Data from a long-term prospective study of healthy, middle-aged Norwegian men suggests that a low heart rate during moderate-intensity exercise is linked with future risk of AF.
"We found that the men who did not exceed 100 bpm at the end of six minutes of workload had a significantly increased AF risk," write Dr Irene Grundvold (Oslo University Hospital, Norway) and colleagues in the paper published July 21, 2013 inCirculation: Arrhythmia and Electrophysiology. In an analysis by tertile, those with heart rates <110 bpm after six minutes of moderate-intensity exercise had a significantly increased risk of AF compared with those with a heart rate >125 bpm.
There is evidence that individuals who participate in longstanding endurance training might have an increased risk of AF as they get older, according to the researchers. One other study of Norwegian master cross-country skiers found that a low resting heart rate was a long-term predictor of AF.
With this background, Grundvold et al wanted to determine if a low heart rate during moderate-intensity exercise predicted incident AF in healthy middle-aged Norwegian men. Slightly more than 2000 men participated in the prospective cardiovascular health survey between 1972 and 1975. All men were healthy and had no evidence of cardiovascular disease.
During a median of 30 years of follow-up, 13% of the men developed AF at a mean age of 71 years. In a multivariate analysis, age, resting systolic blood pressure, relative heart volume, left ventricular hypertrophy, and a low heart rate when engaged in moderate-intensity cycling on a stationary bike (100 W) were all predictors of AF. For those with a heart rate >100 bpm during exercise, the risk of AF decreased by 15% (hazard ratio 0.85; p=0.04) compared with those with lower heart rates.
"The present main results--an increased AF risk associated with low heart rate at moderate exercise in healthy men--might suggest involvement of an inappropriate heart rate response to exercise with prolonged parasympathetic activation," suggest Grundvold and colleagues. "Vagally mediated paroxysmal AF may be particularly important in athletic men without apparent heart disease."
Welcome to my collection of health articles. Most of them contain little nuggets of health wisdom that we can easily apply to our daily lives. As you can gather, I've been consuming all sorts of supplements over the years, most of them from iherb. They deliver on time (DHL), and prices are good. If you're a first-time buyer, use my code 'pot089' to enjoy up to $10 off.
Sunday 4 August 2013
Friday 19 July 2013
Air Pollution, Even at Low Levels, Tied to Lung Cancer
Prolonged exposure to air pollution is significantly associated with an increased risk for lung cancer, according to the results of a new meta-analysis.
The study adds "substantially to the weight of epidemiological evidence" that links the 2 phenomena, say the authors, led by Ole Raaschou-Nielsen, PhD, from the Danish Cancer Society Research Center, in Copenhagen.
The researchers, who synthesized data from 17 cohort studies in 9 European countries, found that the risk exists even when the levels of particulate matter (PM) air pollution were below the current European limit values.
Sources of PM air pollution include traffic, industry, and domestic heating.
"We found no threshold below which there was no risk; the results showed a picture that 'the more the worse, the less the better,' " said Dr. Raaschou-Nielsen in a press statement.
"Particulate matter air pollution contributes to lung cancer incidence in Europe," the study authors conclude.
The study, which is one of the largest studies of its kind, included data on more than 300,000 individuals and 2095 lung cancer cases and had a median follow-up of 12.8 years. It was published online July 10 in the journal Lancet Oncology.
"At this stage, we might have to add air pollution, even at current concentrations, to the list of causes of lung cancer," write Takashi Yorifuji MD, PhD, from Okayama University Graduate School of Environmental and Life Science, and Saori Kashima, PhD, from Hiroshima University, in Japan, in an accompanying editorial.
Air pollution is not recognized by medical practitioners as a cause of lung cancer, the pair say. For instance, it is not listed in the iconic Harrison's Principles of Internal Medicine as a cause.
It may also be time to "recognise that air pollution has large effects on public health," the Japanese editorialists state.
Evidence for an association between air pollution exposure and lung cancer is "accumulating," they say. Still, the lung cancer risk associated with air pollution is much lower than that associated with smoking. For instance, in the current study, there was a hazard ratio [HR] of 1.22 (per 10 μg/m³ increase in PM10). By contrast, other research indicates that the relative risk [RR] of developing lung cancer is 23.3 for currently smoking men and 12.7 for currently smoking women compared with nonsmokers. However, the editorials point out that 'everybody is exposed to air pollution." Thus, "the public health effect is quite large."
The editorialists also point out that the World Health Organization has estimated that smoking caused 5.1 million deaths and 71% of lung cancer worldwide in 2004, whereas air pollution caused 1.2 million deaths and 8% of lung cancer worldwide in the same year.
Greater Risk for Adenocarcinomas
In the new study, the authors assessed the impact of long-term exposure to nitrogen oxides and particulate matter with a diameter of less than 2.5 micrometers (PM2.5) and less than 10 micrometers (PM10) on the risk for lung cancer.
Air pollution concentration was estimated at individuals' home addresses using land-use regression models. Participants were tracked for new lung cancer diagnoses in cancer registries. The researchers also applied statistical modeling to control for other factors like smoking, diet, and occupation.
The analysis found that for every increase of 5 micrograms per cubic meter of PM2.5 pollution, the risk for lung cancer rose by 18%, and for every increase of 10 micrograms per cubic meter in PM10pollution, the risk increased by 22%.
The risk/HRs were even higher for the lung cancer subtype, adenocarcinomas. The same increments of PM10 and PM2.5 were associated with HRs for adenocarcinomas of the lung of 1.51 and 1.55, respectively.
However, other studies have not found that there is a pronounced relation between air pollution and any particular lung cancer subtype, the authors and editorialists point out.
No association between lung cancer and nitrogen oxides was found.
The HRs for lung cancer were similar with and without restriction to study participants below most of the predefined public safety threshold values, say the authors. This suggests that "exposure of populations to particulate matter air pollution even at concentrations below the existing European Union air quality limit values for PM10 (40 ug/m³) and PM2.5 (25 ug/m³) might increase the risk for lung cancer," they write.
The new study is "sophisticated and overcame several limitations of previous air pollution studies," the editorialists say.
They point out that earlier studies examined the effect of air pollution on lung cancer by assessing the geographical correlations between air pollution concentration data in communities and aggregate data on lung cancer. However, this method is subject to exposure misclassification and confounding, especially by tobacco smoking.
The new study takes advantage of the fact that researchers subsequently tried to reduce these systematic errors by shifting to case-control or cohort studies with area-level exposure assessment.
Dr. Raaschou-Nielsen and colleagues took the next step by conducting a meta-analysis of these newer studies.
The new study also benefited from a high follow-up rate and adjustment of potential confounders, including a set of smoking variables, the editorialists emphasize.
The study adds "substantially to the weight of epidemiological evidence" that links the 2 phenomena, say the authors, led by Ole Raaschou-Nielsen, PhD, from the Danish Cancer Society Research Center, in Copenhagen.
The researchers, who synthesized data from 17 cohort studies in 9 European countries, found that the risk exists even when the levels of particulate matter (PM) air pollution were below the current European limit values.
Sources of PM air pollution include traffic, industry, and domestic heating.
"We found no threshold below which there was no risk; the results showed a picture that 'the more the worse, the less the better,' " said Dr. Raaschou-Nielsen in a press statement.
"Particulate matter air pollution contributes to lung cancer incidence in Europe," the study authors conclude.
The study, which is one of the largest studies of its kind, included data on more than 300,000 individuals and 2095 lung cancer cases and had a median follow-up of 12.8 years. It was published online July 10 in the journal Lancet Oncology.
"At this stage, we might have to add air pollution, even at current concentrations, to the list of causes of lung cancer," write Takashi Yorifuji MD, PhD, from Okayama University Graduate School of Environmental and Life Science, and Saori Kashima, PhD, from Hiroshima University, in Japan, in an accompanying editorial.
Air pollution is not recognized by medical practitioners as a cause of lung cancer, the pair say. For instance, it is not listed in the iconic Harrison's Principles of Internal Medicine as a cause.
It may also be time to "recognise that air pollution has large effects on public health," the Japanese editorialists state.
Evidence for an association between air pollution exposure and lung cancer is "accumulating," they say. Still, the lung cancer risk associated with air pollution is much lower than that associated with smoking. For instance, in the current study, there was a hazard ratio [HR] of 1.22 (per 10 μg/m³ increase in PM10). By contrast, other research indicates that the relative risk [RR] of developing lung cancer is 23.3 for currently smoking men and 12.7 for currently smoking women compared with nonsmokers. However, the editorials point out that 'everybody is exposed to air pollution." Thus, "the public health effect is quite large."
The editorialists also point out that the World Health Organization has estimated that smoking caused 5.1 million deaths and 71% of lung cancer worldwide in 2004, whereas air pollution caused 1.2 million deaths and 8% of lung cancer worldwide in the same year.
Greater Risk for Adenocarcinomas
In the new study, the authors assessed the impact of long-term exposure to nitrogen oxides and particulate matter with a diameter of less than 2.5 micrometers (PM2.5) and less than 10 micrometers (PM10) on the risk for lung cancer.
Air pollution concentration was estimated at individuals' home addresses using land-use regression models. Participants were tracked for new lung cancer diagnoses in cancer registries. The researchers also applied statistical modeling to control for other factors like smoking, diet, and occupation.
The analysis found that for every increase of 5 micrograms per cubic meter of PM2.5 pollution, the risk for lung cancer rose by 18%, and for every increase of 10 micrograms per cubic meter in PM10pollution, the risk increased by 22%.
The risk/HRs were even higher for the lung cancer subtype, adenocarcinomas. The same increments of PM10 and PM2.5 were associated with HRs for adenocarcinomas of the lung of 1.51 and 1.55, respectively.
However, other studies have not found that there is a pronounced relation between air pollution and any particular lung cancer subtype, the authors and editorialists point out.
No association between lung cancer and nitrogen oxides was found.
The HRs for lung cancer were similar with and without restriction to study participants below most of the predefined public safety threshold values, say the authors. This suggests that "exposure of populations to particulate matter air pollution even at concentrations below the existing European Union air quality limit values for PM10 (40 ug/m³) and PM2.5 (25 ug/m³) might increase the risk for lung cancer," they write.
The new study is "sophisticated and overcame several limitations of previous air pollution studies," the editorialists say.
They point out that earlier studies examined the effect of air pollution on lung cancer by assessing the geographical correlations between air pollution concentration data in communities and aggregate data on lung cancer. However, this method is subject to exposure misclassification and confounding, especially by tobacco smoking.
The new study takes advantage of the fact that researchers subsequently tried to reduce these systematic errors by shifting to case-control or cohort studies with area-level exposure assessment.
Dr. Raaschou-Nielsen and colleagues took the next step by conducting a meta-analysis of these newer studies.
The new study also benefited from a high follow-up rate and adjustment of potential confounders, including a set of smoking variables, the editorialists emphasize.
Stop idling, move more to avoid diabetes
Time spent in sedentary behavior — sitting or lying down — has a stronger impact on diabetes risk than does moderate to vigorous physical activity (MVPA) in adults, new research shows.
"This is the first work to demonstrate that sedentary behavior might have a greater bearing on diabetes risk factors than exercise in adults at risk of the disease," said lead author Joseph Henson, a PhD student from the Leicester Diabetes Center, United Kingdom.
Mr. Henson stressed, however, that sedentary behavior "is not simply a lack of exercise," and trying to reduce it "shouldn't be used as a substitute for exercise; they should be treated independently.
"This requires a paradigm shift, so that people at high risk of developing type 2 diabetes think about the balance of sedentary behavior and physical activity throughout the day," he added, noting that sedentary time occupies a much larger portion of the day than time spent in physical activity.
Sedentary Time Affects Glucose, TGs, and HDL Cholesterol
In their study, Mr. Henson and colleagues analyzed individuals with known risk factors for type 2 diabetes from 2 ongoing diabetes-prevention programs in the UK: 153 from the Sedentary Time and Diabetes (STAND) study (mean age, 33 years; 29% men) and 725 from the Walking Away from Diabetes study (mean age, 64 years; 65% men).
They examined the extent to which sedentary time, breaks in sedentary time, MVPA, and total physical activity were independently associated with cardiometabolic risk factors. Accelerometers were used to assess sedentary time, MVPA, and total physical activity. Breaks in sedentary time were defined as a transition from a sedentary to an active state.
Following adjustment for various covariates, including MVPA and body mass index (BMI), there were detrimental linear associations of sedentary time with 2-hour plasma glucose (P < .001), triglycerides (P= .001), and HDL cholesterol (P = .029).
Breaks in sedentary time, total physical activity, and MVPA were significantly inversely associated with measures of adiposity, but not with any other cardiometabolic variables after adjustment for sedentary time and BMI.
The findings were consistent across a diverse age range, providing evidence that the negative consequences of excess sedentary time exist from young adulthood through older ages (ages 18 to 74 years), another unique aspect of the study, said Mr. Henson. He noted that previous studies that have shown detrimental effects of sedentary behavior have been performed in older adults in the general population.
"The findings from this study may have important methodological and public-health implications," he and his colleagues point out. "This…provides novel objective evidence that, in individuals at high risk of type 2 diabetes mellitus, sedentary time may be a more important indicator of cardiometabolic health than MVPA."
Diabetes Prevention Should not Overlook Sedentary Time
The results also have implications for diabetes and cardiovascular disease prevention programs, they say.
"This may raise questions regarding the prescription of optimal daily human movement for health. As such, diabetes and cardiovascular [disease] prevention programs concentrating solely on MVPA may overlook an area that is of fundamental importance to cardiometabolic health.
"Along with messages related to accumulating at least 150 min/week of MVPA, which forms the cornerstone of diabetes-prevention programs, such interventions may be more effective if individuals are further encouraged to simply sit less and move more, regardless of the intensity level," they add.
Future Study Will Try to Tease out Biological Mechanism
Mr. Henson stresses nevertheless that the research "is still only a cross-sectional, observational study," which should serve as a stimulus for further work, including tightly controlled experimental studies in different populations.
To this end, he and his colleagues plan to conduct another study, assessing individuals at risk of diabetes who will be assigned to 1 of 3 groups: sitting all day, walking about for 5-minute intervals twice an hour, and standing for 5-minute intervals twice an hour. They plan to try to tease out the biological mechanisms that are at play, Mr. Henson explained.
"This is the first work to demonstrate that sedentary behavior might have a greater bearing on diabetes risk factors than exercise in adults at risk of the disease," said lead author Joseph Henson, a PhD student from the Leicester Diabetes Center, United Kingdom.
Mr. Henson stressed, however, that sedentary behavior "is not simply a lack of exercise," and trying to reduce it "shouldn't be used as a substitute for exercise; they should be treated independently.
"This requires a paradigm shift, so that people at high risk of developing type 2 diabetes think about the balance of sedentary behavior and physical activity throughout the day," he added, noting that sedentary time occupies a much larger portion of the day than time spent in physical activity.
Sedentary Time Affects Glucose, TGs, and HDL Cholesterol
In their study, Mr. Henson and colleagues analyzed individuals with known risk factors for type 2 diabetes from 2 ongoing diabetes-prevention programs in the UK: 153 from the Sedentary Time and Diabetes (STAND) study (mean age, 33 years; 29% men) and 725 from the Walking Away from Diabetes study (mean age, 64 years; 65% men).
They examined the extent to which sedentary time, breaks in sedentary time, MVPA, and total physical activity were independently associated with cardiometabolic risk factors. Accelerometers were used to assess sedentary time, MVPA, and total physical activity. Breaks in sedentary time were defined as a transition from a sedentary to an active state.
Following adjustment for various covariates, including MVPA and body mass index (BMI), there were detrimental linear associations of sedentary time with 2-hour plasma glucose (P < .001), triglycerides (P= .001), and HDL cholesterol (P = .029).
Breaks in sedentary time, total physical activity, and MVPA were significantly inversely associated with measures of adiposity, but not with any other cardiometabolic variables after adjustment for sedentary time and BMI.
The findings were consistent across a diverse age range, providing evidence that the negative consequences of excess sedentary time exist from young adulthood through older ages (ages 18 to 74 years), another unique aspect of the study, said Mr. Henson. He noted that previous studies that have shown detrimental effects of sedentary behavior have been performed in older adults in the general population.
"The findings from this study may have important methodological and public-health implications," he and his colleagues point out. "This…provides novel objective evidence that, in individuals at high risk of type 2 diabetes mellitus, sedentary time may be a more important indicator of cardiometabolic health than MVPA."
Diabetes Prevention Should not Overlook Sedentary Time
The results also have implications for diabetes and cardiovascular disease prevention programs, they say.
"This may raise questions regarding the prescription of optimal daily human movement for health. As such, diabetes and cardiovascular [disease] prevention programs concentrating solely on MVPA may overlook an area that is of fundamental importance to cardiometabolic health.
"Along with messages related to accumulating at least 150 min/week of MVPA, which forms the cornerstone of diabetes-prevention programs, such interventions may be more effective if individuals are further encouraged to simply sit less and move more, regardless of the intensity level," they add.
Future Study Will Try to Tease out Biological Mechanism
Mr. Henson stresses nevertheless that the research "is still only a cross-sectional, observational study," which should serve as a stimulus for further work, including tightly controlled experimental studies in different populations.
To this end, he and his colleagues plan to conduct another study, assessing individuals at risk of diabetes who will be assigned to 1 of 3 groups: sitting all day, walking about for 5-minute intervals twice an hour, and standing for 5-minute intervals twice an hour. They plan to try to tease out the biological mechanisms that are at play, Mr. Henson explained.
Friday 28 June 2013
Eczema: Evening Primrose Oil, Borage Oil not helpful
Evening primrose oil (EPO) and borage oil (BO) provide little benefit for the relief of atopic eczema compared with placebo, according to a new review published in the April issue of the Cochrane Database of Systematic Reviews.
Joel Bamford, MD, from the University of Minnesota Medical School in Duluth, and colleagues identified 27 studies (19 EPO and 8 BO; 1596 adults and children overall) that evaluated the use of oral EPO or BO for treatment of eczema compared with placebo. The review authors searched the main scientific literature databases up to August 29, 2012.
A meta-analysis of 7 EPO studies showed no significant increase in symptom relief compared with placebo. Studies of BO also failed to show any significant symptom improvement; however, a meta-analysis of studies was not performed because of differences in study reporting.
