had a 45 percent reduced risk of deaths from lung cancer.

“The most interesting finding was that there is a strong inverse association with stroke which could be protective,” says Dr. Blaser. “There is some precedent for this and it is possible that the same cells (T reg cells) that H. pylori induces that protect against childhood asthma could be the protective agents, however, the findings need to be confirmed.”

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Authors: Yu Chen. PhD, MPH, associate professor, Departments of Population Health and Environmental Medicine; Stephanie Segers, MPH, statistician, Department of Population Health; Martin J. Blaser, MD, professor, Departments of Medicine and Microbiology.

Competing Interests: None reported.

Funding/Support: This work was supported in part by grants R01DK090989, R01GM63270, ES000260, and P30CA16087 from the National Institutes of Health, and by the Diane Belfer Program for Human Microbial Ecology.

About NYU School of Medicine:

NYU Langone Medical Center, a world-class, patient-centered, integrated, academic medical center, is one on the nation’s premier centers for excellence in clinical care, biomedical research and medical education. Located in the heart of Manhattan, NYU Langone is composed of three hospitals – Tisch Hospital, its flagship acute care facility; the Rusk Institute of Rehabilitation Medicine, the world’s first university-affiliated facility devoted entirely to rehabilitation medicine; and the Hospital for Joint Diseases, one of only five hospitals in the nation dedicated to orthopaedics and rheumatology – plus the NYU School of Medicine, which since 1841 has trained thousands of physicians and scientists who have helped to shape the course of medical history. The medical center’s tri-fold mission to serve, teach and discover is achieved 365 days a year through the seamless integration of a culture devoted to excellence in patient care, education and research.

High fiber diet prevents prostate cancer progression

By Garth Sundem in In the Lab · January 9, 2013 · No comments

Komal Raina, PhD, shows that prostate cancers in mice fed a high-fiber diet fail to progress.

A high-fiber diet may have the clinical potential to control the progression of prostate cancer in patients diagnosed in early stages of the disease.

The rate of prostate cancer occurrence in Asian cultures is similar to the rate in Western cultures, but in the West, prostate cancer tends to progress, whereas in Asian cultures it does not. Why? A University of Colorado Cancer Center study published in the January 2013 issue of the journal Cancer Prevention Research shows that the answer may be a high-fiber diet.

The study compared mice fed with of inositol hexaphosphate (IP6), a major component of high-fiber diets, to control mice that were not. Then the study used MRI to monitor the progression of prostate cancer in these models.

“The study’s results were really rather profound. We saw dramatically reduced tumor volumes, primarily due to the anti-angiogenic effects of IP6,” says Komal Raina, PhD, research instructor at the Skaggs School of Pharmacy and Pharmaceutical Sciences, working in the lab of CU Cancer Center investigator and School of Pharmacy faculty member, Rajesh Agarwal, PhD.

Basically, feeding with the active ingredient of a high-fiber diet kept prostate tumors from making the new blood vessels they needed to supply themselves with energy. Without this energy, prostate cancer couldn’t grow. Likewise, treatment with IP6 slowed the rate at which prostate cancers metabolized glucose.

Possible mechanisms for the effect of IP6 against metabolism include a reduction in a protein called GLUT-4, which is instrumental in transporting glucose.

“Researchers have long been looking for genetic variations between Asian and Western peoples that could explain the difference in prostate cancer progression rates, but now it seems as if the difference may not be genetic but dietary. Asian cultures get IP6 whereas Western cultures generally do not,” Raina says.

The research provides the cover image of this month’s issue of the journal.

Support provided in part by NCI RO1grant CA116636, the NCI Cancer Center P30 CA046934, and the NCRR CTSA UL1 RR025780

Herbal treatments for postmenopausal symptoms can be recommended as an alternative to HRT

Herbal and complementary medicines could be recommended as an alternative to hormone replacement therapy (HRT) for treating postmenopausal symptoms says a new review published today in The Obstetrician and Gynaecologist (TOG).

The review outlines the advantages and limitations of both pharmacological and herbal and complementary treatments for women with postmenopausal symptoms.

The menopause is defined as the time after a woman’s menstrual periods have ceased (12 months after a woman’s final menstrual period). It is associated with an estrogen deficiency and can cause an increase in vasomotor symptoms (hot flushes), genitourinary symptoms (vaginal dryness, sexual dysfunction, frequent urinary tract infections, urinary incontinence), and musculoskeletal symptoms (joint pain) as well as sleep and mood disturbance.

One of the most common menopausal symptoms is hot flushes; approximately two-thirds of postmenopausal women will experience them, and 20% of women can experience them for up to 15 years, states the review.

Estrogen deficiency can also lead to longer-term health issues such as cardiovascular disease and osteoporosis. While pharmacological agents are available to treat postmenopausal symptoms, many non-pharmacological treatment options are also available.

HRT is the most effective treatment of hot flushes, improving symptoms in 80 – 90% of women, says the review. However, the author notes that there are possible health risks associated with HRT, such as links to breast cancer, blood clots, stroke, and cardiovascular problems.

Due to these possible risks, other treatment options may be equally effective, such as behaviour modification and herbal and complimentary medicines, says the author.

The review states that as many as 50 – 75% of postmenopausal women use herbal options to treat hot flushes, and of the complimentary therapies, soy, red clover and black cohosh have been the most investigated.

Soy is the most common plant containing estrogen, found naturally in food and supplements. Previous research has shown a reduction in hot flush symptoms with soy ranging from 20 – 55%. Red clover, a legume also containing estrogen, and black cohosh, a plant originating from the eastern United States and Canada, have also been reported to ease postmenopausal symptoms.

The author of the review recommends these herbal treatments as there are no significant adverse side effects associated with them, as long as they are used in women who do not have a personal history of breast cancer, are not at high risk for breast cancer, and are not taking tamoxifen. However, the review notes that herbal medicines are not regulated in many countries, and therefore the contents of a given product may vary from sample to sample.

