Release Date 26 FEB 2015
Draft Report Compiled by
In this Issue:
1. Anti-inflammatory mechanism of dieting and fasting revealed
2. Mothers can pass traits to offspring through bacteria’s DNA
3. In the short run, a high-fat diet may help minimize heart attack damage
4. One simple dietary change may be enough to lose weight, improve health
5. Individuals with type 2 diabetes should exercise after dinner
6. Stalking a wily foe: Scientists figure out how C. difficile bacteria wreak havoc in guts
7. Popular soda ingredient poses cancer risk to consumers
8. People with multiple sclerosis may have lower levels of key nutrients
9. Safety and life-saving efficacy of statins have been exaggerated, says USF scientist
10. Marine oil supplement has positive effects on post-exercise muscle damage
11. Garlic extract could help cystic fibrosis patients fight infection
12. Oat breakfast cereals may contain a common mold-related toxin
13. Widely used food additive promotes colitis, obesity and metabolic syndrome, research shows
Anti-inflammatory mechanism of dieting and fasting revealed
Researchers at Yale School of Medicine have found that a compound produced by the body when dieting or fasting can block a part of the immune system involved in several inflammatory disorders such as type 2 diabetes, atherosclerosis, and Alzheimer’s disease.
In their study, published in the Feb. 16 online issue of Nature Medicine, the researchers described how the compound β-hydroxybutyrate (BHB) directly inhibits NLRP3, which is part of a complex set of proteins called the inflammasome. The inflammasome drives the inflammatory response in several disorders including autoimmune diseases, type 2 diabetes, Alzheimer’s disease, atherosclerosis, and autoinflammatory disorders.
“These findings are important because endogenous metabolites like BHB that block the NLRP3 inflammasome could be relevant against many inflammatory diseases, including those where there are mutations in the NLRP3 genes,” said Vishwa Deep Dixit, professor in the Section of Comparative Medicine at Yale School of Medicine.
BHB is a metabolite produced by the body in response to fasting, high-intensity exercise, caloric restriction, or consumption of the low-carbohydrate ketogenic diet. Dixit said it is well known that fasting and calorie restriction reduces inflammation in the body, but it was unclear how immune cells adapt to reduced availability of glucose and if they can respond to metabolites produced from fat oxidation.
Working with mice and human immune cells, Dixit and colleagues focused on how macrophages — specialized immune cells that produce inflammation — respond when exposed to ketone bodies and whether that impacts the inflammasone complex.
The team introduced BHB to mouse models of inflammatory diseases caused by NLP3. They found that this reduced inflammation, and that inflammation was also reduced when the mice were given a ketogenic diet, which elevates the levels of BHB in the bloodstream.
“Our results suggest that the endogenous metabolites like BHB that are produced during low-carb dieting, fasting, or high-intensity exercise can lower the NLRP3 inflammasome,” said Dixit.
Mothers can pass traits to offspring through bacteria’s DNA
It’s a firmly established fact straight from Biology 101: Traits such as eye color and height are passed from one generation to the next through the parents’ DNA.
But now, a new study in mice by researchers at Washington University School of Medicine in St. Louis has shown that the DNA of bacteria that live in the body can pass a trait to offspring in a way similar to the parents’ own DNA. According to the authors, the discovery means scientists need to consider a significant new factor – the DNA of microbes passed from mother to child – in their efforts to understand how genes influence illness and health.
The study appears online Feb. 16 in Nature.
“We have kept bacteria on one side of a line separating the factors that shape our development — the environmental side of that line, not the genetic side,” said co-senior author Herbert W. Virgin IV, MD, PhD. “But our results show bacteria stepping over the line. This suggests we may need to substantially expand our thinking about their contributions, and perhaps the contributions of other microorganisms, to genetics and heredity.”
Bacteria are most familiar through their roles in harmful infections. But scientists have realized that such bacteria are only a tiny fraction of the bacterial communities that live in and on our bodies. Most bacteria are commensal, which means they do not cause harm and often confer benefits.
Commensal bacteria influence traits such as weight and behavior. But until now, researchers thought the bacteria that exerted these effects were acquired during a person’s life. The study is the first to show that bacterial DNA can pass from parent to offspring in a manner that affects specific traits such as immunity and inflammation.
The researchers linked commensal bacteria in mice to the animals’ susceptibility to a gut injury. Mice with certain inherited bacteria are susceptible to the injury, which is caused by exposure to a chemical. Female mice pass the bacteria to their offspring, making them vulnerable to the injury. Others carrying different bacteria are less susceptible.
In the short term, the findings may help scientists eliminate a significant “bug” in studies of genetically engineered mice. In several fields of research, scientists have been confronted intermittently with the sudden, unexplained appearance of new or altered traits in mice. The traits often spread from one mouse habitat to the next, suggesting a spreading microbial infection is responsible. But the traits also consistently pass from mother to offspring, suggesting a genetic cause.