Adverse effects were mild but similar for EPO and BO, were primarily gastrointestinal in nature, and ranged in frequency from 7% to 15%. One study reported that EPO may increase bleeding risk among patients receiving warfarin.
According to the researchers, 67% of the included studies were judged as having a low risk of bias for random sequence generation, 44% had a low risk of bias for allocation concealment, and 59% had a low risk of bias for blinding.
"[EPO and BO] do not seem to add any benefit to eczema as measured in this systematic review," Dr. Bamford and colleagues write.
"Noting that the confidence intervals between the active and placebo treatments are so narrow to exclude the possibility of any clinically useful difference, we conclude that further studies [of] EPO or BO for eczema would be hard to justify," they write.
Hywel Williams, PhD, FRCP, from the Center of Evidence Based Dermatology, University of Nottingham, United Kingdom, wrote: "Although some of us always suspected that EPO was not especially useful in atopic eczema, this study provides robust evidence from the totality of evidence to suggest that it is of very little value, if any."
Dr. Williams agreed with the review authors that more research in this area is not needed and that "research monies should be spent elsewhere on eczema, such as finding out how best to prevent it."
Joel Bamford, MD, from the University of Minnesota Medical School in Duluth, and colleagues identified 27 studies (19 EPO and 8 BO; 1596 adults and children overall) that evaluated the use of oral EPO or BO for treatment of eczema compared with placebo. The review authors searched the main scientific literature databases up to August 29, 2012.
A meta-analysis of 7 EPO studies showed no significant increase in symptom relief compared with placebo. Studies of BO also failed to show any significant symptom improvement; however, a meta-analysis of studies was not performed because of differences in study reporting.
Adverse effects were mild but similar for EPO and BO, were primarily gastrointestinal in nature, and ranged in frequency from 7% to 15%. One study reported that EPO may increase bleeding risk among patients receiving warfarin.
According to the researchers, 67% of the included studies were judged as having a low risk of bias for random sequence generation, 44% had a low risk of bias for allocation concealment, and 59% had a low risk of bias for blinding.
"[EPO and BO] do not seem to add any benefit to eczema as measured in this systematic review," Dr. Bamford and colleagues write.
"Noting that the confidence intervals between the active and placebo treatments are so narrow to exclude the possibility of any clinically useful difference, we conclude that further studies [of] EPO or BO for eczema would be hard to justify," they write.
Hywel Williams, PhD, FRCP, from the Center of Evidence Based Dermatology, University of Nottingham, United Kingdom, wrote: "Although some of us always suspected that EPO was not especially useful in atopic eczema, this study provides robust evidence from the totality of evidence to suggest that it is of very little value, if any."
Dr. Williams agreed with the review authors that more research in this area is not needed and that "research monies should be spent elsewhere on eczema, such as finding out how best to prevent it."
Vitamin D levels linked to respiratory disease
Having severe vitamin D deficiency may put people aged 65 years and older at more than twice the risk of having self-reported respiratory disease, according to an article published online May 6 in theJournal of the American Geriatrics Society.
However, the question remains as to whether respiratory disease is a cause rather than a consequence of low vitamin D concentrations.
Vasant Hirani, PhD, from the Department of Epidemiology and Public Health, University College London Medical School, United Kingdom, analyzed the records of 2070 people (1120 women) who participated in the 2005 Health Survey for England and who were also interviewed by a nurse and had a blood sample taken.
Dr. Hirani found that after adjusting for age, sex, season, smoking status, and social class, people with less than 35 nmol/L serum 25(OH)D were more than twice as likely to report having respiratory disease as those individuals with a serum level of 64 nmol/L or higher. Individuals with intermediate serum levels also had greater risk compared with those with levels above 64 nmol/L.
Prevalence of respiratory disease among the study population ranged from 8.9% for people with vitamin D levels of 75 nmol/L and greater to 45.5% for people with levels of 25.0 to 49.9 nmol/L. The association was not consistent, however, as only 14.7% of individuals with serum 25(OH)D levels lower than 25 nmol/L reported having respiratory disease.
Although Dr. Hirani found associations in unadjusted analyses between low vitamin D levels and smoking tobacco, lower social class, fair or poor general health, and self-reported heart disease, cancer, and pain, she found no associations between low vitamin D levels and age, sex, body mass index, alcohol consumption, or use of vitamin supplements.
It is "biologically plausible" for vitamin D to be associated with respiratory health, she writes, because of vitamin D's role in the lung's immunity response to virus infection.
"It is also likely that individuals with a respiratory condition are less likely to spend time outdoors and may also limit their activities, resulting in less sunlight exposure and thus vitamin D deficiency," she writes. More research is needed to clarify the cause and effect of the association, she notes.
Although definitive conclusions as to whether low vitamin D is truly linked to respiratory disease, she writes, the study population is nationally representative of people of that age in England.
She concludes, "Regardless of the direction of causation, the higher-than-expected co-occurrence of vitamin D deficiency and respiratory conditions is an important public health question for older populations living in northern latitudes because both are common, and both have substantial adverse health consequences."
Dr. Hirani is currently funded by the National Health Services Information Centre and is an editor and chapter author on the Health Survey for England, funded by the English Department of Health.
However, the question remains as to whether respiratory disease is a cause rather than a consequence of low vitamin D concentrations.
Vasant Hirani, PhD, from the Department of Epidemiology and Public Health, University College London Medical School, United Kingdom, analyzed the records of 2070 people (1120 women) who participated in the 2005 Health Survey for England and who were also interviewed by a nurse and had a blood sample taken.
Dr. Hirani found that after adjusting for age, sex, season, smoking status, and social class, people with less than 35 nmol/L serum 25(OH)D were more than twice as likely to report having respiratory disease as those individuals with a serum level of 64 nmol/L or higher. Individuals with intermediate serum levels also had greater risk compared with those with levels above 64 nmol/L.
Prevalence of respiratory disease among the study population ranged from 8.9% for people with vitamin D levels of 75 nmol/L and greater to 45.5% for people with levels of 25.0 to 49.9 nmol/L. The association was not consistent, however, as only 14.7% of individuals with serum 25(OH)D levels lower than 25 nmol/L reported having respiratory disease.
Although Dr. Hirani found associations in unadjusted analyses between low vitamin D levels and smoking tobacco, lower social class, fair or poor general health, and self-reported heart disease, cancer, and pain, she found no associations between low vitamin D levels and age, sex, body mass index, alcohol consumption, or use of vitamin supplements.
It is "biologically plausible" for vitamin D to be associated with respiratory health, she writes, because of vitamin D's role in the lung's immunity response to virus infection.
"It is also likely that individuals with a respiratory condition are less likely to spend time outdoors and may also limit their activities, resulting in less sunlight exposure and thus vitamin D deficiency," she writes. More research is needed to clarify the cause and effect of the association, she notes.
Although definitive conclusions as to whether low vitamin D is truly linked to respiratory disease, she writes, the study population is nationally representative of people of that age in England.
She concludes, "Regardless of the direction of causation, the higher-than-expected co-occurrence of vitamin D deficiency and respiratory conditions is an important public health question for older populations living in northern latitudes because both are common, and both have substantial adverse health consequences."
Dr. Hirani is currently funded by the National Health Services Information Centre and is an editor and chapter author on the Health Survey for England, funded by the English Department of Health.
Low back pain linked to bacterial infection
New research suggests that some 40% of chronic lower back pain (CLBP) could be caused by bacteria, and that a significant percentage of people with lower back pain following a herniated disc and swelling in the spine could find relief by taking an antibiotic.
Investigators from the Research Department of the Spine Center of Southern Denmark, University of Southern Denmark, Odense, led by Hanne B. Albert, PhD, conclude that antibiotics may be considered as a treatment option for patients with chronic low back pain, but with caution.
The authors suggest that long-term antibiotics should not be prescribed "without due consideration." Low back pain is so common in the community that there could be hazards if used indiscriminately, they write.
"However, as many patients, as in this trial, are on sick leave at risk of losing their jobs and have a high analgesic intake, we suggest that antibiotics, when applied along the lines of this MAST [Modic antibiotic spine therapy] protocol may be appropriate in this subgroup, i.e., CLBP with Modic type 1 changes. We do not support the proposition that all patients with lumbar pain should have a trial course of antibiotics."
Their findings, published in 2 papers, 1 a randomized trial of antibiotics for low back pain, are published in the April issue of the European Spine Journal.
Positive cultures
An estimated 80% of Americans have low back pain at some point in their life, the authors write, and back pain is the most common reason for workplace absence.
The first of 2 studies shows that patients with an anaerobic infected disc are more likely to develop Modic change (MC) (bone edema) in the adjacent vertebrae after disc herniation, suggesting a role of bacteria in developing Modic changes.
The study included 61 adults (mean age, 46.4 years; 27% female) who had MRI-confirmed lumbar disc herniation and were undergoing surgery. All patients were immunocompetent. No patient had received a previous epidural steroid injection or had previous back surgery.
Using stringent antiseptic sterile protocols, researchers collected 5 tissue samples from each patient. In total, microbiological cultures were positive in 46% of the patients. Anaerobic cultures were positive in 43% of patients, and of these, 7% had dual microbial infections, containing 1 aerobic and 1 anaerobic culture. No tissue specimens had more than 2 types of bacteria.
The anaerobic microorganism Propionibacterium acnes was found in 40% of the total cohort and in 86% of those with positive microbiology. These bacteria typically live in human skin and hair follicles and gums.
The results showed that in the discs with a nucleus with anaerobic bacteria, 80% developed new MC in the vertebrae adjacent to the previous disc herniation. In contrast, none of the patients with aerobic bacteria and only 44% of those with negative cultures developed new MC.
The association between an anaerobic culture and new MCs was highly statistically significant.
The authors said that the detected bacteria are unlikely the result of intraoperative skin contamination. They pointed out that the procedures were conducted under the strictest of sterile conditions. As well, if skin contamination was the cause of the infection, a pattern of multiple skin bacteria cultures would be observed, which was not the case.
Why would some patients develop MC when no microorganisms are present in their herniated nuclear tissue? The authors speculate this could be due to a biochemical effect reflecting edema secondary to microfractures and subsequent inflammation, or the result of an inflammatory process from proinflammatory chemicals penetrating through the microfractures from the nucleus pulposus.
Antibiotic randomized trial
The second study, a double-blind, randomized trial, showed that an antibiotic protocol was significantly more effective than placebo in reducing pain and disability. This study included 162 adults who had chronic lower back pain that had developed after a previous disc herniation and had lasted more than 6 months.
These patients also had bone edema, as shown by Modic type 1 changes in the vertebrae adjacent to the previous herniation. Such changes in the vertebrae are present in 6% of the general population and 35% to 40% of those with low back pain.
The patients were randomly assigned to amoxicillin-clavulanate (500 mg/125 mg;Bioclavid) or identical placebo 3 times daily for 100 days and were blindly evaluated at baseline, end of treatment, and 1 year.
The analysis included 144 patients who completed the 1-year follow-up. The antibiotic group improved on all primary outcome measures, including disease-specific score on Roland Morris Disability Questionnaire (RMDQ), and lumbar pain. The improvement continued from the 100-day follow-up until the 1-year follow up.
The improvements in the antibiotic group were highly statistically significant on all outcomes measured, including secondary outcomes of leg pain, number of hours with pain in the last 4 weeks, global perceived health, and days with sick leave, among others.
For example, at baseline, 100 days, and 1 year, the disease-specific disability-RMDQ scores for the antibiotic group were 15.0, 11.5, and 7.0, and for placebo they were 15.0, 14.0, and 14.0 (P = .0001 for the difference between placebo and antibiotic group at 1 year follow up). For back pain, the figures for the antibiotic group were 6.7, 5.0, and 3.7 and for placebo they were 6.3, 6.3, and 6.3. (P = .0001 for difference).
For low back pain, which was experienced by all patients at the beginning of the study, 67.5% of the antibiotic group reported this pain after 1 year compared with 94.0% of the placebo group (P = .0001 for difference). The percentage of those with constant pain was reduced from 73.5% to 19.5% in the antibiotic group and from 73.1% to 67.2% in the placebo group (P = .0001 for difference).
There was a trend toward a dose-response relationship, with double-dose antibiotics being more effective; however, this was not statistically significant because the study was not powered for this comparison.
Adverse events were more common in the antibiotic group (65% of participants) than in the placebo group (23%).
Surgical setting
In an editorial accompanying the publication, Max Aebi, MD, from the MEM Research Center for Orthopaedic Surgery, Institute for Evaluative Research in Orthopedic Surgery, University of Berne, Switzerland, and editor-in-chief of the European Spine Journal, points out that previous studies have shown that MC I occurs 6 times more frequently in the low back pain population than the general population. The relationship may be mechanical, he writes, "but under certain circumstances, low virulent infections may play a key role."
These new papers not only demonstrate that patients infected with herniated nucleus material by anaerobic bacteria in lumbar disc herniation develop new MC I in adjacent vertebrae but also that patients with low back pain and MC I after lumbar disc herniation improved significantly with an antibiotic protocol, Dr. Aebi writes.
"This strongly suggests one cause of low back pain in combination of MC I to be of low-grade infectious nature in case of previous disc herniation," he said.
However, he cautions that it is ethically impossible to take biopsy samples from all of these patients; this could be done only those who have surgery subsequent to disc herniation. The authors ask "the obvious key question" of whether the bacteria found in the nuclear material results from infection or could be due to intraoperative contamination, he writes, and then provide a "plausible" answer as to why such contamination is "highly improbable."
"Nevertheless," Dr. Aebi writes, "further research is necessary to show what exactly happens in patients with disc herniation who develop MC I and low back pain and who have not been operated on. How could we show that in this fraction of patients there could be the same number of anaerobic infections of the nucleus material? By markers of the anaerobic bacteria or of specific infectious tissue, which could be made visible in imaging? By fine needle biopsy?"
Knowing these answers would make the current study results "even more explosive" in terms of better understanding low back pain and corresponding MRI changes, said Dr. Aebi. "We are keen to wait for further innovative research in this field."
Investigators from the Research Department of the Spine Center of Southern Denmark, University of Southern Denmark, Odense, led by Hanne B. Albert, PhD, conclude that antibiotics may be considered as a treatment option for patients with chronic low back pain, but with caution.
The authors suggest that long-term antibiotics should not be prescribed "without due consideration." Low back pain is so common in the community that there could be hazards if used indiscriminately, they write.
"However, as many patients, as in this trial, are on sick leave at risk of losing their jobs and have a high analgesic intake, we suggest that antibiotics, when applied along the lines of this MAST [Modic antibiotic spine therapy] protocol may be appropriate in this subgroup, i.e., CLBP with Modic type 1 changes. We do not support the proposition that all patients with lumbar pain should have a trial course of antibiotics."
Their findings, published in 2 papers, 1 a randomized trial of antibiotics for low back pain, are published in the April issue of the European Spine Journal.
Positive cultures
An estimated 80% of Americans have low back pain at some point in their life, the authors write, and back pain is the most common reason for workplace absence.
The first of 2 studies shows that patients with an anaerobic infected disc are more likely to develop Modic change (MC) (bone edema) in the adjacent vertebrae after disc herniation, suggesting a role of bacteria in developing Modic changes.
The study included 61 adults (mean age, 46.4 years; 27% female) who had MRI-confirmed lumbar disc herniation and were undergoing surgery. All patients were immunocompetent. No patient had received a previous epidural steroid injection or had previous back surgery.
Using stringent antiseptic sterile protocols, researchers collected 5 tissue samples from each patient. In total, microbiological cultures were positive in 46% of the patients. Anaerobic cultures were positive in 43% of patients, and of these, 7% had dual microbial infections, containing 1 aerobic and 1 anaerobic culture. No tissue specimens had more than 2 types of bacteria.
The anaerobic microorganism Propionibacterium acnes was found in 40% of the total cohort and in 86% of those with positive microbiology. These bacteria typically live in human skin and hair follicles and gums.
The results showed that in the discs with a nucleus with anaerobic bacteria, 80% developed new MC in the vertebrae adjacent to the previous disc herniation. In contrast, none of the patients with aerobic bacteria and only 44% of those with negative cultures developed new MC.
The association between an anaerobic culture and new MCs was highly statistically significant.
The authors said that the detected bacteria are unlikely the result of intraoperative skin contamination. They pointed out that the procedures were conducted under the strictest of sterile conditions. As well, if skin contamination was the cause of the infection, a pattern of multiple skin bacteria cultures would be observed, which was not the case.
Why would some patients develop MC when no microorganisms are present in their herniated nuclear tissue? The authors speculate this could be due to a biochemical effect reflecting edema secondary to microfractures and subsequent inflammation, or the result of an inflammatory process from proinflammatory chemicals penetrating through the microfractures from the nucleus pulposus.
Antibiotic randomized trial
The second study, a double-blind, randomized trial, showed that an antibiotic protocol was significantly more effective than placebo in reducing pain and disability. This study included 162 adults who had chronic lower back pain that had developed after a previous disc herniation and had lasted more than 6 months.
These patients also had bone edema, as shown by Modic type 1 changes in the vertebrae adjacent to the previous herniation. Such changes in the vertebrae are present in 6% of the general population and 35% to 40% of those with low back pain.
The patients were randomly assigned to amoxicillin-clavulanate (500 mg/125 mg;Bioclavid) or identical placebo 3 times daily for 100 days and were blindly evaluated at baseline, end of treatment, and 1 year.
The analysis included 144 patients who completed the 1-year follow-up. The antibiotic group improved on all primary outcome measures, including disease-specific score on Roland Morris Disability Questionnaire (RMDQ), and lumbar pain. The improvement continued from the 100-day follow-up until the 1-year follow up.
The improvements in the antibiotic group were highly statistically significant on all outcomes measured, including secondary outcomes of leg pain, number of hours with pain in the last 4 weeks, global perceived health, and days with sick leave, among others.
For example, at baseline, 100 days, and 1 year, the disease-specific disability-RMDQ scores for the antibiotic group were 15.0, 11.5, and 7.0, and for placebo they were 15.0, 14.0, and 14.0 (P = .0001 for the difference between placebo and antibiotic group at 1 year follow up). For back pain, the figures for the antibiotic group were 6.7, 5.0, and 3.7 and for placebo they were 6.3, 6.3, and 6.3. (P = .0001 for difference).