Iris Tong, Director of Women’s Primary Care at the Women’s Medicine Collaborative, The Warren Alpert Medical School of Brown University, Rhode Island, and author of the review said:

“Up to 75% of women use herbal and complimentary medicines to treat their postmenopausal symptoms. Therefore, it is vitally important for healthcare providers to be aware of and informed about the non-pharmacological therapies available for women who are experiencing postmenopausal symptoms and who are looking for an alternative to HRT.”

TOG‘s Editor –in-Chief, Jason Waugh said:

“Postmenopausal symptoms can be very distressing and it is important to review the advantages and limitations of the non-pharmacological treatments available as well as the pharmacological ones. Even simple behaviour modification can make a difference to postmenopausal symptoms, including keeping the room temperature cool, wearing layered clothing, relaxation techniques and smoking cessation.”

High Fructose Corn Syrup Direct Correlation with Autism in the U.S. – Clin Epigenetics. 2012 (Excerpt)

EEV: Highlights Although there are many potential causes. We chose to highlight HFCS, due to its toxin amplification.

1) Ca, Mg and Zn, or losses or displacement of any of these minerals from the consumption of HFCS

2) mercury (Hg) and fructose may both modulate PON1 activity

3) mercury (Hg) that may occur from the low Hg concentrations sometimes found in HFCS as a result of the manufacturing process

4) HFCS, may further enhance the toxic effects of lead (Pb) on cognitive and behavioral development in children

2nd Source http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378453/

Initial Study date: 10 APR 2012

A macroepigenetic approach to identify factors responsible for the autism epidemic in the United States

Abstract

The number of children ages 6 to 21 in the United States receiving special education services under the autism disability category increased 91% between 2005 to 2010 while the number of children receiving special education services overall declined by 5%. The demand for special education services continues to rise in disability categories associated with pervasive developmental disorders. Neurodevelopment can be adversely impacted when gene expression is altered by dietary transcription factors, such as zinc insufficiency or deficiency, or by exposure to toxic substances found in our environment, such as mercury or organophosphate pesticides. Gene expression patterns differ geographically between populations and within populations. Gene variants of paraoxonase-1 are associated with autism in North America, but not in Italy, indicating regional specificity in gene-environment interactions. In the current review, we utilize a novel macroepigenetic approach to compare variations in diet and toxic substance exposure between these two geographical populations to determine the likely factors responsible for the autism epidemic in the United States.

A macroepigenetic model to explain gene-environment interactions in autism

In public health, epidemiology arguably has led the way in researching gene-environment interactions by studying how genotypes, environmental exposures and disorder outcomes occur in the human population [5]. However, this epidemiological approach has often resulted in contradictory scientific conclusions when its practitioners do not consider the dietary factors that interact and modulate the molecular and genetic mechanisms underlying human metabolism and brain function [14]. This has been the case despite the existence of literature from the field of “nutrigenomics”, which has specifically studied the effects of food and food ingredients on gene expression. In identifying the public health and the social and/or environmental determinants of disease, it seems invalid to study epidemiology without nutrigenomics, or vice versa. In other words, a more macro-level approach to unraveling the full range of environmental and genetic factors contributing to these kinds of neurological disorders ought to include nutrition factors as a component of the environment. By combining information derived from both nutrigenomic and epidemiology studies, a macroepigenetic model has already been developed to explain some of the gene-environment interactions with dietary factors that lead to the development of autism and ADHD [4].

Figure 1 shows the Mercury Toxicity model that provides a macroepigenetic explanation of how human neurodevelopment can be adversely impacted when gene expression is altered by dietary transcription factors such as zinc insufficiency or deficiency, or by exposure to toxic substances found in our environment, such as the heavy metals mercury and copper [4]. Elimination of heavy metals requires the expression of the metallothionein (MT) gene, which synthesizes the Zn-dependent metal binding protein metallothionein [15]. With dietary zinc (Zn) loss and copper (Cu) gain from the consumption of high fructose corn syrup (HFCS) [16], metabolic processes required to eliminate heavy metals are impaired in children with autism [4]. Mercury has been found in samples of high fructose corn syrup and is allowable in trace amounts in certain food colors so long as the concentration does not exceed one part per million [17,18]. Mercury (Hg) and specific other heavy metals, including lead (Pb), copper (Cu), cadmium (Cd), silver (Ag) and bismuth (Bi), are capable of displacing the Zn atom in the MT protein molecule [15]. This ‘pathogenic’ displacement of Zn impairs the MT molecule and its ability to pick up the heavy metal and carry it out of the body. If the diet is deficient in Zn or the absorption of Zn is impaired, then the body may not produce enough MT protein to carry and excrete the heavy metal load [19,20]. Children with autism may be Zn deficient and often have MT dysfunction [2123]. Because of their diminished capacity to excrete toxic heavy metals, the severity of their condition is associated with their toxic metal burden [24]. This macroepigenetic model proposes that autism prevalence is related to the consumption of HFCS and the overall exposure to Hg in the U.S. [4]. However, other dietary factors associated with the consumption of HFCS may further contribute to the development of autism in the U.S.

                        Figure 1. The original Mercury Toxicity Model. The original Mercury Toxicity Model was published in 2009 by Dufault et al. in the Behavioral and Brain Functions journal. The model is a flow chart of what can happen in the body when there is exposure to mercury (Hg) from ingestion of foods (via HFCS, food colors and fish) or inhalation of air. Human neurodevelopment can be adversely impacted when MT gene expression is altered or suppressed by dietary transcription factors such as zinc (Zn) insufficiency or deficiency. Without proper MT expression and function, mercury excretion may not be possible and oxidative stress in the brain from mercury insult leads to reduced neuronal plasticity and impaired learning. Hg in fish is a problem when there is not enough selenium (Se) in the fish to counteract the Hg and the glutathione (GSH) system is disrupted leading to further oxidative stress.

