OREGON STATE UNIVERSITY

heath and nutrition

One in five older Americans take medications that work against each other

PORTLAND, Ore. – About three out of four older Americans have multiple chronic health conditions, and more than 20 percent of them are being treated with drugs that work at odds with each other – the medication being used for one condition can actually make the other condition worse.

This approach of treating conditions “one at a time” even if the treatments might conflict with one another is common in medicine, experts say, in part because little information exists to guide practitioners in how to consider this problem, weigh alternatives and identify different options.

One of the first studies to examine the prevalence of this issue, however, found that 22.6 percent of study participants received at least one medication that could worsen a coexisting condition. The work was done by researchers in Connecticut and Oregon, and published in PLOS One.

In cases where this “therapeutic competition” exists, the study found that it changed drug treatments in only 16 percent of the cases. The rest of the time, the competing drugs were still prescribed.

“Many physicians are aware of these concerns but there isn’t much information available on what to do about it,” said David Lee, an assistant professor in the Oregon State University/Oregon Health & Science University College of Pharmacy.

“Drugs tend to focus on one disease at a time, and most physicians treat patients the same way,” Lee said. “As a result, right now we’re probably treating too many conditions with too many medications. There may be times it’s best to just focus on the most serious health problem, rather than use a drug to treat a different condition that could make the more serious health problem even worse.”

More research in this field and more awareness of the scope of the problem are needed, the scientists said. It may be possible to make better value judgments about which health issue is of most concern, whether all the conditions should be treated, or whether this “competition” between drug treatments means one concern should go untreated. It may also be possible in some cases to identify ways to treat both conditions in ways that don’t conflict with one another.

A common issue, for example, is patients who have both coronary heart disease and chronic obstructive pulmonary disease, or COPD. Beta blockers are often prescribed to treat the heart disease, but those same drugs can cause airway resistance that worsens the COPD.

“There are several types of beta blocker that don’t cause this negative interaction, but many of the other types are still prescribed anyway,” Lee said. “It’s this type of information that would be of value in addressing these issues if it were more widely known and used.”

The chronic conditions in which competing therapies come into play include many common health concerns – coronary artery disease, diabetes, COPD, dementia, heart failure, hypertension, high cholesterol, osteoarthritis and others.

This study was done by researchers from OSU and the Yale University School of Medicine, with 5,815 community-living adults between the years 2007-09. The lead author of the study was Dr. Mary E. Tinetti at Yale University, and it was supported by the National Institutes of Health. The analysis included a nationally representative sample of older adults, and both men and women.

The research identified some of the most common competing chronic conditions, in which medications for one condition may exacerbate the other. They included hypertension and osteoarthritis; hypertension and diabetes; hypertension and COPD; diabetes and coronary artery disease; and hypertension and depression. These issues affect millions of older Americans.

“More than 9 million older adults in the U.S. are being prescribed medications that may be causing them more harm than benefit,” said Jonathan Lorgunpai, a medical student at the Yale School of Medicine and co-author of the study. “Not only is this potentially harmful for individual patients, it is also very wasteful for our health care system.”

Direct competition between medications is just one of the concerns, the report noted. Use of multiple medications can also lead to increased numbers of falls and delirium, dizziness, fatigue and anorexia.

The researchers pointed out that the presence of competing conditions does not necessarily contraindicate the use of needed medications, but rather the need for this competition to be more seriously considered in treatment.

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David Lee, 503-494-2258

Low birth weight reduces ability to metabolize drugs

PORTLAND, Ore. – Researchers have identified another concern related to low birth weight – a difference in how the body reacts to drugs, which may last a person’s entire life and further complicate treatment of illnesses or diseases that are managed with medications.

The findings add to the list of health problems that are already known to correspond to low birth weight, such as a predisposition for adult-onset diabetes, hypertension, and obesity. The implication, researchers say, is that low birth weight may not only cause increased disease, but it may also lessen the effectiveness of the drugs used to treat those diseases.

The research is among the first of its type to implicate low birth weight as a permanent factor in drug response. It was published in the European Journal of Pharmacology, by researchers from Oregon State University and Oregon Health & Science University. Funding was provided by both universities and the National Institutes of Health.