Thaddeus Stappenbeck, MD, PhD, a professor of pathology and immunology, and co-senior author Virgin, the Edward Mallinckrodt Professor of Pathology and head of the Department of Pathology and Immunology, encountered this problem in their studies of inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis. They were surprised to find that roughly half their mice had low levels in the gut of IgA, an antibody linked to these disorders.
IgA helps defend the body against harmful invaders. It is commonly present in mucus made by the body in areas where the exterior world encounters the body’s interior, such as the eyes, nose, throat and gut.
When the scientists housed mice with low levels of the antibody with mice that had high levels of the antibody, all of the mice ended up with low antibody levels in a few weeks. When they bred the mice, the offspring whose mothers had low levels of the antibody also had low levels.
Eventually, the scientists learned that one of the culprits likely responsible for the spread of low antibody levels is a bacterium called Sutterella. This bacterium and others found in the low-IgA mice could explain both ways that decreased antibody levels were spreading: Mice that were housed together acquired low antibody levels through normal spread of the bacteria, and mouse mothers passed the same bacteria to their descendants.
The latter explanation involves a major change in thinking because it suggests that traits affected by bacteria can pass from mothers to their offspring in the same manner as traits affected by mouse DNA.
To prove that this change in antibody levels represented a significant change in the mice that could be thought of as a trait, the researchers fed the mice a chemical they use to characterize the gut’s response to injury as part of their studies of inflammatory bowel diseases. In mice with low levels of the antibody, the compound caused much more damage.
“The implications for mouse experiments are profound and could help us cut through some persistent sources of confusion,” Stappenbeck said. “When we study mice, we have to account for the possibility that inherited bacteria and their genes could be influencing the trait we’re trying to learn about.”
According to Stappenbeck, one way to do this will be to stop housing experimental and control mice in separate colonies. This would help ensure that any inherited microbes that influence a trait of interest are present in both groups.
In the long term, Virgin expects the expanded model of heredity to produce a more complicated but also much more insightful picture of how human, bacterial and viral genes influence human health.
In the short run, a high-fat diet may help minimize heart attack damage
MAYWOOD, Il. – It’s well known that over the long run, a high-fat diet increases the risk of heart attack and stroke.
But a new study has found that a high-fat diet, eaten one day to two weeks days before a heart attack, actually reduced heart attack damage in mice by about 50 percent.
The finding by a team led by W. Keith Jones, PhD, of Loyola University Chicago Stritch School of Medicine, is published in the American Journal of Physiology – Heart and Circulatory Physiology.
“The study improves our understanding of the relationship between diet and health,” Dr. Jones said. “Learning about how fat, in the short run, protects against heart attacks could help in the development of better therapies.”
Dr. Jones emphasized the study is not a license to eat a lot of cheeseburgers and ice cream.
The study may provide new insight into the “obesity paradox”: Obesity is a major risk factor for heart disease. But once a heart attack or heart failure does occur, moderately obese patients tend to live longer.
In the study, mice were given a high-fat diet (60 percent of calories from animal fat) before experiencing heart attacks. Mice that consumed a high-fat diet for either one day, one week or two weeks before the heart attack experienced about half as much heart damage as mice that ate a control diet. The benefit was greatest among mice that ate a high-fat diet for one week before the heart attack. But in mice that ate a high-fat diet for six weeks, the protective effect disappeared. Further research is needed to understand why this is so; the reason may be due to the bad effects of a persistent high-fat diet, Dr. Jones said.
Dr. Jones said that in the short-term, a high-fat diet protects the heart through a mechanism called autophagy, which works somewhat like a garbage truck. Proteins damaged by the heart attack are removed from heart cells as if they were garbage, thus increasing the chances the cells will survive. Acutely, a high-fat diet increases levels of a molecule in the blood that activates protective pathways in heart muscle. This increases the readiness of the “garbage trucks,” which means that the cell becomes resistant to damage when the heart attack occurs. As a result, more heart muscle survives. Dr. Jones’s team is studying the nature of the blood-borne molecule and will report results of this research in a later publication.
The current study “opens a new perspective on the acute effects of a high-fat diet,” first author Lauren Haar, PhD and colleagues wrote. “Future work will determine whether these effects are linked to the obesity paradox and whether studying the mechanism can identify therapeutic targets for cardioprotection.”
The authors added that, given the increasing number of obese people in both developed and developing countries, understanding the relationship between fat intake and heart health is “critically important.”
One simple dietary change may be enough to lose weight, improve health
Dietary advice that emphasizes just one rule – consume at least 30g of fiber a day – is nearly as effective as advice to follow the more complicated American Heart Association (AHA) diet plan for inducing weight loss and improving metabolic symptoms, according to an article published in Annals of Internal Medicine.