Additional dietary factors associated with consumption of HFCS

U.S. per capita consumption of HFCS in 2009 was 35.7 pounds per year [25]. The peak years for annual consumption of HFCS coincided with the peak growth rates of ASD in California, the only state that reports number of cases of ASD dating back to the mid-1980s [4]. The Mercury Toxicity Model shows the HFCS characteristics most likely contributing to autism include the zinc-depleting effect that comes from consuming HFCS and certain food colors found in processed foods, and the additional Hg exposure that may occur from the low Hg concentrations sometimes found in HFCS as a result of the manufacturing process [4,17]. This model can be expanded to include additional adverse effects associated with the consumption of HFCS that likely contribute to the development of autism through PON1 gene modulation and lead intoxication.

U.S. Department of Agriculture (USDA) scientists warn that when dietary intake of magnesium (Mg) is low, consumption of HFCS leads to lower calcium (Ca) and phosphorus (P) balances adversely affecting macromineral homeostasis in humans [26]. This is an unfortunate finding because there is evidence to suggest that dietary intake of Mg is low among Americans, most of whom consume a high fructose diet. In 2003, CDC scientists reported that substantial numbers of U.S. adults fail to consume adequate Mg in their diets [27]. Children with autism were found to have significantly lower plasma Mg concentrations than normal subjects [28]. Adams et al. found significant reductions in red blood cell (RBC) Ca, serum and white blood cell (WBC) Mg and an increase in RBC copper in autistic children as compared to controls [29]. Recently, USDA scientists reported that the National Health and Nutrition Examination Survey (NHANES) data for 2005 to 2006 indicate that overall, nearly one half of all individuals one year and over had inadequate intakes of dietary Mg [30]. With a substantial number of Americans consuming inadequate amounts of dietary Mg along with HFCS diets, one may predict that substantial numbers of Americans are likely experiencing a calcium (Ca) deficit as well.

Insufficient intake of dietary Ca, Mg and Zn, or losses or displacement of any of these minerals from the consumption of HFCS, may further enhance the toxic effects of lead (Pb) on cognitive and behavioral development in children [31]. A significant and independent inverse relationship between dietary Ca intake and blood Pb concentrations was found in 3,000 American children examined as part of NHANES II [32]. Elevated blood Pb levels are indicative of Pb intoxication, which is found in some children diagnosed with autism and associated with the development of ADHD [33,34]. It may be that inadequate intake of Ca or Mg combined with a HFCS zinc-depleting diet increases the risk of developing autism and ADHD from Pb intoxication.

Inadequate intake of Ca or Mg may further contribute to these developmental disorders by impacting human serum paraoxonase-1 (PON1) gene expression. PON1 is a calcium dependent enzyme responsible for OP pesticide detoxification as well as hydrolysis of the thiolactone form of homocysteine [35,36]. PON1 is synthesized in the liver and secreted in blood where it is incorporated into high density lipoproteins (HDL). The availability and catalytic activity of PON1 are impaired in many children with ASD making them more susceptible to the toxic effects of OP pesticide residues which are most frequently found in grain [37,38]. Figure 2 shows the expanded Mercury Toxicity Model that includes changes both in Pb toxicity and PON1 activity when dietary intake of Mg is low and consumption of HFCS leads to greater loss of calcium (Ca) and phosphorus (P), thereby adversely affecting macromineral homeostasis.

Figure 2. The expanded Mercury Toxicity Model. Figure 2 shows the expanding Mercury Toxicity Model that includes changes both in lead (Pb) toxicity and human serum paraoxonase (PON1) activity when dietary intake of Mg is low and consumption of high fructose corn syrup (HFCS) leads to lower calcium (Ca) and phosphorus (P) balances, adversely affecting macromineral homeostasis. With insufficient dietary intake of Ca and/or Mg, children become more susceptible to Pb intoxication and OP exposures with decreasing PON1 activity. Pb intoxication and OP exposures can both lead to oxidative stress in the brain reducing neuronal plasticity.

PON1 activity and organophosphate exposure in U.S

One can assert that with the consumption of a HFCS intensive diet and inadequate Mg intakes, PON1 activity may decrease, along with resulting Ca losses in genetically predisposed individuals. Although there are no human data yet to support this assertion, PON1 activity in rats decreased when fed a HFCS diet to mimic the human metabolic syndrome [39]. PON1 activity has been extensively studied in humans and there are a number of factors known to modulate or alter PON1 expression including, but not limited to, Hg exposure, sex and age [40,41]. Age plays the most relevant role, as PON1 activity is very low before birth and gradually increases during the first few years of life in humans [41]. In one study, scientists at UC Berkeley found the PON1 levels in many children may remain lower than those of their mothers for several years, especially those with genotypes associated with decreased PON1 activities [42]. The scientists concluded that these children may be more susceptible to OP pesticides throughout their childhood and more vulnerable to conditions associated with oxidative stress such as autism [42]. In a different study, scientists at UC Berkeley found that two-year-old children were less likely to display symptoms of PDD when their mothers had higher paraoxonase levels during their pregnancy [43]. Proper function and adequate expression of the PON1 gene is essential both for prenatal development and child health because exposure to OP pesticides is a common occurrence in the U.S.

The CDC tracks exposure to OP pesticides or their metabolites through the National Biomonitoring Program (NBP). Exposure data are reported for the population as a whole and for subgroups. While most American groups are exposed to OP pesticides, children ages 6 to 11 have significantly higher exposures than adults and are at greatest risk from OP neurotoxicity [44]. Harvard University researchers recently reported finding OP pesticide residues in a number of foods frequently consumed by children [45]. The researchers expressed concern that the children were at times being exposed to multiple pesticide residues in single food commodities. OP pesticide exposures occur primarily from the consumption of foods containing pesticide residues.