For low back pain, which was experienced by all patients at the beginning of the study, 67.5% of the antibiotic group reported this pain after 1 year compared with 94.0% of the placebo group (P = .0001 for difference). The percentage of those with constant pain was reduced from 73.5% to 19.5% in the antibiotic group and from 73.1% to 67.2% in the placebo group (P = .0001 for difference).
There was a trend toward a dose-response relationship, with double-dose antibiotics being more effective; however, this was not statistically significant because the study was not powered for this comparison.
Adverse events were more common in the antibiotic group (65% of participants) than in the placebo group (23%).
Surgical setting
In an editorial accompanying the publication, Max Aebi, MD, from the MEM Research Center for Orthopaedic Surgery, Institute for Evaluative Research in Orthopedic Surgery, University of Berne, Switzerland, and editor-in-chief of the European Spine Journal, points out that previous studies have shown that MC I occurs 6 times more frequently in the low back pain population than the general population. The relationship may be mechanical, he writes, "but under certain circumstances, low virulent infections may play a key role."
These new papers not only demonstrate that patients infected with herniated nucleus material by anaerobic bacteria in lumbar disc herniation develop new MC I in adjacent vertebrae but also that patients with low back pain and MC I after lumbar disc herniation improved significantly with an antibiotic protocol, Dr. Aebi writes.
"This strongly suggests one cause of low back pain in combination of MC I to be of low-grade infectious nature in case of previous disc herniation," he said.
However, he cautions that it is ethically impossible to take biopsy samples from all of these patients; this could be done only those who have surgery subsequent to disc herniation. The authors ask "the obvious key question" of whether the bacteria found in the nuclear material results from infection or could be due to intraoperative contamination, he writes, and then provide a "plausible" answer as to why such contamination is "highly improbable."
"Nevertheless," Dr. Aebi writes, "further research is necessary to show what exactly happens in patients with disc herniation who develop MC I and low back pain and who have not been operated on. How could we show that in this fraction of patients there could be the same number of anaerobic infections of the nucleus material? By markers of the anaerobic bacteria or of specific infectious tissue, which could be made visible in imaging? By fine needle biopsy?"
Knowing these answers would make the current study results "even more explosive" in terms of better understanding low back pain and corresponding MRI changes, said Dr. Aebi. "We are keen to wait for further innovative research in this field."
Eating peppers may help ward off Parkinson's Disease
Eating foods that contain even a small amount of nicotine, such as peppers, may reduce the risk for Parkinson's disease (PD), new research hints.
Peppers are in the same botanical family as tobacco — the Solanaceae family. In a population-based study, researchers found that increasing consumption of edible forms of Solanaceae plants was associated with a lower risk of developing PD, with peppers displaying the strongest association.
"If our results are confirmed in similar studies, and we also learn more about why peppers might be protective, then the research may be of particular interest to people who want to eat foods that might benefit their health, especially people without PD already," Susan Searles Nielsen, PhD, who led the study, told Medscape Medical News.
"We weren't able to explore whether peppers or other foods slow progression of the disease once you have it, although research to address that question might be a natural extension," added Dr. Searles Nielsen, research scientist in the Department of Environmental and Occupational Health Sciences, University of Washington, Seattle.
The study was published online May 9 in Annals of Neurology
Consistent inverse association with tobacco
Research has consistently shown an inverse association between PD and tobacco use, with people who have ever regularly smoked cigarettes less likely to develop PD than others. Some animal studies indicate that nicotine might help protect neurons. "However, it's unclear whether nicotine or something else in tobacco is actually protective, or whether people predisposed to PD simply don't respond well to tobacco smoke and therefore avoid it," Dr. Searles Nielsen explained.
"A few studies suggest that secondhand smoke might be associated with a reduced risk of PD, so that prompted us to look at another source of a relatively small amount of nicotine — foods in the same plant family as tobacco," she added.
The researchers assessed whether nicotine from edible Solanaceae influences risk for PD in 490 adults with newly diagnosed PD and 644 unrelated, neurologically healthy controls. They used questionnaires to assess participants' lifetime diets and tobacco use.
They report that PD was inversely associated with consumption of all edible Solanaceae combined (relative risk [RR], 0.81; 95% confidence interval [CI], 0.65 - 1.01), but not consumption of all other vegetables combined (RR, 1.00; 95% CI, 0.92 - 1.10).
They found that the trend "strengthened" when they weighted edible Solanaceae by nicotine concentration.
An inverse association was also evident for peppers specifically. Eating peppers 2 to 4 times per week was "consistently" associated with a 30% reduction in risk for PD the researchers report.
The potentially protective effect of peppers was mainly in people who had little or no prior tobacco use, which is "intriguing," Dr. Searles Nielsen said. "That is where you would expect to see the clearest association if something in both tobacco and peppers, such as nicotine, is protective."
"This lends strength to our findings, along with our observations that the association grew stronger with greater consumption of peppers and that there was no association between PD and eating vegetables outside this plant family. However, more research is needed to fully understand whether eating peppers might help prevent PD," Dr. Searles Nielsen said.
Novel approach, new evidence
The observation that smokers have a lower risk for PD has been "consistently reported in more than 60 epidemiological studies," Honglei Chen, MD, PhD, from the National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, who wasn't involved in the study, told Medscape Medical News.
"All previous studies on this topic have focused on analysis of smoking behaviors, while this study took a very different and novel approach by examining nicotine from diet in relation to Parkinson risk. Although this study did not settle the controversies regarding smoking and PD, it offers new evidence that supports a causal explanation," Dr. Chen said.
He cautioned, however, that this is a "preliminary finding that needs to be replicated, particularly from prospective studies that assess dietary habit before PD diagnosis.
"This study, however, is an excellent example of a novel approach for studying the relationship between smoking and PD. Further, if this finding could be confirmed, it adds to the health benefits of eating tomatoes and green peppers," Dr. Chen said.
Peppers are in the same botanical family as tobacco — the Solanaceae family. In a population-based study, researchers found that increasing consumption of edible forms of Solanaceae plants was associated with a lower risk of developing PD, with peppers displaying the strongest association.
"If our results are confirmed in similar studies, and we also learn more about why peppers might be protective, then the research may be of particular interest to people who want to eat foods that might benefit their health, especially people without PD already," Susan Searles Nielsen, PhD, who led the study, told Medscape Medical News.
"We weren't able to explore whether peppers or other foods slow progression of the disease once you have it, although research to address that question might be a natural extension," added Dr. Searles Nielsen, research scientist in the Department of Environmental and Occupational Health Sciences, University of Washington, Seattle.
The study was published online May 9 in Annals of Neurology
Consistent inverse association with tobacco
Research has consistently shown an inverse association between PD and tobacco use, with people who have ever regularly smoked cigarettes less likely to develop PD than others. Some animal studies indicate that nicotine might help protect neurons. "However, it's unclear whether nicotine or something else in tobacco is actually protective, or whether people predisposed to PD simply don't respond well to tobacco smoke and therefore avoid it," Dr. Searles Nielsen explained.
"A few studies suggest that secondhand smoke might be associated with a reduced risk of PD, so that prompted us to look at another source of a relatively small amount of nicotine — foods in the same plant family as tobacco," she added.
The researchers assessed whether nicotine from edible Solanaceae influences risk for PD in 490 adults with newly diagnosed PD and 644 unrelated, neurologically healthy controls. They used questionnaires to assess participants' lifetime diets and tobacco use.
They report that PD was inversely associated with consumption of all edible Solanaceae combined (relative risk [RR], 0.81; 95% confidence interval [CI], 0.65 - 1.01), but not consumption of all other vegetables combined (RR, 1.00; 95% CI, 0.92 - 1.10).
They found that the trend "strengthened" when they weighted edible Solanaceae by nicotine concentration.
An inverse association was also evident for peppers specifically. Eating peppers 2 to 4 times per week was "consistently" associated with a 30% reduction in risk for PD the researchers report.
The potentially protective effect of peppers was mainly in people who had little or no prior tobacco use, which is "intriguing," Dr. Searles Nielsen said. "That is where you would expect to see the clearest association if something in both tobacco and peppers, such as nicotine, is protective."
"This lends strength to our findings, along with our observations that the association grew stronger with greater consumption of peppers and that there was no association between PD and eating vegetables outside this plant family. However, more research is needed to fully understand whether eating peppers might help prevent PD," Dr. Searles Nielsen said.
Novel approach, new evidence
The observation that smokers have a lower risk for PD has been "consistently reported in more than 60 epidemiological studies," Honglei Chen, MD, PhD, from the National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, who wasn't involved in the study, told Medscape Medical News.
"All previous studies on this topic have focused on analysis of smoking behaviors, while this study took a very different and novel approach by examining nicotine from diet in relation to Parkinson risk. Although this study did not settle the controversies regarding smoking and PD, it offers new evidence that supports a causal explanation," Dr. Chen said.
He cautioned, however, that this is a "preliminary finding that needs to be replicated, particularly from prospective studies that assess dietary habit before PD diagnosis.
"This study, however, is an excellent example of a novel approach for studying the relationship between smoking and PD. Further, if this finding could be confirmed, it adds to the health benefits of eating tomatoes and green peppers," Dr. Chen said.
Probiotics affect brain activity
A new study provides the first evidence in humans that probiotics in the diet can modulate brain activity.
In a proof-of-concept study using functional MRI (fMRI), researchers found that women who regularly consumed probiotic-containing yogurt showed altered activity of brain regions that control central processing of emotion and sensation. The study was funded by Danone Research.
"This study is unique because it is the first to show an interaction between a probiotic and the brain in humans," lead author Kirsten Tillisch, MD, associate professor, Oppenheimer Family Center for Neurobiology of Stress, David Geffen School of Medicine, University of California Los Angeles, toldMedscape Medical News.
"We can't say whether the effects are beneficial; that will take larger studies with more complex designs. One of the areas this will move to is study of disease groups like irritable bowel syndrome and anxiety," she added.
The results appear in the June issue of Gastroenterology.
Modulating brain function
"This is a very important study as up to now most of the evidence that the gut microbiota can influence brain and behavior have emerged from studies in mouse models including our own work," said John Cryan, PhD, professor and head of the Department of Anatomy and Neuroscience, University College Cork, Ireland, who was not involved in the study.
"Tillisch and colleagues now have neatly shown that probiotics can also affect resting brain activity in human subjects using neuroimaging techniques. This gives credence to the idea that we may eventually modulate brain function in disease states using probiotics. That said, it is a small study, only in women, and the mechanism as to how the bacteria are inducing their effects remains unclear," Dr. Cryan said.
The study involved 36 healthy women with no gastrointestinal or psychiatric symptoms. Twice daily for 4 weeks, 12 women ate a fermented yogurt product containing the probiotics Bifidobacterium animalis subsp Lactis, Streptococcus thermophiles, Lactobacillus bulgaricus, and Lactococcus lactis subsp Lactis; 11 women ate a nonfermented milk product (controls), and 13 received no intervention.
The women underwent fMRI before and after the intervention to measure resting brain activity and brain responses to an emotion-recognition task in which they viewed a series of pictures of people with angry or scared faces and matched them to other faces showing the same emotions. The researchers say they chose this task because studies in animals have linked changes in gut flora to changes in affective behaviors.
During the emotional reactivity task, the probiotic group showed significantly reduced activity in a widely distributed functional network containing affective, viscerosensory, and somatosensory cortices.
During resting fMRI, the probiotic group showed greater connectivity between the periaqueductal grey matter of the midbrain and cognition-associated areas of the prefrontal cortex.
These changes were not observed in the group that consumed the nonfermented milk product; "thus the findings appear to be related to the ingested bacteria strains and their effects on the host," the authors say.
Gut-brain interactions
This study, they say, "clearly demonstrates" an effect of probiotic ingestion on evoked brain responses and resting-state networks in women. However, it was not designed to address the mechanisms mediating this effect.
Going forward, they say, "identification of the signaling pathways between the microbiota and the brain in humans is needed to solidify our understanding of microbiota gut-brain interactions. If confirmed, modulation of the gut flora can provide novel targets for the treatment of patients with abnormal pain and stress responses associated with gut dysbiosis."
"The knowledge that signals are sent from the intestine to the brain and that they can be modulated by a dietary change is likely to lead to an expansion of research aimed at finding new strategies to prevent or treat digestive, mental and neurological disorders," Emeran Mayer, MD, professor of medicine, physiology, and psychiatry at the David Geffen School of Medicine at UCLA and the study's senior author, told Medscape Medical News.
In a proof-of-concept study using functional MRI (fMRI), researchers found that women who regularly consumed probiotic-containing yogurt showed altered activity of brain regions that control central processing of emotion and sensation. The study was funded by Danone Research.
"This study is unique because it is the first to show an interaction between a probiotic and the brain in humans," lead author Kirsten Tillisch, MD, associate professor, Oppenheimer Family Center for Neurobiology of Stress, David Geffen School of Medicine, University of California Los Angeles, toldMedscape Medical News.
"We can't say whether the effects are beneficial; that will take larger studies with more complex designs. One of the areas this will move to is study of disease groups like irritable bowel syndrome and anxiety," she added.
The results appear in the June issue of Gastroenterology.
Modulating brain function
"This is a very important study as up to now most of the evidence that the gut microbiota can influence brain and behavior have emerged from studies in mouse models including our own work," said John Cryan, PhD, professor and head of the Department of Anatomy and Neuroscience, University College Cork, Ireland, who was not involved in the study.
"Tillisch and colleagues now have neatly shown that probiotics can also affect resting brain activity in human subjects using neuroimaging techniques. This gives credence to the idea that we may eventually modulate brain function in disease states using probiotics. That said, it is a small study, only in women, and the mechanism as to how the bacteria are inducing their effects remains unclear," Dr. Cryan said.
The study involved 36 healthy women with no gastrointestinal or psychiatric symptoms. Twice daily for 4 weeks, 12 women ate a fermented yogurt product containing the probiotics Bifidobacterium animalis subsp Lactis, Streptococcus thermophiles, Lactobacillus bulgaricus, and Lactococcus lactis subsp Lactis; 11 women ate a nonfermented milk product (controls), and 13 received no intervention.
The women underwent fMRI before and after the intervention to measure resting brain activity and brain responses to an emotion-recognition task in which they viewed a series of pictures of people with angry or scared faces and matched them to other faces showing the same emotions. The researchers say they chose this task because studies in animals have linked changes in gut flora to changes in affective behaviors.
During the emotional reactivity task, the probiotic group showed significantly reduced activity in a widely distributed functional network containing affective, viscerosensory, and somatosensory cortices.
During resting fMRI, the probiotic group showed greater connectivity between the periaqueductal grey matter of the midbrain and cognition-associated areas of the prefrontal cortex.
These changes were not observed in the group that consumed the nonfermented milk product; "thus the findings appear to be related to the ingested bacteria strains and their effects on the host," the authors say.
Gut-brain interactions
This study, they say, "clearly demonstrates" an effect of probiotic ingestion on evoked brain responses and resting-state networks in women. However, it was not designed to address the mechanisms mediating this effect.
Going forward, they say, "identification of the signaling pathways between the microbiota and the brain in humans is needed to solidify our understanding of microbiota gut-brain interactions. If confirmed, modulation of the gut flora can provide novel targets for the treatment of patients with abnormal pain and stress responses associated with gut dysbiosis."
"The knowledge that signals are sent from the intestine to the brain and that they can be modulated by a dietary change is likely to lead to an expansion of research aimed at finding new strategies to prevent or treat digestive, mental and neurological disorders," Emeran Mayer, MD, professor of medicine, physiology, and psychiatry at the David Geffen School of Medicine at UCLA and the study's senior author, told Medscape Medical News.
Hepatitis B viral levels soar when vitamin D drops
Insufficient serum levels of vitamin D, which ebb and flow with sun exposure, are associated with high levels of hepatitis B virus (HBV) replication in treatment-naive people who suffer from chronic infection.
Harald Farnik, from the Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Germany, and colleagues report the results of their study in an article published online May 22 in Hepatology.
HBV infection remains one of the most significant infectious diseases worldwide. According to the World Health Organization, 2 billion people worldwide have been infected with HBV, and roughly 600,000 die each year. Without antiviral therapy, the virus can attack the liver, and chronic infections progress to liver disease and cirrhosis. An emerging body of evidence has shown that vitamin D plays a role in inflammatory and metabolic liver diseases and that vitamin D can have a therapeutic effect for patients with tuberculosis. Although previous research has failed to demonstrate a correlation between hepatitis C viral load and circulating vitamin D levels, Dr. Farnik and colleagues sought to characterize the relationship between vitamin D metabolism and chronic hepatitis B.
They analyzed serum samples from treatment-naive patients with chronic hepatitis who visited the outpatient liver clinic of the Johann Wolfgang Goethe University Hospital in Frankfurt, Germany from January 2009 to December 2012. Two hundred and three patients were enrolled in the study. Every 3 HBV-infected patients enrolled in the study were randomly matched, according to age and sex, with 2 HCV-infected patients. Sixty-nine of the patients had severe vitamin D deficiency (25(OH)D3 levels < 10 ng/mL), 95 had vitamin D insufficiency (25(OH)D3 ≥ 10 ng/mL and < 20 ng/mL), and 39 had normal vitamin D levels (25(OH)D3 ≥ 20 ng/mL), Dr. Farnik and colleagues write.
"25(OH)D3 and HBV DNA serum levels showed a significant, inverse correlation (P=0.0003)," the authors write. "In both uni- and multivariate analyses, HBV DNA was the strongest determinant of low 25(OH)D3 serum concentration in our cohort (P=0.0007 and P=0.000048), respectively.
Additional studies will be needed to establish a causal relationship between vitamin D metabolism and HBV replication, the researchers write, as well as to explore the effect of adding supplemental vitamin D to existing therapies to improve the durability of treatment.
"In conclusion, we demonstrate a significant association between low 25(OH)D3 serum levels and high levels of HBV replication in chronically infected patients," they authors write. "Future studies to evaluate a therapeutic value of vitamin D and its analogs in HBV infection may be justified."
Source:
Harald Farnik, from the Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Germany, and colleagues report the results of their study in an article published online May 22 in Hepatology.