The AHA diet is proven effective for preventing and treating metabolic syndrome, but the diet’s many rules may make adherence a challenge for some. Researchers hypothesized that a more permissive diet that focused on one dietary change would be superior to the AHA intervention for weight loss, dietary quality, metabolic health, and adherence. The researchers randomly assigned 240 adults with metabolic syndrome to follow either the AHA diet plan (eat more fruits and vegetables; eat whole grain/high fiber foods; eat fish twice weekly; consume lean proteins; minimize sugar and sodium intake; limit alcohol; aim for a specific ratio of carbohydrates, proteins, and fats; and limit saturated fats, trans fats, and cholesterol) or to increase their daily fiber intake to at least 30g a day. Patients in both groups were given instructions on their diets but had no exercise requirements.
At one year, participants in both diet groups lost weight and showed improvement in blood pressure, dietary quality, and insulin resistance. While the AHA diet group lost more weight (up to 3.7 lbs), the authors conclude that a simplified approach to weight reduction may be a reasonable alternative for persons with difficulty adhering to more complicated diet regimens.
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Individuals with type 2 diabetes should exercise after dinner
Exercising after a meal can more effectively reduce risks of cardiovascular disease
COLUMBIA, Mo. – Individuals with Type 2 diabetes have heightened amounts of sugars and fats in their blood, which increases their risks for cardiovascular diseases such as strokes and heart attacks. Exercise is a popular prescription for individuals suffering from the symptoms of Type 2 diabetes, but little research has explored whether these individuals receive more benefits from working out before or after dinner. Now, researchers at the University of Missouri have found that individuals with Type 2 diabetes can lower their risks of cardiovascular diseases more effectively by exercising after a meal.
“This study shows that it is not just the intensity or duration of exercising that is important but also the timing of when it occurs,” said Jill Kanaley, professor in the MU Department of Nutrition and Exercise Physiology. “Results from this study show that resistance exercise has its most powerful effect on reducing glucose and fat levels in one’s blood when performed after dinner.”
Kanaley and her colleagues studied a group of obese individuals with Type 2 diabetes. On one occasion, participants performed resistance exercises before eating dinner. During another visit, participants exercised 45 minutes after eating dinner. Participants performed resistance exercises such as leg curls, seated calf raises and abdominal crunches. Compared to levels on a non-exercise day, Kanaley found that the participants who exercised before dinner were able to only reduce the sugar levels in their blood; however, participants who exercised after dinner were able to reduce both sugar and fat levels. Participants consumed a moderate carbohydrate dinner on the evenings of the study.
Kanaley said her research is particularly helpful for health care providers who have patients who exercise every day but are not seeing benefits.
“Knowing that the best time to exercise is after a meal could provide health care professionals with a better understanding of how to personalize exercise prescriptions to optimize health benefits,” Kanaley said.
Kanaley also found that improvements in participants’ blood sugar and fat levels were short-lived and did not extend to the next day. She suggests individuals practice daily resistance exercise after dinner to maintain improvements.
“Individuals who exercise in the morning have usually fasted for 10 hours beforehand,” Kanaley said. “Also, it is natural for individuals’ hormone levels to be different at different times of day, which is another factor to consider when determining the best time to exercise.”
In the future, Kanaley said she plans to research how exercising in the morning differs from exercising after dinner and how individuals’ hormone levels also affect exercise results.
The study, “Post-dinner resistance exercise improves postprandial risk factors more effectively than pre-dinner resistance exercise in patients with type 2 diabetes,” was published in the Journal of Applied Physiology.
Stalking a wily foe: Scientists figure out how C. difficile bacteria wreak havoc in guts
Study in mice could lead to better treatment and prevention for humans
University of Michigan Health System
ANN ARBOR, Mich. — Sometimes, science means staying awake for two days straight.
But losing sleep is a small sacrifice to make, if you want to learn more about tiny bacteria that sicken half a million Americans each year, kill more than 14,000 of them, and rack up $4.8 billion in health care costs.
That’s what drove a team of University of Michigan scientists to work around the clock to study the bacterium called Clostridium difficile, or C. difficile, the bane of hospitals and nursing homes. Most patients develop it after taking antibiotics.
In a new paper in the journal Infection and Immunity, the researchers lay out for the first time exactly how C. difficile wreaks havoc on the guts of animals in a short time, and causes severe diarrhea and life-threatening disease in humans.
Despite the heavy toll the organism takes, no team had ever been able to measure C. difficile activity over time in this way. Their findings could help lead to better prevention and treatment of C. difficile infections.
A fast track to disease
The researchers started by introducing C. difficile spores into mice via their mouths – similar to what might happen in a hospital environment where spores from past patients’ infections abound. Then, they studied what happened after the spores entered the body, by taking gut samples at regular intervals and studying them under special conditions. The animals had all received antibiotics.
Through their hours-long surveillance, the researchers found that it took C. difficile only about 24 hours to go from hard spores to toxin-producing, diarrhea-inducing cells all the way at the other end of the digestive tract, in the large intestine.
The researchers also show that bile acids in the gut “woke up” the dormant bacteria spores, and that they grow into cells in the small intestine within 24 hours of exposure. Because antibiotics disrupted the gut’s normal community of other bacteria – called the gut microbiome — C. difficile cells could continue to the large intestine and start their toxic effects on the cells that line the gut. When they tested the contents of the small intestine separately, they also showed this happens whether or not the animals have received antibiotics.
