CNO Report 185
Release Date 12 JUL 2014
Draft Report Compiled by
In This Issue:
1. Insulin, other drugs may do more harm than good for some type 2 diabetes patients
2. Chinese Herbal Extract May Help Kill Off Pancreatic Cancer Cells
3. Brisk walking may improve symptoms of Parkinson’s
4. Polyphenols could yield small benefit for people with PAD
5. Only 25 minutes of mindfulness meditation alleviates stress
6. Researchers uncover new knowledge about our intestines
7. Study suggests consuming whey protein before meals could help improve blood glucose control in people with diabetes
8. Less exercise, not more calories, responsible for expanding waistlines
9. Sandalwood scent facilitates wound healing and skin regeneration
10. Cinnamon May Be Used to Halt the Progression of Parkinson’s disease
11. Think Fun when Exercising and You’ll Eat Less Later!
12. Sunshine vitamin ups bowel cancer survival odds, study finds
13. Scientist finds link between antibiotics, bacterial biofilms and chronic infections
14. New research: Fresh avocado enhances absorption of essential nutrients for healthy living
15. Omega 3 Fatty Acids Lessen Severity of Osteoarthritis in Mice
16. Major study documents nutritional and food safety benefits of organic farming
17. Growing up on a livestock farm halves the risk of inflammatory bowel diseases
Insulin, other drugs may do more harm than good for some type 2 diabetes patients
Harm to quality of life outweighs benefits of treatment for older patients and those with negative feelings about side effects, burden of medication
ANN ARBOR, Mich. — For patients with type 2 diabetes – especially those over age 50 – the negative impact of side effects like weight gain and burdens like frequent insulin shots trumps the benefits of drugs, says a new study by the University of Michigan Health System, the VA Ann Arbor Healthcare System, and University College London.
The findings, which appear in today’s Journal of the American Medical Association Internal Medicine, show that for many, the benefits of taking diabetes medications are so small that they are outweighed by the minor hassles and risks.
These findings suggest that, contrary to current guidelines for type 2 diabetes that recommend intensifying treatment until a person’s blood sugar level reaches a certain goal, the overall benefit of taking a new medicine depends less on blood sugar and more on the hassles, safety and side effects of taking the treatment.
“For people with type 2 diabetes, the goal of managing blood sugar levels is to prevent associated diabetes complications, such as kidney, eye and heart disease, but it is essential to balance complication risks and treatment burdens when deciding how aggressively to treat blood sugars,” says lead author Sandeep Vijan M.D., M.S., professor of Internal Medicine at the U-M Medical School and research scientist at the Center for Clinical Management Research at the VA Ann Arbor Healthcare System.
“If you’re a patient with fairly low complication risks, but are experiencing symptoms from low blood sugar, gaining weight or find frequent insulin shots to be disruptive to your daily life, then the drugs are doing more harm than good. Prescribing medicine isn’t just about reducing risks of complications, but also about helping patients improve their quality of life.”
Vijan notes that for many patients, once moderate levels of glucose control are achieved, there is little additional benefit to intensive blood sugar treatment, but treatment costs, burdens and risks increase substantially. The study finds that the benefits of treatment decline with age and by age 75 the harms of most treatments are likely to outweigh any benefits.
The findings exclude the 15-20 percent of people with type 2 diabetes who have very high blood glucose levels (which are defined by what’s called an A1c test ) and need more aggressive treatment to manage the disease.
Individualized treatment recommendations determined by patients’ estimated risk of diabetes complications – influenced by their age and degree of blood glucose elevation – and considering the side effects and amount of safety data of the medication being considered, is a much better approach than focusing solely on glucose goals, the researchers argue.
“Drugs that lower blood sugar levels are extremely beneficial in some patients but offer almost no benefit for others. These results have major implications for the millions of people who are currently being told that they need to increase medication in order to achieve their ‘glucose goal,'” says senior author Rodney Hayward, M.D., professor of medicine in the U-M Medical School and senior research scientist at the Center for Clinical Management Research at the VA Ann Arbor Healthcare System.
“Current quality measures do not allow doctors and patients to make good decisions for each patient because they emphasize reaching targets instead of thinking of the risks and benefits of starting new medications based on individual circumstances and preferences.”
The study is the latest to challenge “treat-to-target” guidelines in medicine. Research concluding that risks outweighed benefits of drugs intended to achieve specific blood pressure goals in some patients prompted a significant change in hypertension guidelines last year and similar recommendations were implemented for lipid lowering therapy.
Chinese Herbal Extract May Help Kill Off Pancreatic Cancer Cells
Bethesda, Md. (July 1, 2014) — A diagnosis of pancreatic cancer—the fourth most common cause of cancer death in the U.S.—can be devastating. Due in part to aggressive cell replication and tumor growth, pancreatic cancer progresses quickly and has a low five-year survival rate (less than 5 percent).
GRP78, a protein that protects cells from dying, is more abundant in cancer cells and tissue than in normal organs and is thought to play a role in helping pancreatic cancer cells survive and thrive. Researchers at the University of Minnesota have found triptolide, an extract of the Chinese herb thunder god vine (Tirpterygium wilforii), suppresses GRP78, eventually leading to pancreatic cancer cell death.
For mammals to use the proteins in our bodies, a process called protein folding must occur in the endoplasmic reticulum (ER) of cells. If proteins are not folded fast enough, unfolded proteins begin to build up and the cell becomes stressed. Prolonged ER stress activates a cellular process called the “unfolded protein response (UPR)”. Initially, the UPR helps kick-start the cell’s protein-folding ability, allowing it to function properly again. But if the problem doesn’t resolve, the UPR triggers cell death.
GRP78 helps cells survive long enough for the UPR to kick in and correct protein-folding problems. However, GRP78 is available in higher quantities in pancreatic cancer cells, which assists the cancer cells in evading cell death, allowing them to live and multiply.