HBV infection remains one of the most significant infectious diseases worldwide. According to the World Health Organization, 2 billion people worldwide have been infected with HBV, and roughly 600,000 die each year. Without antiviral therapy, the virus can attack the liver, and chronic infections progress to liver disease and cirrhosis. An emerging body of evidence has shown that vitamin D plays a role in inflammatory and metabolic liver diseases and that vitamin D can have a therapeutic effect for patients with tuberculosis. Although previous research has failed to demonstrate a correlation between hepatitis C viral load and circulating vitamin D levels, Dr. Farnik and colleagues sought to characterize the relationship between vitamin D metabolism and chronic hepatitis B.
They analyzed serum samples from treatment-naive patients with chronic hepatitis who visited the outpatient liver clinic of the Johann Wolfgang Goethe University Hospital in Frankfurt, Germany from January 2009 to December 2012. Two hundred and three patients were enrolled in the study. Every 3 HBV-infected patients enrolled in the study were randomly matched, according to age and sex, with 2 HCV-infected patients. Sixty-nine of the patients had severe vitamin D deficiency (25(OH)D3 levels < 10 ng/mL), 95 had vitamin D insufficiency (25(OH)D3 ≥ 10 ng/mL and < 20 ng/mL), and 39 had normal vitamin D levels (25(OH)D3 ≥ 20 ng/mL), Dr. Farnik and colleagues write.
"25(OH)D3 and HBV DNA serum levels showed a significant, inverse correlation (P=0.0003)," the authors write. "In both uni- and multivariate analyses, HBV DNA was the strongest determinant of low 25(OH)D3 serum concentration in our cohort (P=0.0007 and P=0.000048), respectively.
Additional studies will be needed to establish a causal relationship between vitamin D metabolism and HBV replication, the researchers write, as well as to explore the effect of adding supplemental vitamin D to existing therapies to improve the durability of treatment.
"In conclusion, we demonstrate a significant association between low 25(OH)D3 serum levels and high levels of HBV replication in chronically infected patients," they authors write. "Future studies to evaluate a therapeutic value of vitamin D and its analogs in HBV infection may be justified."
Source:
Food supplement linked to lower PSA in prostate cancer
A commercially available food supplement that contains pomegranate, broccoli, green tea, and turmeric significantly lowers prostate-specific antigen (PSA) levels, compared with placebo, in patients with prostate cancer, a double-blind placebo-controlled randomized trial has shown.
The study results, presented here at the 2013 Annual Meeting of the American Society of Clinical Oncology, made headlines around the world and caused the polyphenol-rich supplement, known as Pomi-T (nature Medical Products), to sell out within hours.
This is a "promising new therapy," said Tomasz Beer, MD, professor of medicine and director of the prostate cancer research program at the Oregon Health and Science University in Portland, during a "highlights of the day" session.
"We have been staggered by the level of interest...from medical professionals and the public," Marcus Williams, owner and director of natureMedical Products, told Medscape Medical News. As soon as the results of this study were released, the company, based in Porthcawl, South Wales, United Kingdom, received a rush of orders from customers in Australia, Canada, the United Kingdom, and the United States.
"It's awesome," the study's lead investigator, Robert Thomas, MD, a consultant oncologist at Bedford Hospital and Addenbrooke's Hospital, in the United Kingdom, told Medscape Medical News.
"We didn't expect such a big response. People are seeing that this can change practice...because men and their doctors do look at their PSA as a deciding factor in whether to stop active management," he explained.
Significantly different than placebo
The study involved 203 men (average age, 74 years) with a PSA relapse after radiotherapy or surgery for localized prostate cancer. The men, who were being managed with active surveillance, were randomized to receive the supplement 3 times a day for 6 months or placebo.
At 6-month follow-up, the median increase in PSA was 63.8% lower in the supplement groups than in the placebo group (14.7% vs 78.5; P =.0008). In addition, PSA levels were stable or lower than baseline more often in the supplement group (46% vs 14%;P = .00001).
Fewer men in the supplement group than in the placebo group went on to receive brachytherapy, radiotherapy, surgery, or androgen-deprivation therapy (7.4% vs 26.0%; P = 0.01).
At the end of the study, more men in the supplement group than in the placebo group continued on active surveillance (92.6% vs 74.0%). "This is an end point we feel is important: more men were choosing to stay on treatments with less toxicity," Dr. Thomas noted.
There were no differences between the supplement and placebo groups for baseline and serial measurements of cholesterol, blood pressure, serum glucose, C-reactive protein, or adverse events.
"Pomi-T was well tolerated," he said. "More men experienced nonsignificant bloating or diarrhea, but 15% of men reported beneficial effects, including better digestion and improvement of urinary symptoms."
Previous research has shown that the polyphenols and antioxidants in pomegranate, broccoli, green tea, and turmeric have individual anticancer properties, but "we believe there's a synergistic effect in the supplement," said Dr. Thomas.
In addition, the fact that each ingredient originates from a separate food category (fruit, vegetable, herb, and spice) might prevent potential adverse effects from the overconsumption of one particular type of polyphenol, he noted.
In the lab, polyphenols have been shown to have antiproliferative, antiangiogenic, proadhesion, antimetastatic, and proapoptotic properties, and notably, they have no phytoestrogenic or hormonal effects. "We specifically chose to steer away from anything that might have a hormonal effect."
Because of the supplement's effect is likely not hormonal, future trials will involve men with different stages of prostate cancer and those receiving androgen-deprivation therapy, he said. In addition, the researchers hope to look at the impact of the supplement on other slow-growing cancers and even on cancer prevention.
The study received no funding from the manufacturer of the supplement; however, the company worked very closely with the research team to develop the product, said Williams. "Unlike other nutritional supplement products, the manufacture of this supplement was significantly more time-consuming because Dr. Thomas and colleagues, for whom this was initially made, insisted on a great deal of quality assurance, over and above that normally required by the US Food and Drug Administration or European Commission, particularly in terms of purity and authenticity."
He said the study signals "a new era for the nutritional supplement industry, which has previously relied on advertising and marketing rather than evidence of benefit. Clearly, it's the latter that the public wants."
Dr. Beer noted that the product's significant effect on adherence to active surveillance is "potentially clinically meaningful... If this can be confirmed, this is really interesting," he said, although he added that "these patients were more severe than the sort of patients that we would follow [with active surveillance] here in the United States."
Prostate Cancer UK reacted more cautiously to the news, releasing a statment saying that "there is not yet enough evidence that Pomi-T food supplements have a significant impact."
Kate Holmes, MD, head of research at Prostate Cancer UK, said in a statement that "there is increasing evidence showing that men who have a healthy lifestyle, including a balanced diet and regular exercise, have better prostate cancer outcomes than those who do not. At this stage, however, we simply do not have enough evidence to suggest that any particular foods or supplements have a significant impact and these should certainly not be substituted for conventional treatments."
Source: http://www.medscape.com/viewarticle/805549?nlid=31706_1301&src=wnl_edit_dail&uac=129655SZ
The study results, presented here at the 2013 Annual Meeting of the American Society of Clinical Oncology, made headlines around the world and caused the polyphenol-rich supplement, known as Pomi-T (nature Medical Products), to sell out within hours.
This is a "promising new therapy," said Tomasz Beer, MD, professor of medicine and director of the prostate cancer research program at the Oregon Health and Science University in Portland, during a "highlights of the day" session.
"We have been staggered by the level of interest...from medical professionals and the public," Marcus Williams, owner and director of natureMedical Products, told Medscape Medical News. As soon as the results of this study were released, the company, based in Porthcawl, South Wales, United Kingdom, received a rush of orders from customers in Australia, Canada, the United Kingdom, and the United States.
"It's awesome," the study's lead investigator, Robert Thomas, MD, a consultant oncologist at Bedford Hospital and Addenbrooke's Hospital, in the United Kingdom, told Medscape Medical News.
"We didn't expect such a big response. People are seeing that this can change practice...because men and their doctors do look at their PSA as a deciding factor in whether to stop active management," he explained.
Significantly different than placebo
The study involved 203 men (average age, 74 years) with a PSA relapse after radiotherapy or surgery for localized prostate cancer. The men, who were being managed with active surveillance, were randomized to receive the supplement 3 times a day for 6 months or placebo.
At 6-month follow-up, the median increase in PSA was 63.8% lower in the supplement groups than in the placebo group (14.7% vs 78.5; P =.0008). In addition, PSA levels were stable or lower than baseline more often in the supplement group (46% vs 14%;P = .00001).
Fewer men in the supplement group than in the placebo group went on to receive brachytherapy, radiotherapy, surgery, or androgen-deprivation therapy (7.4% vs 26.0%; P = 0.01).
At the end of the study, more men in the supplement group than in the placebo group continued on active surveillance (92.6% vs 74.0%). "This is an end point we feel is important: more men were choosing to stay on treatments with less toxicity," Dr. Thomas noted.
There were no differences between the supplement and placebo groups for baseline and serial measurements of cholesterol, blood pressure, serum glucose, C-reactive protein, or adverse events.
"Pomi-T was well tolerated," he said. "More men experienced nonsignificant bloating or diarrhea, but 15% of men reported beneficial effects, including better digestion and improvement of urinary symptoms."
Previous research has shown that the polyphenols and antioxidants in pomegranate, broccoli, green tea, and turmeric have individual anticancer properties, but "we believe there's a synergistic effect in the supplement," said Dr. Thomas.
In addition, the fact that each ingredient originates from a separate food category (fruit, vegetable, herb, and spice) might prevent potential adverse effects from the overconsumption of one particular type of polyphenol, he noted.
In the lab, polyphenols have been shown to have antiproliferative, antiangiogenic, proadhesion, antimetastatic, and proapoptotic properties, and notably, they have no phytoestrogenic or hormonal effects. "We specifically chose to steer away from anything that might have a hormonal effect."
Because of the supplement's effect is likely not hormonal, future trials will involve men with different stages of prostate cancer and those receiving androgen-deprivation therapy, he said. In addition, the researchers hope to look at the impact of the supplement on other slow-growing cancers and even on cancer prevention.
The study received no funding from the manufacturer of the supplement; however, the company worked very closely with the research team to develop the product, said Williams. "Unlike other nutritional supplement products, the manufacture of this supplement was significantly more time-consuming because Dr. Thomas and colleagues, for whom this was initially made, insisted on a great deal of quality assurance, over and above that normally required by the US Food and Drug Administration or European Commission, particularly in terms of purity and authenticity."
He said the study signals "a new era for the nutritional supplement industry, which has previously relied on advertising and marketing rather than evidence of benefit. Clearly, it's the latter that the public wants."
Dr. Beer noted that the product's significant effect on adherence to active surveillance is "potentially clinically meaningful... If this can be confirmed, this is really interesting," he said, although he added that "these patients were more severe than the sort of patients that we would follow [with active surveillance] here in the United States."
Prostate Cancer UK reacted more cautiously to the news, releasing a statment saying that "there is not yet enough evidence that Pomi-T food supplements have a significant impact."
Kate Holmes, MD, head of research at Prostate Cancer UK, said in a statement that "there is increasing evidence showing that men who have a healthy lifestyle, including a balanced diet and regular exercise, have better prostate cancer outcomes than those who do not. At this stage, however, we simply do not have enough evidence to suggest that any particular foods or supplements have a significant impact and these should certainly not be substituted for conventional treatments."
Source: http://www.medscape.com/viewarticle/805549?nlid=31706_1301&src=wnl_edit_dail&uac=129655SZ
Tea and coffee lower blood pressure
A large French retrospective analysis provides good news for caffeine lovers: investigators showed that drinking tea or coffee was associated with a small but statistically significant reduction in systolic and diastolic blood pressure. In addition, drinking tea and coffee was also associated with a significant reduction in pulse pressure and heart rate, although the heart-rate reductions were greater with tea.
Presenting the results at the European Society of Hypertension (ESH) 2013 Scientific Sessions, Dr Bruno Pannier (Centre d'Investigations Préventives et Cliniques, Paris, France) said that other studies have suggested a relationship between coffee and tea consumption and blood pressure, but these analyses haven't been conclusive. Some have suggested a benefit, while others found no relationship between tea/coffee consumption and blood pressure.
Presenting the data on 176 437 subjects aged 16 to 95 years of age who had a checkup at their center between 2001 and 2011, Pannier explained that the analysis was simply based on a questionnaire asking participants how much coffee or tea they drank per day. Individuals were classified into three groups: those who drank no coffee/tea, those who drank one to four cups, and those who drank more than four cups.
Overall, coffee is consumed more frequently than tea, although there were differences between the sexes, said Pannier. Men were more likely to drink coffee, while women were more commonly tea drinkers. Coffee consumption was also significantly associated with tobacco consumption, higher cholesterol levels, and higher scores on stress and depression indexes. Tea consumption, on the other hand, was associated with lower cholesterol levels but similarly high scores on the stress and depression measurements.
After adjustments that included these and other potential confounding variables, both coffee and tea consumption was associated with a significant reduction in systolic and diastolic blood pressure, as well as other variables.
Speaking during the session, Pannier explained that the group did not differentiate between green, black, or herbal tea consumption, which is one of the limitations of the analysis. In addition, the questionnaire is not sophisticated enough to address estimates in the caffeine content of the coffee consumed in France.
That said, Pannier believes that tea is a major source of flavonoids in the diet, and these compounds can improve vasodilation. "The vasorelaxing compounds included in these beverages might be involved in these results, something that has been suggested by the experimental data," he said.
Source: http://www.medscape.com/viewarticle/806516?nlid=31779_1301&src=wnl_edit_dail&uac=129655SZ
Presenting the results at the European Society of Hypertension (ESH) 2013 Scientific Sessions, Dr Bruno Pannier (Centre d'Investigations Préventives et Cliniques, Paris, France) said that other studies have suggested a relationship between coffee and tea consumption and blood pressure, but these analyses haven't been conclusive. Some have suggested a benefit, while others found no relationship between tea/coffee consumption and blood pressure.
Presenting the data on 176 437 subjects aged 16 to 95 years of age who had a checkup at their center between 2001 and 2011, Pannier explained that the analysis was simply based on a questionnaire asking participants how much coffee or tea they drank per day. Individuals were classified into three groups: those who drank no coffee/tea, those who drank one to four cups, and those who drank more than four cups.
Overall, coffee is consumed more frequently than tea, although there were differences between the sexes, said Pannier. Men were more likely to drink coffee, while women were more commonly tea drinkers. Coffee consumption was also significantly associated with tobacco consumption, higher cholesterol levels, and higher scores on stress and depression indexes. Tea consumption, on the other hand, was associated with lower cholesterol levels but similarly high scores on the stress and depression measurements.
After adjustments that included these and other potential confounding variables, both coffee and tea consumption was associated with a significant reduction in systolic and diastolic blood pressure, as well as other variables.
Blood Pressure Among Coffee Drinkers
| Variable | None | 1 to 4 cups | >4 cups | p (for trend) |
| Systolic blood pressure (mm Hg) | 127.9 | 126.7 | 125.5 | <0.0001 |
| Diastolic blood pressure (mm Hg) | 76.0 | 76.0 | 75.7 | 0.02 |
| Pulse pressure (mm Hg) | 51.9 | 50.7 | 49.8 | <0.0001 |
| Heart rate (beats/min) | 63.2 | 62.9 | 63.2 | 0.001 |
Blood Pressure Among Tea Drinkers
| Variable | None | 1 to 4 cups | >4 cups | p (for trend) |
| Systolic blood pressure (mm Hg) | 127.3 | 126.3 | 125.3 | <0.0001 |
| Diastolic blood pressure (mm Hg) | 76.2 | 75.6 | 75.0 | <0.0001 |
| Pulse pressure (mmHg) | 51.1 | 50.7 | 50.3 | <0.0001 |
| Heart rate (beats/min) | 63.5 | 62.7 | 62.0 | <0.0001 |
Speaking during the session, Pannier explained that the group did not differentiate between green, black, or herbal tea consumption, which is one of the limitations of the analysis. In addition, the questionnaire is not sophisticated enough to address estimates in the caffeine content of the coffee consumed in France.
That said, Pannier believes that tea is a major source of flavonoids in the diet, and these compounds can improve vasodilation. "The vasorelaxing compounds included in these beverages might be involved in these results, something that has been suggested by the experimental data," he said.
Source: http://www.medscape.com/viewarticle/806516?nlid=31779_1301&src=wnl_edit_dail&uac=129655SZ
Mindful meditation has antianxiety effects
Individuals with no experience in meditation who participate in mindful meditation training sessions for as little as 4 days show changes in specific brain mechanisms that correlate with a reduction in anxiety, a new imaging study shows.
"There is plenty of evidence that meditation can improve a host of issues, such as pain and cognitive function, and anxiety is perhaps at the top of the list," explained lead author Fadel Zeidan, PhD, a postdoctoral research fellow in neurobiology and anatomy at Wake Forest School of Medicine, in Winston-Salem, North Carolina.
"But what we've been able to do is to correlate, through imaging, changes in specific brain regions that are related to anxiety, even in a cohort of people with no anxiety or depression."
The findings were published online April 24 in Social Cognitive and Affective Neuroscience.
Buffer to anxiety
For the study, Dr. Zeidan and his colleagues recruited 15 healthy volunteers with normal levels of anxiety and no experience in meditation to participate in four 20-minute training sessions to learn the technique for mindful meditation.
This involves a focus on breathing and a conscious acknowledging of distracting thoughts and emotions, combined with a decision not to react to them.
"You're trained to focus on keeping a very straight posture and the sensations of the rise and fall of your chest and abdomen as you breathe," Dr. Zeidan explained.
"If your mind becomes distracted, you acknowledge the distraction, let it go, and focus back on the breathing. You are regulating your emotional responses."
Before and after each meditation training session, the participants, who included graduate students and faculty, received brain activity imaging with pulsed arterial spin labeling magnetic resonance imaging (MRI).
The participants also were administered the State Anxiety Inventory, a 20-item subscale of the State Trait Anxiety Inventory, before and after the brain imaging.
While the participants reported meditation-related reductions in anxiety ratings by as much as 22%, the MRIs showed anxiety relief to be associated with activation of the anterior cingulate cortex and ventromedial prefrontal cortex (vmPFC), which show decreases in activity when anxiety is present.
