Friday, June 28, 2019

Pink noise boosts deep sleep in mild cognitive impairment patients


Gentle sound stimulation played during specific times during deep sleep enhanced deep or slow-wave sleep for people with mild cognitive impairment, who are at risk for Alzheimer's disease.
The individuals whose brains responded the most robustly to the sound stimulation showed an improved memory response the following day.
"Our findings suggest slow-wave or deep sleep is a viable and potentially important therapeutic target in people with mild cognitive impairment," said Dr. Roneil Malkani, assistant professor of neurology at Northwestern University Feinberg School of Medicine and a Northwestern Medicine sleep medicine physician. "The results deepen our understanding of the importance of sleep in memory, even when there is memory loss."
Deep sleep is critical for memory consolidation. Several sleep disturbances have been observed in people with mild cognitive impairment. The most pronounced changes include reduced amount of time spent in the deepest stage of sleep.
"There is a great need to identify new targets for treatment of mild cognitive impairment and Alzheimer's disease," Malkani added. Northwestern scientists had previously shown that sound stimulation improved memory in older adults in a 2017 study.
Because the new study was small -- nine participants -- and some individuals responded more robustly than others, the improvement in memory was not considered statistically significant. However, there was a significant relationship between the enhancement of deep sleep by sound and memory: the greater the deep sleep enhancement, the better the memory response.
"These results suggest that improving sleep is a promising novel approach to stave off dementia," Malkani said.
The paper will be published June 28 in the Annals of Clinical and Translational Neurology.
For the study, Northwestern scientists conducted a trial of sound stimulation overnight in people with mild cognitive impairment. Participants spent one night in the sleep laboratory and another night there about one week later. Each participant received sounds on one of the nights and no sounds on the other. The order of which night had sounds or no sounds was randomly assigned.  Participants did memory testing the night before and again in the morning. Scientists then compared the difference in slow-wave sleep with sound stimulation and without sounds, and the change in memory across both nights for each participant.
The participants were tested on their recall of 44 word pairs. The individuals who had 20% or more increase in their slow wave activity after the sound stimulation recalled about two more words in the memory test the next morning. One person with a 40% increase in slow wave activity remembered nine more words.
The sound stimulation consisted of short pulses of pink noise, similar to white noise but deeper, during the slow waves. The system monitored the participant's brain activity. When the person was asleep and slow brain waves were seen, the system delivered the sounds. If the patient woke up, the sounds stopped playing.
"As a potential treatment, this would be something people could do every night," Malkani said.

The next step, when funding is available, is to evaluate pink noise stimulation in a larger sample of people with mild cognitive impairment over multiple nights to confirm memory enhancement and see how long the effect lasts, Malkani said. 



Students chowing down tuna in dining halls are unaware of mercury exposure risks


A surprising number of students eating in university dining halls have been helping themselves to servings of tuna well beyond the amounts recommended to avoid consuming too much mercury, a toxic heavy metal.
Researchers at UC Santa Cruz surveyed students outside of campus dining halls on their tuna consumption habits and knowledge of mercury exposure risks, and also measured the mercury levels in hair samples from the students. They found that hair mercury levels were closely correlated with how much tuna the students said they ate. And for some students, their hair mercury measurements were above what is considered a "level of concern."
"It doesn't necessarily mean that they would be experiencing toxic effects, but it's a level at which it's recommended to try to lower your mercury exposure," said Myra Finkelstein, an associate adjunct professor of environmental toxicology at UC Santa Cruz. "Our results were consistent with other studies of mercury levels in hair from people who eat a lot of fish."
Tuna and other large fish contain significant amounts of mercury in its most toxic form (methylmercury), and exposure to high levels of methylmercury can cause neurological damage. Because of its effects on neurological development and reproductive health, concerns about mercury exposure are greatest for pregnant women and children. Finkelstein said college students should also limit their exposure to mercury because their nervous systems are still developing and they are of reproductive age.
She said the study was prompted by her experiences teaching students about mercury in the environment and hearing about how much tuna some students eat. "I've been dumbfounded when students have told me they eat tuna every day," Finkelstein said. "Their lack of knowledge about the risk of exposure to mercury is surprising."
Graduate student Yasuhiko Murata led the study and is first author of a paper on their findings, which has been accepted for publication in Environmental Toxicology and Chemistry and is available online. In the surveys, about a third of students reported weekly tuna consumption, and 80 percent of their tuna meals were at the campus dining halls, where tuna is regularly available from the salad bar. Half of the tuna eaters reported eating three or more tuna meals per week, potentially exceeding the "reference dose" established by the U.S. Environmental Protection Agency (EPA), considered a maximum safe level (0.1 micrograms of methylmercury per kilogram of body weight per day).
Before the results were published, Finkelstein discussed her team's findings with UCSC administrators who oversee the dining halls. New signs in the campus dining halls will now give students information about mercury in tuna and guidelines for fish consumption. Other changes may be made after a more thorough assessment, said William Prime, executive director of dining services.
Finkelstein said this issue could be a concern for all kinds of institutions with dining halls, especially those serving children, such as boarding schools. "Any time you have a dining hall situation where people are helping themselves, some residents may be eating way too much tuna," she said.
Nearly all fish contain some mercury, but tuna, especially the larger species, are known to accumulate relatively high levels of the toxic metal. Consumers are advised to eat no more than two to three servings per week of low-mercury fish (including skipjack and tongol tuna, often labeled "chunk light") or one serving per week of fish with higher levels of mercury (including albacore and yellow fin tuna).
Some of the students surveyed at UC Santa Cruz reported having more than 20 servings of tuna per week. The researchers analyzed the mercury content of the tuna being served in the dining halls, collecting samples periodically over several months, and found that the mercury content was variable, with some samples having five times as much mercury as others.
"Some chunk light tuna was actually quite high in mercury, although typically it has only half or one-third as much as albacore," Finkelstein said.
The researchers calculated that, to stay below the EPA reference dose, a 140-pound person could consume up to two meals per week of the lower-mercury tuna but less than one meal per week of the higher-mercury tuna.
After conducting an initial survey and hair analysis, the researchers conducted a second survey with more detailed questions designed to probe students' knowledge about mercury in tuna and recommended consumption rates. Whether they were tuna eaters or not, most students had very little knowledge about this issue, Finkelstein said. A majority of students answered that it is safe to eat two to three times as much tuna per week as is recommended.
"It was not a large sample size, but only one out of 107 students surveyed had a high level of knowledge as well as confidence in that knowledge, so I think it's important to provide students with more information about safe levels of tuna consumption," she said.
Recommendations regarding consumption of tuna and other fish are complicated by the fact that fish is highly nutritious and contains beneficial omega-3 fatty acids and other nutrients. In addition, mercury concentrations vary widely among different types of fish. The U.S. Food and Drug Administration and EPA have issued advice on eating fish for pregnant women, parents, and caregivers of young children.

Short sleep duration and sleep variability blunt weight loss


This is one of the conclusions of the Predimed-Plus study, Prevention with the Mediterranean Diet, which has been published in the June issue of the International Journal of Obesity. It is the first study to examine whether the quality of sleep is related to weight loss and a reduction in adipose tissue.

In their study, the researchers from the Human Nutrition Unit of the Rovira i Virgili University, in conjunction with other research groups involved in the Predimed-Plus study, assessed the changes in weight and adiposity - body fat - of the 1,986 individuals who took part in the study for a whole year, all of whom presented overweight, obesity and the metabolic syndrome. The patients followed an intensive intervention programme in terms of lifestyle designed for weight loss. It was based on a low-calorie Mediterranean diet, physical activity and behaviour therapy.

The researchers observed that the individuals with highly variable sleep patterns - that's to say, who did not sleep the same number of hours every night - at the beginning of the study lost less weight after a follow-up period of 12 months. What is more, a high sleep variability and sleeping little - less than six hours - a day was associated with a lower decrease in body mass index and waist circumference.

These results reveal that adopting measures to achieve an appropriate sleep pattern may have an impact on maintaining the correct weight and preventing other metabolic disorders associated with excess body fat.

