180  03 MAY 2014 /  Compiled by Ralph Turchiano

 

• Detailed research references and further affiliations on each article are posted at http://www.healthreserachreport.me .

 

In This Issue:

• Cancer stem cells linked to drug resistance
• Why alcoholism saps muscle strength
• Ginseng can treat and prevent influenza and RSV, researcher finds
• Research shows impact of Facebook unfriending
• Biting into Whole Foods can Make Children Rowdy
• Acupuncture at Waiguan improves activation of functional brain areas of stroke patients
• Are almonds an optimal snack?
• Today’s statin users consume more calories and fat than their predecessors
• High doses of antidepressants appear to increase risk of self-harm in children young adult
• Study: Tart cherry juice increases sleep time in adults with insomnia
• Higher calcium intake may reduce body fat, mitigating genetic risk for diabetes
• Heart attack survivors who eat lots of fiber live longer
• Vitamin D may raise survival rates among cancer patients
• Discovery of anti-appetite molecule released by fiber could help tackle obesity
• Initial research: Mango’s effects on ulcerative colitis and bone parameters in animal models
• Vitamin D deficiency may be linked to aggressive prostate cancer

Cancer stem cells linked to drug resistance

Discovery of previously undefined molecular pathway is step toward novel clinical trial

Most drugs used to treat lung, breast and pancreatic cancers also promote drug-resistance and ultimately spur tumor growth. Researchers at the University of California, San Diego School of Medicine have discovered a molecule, or biomarker, called CD61 on the surface of drug-resistant tumors that appears responsible for inducing tumor metastasis by enhancing the stem cell-like properties of cancer cells.

The findings, published in the April 20, 2014 online issue of Nature Cell Biology, may point to new therapeutic opportunities for reversing drug resistance in a range of cancers, including those in the lung, pancreas and breast.

“There are a number of drugs that patients respond to during their initial cancer treatment, but relapse occurs when cancer cells become drug-resistant,” said David Cheresh, PhD, Distinguished Professor of Pathology and UC San Diego Moores Cancer Center associate director for Innovation and Industry Alliances. “We looked at the cells before and after they became resistant and asked, ‘What has changed in the cells?'”

Cheresh and colleagues investigated how tumor cells become resistant to drugs like erlotinib or lapatinib, known as receptor tyrosine kinase inhibitors and commonly used in standard cancer therapies. They found that as drug resistance occurs, tumor cells acquire stem cell-like properties that give them the capacity to survive throughout the body and essentially ignore the drugs.

Specifically, the scientists delineated the molecular pathway that facilitates both cancer stemness and drug resistance, and were able to identify existing drugs that exploit this pathway. These drugs not only reverse stem cell-like properties of tumors, but also appear to re-sensitize tumors to drugs that the cancer cells had developed resistance to.

“The good news is that we’ve uncovered a previously undefined pathway that the tumor cells use to transform into cancer stem cells and that enable tumors to become resistant to commonly used cancer drugs,” said Cheresh.

Based on these findings, Hatim Husain, MD, an assistant professor who treats lung and brain cancer patients at Moores Cancer Center, has designed a clinical trial to attack this pathway in patients whose tumors are drug-resistant. The trial will be open to patients with lung cancer who have experienced cancer progression and drug resistance to erlotinib. It is expected to begin in the next year.

“Resistance builds to targeted therapies against cancer, and we have furthered our understanding of the mechanisms by which that happens,” said Husain. “Based on these research findings we now better understand how to exploit the ‘Achilles heel’ of these drug-resistant tumors. Treatments will evolve into combinational therapies where one may keep the disease under control and delay resistance mechanisms from occurring for extended periods of time.”

Although the trial is expected to begin with patients who have already experienced drug resistance, Husain hopes to extend the study to reach patients in earlier stages to prevent initial resistance.

Why alcoholism saps muscle strength

Mitochondrial repair may be to blame for muscle weakness in mitochondrial diseases and in long-time alcoholics

(PHILADELPHIA) — Muscle weakness is a common symptom of both long-time alcoholics and patients with mitochondrial disease. Now researchers have found a common link: mitochondria that are unable to self-repair. The results will be published online April 21 in The Journal of Cell Biology. The link to self-repair provides researchers both a new way to diagnose mitochondrial disease, and a new drug target.

Mitochondria — organelles that produce the energy needed for muscle, brain, and every other cell in the body — repair their broken components by fusing with other mitochondria and exchanging their contents. Damaged parts are segregated for recycling and replaced with properly functioning proteins donated from healthy mitochondria.

While fusion is one major method for mitochondrial quality control in many types of cells, researchers have puzzled over the repair mechanism in skeletal muscle — a type of tissue that relies constantly on mitochondria for power, making repair a frequent necessity. However, mitochondria are squeezed so tightly in between the packed fibers of muscle cells, that most researchers assumed that fusion among mitochondria in this tissue type was impossible.

An inkling that fusion might be important for the normal muscle function came from research on two mitochondrial diseases: Autosomal Dominant Optical Atropy (ADOA) disease, and a type of Charcot-Marie-Tooth disease (CMT). A symptom of both disease is muscle weakness and patients with both these diseases carry a mutation in one of the three genes involved in mitochondrial fusion.

To investigate whether mitochondria in the muscle could indeed fuse to regenerate, first author Veronica Eisner, Ph.D., a postdoctoral fellow at Thomas Jefferson University created a system to tag the mitochondria in skeletal muscle of rats with two different colors and then watch if they mingled. First, she created a rat model whose mitochondria expressed the color red at all times. She also genetically engineered the mitochondria in the cells to turn green when zapped with a laser, creating squares of green-shining mitochondria within the red background. To her surprise, the green mitochondria not only mingled with the red, exchanging contents, but were also able to travel to other areas where only red-colored mitochondria had been. The results were exciting in that they showed “for the first time that mitochondrial fusion occurs in muscle cells,” says Dr. Eisner.

The researcher team, led by Dr. Gyorgy Hajnoczky, M.D., Ph.D., Director of Jefferson’s MitoCare Center and professor in the department of Pathology, Anatomy & Cell Biology, then showed that of the mitofusin (Mfn) fusion proteins, Mfn1 was most important in skeletal muscle cells.