It is well known that pesticide exposure can impair neurodevelopment in children, but recent studies have found that pesticide exposure during pregnancy can also cause delayed mental development in children [46]. A review of epidemiological studies in 2008 found that prenatal and childhood exposure to OPs impairs neurobehavioral development [47]. Higher concentrations of urinary dialkyl phosphate (DAP) measured during pregnancy was significantly associated with lower cognitive scores in children at seven years of age. Those children in the highest quintile of maternal DAP concentrations had an IQ score seven points lower than those children in the lowest quintile [48]. In a group of newborns with the highest levels of the organophosphate chlorpyrifos measurable in their umbilical cord blood, birth weight averaged 150 grams less than the group with the lowest exposure [49]. Prenatal pesticide exposure showed deficits consistent with developmental delays of 1.5 to 2 years [49].

Diet is the main source of OP exposure in children. Under the 1996 Food Quality Protection Act, the U.S. Secretary of Agriculture is directed to collect pesticide residue data on commodities frequently consumed by infants and children. USDA Pesticide Data Program (PDP) provides the residue data to comply with this law [50]. We reviewed the PDP data from 2004 to 2008 and identified the foods most frequently found to contain organophosphate insecticide residues. In addition, we obtained the per capita availability data from the USDA to determine the amount of each food commodity the average American consumes [25]. The results of our review indicate that wheat and corn are the commodities most likely contributing to OP exposure in U. S. children. Estimated per capita wheat consumption was approximately 95 pounds per year while estimated per capita corn consumption was approximately 23 pounds per year. The primary use of corn is for the production of corn sweeteners, such as HFCS; however, pesticide residue data were not gathered for this commodity by the PDP. Table 2 provides a complete breakdown of the results of this data review.

Table 2. PDP residue detections by year sampled wi th U.S. per capita consumption data

From Table 2 it is clear consumers are at risk of exposure to multiple OP pesticide residues from consuming the very same commodity. Cumulative exposures will continue to occur in the U.S. where OP pesticide use is widespread by the agricultural industry. Although OP pesticide use is equally widespread in other countries, there is genetic variation across populations that determine degree of susceptibility to OP exposure. The PON1 gene variants associated with autism in subgroups of the U.S. population but not in Italy could be attributed to the fact that HFCS consumption rarely occurs in Italy, thereby lessening the conditions for PON1 modulation.

HFCS consumption and PON1 modulation in autism in the U.S

In the 27-member European Union (EU), of which Italy is an original participant, HFCS is known as “isoglucose” and currently it is rarely consumed by Italians. Americans on the other hand consume on average 35.7 pounds per year, which may increase their overall Hg exposure [17,25]. Figure 3 shows U.S. per capita food consumption in pounds per year for HFCS beginning in the early 1970s and increasing throughout the 1980s to reach a peak between 1999 and 2002. In our previous publication, we reported the peak years for annual consumption of HFCS in the U.S. occurred within the same period as when the annual growth rates of autism peaked in California [4].

Figure 3. U.S. per capita consumption of high fructose corn syrup 1966-2004. Figure 3 shows the United States (US) per capita consumption of high fructose corn syrup (HFCS) in pounds per year as calculated by the United States Department of Agriculture (USDA)/Economic Research Service.

American per capita consumption of HFCS has exceeded 20 pounds per year since 1980 while Italians consume negligible amounts of the same ingredient. As was previously mentioned, mercury (Hg) and fructose may both modulate PON1 activity [3941]. While excessive fructose exposure in the U.S. may primarily occur through the consumption of foods containing HFCS, mercury exposure may occur in a number of ways. A comparison of common sources of mercury exposure in the U.S. and Italy may offer a further explanation of the PON1 gene variation associated with autism in the U.S. but not in Italy.

In addition to HFCS, primary sources of inorganic and elemental Hg exposure may occur from consumption of food colors and preservatives made with mercury-cell chlorine or chlor-alkali products, seafood consumption, Hg in dental amalgam, thimerosal in vaccines, and depending on geographic location, inhalation of Hg contaminated air [4,5154]. Children living near coal-fired power plants are often exposed to higher levels of Hg in their breathing air and have a higher prevalence of autism [55]. Because Hg emissions from coal-fired power plants are not yet regulated in either the U.S. or Italy, this particular source of Hg exposure is unlikely to explain the overall difference in autism prevalence between these two countries. With respect to the consumption of seafood, use of Hg dental amalgam, thimerosal in vaccines or Hg-containing food colors and preservatives, there is also no appreciable difference between Italy and the U.S. [5658]. The only remaining variable in our model is the excessive consumption of HFCS by Americans, which results in greater chronic exposures to both inorganic Hg and, by definition, fructose [4].

Inorganic Hg may interact with cysteine residues on PON1 preventing its activation in the liver and impairing the body’s ability to protect itself against OP pesticides and oxidative stressors involved in autism [41]. As noted above, PON1 is responsible for hydrolysis of homocysteine thiolactone, and plasma PON1 activity is negatively correlated with homocysteine levels [36,59]. Homocysteine is a metabolic biomarker for oxidative stress and impaired methylation capacity. A recent study of the Inuit population found a significant inverse correlation between PON1 activity and Hg levels, as well as a direct correlation with selenium levels [60]. With increasing Hg and fructose exposure and reductions in dietary Ca, one can expect to see reduced PON1 activity and increasing homocysteine levels in children with ASD.

Indeed, Pasca et al. recently reported finding that both PON1 arylesterase and PON1 paraoxonase activities were decreased in children with autism [61,62]. James et al. found that children with autism had higher plasma homocysteine levels than controls but demonstrated significant improvements in transmethylation metabolites and glutathione (GSH) after receiving folate and vitamin B12 [63]. Patel and Curtis found that in addition to glutathione and B12 injections one to three times per week, children with autism and ADHD showed significant improvement in many areas of social interaction, concentration, writing, language and behavior when fed an organic diet low in fructose and free of food additives and food colors [64].