Low social engagement may be a marker of cognitive vulnerability in older adults


Social relationships are essential to aging well; research has shown an association between lack of social engagement and increased risk of dementia. A new study by investigators from Brigham and Women's Hospital found that higher brain amyloid-β in combination with lower social engagement in elderly men and women was associated with greater cognitive decline over three years. The results of the study were published last month in the American Journal of Geriatric Psychiatry.
"Social engagement and cognitive function are related to one another and appear to decline together," said senior author Nancy Donovan, MD, chief of the Division of Geriatric Psychiatry at the Brigham. "This means that social engagement may be an important marker of resilience or vulnerability in older adults at risk of cognitive impairment."
The investigators sampled 217 men and women enrolled in the Harvard Aging Brain Study, a longitudinal observational study looking for early neurobiological and clinical signs of Alzheimer's disease. The participants, aged 63-89, were cognitively normal, but some individuals showed high levels of amyloid-β protein, a pathologic hallmark of Alzheimer's disease detected with neuroimaging techniques.
The investigators used standard questionnaires and examinations to assess participants' social engagement (including activities such as spending time with friends and family and doing volunteer work) and cognitive performance at baseline and three years later.
Social engagement was particularly relevant to cognition in participants with evidence of Alzheimer's disease brain changes. The researchers report that, among cognitively normal older adults with high levels of amyloid-β, those who had lower social engagement at baseline showed steeper cognitive decline than those who were more socially engaged. This association was not observed in those with low amyloid-β.
Donovan and her team used a standard measure of social engagement that did not capture all the intricacies of digital communication or the qualitative aspects of relationships. They reported that a more contemporary and comprehensive assessment of social engagement could be a valuable outcome measure in future clinical trials of Alzheimer's disease.
The team cited that future studies with follow-up periods longer than three years may further gauge cognitive decline over time and help untangle the complex mechanisms of Alzheimer's disease progression.
"We want to understand the breadth of this issue in older people and how to intervene to protect high-risk individuals and preserve their health and well-being," said Donovan.

Keeping active or becoming more active in middle and older age linked to longer life



Keeping physically active or becoming more active during middle and older age is associated with a lower risk of death, regardless of past activity levels or existing health conditions, suggests a large UK study published by The BMJ today.
At the population level, meeting and maintaining at least the minimum public health recommendations (150 minutes per week of moderate-intensity physical activity) would potentially prevent 46% of deaths associated with physical inactivity, say the researchers.
Previous studies have linked physical activity to lower risk of death, cardiovascular disease, and certain cancers. But few studies have looked at how changes in physical activity over time are associated with subsequent risk of death.
So to address this knowledge gap, researchers from the MRC Epidemiology Unit at the University of Cambridge analysed how long term changes in physical activity are associated with risk of all-cause, cardiovascular and cancer deaths.
They used data for 14,599 men and women aged 40-79 from the European Prospective Investigation into Cancer and Nutrition-Norfolk (EPIC-Norfolk) study, who were recruited between 1993-1997.
Participants were assessed at the start of the study and then a further three times over an average of 7.6 years, along with other risk factors up to 2004. From this point in time, mortality was assessed up to 2016, for an average of 12.5 years of follow-up.
Physical activity energy expenditure (PAEE) was derived from questionnaires and calibrated against combined movement and heart monitoring measurements.
Overall physical activity included activity at work (e.g. sedentary office work, standing work, physical and heavy manual work) and leisure-time activity, such as cycling, sports and recreational activities.
During the study period, there were 3,148 deaths, including 950 deaths from cardiovascular disease and 1,091 deaths from cancer.
After controlling for existing physical activity and other risk factors such as diet, bodyweight, medical history, blood pressure and cholesterol levels, higher physical activity levels and increases in physical activity over time were associated with a lower risk of death.
For each 1kJ/kg/day per year increase in PAEE (equivalent to being inactive at the start of the study and gradually, over five years, meeting minimum physical activity guidelines), the researchers found a 24% lower risk of death from any cause, a 29% lower risk of cardiovascular death, and an 11% lower risk of cancer death.
Results were similar in those with and without a history of cardiovascular disease and cancer. What's more, compared with consistently inactive people, those who became more active over time had a lower risk of death from all causes, regardless of past activity levels.
But the benefits were greatest for those with existing high levels of physical activity who became even more active over time, with a 42% lower risk of mortality.
This is an observational study, and as such, can't establish cause. And the authors point out that the sample was made up of people who were available for follow-up almost a decade after initial recruitment, which may influence generalisability of the results.
But they say that this is a large study with long follow-up and repeat monitoring, that controlled for established risk factors.
"These results are encouraging, not least for middle aged and older adults with existing cardiovascular disease and cancer, who can still gain substantial longevity benefits by becoming more active, lending further support to the broad public health benefits of physical activity," they write.
"In addition to shifting the population towards meeting the minimum physical activity recommendations, public health efforts should also focus on the maintenance of physical activity levels, specifically preventing declines over mid to late life," they conclude.

Are testosterone-boosting supplements effective? Not likely



Men who want to improve their libido or build body mass may want to think twice before using testosterone-boosting supplements -- also known as "T boosters" -- as research shows these alternatives to traditional testosterone replacement therapy may not have ingredients to support their claims, according to Mary K. Samplaski, MD, assistant professor of clinical urology at the Keck School of Medicine of USC.
"Many supplements on the market merely contain vitamins and minerals, but don't do anything to improve testosterone," says Samplaski. "Often, people can be vulnerable to the marketing component of these products, making it difficult to tease out what is myth and what is reality."
Testosterone is the primary male sex hormone and the reason why men produce sperm and have Adam's apples. It's also why men develop more "masculine" features like bulging muscles, a deep voice, broad shoulders and a hairy chest. After age 30, most men experience a gradual decline in testosterone, sometimes causing these features to diminish or new symptoms to occur, like erectile dysfunction. In an attempt to turn back the hands of time, some men will turn to T boosters.
Using a structured review approach, Samplaski and a team of researchers explored the active ingredients and advertised claims of 50 T boosting supplements. Their findings were published as an original article in The World Journal of Men's Health.
Researchers performed a Google search with the search term "Testosterone Booster," thus mimicking a typical internet research for someone looking to increase testosterone levels, and then selected the first 50 products that came up in their search. Then, the team reviewed published scientific literature on testosterone and the 109 components found in the supplements. Zinc, fenugreek extract and vitamin B6 were three of the most common components in the supplements.
The team also compared the content for each supplement with the Food and Drug Administration's (FDA) Recommended Daily Allowance (RDA) and the upper tolerable intake level (UL) as set by the Institute of Medicine of the National Academy of Science.
Of the 150 supplements, researchers came across 16 general claims to benefit patients, including claims to "boost T or free T," "build body lean mass or muscle mass," or "increase sex drive or libido."
While 90% of the T booster supplements claimed to boost testosterone, researchers found that less than 25% of the supplements had data to support their claims. Many also contained high doses of vitamins and minerals, occasionally more than the tolerable limit.
Unlike drugs, supplements are not intended to treat, diagnose, prevent, or cure diseases, according to the FDA. As such, Samplaski would like to see more regulation around testosterone-boosting supplements to protect consumers. She also would like to explore disseminating handouts to her patients with more accurate information in the hopes that it encourages patients to seek a medical professional for low testosterone issues.
While no one can escape the effects of aging, Samplaski says there is something men can do to address their concerns. "The safest and most effective way for men to boost low testosterone levels is to talk with a medical professional or a nutritionist."

Thursday, June 27, 2019

Disrupted sleep in one's 50s, 60s raises risk of Alzheimer's disease


Protein tangles in the aging brain throw sleep rhythms out of sync, likely leading to memory loss