In the large intestine, they even saw how C. difficile cells formed spores again – allowing them to survive the exit from the body in feces and go on to infect a new host.
“If we can understand the process that specific bacteria use to germinate and get established, we may be able to intervene more effectively,” says Vincent Young, M.D., Ph.D., the senior author of the new study, a professor at the U-M Medical School and co-leader of the school’s Host Microbiome Initiative. “We assume that antibiotics change the gut microbiome, but we haven’t known how that allows C. difficile to gain a foothold and begin to ramp up growth.”
First author Mark Koenigsknecht, Ph.D., a postdoctoral fellow in Young’s lab who is now continuing his research at the U-M College of Pharmacy, was one of the researchers who was up all night to get data for the experiment.
“We introduced 100 spores through the mouth, and within six hours we could find 1,000 cells in the intestinal tract,” he notes. “We chose this strain of C. difficile because of its rapid ability to cause disease in animals, but we didn’t think it would happen that quickly.”
Tracking C. difficile‘s effect on the gut
The U-M team used a mouse model they developed, and a common antibiotic in the cephalosporin class. The strain of C. difficile used in the experiment originated with a patient years ago, but is available for purchase as a laboratory culture.
Working in facilities made possible by the Host Microbiome Initiative, they took samples at regular intervals from seven difficileerent areas of the digestive tracts of the mice. They then whisked the samples into special oxygen-free facilities, called anaerobic chambers, that allowed them to see the amount and forms of C. difficile present in each gut region.
With the help of Patrick Schloss, Ph.D., a professor in the Department of Microbiology & Immunology, the researchers used DNA analysis to see what the entire gut microbiome looked like in antibiotic-treated animals and those that hadn’t been treated. The antibiotics really disrupted the community of bacteria in the small intestine, and C. difficile came to dominate in 36 hours.
They also examined the intestinal tract under a microscope. The toxin produced by C. difficile cells in their vegetative, or growing, state causes an effect on the cells that line the digestive tract, causing them to become “leaky”, raising the alarm among nearby immune system cells, and leading to diarrhea. The cell changes were seen in the large intestine about 30 hours after spore introduction.
Koenigsknecht notes that this is the first time researchers have seen in a living animal that toxin production, and production of new spores of C. difficile capable of surviving outside the body, occur at the same time. This indication that the two processes are linked, and that they are switched on by some factor in the body, is intriguing, he says.
Now, the effort to figure out what that signal is, whether different strains of C. difficile act differently, and who is most vulnerable to its effects, will continue.
Koenigsknecht has teamed with College of Pharmacy professors to test the use of a seven-foot-long tube that can be threaded down the human digestive tract and used to retrieve samples at difficileerent locations along the way. Originally developed for testing how drugs are broken down and used by the body, it could provide an entirely new window into the human microbiome.
“Now that we understand what C. difficile is doing, we can also go and ask more questions about how the machinery inside the cell is turning on,” he says. “We have to know how to study it before we can cure it.” Animal-based research is vital to this effort.
Young notes that there are many ways C. difficile could take over an antibiotic-decimated gut. “Does it prevent other bacteria from growing, or outcompete them by eating faster? Does it communicate with the cells of the gut lining? We’re trying to figure out the interaction between the ‘good bugs’ and the ‘bad bugs’, and the lining of the gut.” Young is an associate professor of infectious diseases and of microbiology and immunology.
Popular soda ingredient poses cancer risk to consumers
Research analysis suggests that soda drinkers consume 1 or more cans per day — possibly exposing them to 4-methylimidazole, a potential carcinogen
Public health researchers have analyzed soda consumption data in order to characterize people’s exposure to a potentially carcinogenic byproduct of some types of caramel color. Caramel color is a common ingredient in colas and other dark soft drinks. The results show that between 44 and 58 percent of people over the age of six typically have at least one can of soda per day, possibly more, potentially exposing them to 4-methylimidazole (4-MEI), a possible human carcinogen formed during the manufacture of some kinds of caramel color.
The results were published online today in PLOS One.
Building on an analysis of 4-MEI concentrations in 11 different soft drinks first published by Consumer Reports in 2014, researchers led by a team at the Johns Hopkins Center for a Livable Future (CLF) estimated exposure to 4-MEI from caramel-colored soft drinks and modeled the potential cancer burden related to routine soft drink consumption levels in the United States.
“Soft drink consumers are being exposed to an avoidable and unnecessary cancer risk from an ingredient that is being added to these beverages simply for aesthetic purposes,” says Keeve Nachman, PhD, senior author of the study and director of the Food Production and Public Health Program at the CLF and an assistant professor at the Johns Hopkins Bloomberg School of Public Health. “This unnecessary exposure poses a threat to public health and raises questions about the continued use of caramel coloring in soda.”