Mothers of autistic children in the U.S. were also found to have significant increases in mean plasma homocysteine levels compared to controls [65]. Schmidt et al. found that women who took vitamin supplements during the periconceptional period reduced the risk of autism in their children [66]. Those women who did not take vitamins during this period were more likely to have a child with autism and were at even greater risk when they had specific genetic variants within one-carbon metabolism pathways. This suggests that folate and other dietary methyl donors may alter epigenetic regulation of gene expression in their children, thereby reducing the risk of autism [66].

Methionine synthase links oxidation to epigenetics

Epigenetic regulation of gene expression is highly dependent upon methylation of both DNA and histones, and methylation capacity is in turn dependent upon activity of the folate and vitamin B12-dependent enzyme methionine synthase, which converts homocysteine to methionine. Lower methionine synthase activity decreases the level of the methyl donor S-adenosylmethionine (SAM) while simultaneously increasing the level of the methylation inhibitor S-adenosylhomocysteine (SAH) [67]. The combined effect of changes in the SAM to SAH ratio, therefore, exerts a powerful influence over more than 200 methylation reactions, including DNA and histone methylation [68].

Methionine synthase activity is inhibited by oxidative stress, and its inhibition results in the diversion of homocysteine to produce the antioxidant glutathione (GSH), providing an important adaptive response [69]. However, oxidative inhibition of methionine synthase leads to epigenetic effects via the resultant decrease in the SAM to SAH ratio and decreased DNA and histone methylation. Epigenetic changes in gene expression can recruit further adaptive responses to oxidative stress. Figure 4 illustrates how these changes may occur when the body is under oxidative stress from exposure to OP pesticides, heavy metals, and calcium depleting substances, such as HFCS. Decreased methionine synthase activity during oxidative stress also increases homocysteine thiolactone formation [70], raising the importance of PON1. As was previously mentioned, PON1 is essential for reducing homocysteine levels, which are thought to be harmful. Elevated plasma homocysteine (tHcy) levels are associated with genome-wide DNA hypomethylation that may carry over from one generation to the next, increasing the risk of autism [71]. Epigenetic changes affecting germline cells can give rise to these transgenerational effects [72]. James et al. found that parents share similar metabolic deficits in methylation capacity and glutathione-dependent antioxidant/detoxification capacity with their children with autism [71].

Figure 4. Methionine synthase links oxidative stress to epigenetic regulation. Figure 4 shows how exposure to toxic substances, such as OP pesticides, HFCS, or heavy metals, inhibits methionine synthase through effects of oxidative stress. As a result, decrease of SAM to SAH ratio will lead to a decrease in DNA methylation and consequently to altered PON1 gene expression.

Synergistic effect of multiple neurotoxins

Based upon the discussion above, it is clear that methionine synthase activity is crucial for translating changes in oxidative status into epigenetic effects, and this role is confirmed by the improved metabolic profile in autistic subjects given folate and vitamin B12 [63]. This relationship has given rise to the “Redox/Methylation Hypothesis of Autism”, which proposed that oxidative insults arising from environmental exposures, such as Hg and pesticides, can cause neurodevelopmental disorders by disrupting epigenetic regulation [73]. The macroepigenetic Mercury Toxicity Model expanded in this paper provides additional support for the “Redox/Methylation Hypothesis of Autism” while contributing important insight into the oxidative stress feedback mechanisms that may occur as a result of malnutrition resulting from dietary exposures to toxins. The delivery of children exhibiting autistic behaviors might be associated with the prenatal diet of their mothers. The severity of these behaviors can be further exacerbated by toxic dietary exposures of the children, which can improve with dietary changes aimed at eliminating these exposures. Children with autism could well be exhibiting an epigenetic response to several neurotoxic substances at once, including, but not limited to, inorganic Hg, Pb, OP pesticides and/or HFCS. The combined effect of these substances acting together is likely greater than the sum of the effects of the substances acting by themselves. This effect likely reduces neuronal plasticity and impairs learning capacity in autistic children.

Conclusion

The number of children ages 6 to 21 in the U.S. receiving special education services under the autism disability category increased 91% between 2005 to 2010 despite fewer children receiving special education services overall during the same time period. A comparison of autism prevalence between the U.S. and Italy using the Mercury Toxicity Model suggests the increase in autism in the U.S. is not related to mercury exposure from fish, coal-fired power plants, thimerosal, or dental amalgam but instead to the consumption of HFCS. Consumption of HFCS may lead to mineral imbalances, including Zn, Ca and P loss and Cu gain and is a potential source of inorganic mercury exposure. These mineral imbalances create multiple pathways for oxidative stress in the brain from exposure to OP pesticides and heavy metals, such as Pb or Hg. Inorganic mercury and fructose exposure from HFCS consumption may both modulate PON1 gene expression. With a reduction in PON1 activity, there is a potential for increasing homocysteine levels which are associated with genome-wide DNA hypomethylation that may carry over from one generation to the next, affecting both neurodevelopment and autism prevalence.

v

These reports are done with the appreciation of all the Doctors, Scientist, and other Medical Researchers who sacrificed their time and effort. In order to give people the ability to empower themselves. Without base aspirations of fame, or fortune. Just honorable people, doing honorable things.

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Health Research Report

146th Issue Date 11 JAN 2013

Compiled By Ralph Turchiano

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Cholesterol medicine affects energy production in muscles: Up to 75 per cent of patients

Painful side effects

Up to 75 per cent of patients who take statins to treat elevated cholesterol levels may suffer from muscle pain. Scientists at the Center for Healthy Aging at the University of Copenhagen have now identified a possible mechanism underlying this unfortunate side effect. The results have just been published in the well-reputed Journal of American College of Cardiology.

Statin is a class of drugs which are used to treat high levels of blood cholesterol by way of inhibiting the liver’s ability to produce cholesterol. Statins are the most potent drugs on the market for lowering low-density cholesterol (LDL). At present 600,000 Danes with elevated cholesterol levels take statins daily. 30-40 per cent of the older Danish population (ages 65+) are currently undergoing treatment.