University of California - Berkeley
IMAGE
IMAGE: Greater levels of pathological tau protein, primarily in the brain's medial temporal lobe (orange and yellow at bottom in cross section of the brain), were associated with weaker synchrony of... view more 
Credit: UC Berkeley image by Matthew Walker and Joseph Winer
People who report a declining quality of sleep as they age from their 50s to their 60s have more protein tangles in their brain, putting them at higher risk of developing Alzheimer's disease later in life, according to a new study by psychologists at the University of California, Berkeley.
The new finding highlights the importance of sleep at every age to maintain a healthy brain into old age.
"Insufficient sleep across the lifespan is significantly predictive of your development of Alzheimer's disease pathology in the brain," said the study's senior author, Matthew Walker, a sleep researcher and professor of psychology. "Unfortunately, there is no decade of life that we were able to measure during which you can get away with less sleep. There is no Goldilocks decade during which you can say, 'This is when I get my chance to short sleep.'"
Walker and his colleagues, including graduate student and first author Joseph Winer, found that adults reporting a decline in sleep quality in their 40s and 50s had more beta-amyloid protein in their brains later in life, as measured by positron emission tomography, or PET. Those reporting a sleep decline in their 50s and 60s had more tau protein tangles. Both beta-amyloid and tau clusters are associated with a higher risk of developing dementia, though not everyone with protein tangles goes on to develop symptoms of dementia.
Based on the findings, the authors recommend that doctors ask older patients about changes in sleep patterns and intervene when necessary to improve sleep to help delay symptoms of dementia. This could include treatment for apnea, which leads to snoring and frequent halts in breathing that interrupt sleep, and cognitive behavioral therapy for insomnia (CBT-I), a highly effective way to develop healthy sleep habits. It may even include simple sleep counseling to convince patients to set aside time for a full eight hours of sleep and simple sleep hygiene tricks to accomplish that.
"The idea that there are distinct sleep windows across the lifespan is really exciting. It means that there might be high-opportunity periods when we could intervene with a treatment to improve people's sleep, such as using a cognitive behavioral therapy for insomnia," Winer said. "Beyond the scientific advance, our hope is that this study draws attention to the importance of getting more sleep and points us to the decades in life when intervention might be most effective."
The 95 subjects in the study were part of the Berkeley Aging Cohort Study (BACS), a group of healthy older adults -- some as old as 100 years of age -- who have had their brains scanned with PET, the only technique capable of detecting both beta-amyloid tangles and, very recently, tau tangles, in the brain.
Winer, Walker and their colleagues reported their results online last week in the Journal of Neuroscience.
Brain waves out of sync The team also made a second discovery. They found that people with high levels of tau protein in the brain were more likely to lack the synchronized brain waves that are associated with a good night's sleep. The synchronization of slow brain waves throughout the cortex of the sleeping brain, in lockstep with bursts of fast brain waves called sleep spindles, takes place during deep or non-rapid eye movement (NREM) sleep. The team reported that the more tau protein older adults had, the less synchronized these brain waves were. This impaired electrical sleep signature may therefore act as a novel biomarker of tau protein in the human brain.
"There is something special about that synchrony," given the consequences of this tau protein disruption of sleep, Walker said. "We believe that the synchronization of these NREM brain waves provides a file-transfer mechanism that shifts memories from a short-term vulnerable reservoir to a more permanent long-term storage site within the brain, protecting those memories and making them safe. But when you lose that synchrony, that file-transfer mechanism becomes corrupt. Those memory packets don't get transferred, as well, so you wake up the next morning with forgetting rather than remembering."
Indeed, last year, Walker and his team demonstrated that synchronization of these brain oscillations helps consolidate memory, that is, hits the "save" button on new memories.
Several years ago, Walker and his colleagues initially showed that a dip in the amplitude of slow wave activity during deep NREM sleep was associated with higher amounts of beta-amyloid in the brain and memory impairment. Combined with these new findings, the results help identify possible biomarkers for later risk of dementia.
"It is increasingly clear that sleep disruption is an underappreciated factor contributing to Alzheimer's disease risk and the decline in memory associated with Alzheimer's," Walker said. "Certainly, there are other contributing factors: genetics, inflammation, blood pressure. All of these appear to increase your risk for Alzheimer's disease. But we are now starting to see a new player in this space, and that new player is called insufficient sleep."
The brain rhythms were recorded over a single eight-hour night in Walker's UC Berkeley sleep lab, during which most of the 31 subjects wore a cap studded with 19 electrodes that recorded a continual electroencephalogram (EEG). All had previously had brain scans to assess their burdens of tau and beta-amyloid that were done using a PET scanner at the Lawrence Berkeley National Laboratory and operated by study co-author William Jagust, professor of public health and a member of Berkeley's Helen Wills Neuroscience Institute.
Is sleep a biomarker for dementia? Doctors have been searching for early markers of dementia for years, in hopes of intervening to stop the deterioration of the brain. Beta-amyloid and tau proteins are predictive markers, but only recently have they become detectable with expensive PET scans that are not widely accessible.
Yet, while both proteins escalate in the brain in old age and perhaps to a greater extent in those with dementia, it is still unknown why some people with large burdens of amyloid and tau do not develop symptoms of dementia.
"The leading hypothesis, the amyloid cascade hypothesis, is that amyloid is what happens first on the path to Alzheimer's disease. Then, in the presence of amyloid, tau begins to spread throughout the cortex, and if you have too much of that spread of tau, that can lead to impairment and dementia," Winer said.
Walker added that, "A lack of sleep across the lifespan may be one of the first fingers that flicks the domino cascade and contributes to the acceleration of amyloid and tau protein in the brain."
The hypothesis is supported, in part, by Jagust's PET studies, which have shown that higher levels of beta-amyloid and tau protein tangles in the brain are correlated with memory decline, tau more so than amyloid. Tau occurs naturally inside the brain's neurons, helping to stabilize their internal skeleton. With age, tau proteins seem to accumulate inside cells of the medial temporal lobe, including the hippocampus, the seat of short-term memory. Only later do they spread more widely throughout the cortex.
While Jagust has run PET scans on the brains of many healthy people, as well as those with dementia, many more subjects are needed to confirm the relationship between protein tangles and dementias like Alzheimer's disease. Because PET scanners are currently expensive and rare, and because they require injection of radioactive tracers, other biomarkers are needed, Walker said.
The new study suggests that sleep changes detectable in a simple overnight sleep study may be less intrusive biomarkers than a PET scan.
"As wearable technology improves, this need not be something you have to come to a sleep laboratory for," said Walker. "Our hope is that, in the future, a small head device could be worn by people at home and provide all the necessary sleep information we'd need to assess these Alzheimer's disease proteins. We may even be able to track the effectiveness of new drugs aimed at combating these brain proteins by assessing sleep."
"I think the message is very clear," Walker added. "If you are starting to struggle with sleep, then you should go and see your doctor and find ways, such as CBT-I, that can help you improve your sleep. The goal here is to decrease your chances of Alzheimer's disease."

Low-carb 'keto' diet ('Atkins-style') may modestly improve cognition in older adults




In a pilot study of 14 older adults with mild cognitive problems suggestive of early Alzheimer's disease, Johns Hopkins Medicine researchers report that a high-fat, low-carbohydrate diet may improve brain function and memory.
Although the researchers say that finding participants willing to undertake restrictive diets for the three-month study -- or partners willing to help them stick to those diets -- was challenging, those who adhered to a modified Atkins diet (very low carbohydrates and extra fat) had small but measurable improvements on standardized tests of memory compared with those on a low-fat diet.
The short-term results, published in the April issue of the Journal of Alzheimer's Disease, are far from proof that the modified Atkins diet has the potential to stave off progression from mild cognitive impairment to Alzheimer's disease or other dementias. However, they are promising enough, the researchers say, to warrant larger, longer-term studies of dietary impact on brain function.
"Our early findings suggest that perhaps we don't need to cut carbs as strictly as we initially tried. We may eventually see the same beneficial effects by adding a ketone supplement that would make the diet easier to follow," says Jason Brandt, Ph.D., professor of psychiatry and behavioral sciences and neurology at the Johns Hopkins University School of Medicine. "Most of all, if we can confirm these preliminary findings, using dietary changes to mitigate cognitive loss in early-stage dementia would be a real game-changer. It's something that 400-plus experimental drugs haven't been able to do in clinical trials."
Brandt explains that, typically, the brain uses the sugar glucose -- a product of carbohydrate breakdown -- as a primary fuel. However, research has shown that in the early stage of Alzheimer's disease the brain isn't able to efficiently use glucose as an energy source. Some experts, he says, even refer to Alzheimer's as "type 3 diabetes."
Using brain scans that show energy use, researchers have also found that ketones -- chemicals formed during the breakdown of dietary fat -- can be used as an alternative energy source in the brains of healthy people and those with mild cognitive impairment. For example, when a person is on a ketogenic diet, consisting of lots of fat and very few sugars and starches, the brain and body use ketones as an energy source instead of carbs.
For the current study, the researchers wanted to see if people with mild cognitive impairment, often an indicator of developing Alzheimer's disease, would benefit from a diet that forced the brain to use ketones instead of carbohydrates for fuel.
After 2 1/2 years of recruitment efforts, the researchers were able to enroll 27 people in the 12-week diet study. There were a few dropouts, and so far, 14 participants have completed the study. The participants were an average age of 71. Half were women, and all but one were white.
To enroll, each participant required a study partner (typically a spouse) who was responsible for ensuring that the participant followed one of two diets for the full 12 weeks. Nine participants followed a modified Atkins diet meant to restrict carbs to 20 grams per day or less, with no restriction on calories. The typical American consumes between 200 and 300 grams of carbs a day. The other five participants followed a National Institute of Aging diet, similar to the Mediterranean diet, that doesn't restrict carbohydrates, but favors fruits, vegetables, low- or fat-free dairy, whole grains and lean proteins such as seafood or chicken.
The participants and their partners were also asked to keep food diaries. Prior to starting the diets, those assigned to the modified Atkins diet were consuming about 158 grams of carbs per day. By week six of the diet, they had cut back to an average of 38.5 grams of carbs per day and continued dropping at nine weeks, but still short of the 20-gram target, before rising to an average of 53 grams of carbs by week 12. Participants on the National Institute of Aging diet continued to eat well over 100 grams of carbs per day.
Each participant also gave urine samples at the start of the dietary regimens and every three weeks up to the end of the study, which were used to track ketone levels. More than half of the participants on the modified Atkins diet had at least some ketones in their urine by six weeks into the diet until the end; as expected, none of the participants on the National Institute of Aging control diet had any detectable ketones.
Participants completed the Montreal Cognitive Assessment, the Mini-Mental State Examination and the Clinical Dementia Rating Scale at the start of the study. They were tested with a brief collection of neuropsychological memory tests before starting their diets and at six weeks and 12 weeks on the diet. At the six-week mark, the researchers found a significant improvement on memory tests, which coincided with the highest levels of ketones and lowest carb intakes.
When comparing the results of tests of delayed recall -- the ability to recollect something they were told or shown a few minutes earlier -- those who stuck to the modified Atkins diet improved by a couple of points on average (about 15% of the total score), whereas those who didn't follow the diet on average dropped a couple of points.
The researchers say the biggest hurdle for researchers was finding people willing to make drastic changes to their eating habits and partners willing to enforce the diets. The increase in carbohydrate intake later in the study period, they said, suggests that the diet becomes unpalatable over long periods.
"Many people would rather take a pill that causes them all kinds of nasty side effects than change their diet," says Brandt. "Older people often say that eating the foods they love is one of the few pleasures they still enjoy in life, and they aren't willing to give that up."
But, because Brandt's team observed promising results even in those lax with the diet, they believe that a milder version of the high-fat/low-carb diet, perhaps in conjunction with ketone supplement drinks, is worth further study. As this study also depended on caregivers/partners to do most of the work preparing and implementing the diet, the group also wants to see if participants with less severe mild cognitive impairment can make their own dietary choices and be more apt to stick to a ketogenic diet.
A standardized modified Atkins diet was created and tested at Johns Hopkins Medicine in 2002, initially to treat some seizure disorders. It's still used very successfully for this purpose.
According to the Alzheimer's Association, about 5.8 million Americans have Alzheimer's disease, and by 2050 the number is projected to increase to 14 million people.