When more fully understood, low birth weight may be added to the list of factors already being considered in medication dosages, such as age, weight, gender and ethnicity. Some of that is already being done in infants. But right now it’s not one of the factors considered in adults, scientists say, and more work needs to be done before such consideration is warranted.

“Low birth weight affects the development of organs, as the fetus tries to finish development of the brain and, in a sense, sacrifice as necessary the ordinary development of organs such as the kidney,” said Ganesh Cherala, an assistant professor in the OSU/OHSU College of Pharmacy.  “But the kidney is one of the primary filtering agents in the body, and is directly involved in drug elimination.”

The kidneys of low birth weight individuals have a significantly impaired ability to filter and excrete foreign compounds, Cherala said. Since the biologic impact of a medication is affected by its absorption, metabolism and excretion, low birth weight individuals might be less able to excrete drugs.

However, the biologic processes are not that simple, Cherala said. Because of liver metabolism and other issues, in many cases low birth weight individuals end up having less response to a drug, instead of more.

“A pain killer, for instance, might end up being metabolized in the liver instead of making its way to the brain where it is supposed to function,” Cherala said. “You might need more of that same drug in a low birth weight individual to have the same effect.”

The complexities of these processes need additional study before recommendations could be made to alter drug dosages based on low birth weight status, Cherala said. But this issue could be important and should be further explored, he said.

In developed countries about 8-10 percent of individuals are born with low birth weight, but the issue is of higher concern in some developing nations where 20-25 percent of babies are born with this condition. Low birth weight is generally caused by poor nutrition during pregnancy.

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Ganesh Cherala, 503-418-0447

Aging men: More uplifts, fewer hassles until the age of 65-70

CORVALLIS, Ore. – A new study of how men approach their golden years found that how happy individuals are remains relatively stable for some 80 percent of the population, but perceptions of unhappiness – or dealing with “hassles” – tends to get worse once you are about 65-70 years old.

The reasons vary, researchers say, but may be because of health issues, cognitive decline or the loss of a spouse or friends.

“In general, life gets better as you age in the sense that older adults on average have fewer hassles – and respond to them better – than younger adults,” said Carolyn Aldwin, a gerontology professor in the College of Public Health and Human Sciences at Oregon State University and lead author on the study. “And they also experienced more uplifts – a least, until their mid-70s.”

“But once you turn 70, how you react to these hassles changes and may be dependent on your resources or your situation in life,” added Aldwin, the Jo Anne Leonard endowed director of OSU’s Center for Healthy Aging Research.

Results of the study, which was funded by the National Institutes of Health and the Department of Veterans Affairs, are being published in the journal Psychology and Aging.

The researchers used data from the Veterans Affairs Normative Aging Study, which looked at 1,315 men ages 53 to 85 years of age – predominantly comprised of white males who were initially in good health at entry into the study in the 1960s. This particular study aimed to take a fresh look at the emotional reactions of older adults and evaluate whether three previously established, yet contradictory models of aging had validity.

One of those models, known as the hedonic treadmill model, suggests that how happy or unhappy you are is relatively stable through your life, outside of a few up-or-down blips. A second theory posits that in general things get better as you age, while the third says your life will spiral downhill rapidly once you turn 80.

The new study, led by researchers from Oregon State and Boston University, found some support for all three models, depending on whether you looked at hassles or uplifts – and the age of the men. How men appraised their uplifts was stable, the researchers say, supporting the hedonic treadmill theory. But how they appraised hassles depended on their age: Appraisals got better through their 60s, but then started to become more severe in their 70s.

Nonetheless, Aldwin noted, some men respond more intensely to life’s ups and downs than others, but both the perception and intensity of these events is highly variable among individuals.

“What we found was that among 80 percent of the men in the study, the hassles they encounter from their early 50s on tended to decline until they reached about 65 to 70 years of age, and then they rose,” Aldwin pointed out. “Conversely, about 20 percent of the men perceived experiencing more uplifting events until they turned 65-70 and they begin to decline.”