Triptolide has previously been shown to have a negative effect on pancreatic cancer cell viability and to block growth and spread of these cells. In this study led by Ashok Saluja, Ph.D., researchers observed the effects of triptolide on human pancreatic cancer cells and tissue. They found that the UPR worked properly in triptolide-treated cells to allow cell death in malfunctioning cells.
“Our study shows that although increased expression of GRP78 confers a survival advantage to the tumor cells, prolonged exposure to triptolide induces chronic ER stress, which eventually leads to cell death,” the authors stated. “In this context, inhibition of GRP78 by activation of the ER stress pathway by triptolide offers a novel mechanism for inhibiting the growth and survival of pancreatic cancer cells.”
The article “Triptolide activates unfolded protein response leading to chronic ER stress in pancreatic cancer cells” is published in the American Journal of Physiology—Gastrointestinal and Liver Physiology. It is highlighted as one of this month’s “best of the best” as part of the American Physiological Society’s APSselect program. View the full study here: ow.ly/yxpMq. Read all of this month’s selected research articles at apsselect.physiology.org/.
Brisk walking may improve symptoms of Parkinson’s
MINNEAPOLIS – People with mild to moderate Parkinson’s disease who regularly walk for exercise may improve their motor function, mood, tiredness, fitness and some aspects of thinking abilities, according to a study published in the July 2, 2014, online issue of Neurology®, the medical journal of the American Academy of Neurology.
“The results of our study suggest that walking may provide a safe and easily accessible way of improving the symptoms of Parkinson’s disease and improve quality of life,” said study author Ergun Y. Uc, MD, with the University of Iowa in Iowa City and the Veterans Affairs Medical Center of Iowa City. Uc is also a member of the American Academy of Neurology.
The study included 60 people who took part in sessions of walking at moderate intensity while wearing heart rate monitors three times a week for 45 minutes per session for six months. The participants also took tests that measured their motor function, aerobic fitness, mood, tiredness, and memory and thinking abilities.
The average walking speed was about 2.9 miles per hour, and participants were exercising at 47 percent of their heart rate reserve, which meets the definition of moderate intensity aerobic exercise.
The study found that brisk walking improved motor function and mood by 15 percent, attention/response control scores by 14 percent, reduced tiredness by 11 percent, and increased aerobic fitness and gait speed by seven percent. On the test of motor function, participants improved by an average of 2.8 points, which is considered a clinically important difference.
“People with mild-moderate Parkinson’s who do not have dementia and are able to walk independently without a cane or walker can safely follow the recommended exercise guidelines for healthy adults, which includes 150 minutes per week of moderate intensity aerobic activity, and experience benefits,” said Uc. He added that these results need to be confirmed in a randomized study with a control group.
Polyphenols could yield small benefit for people with PAD
American Heart Association Rapid Access Journal Report
July 02, 2014 | Categories: Heart News
•Polyphenols – compounds found in cocoa and other foods may help people with peripheral artery disease walk a little longer and farther before pain sets in.
•More research is needed to see whether long-term use of these compounds in dark chocolate can improve circulation and aid patients.
Embargoed until 3 p.m. CT/4 p.m. ET Wednesday, July 2, 2014
DALLAS, July 2, 2014 — In a small study, people with artery problems in their legs walked a little longer and farther when they ate dark chocolate – a food rich in polyphenols, according to new research in Journal of the American Heart Association.
Peripheral artery disease (PAD) is a narrowing of the peripheral arteries to the legs, stomach, arms, and head – most commonly in the arteries of the legs. Reduced blood flow can cause pain, cramping or fatigue in the legs or hips while walking.
In this pilot study of patients with PAD (14 men and six women, ages 60-78), study participants increased their ability to walk unassisted after eating dark chocolate, compared to when they ate milk chocolate. The authors suggest that compounds found in cocoa – polyphenols – may reduce oxidative stress and improve blood flow in peripheral arteries.
The patients were tested on a treadmill in the morning and again two hours after eating 40 grams of dark and milk chocolate (about the size of an average American plain chocolate bar) on separate days. The dark chocolate in the study had a cocoa content of more than 85 percent, making it rich in polyphenols. The milk chocolate, with a cocoa content below 30 percent, had far fewer polyphenols.
After eating the dark chocolate, they walked an average 11 percent farther and 15 percent longer (almost 12 meters/39 feet farther and about 17 seconds longer) than they could earlier that day. But distance and time didn’t improve after eating milk chocolate.
The improvements were modest. Still, the benefit of dark chocolate polyphenols is “of potential relevance for the quality of life of these patients,” said Lorenzo Loffredo, M.D., the study’s co-author and assistant professor at the Sapienza University of Rome in Italy.
Levels of nitric oxide — a gas linked to improved blood flow — were higher when participants ate dark chocolate. Other biochemical signs of oxidative stress were also lower. Based on these observations and other laboratory experiments, the authors suggest that the higher nitric oxide levels may be responsible for dilating peripheral arteries and improving walking independence.
“Polyphenol-rich nutrients could represent a new therapeutic strategy to counteract cardiovascular complications,” said, Francesco Violi, M.D., study senior author and professor of internal medicine at the Sapienza University of Rome.
The researchers said the improvements linked to these compounds in dark chocolate need to be confirmed in a larger study involving long-term consumption. The current study lacked a placebo group, and patients knew which kind of chocolate they were given, a factor that could influence the results.
American Heart Association spokesperson Dr. Mark Creager noted that it’s far too early to recommend polyphenols or dark chocolate for cardiovascular health.
“Other investigations have shown that polyphenols including those in dark chocolate may improve blood vessel function. But this study is extremely preliminary and I think everyone needs to be cautious when interpreting the findings,” said Creager, who is director of the Vascular Center at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School in Boston.