In 2013 and early 2014, Consumer Reports partnered with the CLF to analyze 4-MEI concentrations of 110 soft drink samples purchased from retail stores in California and the New York metropolitan area. This study pairs those results with population beverage consumption data from the National Health and Nutrition Examination Survey (NHANES) in order to estimate the population risks and cancer burden associated with 4-MEI exposures through soda.
While the 2014 study of the 110 samples of soda brands was not large enough to recommend one brand over another or draw conclusions about specific brands, results indicated that levels of 4-MEI could vary substantially across samples, even for the same type of beverage. “For example, for diet colas, certain samples had higher or more variable levels of the compound, while other samples had very low concentrations,” says Tyler Smith, lead author of the study and a program officer with the CLF.
While there’s currently no federal limit for 4-MEI in food or beverages, Consumer Reports petitioned the Food and Drug Administration to set limits for the potential carcinogen last year. It also shared the findings with the California Attorney General’s office, which enforces the state’s Proposition 65 law aimed at reducing consumers’ exposure to toxic chemicals. Under this state law, any food or beverage sold in the state that exposes consumers to more than a specific amount of 4-MEI per day requires a health-warning label.
“This new analysis underscores our belief that people consume significant amounts of soda that unnecessarily elevate their risk of cancer over the course of a lifetime,” says Urvashi Rangan, PhD, executive director for Consumer Reports’ Food Safety and Sustainability Center. “We believe beverage makers and the government should take the steps needed to protect public health. California has already taken an important step by setting a threshold for prompting Prop 65 labeling based on daily 4-MEI exposure from a food or beverage, such as a soda. This study sought to answer a critical question: How much soda do American consumers drink on average?”
Researchers also found sharply contrasting levels of 4-MEI in some soft drinks purchased in the New York metropolitan area, versus California. “Our study also found that some of the soft drink products sold in California that we sampled had lower levels of 4-MEI than the samples we looked at of the same beverages sold outside the state, particularly in our earlier rounds of testing. It appears that regulations such as California’s Proposition 65 may be effective at reducing exposure to 4-MEI from soft drinks, and that beverages can be manufactured in ways that produce less 4-MEI,” suggests Nachman. “An FDA intervention, such as determining maximum levels for 4-MEI in beverages, could be a valuable approach to reducing excess cancer risk attributable to 4-MEI exposure in the U.S. population.”
People with multiple sclerosis may have lower levels of key nutrients
WASHINGTON, DC – Women with multiple sclerosis (MS) may have lower levels of important antioxidant and anti-inflammatory nutrients, such as folate from food and vitamin E, than healthy people, according to a new study released today that will be presented at the American Academy of Neurology’s 67th Annual Meeting in Washington, DC, April 18 to 25, 2015.
For the study, researchers identified 27 Caucasian women with MS and compared them to 30 healthy Caucasian women between the ages of 18-60 and with body mass index of less than or equal to 30 kg/m2. Participants reported on their diet and nutrition over the previous year prior to starting vitamin D supplementation.
On average, the women who had MS had lower levels of five nutrients with antioxidant or anti-inflammatory properties: food folate, vitamin E, magnesium, lutein-zeaxanthin and quercetin. For food folate, the women with MS had average intake of 244 micrograms (mcg), while the healthy women had an average intake of 321 mcg. The recommended daily allowance is 400 mcg. For magnesium, the women with MS had average intake of 254 milligrams (mg), while the healthy women met the recommended daily allowance of 320 mg with an average of 321 mg. The women with MS also had a lower average percentage of their calories from fat than the healthy participants.
“Since MS is a chronic inflammatory disorder, having enough nutrients with anti-inflammatory properties may help prevent the disease or reduce the risk of attacks for those who already have MS,” said study author Sandra D. Cassard, ScD, with John Hopkins University in Baltimore, MD. “Antioxidants are also critical to good health and help reduce the effects of other types of damage that can occur on a cellular level and contribute to neurologic diseases like MS. Whether the nutritional differences that we identified in the study are a cause of MS or a result of having it is not yet clear.”
Safety and life-saving efficacy of statins have been exaggerated, says USF scientist
By using statistical tool that amplifies the beneficial effects of statins, advocates have created the appearance that cholesterol-lowering drugs are wonder drugs that have substantially reduced cardiovascular disease.
University of South Florida (USF Health)
Tampa, Florida (Feb. 20, 2015) – Hailed as miracle drugs when they hit the market two decades ago, statins, the cholesterol-lowering drugs prescribed to prevent heart attacks, are not as effective nor as safe as we have been led to believe, say Dr. David M. Diamond, a professor of psychology, molecular pharmacology and physiology at the University of South Florida, and Dr. Uffe Ravnskov, an independent health researcher and an expert in cholesterol and cardiovascular disease.
According to Diamond and Ravnskov, statins produce a dramatic reduction in cholesterol levels, but they have “failed to substantially improve cardiovascular outcomes.” They further state that the many studies touting the efficacy of statins have not only neglected to account for the numerous serious adverse side effects of the drugs, but supporters of statins have used what the authors refer to as “statistical deception” to make inflated claims about their effectiveness.