Once they had identified Mfn1, they were able to test whether mitochondrial fusion was the culprit in other examples of muscle weakness, such as alcoholism. One long-term symptom of alcoholism is the loss of muscle strength. The researchers showed that the Mfn1 abundance went down as much as 50 percent in rats on a regular alcohol diet-while other fusion proteins were unchanged, and that this decrease was coupled with a massive decrease in mitochondrial fusion. When Mfn1 was restored, so was the mitochondrial fusion. They also linked the decreased Mfn1 and mitochondrial fusion to increased muscle fatigue.

“That alcohol can have a specific effect on this one gene involved in mitochondrial fusion suggests that other environmental factors may also specifically alter mitochondrial fusion and repair,” says Dr. Hajnoczky.

“The work provides more evidence to support the concept that fission and fusion — or mitochondrial dynamics — may be responsible for more than just a subset of mitochondrial diseases we know of,” says Dr. Hajnoczky. “In addition, knowing the proteins involved in the process gives us the possibility of developing a drug.”

Ginseng can treat and prevent influenza and RSV, researcher finds

ATLANTA–Ginseng can help treat and prevent influenza and respiratory syncytial virus (RSV), a respiratory virus that infects the lungs and breathing passages, according to research findings by a scientist in Georgia State University’s new Institute for Biomedical Sciences.

In a recent issue of Nutrients and an upcoming publication of the International Journal of Molecular Medicine, Sang-Moo Kang reports the beneficial effects of ginseng, a well-known herbal medicine, on human health.

Kang’s primary research focuses on designing and developing effective vaccines against viral diseases such as influenza virus and RSV, but he partnered with a university and research institutes in South Korea that wanted international collaborative projects to study if ginseng can be used to improve health and protect against disease because of the potential benefit in fighting these viruses. Ginseng has been reported to have anticancer, anti-inflammatory and immune modifying abilities.

Seasonal influenza is a serious respiratory disease that causes annual epidemics in humans worldwide, resulting in about three to five million cases of severe illness and about 250,000 to 500,000 deaths, according to the World Health Organization. Influenza can spread quickly, and new, unexpected pandemic influenza viruses may emerge at any time and cross over to different species. The H1N1 influenza virus, a new strain known as swine flu that emerged in 2009, spread rapidly to more than 74 countries. There are also challenges with existing influenza vaccines, such as required annual updates and no protection against pandemic strains and bird flu.

In addition, there are no vaccines available for RSV, which affects millions and is the leading cause of inflammatory bronchiolitis pneumonia and viral death in infants and in some elderly adults.

In his study published in Nutrients, Kang investigated whether red ginseng extract has preventive effects on influenza A virus infection. He found that red ginseng extract improves the survival of human lung epithelial cells infected with influenza virus. Also, treatment with red ginseng extract reduced the expression of genes that cause inflammation.

After infection with influenza A virus, mice that were orally administered ginseng over a long time showed multiple immune modifying effects, such as stimulated antiviral production of proteins important in immune response and fewer inflammatory cells in their bronchial walls. The study indicates the beneficial effects of red ginseng extract on preventing influenza A virus infections could result from immune modifying capabilities of ginseng.

In his upcoming publication in the International Journal of Molecular Medicine, Kang investigated whether Korean red ginseng extract has antiviral effects, or the ability to treat RSV infection. Kang found Korean red ginseng extract improved the survival of human lung epithelial cells against RSV infection and inhibited the virus from replicating, or multiplying, in the body. In addition, treatment with Korean red ginseng extract suppressed the expression of RSV-induced inflammatory genes and the formation of chemically reactive molecules containing oxygen, which play a role in virus-induced epithelial damage in RSV.

Also, mice that were orally administered Korean red ginseng extract had lower viral levels after infection with RSV. The results suggest that Korean red ginseng extract has antiviral activity against RSV infection.

Kang has further demonstrated ginseng’s beneficial effects on influenza and RSV in previously published studies.

Research shows impact of Facebook unfriending

High school friends often first to go

DENVER (April 22, 2014) – Two studies from the University of Colorado Denver are shedding new light on the most common type of `friend’ to be unfriended on Facebook and their emotional responses to it.

The studies, published earlier this year, show that the most likely person to be unfriended is a high school acquaintance.

“The most common reason for unfriending someone from high school is that the person posted polarizing comments often about religion or politics,” said Christopher Sibona, a doctoral student in the Computer Science and Information Systems program at the CU Denver Business School. “The other big reason for unfriending was frequent, uninteresting posts.”

Sibona’s first study examined `context collapse and unfriending behaviors’ on Facebook and his second looked at `the emotional response to being unfriended.’

Both studies were based on a survey of 1,077 people conducted on Twitter.

The first study found that the top five kinds of people respondents unfriended were:

1. High School friends
2. Other
3. Friend of a friend
4. Work friends
5. Common interest friend

“We found that people often unfriend co-workers for their actions in the real world rather than anything they post on Facebook,” Sibona said.

One reason he believes high school friends are top targets for unfriending is that their political and religious beliefs may not have been as strong when they were younger. And if those beliefs have grown more strident over time, it becomes easier to offend others.

“Your high school friends may not know your current political or religious beliefs and you may be quite vocal about them,” Sibona said. “And one thing about social media is that online disagreements escalate much more quickly.”

The second study looked at the emotional impact of being unfriended.

Sibona found a range of emotions connected to unfriending, from being bothered to being amused.

The most common responses to being unfriended were:

1. I was surprised
2. It bothered me
3. I was amused
4. I felt sad

“The strongest predictor is how close you were at the peak of your friendship when the unfriending happened,” said Sibona, who has studied the real world consequences of Facebook unfriending since 2010. “You may be more bothered and saddened if your best friend unfriends you.”

The study found four factors that predicted someone’s emotional response to being unfriended. Two factors predicted that a user would be negatively affected – if the unfriended person was once a close friend to the one who unfriended them and how closely the person monitored their own friend’s list.

Two other factors predicted that a user would be less negatively affected – if difficulties were discussed between the friends before the unfriending and if the person unfriended talked about it with others after the unfriending.