“We know from other studies of antioxidants — vitamin C and vitamin E for example — that these interventions have not gone on to show improvement in cardiovascular health.”
Chocolate adds calories to the diet. The American Heart Association recommends that men consume no more than 150 calories per day from added sugars (9 teaspoons) and women should consume no more than 100 calories (6 teaspoons) from added sugar per day and 5 percent -6 percent of calories from saturated fat. A typical American chocolate bar provides 94 calories from sugar (24 grams) and 8 grams of saturated fat.
Many other polyphenol-rich foods would offer less added sugar, saturated fats, and calories than dark chocolate, such as cloves, dried peppermint, celery seed, capers, and hazelnuts, to name a few.
Only 25 minutes of mindfulness meditation alleviates stress
PITTSBURGH—Mindfulness meditation has become an increasingly popular way for people to improve their mental and physical health, yet most research supporting its benefits has focused on lengthy, weeks-long training programs.
New research from Carnegie Mellon University is the first to show that brief mindfulness meditation practice – 25 minutes for three consecutive days – alleviates psychological stress. Published in the journal Psychoneuroendocrinology, the study investigates how mindfulness meditation affects people’s ability to be resilient under stress.
“More and more people report using meditation practices for stress reduction, but we know very little about how much you need to do for stress reduction and health benefits,” said lead author J. David Creswell, associate professor of psychology in the Dietrich College of Humanities and Social Sciences.
For the study, Creswell and his research team had 66 healthy individuals aged 18-30 years old participate in a three-day experiment. Some participants went through a brief mindfulness meditation training program; for 25 minutes for three consecutive days, the individuals were given breathing exercises to help them monitor their breath and pay attention to their present moment experiences. A second group of participants completed a matched three-day cognitive training program in which they were asked to critically analyze poetry in an effort to enhance problem-solving skills.
Following the final training activity, all participants were asked to complete stressful speech and math tasks in front of stern-faced evaluators. Each individual reported their stress levels in response to stressful speech and math performance stress tasks, and provided saliva samples for measurement of cortisol, commonly referred to as the stress hormone.
The participants who received the brief mindfulness meditation training reported reduced stress perceptions to the speech and math tasks, indicating that the mindfulness meditation fostered psychological stress resilience. More interestingly, on the biological side, the mindfulness mediation participants showed greater cortisol reactivity.
“When you initially learn mindfulness mediation practices, you have to cognitively work at it – especially during a stressful task,” said Creswell. “And, these active cognitive efforts may result in the task feeling less stressful, but they may also have physiological costs with higher cortisol production.”
Creswell’s group is now testing the possibility that mindfulness can become more automatic and easy to use with long-term mindfulness meditation training, which may result in reduced cortisol reactivity.
Researchers uncover new knowledge about our intestines
Researchers from DTU Systems Biology have mapped 500 previously unknown microorganisms in human intestinal flora as well as 800 also unknown bacterial viruses (also called bacteriophages) which attack intestinal bacteria.
To map the microorganisms, the researchers have developed a new principle for analysing DNA sequence data, which they have named the co-abundance principle. A principle which basically assumes that different pieces of DNA from the same organism will occur in the same amount in a sample, and that this amount will vary over a series of samples.
“Using our method, researchers are now able to identify and collect genomes from previously unknown microorganisms in even highly complex microbial societies. This provides us with an overview we have not enjoyed previously,” says Professor Søren Brunak who has co-headed the study together with Associate Professor Henrik Bjørn Nielsen.
So far, 200-300 intestinal bacterial species have been mapped. Now, the number will be more than doubled, which could significantly improve our understanding and treatment of a large number of diseases such as type 2 diabetes, asthma and obesity.
Viruses—not antimicrobial agents.
The two researchers have also studied the mutual relations between bacteria and viruses.
“Our study tells us which bacterial viruses attack which bacteria, something which has a noticeable effect on whether the attacked bacteria will survive in the intestinal system in the long term,” says Henrik Bjørn Nielsen
Previously, bacteria were studied individually in the laboratory, but researchers are becoming increasingly aware that in order to understand the intestinal flora, you need to look at the interaction between the many different bacteria found.
And when we know the intestinal bacteria interactions, we can potentially develop a more selective way to treat a number of diseases.
“Ideally we will be able to add or remove specific bacteria in the intestinal system and in this way induce a healthier intestinal flora,” says Søren Brunak.
It is particularly interesting in relation to the increasing problem of antimicrobial resistance which many consider a real threat to global health.
“We have previously been experimenting with using bacteria and viruses to fight disease, but this was shelved because antimicrobial agents have been so effective in combating many infectious diseases. If we can learn more about who attacks who, then bacterial viruses could be a viable alternative to antimicrobial agents. It is therefore extremely important that we now can identify and describe far more relations between bacteria and the viruses that attack them,” says Henrik Bjørn Nielsen.
Study suggests consuming whey protein before meals could help improve blood glucose control in people with diabetes
New research published in Diabetologia (the journal of the European Association for the Study of Diabetes) suggests that consuming whey protein before a regular breakfast reduces the blood sugar spikes seen after meals and also improves the body’s insulin response. Thus whey protein could be an additional tool to help control blood sugar in patients with diabetes. The research was conducted in Israel by Professor Daniela Jakubowicz and Dr Julio Wainstein (Wolfson Medical Center, Tel Aviv University), Professor Oren Froy (Hebrew University of Jerusalem), Professor Bo Ahrén (Lund University, Sweden) and colleagues.
Protein consumption is known to stimulate the production of glucagon-like peptide-1 (GLP-1), a gut hormone that in turn stimulates insulin production. Thus the researchers hypothesised that stimulating GLP-1 production by consuming whey protein before a meal would improve the body’s blood sugar control following a meal.