Their critique of the exaggerated claims regarding statins’ ability to prevent strokes, heart attacks and heart disease-related deaths on a large scale has been published in the medical journal “Expert Review of Clinical Pharmacology” at http://informahealthcare.com/ .
Their paper is an analysis of the data in the statin trials which led them to conclude that “statin advocates have used statistical deception to create the illusion that statins are ‘wonder drugs,’ when the reality is that their modest benefits are more than offset by their adverse effects.”
The paper also describes how the basis of the deception is in how authors of the statin studies present the rate of beneficial and adverse effects. The effect of the drugs on the population is called the ‘absolute risk,’ which has shown that statins benefit only about 1% of the population. This means that only one out of 100 people treated with a statin will have one less heart attack. Statin researchers, however, don’t present the 1% effect to the public. Instead they transform the 1% effect using another statistic, called the “relative risk,” which creates the appearance that statins benefit 30-50% of the population.
The exaggeration of beneficial effects of statin treatment was illustrated in their analysis of a subset of statin studies, including the Jupiter Trial (Crestor), the Anglo-Scandinavian Cardiac Outcomes Trial Lipid Lowering Arm (ASCOT-LLA), and the British Heart Protection Study.
“In the Jupiter trial, the public and healthcare workers were informed of a 54 percent reduction in heart attacks, when the actual effect in reduction of coronary events was less than 1 percentage point,” said Ravnskov and Diamond, who is also a Career Research Scientist with the Medical Research Service at the James A. Haley Veterans Hospital in Tampa, Florida. “In the ASCOT-LLA study, which was terminated early because it was considered to have such outstanding results, there were heart attacks and deaths in 3% of the placebo (no treatment) group as compared to 1.9% in the Lipitor group. The improvement in outcome with Lipitor treatment was only 1.1 percentage point, but when this study was presented to the public, the advertisements used the inflated (relative risk) statistic, which transformed the 1.1% effect into a 36% reduction in heart attack risk.
The inflated claims for statin effectiveness, and minimized portrayal of the adverse effects, has played a role in the health care providers and the public’s enthusiasm for cholesterol-lowering drugs, say the authors.
“The adverse effects suffered by people taking statins are more common than reported in the media and at medical conferences” explains Diamond and Ravnskov. According to the authors, “Increased rates of cancer, cataracts, diabetes, cognitive impairments and musculoskeletal disorders more than offset the modest cardiovascular benefits of statin treatment.”
The authors emphasized that low cholesterol levels related to statin use have frequently been associated with an increased risk of cancer. They also noted that most statin trials are terminated within two to five years, a period too short to see most cancers develop. Nevertheless, studies have shown a greater incidence of cancer in people who take statins, and one long-term study demonstrated a dramatic increase in the incidence of breast cancer among women who had used statins for more than 10 years.
They emphasized that the public needs to be wary of conflicts of interest in the medical community and pharmaceutical industry when it comes to touting the benefits of statins and skewing the data in such a way as to make the drugs seem more effective at lowering cardiovascular disease and heart attack risks than they may actually be.
Diamond and Ravnskov’s paper is particularly relevant at this time as reports out of Britain have revealed that leaders in health care and research, including the editor in chief of the British Medical Journal, Fiona Godlee, and the chair of Britain’s Commons Health Select Committee, Sarah Wollaston, have called for drug companies to release all of their records involving undisclosed adverse effects of statins in their clinical trials.
“We welcome more medical journals to follow the new rules introduced by the British Medical Journal stating that ‘clinical education articles will be authored by experts without financial ties to industry’,” say Diamond and Ravnskov.
The authors advocate other health beneficial strategies that are known to reduce cardiovascular risk, such as cessation of smoking, weight control, exercise and stress reduction. They also emphasized the great value of a low carbohydrate diet for normalizing all of the biomarkers of cardiovascular risk, with excellent outcomes, especially for people with type 2 diabetes.
Diamond and Ravnskov concluded their paper with the sobering statement that “There is a great appeal to the public to take a pill that offers the promise of a longer life and to live heart attack free. The reality, however, is that statins actually produce only small beneficial effects on cardiovascular outcomes, and their adverse effects are far more substantial than is generally known.”
Marine oil supplement has positive effects on post-exercise muscle damage
BLOOMINGTON, Ind. — An Indiana University study has revealed that there may be a greater connection between mussels and muscles than previously thought.
The study, by kinesiology professor Timothy Mickleborough at the IU School of Public Health-Bloomington, found that taking a pre-exercise supplement of the omega-3 PCSO-524, a marine oil lipid derived from the New Zealand green-lipped mussel, has significant positive effects on post-exercise muscle damage.
The pharmaceutical name of the supplement is Lyprinol, or Omega XL in the United States, and it has previously been used to effectively reduce the effects of osteoarthritis, rheumatoid arthritis, inflammatory bowel disease and exercise-induced asthma. Pharmalink International LTD, which funded the study, develops it.