Higher salt intake can cause bloating



A study led by researchers at the Johns Hopkins Bloomberg School of Public Health found that individuals reported more gastrointestinal bloating when they ate a diet high in salt.
The scientists re-analyzed data from a large clinical trial--the Dietary Approaches to Stop Hypertension-Sodium trial (DASH-Sodium)--conducted two decades ago, and found that high sodium intake increased bloating among trial participants. The researchers also found that the high-fiber DASH diet increased bloating among trial participants compared to a low-fiber control diet.
The study was published June 17 in the American Journal of Gastroenterology.
"Bloating is one of the leading gastrointestinal complaints in the U.S. and can be exacerbated in some people by a high-fiber diet; our results suggest that they might be able to reduce that bloating, without compromising on healthy fiber, by lowering their sodium intake," says study senior author Noel Mueller, PhD, MPH, an assistant professor in the Department of Epidemiology at the Bloomberg School.
Bloating is estimated to affect up to a third of U.S. adults overall, and more than 90 percent of those with irritable bowel syndrome. Bloating features a buildup of excess gas in the gut. The production of gas can be attributed to gas-producing gut bacteria breaking down fiber. There is also some evidence that sodium can stimulate bloating. The study by Mueller and colleagues is the first to examine sodium as a cause of bloating in the context of low- and high-fiber diets.
The study analyzed data from the DASH-Sodium trial, which was co-led by Bloomberg School researcher Lawrence Appel, MD, MPH, and sponsored by the National Heart, Lung and Blood Institute. Conducted at four clinical centers during 1998-99, it tested the DASH diet, a high-fiber diet which is relatively low in fat and high in fruits, nuts, and vegetables, against a low-fiber control diet. Each of the two diets was tested at three levels of sodium, and the 412 participants all had high blood pressure at the trial start. The trial was set up chiefly to determine the effect of dietary sodium and other factors on blood pressure, but included data on participants' reports of bloating--data that Mueller and colleagues analyzed for the new study.
The team found that prior to the trial, 36.7 percent of the participants reported bloating, which is more or less in line with national surveys of bloating prevalence. They found too that the high-fiber DASH diet increased the risk of bloating by about 41 percent, compared to the low-fiber control diet--and men were more susceptible to this effect, compared to women. But the scientists also determined that sodium was a factor in bloating. When they combined data from the DASH and control diets, and compared the highest level of sodium intake to the lowest, they found that the high-sodium versions of those diets collectively increased the risk of bloating by about 27 percent compared to the low-sodium versions.
The key implication is that reducing sodium can be an effective way to reduce bloating--and in particular may be able to help people maintain a healthy, high-fiber diet.
How sodium causes bloating is still being studied. Salt causes water retention, and that may be one factor. "We hypothesize that sodium intake also alters the gut microbiome in a manner that modifies bacterial sulfide production," Mueller says.
He and his team are now researching how bloating is affected by the major dietary macronutrients: protein, carbs and fat.

Extreme exercise can strain the heart without causing permanent damage


Researchers have found no evidence of elevated cardiac risk in runners who completed a 24-hour ultramarathon (24UM), despite the transient elevation of blood biomarkers that measure cardiac health. According to the study in the journal Heliyon, published by Elsevier, trained runners were more likely than their novice counterparts to experience raised levels, reflecting the greater cardiac load and pituitary-adrenocortical response to extremely strenuous exercise.
"Experienced runners performed with greater intensity and speed, which placed strains on their hearts. Novice runners ran with less intensity, which resulted in lower cardiac biomarker levels," explained co-lead investigator, Rodrigo Hohl, PhD, Department of Physiology, Institute of Biological Sciences, Federal University of Juiz de Fora, Juiz de Fora, Brazil. Prof. Hohl also noted that 24UM participants self-pace for a set time and towards an established endpoint. Runners with differences in training experience and competitive performances present variations in running speeds and, therefore, cardiac biomarker responses.
"The good news is that while experienced runners pushed their heart limits during the ultramarathon, they did not show evidence of cardiac risk assessed through elevated biomarkers," Prof. Hohl noted. "Novice runners appear to pace themselves well below their cardiac limit, self-selecting a safe pacing strategy for their hearts.
The study examined the relationship between self-selected exercise intensity with cardiac biomarkers comparing experienced and novice runners able to finish a 24UM. Biomarkers that measure necrosis, inflammation, cardiac function/injury, and ischemia were used to understand the impact of acute exercise on the cardiac health of runners with different training levels and performance, including cortisol, total creatine kinase, C-reactive protein, and leukocyte levels. The findings showed higher levels of cortisol in the experienced group and confirmed previous research that cortisol is a good predictor of speed during a 24UM.
Although the study did not show clear evidence of cardiac risk when comparing cardiac biomarker levels with clinical cut-off values, it did establish that prolonged heart overload varies according to running speed. The wide range of ultramarathon distances and durations makes it challenging to generalize about cardiac risks and biomarkers response. Moreover, competitors modulate running intensity according to individual exercise tolerance and motivations to push themselves to increase levels of physical endurance, and little is known about the effect of extreme environmental conditions. Therefore, experienced ultramarathon runners should not consider themselves free of risk.
"Our study provides evidence for caution and self-monitoring especially for experienced runners. After participating in an ultramarathon, runners should recover for at least two days before running any significant distance. This time is needed to normalize cardiac markers and allow the heart time to recover after such a challenge," cautioned Prof. Hohl.

A total of 25 runners participated in the study, which involved observation of a 24UM and blood tests before and after the event. Eleven runners in the experienced group had trained a distance of more than 100 km a week over a five-year period. Fourteen novices had previously run at least one regular marathon but had not participated in an ultramarathon. Exclusion criteria eliminated smokers, steroid users, as well as anyone with cardiovascular or metabolic disease or musculoskeletal injury from the study group.



Heart-healthy effects of soy


Researchers at the University of Toronto have found a consistent cholesterol-lowering effect for soy protein, with pooled data from dozens of clinical trials that span the last two decades.
The study calls into question the U.S. Food and Drug Administration's current proposal to revoke the health claim for soy protein and heart disease.
"At no time since the original claim for soy as a reducer of serum cholesterol has its ability been in question," says David Jenkins, professor of nutritional sciences and of medicine at U of T. "It's been consistent since 1999. The data have not changed."
The researchers showed a reduction from soy in both total cholesterol and low-density lipoprotein cholesterol, which can damage the heart. The effect is steady across all 46 trials that the FDA cited in 2017, when it first proposed to revoke the health claim for soy based on recent trials that showed variable results.
The Journal of the American Heart Association published the findings today.
"Sometimes you see a regression to the mean, where analyses with small studies produce big effects that diminish over time as sample sizes increase and results get more precise," says John Sievenpiper, a professor of nutritional sciences at U of T and clinician-scientist at St. Michael's Hospital who co-authored the study. "We saw that with fish oil, for example. But in this case nothing has changed."
The researchers performed a cumulative meta-analysis, which let them look at the effect of soy in all the trials combined, but at different points in time with the addition of data from each new trial. The FDA will likely make a decision on the health claim for soy this summer; options include a full retraction and retention of a qualified health claim.
"These data strongly support the rationale behind the original FDA heart health claim for soy," says Jenkins, who is also a researcher in the Joannah & Brian Lawson Centre for Child Nutrition at U of T and a clinician-scientist at St. Michael's Hospital. "And it's important to note that while the reduction in cholesterol was less than five percent, if you put that together with other plant-based foods in a portfolio you get a much stronger effect."
Jenkins and his colleagues in the 1980s pioneered the glycemic index, which shows the effect of various foods on blood sugar levels. More recently, he helped develop a dietary portfolio that includes nuts, plant-based protein, viscous fibre and plant sterols, which together can lower risk factors for heart disease by up to 30 per cent.
This portfolio of foods has been incorporated into dietary guidelines by Heart UK and the European Atherosclerosis Society, among others. Health Canada released a national food guide that encourages plant-based eating this year, and the FDA maintains health claims for several other plant foods in the dietary portfolio.
"It's disheartening that the FDA has focused on soy," says Jenkins. "We see similar data for other foods in the portfolio. If you knock out one leg of that stool then the others could be up for grabs, right when concerns about health and the environment are bringing plant-based eating into the mainstream."
Companies such as Beyond Meat and Impossible Foods have seen huge growth this year with plant-based alternatives to meat. Burger King plans to offer its soy-based burger nation-wide in the U.S. by the end of 2019.
"We're moving into an age of plant-based protein, and it would be a shame to see that shift undermined," says Jenkins. "Plant-based food producers, industry and retailers need all the help they can get, to make their products accessible."
Professors Jenkins and Sievenpiper have received support from government, non-profit and industry funding sources, some of which include companies and industry groups that produce or promote soy and other plant-based foods. See the Disclosures section at the end of the study for a full list of their funding sources and industry connections.