The study included 15 people with well-controlled type 2 diabetes who were not taking any medications except for sulfonylureas or metformin (oral diabetes drugs). These participants consumed, on two separate days, 50 g whey in 250 ml water or placebo (250 ml water) followed by a standardised high-glycaemic-index breakfast in a hospital setting. The breakfast contained 3 slices of white bread and sugar-containing jelly, a meal designed to produce the maximum post-meal glucose spike. A blood sample was taken 30 minutes before the meal, and the whey protein or placebo drink was served at that point. Further blood samples were taken when the meal was served (0 mins) and at 15, 30, 60, 90, 120, 150 and 180 mins.
Patients were randomised to either the whey protein or placebo arm of the study, but the crossover design of the trial meant that all participants did both the whey protein and placebo arms, with two weeks between visits. This design also means that the study was statistically well powered despite the small number of participants.
The results showed that over the whole 180 min post-meal period, glucose levels were reduced by 28% after whey protein pre-load compared with no whey protein. Insulin and C-peptide (a building block of insulin) responses were both significantly higher (by 105% and 43%, respectively) in the whey protein group. Notably, the early insulin response (meaning within the first 30 minutes following breakfast) was 96% higher after whey protein than with placebo. This is especially important since the loss of early insulin response is the most important deficiency in diabetic individuals and a major contributor to the post-meal rise in blood glucose. Additionally, both total GLP-1 (tGLP-1) and intact GLP-1 (iGLP-1) levels were significantly higher (by 141% and 298%, respectively) with whey protein pre-load.
The authors conclude: “In summary, consumption of whey protein shortly before a high-glycaemic-index breakfast increased the early and late post-meal insulin secretion, improved GLP-1 responses and reduced post-meal blood sugar levels in type 2 diabetic patients. Whey protein may therefore represent a novel approach for enhancing glucose-lowering strategies in type 2 diabetes.” They add that such treatment would be cheap and easy to administer, with patients able to use any brand of whey protein concentrate which has no added sugar or other nutrients.
Based on the findings of this study, the authors are considering conducting a long-term clinical trial to discover if the beneficial effects of administering whey protein on blood sugar, insulin, and GLP-1 are long lasting.
Less exercise, not more calories, responsible for expanding waistlines
Lack of leisure-time physical activity linked to increased obesity, particularly in young women, reports the American Journal of Medicine
Philadelphia, PA, July 7, 2014 – Sedentary lifestyle and not caloric intake may be to blame for increased obesity in the US, according to a new analysis of data from the National Health and Nutrition Examination Survey (NHANES). A study published in the American Journal of Medicine reveals that in the past 20 years there has been a sharp decrease in physical exercise and an increase in average body mass index (BMI), while caloric intake has remained steady. Investigators theorized that a nationwide drop in leisure-time physical activity, especially among young women, may be responsible for the upward trend in obesity rates.
By analyzing NHANES data from the last 20 years, researchers from Stanford University discovered that the number of US adult women who reported no physical activity jumped from 19.1% in 1994 to 51.7% in 2010. For men, the number increased from 11.4% in 1994 to 43.5% in 2010. During the period, average BMI has increased across the board, with the most dramatic rise found among young women ages 18-39.
“These changes have occurred in the context of substantial increases in the proportion of adults reporting no leisure-time physical activity, but in the absence of any significant population-level changes in average daily caloric intake,” explains lead investigator Uri Ladabaum, MD, MS, Associate Professor of Medicine (Gastroenterology and Hepatology), Stanford University School of Medicine. “At the population level, we found a significant association between the level of leisure-time physical activity, but not daily caloric intake, and the increases in both BMI and waist circumference.”
The study looked at the escalation of obesity in terms of both exercise and caloric intake. While investigators did not examine what types of foods were consumed, they did observe that total daily calorie, fat, carbohydrate, and protein consumption have not changed significantly over the last 20 years, yet the obesity rate among Americans is continuing to rise.
Researchers also tracked the rise in abdominal obesity, which is an independent indicator of mortality even among people with normal BMIs. Abdominal obesity is defined by waist circumference of 88 cm (34.65 in) or greater for women and 102 cm (40.16 in) or greater for men. Data showed that average waist circumference increased by 0.37% per year for women and 0.27% per year for men. Just like the rise in average BMIs, the group most affected by increased rates of abdominal obesity was women.
“The prevalence of abdominal obesity has increased among normal-weight women and overweight women and men,” observes Dr. Ladabaum. “It remains controversial whether overweight alone increases mortality risk, but the trends in abdominal obesity among the overweight are concerning in light of the risks associated with increased waist circumference independent of BMI.”
When Ladabaum et al grouped respondents to the most recent NHANES survey by race/ethnicity and age, they found that more than 50% of the workforce-aged adults in eight demographic subgroups reported no leisure-time physical activity. The following chart displays the results and highlights the differences between the 1994 survey results and those collected in 2010 (albeit, with slightly different survey methods). According to this data, women, and black and Mexican-American women in particular, showed the greatest decreases in reported exercise.
While increased caloric intake is often blamed for rising rates of obesity, no association between these was found in this study; in contrast, an association was found between the trends over time for lack of physical activity and high BMI numbers. “Our findings do not support the popular notion that the increase of obesity in the United States can be attributed primarily to sustained increase over time in the average daily caloric intake of Americans,” concludes Dr. Ladabaum. “Although the overall trends in obesity in the United States are well appreciated and obesity prevalence may be stabilizing, our analyses highlight troublesome trends in younger adults, in women, and in abdominal obesity prevalence, as well as persistent racial/ethnic disparities.”