From 30-40% of the older Danish population (ages 65+) are currently undergoing treatment with statins.

“A well-known side effect of statin therapy is muscle pain. Up to 75 per cent of the physically active patients undergoing treatment for high cholesterol experience pain. This may keep people away from either taking their medicine or from taking exercise – both of which are bad choices,” says Professor Flemming Dela from the Center for Healthy Aging at the University of Copenhagen. He continues:

“We have now shown that statin treatment affects the energy production in muscles. We are working on the assumption that this can be the direct cause of muscle weakness and pain in thepatients.”

Scientists also showed that the patients examined who were being treated with statins had low levels of the key protein Q10. Q10 depletion and ensuing lower energy production in the muscles could be the biological cause of the muscle pain that is a problem for many patients.

Side effects of statin therapy

About 40 per cent of the patients being treated with statins in Denmark are in so-called ’mono therapy’ and thus are prescribed only this one drug. Presumably these are people who ‘only’ have high cholesterol and no other risk factors that could influence heart health:
“The effect of statins is marginal for these patients – in a previous published Cochrane analysis only 0.5% reduction in all-cause mortality was detected, indicating that for every 200 patients taking statins daily for five years, one death would be prevented. This patient group is obviously interesting in light of the side effects of statin therapy,” comments Professor Flemming Dela.

The media influence patients

“The new study is the basis for a large planned research project, where we will focus broadly on patients undergoing statin treatment. We will look at statin consumption from a medical point of view, and will also investigate the media’s influence on patients’ acceptance or rejection of statins as a treatment option. Many contradictory views find their way into the public forum, and it can be difficult for patients to distinguish between fact and fiction,” continues Professor Flemming Dela.
Scientists will also be looking at how home-monitoring of cholesterol levels influences patients – for example, does it make patients feel more or less secure when they take responsibility for their own health in this manner? The Center for Healthy Aging is currently seeking funding for the research project.

See scientific article Simvastatin Effects on Skeletal Muscle in Journal of American College of Cardiology.

Contact:

Professor Flemming Dela Phone: +45 35 32 74 25

Foetus suffers when mother lacks vitamin C

Healthy pregnancy

Maternal vitamin C deficiency during pregnancy can have serious consequences for the foetal brain. And once brain damage has occurred, it cannot be reversed by vitamin C supplements after birth. This is shown through new research at the University of Copenhagen just published in the scientific journal PLOS ONE.

vitamin C supplements are important during pregnancy.
Photo: Wikimedia Commons af Tom & Katrien.

Population studies show that between 10-20 per cent of all adults in the developed world suffer from vitamin C deficiency. Therefore, pregnant women should think twice about omitting the daily vitamin pill.

“Even marginal vitamin C deficiency in the mother stunts the foetal hippocampus, the important memory centre, by 10-15 per cent, preventing the brain from optimal development,” says Professor Jens Lykkesfeldt. He heads the group of scientists that reached this conclusion by studying pregnant guinea pigs and their pups. Just like humans, guinea pigs cannot produce vitamin C themselves, which is why they were chosen as the model.

“We used to think that the mother could protect the baby. Ordinarily there is a selective transport from mother to foetus of the substances the baby needs during pregnancy. However, it now appears that the transport is not sufficient in the case of vitamin C deficiency. Therefore it is extremely important to draw attention to this problem, which potentially can have serious consequences for the children affected,” says Jens Lykkesfeldt.

Too late when damage is done

The new results sharpen the focus on the mother’s lifestyle and nutritional status during pregnancy. The new study has also shown that the damage done to the foetal brain cannot be repaired, even if the baby is given vitamin C after birth.
When the vitamin C deficient guinea pig pups were born, scientists divided them into two groups and gave one group vitamin C supplements. However, when the pups were two months old, which corresponds to teenage in humans, there was still no improvement in the group that had been given supplements.
The scientists are now working to find out how early in the pregnancy vitamin C deficiency influences the development of foetal guinea pigs. Preliminary results show that the impact is already made early in the pregnancy, as the foetuses were examined in the second and third trimesters. Scientists hope in the long term to be able to use population studies to illuminate the problem in humans.

Vulnerable groups

There are some groups that may be particularly vulnerable of vitamin C deficiency:
“People with low economic status who eat poorly – and perhaps also smoke – often suffer from vitamin C deficiency. Comparatively speaking, their children risk being born with a poorly developed memory potential. These children may encounter learning problems, and seen in a societal context, history repeats itself because these children find it more difficult to escape the environment into which they are born,” says Jens Lykkesfeldt.
He emphasises that if pregnant women eat a varied diet, do not smoke, and for instance take a multi-vitamin tablet daily during pregnancy, there is no reason to fear vitamin C deficiency.
“Because it takes so little to avoid vitamin C deficiency, it is my hope that both politicians and the authorities will become aware that this can be a potential problem,” concludes Jens Lykkesfeldt.

Read the article in the scientific journal PLOS ONE.

Contact

Professor Jens Lykkesfeldt, Department of Veterinary Disease Biology, Biomedicine
Phone: +45 35333125

Vitamin C deficiency impairs early brain development: The brain retains vitamin C

Contact: Professor Jens Lykkesfeldt jopl@life.ku.dk 453-533-3163 University of Copenhagen

New research at LIFE — Faculty of Life Sciences at University of Copenhagen shows that vitamin C deficiency may impair the mental development of newborn babies

New research at LIFE – Faculty of Life Sciences at University of Copenhagen shows that vitamin C deficiency may impair the mental development of new-born babies.

In the latest issue of the well-known scientific journal the American Journal of Clinical Nutrition, a group of researchers headed by professor Jens Lykkesfeldt shows that guinea pigs subjected to moderate vitamin C deficiency have 30 per cent less hippocampal neurones and markedly worse spatial memory than guinea pigs given a normal diet. Like guinea pigs, human beings are dependent on getting vitamin C through their diet, and Jens Lykkesfeldt therefore speculate that vitamin C deficiency in pregnant and breast-feeding women may also lead to impaired development in foetuses and new-born babies.