Vitamin E taken as part of a dietary supplement also increases the chances of lung cancer spread


A new study explains why lung cancer spreads faster in patients with certain genetic changes, and suggests that taking vitamin E, long thought of as preventive, may cause the same spread.
Led by researchers at NYU School of Medicine and Perlmutter Cancer Center, experiments in mice and human tissue revealed how mechanisms that protect cancer cells from the byproducts of their own aggressive growth are connected by the protein BACH1 to cancer cell migration and tissue invasion.
Published online on June 27 in the journal Cell, the study results reflect the nature of cancer cells, which arise in one place, but often spread (metastasize) and take root elsewhere. Lung cancer metastasis is the leading cause of cancer death in the United States.
About 40 percent of lung cancers are adenocarcinomas, which form from mucous-producing cells, and which have already spread beyond lung tissue in 22 percent of cases by the time they are diagnosed.
"Our results finally clarify the web of mechanisms surrounding the BACH 1 signal, and suggest that an already approved drug class may counter cancer spread in about 30 percent of lung adenocarcinoma patients," says senior study author Michele Pagano, MD, chair of the Department of Biochemistry and Molecular Pharmacology at NYU School of Medicine.
The Price of Fuel
The newly published work revolves around random changes, called mutations, which occur continually throughout the DNA code. While many are weeded out, some persist to either make no difference, cause disease, or help cells to better survive changing conditions as part of evolution.
Such changes are known to, for instance, help lung adenocarcinoma cells survive oxidative stress, a process where highly-reactive, cell-damaging molecules (oxidants) are made as a side effect of "burning" fuel to make energy. Cancer cells need extra fuel to support aggressive growth, produce more oxidants, and depend more on naturally occurring antioxidants to neutralize them.
Along these lines, past studies have shown that about 30 percent of non-small cell lung cancers (which include adenocarcinomas) thrive by acquiring mutations that ether increase levels of the protein NRF2 - known to turn on genes that increase antioxidant production - or that disable KEAP1, which targets NRF2 for destruction.
Complicating matters, oxidative stress is known to cause the release a chemical compound called heme. Best known for its role in hemoglobin - the oxygen-carrying red blood cell pigment - heme, in its free form, also amplifies oxidative stress. Cells protect themselves from the heme-driven wave of oxidants by making more of the enzyme heme oxygenase-1 (HO1), which neutralizes heme.
By engineering mice with lung adenocarcinoma cells that lacked Keap1 gene (and thereby increasing levels of NRF2), the study authors were able to show that too high NRF2 levels, and the related overproduction of antioxidants, encourages HO1 production. More HO1 activity means lower amounts of active heme.
This became even more important when the researchers discovered that heme partners with the protein FBOX22 to cause the breakdown of BACH1, explaining how increased NRF2 activity increases BACH1 levels.
Normally, say the authors, NRF2-driven, antioxidant-dependent increases in BACH1 levels are short-lived, activated only during brief blasts of oxidative stress, and possibly not rising to levels that trigger cell migration through BACH1. But the new data suggest that big enough increases override mechanisms that would otherwise limit BACH1 levels.
Furthermore, analyses of human tumor tissue revealed that HO1 and BACH1 are found in significantly higher levels in human lung cancer cells that have spread, and in lung cancers of advanced stage and grade. One theory holds that oxidative stress defenses and migration evolved to overlap so that cells faced with extreme stress locally could migrate in search of a better home.
Moving forward, the team seeks to explore whether HO1 inhibitors - already FDA approved the treatment of inherited disorders called porphyrias - could be tested in a clinical trial to slow or prevent lung cancer spread.
Importantly, a second paper publishing in the same edition of Cell, and led by Martin Bergo of the Department of Biosciences and Nutrition at Karolinska Institutet in Sweden, suggests that vitamin E taken as part of a dietary supplement also increases the chances of lung cancer spread through its effect on BACH1.
"For lung cancer patients, taking vitamin E may cause the same increases in cancer's ability to spread as the NRF2 and KEAP1 mutations that our team has linked to shorter survival," says study author Thales Papagiannakopoulos, PhD, assistant professor in the Department of Pathology at NYU School of Medicine. "We hope these findings help to dispel the myth that antioxidants like vitamin E help to prevent every type of cancer."

Wednesday, June 26, 2019

22 percent of young men, 5 percent of young women engage in 'disordered eating' to bulk up


Summary:
New research finds that adolescents who see themselves as puny and who exercise to gain weight may be at risk of so-called muscularity-oriented disordered eating behaviors.

Adolescents who see themselves as puny and who exercise to gain weight may be at risk of so-called muscularity-oriented disordered eating behaviors, say researchers led by UCSF Benioff Children's Hospitals.
The researchers found that 22 percent of males and 5 percent of females ages 18-to-24 exhibit these disordered eating behaviors, which are defined as including at least one of the following: eating more or differently to gain weight or bulk up, and use of dietary supplements or anabolic steroids to achieve the same goal.
Left unchecked, these behaviors may escalate to muscle dysmorphia, characterized by rigid diet, obsessive over-exercising and extreme preoccupation with physique, say the researchers in their study publishing in the International Journal of Eating Disorders on June 20, 2019.
"Some eating disorders can be challenging to diagnose," said first author Jason Nagata, MD, of the UCSF Division of Adolescent and Young Adult Medicine. "Unlike anorexia nervosa, which may be easily identified by parents or pediatricians, disordered eating to increase bulk may masquerade as healthy habits and because of this, it tends to go unnoticed."
Heart Failure, Depression, Social Isolation in Worst Cases
At its most extreme, it can lead to heart failure due to insufficient calories and overexertion, as well as muscle dysmorphia, which is associated with social withdrawal and depression, Nagata said.
The 14,891 young adults in the study, who came from throughout the United States, had been followed for seven years. The researchers wanted to see if the early data, when the participants' average age was 15, revealed something about their perceptions and habits that may serve as warning signs.
They found that boys who exercised specifically to gain weight had 142 percent higher odds of this type of disordered eating; among girls, the odds were increased by 248 percent. Boys who perceived themselves as being underweight had 56 percent higher odds; in girls the odds were 271 percent higher. Smoking and alcohol use in boys, and smoking in girls, increased odds moderately.
Additionally, being of black race bolstered odds by 66 percent in boys and 181 percent in girls.
Non-heterosexual identity, which the participants had been asked about when they reached adulthood, was not found to be a risk factor, the researchers said.
In young adulthood, 6.9 percent of males reported supplement use to gain weight or build muscle and 2.8 percent said they used anabolic steroids. Use by young women was significantly lower at 0.7 percent and 0.4 percent respectively.
"Supplements are a black box, since they are not regulated," noted Nagata. "In extreme cases, supplements can cause liver and kidney damage. Anabolic steroids can cause both long-term and short-term health issues, including shrunken testicles, stunted growth and heart disease."
Nagata said that clues that indicate behaviors may approach muscle dysmorphia include a highly restrictive diet that omits fats and carbohydrates, compulsive weighing and checking of appearance, and extensive time dedicated to exercise that may cut into social activities.