The vmPFC is also implicated in the alteration of contextual evaluation of affective processes, the authors write.
"Activation in the vmPFC is associated with modulating higher-order affective appraisals, including cognitive regulation of negative emotions."
In addition, reports of greater anxiety correlated with greater default-related activity (ie, posterior cingulate cortex) on MRI, "possibly reflecting an inability to control self-referential thoughts," the authors write.
The brain mechanisms related to the reduction of anxiety through mindful meditation in healthy people have never been identified, so the findings help confirm that the changes do occur, said Dr. Zeidan.
"It shows that mindful meditation can be sort of this buffer to anxiety. After just a brief training, you can reduce this ruminative thought process, change your attention, and change the context in how you respond to things," he said.
Potential payoff
Amit Sood, MD, director of research and practice in the Mayo Complementary and Integrative Medicine Program at Mayo Clinic, in Rochester, Minnesota, said that such changes are not unexpected over such a short period.
"I'm not surprised to see the correlations with reductions of anxiety in 4 days — other studies looking at brain structure have reported seeing these changes after just 4 to 6 hours of training," said Dr. Sood.
"What I would be surprised to see, however, is if they were still doing it on their own after 6 months," he noted.
"People can learn it quickly, but then they forget. A change in habit requires a lot of effort. People have to carve out the time in their busy days, and what tends to happen is will power depletion."
The study demonstrates, however, the potential payoff, he added.
"I wouldn't call this a landmark study, but it does validate the overall theme we're seeing in this field," Dr. Sood said.
"It adds another bullet point of how we can understand emotional and brain states, and eventually this may help us better classify people based on what is actually happening in the brain, beyond their displayed symptoms."
"There is plenty of evidence that meditation can improve a host of issues, such as pain and cognitive function, and anxiety is perhaps at the top of the list," explained lead author Fadel Zeidan, PhD, a postdoctoral research fellow in neurobiology and anatomy at Wake Forest School of Medicine, in Winston-Salem, North Carolina.
"But what we've been able to do is to correlate, through imaging, changes in specific brain regions that are related to anxiety, even in a cohort of people with no anxiety or depression."
The findings were published online April 24 in Social Cognitive and Affective Neuroscience.
Buffer to anxiety
For the study, Dr. Zeidan and his colleagues recruited 15 healthy volunteers with normal levels of anxiety and no experience in meditation to participate in four 20-minute training sessions to learn the technique for mindful meditation.
This involves a focus on breathing and a conscious acknowledging of distracting thoughts and emotions, combined with a decision not to react to them.
"You're trained to focus on keeping a very straight posture and the sensations of the rise and fall of your chest and abdomen as you breathe," Dr. Zeidan explained.
"If your mind becomes distracted, you acknowledge the distraction, let it go, and focus back on the breathing. You are regulating your emotional responses."
Before and after each meditation training session, the participants, who included graduate students and faculty, received brain activity imaging with pulsed arterial spin labeling magnetic resonance imaging (MRI).
The participants also were administered the State Anxiety Inventory, a 20-item subscale of the State Trait Anxiety Inventory, before and after the brain imaging.
While the participants reported meditation-related reductions in anxiety ratings by as much as 22%, the MRIs showed anxiety relief to be associated with activation of the anterior cingulate cortex and ventromedial prefrontal cortex (vmPFC), which show decreases in activity when anxiety is present.
The vmPFC is also implicated in the alteration of contextual evaluation of affective processes, the authors write.
"Activation in the vmPFC is associated with modulating higher-order affective appraisals, including cognitive regulation of negative emotions."
In addition, reports of greater anxiety correlated with greater default-related activity (ie, posterior cingulate cortex) on MRI, "possibly reflecting an inability to control self-referential thoughts," the authors write.
The brain mechanisms related to the reduction of anxiety through mindful meditation in healthy people have never been identified, so the findings help confirm that the changes do occur, said Dr. Zeidan.
"It shows that mindful meditation can be sort of this buffer to anxiety. After just a brief training, you can reduce this ruminative thought process, change your attention, and change the context in how you respond to things," he said.
Potential payoff
Amit Sood, MD, director of research and practice in the Mayo Complementary and Integrative Medicine Program at Mayo Clinic, in Rochester, Minnesota, said that such changes are not unexpected over such a short period.
"I'm not surprised to see the correlations with reductions of anxiety in 4 days — other studies looking at brain structure have reported seeing these changes after just 4 to 6 hours of training," said Dr. Sood.
"What I would be surprised to see, however, is if they were still doing it on their own after 6 months," he noted.
"People can learn it quickly, but then they forget. A change in habit requires a lot of effort. People have to carve out the time in their busy days, and what tends to happen is will power depletion."
The study demonstrates, however, the potential payoff, he added.
"I wouldn't call this a landmark study, but it does validate the overall theme we're seeing in this field," Dr. Sood said.
"It adds another bullet point of how we can understand emotional and brain states, and eventually this may help us better classify people based on what is actually happening in the brain, beyond their displayed symptoms."
Source: http://www.medscape.com/viewarticle/806288?nlid=31771_1301&src=wnl_edit_dail&uac=129655SZ
Diclofenac poses similar risks as COX-2 Inhibitors
The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) has completed its review of diclofenac and concluded that the drug poses similar risks as selective COX-2 inhibitors, particularly when used in high doses (150 mg) or when used long term [1].
Still, committee says the benefits of diclofenac exceed the risks and that physicians should take the same precautions to minimize thromboembolic events as they do with patients treated with selective COX-2 inhibitors.
"Patients who have serious underlying heart or circulatory conditions, such as heart failure, heart disease, circulatory problems, or a previous heart attack or stroke, should not use diclofenac," according to PRAC. "Patients with certain cardiovascular risk factors (such as high blood pressure, raised blood cholesterol, diabetes, or smoking) should only use diclofenac after careful consideration. Healthcare professionals will also be advised to periodically reassess the need for patients to continue taking the medicine."
The review conducted by PRAC was launched in October 2012 after the EMA completed a report on published information assessing the cardiovascular safety of nonsteroidal anti-inflammatory drugs (NSAIDs). Like PRAC, the EMA concluded that there was a consistent but small increase in the risk of cardiovascular side effects with diclofenac compared with other NSAIDs and that this risk was on par with that observed with COX-2 inhibitors.
The current PRAC conclusions are based on all published and unpublished data. Its recommendations will now be forwarded to the Coordination Group for Mutual Recognition and Decentralized Procedures--Human (CMDh), a regulatory body representing member European Union states, which will adopt a final position.
Still, committee says the benefits of diclofenac exceed the risks and that physicians should take the same precautions to minimize thromboembolic events as they do with patients treated with selective COX-2 inhibitors.
"Patients who have serious underlying heart or circulatory conditions, such as heart failure, heart disease, circulatory problems, or a previous heart attack or stroke, should not use diclofenac," according to PRAC. "Patients with certain cardiovascular risk factors (such as high blood pressure, raised blood cholesterol, diabetes, or smoking) should only use diclofenac after careful consideration. Healthcare professionals will also be advised to periodically reassess the need for patients to continue taking the medicine."
The review conducted by PRAC was launched in October 2012 after the EMA completed a report on published information assessing the cardiovascular safety of nonsteroidal anti-inflammatory drugs (NSAIDs). Like PRAC, the EMA concluded that there was a consistent but small increase in the risk of cardiovascular side effects with diclofenac compared with other NSAIDs and that this risk was on par with that observed with COX-2 inhibitors.
The current PRAC conclusions are based on all published and unpublished data. Its recommendations will now be forwarded to the Coordination Group for Mutual Recognition and Decentralized Procedures--Human (CMDh), a regulatory body representing member European Union states, which will adopt a final position.
Source: http://www.medscape.com/viewarticle/806308?nlid=31771_1301&src=wnl_edit_dail&uac=129655SZ
Silver enhances antibiotic activity against gram-negative bacteria in mice
The use of silver in medicine is as old as western medicine itself. Hippocrates is known to have used it to treat ulcers and wounds, the Romans almost certainly knew of its healing properties, its use continued through the middle ages and up to the present day. In the antibiotic age, interest in silver may have waned a little. But with urgent need to fight antibiotic-resistant bacteria, there is resurgence in its uses.
The reason is that silver can kill bacteria selectively and, more importantly, bacteria are unable to develop resistance against it. Despite silver’s long medical history, we do not know how it operates. A paper published last Thursday in the journal Science Translational Medicine sheds some light on silver’s success against bacteria. The most important find is that silver – unlike most antibiotics – works in more than one way. This is perhaps why bacteria are not able to build resistance to silver.
Here is silver’s multi-pronged approach: first, silver sticks very strongly to sulfur, found in parts of proteins. These sulfur groups normally bond to each other in proteins, holding them together and keeping the protein folded up in its correct shape. But if silver interacts with sulfur then the protein cannot fold correctly, and thus it cannot do its job. Next silver interferes with how bacteria use iron. Iron is often held in the places it is needed by binding to sulfur. And since silver also interacts with sulfur it stops the iron doing so. Finally, silver causes bacteria to produce extremely toxic substances called reactive oxygen species. These go on to cause damage inside the cell, harming the DNA, proteins and even the membranes that surround cells.
The net result of this silver onslaught is bacteria with severely damaged defences. Most importantly the membranes and walls that surround it are leakier after the silver treatment. Once weakened, they are much more susceptible to conventional antibiotics. James Collins, at Boston University, who led the research showed that with added silver, less antibiotic drug is needed to kill the bugs. A great result in itself, but it gets better. Silver also reverses antibiotic resistance of E. coli bacteria making them, once more, susceptible to tetracycline.
These experiments not only worked in a Petri dish. When silver was added to standard antibiotics such as gentamicin and vancomycin, Collins could treat E. coli infections in the bladder and abdomens of mice. Normally these drugs have little effect on E. coli infections because they are designed to attack a completely separate class of bacteria.
Bacteria are broadly classified into two groups called Gram-negative or Gram-positive. Gram-negatives have an extra cell membrane that protects the bacteria, which means that it is much more difficult for some antibiotics, such as gentamicin and vancomycin, to penetrate the cell. It seems that silver negates this advantage and allows even weaker drugs to do their jobs. Finally, Collins showed that the mice themselves remain unharmed by silver. If he is able to repeat this work in humans, then he may actually have a “silver bullet” for antibiotic resistance.
The reason is that silver can kill bacteria selectively and, more importantly, bacteria are unable to develop resistance against it. Despite silver’s long medical history, we do not know how it operates. A paper published last Thursday in the journal Science Translational Medicine sheds some light on silver’s success against bacteria. The most important find is that silver – unlike most antibiotics – works in more than one way. This is perhaps why bacteria are not able to build resistance to silver.
Here is silver’s multi-pronged approach: first, silver sticks very strongly to sulfur, found in parts of proteins. These sulfur groups normally bond to each other in proteins, holding them together and keeping the protein folded up in its correct shape. But if silver interacts with sulfur then the protein cannot fold correctly, and thus it cannot do its job. Next silver interferes with how bacteria use iron. Iron is often held in the places it is needed by binding to sulfur. And since silver also interacts with sulfur it stops the iron doing so. Finally, silver causes bacteria to produce extremely toxic substances called reactive oxygen species. These go on to cause damage inside the cell, harming the DNA, proteins and even the membranes that surround cells.
The net result of this silver onslaught is bacteria with severely damaged defences. Most importantly the membranes and walls that surround it are leakier after the silver treatment. Once weakened, they are much more susceptible to conventional antibiotics. James Collins, at Boston University, who led the research showed that with added silver, less antibiotic drug is needed to kill the bugs. A great result in itself, but it gets better. Silver also reverses antibiotic resistance of E. coli bacteria making them, once more, susceptible to tetracycline.
These experiments not only worked in a Petri dish. When silver was added to standard antibiotics such as gentamicin and vancomycin, Collins could treat E. coli infections in the bladder and abdomens of mice. Normally these drugs have little effect on E. coli infections because they are designed to attack a completely separate class of bacteria.
Bacteria are broadly classified into two groups called Gram-negative or Gram-positive. Gram-negatives have an extra cell membrane that protects the bacteria, which means that it is much more difficult for some antibiotics, such as gentamicin and vancomycin, to penetrate the cell. It seems that silver negates this advantage and allows even weaker drugs to do their jobs. Finally, Collins showed that the mice themselves remain unharmed by silver. If he is able to repeat this work in humans, then he may actually have a “silver bullet” for antibiotic resistance.
Thursday 18 April 2013
High intake of processed meat linked to cancer deaths
Bacon, sausage, and ham are once again being singled out as key culprits driving the association between meat consumption and the world's most common diseases.
One of the largest studies to address this question, published online March 7 in BMC Medicine, found a moderate positive association between processed meat consumption and mortality. This was particularly true for cardiovascular diseases (CVDs), but was also true for cancer.
Over a mean of 12 years, high consumption of processed meat was associated with a near doubling of the risk for all-cause mortality in adults, compared with low consumption. The risk for cancer death was 43% higher and the risk for cardiovascular death was 70% higher in people eating more than 160 g/day of processed meats than in those eating 10.0 to 19.9 g/day.
"The clinical message [is] to limit consumption of processed meat — not every day and not in high amounts," said lead author Sabine Rohrmann, PhD, MPH, head of the Department of Epidemiology and Prevention at the University of Zurich in Switzerland, in an interview.
EPIC data
The new data come from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, which involved 10 countries and almost half a million men and women.
A signal of increased mortality was seen in the highest consumers of red meat in general; however, the risk was much lower with red meat than with processed meats, and lost statistical significance after correction for measurement error, the researchers report. In fact, the high consumption of processed meat was associated with an 18% increased risk for all-cause mortality.
After multivariate adjustment, the consumption of more than 160 g/day of red meat was related to higher all-cause mortality than the consumption of 10.0 to 19.9 g/day (hazard ratio [HR], 1.14; 95% confidence interval [CI], 1.01 to 1.28). The HR was higher for more than 160 g/day of processed meat (1.44; 95% CI, 1.24 to 1.66).
After correction for measurement error, all-cause mortality remained significantly higher only for the consumption of 50 g/day of processed meat (HR, 1.18; 95% CI, 1.11 to 1.25).
A very high consumption of red meat was nonsignificantly associated with increased cancer mortality, but not with deaths caused by CVD or respiratory diseases, diseases of the digestive tract, or any other disease.
As the researchers point out, processed meats tend to contain more saturated fat than unprocessed meat (where the fat is often trimmed off) and more cholesterol and additives (which are part of the smoking or curing process). Some of these are believed to be carcinogenic or precursors to carcinogenic processes.
When the researchers re-examined the association between processed meat intake and cancer risk using the lowest consumption category (0.0 to 9.9 g/d) as a reference, they observed a statistically significantly increased risk for cancer mortality in people who consumed 80.0 to 159.9 g/day (HR, 1.12; 95% CI, 1.01 to 1.24). There was also a nonsignificantly increased risk in the highest consumption category (HR, 1.19; 95% CI, 0.93 to 1.51).
"Another factor is the salt in processed meat products, which is linked to hypertension — a CVD risk factor," noted Dr. Rohrmann. Heme iron also links meat consumption to CVD risk, "but that's not limited to processed meat," she explained.
Dr. Rohrmann and colleagues point out that the high consumption of processed meat typically goes hand in hand with other unhealthy behaviors, including smoking, low levels of physical activity, and low consumption of fruit and vegetables.
"Overall, we estimate that 3% of premature deaths each year could be prevented if people ate less than 20 g of processed meat per day," she said in a press statement.
What about red meat?
Other studies have singled out processed meats as being particularly hazardous to health. Two large long-running American studies have documented the link between meat consumption and CVD and cancer deaths. However, the stronger association with processed meats that Dr. Rohrmann and colleagues found in their European cohort is somewhat at odds with the American data.
A number of studies have examined the link between meat consumption and cancer. For example, one large prospective trial linked the consumption of processed meat to an increased risk for bladder cancer. Another study found that the consumption of red and processed meats increases the risk for colorectal cancer.
"Although we did not find a statistically significant association between unprocessed red meat consumption and mortality in our studies, we would not say that there is definitely no association" between red meat consumption and CVD, Dr. Rohrmann explained.
"Our studies show it that it's okay to eat a moderate amount of meat (300 to 600 g per week), as recommended by many nutrition societies," she said. However, "a balanced vegetarian diet is okay as well," she added.
Significant association with processed meat
In their study, Dr. Rohrmann and colleagues examined the association between risk for early death and the consumption of red meat, processed meat, and poultry. The 448,568 study participants were 35 to 69 years of age, and had no prevalent cancer, stroke, or myocardial infarction, and had complete information on diet, smoking, physical activity, and body mass index.
A total of 26,344 study participants (11,563 men and 14,781 women) died during the median follow-up period of 12.7 years; 5556 died of CVD, 9861 of cancer, 1068 of respiratory diseases, 715 of digestive tract diseases, and 9144 of other causes.
The researchers note that, according to their estimates, "3.3% (95% CI, 1.5% to 5.0%) of deaths could be prevented if all participants had a processed meat consumption of less than 20 g/day."
The consumption of poultry was not related to all-cause mortality.
One of the largest studies to address this question, published online March 7 in BMC Medicine, found a moderate positive association between processed meat consumption and mortality. This was particularly true for cardiovascular diseases (CVDs), but was also true for cancer.
Over a mean of 12 years, high consumption of processed meat was associated with a near doubling of the risk for all-cause mortality in adults, compared with low consumption. The risk for cancer death was 43% higher and the risk for cardiovascular death was 70% higher in people eating more than 160 g/day of processed meats than in those eating 10.0 to 19.9 g/day.
"The clinical message [is] to limit consumption of processed meat — not every day and not in high amounts," said lead author Sabine Rohrmann, PhD, MPH, head of the Department of Epidemiology and Prevention at the University of Zurich in Switzerland, in an interview.
EPIC data
The new data come from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, which involved 10 countries and almost half a million men and women.
A signal of increased mortality was seen in the highest consumers of red meat in general; however, the risk was much lower with red meat than with processed meats, and lost statistical significance after correction for measurement error, the researchers report. In fact, the high consumption of processed meat was associated with an 18% increased risk for all-cause mortality.