The study drew from the perceptions of the men over events in their lives that were big and small, positive and negative. Self-regulation – or how they respond to those events – varied, Aldwin said.

“Some older people continue to find sources of happiness late in life despite dealing with family losses, declining health, or a lack of resources,” she said. “You may lose a parent, but gain a grandchild. The kids may leave the house, but you bask in their accomplishments as adults. You find value in gardening, volunteering, caregiving or civic involvement.”

Aging is neither exclusively rosy nor depressing, Aldwin said, and how you react to hassles and uplifts as a 55- to 60-year-old may change as you enter what researchers call “the fourth age,” from 75 to 100, based on your perceptions and/or your life experiences.

“Who falls into these groups and why can begin to tell us what kind of person ultimately may be happy late in life and who may not,” Aldwin said. “Once we find that out, we can begin interventions.”

The researchers on the study, who included Yu-Jin Jeong and Heidi Igarashi of OSU, and Avron Spiro III of Boston University, hope to expand their research beyond the limited VA sample and look at the mental health outlook for aging women, minorities and persons with varied economic and health backgrounds.

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Carolyn Aldwin, 541-737-2024; Carolyn.aldwin@oregonstate.edu

More benefits emerging for one type of omega-3 fatty acid: DHA

The study this story is based on is available online: http://bit.ly/1dDuf7i

 

CORVALLIS, Ore. – A study of the metabolic effects of omega-3 fatty acids, especially DHA, concludes that these compounds may have an even wider range of biological impacts than previously considered, and suggests they could be of significant value in the prevention of fatty liver disease.

The research, done by scientists at Oregon State University and several other institutions, was one of the first of its type to use “metabolomics,” an analysis of metabolites that reflect the many biological effects of omega-3 fatty acids on the liver. It also explored the challenges this organ faces from the “Western diet” that increasingly is linked to liver inflammation, fibrosis, cirrhosis and sometimes liver failure.

The results were surprising, researchers say.

Supplements of DHA, used at levels that are sometimes prescribed to reduce blood triglycerides, appeared to have many unanticipated effects. There were observable changes in vitamin and carbohydrate metabolism, protein and amino acid function, as well as lipid metabolism.

Supplementation with DHA partially or totally prevented metabolic damage through those pathways often linked to the Western diet – excessive consumption of red meat, sugar, saturated fat and processed grains.

The findings were published last month in PLOS One, an online professional journal.

“We were shocked to find so many biological pathways being affected by omega-3 fatty acids,” said Donald Jump, a professor in the OSU College of Public Health and Human Sciences. “Most studies on these nutrients find effects on lipid metabolism and inflammation.

“Our metabolomics analysis indicates that the effects of omega-3 fatty acids extend beyond that, and include carbohydrate, amino acid and vitamin metabolism,” he added.

Omega-3 fatty acids have been the subject of much recent research, often with conflicting results and claims. Possible reasons for contradictory findings, OSU researchers say, are the amount of supplements used and the relative abundance of two common omega-3s – DHA and EPA. Studies at OSU have concluded that DHA has far more ability than EPA to prevent the formation of harmful metabolites. In one study, it was found that DHA supplementation reduced the proteins involved in liver fibrosis by more than 65 percent.

These research efforts, done with laboratory animals, used a level of DHA supplementation that would equate to about 2-4 grams per day for an average person. In the diet, the most common source of DHA is fatty fish, such as salmon, mackerel or sardines.

The most recent research is beginning to break down the specific processes by which these metabolic changes take place. If anything, the results suggest that DHA may have even more health value than previously thought.

“A lot of work has been done on fatty liver disease, and we are just beginning to explore the potential for DHA in preventing or slowing disease progression,” said Jump, who is also a principal investigator in OSU’s Linus Pauling Institute.

“Fish oils, a common supplement used to provide omega-3, are also not prescribed to regulate blood glucose levels in diabetic patients,” he said. “But our studies suggest that DHA may reduce the formation of harmful glucose metabolites linked to diabetic complications.”

Both diabetes and liver disease are increasing steadily in the United States.