There is no easy answer in our ongoing battle against obesity, but identifying the link between the drop in physical activity and increased BMIs, as well as the groups particularly affected, can assist public health officials to develop targeted, effective interventions. In an accompanying commentary Pamela Powers Hannley, MPH, Managing Editor, the American Journal of Medicine, notes, “If we as a country truly want to take control of our health and our health care costs, the Ladabaum et al paper should be our clarion call. From encouraging communities to provide safe places for physical activity to ensuring ample supply of healthy food to empowering Americans to take control of their health, we must launch a concerted comprehensive effort to control obesity.”
Sandalwood scent facilitates wound healing and skin regeneration
Researchers from Bochum detect olfactory receptors in the skin
Receptor accelerates cell division and migration
Skin cells possess an olfactory receptor for sandalwood scent, as researchers at the Ruhr-Universität Bochum have discovered. Their data indicate that the cell proliferation increases and wound healing improves if those receptors are activated. This mechanism constitutes a possible starting point for new drugs and cosmetics. The team headed by Dr Daniela Busse and Prof Dr Dr Dr med habil Hanns Hatt from the Department for Cellphysiology published their report in the “Journal of Investigative Dermatology”.
The nose is not the only place where olfactory receptors occur
Humans have approximately 350 different types of olfactory receptors in the nose. The function of those receptors has also been shown to exist in, for example spermatozoa, the prostate, the intestine and the kidneys. The team from Bochum has now discovered them in keratinocytes – cells that form the outermost layer of the skin.
Experiments with cultures of human skin cells
The RUB researchers studied the olfactory receptor that occurs in the skin, namely OR2AT4, and discovered that it is activated by a synthetic sandalwood scent, so-called Sandalore. Sandalwood aroma is frequently used in incense sticks and is a popular component in perfumes. The activated OR2AT4 receptor triggers a calcium-dependent signal pathway. That pathway ensures an increased proliferation and a quicker migration of skin cells – processes which typically facilitate wound healing. In collaboration with the Dermatology Department at the University of Münster, the cell physiologists from Bochum demonstrated that effect in skin cell cultures and skin explants.
Additional olfactory receptors in skin detected
In addition to OR2AT4, the RUB scientists have also found a variety of other olfactory receptors in the skin, the function of which they are planning to characterise more precisely. “The results so far show that they possess therapeutic and cosmetic potential,” says Prof Hanns Hatt. “Still, we mustn’t forget that concentrated fragrances should be handled with care, until we have ascertained which functions the different types of olfactory receptors in skin cells have.”
Cinnamon May Be Used to Halt the Progression of Parkinson’s disease
Study Results Published in the Journal of Neuroimmune Pharmacology
(CHICAGO) – Neurological scientists at Rush University Medical Center have found that using cinnamon, a common food spice and flavoring material, can reverse the biomechanical, cellular and anatomical changes that occur in the brains of mice with Parkinson’s disease (PD). The results of the study were recently published in the June 20 issue of the Journal of Neuroimmune Pharmacology.
“Cinnamon has been used widely as a spice throughout the world for centuries,” said Kalipada Pahan, PhD, study lead researcher and the Floyd A. Davis professor of neurology at Rush. “This could potentially be one of the safest approaches to halt disease progression in Parkinson’s patients.”
“Cinnamon is metabolized in the liver to sodium benzoate, which is an FDA-approved drug used in the treatment for hepatic metabolic defects associated with hyperammonemia,” said Pahan. It is also widely used as a food preservative due to its microbiocidal effect.
Chinese cinnamon (Cinnamonum cassia) and original Ceylon cinnamon (Cinnamonum verum) are two major types of cinnamon that are available in the US.
“Although both types of cinnamon are metabolized into sodium benzoate, by mass spectrometric analysis, we have seen that Ceylon cinnamon is much more pure than Chinese cinnamon as the latter contains coumarin, a hepatotoxic molecule,” said Pahan.
“Understanding how the disease works is important to developing effective drugs that protect the brain and stop the progression of PD,” said Pahan. “It is known that some important proteins like Parkin and DJ-1 decrease in the brain of PD patients.”
The study found that after oral feeding, ground cinnamon is metabolized into sodium benzoate, which then enters into the brain, stops the loss of Parkin and DJ-1, protects neurons, normalizes neurotransmitter levels, and improves motor functions in mice with PD.
Think Fun when Exercising and You’ll Eat Less Later!
Think of your next exercise workout as a “fun run” or as a well-deserved break, and you’ll eat less afterward. Think of it as exercise or as a workout and you’ll later eat more dessert and snacks to reward yourself.
These new findings from the Cornell Food and Brand Lab study involved two studies where adults were led on a 2 km walk around a small lake and were either told it was going to be an exercise walk or a scenic walk. In the first study, 56 adults completed their walk and were then given lunch. Those who believed they had been on an exercise walk served and ate 35% more chocolate pudding for dessert than those who believed they had been on a scenic walk.
In the second study, 46 adults were given mid-afternoon snacks after their walk. Those thinking they taken an exercise walk ate 206 more calories of M&Ms, which was over twice as much – 124% more – than those who had been told they were on a scenic walk. “Viewing their walk as exercise led them to be less happy and more fatigued,” says lead author, Carolina Werle, professor at Grenoble Ecole de Management in France.
Together, these studies point to one reason why people in exercise programs often find themselves gaining weight. According to Werle, the notion is that some exercisers have a tendency to reward themselves by overeating after their workout.”
For beginning or veteran exercisers, the bottom line is this: “Do whatever you can to make your workout fun. Play music, watch a video, or simply be grateful that you’re working out instead of working in the office,” said Brian Wansink, author and Director of the Cornell Food and Brand Lab. “Anything that brings a smile, is likely to get you to eat less,” he added.
Sunshine vitamin ups bowel cancer survival odds, study finds
Bowel cancer patients with high levels of vitamin D in their blood are more likely to survive the disease, a study shows.
Patients with the highest levels of vitamin D have half the risk of dying compared with those with the lowest levels, the findings reveal.