The research showed that unfriending happens more often to friends who were once close than to those who are acquaintances.

“Despite the preponderance of weak ties throughout online social networks, these findings help to place unfriending within the greater context of relationship dissolution,” the study said.

Sibona said that the ‘one size fits all’ method of ending digital relationships is unique but with real world consequences that warrant additional research.

“If you have a lot of friends on Facebook, the cost of maintaining those friendships is pretty low,” he said. “So if you make a conscious effort to push a button to get rid of someone, that can hurt.”

The two studies were published in the 2014 47th Hawaii International Conference on System Sciences.

Biting into Whole Foods can Make Children Rowdy

There’s a new secret to get your child to behave at the dinner table—cut up their food and they’ll relax.

A new Cornell study published in Eating Behaviors, found that when 6-10 year old children ate foods they had to bite with their front teeth— such as drumsticks, whole apples, or corn on the cob— they were  rowdier than when these foods had been cut.  “They were twice as likely to disobey adults and twice as aggressive toward other kids,” said Brian Wansink, Professor and Director of the Cornell Food and Brand Lab.

During a 4-H summer camp, 12 elementary children were observed for this 2-day study. On the first day, half of the children were seated at one picnic table and were given chicken on the bone that had to be bitten into with their front teeth; the other half were seated at a nearby picnic table and given chicken cut into bite sized pieces. On the second day, the conditions were reversed. Each day, two camp counselors instructed the children to stay inside a circle with a 9-foot radius. Both meal sessions were videotaped and evaluated by trained coders who indicated how aggressive or compliant the children were, and if they exhibited any atypical behaviors, such as jumping and standing on the picnic tables.

Results from both the counselors and coders observations indicated that when children were served chicken on the bone, they acted twice as aggressively, and were twice as likely to disobey adults, than when they were served bite sized pieces of chicken. Furthermore, the children who were served chicken on the bone left the circle without permission more frequently and were more likely to jump and stand on the picnic tables.

Cornell study shows that cutting your child’s food makes them twice as obedient and half as aggressive toward their siblings!

Along with Wansink, the research was conducted with Guido Camps now at Wageningen University and Research Center; Francesca Zampollo now at Auckland University of Technology; and Mitsuru Shimizu, now at Southern Illinois University Edwardsville.

In conclusion, the researchers note that when children need to bite into food with their front teeth, they are more likely to get rowdy!  The bottom line for parents is this “If you want a nice quiet, relaxing meal with your kids, cut up their food,” according to Wansink. He had different bottom line advice for school lunchroom staff, “If drumsticks, apples, or corn on the cob are on the menu, duck!”

Article Summary by Katherine Baildon and Rosemarie Hanson

Acupuncture at Waiguan improves activation of functional brain areas of stroke patients

Both acupuncture at Waiguan (SJ5) and sham acupuncture can activate/deactivate several brain regions in patients with ischemic stroke, but there are some difference in Brodmann areas 4, 6, 8, Brodmann areas 7, 39, 40, Brodmann areas 18, 19, 22 and Brodmann areas 13, 24, 32, 28. Most studies addressing the specificity of meridians and acupuncture points have focused mainly on the different neural effects of acupuncture at different points in healthy individuals. Dr. Ji Qi and co-workers from School of Traditional Chinese Medicine, Southern Medical University in China examined the effects of acupuncture on brain function in a pathological context, and compared the effects between Waiguan and sham points in 16 patients with ischemic stroke. Compared with sham acupuncture, acupuncture at Waiguan in stroke patients inhibited Brodmann area 5 on the healthy side. These findings, published in the Neural Regeneration Research (Vol. 9, No. 3, 2014), indicated that the altered specificity of sensation-associated cortex (Brodmann area 5) is possibly associated with a central mechanism of acupuncture at Waiguan for stroke patients.

Qi J, Chen JQ, Huang Y, Lai XS, Tang CZ, Yang JJ, Chen H, Qu SS. Acupuncture at Waiguan and sham points influences activation of functional brain areas of ischemic stroke patients: a functional magnetic resonance imaging study. Neural Regen Res. 2014;9(3):293-300.

Are almonds an optimal snack?

Almonds examined for effects on diet quality, appetite, adiposity and cardiovascular disease risk factors at Experimental Biology 2014

Modesto, CA (April 25, 2014) – Six new almond-related research studies will be presented next week in San Diego at the American Society of Nutrition (ASN)’s Scientific Sessions and Annual Meeting, held in conjunction with Experimental Biology 2014 (EB). The conference attracts an international audience of approximately 13,000 leading scientists specializing in various health disciplines.

The science presented will reveal new insights on the effects of almond consumption on overall diet quality and health status, abdominal adiposity, measures of appetite and satiety, and cardiovascular risk factors.

“Presenting new research to this audience of scientists and health professionals is critical to turning the findings into practical application and recommendations, said Dr. Karen Lapsley, Chief Science Officer for the Almond Board of California. “These results help to advance the evolution of our understanding of almonds’ beneficial effects as part of a healthy diet.” In a satellite session on Sunday, April 27 (1), researchers will explore the question, “Are Almonds an Optimal Snack?” a hot topic given that snacking has become a way of life for most Americans. In fact, 97% of Americans report eating at least one snack a day, with 40% consuming three to four snacks per day (2), so understanding and education about smart snacking is increasingly important.

• Dr. Carol O’Neil of Louisiana State University will present a new analysis of 24,808 adults 19 and older, using National Health and Nutrition Examination Survey data from 2000-2010 showing that almond consumers (n=395; defined as those who reported eating any amount of almonds or almond butter in the previous 24 hours) had increased nutrient intake, improved overall dietary quality and better physiological status compared with non-almond consumers (3). This is a cross-sectional study; therefore, the data cannot be used to draw causal relationships, but suggests an association between almond consumption and positive health status.
• Many commonly consumed snack foods are nutrient-poor and elicit weak dietary compensation. Dr. Richard Mattes from Purdue University examined the effects of snacking on nutrient-rich almonds in 137 adult participants at risk for Type II diabetes (4). Consuming 1.5 ounces of dry-roasted, lightly salted almonds daily helped curb participants’ appetites and moderate blood glucose concentrations, while significantly improving vitamin E and monounsaturated fat intake. After a month of snacking on 250 calories from almonds daily, participants did not gain weight. While the study was only four weeks long, it suggests that snacking on almonds could be a weight-wise strategy.
• Dr. Penny-Kris Etherton from Pennsylvania State University will be sharing results from a new randomized, controlled clinical study examining the effects of consuming 1.5 ounces of almonds vs. a calorie-matched, high carbohydrate snack on body weight in 52 adults with elevated LDL cholesterol (5). Total body weight did not differ between the two treatments, but the almond diet reduced overall abdominal mass, abdominal fat mass, and waist circumference compared to the high-carbohydrate snack. Although the study was just six weeks long, preliminary results suggest that snacking on almonds may help decrease abdominal fat, an important risk factor for metabolic syndrome.