The American Liver Foundation has estimated that about 25 percent of the nation’s population, and 75 percent of those who are obese, have nonalcoholic fatty liver disease. This can progress to nonalcoholic steatohepatitis, cirrhosis and cancer.

This study established that the main target of DHA in the liver is the control of inflammation, oxidative stress and fibrosis, which are the characteristics of more progressively serious liver problems. Omega-3 fatty acids appear to keep cells from responding to and being damaged by whatever is causing inflammation.

Collaborators on this research were from OSU, the Baylor College of Medicine, Vanderbilt University Medical Center, and Metabolon, Inc. It was supported by the USDA and the National Institutes of Health.

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Donald Jump, 541-737-4007

Study: Even low-intensity activity shows benefits for health

CORVALLIS, Ore. – A newly published study looking at activity trends and outcomes among American adults found that you don’t need to kill yourself by running 10 miles a day to gain health benefits – you merely need to log more minutes of light physical activity than of sedentary behavior.

And the bar is pretty low for what constitutes light physical activity, researchers say. It can mean sauntering through a mall window-shopping instead of ordering online, fishing along a riverbank, or ballroom dancing.

In other words, casting a spinner or spinning on the dance floor can help offset our sedentary ways.

The problem, the authors say, is that nearly half of Americans surveyed did not engage in a sufficient amount of moderate-to-vigorous physical activity (more than 150 minutes a week) and, in fact, spent more time in sedentary mode than even doing light physical activity.

“That’s actually rather frightening,” said Bradley Cardinal, co-director of the Sport and Exercise Psychology Program at Oregon State University and co-author on the study. “About half of the people in this country are incredibly sedentary – basically, couch potatoes. And that can have some very negative effects on one’s health.”

Results of the study have been published online in the journal Preventive Medicine.

The study looked at the activity patterns of more than 5,500 adults through the National Health and Nutrition Examination Survey.  Participants wore accelerometers recording movements that could be broken down by the minute, and the researchers found that 47.2 percent of Americans engaged in less than 150 minutes a week of moderate-to-vigorous physical activity and, perhaps more importantly, logged fewer minutes of light physical activity than of sedentary behavior.

They found that when the balance was on the positive side – adults spent more time moving than sitting – there was a strong association with favorable levels of triglycerides and insulin.

“It is preferable to get at least 30 minutes a day of moderate-to-vigorous physical activity in each day, but we now know that if you sit for the remainder of the day after getting this dose of exercise, you might not necessarily be escaping the risk of developing chronic disease,” said Paul Loprinzi, a former doctoral student under Cardinal in OSU’s College of Public Health and Human Sciences. Now an assistant professor at Bellarmine University, Loprinzi is lead author on the study.

“These findings demonstrate the importance of minimizing sedentary activities and replacing some of them with light-intensity activities, such as pacing back and forth when on the phone, standing at your desk periodically instead of sitting, and having walking meetings instead of sit-down meetings,” he added.

Cardinal said results can vary with individuals, based on age, fitness levels, movement “pace” and other factors. In general, however, when even light activity minutes in a day surpass sedentary minutes, it can result in improved triglyceride and insulin levels.

“Someone just ambling along on a leisurely stroll may not get the same benefits as someone moving briskly – what we call a ‘New York City walk,’” Cardinal said, “but it still is much better than lying on the couch watching TV. Even sitting in a rocking chair and rocking back-and-forth is better than lying down or just sitting passively.

“Think about all the small things you can do in a day and you’ll realize how quickly they can add up,” Cardinal pointed out.

Some of the ways Americans can get in some light physical activity without Olympic-style training:

  • Go on a leisurely bicycle ride, at about 5-6 miles an hour;
  • Use a Wii Fit program that requires a light effort, like yoga or balancing;
  • Do some mild calisthenics or stretching;
  • If you want to watch television, do it sitting on a physioball;
  • Play a musical instrument;
  • Work in the garden.

“Even everyday home activities like sweeping, dusting, vacuuming, doing dishes, watering the plants, or carrying out the trash have some benefits,” Cardinal said.