After multivariate adjustment, the consumption of more than 160 g/day of red meat was related to higher all-cause mortality than the consumption of 10.0 to 19.9 g/day (hazard ratio [HR], 1.14; 95% confidence interval [CI], 1.01 to 1.28). The HR was higher for more than 160 g/day of processed meat (1.44; 95% CI, 1.24 to 1.66).
After correction for measurement error, all-cause mortality remained significantly higher only for the consumption of 50 g/day of processed meat (HR, 1.18; 95% CI, 1.11 to 1.25).
A very high consumption of red meat was nonsignificantly associated with increased cancer mortality, but not with deaths caused by CVD or respiratory diseases, diseases of the digestive tract, or any other disease.
As the researchers point out, processed meats tend to contain more saturated fat than unprocessed meat (where the fat is often trimmed off) and more cholesterol and additives (which are part of the smoking or curing process). Some of these are believed to be carcinogenic or precursors to carcinogenic processes.
When the researchers re-examined the association between processed meat intake and cancer risk using the lowest consumption category (0.0 to 9.9 g/d) as a reference, they observed a statistically significantly increased risk for cancer mortality in people who consumed 80.0 to 159.9 g/day (HR, 1.12; 95% CI, 1.01 to 1.24). There was also a nonsignificantly increased risk in the highest consumption category (HR, 1.19; 95% CI, 0.93 to 1.51).
"Another factor is the salt in processed meat products, which is linked to hypertension — a CVD risk factor," noted Dr. Rohrmann. Heme iron also links meat consumption to CVD risk, "but that's not limited to processed meat," she explained.
Dr. Rohrmann and colleagues point out that the high consumption of processed meat typically goes hand in hand with other unhealthy behaviors, including smoking, low levels of physical activity, and low consumption of fruit and vegetables.
"Overall, we estimate that 3% of premature deaths each year could be prevented if people ate less than 20 g of processed meat per day," she said in a press statement.
What about red meat?
Other studies have singled out processed meats as being particularly hazardous to health. Two large long-running American studies have documented the link between meat consumption and CVD and cancer deaths. However, the stronger association with processed meats that Dr. Rohrmann and colleagues found in their European cohort is somewhat at odds with the American data.
A number of studies have examined the link between meat consumption and cancer. For example, one large prospective trial linked the consumption of processed meat to an increased risk for bladder cancer. Another study found that the consumption of red and processed meats increases the risk for colorectal cancer.
"Although we did not find a statistically significant association between unprocessed red meat consumption and mortality in our studies, we would not say that there is definitely no association" between red meat consumption and CVD, Dr. Rohrmann explained.
"Our studies show it that it's okay to eat a moderate amount of meat (300 to 600 g per week), as recommended by many nutrition societies," she said. However, "a balanced vegetarian diet is okay as well," she added.
Significant association with processed meat
In their study, Dr. Rohrmann and colleagues examined the association between risk for early death and the consumption of red meat, processed meat, and poultry. The 448,568 study participants were 35 to 69 years of age, and had no prevalent cancer, stroke, or myocardial infarction, and had complete information on diet, smoking, physical activity, and body mass index.
A total of 26,344 study participants (11,563 men and 14,781 women) died during the median follow-up period of 12.7 years; 5556 died of CVD, 9861 of cancer, 1068 of respiratory diseases, 715 of digestive tract diseases, and 9144 of other causes.
The researchers note that, according to their estimates, "3.3% (95% CI, 1.5% to 5.0%) of deaths could be prevented if all participants had a processed meat consumption of less than 20 g/day."
The consumption of poultry was not related to all-cause mortality.
Source: http://www.medscape.com/viewarticle/780553?nlid=29163_1301&src=wnl_edit_dail
Domperidone under scrutiny in Europe for cardiac risks
European Union (EU) drug regulators announced yesterday that they have begun a review of domperidone, an antiemetic, because of concerns about adverse cardiac events, including QT prolongation and arrhythmias.
Domperidone-containing antiemetics, sold under brand names such as Motilium (Janssen), Mirax (Berlin), and Domper(Opalia, YSP, and Yung Shin), are widely available over the counter or by prescription in a number of European countries. The drugs also have been used on an off-label basis to increase lactation in breast-feeding mothers.
The US Food and Drug Administration (FDA) has not approved domperidone for any indication. In 2004, the FDAwarned clinicians and breast-feeding mothers not to use domperidone to boost milk production because of the risk for adverse events. The agency cited reports of cardiac arrhythmias, cardiac arrest, and sudden death in patients receiving an intravenous form of domperidone that has been discontinued in several countries. However, the European Medicines Agency (EMA) — the EU equivalent of the FDA — continued to receive reports of these adverse events with other forms of the drug.
The FDA noted in 2004 that breast-feeding women in the United States were buying the drug from Internet pharmacies and US compounding pharmacies. The FDA sent warning letters to 6 such compounding pharmacies about the illegal trade in domperidone. A similar letter was issued in 2010 to a compounding pharmacy in Virginia. However, Internet pharmacies still continue to advertise the drug.
The EMA said yesterday that it began its review of domperidone at the request of drug regulators in Belgium, who learned of new cases of cardiotoxicity. Those regulators have proposed that the drug be contraindicated for patients with QT prolongation, significant electrolyte disturbances, or underlying cardiac diseases such as congestive heart failure.
The EMA said that its Pharmacovigilance Risk Assessment Committee will study domperidone-containing drugs, assess whether their benefits outweigh their risks, and recommend possible regulatory action, which could include withdrawing the drugs from the market or revising their label instructions.
Domperidone-containing antiemetics, sold under brand names such as Motilium (Janssen), Mirax (Berlin), and Domper(Opalia, YSP, and Yung Shin), are widely available over the counter or by prescription in a number of European countries. The drugs also have been used on an off-label basis to increase lactation in breast-feeding mothers.
The US Food and Drug Administration (FDA) has not approved domperidone for any indication. In 2004, the FDAwarned clinicians and breast-feeding mothers not to use domperidone to boost milk production because of the risk for adverse events. The agency cited reports of cardiac arrhythmias, cardiac arrest, and sudden death in patients receiving an intravenous form of domperidone that has been discontinued in several countries. However, the European Medicines Agency (EMA) — the EU equivalent of the FDA — continued to receive reports of these adverse events with other forms of the drug.
The FDA noted in 2004 that breast-feeding women in the United States were buying the drug from Internet pharmacies and US compounding pharmacies. The FDA sent warning letters to 6 such compounding pharmacies about the illegal trade in domperidone. A similar letter was issued in 2010 to a compounding pharmacy in Virginia. However, Internet pharmacies still continue to advertise the drug.
The EMA said yesterday that it began its review of domperidone at the request of drug regulators in Belgium, who learned of new cases of cardiotoxicity. Those regulators have proposed that the drug be contraindicated for patients with QT prolongation, significant electrolyte disturbances, or underlying cardiac diseases such as congestive heart failure.
The EMA said that its Pharmacovigilance Risk Assessment Committee will study domperidone-containing drugs, assess whether their benefits outweigh their risks, and recommend possible regulatory action, which could include withdrawing the drugs from the market or revising their label instructions.
Male-pattern baldness linked with heart disease
Vertex baldness, more commonly known as male-pattern baldness, is associated with an increased risk of coronary heart disease, according to the results of a new meta-analysis[1]. The severity of male pattern baldness increased the risk of coronary disease even in younger subjects, report investigators.
A receding hairline, on the other hand, was not associated with an increased risk of heart disease (relative risk 1.11, 95% CI 0.92–1.32; p=0.28).
"These findings suggest that vertex baldness is more closely associated with systemic atherosclerosis than . . . frontal baldness [is]," say Dr Kazuo Hara (University of Tokyo, Japan) and colleagues in their report, published online April 3, 2013 in BMJ Open. "Thus, cardiovascular risk factors should be reviewed carefully in men with vertex baldness, especially younger men, and they probably should be encouraged to improve their cardiovascular risk profile."
The researchers included six studies with 36 990 participants in the meta-analysis, including three cohort studies and three case-control studies. In the three cohort studies, the adjusted risk of coronary heart disease was 32% higher among individuals with severe vertex baldness compared with men with full hair. In the case-control studies, the risk of coronary heart disease was 70% higher among bald subjects compared with those without baldness. The increased relative risk of coronary disease was statistically significant in both analyses. When the analysis was restricted to younger subjects, those <55 or <60 years at baseline, the association between vertex baldness and coronary heart disease remained.
Three studies classified the severity of baldness. In this analysis, the risk of coronary heart disease was 48%, 36%, and 18% higher among subjects with severe, moderate, and mild vertex baldness compared with subjects without baldness. "When baldness was classified by the Hamilton-Norwood scale, which is the most commonly used classification of pattern baldness worldwide, the relationship between coronary heart disease and baldness was shown to be dependent on the severity of baldness," state the researchers.
The reason for the association between vertex baldness and coronary heart disease is not known. The current working hypothesis is that insulin resistance can impair the supply of nutrients to the hair follicles or a proinflammatory state could increase the inflammatory cytokines in the hair follicles. The researchers state that further studies are needed to confirm these findings, as well as to identify mechanisms for the association.
Source: http://www.medscape.com/viewarticle/781931?nlid=30099_1301&src=wnl_edit_dail
Omega-3 plasma levels predict mortality and heart disease
The highest levels of plasma phospholipid omega-3 polyunsaturated fatty acids (PUFA), as measured in over 2,500 older adults initially without coronary heart disease or a history of stroke, predicted the lowest mortality in the observational, prospective Cardiovascular Health Study(CHS)[1].
In comparisons of the highest quintile of omega-3 PUFA levels vs the lowest quintile, all-cause mortality fell by 27%, with most of the benefit due to a reduction in cardiovascular death. The rate of arrhythmic death, in particular, fell by nearly one-half.
Such cardiovascular-outcome effects are consistent with abundant evidence from laboratory and clinical studies that omega-3 PUFA intake may benefit heart rate, blood pressure, myocardial contractile function and electrical stability, and endothelial, autonomic, and hemostatic function, write the study's authors, led by Dr Dariush Mozaffarian (Harvard School of Public Health, Boston, MA). Their analysis was published in the April 2, 2013 issue of the Annals of Internal Medicine.
The CHS longitudinal data allowed the group not only to link plasma omega-3 PUFA levels with survival, Mozaffarian told heartwire , it allowed them to estimate the benefit: in this population, starting at age 65, he said, about 2.2 extra years for people in the highest compared with the lowest plasma-level quintile.
Outcomes also varied by individual omega-3 PUFAs. For a number of end points, importantly heart-disease mortality and arrhythmic mortality, there was a pattern of greater benefit from highest levels of docosahexaenoicacid (DHA) vs highest levels of eicosapentaenoic acid (EPA) and an even greater benefit from highest levels of total omega-3 PUFA.
For the end point of heart-disease death, "DHA seems to have stronger association" than EPA, according to Mozaffarian; the effect, he noted, appears to be dominated by a difference in arrhythmic death. But EPA at the highest levels vs the lowest levels showed a weakly significant trend (p=0.04) of benefit for nonfatal MI, while DHA and total omega-3 PUFA were unquestionably nonsignificant. Still, he said, given the "borderline" p value for EPA, "maybe none of them are significantly associated" with respect to nonfatal MI.
That outcomes varied by type of omega-3 PUFA has implications for dietary recommendations as well as therapeutic preparations of omega-3 PUFA.
"I think that our results support DHA, in particular, being important for heart-disease death and leaves open the question of whether EPA . . . [has] additional benefit." Consuming both together is probably wise, as there appear to be "complementary effects," Mozaffarian said. Based on the current analysis, "If you're going to consume omega-3s, you should at least be sure you're getting DHA. EPA alone might not have the same benefit; I think that's fair to say."
The CHS enrolled 5201 adults aged >65 years in four US communities, two in the East and one in California from 1989 to 1990, plus 687 additional African Americans from 1992 to 1993. The current analysis includes 2692 without CHD, stroke, or heart failure at baseline who were not taking fish-oil supplements and in whom levels of plasma phospholipid omega-3 PUFA were measured in 1992–1993. Their mean age at baseline was 74 years, 64% were women, and 88% were white; they were followed until 2000.
The adjusted hazard ratio (HR) for total mortality was 0.83 for the highest quintile of EPA vs the lowest quintile (p=0.005), 0.80 for DHA (p=0.006), and 0.73 for total omega-3 PUFA (p<0.001).
Decreases in HR for total heart-disease mortality were significant only for DHA (p=0.003) and total omega-3 PUFA (p=0.002). The same was true for arrhythmic death: DHA (p=0.028) and total omega-3 PUFA (p=0.008).
Acknowledging that "this is an observational study--it doesn't prove cause and effect," Mozaffarian said that it at least supports high plasma levels of omega-3 PUFAs as directly affecting survival. "If there was confounding--if it was just that people were more educated or had healthy lifestyles--you'd expect that higher [omega-3 PUFA plasma levels] would relate very similarly to a lower risk of every kind of death: [including] respiratory death, infectious death, cancer death, and stroke death. But the bulk of the association seems to be from heart-disease death, and [especially] heart disease death from arrhythmia."
As for the possible advantage high plasma DHA levels may have over high EPA levels with respect to total and heart-disease mortality, which would conceivably conflict with the higher elevations in LDL cholesterol observed with DHA vs EPA supplementation, Mozaffarian said doesn't see a paradox.
"The LDL-raising effect of omega-3s is very modest." If there is any such effect, he said, "it's to make the particles larger and fluffier and therefore potentially less atherogenic." According to Mozaffarian, "it's just hype" to say that an omega-3 PUFA supplement that delivers only EPA should be preferred over a mixed EPA/DHA supplement because of a difference in LDL effects.
In addition to many brands of nonprescription mixed EPA/DHA supplements on the market, in the US there is the prescription-only mixed formulation Lovaza (GlaxoSmithKline); and just last year, the FDAapproved the synthetic EPA-only preparation Vascepa (Amarin), which contains ethyl eicosapentaenoic acid.
In comparisons of the highest quintile of omega-3 PUFA levels vs the lowest quintile, all-cause mortality fell by 27%, with most of the benefit due to a reduction in cardiovascular death. The rate of arrhythmic death, in particular, fell by nearly one-half.
Such cardiovascular-outcome effects are consistent with abundant evidence from laboratory and clinical studies that omega-3 PUFA intake may benefit heart rate, blood pressure, myocardial contractile function and electrical stability, and endothelial, autonomic, and hemostatic function, write the study's authors, led by Dr Dariush Mozaffarian (Harvard School of Public Health, Boston, MA). Their analysis was published in the April 2, 2013 issue of the Annals of Internal Medicine.
The CHS longitudinal data allowed the group not only to link plasma omega-3 PUFA levels with survival, Mozaffarian told heartwire , it allowed them to estimate the benefit: in this population, starting at age 65, he said, about 2.2 extra years for people in the highest compared with the lowest plasma-level quintile.
Outcomes also varied by individual omega-3 PUFAs. For a number of end points, importantly heart-disease mortality and arrhythmic mortality, there was a pattern of greater benefit from highest levels of docosahexaenoicacid (DHA) vs highest levels of eicosapentaenoic acid (EPA) and an even greater benefit from highest levels of total omega-3 PUFA.
For the end point of heart-disease death, "DHA seems to have stronger association" than EPA, according to Mozaffarian; the effect, he noted, appears to be dominated by a difference in arrhythmic death. But EPA at the highest levels vs the lowest levels showed a weakly significant trend (p=0.04) of benefit for nonfatal MI, while DHA and total omega-3 PUFA were unquestionably nonsignificant. Still, he said, given the "borderline" p value for EPA, "maybe none of them are significantly associated" with respect to nonfatal MI.
That outcomes varied by type of omega-3 PUFA has implications for dietary recommendations as well as therapeutic preparations of omega-3 PUFA.
"I think that our results support DHA, in particular, being important for heart-disease death and leaves open the question of whether EPA . . . [has] additional benefit." Consuming both together is probably wise, as there appear to be "complementary effects," Mozaffarian said. Based on the current analysis, "If you're going to consume omega-3s, you should at least be sure you're getting DHA. EPA alone might not have the same benefit; I think that's fair to say."
The CHS enrolled 5201 adults aged >65 years in four US communities, two in the East and one in California from 1989 to 1990, plus 687 additional African Americans from 1992 to 1993. The current analysis includes 2692 without CHD, stroke, or heart failure at baseline who were not taking fish-oil supplements and in whom levels of plasma phospholipid omega-3 PUFA were measured in 1992–1993. Their mean age at baseline was 74 years, 64% were women, and 88% were white; they were followed until 2000.
The adjusted hazard ratio (HR) for total mortality was 0.83 for the highest quintile of EPA vs the lowest quintile (p=0.005), 0.80 for DHA (p=0.006), and 0.73 for total omega-3 PUFA (p<0.001).
Decreases in HR for total heart-disease mortality were significant only for DHA (p=0.003) and total omega-3 PUFA (p=0.002). The same was true for arrhythmic death: DHA (p=0.028) and total omega-3 PUFA (p=0.008).
Acknowledging that "this is an observational study--it doesn't prove cause and effect," Mozaffarian said that it at least supports high plasma levels of omega-3 PUFAs as directly affecting survival. "If there was confounding--if it was just that people were more educated or had healthy lifestyles--you'd expect that higher [omega-3 PUFA plasma levels] would relate very similarly to a lower risk of every kind of death: [including] respiratory death, infectious death, cancer death, and stroke death. But the bulk of the association seems to be from heart-disease death, and [especially] heart disease death from arrhythmia."
As for the possible advantage high plasma DHA levels may have over high EPA levels with respect to total and heart-disease mortality, which would conceivably conflict with the higher elevations in LDL cholesterol observed with DHA vs EPA supplementation, Mozaffarian said doesn't see a paradox.
"The LDL-raising effect of omega-3s is very modest." If there is any such effect, he said, "it's to make the particles larger and fluffier and therefore potentially less atherogenic." According to Mozaffarian, "it's just hype" to say that an omega-3 PUFA supplement that delivers only EPA should be preferred over a mixed EPA/DHA supplement because of a difference in LDL effects.
In addition to many brands of nonprescription mixed EPA/DHA supplements on the market, in the US there is the prescription-only mixed formulation Lovaza (GlaxoSmithKline); and just last year, the FDAapproved the synthetic EPA-only preparation Vascepa (Amarin), which contains ethyl eicosapentaenoic acid.