Additional research examining the relationship between almond consumption and cardiovascular and diabetes risk factors will be showcased in a number of poster presentations at the conference:

• A randomized, parallel-arm controlled study investigated the effects of adding 1.5 ounces of almonds daily to the diets of adult subjects with poorly controlled type II diabetes on C-reactive protein – without any dietary advice provided (6).
• Another crossover, randomized clinical trial examined the metabolic response of 2 ounces of almonds compared to dairy fat in isocaloric and equal macronutrient meals consumed by overweight/obese pregnant women. Preliminary results suggest that almonds may help improve satiety, reduce appetite, and may help promote healthy weight gain during pregnancy, although further research is needed (7).

The body of evidence that will be presented suggests snacking can be a weight-wise strategy, depending upon the foods consumed. The nutrient profile of almonds – low on the glycemic index and providing a powerful nutrient package including hunger-fighting protein (6 g/oz), filling dietary fiber (4 g/oz), “good” monounsaturated fats (13 g/oz) (8), and important vitamins and minerals such as vitamin E (7.4 mg/oz), magnesium (200 mg/oz) and potassium (77 mg/oz), makes them a satisfying, heart-smart (8) snack choice that can help support a healthy weight.

The research presented reflects the Almond Board of California’s strong commitment to the advancement of nutrition science. Lapsley said, “To date, the California almond industry has invested over $15 million in nutrition research that has resulted in more than 100 papers published by internationally recognized scientists in peer review journals. The Almond Board of California is proud to present science at the elite level of Experimental Biology.”

Today’s statin users consume more calories and fat than their predecessors

People who take statin drugs to lower their cholesterol appear to have developed a false sense of security that could lead to heart disease and other obesity-related illnesses.

A new UCLA-led study suggests that people who took statins in the 2009–10 year were consuming more calories and fat than those who used statins 10 years earlier. There was no similar increase in caloric and fat intake among non–stain users during that decade, researchers said.

In 1999–2000, statin users were consuming fewer calories and less fat than individuals who didn’t take these medications, but that is no longer the case. Increases in body mass index — a measure of obesity that considers body weight and height — were greater for statin-users than for non-users.

“We believe that this is the first major study to show that people on statins eat more calories and fat than people on those medications did a decade earlier,” said the study’s primary investigator, Takehiro Sugiyama, who led the research while a visiting scholar in the division of general internal medicine and health services research at the David Geffen School of Medicine at UCLA. “Statins are used by about one-sixth of adults. We may need to reemphasize the importance of dietary modification for those who are taking these medications, now that obesity and diabetes are important problems in society.”

The study, subtitled “Gluttony in the Time of Statins?”, is published online in the peer-reviewed journal JAMA Internal Medicine. The findings were also presented April 24 at the annual meeting of the Society of General Internal Medicine.

For the study, the researchers used data from the National Health and Nutrition Examination Survey to compare fat and caloric intake among statin users and non-users in 1999–2000 and 2009–10. They found that caloric intake among statin users had risen by 9.6 percent over that decade and that fat consumption had jumped by 14.4 percent. In contrast, caloric and fat intake by non–statin users did not change significantly during the 10-year period.

Statin-users ate roughly 180 kilogram calories less each day and 9 grams of fat less each day than non-users in 1999–2000. But as a result of increases over the decade, the researchers observed no difference in caloric and fat intake between statin users and non-users in 2009–10.

The differences may be explained by the fact that statin users simply don’t feel the urgency to reduce their caloric and fat consumption or to lose weight the way statin users 10 years ago did, said Sugiyama, who is now a clinical fellow at the National Center for Global Health and Medicine in Japan. Also, doctors today may be more likely to prescribe statins for patients who eat and weigh more.

Because of the design of this study, the researchers were not able to disentangle the mechanism of the different dietary intake trends. Longitudinal study will be required to answer this question.

“Regardless of the mechanism, there are problems, because eating more fat, especially saturated fat, will lead to higher cholesterol levels, which will undermine the effect of statins and may lead to unnecessary cost of medications,” Sugiyama said. “Being overweight also increases the risk of diabetes and hypertension, which also are risk factors for heart disease and stroke.

“Ethical considerations should be included in the discussion. We believe that when physicians prescribe statins, the goal is to decrease patients’ cardiovascular risks that cannot be achieved without medications, not to empower them to put butter on steaks.”

High doses of antidepressants appear to increase risk of self-harm in children young adult

Bottom Line: Children and young adults who start antidepressant therapy at high doses, rather than the “modal” [average or typical] prescribed doses, appear to be at greater risk for suicidal behavior during the first 90 days of treatment.

Author: Matthew Miller, M.D., Sc.D., of the Harvard School of Public Health, Boston, and colleagues.

Background: A previous meta-analysis by the U.S. Food and Drug Administration (FDA) of antidepressant trials suggested that children who received antidepressants had twice the rate of suicidal ideation and behavior than children who were given a placebo. The authors of the current study sought to examine suicidal behavior and antidepressant dose, and whether risk depended on a patient’s age.

How the Study Was Conducted: The study used data from 162,625 people (between the ages of 10 to 64 years) with depression who started antidepressant treatment with a selective serotonin reuptake inhibitor at modal (the most prescribed doses on average) or at higher than modal doses from 1998 through 2010.