“Remember, it’s making sure you’re moving more than you’re sitting that’s the key.”

The study was supported by Oregon State University. Hyo Lee, a former Ph.D. student at OSU now with Sangmyung University in Korea, is also a co-author on the study.

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Brad Cardinal, 541-737-2506; brad.cardnal@oregonstate.edu; Paul Loprinzi, 502-272-8008; ploprinzi@bellarmine.edu

Amber fossil reveals ancient reproduction in flowering plants

CORVALLIS, Ore. – A 100-million-year old piece of amber has been discovered which reveals the oldest evidence of sexual reproduction in a flowering plant – a cluster of 18 tiny flowers from the Cretaceous Period – with one of them in the process of making some new seeds for the next generation.

The perfectly-preserved scene, in a plant now extinct, is part of a portrait created in the mid-Cretaceous when flowering plants were changing the face of the Earth forever, adding beauty, biodiversity and food. It appears identical to the reproduction process that “angiosperms,” or flowering plants still use today.

Researchers from Oregon State University and Germany published their findings on the fossils in the Journal of the Botanical Institute of Texas.

The flowers themselves are in remarkable condition, as are many such plants and insects preserved for all time in amber. The flowing tree sap covered the specimens and then began the long process of turning into a fossilized, semi-precious gem. The flower cluster is one of the most complete ever found in amber and appeared at a time when many of the flowering plants were still quite small.

Even more remarkable is the microscopic image of pollen tubes growing out of two grains of pollen and penetrating the flower’s stigma, the receptive part of the female reproductive system. This sets the stage for fertilization of the egg and would begin the process of seed formation – had the reproductive act been completed.

“In Cretaceous flowers we’ve never before seen a fossil that shows the pollen tube actually entering the stigma,” said George Poinar, Jr., a professor emeritus in the Department of Integrative Biology at the OSU College of Science. “This is the beauty of amber fossils. They are preserved so rapidly after entering the resin that structures such as pollen grains and tubes can be detected with a microscope.”

The pollen of these flowers appeared to be sticky, Poinar said, suggesting it was carried by a pollinating insect, and adding further insights into the biodiversity and biology of life in this distant era. At that time much of the plant life was composed of conifers, ferns, mosses, and cycads.  During the Cretaceous, new lineages of mammals and birds were beginning to appear, along with the flowering plants. But dinosaurs still dominated the Earth.

“The evolution of flowering plants caused an enormous change in the biodiversity of life on Earth, especially in the tropics and subtropics,” Poinar said.

“New associations between these small flowering plants and various types of insects and other animal life resulted in the successful distribution and evolution of these plants through most of the world today,” he said. “It’s interesting that the mechanisms for reproduction that are still with us today had already been established some 100 million years ago.”

The fossils were discovered from amber mines in the Hukawng Valley of Myanmar, previously known as Burma. The newly-described genus and species of flower was named Micropetasos burmensis.

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George Poinar, 541-752-0917

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Review: Most clinical studies on vitamins flawed by poor methodology

 

 

The study this story is based on is available online: http://bit.ly/1lbi4PB

CORVALLIS, Ore. – Most large, clinical trials of vitamin supplements, including some that have concluded they are of no value or even harmful, have a flawed methodology that renders them largely useless in determining the real value of these micronutrients, a new analysis suggests.

Many projects have tried to study nutrients that are naturally available in the human diet the same way they would a powerful prescription drug. This leads to conclusions that have little scientific meaning, even less accuracy and often defy a wealth of other evidence, said Balz Frei, professor and director of the Linus Pauling Institute at Oregon State University, in a new review published in the journal Nutrients.

These flawed findings will persist until the approach to studying micronutrients is changed, Frei said. Such changes are needed to provide better, more scientifically valid information to consumers around the world who often have poor diets, do not meet intake recommendations for many vitamins and minerals, and might greatly benefit from something as simple as a daily multivitamin/mineral supplement.