The brain retains vitamin C

Several factors indicate that the neonatal brain, in contrast to other tissue, is particularly vulnerable to even a slight lowering of the vitamin C level. The highest concentration of vitamin C is found in the neurons of the brain and in case of a low intake of vitamin C, the remaining vitamin is retained in the brain to secure this organ. The vitamin thus seems to be quite important to brain activity. Tests have shown that mouse foetuses that were not able to transport vitamin C develop severe brain damage. Brain damage which resembles the ones found in premature babies and which are linked to learning and cognitive disabilities later in life.

Widespread vitamin C deficiency

In some areas in the world, vitamin C deficiency is very common – population studies in Brazil and Mexico have shown that 30 to 40 per cent of the pregnant women have too low levels of vitamin C, and the low level is also found in their foetuses and new-born babies. It is not yet known to what extent new-born babies in Denmark or the Western World suffer from vitamin C deficiency but a conservative estimate would be 5 to 10 per cent based on the occurrence among adults.

“We may thus be witnessing that children get learning disabilities because they have not gotten enough vitamin C in their early life. This is unbearable when it would be so easy to prevent this deficiency by giving a vitamin supplement to high-risk pregnant women and new mothers” says Jens Lykkesfeldt whose research group is currently studying how early in pregnancy vitamin C deficiency affects the embryonic development of guinea pigs and whether the damage may be reversed after birth.

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Read more in the scientific article Vitamin C deficiency in early postnatal life impairs spatial memory and reduces the number of hippocampal neurons in guinea pigs in the online edition of American Journal of Clinical Nutrition

Please contact Professor Jens Lykkesfeldt, Faculty of Life Sciences, University of Copenhagen for more information at tel. +45 353 33163 or by mail jopl@life.ku.dk

Prebiotic may help patients with intestinal failure grow new and better gut

Contact: Phyllis Picklesimer
p-pickle@illinois.edu
217-244-2827
University of Illinois College of Agricultural, Consumer and Environmental Sciences

URBANA – Adding the right prebiotic to the diets of pediatric patients with intestinal failure could replace intravenous feeding, says a new University of Illinois study.

“When we fed the carbohydrate fructooligosacharide (FOS) as a prebiotic, the gut grew and increased in function,” said Kelly A. Tappenden, a U of I professor of nutrition and gastrointestinal physiology. “The study showed that using the correct pre- and probiotic in combination could enhance these results even more.”

When FOS enters the intestines, bacteria convert it into butyrate, a short-chain fatty acid that increases the size of the gut and its ability to digest and absorb nutrients, she said.

But today’s IV solutions don’t contain butyrate and adding it would entail drug development trials and regulatory red tape. She wanted to see if adding this carbohydrate to the diet while continuing to provide most nutrients intravenously would cause the gut to start producing butyrate on its own. It worked.

According to Tappenden, at least 10,000 U.S. patients are totally reliant on intravenous feeding because their intestines have been surgically shortened.

Many of these patients are premature infants who develop necrotizing enterocolitis, a kind of gangrene of the intestine. In the U.S., one in eight infants is a preemie, and removing necrotized, or dead, intestine is the most common surgical emergency in these babies.

“Surgery saves their lives, but with so much intestine removed, they’re unable to digest or absorb nutrients. These babies are also at risk for long-term complications, such as bone demineralization and liver failure. Our goal is to take kids who’ve had this resection and cause their gut to grow and adapt,” she said.

She tested her hypothesis about butyrate using newborn piglets, an excellent model for the human infant in metabolism and physiology. Piglets with intestinal failure were assigned to one of four groups: a control group; a group whose diet contained FOS, a carbohydrate given as a prebiotic to stimulate the production of butyrate by beneficial bacteria; a probiotic, or actual live bacteria; and a combination of pre- and probiotics.

“We believed that bacteria in the gut would use the prebiotic to make butyrate and support intestinal growth. But we thought that might only happen in the group that received both pre- and probiotics because we didn’t know if the newborn gut would have enough bacteria to make this important short-chain fatty acid.”

Actually, the neonatal piglets did have enough bacteria in their guts, and the prebiotic alone was effective in increasing intestinal function and structure, she said.

“In fact, the probiotic that we used in one of the groups eliminated the beneficial effect of the prebiotic. That shows us that we need to be exceptionally careful in selecting the probiotic we use, matching it to the specific disease,” she noted. Many consumers believe all probiotics are equal, but the effect of specific bacterial strains is different, she said.

“At this point, we can only recommend consumption of the FOS prebiotic alone,” she added.

The article appears in the September 2012 issue of the Journal of Parenteral and Enteral Nutrition and is available online at http://pen.sagepub.com/content/current. Jennifer L. Barnes of the U of I and Bolette Hartmann and Jens J. Holst of the University of Copenhagen, Copenhagen, Denmark, are co-authors of the study, which was funded by grants from the National Institutes of Health.

 

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Chloroquine makes comeback to combat malaria

global health

Malaria-drug monitoring over the past 30 years has shown that malaria parasites develop resistance to medicine, and the first signs of resistance to the newest drugs have just been observed. At the same time, resistance monitoring at the University of Copenhagen shows that the previously efficacious drug chloroquine is once again beginning to work against malaria. In time that will ensure cheaper treatment for the world’s poor.

Child being tested for malaria in Senegal

Scientists and healthcare personnel the world over fear that the malaria parasite will develop resistance to the current frontline treatment against malaria, Artemisinin-based Combination Therapies (ACTs). Therefore, it is especially good news that resistance monitoring at the University of Copenhagen shows that in several African countries, malaria parasites are succumbing to the formerly used drug chloroquine. The results have just been published in the American Journal of Tropical Medicine and Hygiene.