Results: The rate of suicidal behavior (deliberate self-harm or DSH) among children and adults (24 years or younger) who started antidepressant therapy at high doses was about twice as high compared with a matched group of patients who received generally prescribed doses. The authors suggest this corresponds to about one additional event of DSH for every 150 patients treated with high-dose therapy. For adults 25 to 64 years old, the difference in risk for suicidal behavior was null. The study does not address why higher doses might lead to higher suicide risk.

Discussion: “Considered in light of recent meta-analyses concluding that the efficacy of antidepressant therapy for youth seems to be modest, and separate evidence that dose is generally unrelated to the therapeutic efficacy of antidepressants, our findings offer clinicians an additional incentive to avoid initiating pharmacotherapy at high-therapeutic doses and to monitor all patients starting antidepressants, especially youth, for several months and regardless of history of DSH.”

(JAMA Intern Med. Published online April 28, 2014. doi:10.1001/jamainternmed.2014.1053. Available pre-embargo to the media at http://media.jamanetwork.com.)

Editor’s Note: Authors made a conflict of interest and funding disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Commentary: Initial Dose of Antidepressants, Suicidal Behavior in Youth

In a related commentary, David A. Brent, M.D., of the University of Pittsburgh, and Robert Gibbons, Ph.D., of the University of Chicago, write: “In summary Miller et al are to be commended on a thoughtful and careful analysis of the effects of initiating antidepressants at higher than modal doses.”

“Their findings suggest that higher than modal initial dosing leads to an increased risk for DSH and adds further support to current clinical recommendations to begin treatment with lower antidepressant doses. While initiation at higher than modal doses of antidepressants may be deleterious, this study does not address the effect of dose escalation,” they continue.

“Moreover, while definitive studies on the impact of dose escalation in the face of nonresponse remain to be done, there are promising studies that suggest in certain subgroups, dose escalation can be of benefit. Finally it should be noted that in this study, there was no pre-exposure to post-exposure increase in suicidal behavior after the initiation of antidepressants in youth treated at the modal dosage,” they conclude.

(JAMA Intern Med. Published online April 28, 2014. doi:10.1001/jamainternmed.2013.14016. Available pre-embargo to the media at http://media.jamanetwork.com.)

Editor’s Note: Authors made conflict of interest and funding disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Study: Tart cherry juice increases sleep time in adults with insomnia

SAN DIEGO, Calif. April 28, 2014 – A morning and evening ritual of tart cherry juice may help you sleep better at night, suggests a new study presented today at the Experimental Biology 2014 meeting. Researchers from Louisiana State University found that drinking Montmorency tart cherry juice twice a day for two weeks helped increase sleep time by nearly 90 minutes among older adults with insomnia.

These findings were presented Monday, April 28, at the “Dietary Bioactive Components: Antioxidant and Anti-inflammatory Effects of Dietary Bioactive Components” section of the annual meeting of the American Society of Nutrition, which is being held in conjunction with the Experimental Biology 2014 meeting in San Diego. The findings have been submitted for publication in a peer-reviewed journal.

Insomnia is a common health problem among older adults, impacting an estimated 23 to 34 percent of the population ages 65 and older. Insomnia – defined as trouble sleeping on average more than three nights per week – can be an annoyance for some, but long-lasting sleeplessness can seriously affect health, especially in the elderly.

Insomnia is linked to a higher prevalence of chronic pain, high blood pressure, type 2 diabetes and a decline of cognitive function, or dementia. Individuals with insomnia may turn to sleeping pills; however, these sedative medications have been found to increase risk of falls in the elderly – which makes it increasingly important to find more natural sleep-aids without these apparent side effects, said co-author Frank L. Greenway, MD, director of the outpatient research clinic at the Pennington Biomedical Research Center at Louisiana State University.

“Sleeping pills may be an option for younger insomniacs, but for older people these medications quadruple the risk of falling, which can lead to broken hips and, often, earlier death,” Greenway said.

For the randomized crossover clinical trial, seven older adults (average age 68) with insomnia consumed 8 ounces of tart cherry juice twice daily for two weeks, followed by a two-week washout period, then a two-week period when another beverage was consumed (placebo). Greenway and his colleagues studied their slumber in a controlled setting, using overnight polysomnography to evaluate sleep efficiency, such as sleep onset and duration. Participants also completed questionnaires related to sleep, fatigue, depression and anxiety. Additionally, blood work was conducted on each participant.

The researchers found that those who drank the Montmorency tart cherry juice in the morning and at night were able to sleep more than an hour longer each night (averaging 84 minutes) compared to the placebo, and their sleep tended to be more efficient.

Montmorency tart cherries are a natural source of melatonin, a hormone that helps regulate the sleep-wake cycle. While previous studies have suggested that tart cherry juice has sleep-enhancing benefits, Greenway and colleagues set out to help explain why. They wanted to understand if the benefits were due to the melatonin content or another component in Montmorency tart cherries.

They believe the ruby red pigments in tart cherry juice, known as proanthocyanidins, also play a role. These natural polyphenolic compounds are especially abundant in Montmorency tart cherries. In the study, tart cherry juice helped to increase the availability of tryptophan, an essential amino acid and a precursor to serotonin that helps with sleep. The juice was shown in cells to inhibit an enzyme (indoleamine 2,3 dioxygenase) that degrades tryptophan. Tryptophan degradation is a known predictor of insomnia and is also related to inflammation, said co-authors Jack Losso and John Finley, professors in the School of Nutrition and Food Sciences at Louisiana State University Agricultural Center.

“Even though the amount of tryptophan in tart cherry juice is smaller than a normal dose given to aid sleep, the compounds in tart cherries could prevent the tryptophan from breaking down so it’s able to work in the body more effectively,” Greenway explained. “These compounds may help to improve tryptophan bioavailability for serotonin synthesis, which could have a positive effect on sleep. Increasing serotonin also helps improve mood and decrease inflammation.”

Greenway believes it’s the unique combination of melatonin and tryptophan in Montmorency tart cherries that is likely contributing to the sleep benefits. He and his colleagues conclude that drinking a glass of tart cherry juice in the morning and the evening may be a better and a safer way to treat insomnia.