Needed are new methodologies that accurately measure baseline nutrient levels, provide supplements or dietary changes only to subjects who clearly are inadequate or deficient, and then study the resulting changes in their health. Tests must be done with blood plasma or other measurements to verify that the intervention improved the subjects’ micronutrient status along with biomarkers of health. And other approaches are also needed that better reflect the different ways in which nutrients behave in cell cultures, lab animals and the human body.

The new analysis specifically looked at problems with the historic study of vitamin C, but scientists say many of the observations are more broadly relevant to a wide range of vitamins, micro nutrients and studies.

“One of the obvious problems is that most large, clinical studies of vitamins have been done with groups such as doctors and nurses who are educated, informed, able to afford healthy food and routinely have better dietary standards than the public as a whole,” said Frei, an international expert on vitamin C and antioxidants.

Vitamin or mineral supplements, or an improved diet, will primarily benefit people who are inadequate or deficient to begin with, OSU researchers said. But most modern clinical studies do not do baseline analysis to identify nutritional inadequacies and do not assess whether supplements have remedied those inadequacies. As a result, any clinical conclusion made with such methodology is pretty much useless, they said.

“More than 90 percent of U.S. adults don’t get the required amounts of vitamins D and E for basic health,” Frei said. “More than 40 percent don’t get enough vitamin C, and half aren’t getting enough vitamin A, calcium and magnesium. Smokers, the elderly, people who are obese, ill or injured often have elevated needs for vitamins and minerals.

“It’s fine to tell people to eat better, but it’s foolish to suggest that a multivitamin which costs a nickel a day is a bad idea.”

Beyond that, many scientists studying these topics are unaware of ways in which nutrients may behave differently in something like a cell culture or lab animal, compared to the human body. This raises special challenges with vitamin C research in particular.

“In cell culture experiments that are commonly done in a high oxygen environment, vitamin C is unstable and can actually appear harmful,” said Alexander Michels, an LPI research associate and lead author on this report. “And almost every animal in the world, unlike humans, is able to synthesize its own vitamin C and doesn’t need to obtain it in the diet. That makes it difficult to do any lab animal tests with this vitamin that are relevant to humans.”

Even though such studies often significantly understate the value of vitamin supplements, the largest and longest clinical trial of multivitamin/mineral supplements found a total reduction of cancer and cataract incidence in male physicians over the age of 50. It suggested that if every adult in the U.S. took such supplements it could prevent up to 130,000 cases of cancer each year, Frei said.

“The cancer reduction would be in addition to providing good basic health by supporting normal function of the body, metabolism and growth,” he said. “If there’s any drug out there that can do all this, it would be considered unethical to withhold it from the general public. But that’s basically the same as recommending against multivitamin/mineral supplements.”

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Balz Frei, 541-737-5078

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Drug interactions causing a significant impact on statin use

CORVALLIS, Ore. – A new study has found that many people who stopped taking cholesterol-lowering statin drugs were also taking an average of three other drugs that interfered with the normal metabolism of the statins.

The other drugs can contribute to a common side effect of taking statins - muscle pain – and often led people to discontinue use of a medication that could otherwise help save their life, researchers learned.

The interactions of many drugs with statins have been known of for some time, researchers said, but are not being adequately managed by physicians and pharmacists, who could often choose different medications or adjust dosages to retain the value of statin drugs without causing this side effect.

The research, done as part of a survey of more than 10,000 current and former statin users, found that use of medications which interfere with statin metabolism almost doubles the chance that a person will discontinue statin use due to muscle pain.

The issue is of growing importance because statin drugs are some of the most widely used medications in the world, proven to lower LDL, or “bad” cholesterol, and decrease the risk of heart attacks, heart disease, strokes and death. About 20 million people in the U.S. now take statins, and new guidelines have just been issued to further expand the types of health conditions for which statins may be of benefit. Based on those guidelines, the number of statin users could increase to more than 30 million.

The findings were published in the Journal of Clinical Lipidology by scientists from Oregon State University and four other universities or research institutes.

“We’ve known for some time of many medications that can interact with statins, but only now is it becoming clear that this is a significant contributor to the side effects, and often the reason some patients stop taking statins,” said Matt Ito, a professor in the OSU College of Pharmacy and president of the National Lipid Association, which funded this study.