Source: http://www.medscape.com/viewarticle/781931?nlid=30099_1301&src=wnl_edit_dail
Dietary nitrate in beet lowers blood pressure
A small, proof-of-principle study has demonstrated that the blood-pressure lowering effects of dietary nitrates--already documented in normotensives--are also seen in subjects with established hypertension[1].
Dr Amrita Ahluwalia (Barts and the London School of Medicine and Dentistry, UK) and colleagues have a track record of studying the interaction between dietary sources of biologically inert nitrate (NO3) and oral microflora, which converts the NO3 into bioactive nitrite (NO2). Circulating NO2 is known to cause vasodilation and lower blood pressure. Ahluwalia et al have previously proposed a pathway for nitrate-nitrite conversion, showing that beet juice, after coming into contact with human saliva, increases levels of plasma nitrate and nitrite, and leads to significant blood-pressure decreases in healthy volunteers.
In their latest study, published online April 15, 2013 in Hypertension, Ahluwalia and colleagues, including senior author Dr Suborno Ghosh (Queen Mary University of London, UK) turned again to beetroot, which, along with green leafy vegetables, has high concentrations of inorganic nitrate. In a mouse model of hypertension, investigators first established a threshold nitrite dose at which blood pressure decreased in the hypertensive mice, but not in normotensive control mice. At higher doses, however, both strains of mice saw blood-pressure decreases.
The authors then tested the beet-juice effects in 15 hypertensive, drug-naive patients, randomized to either 250ml of inorganic nitrate-rich beetroot juice or an equal volume of water. The "dose" of juice elevates nitrite levels approximately 1.5 fold--a rise previously shown to have no significant BP-lowering effect in subjects with normal blood pressure.
In patients who drank the juice, systolic blood pressure dropped by a mean of 11.2 mm Hg between three and six hours after consumption (vs 0.7 mm Hg in subjects who drank water). By 24 hours, clinic systolic BP remained significantly lower in the beet-juice group and roughly 7.2 mm Hg lower than baseline. Peak drop in diastolic BP also occurred within the first six hours, dropping by a mean of 9.6 mm Hg. Pulse-wave velocity also decreased in the beet-juice group, but not in the controls.
"Our observations . . . support the concept of dietary nitrate supplementation as an effective, but simple and inexpensive, antihypertensive strategy," the authors conclude.
Ahluwalia underscored the finding that nitrate in beets appears to be even more potent in hypertensives than in normotensives. "In this new study we used a dose that had little to no effect upon blood pressure in healthy volunteers; in contrast, this dose caused a substantial decrease in blood pressure (~12 mm Hg) in the patients, suggesting that dietary nitrate is more potent, and therefore potentially one needs less to produce an important blood-pressure–lowering effect."
She added: "It is also true that while we all know that eating fruits and vegetables is good for the cardiovascular system, exactly why this is the case is not certain. Studies have shown that of all the different fruit and vegetables out there it is the green leafy vegetables that provide the greatest protection against heart attacks and strokes. What is true about these vegetables is that they represent the major source of nitrate in our diet."
She also stressed the limitations of the study: while "impressive," the BP-lowering effects of beet juice consumption were measured only over 24 hours and in very small numbers. "Whether this effect can be sustained in the long term is not yet known, and further clinical studies that assess the effects over longer periods of time and in larger cohorts are needed," she said.
Dr Amrita Ahluwalia (Barts and the London School of Medicine and Dentistry, UK) and colleagues have a track record of studying the interaction between dietary sources of biologically inert nitrate (NO3) and oral microflora, which converts the NO3 into bioactive nitrite (NO2). Circulating NO2 is known to cause vasodilation and lower blood pressure. Ahluwalia et al have previously proposed a pathway for nitrate-nitrite conversion, showing that beet juice, after coming into contact with human saliva, increases levels of plasma nitrate and nitrite, and leads to significant blood-pressure decreases in healthy volunteers.
In their latest study, published online April 15, 2013 in Hypertension, Ahluwalia and colleagues, including senior author Dr Suborno Ghosh (Queen Mary University of London, UK) turned again to beetroot, which, along with green leafy vegetables, has high concentrations of inorganic nitrate. In a mouse model of hypertension, investigators first established a threshold nitrite dose at which blood pressure decreased in the hypertensive mice, but not in normotensive control mice. At higher doses, however, both strains of mice saw blood-pressure decreases.
The authors then tested the beet-juice effects in 15 hypertensive, drug-naive patients, randomized to either 250ml of inorganic nitrate-rich beetroot juice or an equal volume of water. The "dose" of juice elevates nitrite levels approximately 1.5 fold--a rise previously shown to have no significant BP-lowering effect in subjects with normal blood pressure.
In patients who drank the juice, systolic blood pressure dropped by a mean of 11.2 mm Hg between three and six hours after consumption (vs 0.7 mm Hg in subjects who drank water). By 24 hours, clinic systolic BP remained significantly lower in the beet-juice group and roughly 7.2 mm Hg lower than baseline. Peak drop in diastolic BP also occurred within the first six hours, dropping by a mean of 9.6 mm Hg. Pulse-wave velocity also decreased in the beet-juice group, but not in the controls.
"Our observations . . . support the concept of dietary nitrate supplementation as an effective, but simple and inexpensive, antihypertensive strategy," the authors conclude.
Ahluwalia underscored the finding that nitrate in beets appears to be even more potent in hypertensives than in normotensives. "In this new study we used a dose that had little to no effect upon blood pressure in healthy volunteers; in contrast, this dose caused a substantial decrease in blood pressure (~12 mm Hg) in the patients, suggesting that dietary nitrate is more potent, and therefore potentially one needs less to produce an important blood-pressure–lowering effect."
She added: "It is also true that while we all know that eating fruits and vegetables is good for the cardiovascular system, exactly why this is the case is not certain. Studies have shown that of all the different fruit and vegetables out there it is the green leafy vegetables that provide the greatest protection against heart attacks and strokes. What is true about these vegetables is that they represent the major source of nitrate in our diet."
She also stressed the limitations of the study: while "impressive," the BP-lowering effects of beet juice consumption were measured only over 24 hours and in very small numbers. "Whether this effect can be sustained in the long term is not yet known, and further clinical studies that assess the effects over longer periods of time and in larger cohorts are needed," she said.
Source: http://www.medscape.com/viewarticle/782590?nlid=30483_1301&src=wnl_edit_dail
Friday 12 April 2013
Carnitine in red meat ups atherosclerosis risk via gut flora
Research in mice and human volunteers has suggested a mechanism that may contribute to an association between eating red meat and increased risk of cardiovascular disease[1]. It involves microbes in the gut.
People who regularly eat red meat have an increased colonization of intestinal bacteria that break down the carnitine in red meat into a metabolite that promotes increased cholesterol deposition in the artery wall, the researchers report. Their study was published online April 7, 2013 inNature Medicine.
Energy drinks are another major source of carnitine. If someone regularly eats red meat or drinks energy drinks, "microbes that like carnitine become more abundant [in the gut], and now you are much more capable of making this metabolite . . . trimethylamine-N-oxide (TMAO)," he said. "This paper showed [that TMAO] . . . essentially leads to an enhanced capacity to deposit cholesterol on the cells of your artery wall."
Previously, the researchers showed that dietary choline and phosphatidylcholine (lecithin) are metabolized in mice and humans by intestinal microbes to produce trimethylamine, which is rapidly metabolized to TMAO, which is linked to accelerated atherosclerosis. Hypothesizing that carnitine, which has a similar molecular structure to choline, behaves this way, the researchers performed a series of experiments.
Carnitine linked to TMAO levels
First, they showed, for what they believe is the first time, that humans need gut microbes to form TMAO from dietary carnitine. After an overnight fast, volunteer omnivores were given a carnitine challenge--they were fed a capsule of carnitine plus an 8-oz sirloin steak--and their TMAO plasma and urine levels were measured. The volunteers were then given oral, broad-spectrum antibiotics for a week to suppress their gut microbes, after which they received a second carnitine challenge. Then after three weeks to allow their gut organisms to repopulate, they received a third carnitine challenge. Their TMAO levels were almost undetectable after the antibiotic regimen, but the levels rebounded after their gut flora repopulated.
The researchers also showed that after ingesting carnitine capsules, vegans and vegetarians produced markedly lower levels of TMAO than omnivores.
TMAO, not carnitine, drives CVD
Next, in a cohort of 2595 subjects undergoing elective cardiovascular evaluation, the researchers determined that increased plasma carnitine was associated with increased risk of having or soon developing CAD, peripheral artery disease (PAD), or other CVD. However, after adjustment for traditional cardiovascular risk factors, an elevated carnitine concentration predicted a higher three-year risk of MI, stroke, or death only in subjects with high plasma TMAO levels. Thus TMAO, not carnitine, drives the cardiovascular outcomes, the researchers conclude.
Their mouse studies suggest a possible, multifaceted mechanism for the development of atherosclerosis. In mice, dietary carnitine promoted cholesterol buildup in the artery wall, which was completely inhibited after treatment with an antibiotic cocktail. In other mice with intact intestinal microbes, receiving TMAO and carnitine or lecithin led to inhibition of the reverse cholesterol transport pathway.
For now, eat well; in future, also take a pill?
Does this mean that physicians should advise all their patients to become vegetarians and avoid drinking energy drinks? Hazen says that people need to be aware that "a can of an energy drink can have more carnitine than a porterhouse steak." Carnitine is obtained from many sources, since it is derived from lysine, the most abundant amino acid in animal and vegetable protein in the diet, he noted.
For now, "it makes sense to adhere to a lower-cholesterol, lower-saturated-fat diet [that will be] more heart healthy in terms of decreasing the nutrients that give rise to forming TMAO, [since] this may be one of the hidden contributors to heart disease."
In the future, there might be a TMAO test and a drug that targets TMAO, Hazen speculated. "Measuring TMAO can be a very strong predictor of cardiovascular risk, and it will become a test that is available for clinical use in the future," he hypothesized. "Down the road, we think we are going to be able to go after this, just like we take a statin . . . to decrease the [risk of] development of heart disease."
Source: http://www.medscape.com/viewarticle/782236?nlid=30183_1301&src=wnl_edit_dail
People who regularly eat red meat have an increased colonization of intestinal bacteria that break down the carnitine in red meat into a metabolite that promotes increased cholesterol deposition in the artery wall, the researchers report. Their study was published online April 7, 2013 inNature Medicine.
Energy drinks are another major source of carnitine. If someone regularly eats red meat or drinks energy drinks, "microbes that like carnitine become more abundant [in the gut], and now you are much more capable of making this metabolite . . . trimethylamine-N-oxide (TMAO)," he said. "This paper showed [that TMAO] . . . essentially leads to an enhanced capacity to deposit cholesterol on the cells of your artery wall."
Previously, the researchers showed that dietary choline and phosphatidylcholine (lecithin) are metabolized in mice and humans by intestinal microbes to produce trimethylamine, which is rapidly metabolized to TMAO, which is linked to accelerated atherosclerosis. Hypothesizing that carnitine, which has a similar molecular structure to choline, behaves this way, the researchers performed a series of experiments.
Carnitine linked to TMAO levels
First, they showed, for what they believe is the first time, that humans need gut microbes to form TMAO from dietary carnitine. After an overnight fast, volunteer omnivores were given a carnitine challenge--they were fed a capsule of carnitine plus an 8-oz sirloin steak--and their TMAO plasma and urine levels were measured. The volunteers were then given oral, broad-spectrum antibiotics for a week to suppress their gut microbes, after which they received a second carnitine challenge. Then after three weeks to allow their gut organisms to repopulate, they received a third carnitine challenge. Their TMAO levels were almost undetectable after the antibiotic regimen, but the levels rebounded after their gut flora repopulated.
The researchers also showed that after ingesting carnitine capsules, vegans and vegetarians produced markedly lower levels of TMAO than omnivores.
TMAO, not carnitine, drives CVD
Next, in a cohort of 2595 subjects undergoing elective cardiovascular evaluation, the researchers determined that increased plasma carnitine was associated with increased risk of having or soon developing CAD, peripheral artery disease (PAD), or other CVD. However, after adjustment for traditional cardiovascular risk factors, an elevated carnitine concentration predicted a higher three-year risk of MI, stroke, or death only in subjects with high plasma TMAO levels. Thus TMAO, not carnitine, drives the cardiovascular outcomes, the researchers conclude.
Their mouse studies suggest a possible, multifaceted mechanism for the development of atherosclerosis. In mice, dietary carnitine promoted cholesterol buildup in the artery wall, which was completely inhibited after treatment with an antibiotic cocktail. In other mice with intact intestinal microbes, receiving TMAO and carnitine or lecithin led to inhibition of the reverse cholesterol transport pathway.
For now, eat well; in future, also take a pill?
Does this mean that physicians should advise all their patients to become vegetarians and avoid drinking energy drinks? Hazen says that people need to be aware that "a can of an energy drink can have more carnitine than a porterhouse steak." Carnitine is obtained from many sources, since it is derived from lysine, the most abundant amino acid in animal and vegetable protein in the diet, he noted.
For now, "it makes sense to adhere to a lower-cholesterol, lower-saturated-fat diet [that will be] more heart healthy in terms of decreasing the nutrients that give rise to forming TMAO, [since] this may be one of the hidden contributors to heart disease."
In the future, there might be a TMAO test and a drug that targets TMAO, Hazen speculated. "Measuring TMAO can be a very strong predictor of cardiovascular risk, and it will become a test that is available for clinical use in the future," he hypothesized. "Down the road, we think we are going to be able to go after this, just like we take a statin . . . to decrease the [risk of] development of heart disease."
Source: http://www.medscape.com/viewarticle/782236?nlid=30183_1301&src=wnl_edit_dail
Thursday 4 April 2013
Green tea and coffee protects against stroke
Green tea and coffee consumption may help protect against stroke, according to a large Japanese population-based study.
The study showed that people who drank green tea or coffee regularly had about a 20% lower risk for stroke than their peers who seldom drank these beverages.
"This is the first large-scale study to examine the combined effects of both green tea and coffee on stroke risks," Yoshihiro Kokubo, MD, PhD, head of the Department of Preventive Cardiology, National Cerebral and Cardiovascular Center in Osaka, said in a statement.
Their findings were published online March 14 in Stroke.
Inverse link
The study involved 82,369 Japanese adults aged 45 to 65 years without cardiovascular disease or cancer at baseline who were followed for a mean of 13 years. "Green tea and coffee consumption was assessed by self-administered food-frequency questionnaire at baseline," Dr. Kokubo toldMedscape Medical News.
During more than 1 million person-years of follow-up, the researchers documented 3425 strokes (1964 cerebral infarctions, 1001 intracerebral hemorrhages, and 460 subarachnoid hemorrhages) and 910 coronary heart disease (CHD) events (489 definite myocardial infarctions and 28 sudden cardiac deaths).
In multivariate analysis, higher coffee and green tea consumption were inversely associated with risk for cardiovascular disease (CVD) and stroke.
For example, people who drank at least 1 cup of coffee daily had a 20% lower risk for any stroke (adjusted hazard ratio [aHR], 0.80; 95% confidence interval [CI], 0.72 - 0.90) compared with those who seldom drank coffee.
People who drank 2 to 3 cups of green tea daily had a 14% lower risk for any stroke (aHR, 0.86; 95% CI, 0.78 - 0.95), and those who consumed at least 4 cups had a 20% lower risk (aHR, 0.80; 95% CI, 0.73 - 0.89), compared with those who seldom drank green tea.
The risk reduction for intracerebral hemorrhage was 17% (aHR, 0.83; 95% CI, 0.68 - 1.02) with consumption of at least 1 cup of coffee daily and 23% (aHR, 0.77; 95% CI, 0.63 - 0.92) for 2 cups of green tea daily compared with rare consumption of either beverage.
There was no significant association between coffee and tea consumption and CHD, largely mirroring findings from other studies.
Experts weigh in
Victoria J. Burley, PhD, senior lecturer in nutritional epidemiology, School of Food Science and Nutrition, University of Leeds, United Kingdom, who wasn't involved in the study, called it "very interesting."
She noted that "both high-fiber foods and these particular beverages may have anti-inflammatory properties. Whole grains, fruit and vegetables, and these beverages are all rich in polyphenols, which appear to have multiple potential actions on markers of CVD risk: blood pressure, glucose homeostasis, lipid metabolism, and so on."
"This appears to be a well-conducted study," Dr. Burley said, "with good power (plenty of cases), with long follow-up and a respectable method of assessing green tea and coffee intake (for these dietary aspects I think an FFQ [food-frequency questionnaire] is likely the best approach)."
She cautioned, however, that the intakes of green tea in this Japanese cohort "far exceed" usual consumption in western populations and that, conversely, intakes of coffee may generally be somewhat lower in Japan.
"The highest coffee intake category was 2-3 cups per day, which is not particularly high. Other studies (eg, conducted in Sweden) have reported elevated CVD risk in people with much higher intakes ( > 7 cups per day), so in setting their highest category this low these study authors may not have been able to pick up evidence of increased CVD risk with greater intakes," Dr. Burley said.
"Overall, it's encouraging data that suggest people who incorporate coffee and green tea in their diet may experience lower CVD risk in later life," she added.
Commenting on the coffee findings, Susanna C. Larsson, PhD, from the Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, found it "interesting that such a small amount as 1 cup of coffee per day reduces the risk of stroke by 20% (quite a large reduction in risk)."
"Otherwise, this Japanese study confirms results from studies conducted in the US and Europe showing an inverse association between coffee consumption and stroke risk. This study adds further support that moderate coffee consumption may lower the risk of stroke," said Dr. Larsson, who was not involved in the study.
The study showed that people who drank green tea or coffee regularly had about a 20% lower risk for stroke than their peers who seldom drank these beverages.
"This is the first large-scale study to examine the combined effects of both green tea and coffee on stroke risks," Yoshihiro Kokubo, MD, PhD, head of the Department of Preventive Cardiology, National Cerebral and Cardiovascular Center in Osaka, said in a statement.
Their findings were published online March 14 in Stroke.
