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
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.
Friday, 12 April 2013
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
Energy drink consumption negatively affects heart health
Tossing back one to three energy drinks may result in more than just a buzz. A small-meta analysis found that immediately afterward, subjects had increased systolic blood pressure and, more troubling, they also had, on average, a 10-msec prolongation in their QT interval [1].
The study, by Dr Sachin Shah (University of the Pacific, Stockton, CA) and colleagues, was presented at EPI-NPAM 2013, the Epidemiology and Prevention/Nutrition, Physical Activity and Metabolism 2013 Scientific Sessions.
"The blood-pressure finding falls in line with what we would suspect because of the caffeine content," Shah told heartwire . "The QT prolongation that we are seeing--I was very surprised with that. It's a bit of a wake-up call for us investigators to start studying it a bit more thoroughly, and it needs to happen sooner rather than later."
The group aimed to see how energy drinks affect heart health, given that these drinks, along with dietary supplements, are not regulated as stringently as new drugs that must meet Food and Drug Administration (FDA) safety requirements, Shah said.
In a literature search, they identified seven observational and interventional trials that evaluated the impact of energy drinks on QT interval, blood pressure, and heart rate.
Three studies with a pooled sample of 93 subjects had QT/QTc data. Six studies with a pooled sample of 132 subjects had blood-pressure data, and seven studies investigated heart rate.
The patients, who were all young (aged 18 to 45) and healthy, underwent ECG and blood-pressure testing before and just after drinking one to three cans of energy drink--most commonly Red Bull, but also others such as Full Throttle and Meltdown RTD. An 8.4-oz can of Red Bull contains 80 mg of caffeine, compared with 35 mg of caffeine in a 12-oz Coke or about 100 mg of caffeine in an average cup of coffee, Shah said.
Shortly after drinking the energy drinks, the pooled subjects had a systolic blood pressure increase of an average 3.5 mm Hg. "If people are drinking energy drinks every day, that change in blood pressure could be very significant," Shah noted, adding that, as reported by heartwire , research on torcetrapibwas terminated because of a similar 3-mm-Hg increase in blood pressure.
People who don't normally drink coffee might have a heightened blood-pressure response to an energy drink, he added.
In a clinical setting, physicians are usually concerned if a patient has a QT-interval increase of about 30 msec from baseline, Shah noted. He acknowledges that this was a small study, but it did uncover a disturbing signal that needs to be further investigated.
Diastolic BP and heart rate increased nonsignificantly.
Although the 10-msec prolongation in the QT interval is a "small number, if it were consistently produced by a drug being considered by the FDA, the FDA would require more testing to make sure that there was not a liability for producing further, more serious, and life-threatening prolongation of the QT interval and associated arrhythmias," AHA spokesperson and past president Dr Gordon F Tomaselli (Johns Hopkins University, Baltimore, MD) commented.
Both Shah and Tomaselli pointed out that people who are older or who have underlying CVD might have even more heart-related side effects from energy drinks than the young, healthy people in this meta-analysis.
The study, by Dr Sachin Shah (University of the Pacific, Stockton, CA) and colleagues, was presented at EPI-NPAM 2013, the Epidemiology and Prevention/Nutrition, Physical Activity and Metabolism 2013 Scientific Sessions.
"The blood-pressure finding falls in line with what we would suspect because of the caffeine content," Shah told heartwire . "The QT prolongation that we are seeing--I was very surprised with that. It's a bit of a wake-up call for us investigators to start studying it a bit more thoroughly, and it needs to happen sooner rather than later."
The group aimed to see how energy drinks affect heart health, given that these drinks, along with dietary supplements, are not regulated as stringently as new drugs that must meet Food and Drug Administration (FDA) safety requirements, Shah said.
In a literature search, they identified seven observational and interventional trials that evaluated the impact of energy drinks on QT interval, blood pressure, and heart rate.
Three studies with a pooled sample of 93 subjects had QT/QTc data. Six studies with a pooled sample of 132 subjects had blood-pressure data, and seven studies investigated heart rate.
The patients, who were all young (aged 18 to 45) and healthy, underwent ECG and blood-pressure testing before and just after drinking one to three cans of energy drink--most commonly Red Bull, but also others such as Full Throttle and Meltdown RTD. An 8.4-oz can of Red Bull contains 80 mg of caffeine, compared with 35 mg of caffeine in a 12-oz Coke or about 100 mg of caffeine in an average cup of coffee, Shah said.
Shortly after drinking the energy drinks, the pooled subjects had a systolic blood pressure increase of an average 3.5 mm Hg. "If people are drinking energy drinks every day, that change in blood pressure could be very significant," Shah noted, adding that, as reported by heartwire , research on torcetrapibwas terminated because of a similar 3-mm-Hg increase in blood pressure.