The study is the first to correlate total blood levels of vitamin D in bowel cancer patients after their diagnosis – which includes that produced after exposure to sunlight and that obtained from dietary sources – with their long term survival prospects.
The University of Edinburgh team tested blood samples from almost 1600 patients after surgery for bowel cancer.
The greatest benefit of vitamin D was seen in patients with stage 2 disease, at which the tumour may be quite large but the cancer has not yet spread.
Researchers found that three quarters of the patients with the highest vitamin D levels were still alive at the end of five years, compared with less than two thirds of those with the lowest levels.
The results show that vitamin D is associated with a much better chance of cancer survival, although the nature of this relationship is not clear from this study.
The study’s authors aim to set up a clinical trial to test whether taking vitamin D tablets in combination with chemotherapy can improve bowel cancer survival rates.
Measuring vitamin D levels in bowel cancer patients could also provide a useful indication of prognosis, the scientists say.
Professor Malcolm Dunlop, of the Medical Research Council Human Genetics Unit at the University of Edinburgh, said: “Our findings are promising but it is important to note that this is an observational study. We need carefully designed randomised clinical trials before we can confirm whether taking vitamin D supplements offers any survival benefit for bowel cancer patients.”
Scientist finds link between antibiotics, bacterial biofilms and chronic infections
Results may lead to new approach for treatment of chronic ear infections in children
Researchers from the University of Southern California and the Oak Crest Institute of Science have discovered the link between antibiotics and bacterial biofilm formation leading to chronic lung, sinus and ear infections. The study results, published in the current issue of PLOS ONE, illustrate how bacterial biofilms can actually thrive, rather than decrease, when given low doses of antibiotics.
“This research addresses the long standing issues surrounding chronic ear infections and why some children experience repeated ear infections even after antibiotic treatment,” said Paul Webster, PhD, lead author, senior staff scientist at USC and senior faculty at the Oak Crest Institute of Science. “Once the biofilm forms, it becomes stronger with each treatment of antibiotics.”
During the study, non-typeable Haemophilus influenzae (NTHi) bacteria a common pathogen of humans was exposed to non-lethal doses of ampicillin, a class of antibiotics commonly used to treat respiratory, sinus and ear infections, or other beta-lactam antibiotics. The dose of the antibiotic was not enough to kill the bacteria which allowed the bacteria to react to the antibiotic by producing glycogen, a complex sugar often used by bacteria as a food source, to produce stronger biofilms when grown in the laboratory.
Biofilms are highly structured communities of microorganisms that attach to one another and to surfaces. The microorganisms group together and form a slimy, polysaccharide cover. This layer is highly protective for the organisms within it, and when new bacteria are produced they stay within the slimy layer. With the introduction of antibiotic-produced glycogen, the biofilms have an almost endless food source that can be used once antibiotic exposure has ended.
There are currently no approved treatments for biofilm-related infections. Therefore, bacteria forced into forming stronger biofilms will become more difficult to treat and will cause more severe chronic infections. Adults will suffer protracted lung infections as the bacteria hunker down into their protective slime, and children will have repeated ear infections. What may appear to be antibiotic resistance when an infection does not clear up may actually be biofilms at work.
Webster believes modern medicine needs to find ways of detecting and treating biofilm infections before the bacteria are able to form these protective structures. The difficulties of treating biofilm infections, which can be up to 1,000 times more resistant to antibiotics, have prompted some physicians to propose a gradual move away from traditional antibiotic treatments and toward non-antibiotic therapies.
“If antibiotics are to continue to be relevant for treating bacterial infections it is important that their effects on biofilms be explored,” says Dr. Webster.
“One step in this direction would be to develop routine screening methods to test the effects of antibiotics on in vitro formed biofilms.”
New research: Fresh avocado enhances absorption of essential nutrients for healthy living
Study explores improvements in the absorption of vitamin A when avocados are eaten with tomatoes or carrots
IRVINE, Calif. (July 10, 2014) – Consuming a whole fresh avocado with either an orange-colored tomato sauce or raw carrots significantly enhanced provitamin A carotenoid (alpha- and beta-carotene) absorption and conversion of these carotenoids to an active form of vitamin A, according to new research (1) published in The Journal of Nutrition.
Vitamin A is involved in reproductive health and growth promotion; helps support healthy skin, immune function, and vision; and has antioxidant properties. Provitamin A carotenoids, like alpha- and beta-carotene, impart the orange and yellow colors to many fruits and vegetables. The body converts these plant pigments into an active and usable form of vitamin A.
The research, “Avocado consumption enhances human post-prandial absorption and conversion from a novel high beta-carotene tomato sauce and from carrots,” conducted at The Ohio State University and supported by the Hass Avocado Board (HAB), investigated if avocados could help the body better use and absorb vitamin A from carotene-rich foods when eaten together.
Specifically, the research was based on two randomized, two-way crossover feeding studies in 12 healthy men and women. The first study investigated if fresh avocado, when eaten with high beta-carotene tomato sauce, would promote the absorption of provitamin A carotenoids, and the conversion of these carotenoids to an active form of vitamin A. The second study investigated the same outcome, but replaced high beta-carotene tomato sauce with raw carrots.
For the first study, researchers found that compared to a tomato sauce meal without avocado, the addition of one avocado (150 g):
•More than doubled (2.4 times) beta-carotene absorption
•More than quadrupled (4.6 times) the conversion of provitamin A (inactive vitamin form) to vitamin A (active vitamin form)
Similarly, researchers found in the second study that compared to a raw carrot meal without avocado, the addition of one avocado (150 g):
•Significantly increased beta-carotene absorption 6.6 times
•More than quadrupled (4.8 times) alpha-carotene absorption
•Significantly increased (12.6 times) the conversion of provitamin A (inactive vitamin form) to vitamin A (active vitamin form)
“The results of this study strengthen the current body of research on this topic and complements a previous study (2) conducted in my lab that showed a similar enhancement in carotenoid absorption with one-half of an avocado (75 g),” said Steven Schwartz, PhD, Professor, Carl E. Haas Endowed Chair, The Ohio State University. “The results also provide promising clues and a basis for future research to determine avocados’ effect on the conversion of provitamin A to vitamin A.”