“This issue is something physicians, pharmacists and patients all need to be more aware of,” Ito said. “There’s a lot we can do besides discontinue use of these valuable medications. You can change dosages, use drugs that don’t cause interactions, use different types of statins. Patients need to be proactive in understanding this issue and working with their health care providers to address it.”

Persons who have problems taking statins should discuss options with their physicians or pharmacists, Ito said, and not assume the drug has be to discontinued. A Medscape web site at http://reference.medscape.com/drug-interactionchecker also can help individuals learn more about possible interactions between statins and the full range of medications they may be taking.

Statins are usually well-tolerated, but in the recent survey, a muscle-related side effect was reported by 29 percent of participants. In former statin users, 62 percent of the people said that side effects, mostly muscle pain, were the reason they stopped taking the drugs.

There are many drugs that can interfere with statin metabolism, increase systemic exposure to the statin and raise the risk of this muscle pain, the researchers said in their report. This can include some common antibiotics, cardiovascular drugs, and others taken for treatment of cancer, mental health, HIV treatment and other conditions.

These interactions are not always adequately considered by physicians and pharmacists, however. One recent report found that as many as 20 percent of significant statin-drug interactions were missed in 64 pharmacies.

Besides drug interactions, statin side effects are also more common in women and associated with increasing age, history of cardiovascular disease, and some other conditions. Statin discontinuation has been associated with increased cardiovascular morbidity and death.

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Matt Ito, 503-494-3657

Excess omega-3 fatty acids could lead to negative health effects

CORVALLIS, Ore. – A new review suggests that omega-3 fatty acids taken in excess could have unintended health consequences in certain situations, and that dietary standards based on the best available evidence need to be established.

“What looked like a slam dunk a few years ago may not be as clear cut as we thought,” said Norman Hord, associate professor in OSU’s College of Public Health and Human Sciences and a coauthor on the paper.

“We are seeing the potential for negative effects at really high levels of omega-3 fatty acid consumption. Because we lack valid biomarkers for exposure and knowledge of who might be at risk if consuming excessive amounts, it isn’t possible to determine an upper limit at this time.”

Previous research led by Michigan State University’s Jenifer Fenton and her collaborators found that feeding mice large amounts of dietary omega-3 fatty acids led to increased risk of colitis and immune alteration. Those results were published in Cancer Research in 2010.

As a follow-up, in the current issue of the journal Prostaglandins, Leukotrienes & Essential Fatty Acids, Fenton and her co-authors, including Hord, reviewed the literature and discuss the potential adverse health outcomes that could result from excess consumption of omega-3 fatty acids.

Studies have shown that omega-3s, also known as long chain polyunsaturated fatty acids (LCPUFAs), are associated with lower risk of sudden cardiac death and other cardiovascular disease outcomes.

“We were inspired to review the literature based on our findings after recent publications showed increased risk of advanced prostate cancer and atrial fibrillation in those with high blood levels of LCPUFAs,” Fenton said.

Omega-3 fatty acids have anti-inflammatory properties, which is one of the reasons they can be beneficial to heart health and inflammatory issues. However, the researchers said excess amounts of omega-3 fatty acids can alter immune function sometimes in ways that may lead to a dysfunctional immune response to a viral or bacterial infection.

“The dysfunctional immune response to excessive omega-3 fatty acid consumption can affect the body’s ability to fight microbial pathogens, like bacteria,” Hord said.

Generally, the researchers point out that the amounts of fish oil used in most studies are typically above what one could consume from foods or usual dosage of a dietary supplement. However, an increasing amount of products, such as eggs, bread, butters, oils and orange juice, are being “fortified” with omega-3s. Hord said this fortified food, coupled with fish oil supplement use, increases the potential for consuming these high levels.

“Overall, we support the dietary recommendations from the American Heart Association to eat fish, particularly fatty fish like salmon, mackerel, lake trout or sardines, at least two times a week, and for those at risk of coronary artery disease to talk to their doctor about supplements,” he said.