Mickleborough said his initial study of this particular marine oil supplement led him to further test its healing properties on other parts of the body.
“I’ve worked with Pharmalink before when they approached me to do a study with this particular oil and its effects on exercise-induced asthma and respiratory inflammation,” Mickleborough said. “I thought if it can be used as an anti-inflammatory for lungs, perhaps it could reverse muscle inflammation as well.”
For the study, lead author Mickleborough and his colleagues tested 32 “untrained male subjects” — men who exercise less than three times a week for less than 30 minutes at a time — who would elicit a greater muscle response than an athlete who is used to regular muscle damage. The subjects were randomly given either the marine oil supplement or a placebo for 26 days before a muscle-damaging exercise session and for 96 hours afterwards.
The exercise session consisted of running at fairly high intensity for 20 minutes downhill on a treadmill. The body’s reaction to the muscle-damaging exercise regimen was tested immediately, and at 24, 48, 72 and 96 hours post-workout.
The men who were given the PCSO-524 marine oil supplement exhibited less muscle soreness, less muscle pain, less strength loss, less fatigue and even less inflammatory proteins evident in their bloodstreams. Overall, they experienced less bodily stress after their workout in comparison to the subjects who were given the placebo.
For people who are looking to start exercising again, or even for those who engage in intense workouts regularly, this discovery can have a variety of positive effects on how their bodies react to muscle damage, Mickleborough said.
“It might have positive implications for triathletes if they’re doing several different types of exercises, and it could potentially help diminish soreness in multisport, recreational athletes as well,” he said. “Essentially, for anyone who is engaging in unaccustomed exercise, it’s a nice product.”
Mickleborough’s study “The effects PCSO-524®, a patented marine oil lipid and omega-3 PUFA blend derived from the New Zealand green lipped mussel (Perna canaliculus), on indirect markers of muscle damage and inflammation after muscle damaging exercise in untrained men: a randomized, placebo controlled trial” is featured in the Feb. 2015 issue of the Journal of the International Society of Sports Nutrition.
Garlic extract could help cystic fibrosis patients fight infection
A chemical found in garlic can kill bacteria that cause life-threatening lung infections in people with cystic fibrosis, research suggests.
The study is the first to show that the chemical – known as allicin – could be an effective treatment against a group of infectious bacteria that is highly resistant to most antibiotics.
Allicin is produced naturally by garlic bulbs to ward off a closely-related group of plant pathogens found in soil and water habitats. In the 1980s, the bacteria – known as the Burkholderia cepacia complex (Bcc) – emerged as a cause of serious and transmissible lung infections in people with cystic fibrosis.
Measures to limit the spread of Bcc infections among people with cystic fibrosis have brought the number of cases down considerably. However, current therapies available to treat infections – that are potentially fatal – are limited and require the use of combinations of three to four antibiotics at a time.
Researchers found that allicin – which can be extracted by crushing raw garlic – inhibits the growth of bacteria and, at higher doses, kills the plant pathogens. The team suggests that allicin kills Bcc bacteria by chemically modifying key enzymes. This deactivates them and halts important biological processes within the pathogens’ cells.
The team believes allicin-containing remedies could be used in combination with existing antibiotics to treat Bcc infections. However, the researchers say it is important to pinpoint the mechanisms by which allicin kills the bacteria before the chemical can be incorporated into new treatments.
The Bcc are highly versatile plant and human pathogens that have not been studied to the same extent as other superbugs – such as MRSA – the team says.
The bacteria produce potent antimicrobial agents which kill bacteria and fungi, making them naturally drug-resistant and allowing them to survive in polluted and antibiotic-rich environments.
The team says the Bcc also have a range of potential uses in the agriculture industry.
The study, published in the journal PLOS ONE, was funded by the University of Edinburgh and the Biotechnology and Biological Sciences Research Council.
Professor John Govan, of the University of Edinburgh’s Centre for Infectious Diseases, who co-led the study, said: “At a time when novel antimicrobial agents are urgently required, chemical and microbiological research has the potential to unlock the rich reservoir of antimicrobial compounds present in plants such as garlic. Allicin-containing compounds merit further investigation as adjuncts to existing treatments for infections caused by Bcc.”
Dr Dominic Campopiano, of the University of Edinburgh’s School of Chemistry, said: “The medicinal power of garlic has a rich history that dates back thousands of years but the chemical structure of allicin was only revealed in the 1940s. Our work suggests that modern methods should be used to further expand our knowledge of this enigmatic molecule and rejuvenate its potential applications.”
Oat breakfast cereals may contain a common mold-related toxin
Oats are often touted for boosting heart health, but scientists warn that the grain and its products might need closer monitoring for potential mold contamination. They report in ACS’ Journal of Agricultural and Food Chemistry that some oat-based breakfast cereals in the U.S. contain a mold-related toxin called ochratoxin A (OTA) that’s been linked to kidney cancer in animal studies. The findings could have implications for consumer health.