“Pairing certain foods together is more than just about taste – specific foods eaten together can help your body utilize the benefits more effectively. We know that avocado consumers are interested in foods that act like a ‘nutrient booster,’ ” said Nikki A. Ford, PhD, Director of Nutrition, HAB. “While additional studies are needed to determine if these results can be applied to everyone, the studies’ outcomes help to strengthen and advance the body of published research on avocado benefits and their role in everyday healthy living. Avocados are a nutrient dense, cholesterol-free fruit with naturally good fats, and are a delicious and easy way to add more fruits and vegetables to everyday healthy eating plans.”
Omega 3 Fatty Acids Lessen Severity of Osteoarthritis in Mice
By Duke Medicine News and Communications
DURHAM, N.C. — Mice consuming a supplement of omega 3 fatty acids had healthier joints than those fed diets high in saturated fats and omega 6 fatty acids, according to Duke Medicine researchers.
The findings, published in the Annals of the Rheumatic Diseases (10.1136/annrheumdis-2014-205601) on July 11, 2014, suggest that unhealthy dietary fats – not just obesity – may contribute to worsening osteoarthritis.
“Our results suggest that dietary factors play a more significant role than mechanical factors in the link between obesity and osteoarthritis,” said Farshid Guilak, Ph.D., Laszlo Ormandy Professor of Orthopaedic Surgery at Duke and the study’s senior author.
Obesity is one of the primary risk factors for osteoarthritis, although the mechanisms linking these conditions are not fully understood. It has been assumed that increased weight wears the joints out, but this doesn’t explain why arthritis is also found in hands and other joints that don’t bear weight.
Guilak and his colleagues began studying systemic factors other than body weight to determine their effect on arthritis, and in an earlier study in obese mice, found that the lack of appetite hormone leptin predicted whether the mice had arthritis.
“This made us think that maybe it’s not how much weight you gain, but what you eat,” Guilak said.
In this study, the researchers focused on mice with osteoarthritis of the knee caused by injury to the joint. Arthritis resulting from trauma or injury is thought to account for 10 to 15 percent of all cases of arthritis.
The mice were fed one of three high-fat diets: one rich in saturated fat, one rich in omega 6 fatty acids, and one rich in omega 6 fatty acids but supplemented with a small amount of omega 3 fatty acids.
Saturated fat, which usually comes from animal sources, is known to raise cholesterol levels. Omega 6 fatty acids, often found in corn oil, soybean oil, nuts and seeds, are thought to be a healthier source of fat.
Omega 3 fatty acids, commonly found in fish or fish oil supplements, are often touted as “healthy fat” given their heart-healthy and anti-inflammatory properties. Unfortunately, most Americans eat significantly more saturated fat and omega 6 fatty acids than omega 3 fatty acids.
“A healthy diet would include roughly equal ratios of these fats, but we’re way off the scale in the Western diet,” Guilak said.
The researchers found that arthritis was significantly associated with the mice’s diets, but not with body weight. The mice that ate diets high in saturated fat or omega 6 fatty acids experienced significant worsening of their arthritis, while mice consuming a small supplement of omega 3 fatty acids had healthier joints.
“While omega 3 fatty acids aren’t reversing the injury, they appear to slow the progression of arthritis in this group of mice,” Guilak said. “In fact, omega 3 fatty acids eliminated the detrimental effects of obesity in obese mice.”
The researchers also looked at the mice’s ability to heal wounds, which may help them to understand the relationships between arthritis and wound healing. In mice consuming omega 3 fatty acids, a small ear punch typically used to differentiate mice healed much more quickly than it did in animals that did not receive the supplement.
“We found that independent of body weight, dietary fatty acids regulate ear wound healing and severity of osteoarthritis following joint injury in obese mice,” said Chia-Lung Wu, a biomedical engineering graduate student in the Duke Orthopaedic Research Laboratories and the study’s lead author.
The researchers are working to translate their findings to humans.
“A great next step would be to do a clinical study to look at effect of omega 3 fatty acids post-injury,” Guilak said.
In addition to Guilak and Wu, study authors include Deeptee Jain, Jenna N. McNeill, Dianne Little, John A. Anderson, Janet L. Huebner, Virginia B. Kraus, Ramona M. Rodriguiz and William C. Wetsel.
This study was supported by the National Institutes of Health (AR50245, AG15768, AR48852, AR48182, AG46927), a Taiwan GSSA graduate fellowship, the North Carolina Biotechnology Center and the Arthritis Foundation.
Major study documents nutritional and food safety benefits of organic farming
More antioxidants, fewer pesticides
PULLMAN, Wash.—The largest study of its kind has found that organic foods and crops have a suite of advantages over their conventional counterparts, including more antioxidants and fewer, less frequent pesticide residues.
The study looked at an unprecedented 343 peer-reviewed publications comparing the nutritional quality and safety of organic and conventional plant-based foods, including fruits, vegetables, and grains. The study team applied sophisticated meta-analysis techniques to quantify differences between organic and non-organic foods.
“Science marches on,” said Charles Benbrook, a Washington State University researcher and the lone American co-author of the paper, published in the British Journal of Nutrition. “Our team learned valuable lessons from earlier reviews on this topic, and we benefited from the team’s remarkable breadth of scientific skills and experience.”
Most of the publications covered in the study looked at crops grown in the same area, on similar soils. This approach reduces other possible sources of variation in nutritional and safety parameters.