“Our main concern here is the hyper-supplemented individual, who may be taking high-dose omega-3 supplements and eating four to five omega-3-enriched foods per day,” Hord added. “This could potentially get someone to an excessive amount. As our paper indicates, there may be subgroups of those who may be at risk from consuming excess amounts of these fatty acids.”

Hord said there are no evidence-based standards for omega-3 intake and no way to tell who might be at health risk if they consume too high a level of these fatty acids.

“We’re not against using fish oil supplements appropriately, but there is a potential for risk,” Hord said. “As is all true with any nutrient, taking too much can have negative effects. We need to establish clear biomarkers through clinical trials. This is necessary in order for us to know who is eating adequate amounts of these nutrients and who may be deficient or eating too much.

“Until we establish valid biomarkers of omega-3 exposure, making good evidence-based dietary recommendations across potential dietary exposure ranges will not be possible.”

Sanjoy Ghosh from University of BC-Okanagan, Canada and Eric Gurzell from Michigan State University also contributed to this study, which was supported by grants from the National Institutes of Health and the Canadian Diabetes Association.

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Norman Hord, 541-737-5923

Beyond antibiotics: “PPMOs” offer new approach to bacterial infection

CORVALLIS, Ore. – Researchers at Oregon State University and other institutions today announced the successful use of a new type of antibacterial agent called a PPMO, which appears to function as well or better than an antibiotic, but may be more precise and also solve problems with antibiotic resistance.

In animal studies, one form of PPMO showed significant control of two strains of Acinetobacter, a group of bacteria of global concern that has caused significant mortality among military personnel serving in Middle East combat.

The new PPMOs offer a fundamentally different attack on bacterial infection, researchers say.

They specifically target the underlying genes of a bacterium, whereas conventional antibiotics just disrupt its cellular function and often have broader, unwanted impacts. As they are further developed, PPMOs should offer a completely different and more precise approach to managing bacterial infection, or conceptually almost any disease that has an underlying genetic component.

The findings were published today in the Journal of Infectious Diseases, by researchers from OSU, the University of Texas Southwestern Medical Center, and Sarepta, Inc., a Corvallis, Ore., firm.

“The mechanism that PPMOs use to kill bacteria is revolutionary,” said Bruce Geller, a professor of microbiology in the OSU College of Science and lead author on the study. “They can be synthesized to target almost any gene, and in that way avoid the development of antibiotic resistance and the negative impacts sometimes associated with broad-spectrum antibiotics.

“Molecular medicine,” Geller said, “is the way of the future.”

PPMO stands for a peptide-conjugated phosphorodiamidate morpholino oligomer – a synthetic analog of DNA or RNA that has the ability to silence the expression of specific genes. Compared to conventional antibiotics, which are often found in nature, PPMOs are completely synthesized in the laboratory with a specific genetic target in mind.

In animal laboratory tests against A. baumannii, one of the most dangerous Acinetobacter strains, PPMOs were far more powerful than some conventional antibiotics like ampicillin, and comparable to the strongest antibiotics available today. They were also effective in cases where the bacteria were resistant to antibiotics.

PPMOs have not yet been tested in humans. However, their basic chemical structure, the PMO, has been extensively tested in humans and found safe. Although the addition of the peptide to the PPMO poses an uncertain risk of toxicity, the potency of PPMOs reduces the risk while greatly improving delivery of the PMOs into bacterial cells, Geller said.

Geller said research is being done with Acinetobacter in part because this pathogen has become a huge global problem, and is often spread in hospitals. It can cause respiratory infection, sepsis, and is a special concern to anyone whose immune system is compromised. Wounds in military battle conditions have led to numerous cases in veterans, and A. baumannii is now resistant to many antibiotics. “Urgent new approaches to therapeutics are needed,” the scientists said in their report.

Continued research and eventually human clinical trials will be required before the new compounds are available for health care, the researchers said. This and continued studies have been supported by the National Institutes of Health, the other collaborators and the N.L. Tartar fund.

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Editor’s Note: A scanning electron microscope image of A. baumannii is available online (please provide image credit as indicated at web site): http://bit.ly/GztejR

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Bruce Geller, 541-737-1845