Higher calcium intake may reduce body fat, mitigating genetic risk for diabetes

Study shows calcium intake mitigates genetic risk for increased body fat in African-American children, a population with historically low calcium intake and high risk for diabetes

SAN DIEGO (April 29, 2014) – As the number of people with type 2 diabetes continues to rise and its toll increases, scientists are scrambling to unravel the complex genetic and lifestyle factors behind the disease. A new study finds that African American children with a genetic predisposition to diabetes may be able to reduce their risk by getting the USDA-recommended dose of calcium.

“Even though life expectancy for people with diabetes has gone up, the disease has a significant impact on quality of life, so finding ways to prevent people from developing diabetes is critical,” said Laura Tosi, M.D., director of the bone health program at Children’s National Medical Center and one of the study’s lead investigators. “We were excited to find that higher calcium intake appears to mitigate the impact of some of the risk genes for type 2 diabetes, and we’re eager to see if these results hold true in other populations.”

An estimated 25 million people in the United States have diabetes, or about 1 in 12 people. African Americans are at especially high risk, and the trajectory for the disease is often set in childhood.

The researchers analyzed DNA samples, detailed nutrition information, body mass index and other health indicators in 142 African American children age 5-9. None of the study participants were diabetic, although 40 percent were overweight and 20 percent were obese.

Among children who tested positive for gene variants known to be associated with type 2 diabetes, those who consumed higher amounts of calcium had a significantly lower body mass index and percent body fat than those with lower calcium intake. Body mass index and percent body fat are strong indicators of a child’s risk for developing diabetes later in life.

The USDA recommends children age 4-8 get 1,000 milligrams of calcium per day, the equivalent of about 3.5 8-ounce glasses of milk or 4.5 ounces of cheese. Children age 9-13 years should get about 1,300 milligrams. In addition to dairy products, other calcium-rich foods include tofu, sardines, salmon and some green vegetables.

The study underscores the work of previous researchers, who have shown that many African American children do not get the recommended levels of calcium in their diet. “Twenty percent of participating children consumed no milk in their diet whatsoever and 55 percent consumed less than one serving of milk per day. Only one-quarter of the children met the USDA standard,” said Tosi.

Co-investigator Joseph Devaney, Ph.D., said the study could help lead to a more personalized approach to diabetes prevention. “The ultimate goal would be to be able to predict, from a child’s genotype, his or her specific risk factors for developing type 2 diabetes, and then develop a targeted preventative approach to mitigate those risk factors with specific lifestyle interventions such as increasing calcium intake or physical activity, for example,” said Devaney, director of DNA technologies at Children’s National Medical Center.

Although the researchers do not know the exact reason for the association, they speculate that calcium or related dietary factors may cause epigenetic changes that affect how the diabetes-linked genes are expressed.

“What got us interested in this is the whole question of how the environment—including a person’s diet—influences gene expression,” said Tosi. Although scientists have intensely studied the impact of environmental factors during prenatal development and early infancy, few researchers have examined the impact of such factors later in childhood.

Understanding the interactions of genes and environmental factors in children is especially helpful for a disease as complex as diabetes, said Devaney. By the time an adult is diagnosed with diabetes, there are usually numerous risk factors that need to be addressed. “The earlier you can identify a person’s risk factors, the better the opportunity to prevent, or at least delay, full-blown disease,” said Devaney.

Heart attack survivors who eat lots of fiber live longer

Advising a higher intake of cereal fiber after a myocardial infarction may improve long-term survival rates

People who survive heart attacks have a greater chance of living longer if they increase their dietary intake of fibre – and eating lots of cereal fibre is especially beneficial, finds research published today on bmj.com.

Those who ate most fibre had a 25% lower chance of dying in the nine years after their heart attack compared with those who ate least fibre, the researchers found. Every 10g per day increase in fibre intake was associated with a 15% lower risk of dying over the nine-year follow-up period.

The researchers point out that with more people surviving heart attacks, it will be increasingly important to find out what lifestyle steps they can take alongside their medication to improve their long-term health prospects.

It is well-known that healthy people who have a high intake of dietary fibre have a lower risk of developing coronary heart disease but until now it has been unclear whether advising heart attack survivors to eat more fibre will improve their chances of living longer.

The research team, based in Boston, USA, therefore analysed data from two big US studies, the Nurses’ Health Study of 121,700 female nurses and the Health Professional Follow-up Study of 51,529 male health professionals. In both studies, the participants completed detailed questionnaires on their lifestyle habits every two years.

The researchers looked at the 2,258 women and 1,840 men who survived a first myocardial infarction (MI) – a heart attack – during the course of the studies. They were followed for an average of almost nine years after their heart attack, during which time 682 of the women and 451 of the men died.

Participants were divided into five groups (quintiles) according to how much fibre they ate after their heart attack. The top quintile – the one in five who ate most fibre – had a 25% lower chance of dying from any cause during the nine years after their heart attack compared with the bottom quintile – the one in five who ate least fibre. When considering only cardiovascular causes of death (heart attack, stroke and coronary heart disease), the top quintile had a 13% lower mortality risk than the bottom quintile.

When the researchers looked at the three different fibre types – cereal, fruit and vegetable – only higher cereal fibre intake was strongly associated with an increased chance of long-term survival after a heart attack. Breakfast cereal was the main source of dietary fibre.

All the results were adjusted for other factors that might affect the chance of survival after a heart attack, including age, medical history and other dietary and lifestyle habits.

The researchers point out that heart attack survivors have a higher risk of dying than the general population and are often more motivated to make changes to their lifestyle – yet treatment to improve their chances of living longer generally neglects the importance of a healthier lifestyle in favour of long-term medication.

‘Future research on lifestyle changes post-MI should focus on a combination of lifestyle changes and how they may further reduce mortality rates beyond what is achievable by medical management alone,’ they conclude.

High dietary fibre intake can improve blood lipid levels and reduce the risk of high blood pressure, obesity and diabetes while a low-fibre diet is associated with an increased risk of colorectal cancer.

Less than 5% of Americans consume the minimum recommended fibre intake of 25g per day for women and 38g per day for men. In the UK, adults are recommended to eat at least 18g of fibre daily but dietary surveys suggest people eat an average of only 14g.