People who don't normally drink coffee might have a heightened blood-pressure response to an energy drink, he added.
In a clinical setting, physicians are usually concerned if a patient has a QT-interval increase of about 30 msec from baseline, Shah noted. He acknowledges that this was a small study, but it did uncover a disturbing signal that needs to be further investigated.
Diastolic BP and heart rate increased nonsignificantly.
Although the 10-msec prolongation in the QT interval is a "small number, if it were consistently produced by a drug being considered by the FDA, the FDA would require more testing to make sure that there was not a liability for producing further, more serious, and life-threatening prolongation of the QT interval and associated arrhythmias," AHA spokesperson and past president Dr Gordon F Tomaselli (Johns Hopkins University, Baltimore, MD) commented.
Both Shah and Tomaselli pointed out that people who are older or who have underlying CVD might have even more heart-related side effects from energy drinks than the young, healthy people in this meta-analysis.
Soy improves lung cancer survival in women
The consumption of soy food before a lung cancer diagnosis might favorably affect disease outcomes in women, according to a longitudinal follow-up study from China.
In the Shanghai Women's Health Study, women with lung cancer who ate low levels of soy daily were at greater risk of dying from lung cancer than those who ate average or higher levels of the Asian food staple over their lifetimes.
Specifically, in 301 women with lung cancer, there was an 81% increased risk for death from lung cancer in those in the 10th percentile of soy intake, compared with those in those in the 50th percentile (the median). In contrast, there was an 11% decreased risk for death in women in the 90th percentile of intake, compared with those in the 50th percentile (P for overall significance = .004).
These effect sizes were found after adjustment for a wide variety of factors, including tumor stage and treatment.
In short, soy might have a disease-modulating effect, say the authors, led by Gong Yang, MD, from Vanderbilt University Medical Center in Nashville, Tennessee.
The study results were published online today in the Journal of Clinical Oncology.
"Plant-derived estrogens, such as isoflavones found mainly in soy food, appear to act as natural selective estrogen-receptor modulators," they write.
Thus, soy could compete with a woman's endogenous estrogens in binding to estrogen receptors, the authors explain. Soy might occupy the receptors so they cannot be stimulated by the body's estrogens.
Dr. Yang and his coauthors point out that emerging evidence suggests that female sex hormones negatively affect lung cancer survival. The evidence includes well-publicized data from the Women's Health Initiative, which showed that estrogen-plus-progestin therapy significantly increased the risk for death from lung cancer.
"Soy may have a mechanism of action similar to drugs like tamoxifen," Jyoti Patel, MD, from Northwestern University in Chicago, Illinois, told Medscape Medical News.
"This is the first scientific evidence that soy has a favorable effect on lung cancer survival," said Dr. Patel, who is a spokesperson for the American Society of Clinical Oncology, and provided independent comment on the study.
"It's really exciting," she summarized.
This study is part of a varied body of research that is seeking "hormonal clues" to lung cancer, she explained.
In 2012, Dr. Yang and colleagues found, in the same 74,000-patient cohort of Shanghai women, an approximately 40% reduction in the risk for incident lung cancer associated with the high intake of soy food. Thus, eating soy could both prevent and alter the disease course of lung cancer.
In the current study, the amount of soy consumed by the 301 women with lung cancer that was most protective (>20 g/day) was "not astronomical," said Dr. Patel. "But you have to make a concerted effort [to eat that much]," she added, referring especially to Westerners, who are less likely to include soy in their diet.
Americans typically consume what the study deemed to be a low level of soy (≤12 g/day), said Dr. Patel, who explained that the study results are "likely more applicable" in Asian countries.
More epidemiologic studies are needed to confirm these results, the authors note.
Almost all were non-smokers
There were actually 440 cases of lung cancer in the 74,000-women Shanghai cohort, but only 301 had information about both tumor stage and treatment. The hazard ratios for the 440 women were less dramatic than those for the 301 women reported above.
For example, in the 440 women with lung cancer, there was a 42% increased risk for death from lung cancer in the women who were in the 10th percentile of soy intake, compared with those in the 50th percentile (the median). In the 301 women, that increase was much larger (81%).
Nevertheless, although the effect sizes varied, the evidence in support of a possible protective effect of soy was constant.
As expected in an Asian population, most of the women with lung cancer (about 92%) were never smokers. Mean age at cancer diagnosis was 66.3 years.