Tuesday, June 25, 2019

Educational attainment may improve cardiovascular risk factors and outcomes



Increased educational attainment during childhood is associated with a reduction in heart disease and improvements in several cardiovascular risk factors in adulthood, according to a study published June 25 in the open-access journal PLOS Medicine by Rita Hamad of the University of California San Francisco, United States and colleagues. As noted by the authors, the findings suggest that policies to increase educational attainment could reduce the burden of heart disease at the population level.
Heart disease is a leading cause of mortality in the US, and clinicians are increasingly interested in addressing its social and economic determinants. Education is highly correlated with heart disease, but this may be because education and heart disease have common causes such as parental socioeconomic status and genetic factors. Even if there is a causal relationship, the mechanisms by which education influences heart disease are unclear. As a result, there is ongoing debate as to whether education should be included in cardiovascular disease prediction algorithms, and it is also unclear whether interventions targeting education might affect cardiovascular disease. To address this gap in knowledge, Hamad and colleagues leveraged a natural experiment--variation in US education policies that determine schooling duration--to examine possible effects of education on heart disease and its risk factors.
The authors linked census data on educational attainment during childhood (covering approximately 5.4 million individuals) with health outcomes in adulthood (covering 30,853 and 44,732 participants in two surveys). Increased education was consistently associated with a reduction in heart disease and improvements in several cardiovascular risk factors, including smoking, high-density lipoprotein, and depression. However, increased education was also associated with higher body-mass index and total cholesterol. Taken together, the findings contribute new knowledge on potential pathways through which education may influence cardiovascular disease. According to the authors, the findings strengthen the argument for intervening on education to reduce disparities in cardiovascular disease, and support the inclusion of educational attainment in prediction algorithms and primary prevention guidelines for cardiovascular disease.

Increased walking activity associated with long-term health benefits


Short term pedometer-based walking interventions can have long-term health benefits for adults and older adults, according to new research published in the open-access journal PLOS Medicine on 25 June. Tess Harris and colleagues from St George's University of London, UK and other institutions, conducted two trials of walking interventions which aimed to increase step count and physical activity. Not only did the investigators see sustained increases in physical activity at 3-4 years in the intervention group participants, they also noted fewer cardiovascular events and fractures.

Physical activity has been shown to be protective for many health conditions, and inactivity is a key risk factor contributing to the global burden of disease. However, long-term follow-up of physical activity trials is lacking. Here, two randomised controlled trials of 12-week pedometer-based walking interventions in primary care were followed up with long-term data from primary health records at 4 years.

The team studied data from 1297 participants of the PACE-UP and PACE-Lift trials. People in the intervention arms were less likely to have a cardiovascular event (Hazard Ratio 0.34, 95% CI 0.12-0.91, p = 0.03) or a fracture (HR 0.56, 95% CI 0.35-0.90, p = 0.02) than those in the control arms. No differences were seen in incidence of diabetes or depression in people in the intervention as compared with those in the control arms. Based on these observations, about 61 people would need to receive the walking intervention to prevent one cardiovascular event and 28 people to prevent one fracture. Although the rates of adverse health events were low in this study, and were restricted to only those recorded in primary care records, under-recording would not have differed by intervention status, so should not have led to bias.

The authors note that "short-term walking interventions can produce long-term health benefits and should be more widely used to help address the public heath inactivity challenge."

Women exposed to common antibacterial chemical more likely to break a bone


Women exposed to triclosan are more likely to develop osteoporosis, according to a study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.

Triclosan is an endocrine-disrupting chemical being widely used as an antibacterial in consumer goods and personal care products, including soaps, hand sanitizers, toothpaste, and mouthwash. A person can be exposed to triclosan via consumer products and contaminated water. The FDA also banned triclosan from over-the-counter hand sanitizer in recent years.

"Laboratory studies have demonstrated that triclosan may have potential to adversely affect the bone mineral density in cell lines or in animals. However, little is known about the relationship between triclosan and human bone health," said the study's corresponding author, Yingjun Li, Ph.D., of Hangzhou Medical College School of Public Health in Hangzhou, China. "As far as we know, this is the first epidemiological study to investigate the association between triclosan exposure with bone mineral density and osteoporosis in a nationally representative sample from U.S. adult women."

In this study, researchers analyzed data from 1,848 women in the National Health and Nutrition Examination Survey to determine the link between triclosan and bone health. They found women with higher levels of triclosan in their urine were more likely to have bone issues.

Exercise an effective protection against life-threatening cerebral hemorrhage


A Finnish study demonstrates that as little as half an hour of light exercise per week effectively protects against subarachnoid haemorrhage, the most lethal disorder of the cerebral circulation.
Among disorders of the cerebral circulation, subarachnoid haemorrhage (SAH) is the most lethal kind, with as many as half of those affected dying within three months. As the related mortality rate is high, a feverish search for predisposing factors has been underway across the globe for the past few decades. Previously, smoking and high blood pressure have been observed to heighten the risk of an SAH haemorrhage, but research evidence on the effects of exercise has remained scarce.
In a Finnish follow-up study published in the distinguished Scientific Reports journal, the effects of exercise on SAH risk were investigated in a cohort of roughly 70,000 Finns gained from the FINRISK population survey. The findings indicate that as little as half an hour of light exercise per week reduces the risk of SAH by approximately 5%, with the benefit increasing proportionally to the amount of exercise. This can be achieved, for example, by walking, cycling or, say, skiing to work.
"Even moderate physical exercise, such as a 30-minute walk or bike ride four days a week reduces the risk of SAH by roughly 20%, regardless of age and gender," says physician Joni Lindbohm, the principal author of the research article.
"As such, the finding did not really come as a surprise, as exercise is known to work well in preventing many other cardiovascular diseases. However, the extent and comprehensive nature of the benefit among various groups of people was a positive surprise."
The study also demonstrated the favourable effect of increased exercise in connection with smoking and high blood pressure, the other SAH risk factors. For smokers in particular, exercise reduces the risk as much as twice the amount applicable to the rest of the population.
"However, what must not be overlooked is the fact that smoking remains the number one risk factor for SAH and that quitting smoking is the principal way of preventing the appearance of the disorder," Lindbohm notes.
Most SAH haemorrhages are the result of ruptured cerebral aneurysms, causing blood to flow from the largest cerebral arteries into the space between meninges, the membranes surrounding the brain, which increases intracranial pressure and reduces cerebral circulation.
"Even with no accurate scientific evidence of the biological mechanism of action produced by exercise in terms of SAH, the reduced risk is most likely connected with a reduction in a systemic inflammatory state, which also affects the walls of cerebral arteries," neurosurgeon Miikka Korja explains.
According to Lindbohm and Korja, key to minimising the risk of SAH is quitting smoking, balancing one's blood pressure and exercising regularly.

Cholesterol medication could invite diabetes


A study of thousands of patients' health records found that those who were prescribed cholesterol-lowering statins had at least double the risk of developing type 2 diabetes.
The detailed analysis of health records and other data from patients in a private insurance plan in the Midwest provides a real-world picture of how efforts to reduce heart disease may be contributing to another major medical concern, said Victoria Zigmont, who led the study as a graduate student in public health at The Ohio State University.
Statins are a class of drugs that can lower cholesterol and blood pressure, reducing the risk of heart attack and stroke. More than a quarter of middle-aged adults use a cholesterol-lowering drug, according to recent federal estimates.
Researchers found that statin users had more than double the risk of a diabetes diagnosis compared to those who didn't take the drugs. Those who took the cholesterol-lowering drugs for more than two years had more than three times the risk of diabetes.
"The fact that increased duration of statin use was associated with an increased risk of diabetes - something we call a dose-dependent relationship - makes us think that this is likely a causal relationship," Zigmont said.
"That said, statins are very effective in preventing heart attacks and strokes. I would never recommend that people stop taking the statin they've been prescribed based on this study, but it should open up further discussions about diabetes prevention and patient and provider awareness of the issue."
Researchers also found that statin users were 6.5 percent more likely to have a troublingly high HbA1c value - a routine blood test for diabetes that estimates average blood sugar over several months.
The study, published in the journal Diabetes Metabolism Research and Reviews, included 4,683 men and women who did not have diabetes, were candidates for statins based on heart disease risk and had not yet taken the drugs at the start of the study. About 16 percent of the group - 755 patients - were eventually prescribed statins during the study period, which ran from 2011 until 2014. Participants' average age was 46.
Randall Harris, a study co-author and professor of medicine and public health at Ohio State, said that the results suggest that individuals taking statins should be followed closely to detect changes in glucose metabolism and should receive special guidance on diet and exercise for prevention.
Although statins have clear benefits in appropriate patients, scientists and clinicians should further explore the impact of statins on human metabolism, in particular the interaction between lipid and carbohydrate metabolism, said co-author Steven Clinton, a professor of medicine and member of Ohio State's Comprehensive Cancer Center.
"In addition, researchers conducting large prospective cohort studies should be considering how statins impact human health overall. They should consider both risks and benefits, not just the disease that is being treated by the specific drug," Clinton said.
The study was done retrospectively, meaning that the researchers looked back at existing records from a group of patients to determine if there were any possible connections between statin prescriptions and diabetes. Previous research has suggested a connection, but this study design allowed for a glimpse at what is happening naturally in the clinical setting, rather than what happens in a prospective trial that randomly assigns some people to statins and some people to placebo, said Zigmont, who is now an assistant professor at Southern Connecticut State University.
The study was enriched by the availability of a variety of details on the study population, including data from biometric screenings and a health survey that asked about education, health behaviors and ethnicity, Zigmont said. She also had access to medical claims data and pharmacy claims data.
Zigmont was careful to take a wide variety of confounding factors into account in an effort to better determine if the statins were likely to have caused the diabetes, she said. Those included gender, age, ethnicity, education level, cholesterol and triglyceride readings, body mass index, waist circumference and the number of visits to the doctor.
Programs that help patients improve their fitness and diets could be considered and discussed when doctors are prescribing statins, so that patients can be proactive about diabetes prevention, she said.
It would also be helpful for future research to better determine which statins and which doses might lead to the greatest risk, Zigmont said. Her study didn't allow for an analysis based on different types of statins.
Limitations of the research include the fact that the majority of statin users were white, and that the research team had no way of knowing how closely patients adhered to their doctors' prescriptions. There also was no way of determining who was at elevated risk of diabetes at the study's onset, Zigmont said.