Vitamin D may raise survival rates among cancer patients

Analysis finds strongest evidence of benefit in breast, colorectal cancers

Washington, DC—Cancer patients who have higher levels of vitamin D when they are diagnosed tend to have better survival rates and remain in remission longer than patients who are vitamin D-deficient, according to a new study published in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism (JCEM).

The body naturally produces vitamin D after exposure to sunlight and absorbs it from certain foods. In addition to helping the body absorb the calcium and phosphorus needed for healthy bones, vitamin D affects a variety of biological processes by binding to a protein called a vitamin D receptor. This receptor is present in nearly every cell in the body.

“By reviewing studies that collectively examined vitamin D levels in 17,332 cancer patients, our analysis demonstrated that vitamin D levels are linked to better outcomes in several types of cancer,” said one of the study’s authors, Hui Wang, MD, PhD, Professor of the Institute for Nutritional Sciences at the Shanghai Institutes for Biological Sciences at the Chinese Academy of Sciences in Shanghai, China. “The results suggest vitamin D may influence the prognosis for people with breast cancer, colorectal cancer and lymphoma, in particular.”

The meta-analysis looked at the results of 25 separate studies that measured vitamin D levels in cancer patients at the time of diagnosis and tracked survival rates. In most of the research, patients had their vitamin D levels tested before they underwent any treatment for cancer. The study found a 10 nmol/L increase in vitamin D levels was tied to a 4 percent increase in survival among people with cancer.

Researchers found the strongest link between vitamin D levels and survival in breast cancer, lymphoma and colorectal cancer. There was less evidence of a connection in people with lung cancer, gastric cancer, prostate cancer, leukemia, melanoma or Merkel cell carcinoma, but the available data were positive.

“Considering that vitamin D deficiency is a widespread issue all over the world, it is important to ensure that everyone has sufficient levels of this important nutrient,” Wang said. “Physicians need to pay close attention to vitamin D levels in people who have been diagnosed with cancer.”

Discovery of anti-appetite molecule released by fiber could help tackle obesity

New research has helped unpick a long-standing mystery about how dietary fibre supresses appetite.

In a study led by Imperial College London and the Medical Research Council (MRC), an international team of researchers identified an anti-appetite molecule called acetate that is naturally released when we digest fibre in the gut. Once released, the acetate is transported to the brain where it produces a signal to tell us to stop eating.

The research, published in Nature Communications, confirms the natural benefits of increasing the amount of fibre in our diets to control over-eating and could also help develop methods to reduce appetite. The study found that acetate reduces appetite when directly applied into the bloodstream, the colon or the brain.

Dietary fibre is found in most plants and vegetables but tends to be at low levels in processed food. When fibre is digested by bacteria in our colon, it ferments and releases large amounts of acetate as a waste product. The study tracked the pathway of acetate from the colon to the brain and identified some of the mechanisms that enable it to influence appetite.

“The average diet in Europe today contains about 15 g of fibre per day,” said lead author of the study Professor Gary Frost, from the Department of Medicine at Imperial College London. “In stone-age times we ate about 100g per day but now we favour low-fibre ready-made meals over vegetables, pulses and other sources of fibre. Unfortunately our digestive system has not yet evolved to deal with this modern diet and this mismatch contributes to the current obesity epidemic. Our research has shown that the release of acetate is central to how fibre supresses our appetite and this could help scientists to tackle overeating.”

The study analysed the effects of a form of dietary fibre called inulin which comes from chicory and sugar beets and is also added to cereal bars. Using a mouse model, researchers demonstrated that mice fed on a high fat diet with added inulin ate less and gained less weight than mice fed on a high fat diet with no inulin. Further analysis showed that the mice fed on a diet containing inulin had a high level of acetate in their guts.

Using positron emission tomography (PET) scans, the researchers tracked the acetate through the body from the colon to the liver and the heart and showed that it eventually ended up in the hypothalamus region of the brain, which controls hunger.

In collaboration with Consejo Superior de Investigaciones Científicas (CSIC) in Madrid, the researchers investigated the effects of acetate in the hypothalamus using a cutting-edge scanning technique called High Resolution Magic Angle Spinning (HR-MAS). “This complements the PET scans and allows us to follow the metabolism of acetate in the hypothalamus,” said Professor Sebastian Cerdán from CSIC. “From this we could clearly see that the acetate accumulates in the hypothalamus after fibre has been digested. The acetate then triggers a series of chemical events in the hypothalamus leading to the firing of pro-opiomelanocortin (POMPC) neurons, which are known to supress appetite.”

This is the first demonstration that acetate released from dietary fibre can affect the appetite response in the brain. The research also showed that when acetate was injected into the bloodstream, the colon or the brain it reduced the amount of food eaten by mice.

Co-author on the study Professor Jimmy Bell from the MRC Clinical Sciences Centre said: “It’s exciting that we have started to really understand what lies behind fibre’s natural ability to supress our appetite and identified acetate as essential to the process. In the context of the growing rates of obesity in western countries, the findings of the research could inform potential methods to prevent weight gain.”

Professor Gary Frost added: “The major challenge is to develop an approach that will deliver the amount of acetate needed to supress appetite but in a form that is acceptable and safe for humans. Acetate is only active for a short amount of time in the body so if we focussed on a purely acetate-based product we would need to find a way to drip-feed it and mimic its slow release in the gut. Another option is to focus on the fibre and manipulate it so that it produces more acetate than normal and less fibre is needed to have the same effect, providing a more palatable and comfortable option than massively increasing the amount of fibre in our diet. Developing these approaches will be difficult but it’s a good challenge to have and we’re looking forward to researching possible ways of using acetate to address health issues around weight gain.”

Professor David Lomas, Chair of the MRC’s Population and Systems Medicine Board, added: “It’s becoming increasingly clear that the interaction between the gut and the brain plays a key role in controlling how much food we eat. Being able to influence this relationship, for example using acetate to suppress appetite, may in future lead to new, non-surgical treatments for obesity.”