The researchers assessed soy dietary intake with a food-frequency questionnaire, which covered soy milk, tofu, fried tofu, dried or pressed tofu, fresh green soy beans, dry soy beans, soy sprouts, and other soy products.
Mean intakes, on a dry weight basis, were 18.0 g/day for soy food and 8.8 g/day for soy protein.
The authors report that soy food intake was not related to patient characteristics such as age at diagnosis, smoking, obesity, family history of lung cancer, tumor stage, treatment regimens, or time between baseline dietary assessment and disease diagnosis.
In this study, the median follow-up time after cancer diagnosis was 36 months. During the follow-up period, 318 of the 440 women died; in 301 (94.7%), the primary cause of death was lung cancer, and in 17 (5.3%), it was another cause.
In the Shanghai Women's Health Study, women with lung cancer who ate low levels of soy daily were at greater risk of dying from lung cancer than those who ate average or higher levels of the Asian food staple over their lifetimes.
Specifically, in 301 women with lung cancer, there was an 81% increased risk for death from lung cancer in those in the 10th percentile of soy intake, compared with those in those in the 50th percentile (the median). In contrast, there was an 11% decreased risk for death in women in the 90th percentile of intake, compared with those in the 50th percentile (P for overall significance = .004).
These effect sizes were found after adjustment for a wide variety of factors, including tumor stage and treatment.
In short, soy might have a disease-modulating effect, say the authors, led by Gong Yang, MD, from Vanderbilt University Medical Center in Nashville, Tennessee.
The study results were published online today in the Journal of Clinical Oncology.
"Plant-derived estrogens, such as isoflavones found mainly in soy food, appear to act as natural selective estrogen-receptor modulators," they write.
Thus, soy could compete with a woman's endogenous estrogens in binding to estrogen receptors, the authors explain. Soy might occupy the receptors so they cannot be stimulated by the body's estrogens.
Dr. Yang and his coauthors point out that emerging evidence suggests that female sex hormones negatively affect lung cancer survival. The evidence includes well-publicized data from the Women's Health Initiative, which showed that estrogen-plus-progestin therapy significantly increased the risk for death from lung cancer.
"Soy may have a mechanism of action similar to drugs like tamoxifen," Jyoti Patel, MD, from Northwestern University in Chicago, Illinois, told Medscape Medical News.
"This is the first scientific evidence that soy has a favorable effect on lung cancer survival," said Dr. Patel, who is a spokesperson for the American Society of Clinical Oncology, and provided independent comment on the study.
"It's really exciting," she summarized.
This study is part of a varied body of research that is seeking "hormonal clues" to lung cancer, she explained.
In 2012, Dr. Yang and colleagues found, in the same 74,000-patient cohort of Shanghai women, an approximately 40% reduction in the risk for incident lung cancer associated with the high intake of soy food. Thus, eating soy could both prevent and alter the disease course of lung cancer.
In the current study, the amount of soy consumed by the 301 women with lung cancer that was most protective (>20 g/day) was "not astronomical," said Dr. Patel. "But you have to make a concerted effort [to eat that much]," she added, referring especially to Westerners, who are less likely to include soy in their diet.
Americans typically consume what the study deemed to be a low level of soy (≤12 g/day), said Dr. Patel, who explained that the study results are "likely more applicable" in Asian countries.
More epidemiologic studies are needed to confirm these results, the authors note.
Almost all were non-smokers
There were actually 440 cases of lung cancer in the 74,000-women Shanghai cohort, but only 301 had information about both tumor stage and treatment. The hazard ratios for the 440 women were less dramatic than those for the 301 women reported above.
For example, in the 440 women with lung cancer, there was a 42% increased risk for death from lung cancer in the women who were in the 10th percentile of soy intake, compared with those in the 50th percentile (the median). In the 301 women, that increase was much larger (81%).
Nevertheless, although the effect sizes varied, the evidence in support of a possible protective effect of soy was constant.
As expected in an Asian population, most of the women with lung cancer (about 92%) were never smokers. Mean age at cancer diagnosis was 66.3 years.
The researchers assessed soy dietary intake with a food-frequency questionnaire, which covered soy milk, tofu, fried tofu, dried or pressed tofu, fresh green soy beans, dry soy beans, soy sprouts, and other soy products.
Mean intakes, on a dry weight basis, were 18.0 g/day for soy food and 8.8 g/day for soy protein.
The authors report that soy food intake was not related to patient characteristics such as age at diagnosis, smoking, obesity, family history of lung cancer, tumor stage, treatment regimens, or time between baseline dietary assessment and disease diagnosis.
In this study, the median follow-up time after cancer diagnosis was 36 months. During the follow-up period, 318 of the 440 women died; in 301 (94.7%), the primary cause of death was lung cancer, and in 17 (5.3%), it was another cause.