Dojin Ryu and Hyun Jung Lee note that OTA is one of the most common toxic products released by molds in the world. Previous studies have found the toxin in samples of pork, dried fruits, wine, coffee and other products. Scientists don’t yet know how the toxin affects human health, but the International Agency for Research on Cancer, which is part of the World Health Organization, classifies it as a possible human carcinogen. Animals exposed to OTA in experiments developed kidney tumors. Although the U.S. doesn’t currently regulate the contaminant, the European Union has set maximum limits for OTA in food. Ryu and Lee wanted to see how U.S. breakfast cereals — a staple in many Americans’ diets — measured up to that standard.
The researchers tested close to 500 samples of corn-, rice-, wheat- and oat-based breakfast cereals purchased from U.S. stores over two years. They found that in most samples, OTA levels were lower than the European threshold. But concentrations exceeded the EU standard in 8 percent of oat-based breakfast cereal samples. The researchers conclude that oat production, storage and processing need careful review to better protect consumer health.
Widely used food additive promotes colitis, obesity and metabolic syndrome, research shows
ATLANTA–Emulsifiers, which are added to most processed foods to aid texture and extend shelf life, can alter the gut microbiota composition and localization to induce intestinal inflammation that promotes the development of inflammatory bowel disease and metabolic syndrome, new research shows.
The research, published Feb. 25 in Nature, was led by Georgia State University Institute for Biomedical Sciences’ researchers Drs. Benoit Chassaing and Andrew T. Gewirtz, and included contributions from Emory University, Cornell University and Bar-Ilan University in Israel.
Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, afflicts millions of people and is often severe and debilitating. Metabolic syndrome is a group of very common obesity-related disorders that can lead to type-2 diabetes, cardiovascular and/or liver diseases. Incidence of IBD and metabolic syndrome has been markedly increasing since the mid-20th century.
The term “gut microbiota” refers to the diverse population of 100 trillion bacteria that inhabit the intestinal tract. Gut microbiota are disturbed in IBD and metabolic syndrome. Chassaing and Gewirtz’s findings suggest emulsifiers might be partially responsible for this disturbance and the increased incidence of these diseases.
“A key feature of these modern plagues is alteration of the gut microbiota in a manner that promotes inflammation,” says Gewirtz.
“The dramatic increase in these diseases has occurred despite consistent human genetics, suggesting a pivotal role for an environmental factor,” says Chassaing. “Food interacts intimately with the microbiota so we considered what modern additions to the food supply might possibly make gut bacteria more pro-inflammatory.”
Addition of emulsifiers to food seemed to fit the time frame and had been shown to promote bacterial translocation across epithelial cells. Chassaing and Gewirtz hypothesized that emulsifiers might affect the gut microbiota to promote these inflammatory diseases and designed experiments in mice to test this possibility.
The team fed mice two very commonly used emulsifiers, polysorbate 80 and carboxymethylcellulsose, at doses seeking to model the broad consumption of the numerous emulsifiers that are incorporated into almost all processed foods. They observed that emulsifier consumption changed the species composition of the gut microbiota and did so in a manner that made it more pro-inflammatory. The altered microbiota had enhanced capacity to digest and infiltrate the dense mucus layer that lines the intestine, which is normally, largely devoid of bacteria. Alterations in bacterial species resulted in bacteria expressing more flagellin and lipopolysaccharide, which can activate pro-inflammatory gene expression by the immune system.
Such changes in bacteria triggered chronic colitis in mice genetically prone to this disorder, due to abnormal immune systems. In contrast, in mice with normal immune systems, emulsifiers induced low-grade or mild intestinal inflammation and metabolic syndrome, characterized by increased levels of food consumption, obesity, hyperglycemia and insulin resistance.
The effects of emulsifier consumption were eliminated in germ-free mice, which lack a microbiota. Transplant of microbiota from emulsifiers-treated mice to germ-free mice was sufficient to transfer some parameters of low-grade inflammation and metabolic syndrome, indicating a central role for the microbiota in mediating the adverse effect of emulsifiers.
The team is now testing additional emulsifiers and designing experiments to investigate how emulsifiers affect humans. If similar results are obtained, it would indicate a role for this class of food additive in driving the epidemic of obesity, its inter-related consequences and a range of diseases associated with chronic gut inflammation.
While detailed mechanisms underlying the effect of emulsifiers on metabolism remain under study, the team points out that avoiding excess food consumption is of paramount importance.
“We do not disagree with the commonly held assumption that over-eating is a central cause of obesity and metabolic syndrome,” Gewirtz says. “Rather, our findings reinforce the concept suggested by earlier work that low-grade inflammation resulting from an altered microbiota can be an underlying cause of excess eating.”
The team notes that the results of their study suggest that current means of testing and approving food additives may not be adequate to prevent use of chemicals that promote diseases driven by low-grade inflammation and/or which will cause disease primarily in susceptible hosts.