“70% of the malaria parasites we found in Senegal are reacting once again to chloroquine. This is a trend we have also seen in Tanzania and Mozambique, and which other researchers have shown in Malawi. Our choice of drugs against malaria is limited and related, so when the malaria parasite once again reacts to a substance, it influences several treatment methods,” explains Michael Alifrangis, associate professor at the Center for Medical Parasitology at the University of Copenhagen. He and Magatte Ndiaye, PhD student at Université Cheikh Anta Diop in Senegal, are keeping an eye on the malaria parasite’s sensitivity to drugs by analyzing the parasites’ DNA.

Each well on this plate contains malaria parasite DNA from one patient. The orange wells indicate that the patient is infected with malaria parasites sensitive to chloroquine. This plate shows 88 patients from Senegal 2011.

Cheaper treatment for the poor in Africa

If healthcare personnel in developing countries can begin using chloroquine again, it will open up some promising perspectives. It will be possible to protect the currently used medicine and delay the reappearance of resistance, and it will also give a large group of patients access to cheaper treatment.

“Chloroquine costs only 25 US cents for a four-day cure, while the current and corresponding ACTs cost two dollars. Chloroquine was a fantastic malaria drug that lasted for 50 years. However, it was misused for malaria prevention and ordinary fever, and even mixed with cooking salt, so it can come as no surprise that the malaria parasite became resistant to the active ingredient,” explains Professor Ib Bygbjerg, M.D. He also points out that reuse will require correct drug use and the training of healthcare personnel to make more accurate diagnoses.

Correct use of drugs paralyzes the development of resistance

According to Professor Ib Bygbjerg, three factors determine the extent to which a malaria drug will work: 1) the size of the dose, 2) how sensitive the parasite is to the drug, and 3) the extent to which the patient has developed a natural immunity to malaria.

Chloroquine drug

“In the near future, chloroquine and other malaria drugs not currently on the market will presumably be able to be used again, if we use them correctly. This means that the drug must be given in combination with other medicine and only to patients who have already developed a certain immunity to malaria and are therefore not at high risk. At the same time, we must reserve ACTs for the most exposed non-immune groups such as children. Chloroquine is one of the few drugs that can be given to pregnant women at the beginning of their pregnancy,” points out Ib Bygbjerg, adding that the patient can be treated with a high dose for a short period, another benefit.

In order to maintain the positive development with chloroquine, it is therefore also important that – with the exception of pregnant women – travellers to malaria areas refrain from taking the drug. Otherwise the parasites will quickly develop resistance once again

Taking painkillers increases death risk, second heart attacks in survivors: 59-63% Higher risk of Death

Contact: Maggie Francis
maggie.francis@heart.org
214-706-1382
American Heart Association

— Heart attack survivors who take common painkillers after a heart attack have a higher long-term risk of dying or having a second heart attack, according to a new study published in Circulation, an American Heart Association journal.

The painkillers, known as non-steroidal anti-inflammatory drugs (NSAIDs), include over-the-counter medicines such as ibuprofen and naproxen and prescription drugs such as Celebrex (celecoxib), which is used to treat conditions including arthritis.

“It is important to get the message out to clinicians taking care of patients with cardiovascular disease that NSAIDs are harmful, even several years after a heart attack,” said Anne-Marie Schjerning Olsen, M.D., the study’s lead author and a fellow in the cardiology department at Copenhagen University Hospital Gentofte in Denmark.

Schjerning Olsen and her colleagues used national hospital and pharmacy registries in Denmark to identify almost 100,000 people 30 or older who had a first heart attack between 1997 and 2009, and to see if they were prescribed NSAIDs afterwards.

Forty-four percent of the patients filled at least one NSAID prescription. Among those receiving an NSAID, risk of death from any cause was 59 percent higher one year after their heart attack, and 63 percent higher after five years.

Similarly, risk of having another heart attack or dying from coronary artery disease was 30 percent higher one year later and 41 percent higher after five years. The findings considered other illnesses and medication use in the NSAID patients, as well as differences in age, sex, income and year of hospitalization.

“The results support previous findings suggesting that NSAIDs have no apparent safe treatment window among heart attack patients, and show that coronary risk related to using the drugs remains high, regardless of the time that has passed since the heart attack,” Schjerning Olsen said.

Normally, patients who have a heart attack face higher risk of death or another heart attack within the first year. But the extra risk is gone within five to 10 years.

Because the new study instead showed a persistently higher risk over at least five years for patients on the drugs, “long-term caution with any use of NSAIDS is advised in all patients after heart attack,” Schjerning Olsen said.

A 2007 American Heart Association statement urged doctors to carefully weigh risks versus benefits when considering NSAID use in patients with a history or high risk of cardiovascular disease.

These data showed no difference in risk for men versus women. Because researchers used nationwide data, the findings extend across races, age, income groups and hospitals.

Researchers didn’t test the drugs’ effects in a controlled clinical trial, so the study didn’t definitely show that NSAIDs, rather than other unknown factors, cause additional deaths or heart attacks. But the researchers consider NSAIDs the likely culprit behind the higher risk.

Use of NSAIDS should be limited and their over-the-counter availability should be re-evaluated, Schjerning Olsen said.

“Allowing a drug to be sold without prescription must be perceived by the general public as a strong signal of safety, and may be contrary in this case,” she said.

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Co-authors are: Emil L. Fosbøl, M.D., Ph.D.; Jesper Lindhardsen, M.D.; Fredrik Folke, M.D., Ph.D.; Mette Charlot, M.D., Ph.D.; Christian Selmer, M.D.; Jonas Bjerring Olesen, M.D.; Morten Lamberts, M.D.; Martin H. Ruwald, M.D.; Lars Køber, M.D., D.M.Sc.; Peter R. Hansen, M.D., Ph.D., D.M.Sc.; Christian Torp Pedersen, M.D., D.M.Sc. and Gunnar H. Gislason, M.D., Ph.D.

Author disclosures are on the manuscript.

An unrestricted grant to Dr. Schjerning Olsen from the hospital’s cardiology department funded the study.

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