3mg melatonin may aid migraine prevention
Melatonin, which is widely available in North America as an over-the-counter supplement, is more effective than placebo for migraine prevention and has a more favorable adverse effect profile than the tricyclic antidepressant amitriptyline, new research shows.
Results from a multicenter, randomized, double-blind, placebo-controlled trial showed that 3 mg of melatonin was more effective than placebo and had efficacy similar to that of 25 mg of amitriptyline. Furthermore, it was better tolerated than amitriptyline, with lower rates of daytime sleepiness and no weight gain.
"Melatonin 3 mg was significantly better than placebo with no difference compared to amitriptyline with respect to migraine prevention," principal investigator Mario Peres, MD, PhD, told delegates here attending the American Academy of Neurology (AAN) 65th Annual Meeting.
"But if we look at the proportion of responders, then melatonin had better results than amitriptyline," added Dr. Peres, who is director of São Paulo Headache Center, professor of neurology at ABC Medical School, and senior research associate at the Albert Einstein Brain Research Institute, Brazil.
Link to headache, sleep disorders
Produced by the pineal gland, melatonin is a hormone that helps regulate the sleep/wake cycle. It has been available as a supplement in the United States since the 1990s and is often used to aid sleep and attenuate jet lag.
According to Dr. Peres, melatonin's role in regulating circadian rhythm has been linked to cluster headache, hypnic headache, and migraine.
Further, he noted, melatonin plays an important role in sleep regulation, and disruption of melatonin production has been linked to sleep disorders, including sleep apnea, insomnia, and delayed sleep phase syndrome, which, in turn, are linked to headache.
He also noted that there is a bidirectional relationship in which headache can disrupt sleep and lead to insomnia and excessive daytime sleepiness.
Finally, he pointed out that research has linked low levels of melatonin in plasma and urine and altered peak time in melatonin levels to a variety of headache types, including migraine.
According to Dr. Peres, research into melatonin as a potential treatment for headache has included several case reports and open-label studies but only 2 randomized controlled trials: 1 in cluster headache, which was positive, and 1 negative trial in migraine.
The negative migraine trial, he said, had several limitations, including a small sample size and a short duration of only 8 weeks. It also used a slow-release, 2-mg formulation of melatonin, and, although the response rate in the melatonin group was 44%, the placebo group had an exceptionally high response rate of 40%.
Surprise weight-loss finding
To test the efficacy and tolerability of melatonin and amitriptyline vs placebo for migraine prevention, the investigators recruited 178 men and women who met International Headache Society diagnostic criteria for migraine with and without aura and who had 2 to 8 migraine attacks per month.
All patients underwent a 4-week baseline phase during which each participant kept a diary of migraine frequency.
Participants were then randomly assigned to receive 3 mg melatonin (n = 60), 25 mg amitriptyline (n = 59), or placebo (n = 59) for 3 months. Medication was taken between 10 and 11 pm daily.
The study's primary outcome was a reduction in the number of headache days per month. Secondary endpoints included migraine intensity and duration and analgesic use. Tolerability was also measured in all 3 study groups.
The mean reduction in headache frequency was 2.7 in the melatonin group, 2.18 in the amitriptyline group, and 1.18 in the placebo group.
Although migraine frequency did not differ between the 2 active treatment groups, the proportion of responders was greatest in the melatonin group: 54% vs 39.1% for amitriptyline and 20.4% for placebo.
Melatonin was also "very tolerable" and had significantly fewer adverse effects compared with amitriptyline, said Dr. Peres. Daytime sleepiness was the most frequent symptom in all 3 groups but was most pronounced in the amitriptyline group (n = 24).
Although patients gained weight in both the amitriptyline (n = 3) and placebo (n = 1) groups, melatonin was associated with weight loss.
Timing of administration and formulation is also important. Ideally, said Dr. Peres, melatonin should be taken between 10 pm and 11 pm to mimic the physiologic peak. In addition, a fast-acting rather than a slow-release formula should be used.
Overall, said Dr. Peres, the study's findings are promising and warrant further research.
Worth a try?
Commenting on the study, Tobias Kurth, MD, director of research Institut national de la santé et de la recherche médicale (INSERM), University of Bordeaux in France, and associate epidemiologist, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, said the researchers "very convincingly" showed that melatonin was as effective as amitriptyline and both were superior to placebo.
"If this is true, this is great," said Dr. Kurth.
Although the study's findings are preliminary and need to be replicated, Dr. Kurth said that given its favorable adverse effect profile, melatonin may be worth a try.