Current research into the roles of choline and docosahexaenoic acid (DHA) in maternal and infant nutrition




A review paper in the the journal Nutrients, highlighs current research into the roles of choline and docosahexaenoic acid (DHA) in maternal and infant nutrition. 

National data shows that most adult Americans, more than 90%, do not have adequate dietary intake of choline and DHA, this is found to be especially true in women of child-bearing age and pregnant women. Choline and DHA play a significant role in infant brain and eye development, with inadequate intakes leading to visual and neurocognitive deficits. 

The review paper findings suggest a link between intake of DHA and choline, and that an inadequate intake of one or both nutrients may have an impact on baby's brain and eye development. Furthermore, emerging findings illustrate a synergistic interaction between choline and DHA, indicating that insufficient intakes of one or both could have lifelong impact on both maternal and infant health, particularly brain health. Therefore, supplementation of DHA and choline, particularly for vulnerable populations including women during pregnancy and lactation, should be considered.
"This review paper suggests that prenatal care can be improved with a greater understanding of maternal nutrient needs and how an individual's dietary intake, as well as their genetic and lifestyle factors, may impact metabolism of these important nutrients," said Susan Hazels Mitmesser, PhD, vice president of science & technology at Pharmavite. "As part of prenatal care, it may be beneficial to include testing of key nutrients such as DHA and choline, to ensure adequate intake levels are being met."
Leading health organizations including American Congress of Obstetricians & Gynecologists (ACOG), American Academy of Pediatrics (AAP), Europe Food Safety Authority (EFSA), and World Health Organization (WHO) have highlighted the importance of several key nutrients during pregnancy, including choline and DHA. The 2018 AAP policy statement emphasized the role of nutrition in the first 1000 days of life, including choline and DHA as key nutrients in supporting early neurodevelopment and lifelong mental health.

Goat milk kefir is proven to be good for your health

University of Córdoba
Kefir is a fermented dairy product that is gradually becoming more and more common to see on the shelves of Spanish shops and supermarkets. Since it is a milk-based product, made from lactic acid and alcoholic fermentation, it is assumed to have several health-enhancing functions resulting from its protein and peptide content with biological activity (molecules made up of amino acids, smaller than proteins, that are beneficial for one's health).
However, to date there had never been a complete analysis of what kinds of peptides goat milk kefir has. So, a University of Cordoba research team made up of researchers from the Biochemistry, Proteomics and Biology of Plant and Agroforestry Systems Group as well as from the Headquarters for Research Support (abbreviatd to SCAI in Spanish) led by Professor Manuel Rodríguez decided to characterize the peptidome (set of peptides) of this product in order to open the doors to the study of kefir's positive characteristics.
In order to accomplish this detailed result, they focused on 22 proteins and applied the technique of tandem mass spectrometry to kefir in three fermentation times (12 hours, 24 hours and 36 hours) to detect, in addition to the advantageous compounds, the peaks of concentration depending on fermentation time. A gradual increase in peptide content was found to occur during fermentation for 24 hours. When the 24 hour mark was reached, the concentration was highest and began to descrease.
Once the peptides present in goat milk kefir and their quantities according to fermentation time were determined, the University of Cordoba team had detected 11 beneficial compounds related to antihypertensive, antioxidant and antibacterial activity.
These kinds of exploratory studies will enable different research teams to continue delving deeper into understanding the health benefits of this product, and may well breathe new life into the goat sector.

Milk: Best drink to reduce burn from chili peppers


People who order their Buffalo wings especially spicy and sometimes find them to be too "hot," should choose milk to reduce the burn, according to Penn State researchers, who also suggest it does not matter if it is whole or skim.
The research originated as an effort by the Sensory Evaluation Center in Penn State's College of Agricultural Sciences to identify a beverage to clear the palates of participants in tasting studies involving capsaicin. An extract from chili peppers, capsaicin is considered an irritant because it causes warming and burning sensations.
"We were interested in giving capsaicin solutions to many test participants and we were concerned with the lingering burn at the end of an experiment," said center director John Hayes, associate professor of food science. "Initially, one of our undergrad researchers wanted to figure out the best way to cut the burn for people who found our samples to be too intense."
Widespread consumption of chili peppers and foods such as wings spiced with siracha and hot sauce show that many people enjoy this burn, Hayes added. But these sensations also can be overwhelming. While folklore exists on the ability of specific beverages to mitigate capsaicin burn, quantitative data to support these claims are lacking.
The researchers looked at five beverages and involved 72 people -- 42 women and 30 men. Participants drank spicy Bloody Mary mix, containing capsaicin. Immediately after swallowing, they rated the initial burn.
Then, in subsequent separate trials, they drank purified water, cola, cherry-flavored Kool-Aid, seltzer water, non-alcoholic beer, skim milk and whole milk. Participants continued to rate perceived burn every 10 seconds for two minutes. There were eight trials. Seven included one of the test beverages and one trial did not include a test beverage.
The initial burn of the spicy Bloody Mary mix was, on average, rated below "strong" but above "moderate" by participants and continued to decay over the two?minutes of the tests to a mean just above "weak," according to lead researcher Alissa Nolden. All beverages significantly reduced the burn of the mix, but the largest reductions in burn were observed for whole milk, skim milk and Kool-Aid.
More work is needed to determine how these beverages reduce burn, noted Nolden, a doctoral student in food science at Penn State when she conducted the research, now an assistant professor in the Department of Food Science at the University of Massachusetts. She suspects it is related to how capsaicin reacts in the presence of fat, protein and sugar.
"We weren't surprised that our data suggest milk is the best choice to mitigate burn, but we didn't expect skim milk to be as effective at reducing the burn as whole milk," she said. "That appears to mean that the fat context of the beverage is not the critical factor and suggests the presence of protein may be more relevant than lipid content."
Following the completion of all the trials, the participants answered two questions: "How often do you consume spicy food?" and "Do you like spicy food?" Researchers had hoped to see some correlation between participants' perception of the burn from capsaicin and their exposure to spicy food, Nolden pointed out. But no such relationship emerged from the study.
The findings of the research, recently published in Physiology and Behavior, might surprise some spicy foods consumers, but they should not, Nolden noted.
"Beverages with carbonation such as beer, soda and seltzer water predictably performed poorly at reducing the burn of capsaicin," she said. "And if the beer tested would have contained alcohol, it would have been even worse because ethanol amplifies the sensation."
In the case of Kool-Aid, Nolden and her colleagues do not think that the drink removes the capsaicin but rather overwhelms it with a sensation of sweet.
The study was novel, Nolden believes, because it incorporated products found on food-market shelves, making it more user friendly.
"Traditionally, in our work, we use capsaicin and water for research like this, but we wanted to use something more realistic and applicable to consumers, so we chose spicy Bloody Mary mix," she said. "That is what I think was really cool about this project -- all the test beverages are commercially available, too."