Inverse link
The study involved 82,369 Japanese adults aged 45 to 65 years without cardiovascular disease or cancer at baseline who were followed for a mean of 13 years. "Green tea and coffee consumption was assessed by self-administered food-frequency questionnaire at baseline," Dr. Kokubo toldMedscape Medical News.
During more than 1 million person-years of follow-up, the researchers documented 3425 strokes (1964 cerebral infarctions, 1001 intracerebral hemorrhages, and 460 subarachnoid hemorrhages) and 910 coronary heart disease (CHD) events (489 definite myocardial infarctions and 28 sudden cardiac deaths).
In multivariate analysis, higher coffee and green tea consumption were inversely associated with risk for cardiovascular disease (CVD) and stroke.
For example, people who drank at least 1 cup of coffee daily had a 20% lower risk for any stroke (adjusted hazard ratio [aHR], 0.80; 95% confidence interval [CI], 0.72 - 0.90) compared with those who seldom drank coffee.
People who drank 2 to 3 cups of green tea daily had a 14% lower risk for any stroke (aHR, 0.86; 95% CI, 0.78 - 0.95), and those who consumed at least 4 cups had a 20% lower risk (aHR, 0.80; 95% CI, 0.73 - 0.89), compared with those who seldom drank green tea.
The risk reduction for intracerebral hemorrhage was 17% (aHR, 0.83; 95% CI, 0.68 - 1.02) with consumption of at least 1 cup of coffee daily and 23% (aHR, 0.77; 95% CI, 0.63 - 0.92) for 2 cups of green tea daily compared with rare consumption of either beverage.
There was no significant association between coffee and tea consumption and CHD, largely mirroring findings from other studies.
Experts weigh in
Victoria J. Burley, PhD, senior lecturer in nutritional epidemiology, School of Food Science and Nutrition, University of Leeds, United Kingdom, who wasn't involved in the study, called it "very interesting."
She noted that "both high-fiber foods and these particular beverages may have anti-inflammatory properties. Whole grains, fruit and vegetables, and these beverages are all rich in polyphenols, which appear to have multiple potential actions on markers of CVD risk: blood pressure, glucose homeostasis, lipid metabolism, and so on."
"This appears to be a well-conducted study," Dr. Burley said, "with good power (plenty of cases), with long follow-up and a respectable method of assessing green tea and coffee intake (for these dietary aspects I think an FFQ [food-frequency questionnaire] is likely the best approach)."
She cautioned, however, that the intakes of green tea in this Japanese cohort "far exceed" usual consumption in western populations and that, conversely, intakes of coffee may generally be somewhat lower in Japan.
"The highest coffee intake category was 2-3 cups per day, which is not particularly high. Other studies (eg, conducted in Sweden) have reported elevated CVD risk in people with much higher intakes ( > 7 cups per day), so in setting their highest category this low these study authors may not have been able to pick up evidence of increased CVD risk with greater intakes," Dr. Burley said.
"Overall, it's encouraging data that suggest people who incorporate coffee and green tea in their diet may experience lower CVD risk in later life," she added.
Commenting on the coffee findings, Susanna C. Larsson, PhD, from the Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, found it "interesting that such a small amount as 1 cup of coffee per day reduces the risk of stroke by 20% (quite a large reduction in risk)."
"Otherwise, this Japanese study confirms results from studies conducted in the US and Europe showing an inverse association between coffee consumption and stroke risk. This study adds further support that moderate coffee consumption may lower the risk of stroke," said Dr. Larsson, who was not involved in the study.
Wednesday 3 April 2013
Physical therapy as effective as surgery for meniscal tear
Patients with knee osteoarthritis and a meniscal tear who received physical therapy without surgery had good functional improvement 6 months later, and outcomes did not differ significantly from patients who underwent arthroscopic partial meniscectomy, a new clinical trial shows.
In the Meniscal Tear in Osteoarthritis Research (METEOR) trial, both groups of patients improved substantially in function and pain.
This finding, presented here at the American Academy of Orthopaedic Surgeons 2013 Annual Meeting and published online simultaneously in the New England Journal of Medicine, provides "considerable reassurance regarding an initial nonoperative strategy," the investigators report.
Patients with a meniscal tear and osteoarthritis pose a treatment challenge because it is not clear which condition is causing their symptoms," principal investigator Jeffrey Katz, MD, from Brigham and Women's Hospital in Boston, Massachusetts, told Medscape Medical News.
"These data suggest that there are 2 reasonable pathways for patients with knee arthritis and meniscal tear," Dr. Katz explained. "We hope physicians will use these data to help patients understand their choices."
In an accompanying editorial, clinical epidemiologist Rachelle Buchbinder, PhD, from the Monash University School of Public Health and Preventive Medicine in Victoria, Australia, said that "these results should change practice. Currently, millions of people are being exposed to potential risks associated with a [surgical] treatment that may or may not offer specific benefit, and the costs are substantial."
These results should change practice.
The METEOR trial enrolled 351 patients from 7 medical centers in the United States. Eligible patients were older than 45 years, had osteoarthritic cartilage change documented with magnetic resonance imaging, and had at least 1 symptom of meniscal tear, such as knee clicking or giving way, that lasted at least 1 month despite drug treatment, physical therapy, or limited activity.
In this intent-to-treat analysis, investigators randomly assigned 174 patients to arthroscopic partial meniscectomy plus postoperative physical therapy and 177 to physical therapy alone.
The physical therapy in both regimens was a standardized 3-stage program that allowed patients to advance to the next intensity level at their own pace, Dr. Katz explained. The program involved 1 or 2 sessions a week for about 6 weeks and home exercises. The average number of physical therapy visits was 7 in the surgery group and 8 in the nonsurgery group.
Investigators evaluated patients 6 and 12 months after randomization. The primary outcome was the between-group difference in change in physical function score from baseline to 6 months, assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). At baseline, demographic characteristics and WOMAC physical function scores were similar in the 2 groups.
At 6 months, improvement in the WOMAC function score was comparable in the 2 groups. The mean between-group difference of 2.4 points was not statistically significant after analysis of covariance. There was also no significant difference between groups in pain improvement or frequency of adverse events.
There was 1 death in each group, and 8 patients in the nonsurgery group and 13 in the surgery group withdrew in the first 6 months of the study.
Patients in the nonsurgery group were allowed to cross over to the surgical group at any time. Within 6 months, 30% of patients did so.
"They were not doing very well," Dr. Katz said. His team is still analyzing the reasons these patients did not benefit from intensive physical therapy.
The 12-month results were similar to the 6-month results. In addition, by 12 months, outcomes for the crossover patients and for those in the original surgery group were similar.
Meeting delegate John Mays, MD, an orthopaedic surgeon practicing in Bossier City, Louisiana, who was asked by Medscape Medical News to comment on the findings, said most patients don't choose physical therapy. "In the real world, most people want a quick fix" and choose surgery, he noted.
Dr. Mays said he would have liked to have seen a group of patients who underwent surgery but did not receive postoperative physical therapy. He explained that his patients with osteoarthritis and meniscal tear rarely get physical therapy after arthroscopic meniscectomy; they most often do home-based exercises.
He added that "most insurance plans have limits on the number of physical therapy sessions they allow."
In the Meniscal Tear in Osteoarthritis Research (METEOR) trial, both groups of patients improved substantially in function and pain.
This finding, presented here at the American Academy of Orthopaedic Surgeons 2013 Annual Meeting and published online simultaneously in the New England Journal of Medicine, provides "considerable reassurance regarding an initial nonoperative strategy," the investigators report.
Patients with a meniscal tear and osteoarthritis pose a treatment challenge because it is not clear which condition is causing their symptoms," principal investigator Jeffrey Katz, MD, from Brigham and Women's Hospital in Boston, Massachusetts, told Medscape Medical News.
"These data suggest that there are 2 reasonable pathways for patients with knee arthritis and meniscal tear," Dr. Katz explained. "We hope physicians will use these data to help patients understand their choices."
In an accompanying editorial, clinical epidemiologist Rachelle Buchbinder, PhD, from the Monash University School of Public Health and Preventive Medicine in Victoria, Australia, said that "these results should change practice. Currently, millions of people are being exposed to potential risks associated with a [surgical] treatment that may or may not offer specific benefit, and the costs are substantial."
These results should change practice.
The METEOR trial enrolled 351 patients from 7 medical centers in the United States. Eligible patients were older than 45 years, had osteoarthritic cartilage change documented with magnetic resonance imaging, and had at least 1 symptom of meniscal tear, such as knee clicking or giving way, that lasted at least 1 month despite drug treatment, physical therapy, or limited activity.
In this intent-to-treat analysis, investigators randomly assigned 174 patients to arthroscopic partial meniscectomy plus postoperative physical therapy and 177 to physical therapy alone.
The physical therapy in both regimens was a standardized 3-stage program that allowed patients to advance to the next intensity level at their own pace, Dr. Katz explained. The program involved 1 or 2 sessions a week for about 6 weeks and home exercises. The average number of physical therapy visits was 7 in the surgery group and 8 in the nonsurgery group.
Investigators evaluated patients 6 and 12 months after randomization. The primary outcome was the between-group difference in change in physical function score from baseline to 6 months, assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). At baseline, demographic characteristics and WOMAC physical function scores were similar in the 2 groups.
At 6 months, improvement in the WOMAC function score was comparable in the 2 groups. The mean between-group difference of 2.4 points was not statistically significant after analysis of covariance. There was also no significant difference between groups in pain improvement or frequency of adverse events.
There was 1 death in each group, and 8 patients in the nonsurgery group and 13 in the surgery group withdrew in the first 6 months of the study.
Patients in the nonsurgery group were allowed to cross over to the surgical group at any time. Within 6 months, 30% of patients did so.
"They were not doing very well," Dr. Katz said. His team is still analyzing the reasons these patients did not benefit from intensive physical therapy.
The 12-month results were similar to the 6-month results. In addition, by 12 months, outcomes for the crossover patients and for those in the original surgery group were similar.
Meeting delegate John Mays, MD, an orthopaedic surgeon practicing in Bossier City, Louisiana, who was asked by Medscape Medical News to comment on the findings, said most patients don't choose physical therapy. "In the real world, most people want a quick fix" and choose surgery, he noted.
Dr. Mays said he would have liked to have seen a group of patients who underwent surgery but did not receive postoperative physical therapy. He explained that his patients with osteoarthritis and meniscal tear rarely get physical therapy after arthroscopic meniscectomy; they most often do home-based exercises.
He added that "most insurance plans have limits on the number of physical therapy sessions they allow."
Source: http://www.medscape.com/viewarticle/781102?nlid=29464_1301&src=wnl_edit_dail
Women with low melatonin levels more likely to develop type 2 diabetes
Women secreting low levels of melatonin are more likely to develop type 2 diabetes than those who have higher levels of this hormone, new observational research shows.
"This case-control study is the first prospective evaluation of the link between melatonin secretion and type 2 diabetes and demonstrates an independent association between the 2," lead author Ciaran J. McMullan, MD, from Brigham and Women's Hospital, Boston, Massachusetts, told Medscape Medical News. He and his colleagues report their findings in the April 3 issue of the Journal of the American Medical Association.
"What's fascinating is that cases of diabetes had lower levels of melatonin secretion than controls," Dr. McMullan noted, "and when we compared the lowest category of melatonin secretion with the highest, they had double the risk of diabetes, even after adjustment for many potential confounding factors.
"We've shown that [melatonin] is a risk factor, but we are really interested to see whether it is a modifiable risk factor," he added, noting that the clinical relevance of these findings is currently "unclear; this won't change clinical practice, but it causes us to ask 2 important questions."
First, it should stimulate more research into what can influence melatonin secretion, he said, and second, "if we were to change an individual's melatonin secretion or melatonin levels, do we then change their risk of developing type 2 diabetes?"
Dr. McMullan said the next logical step would be to conduct further studies to see whether increasing melatonin levels — either endogenously via prolonged nighttime dark exposure or exogenously via supplementation — can increase insulin sensitivity and decrease the incidence of type 2 diabetes.
Melatonin levels lower in diabetes cases than controls
Dr. McMullan and colleagues explain that the pineal gland secretes melatonin in response to light exposure, following a diurnal pattern, with levels typically peaking 3 to 5 hours after sleep onset when it is dark. During daylight hours, there is almost no production of melatonin.
Melatonin receptors have been found throughout the body, including in pancreatic islet cells, and several lines of evidence — including animal work and human genomewide-association studies — suggest that the hormone may play a role in glucose metabolism. There have also been a number of cross-sectional studies in humans suggesting a protective effect of melatonin regarding diabetes development, but these have been small "and difficult to interpret," said Dr. McMullan.
In their prospective study, the researchers assessed participants in the Nurses' Health Study who, at baseline in 2000, did not have diabetes and who had provided blood and urine samples. They then identified 370 women who developed type 2 diabetes (self-reported) from 2000 to 2012 and matched them with 370 controls.
Associations between melatonin secretion at baseline — determined from morning urine samples — and incidence of type 2 diabetes were evaluated after researchers controlled for demographic characteristics, lifestyle habits, measures of sleep quality, and biomarkers of inflammation and endothelial dysfunction.
The median urinary ratios of 6-sulfatoxymelatonin to creatinine were 28.2 ng/mg among cases of diabetes and 36.3 ng/mg among controls.
Compared with women in the highest category of 6-sulfatoxymelatonin/creatinine ratio, those in the lowest category had an odds ratio of 2.17 of developing type 2 diabetes.
In absolute terms, the estimated diabetes incidence rate was 9.27 cases/1000 person-years among those in the lowest category of melatonin secretion compared with 4.27 cases/1000 person-years among women in the highest category.
Sleep disruption did not affect association
Dr. McMullan and colleagues note that sleep disruption has also previously been associated with type 2 diabetes. In one study, men who slept less than 5 hours per night were twice as likely to develop diabetes as those who reported sleeping 7 hours a night. Similarly, women who reported snoring on a regular basis were 2.2 times more likely to develop diabetes than women who never snored, even after adjustment for adiposity.
"Consistent with these prior studies, both short sleep duration and snoring frequency were associated with incident type 2 diabetes in our case-control study. Because sleep disruption is also associated with decreased melatonin secretion, it is possible that sleep disruption could confound the association between melatonin and diabetes," they observe.
However, adjustment for sleep duration and snoring frequency in the multivariate analysis "did not significantly alter the association of melatonin secretion with incident type 2 diabetes," they note.
Also, the nurses included in this study were, on average, around 65 years of age, so few of them were still working shifts (only around 4%), Dr. McMullan pointed out.
"This case-control study is the first prospective evaluation of the link between melatonin secretion and type 2 diabetes and demonstrates an independent association between the 2," lead author Ciaran J. McMullan, MD, from Brigham and Women's Hospital, Boston, Massachusetts, told Medscape Medical News. He and his colleagues report their findings in the April 3 issue of the Journal of the American Medical Association.
"What's fascinating is that cases of diabetes had lower levels of melatonin secretion than controls," Dr. McMullan noted, "and when we compared the lowest category of melatonin secretion with the highest, they had double the risk of diabetes, even after adjustment for many potential confounding factors.
"We've shown that [melatonin] is a risk factor, but we are really interested to see whether it is a modifiable risk factor," he added, noting that the clinical relevance of these findings is currently "unclear; this won't change clinical practice, but it causes us to ask 2 important questions."
First, it should stimulate more research into what can influence melatonin secretion, he said, and second, "if we were to change an individual's melatonin secretion or melatonin levels, do we then change their risk of developing type 2 diabetes?"
Dr. McMullan said the next logical step would be to conduct further studies to see whether increasing melatonin levels — either endogenously via prolonged nighttime dark exposure or exogenously via supplementation — can increase insulin sensitivity and decrease the incidence of type 2 diabetes.
Melatonin levels lower in diabetes cases than controls
Dr. McMullan and colleagues explain that the pineal gland secretes melatonin in response to light exposure, following a diurnal pattern, with levels typically peaking 3 to 5 hours after sleep onset when it is dark. During daylight hours, there is almost no production of melatonin.
Melatonin receptors have been found throughout the body, including in pancreatic islet cells, and several lines of evidence — including animal work and human genomewide-association studies — suggest that the hormone may play a role in glucose metabolism. There have also been a number of cross-sectional studies in humans suggesting a protective effect of melatonin regarding diabetes development, but these have been small "and difficult to interpret," said Dr. McMullan.
In their prospective study, the researchers assessed participants in the Nurses' Health Study who, at baseline in 2000, did not have diabetes and who had provided blood and urine samples. They then identified 370 women who developed type 2 diabetes (self-reported) from 2000 to 2012 and matched them with 370 controls.
Associations between melatonin secretion at baseline — determined from morning urine samples — and incidence of type 2 diabetes were evaluated after researchers controlled for demographic characteristics, lifestyle habits, measures of sleep quality, and biomarkers of inflammation and endothelial dysfunction.
The median urinary ratios of 6-sulfatoxymelatonin to creatinine were 28.2 ng/mg among cases of diabetes and 36.3 ng/mg among controls.
Compared with women in the highest category of 6-sulfatoxymelatonin/creatinine ratio, those in the lowest category had an odds ratio of 2.17 of developing type 2 diabetes.
In absolute terms, the estimated diabetes incidence rate was 9.27 cases/1000 person-years among those in the lowest category of melatonin secretion compared with 4.27 cases/1000 person-years among women in the highest category.
Sleep disruption did not affect association
Dr. McMullan and colleagues note that sleep disruption has also previously been associated with type 2 diabetes. In one study, men who slept less than 5 hours per night were twice as likely to develop diabetes as those who reported sleeping 7 hours a night. Similarly, women who reported snoring on a regular basis were 2.2 times more likely to develop diabetes than women who never snored, even after adjustment for adiposity.
"Consistent with these prior studies, both short sleep duration and snoring frequency were associated with incident type 2 diabetes in our case-control study. Because sleep disruption is also associated with decreased melatonin secretion, it is possible that sleep disruption could confound the association between melatonin and diabetes," they observe.
However, adjustment for sleep duration and snoring frequency in the multivariate analysis "did not significantly alter the association of melatonin secretion with incident type 2 diabetes," they note.
Also, the nurses included in this study were, on average, around 65 years of age, so few of them were still working shifts (only around 4%), Dr. McMullan pointed out.
Source: http://www.medscape.com/viewarticle/781819
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