The research team also found the quality and reliability of comparison studies has greatly improved in recent years, leading to the discovery of significant nutritional and food safety differences not detected in earlier studies. For example, the new study incorporates the results of a research project led by WSU’s John Reganold that compared the nutritional and sensory quality of organic and conventional strawberries grown in California. Responding to the new paper’s results, Reganold said, “This is an impressive study, and its major nutritional findings are similar to those reported in our 2010 strawberry paper.”
The British Journal of Nutrition study was led by scientists at Newcastle University in the United Kingdom, with Benbrook helping design the study, write the paper, and review the scientific literature, particularly on studies in North and South America. In general, the team found that organic crops have several nutritional benefits that stem from the way the crops are produced. A plant on a conventionally managed field will typically have access to high levels of synthetic nitrogen, and will marshal the extra resources into producing sugars and starches. As a result, the harvested portion of the plant will often contain lower concentrations of other nutrients, including health-promoting antioxidants.
Without the synthetic chemical pesticides applied on conventional crops, organic plants also tend to produce more phenols and polyphenols to defend against pest attacks and related injuries. In people, phenols and polyphenols can help prevent diseases triggered or promoted by oxidative-damage like coronary heart disease, stroke and certain cancers.
Overall, organic crops had 18 to 69 percent higher concentrations of antioxidant compounds. The team concludes that consumers who switch to organic fruit, vegetables, and cereals would get 20 to 40 percent more antioxidants. That’s the equivalent of about two extra portions of fruit and vegetables a day, with no increase in caloric intake.
The researchers also found pesticide residues were three to four times more likely in conventional foods than organic ones, as organic farmers are not allowed to apply toxic, synthetic pesticides. While crops harvested from organically managed fields sometimes contain pesticide residues, the levels are usually 10-fold to 100-fold lower in organic food, compared to the corresponding, conventionally grown food.
“This study is telling a powerful story of how organic plant-based foods are nutritionally superior and deliver bona fide health benefits,” said Benbrook.
In a surprising finding, the team concluded that conventional crops had roughly twice as much cadmium, a toxic heavy metal contaminant, as organic crops. The leading explanation is that certain fertilizers approved for use only on conventional farms somehow make cadmium more available to plant roots. A doubling of cadmium from food could push some individuals over safe daily intake levels.
More than half the studies in the Newcastle analysis were not available to the research team that carried out a 2009 study commissioned by the UK Food Standards Agency. Another review published by a Stanford University team in 2011 failed to identify any significant clinical health benefits from consumption of organic food, but incorporated less than half the number of comparisons for most health-promoting nutrients.
“We benefited from a much larger and higher quality set of studies than our colleagues who carried out earlier reviews,” said Carlo Leifert, a Newcastle University professor and the project leader.
Growing up on a livestock farm halves the risk of inflammatory bowel diseases
The incidence of inflammatory bowel diseases is rising sharply — particularly among young people
New research conducted at Aarhus University has revealed that people who have grown up on a farm with livestock are only half as likely as their urban counterparts to develop the most common inflammatory bowel diseases: ulcerative colitis and Crohn’s disease. The study findings have recently been published in the European Journal of Epidemiology.
“It is extremely exciting that we can now see that not only allergic diseases, but also more classic inflammatory diseases appear to depend on the environment we are exposed to early in our lives,” relates Vivi Schlünssen, Associate Professor in Public Health at Aarhus University.
Greater difference over the past 60 years
The study indicates that people born after 1952 who spent the first five years of their lives on a livestock farm are much better protected against the common inflammatory bowel diseases than the oldest people in the survey. In fact, results from the oldest age group seem to show that it made no difference whether the subjects grew up in town or country.
“This leads us to believe that there is a correlation between the rise in inflammatory bowel diseases and increasing urbanisation, given that more and more children are growing up in urban settings,” adds Signe Timm, PhD student at Aarhus University.
“We know that development of the immune system is finalised in the first years of our lives, and we suspect that environmental influences may have a crucial effect on this development. The place where you grow up may therefore influence your risk of developing an inflammatory bowel disease later in life.”
Variation of bacteria may have an effect
The new study does not reveal why the difference between growing up in a modern city and a rural setting has an effect on the immune system. However, the researchers have a theory that the body may be dependent on exposure to a wide variety of microorganisms to develop a healthy immune system – in the same way as has been established in studies on allergies and asthma.
“We know that the difference in the microbial environment between city and country has increased over the past century, and that we are exposed to far fewer different bacteria in urban environments today than we were previously. This may in part explain our findings,” says Signe Timm.
Is the protection hereditary?
More than 50,000 Danes suffer from ulcerative colitis or Crohn’s disease. These conditions are now often appearing in young people, who have to live with them for the rest of their lives. Over the past 40–50 years, incidence of the diseases has sky-rocketed in Northern Europe – including Denmark – as well as in Canada and the United States, although they are still relatively rare in developing countries.
As a part of her PhD project, Signe Timm will be contacting the 20,000 or so children of the participants in the current study to establish whether the same tendencies can be found in the next generation. She will also be investigating whether the effect of environmental influences can be handed down to the next generation as a result of a complex interplay between genes and the environment – i.e. if children can ‘inherit’, so to speak, the protective effect their parents have obtained from growing up on a farm with livestock.
• The study is based on a questionnaire survey of 10,864 people from Denmark, Norway, Sweden, Iceland and Estonia, born in the period 1945–1971.
• Participants in the survey have been asked where they spent the first five years of their lives, and researchers have compared results from those who grew up on a farm with livestock, those who were brought up in a village/suburb, and those who spent their early childhood in an urban environment.
• Signe Timm’s PhD project is linked to the generation study entitled ‘RHINESSA’ (Respiratory Health in Northern Europe, Switzerland, Spain and Australia).
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