Commonly prescribed drugs could increase the risk of dementia, says a new study



The study, carried out by experts from the University of Nottingham and funded by the NIHR School for Primary Care Research, found that there was nearly a 50% increased risk of dementia among patients aged 55 and over who had used strong anticholinergic medication daily for three years or more.
Anticholinergic drugs help to contract and relax muscles. They work by blocking acetylcholine, a chemical that transmits messages in the nervous system.
Doctors prescribe the drugs to treat a variety of conditions, including chronic obstructive pulmonary disease, bladder conditions, allergies, gastrointestinal disorders and symptoms of Parkinson's disease.
These medicines can have short-term side effects, including confusion and memory loss, but it is less certain whether long-term use increases the risk of dementia.
The research, published in the JAMA Internal Medicine journal and led by Professor Carol Coupland from the University's Division of Primary Care, looked at the medical records of 58,769 patients with a diagnosis of dementia and 225,574 patients without a diagnosis of dementia, all aged 55 and over and registered with UK GPs contributing data to the QResearch database, between 1 January 2004 and 31 January 2016.
The study findings showed increased risks of dementia for anticholinergic drugs overall and specifically for the anticholinergic antidepressants, antipsychotic drugs, antiparkinsons drugs, bladder drugs and epilepsy drugs after accounting for other risk factors for dementia.
No increased risks were found for the other types of anticholinergic drug studied such as antihistamines and gastrointestinal drugs.
Professor Tom Dening, Head of the Centre for Dementia at the University of Nottingham and a member of the research study team, said: "This study provides further evidence that doctors should be careful when prescribing certain drugs that have anticholinergic properties. However, it's important that patients taking medications of this kind don't just stop them abruptly as this may be much more harmful. If patients have concerns, then they should discuss them with their doctor to consider the pros and cons of the treatment they are receiving."
The 58,769 patients with dementia had an average age of 82 and 63% were women. Each dementia case was matched to five control patients of the same age, sex, and general practice.
Anticholinergic drug exposure was assessed using prescription information over a complete period of 10 years from 1 to 11 years before diagnosis of dementia or the equivalent dates in control patients, and was compared between the two patient groups. Further analysis looked at prescriptions for anticholinergic drugs up to 20 years before diagnosis of dementia.
This is an observational study so no firm conclusions can be drawn about whether these anticholinergic drugs cause dementia, and it is possible that the drugs were being prescribed for very early symptoms of dementia.
Professor Coupland said: "Our study adds further evidence of the potential risks associated with strong anticholinergic drugs, particularly antidepressants, bladder antimuscarinic drugs, anti-Parkinson drugs and epilepsy drugs.
"The risks of this type of medication should be carefully considered by healthcare professionals alongside the benefits when the drugs are prescribed and alternative treatments should be considered where possible, such as other types of antidepressants or alternative types of treatment for bladder conditions. These findings also highlight the importance of carrying out regular medication reviews.
"We found a greater risk for people diagnosed with dementia before the age of 80 which indicates that anticholinergic drugs should be prescribed with caution in middle-aged people as well as in older people."
These results, along with those of a similar study published in 2018 help to clarify which types of anticholinergic drug are associated with the highest risks of dementia.
In the 1-11 years before the dementia diagnosis date or equivalent in controls, nearly 57% of cases and 51% of controls were prescribed at least one strong anticholinergic drug, with an average of six prescriptions in cases and 4 in controls. The most frequently-prescribed types of drugs were antidepressants, anti-vertigo and bladder antimuscarinic drugs - which are used to treat an overactive bladder.
The increased risk associated with these drugs indicates that if the association is causal around 10% of dementia diagnoses could be attributable to anticholinergic drug exposure, which would equate to around 20,000 of the 209,600 new cases of dementia per year in the UK.
This is a sizeable proportion and is comparable with other modifiable risk factors for dementia, including 5% for midlife hypertension, 3% for diabetes, 14% for later life smoking and 6.5% for physical inactivity.

Nutrition is the missing ingredient in home health today


  • Real-world data from Advocate Health Care and Abbott shows prioritizing nutrition care for home health patients helped keep them out of the hospital
  • Improved health outcomes from nutrition intervention and educational support could help save millions of dollars in healthcare costs annually
New research from Advocate Health Care and Abbott found that prioritizing nutrition care* for home health patients at risk for malnutrition had a dramatic impact on helping keep them out of the hospital - resulting in millions of dollars in healthcare cost savings. Nearly 5 million Americans annually rely on home healthcare to recover from an illness, injury or hospitalization.1,† While healthcare providers are constantly striving to improve patients' health and minimize hospitalizations, nutrition is often not top of mind, yet it plays a critical role in helping adults bounce back and resume their normal routine.
In the first-of-its-kind study, published today in the Journal of Parenteral and Enteral Nutrition, more than 1,500 home health patients were followed for 90 days.2 The study found that when patients at risk for malnutrition received a comprehensive nutrition care program, including nutrition drinks, to aid in their recovery:
  • Risk of being hospitalized was significantly reduced by 24% in the first 30 days, nearly 23% after 60 days, and 18% after 90 days.
  • Healthcare costs were reduced by more than $2.3 million or about $1,500 per patient at risk for malnutrition treated over the course of 90 days.
''Our goal as a home healthcare provider is to help patients get back on their feet as quickly as possible and to keep them out of the hospital,'' said Katie Riley, R.N., vice president, post acute chief nursing officer for Advocate Aurora Health and the lead study author. ''While the primary reason people come to home health isn't because they're malnourished or at risk, we have found that when we do pay attention to their nutrition care, it helps promote their strength and prevents them from going back to the hospital, which ultimately reduces healthcare costs.''
A RECIPE FOR RECOVERY
As many as 1 in 3 home health patients are at risk of malnutrition, which can impact their recovery or cause further health issues.1,3 But malnutrition often goes unrecognized as it can be invisible to the eye and can occur in both underweight and overweight individuals. Therefore, more healthcare systems are starting to focus efforts on the identification and management of malnourished or at-risk patients through regular monitoring and follow up.
"It's clear that nutrition can be a simple, cost-effective tool to improve patient outcomes,'' said Suela Sulo, Ph.D., health outcomes researcher at Abbott and a study author. "Healthcare systems are driven to improve patient care while reducing costs. Our research shows that prioritizing nutrition across different settings of care - or from hospital to home - can significantly cut costs while improving patients' health."
While home health often helps jumpstart the road to recovery, it's even more effective when patients are given the necessary nutrition education and tools to take their health by the reins, even after they stop receiving visits from clinicians.
''Educating people on the benefits of proper nutritional care can empower them to continue thinking about their nutrition and drinking their supplements,'' said Gretchen VanDerBosch, R.D., a lead registered dietitian at Advocate Health Care and a study author. ''By maintaining proper nutrition, patients have greater strength, heal faster, have fewer falls and reduced readmissions.''

Monday, June 24, 2019

Can deprescribing drugs linked to cognitive impairment actually reduce risk of dementia?


Regenstrief Institute
IMAGE
IMAGE: Writing in JAMA Internal Medicine, Regenstrief Institute investigators Noll Campbell, Richard Holden and Malaz Boustani call for randomized deprescribing trials to address anticholinergic drug use as a potentially modifiable and... view more 
Credit: Regenstrief Institute
INDIANAPOLIS - In a commentary published in JAMA Internal Medicine, three Regenstrief Institute research scientists write that while they and other researchers have identified a strong and consistent link between anticholinergic drugs and cognitive impairment from observational studies, randomized clinical trials represent the only rigorous method to definitively establish a causal relationship between these frequently used drugs and various dementias.
Drugs with anticholinergic properties are frequently prescribed for anxiety, depression, and certain types of pain or purchased over the counter for conditions including allergies or sleep problems.
The JAMA Internal Medicine commentary by Regenstrief Institute research scientists Noll Campbell, PharmD, M.S., a geriatric pharmacy researcher; Richard Holden, PhD, a human factors engineer and social-cognitive psychologist; and Malaz Boustani, M.D., MPH, a geriatrician and implementation scientist, call for randomized deprescribing trials to address anticholinergic drug use as a potentially modifiable and reversible risk factor for dementia, a growing public health issue.
That call was recently answered by a $3.3 million award from the National Institute on Aging to Dr. Campbell and colleagues to study whether there is a cause and effect relationship between this drug class and cognitive impairment.
If a causal link between anticholinergic medications and dementia is confirmed, changing from an anticholinergic to another drug would be less difficult than many other interventions known to modify dementia risk such as increasing physical activity, controlling diabetes, or decreasing blood pressure.
The three research scientists say that the next and definitive step to determine whether anticholinergic drugs cause dementia is to conduct long-term randomized deprescribing trials - decreasing or eliminating use of these very common medications - as they will be doing later this year, to see if cholinergic neurotransmission in the areas of the brain related to cognitive performance can be improved, ultimately reducing the risk of developing dementia or delaying onset.
Anticholinergics effect the brain by blocking acetylcholine, a nervous system neurotransmitter. These drugs are used by as many as half of older adults and it is not unusual for an older individual to be taking two or more anticholinergic medications regularly.
"Though we learn about potential risk factors through observational studies, the best way to define a causal relationship between anticholinergics and dementia requires a prospective, randomized trial," said commentary lead author and Regenstrief Institute research scientist Dr. Campbell, also a faculty member of Purdue University's College of Pharmacy. "In conducting such a trial, we can also learn about the risks and benefits of deprescribing medications, including the impact on symptom control, withdrawal or other adverse events, quality of life, and healthcare utilization."
Other areas for exploration noted in the commentary include whether a critical window of opportunity exists to capture the cognitive benefit of deprescribing anticholinergics, for example, whether deprescribing must be performed while these neurotransmitters are sufficiently healthy to benefit and show signs of improvement in cognition.
"Clinicians, health policy makers and patients need to understand the benefits and harms of deprescribing anticholinergics," Dr. Campbell added. "The bottom line is that we need as much high-quality evidence to understand risks and benefits of deprescribing a medication as we have to prescribe it. At the same time, we need to be exploring alternative medications which are known not to harm the aging brain and that patients can afford."
The commentary authors conclude that the ideal targets to reduce anticholinergic burden will be those anticholinergic medications that meet three criteria: (1) high risk of harm, (2) commonly used and (3) existence of an alternative drug to manage the patient's medical condition, if necessary.