"I'm not aware of any major side effects associated with melatonin. As long clinicians instruct patients appropriately and emphasize the importance of taking the recommended dose at the same time every day it may be worthwhile," he said.
Results from a multicenter, randomized, double-blind, placebo-controlled trial showed that 3 mg of melatonin was more effective than placebo and had efficacy similar to that of 25 mg of amitriptyline. Furthermore, it was better tolerated than amitriptyline, with lower rates of daytime sleepiness and no weight gain.
"Melatonin 3 mg was significantly better than placebo with no difference compared to amitriptyline with respect to migraine prevention," principal investigator Mario Peres, MD, PhD, told delegates here attending the American Academy of Neurology (AAN) 65th Annual Meeting.
"But if we look at the proportion of responders, then melatonin had better results than amitriptyline," added Dr. Peres, who is director of São Paulo Headache Center, professor of neurology at ABC Medical School, and senior research associate at the Albert Einstein Brain Research Institute, Brazil.
Link to headache, sleep disorders
Produced by the pineal gland, melatonin is a hormone that helps regulate the sleep/wake cycle. It has been available as a supplement in the United States since the 1990s and is often used to aid sleep and attenuate jet lag.
According to Dr. Peres, melatonin's role in regulating circadian rhythm has been linked to cluster headache, hypnic headache, and migraine.
Further, he noted, melatonin plays an important role in sleep regulation, and disruption of melatonin production has been linked to sleep disorders, including sleep apnea, insomnia, and delayed sleep phase syndrome, which, in turn, are linked to headache.
He also noted that there is a bidirectional relationship in which headache can disrupt sleep and lead to insomnia and excessive daytime sleepiness.
Finally, he pointed out that research has linked low levels of melatonin in plasma and urine and altered peak time in melatonin levels to a variety of headache types, including migraine.
According to Dr. Peres, research into melatonin as a potential treatment for headache has included several case reports and open-label studies but only 2 randomized controlled trials: 1 in cluster headache, which was positive, and 1 negative trial in migraine.
The negative migraine trial, he said, had several limitations, including a small sample size and a short duration of only 8 weeks. It also used a slow-release, 2-mg formulation of melatonin, and, although the response rate in the melatonin group was 44%, the placebo group had an exceptionally high response rate of 40%.
Surprise weight-loss finding
To test the efficacy and tolerability of melatonin and amitriptyline vs placebo for migraine prevention, the investigators recruited 178 men and women who met International Headache Society diagnostic criteria for migraine with and without aura and who had 2 to 8 migraine attacks per month.
All patients underwent a 4-week baseline phase during which each participant kept a diary of migraine frequency.
Participants were then randomly assigned to receive 3 mg melatonin (n = 60), 25 mg amitriptyline (n = 59), or placebo (n = 59) for 3 months. Medication was taken between 10 and 11 pm daily.
The study's primary outcome was a reduction in the number of headache days per month. Secondary endpoints included migraine intensity and duration and analgesic use. Tolerability was also measured in all 3 study groups.
The mean reduction in headache frequency was 2.7 in the melatonin group, 2.18 in the amitriptyline group, and 1.18 in the placebo group.
Although migraine frequency did not differ between the 2 active treatment groups, the proportion of responders was greatest in the melatonin group: 54% vs 39.1% for amitriptyline and 20.4% for placebo.
Melatonin was also "very tolerable" and had significantly fewer adverse effects compared with amitriptyline, said Dr. Peres. Daytime sleepiness was the most frequent symptom in all 3 groups but was most pronounced in the amitriptyline group (n = 24).
Although patients gained weight in both the amitriptyline (n = 3) and placebo (n = 1) groups, melatonin was associated with weight loss.
Timing of administration and formulation is also important. Ideally, said Dr. Peres, melatonin should be taken between 10 pm and 11 pm to mimic the physiologic peak. In addition, a fast-acting rather than a slow-release formula should be used.
Overall, said Dr. Peres, the study's findings are promising and warrant further research.
Worth a try?
Commenting on the study, Tobias Kurth, MD, director of research Institut national de la santé et de la recherche médicale (INSERM), University of Bordeaux in France, and associate epidemiologist, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, said the researchers "very convincingly" showed that melatonin was as effective as amitriptyline and both were superior to placebo.
"If this is true, this is great," said Dr. Kurth.
Although the study's findings are preliminary and need to be replicated, Dr. Kurth said that given its favorable adverse effect profile, melatonin may be worth a try.
"I'm not aware of any major side effects associated with melatonin. As long clinicians instruct patients appropriately and emphasize the importance of taking the recommended dose at the same time every day it may be worthwhile," he said.
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