Initial research: Mango’s effects on ulcerative colitis and bone parameters in animal models

Three new mango studies presented at 2014 Experimental Biology Conference

SAN DIEGO, CA – April 30, 2014 – Three new mango-related studies were presented this week at the 2014 Federation of American Societies for Experimental Biology (FASEB) in San Diego, revealing initial findings on the effects of mango consumption on ulcerative colitis and bone parameters in animal models.

“The mango industry’s nutrition research program is committed to advancing our understanding of the role mangos can play as part of a healthy diet,” said Megan McKenna, Director of Marketing for the National Mango Board. “These studies provide important insights that will drive future research.”

• Initial research from the Texas A&M University lab led by Susanne Mertens-Talcott, Ph.D., Assistant Professor and Director of Research, Institute for Obesity Research and Program Evaluation of Texas A&M University, investigated the effects of mango and pomegranate polyphenolics on fecal microbiota and short chain fatty acid (SCFA) production in rats . Rats were administered control, mango, or pomegranate juice, and were exposed to three cycles of 3% DSS followed by a two-weeks recovery period. The results found that mango juice induced changes in SCFAs production while pomegranate juice induced changes in the composition of microbiota. To view the full abstract, visit: http://www.fasebj.org/content/28/1_Supplement/1045.6.abstract?sid=881bd512-b205-4627-b64a-c02e7001d351
• Additional preliminary research from Dr. Mertens-Talcott explored the anti-inflammatory effects and possible mechanisms of mango and pomegranate juice in DSS-induced colitis in rats. The study results suggest that polyphenolics of different predominant structure may differentially regulate inflammation-involved pathways while attenuating DSS-induced colitis. To view the full abstract, visit: http://www.fasebj.org/content/28/1_Supplement/372.8.abstract?sid=88332839-b342-41e9-9dc7-f7b5614e41a7
• Initial research from Edralin Lucas, Ph.D., associate professor of nutritional sciences in the College of Human of Sciences at Oklahoma State University, examined the effects of mango and its polyphenol in preventing bone loss in ovariectomized mice, a model of postmenopausal osteoporosis. The findings suggest that mango supplementation may promote the maintenance of skeletal health in estrogen deficiency through its effects on trabecular bone. To view the full abstract, visit: http://www.fasebj.org/content/28/1_Supplement/1025.9.abstract?sid=16e399c4-2e4b-4a98-ac8c-918b5a66117b

A nutrient rich fruit, mangos contain over 20 different vitamins and minerals, supporting optimal function of processes throughout the body. Mangos are an excellent source of the antioxidant vitamins C and A as well as folate. They are also a good source of fiber, copper, and vitamin B6.

Vitamin D deficiency may be linked to aggressive prostate cancer

PHILADELPHIA — Vitamin D deficiency was an indicator of aggressive prostate cancer and spread of the disease in European-American and African-American men who underwent their first prostate biopsy because of abnormal prostate-specific antigen (PSA) and/or digital rectal examination (DRE) test results, according to a study published in Clinical Cancer Research, a journal of the American Association for Cancer Research.

“Vitamin D is a steroid hormone that is known to affect the growth and differentiation of benign and malignant prostate cells in prostate cell lines and in animal models of prostate cancer,” said Adam B. Murphy, M.D., MBA, assistant professor in the Department of Urology at the Northwestern University Feinberg School of Medicine in Chicago. “In our study, vitamin D deficiency seemed to be a predictor of aggressive forms of prostate cancer diagnosis in European-American and African-American men.

“The stronger associations in African-American men imply that vitamin D deficiency is a bigger contributor to prostate cancer in African-American men compared with European-American men,” added Murphy. “Vitamin D supplementation may be a relevant strategy for preventing prostate cancer incidence and/or tumor progression in prostate cancer patients.”

The most accurate way to measure how much vitamin D we have in our body is to measure levels of 25-hydroxyvitamin D (25-OH D) in our blood. The normal range of 25-OH D is 30 to 80 nanograms per milliliter (ng/ml).

In this study, European-American and African-American men had 3.66 times and 4.89 times increased odds of having aggressive prostate cancer (Gleason grade of 4+4 or higher), respectively, and 2.42 times and 4.22 times increased odds of having tumor stage T2b or higher, respectively, if their 25-OH D levels were less than 12 ng/ml at the time of prostate biopsy. In addition, African-American men had 2.43 times increased odds of being diagnosed with prostate cancer, if their 25-OH D levels were less than 20 ng/ml.

Between 2009 and 2013, Murphy and colleagues enrolled 667 men, ages 40 to 79 years, who were undergoing their first prostate biopsy at one of five urology clinics in Chicago following an abnormal PSA or DRE. Serum 25-OH D levels were measured at recruitment. Of the study participants, 273 were African-American and 275 were European-American, and 168 men from each group had a prostate cancer diagnosis from their biopsy.

The researchers found that the mean 25-OH D levels were significantly lower among African-American men (16.7 ng/ml) compared with European-American men (19.3 ng/ml). The highest 25-OH D level was 71 ng/ml in European-American men, while it was only 45 ng/ml in African-American men.

They categorized the study group into those whose 25-OH D levels were less than 12 ng/ml, less than 16 ng/ml, less than 20 ng/ml, and less than 30 ng/ml, and found a dose-response relationship between tumor grade and vitamin D level for both European-American and African-American men, and the association held true even after adjusting for potential confounders including diet, smoking habits, obesity, family history, and calcium intake.

The researchers also found an association between lower 25-OH D levels and those at high and very high risk for prostate cancer, per National Comprehensive Cancer Network (NCCN) criteria, which take into account prediagnosis PSA levels, tumor stage, and Gleason grade.

While no association was found between vitamin D deficiency and prostate cancer diagnosis in European-American men, this association was significant in African-American men. Further, the association with disease aggressiveness and cancer spread was stronger for African-American men than for European-American men. Skin color, which determines cumulative vitamin D levels from exposure to sun, may partly explain the discrepancies observed between European-American and African-American men, explained Murphy.

“We will next evaluate genetic polymorphisms in the pathways of vitamin D metabolism to better understand the risk alleles underlying this association,” said Murphy. “Vitamin D deficiency seems to be important for general wellness and may be involved in the formation or progression of several human cancers. It would be wise to be screened for vitamin D deficiency and treated.”

Rick Kittles, Ph.D., an associate professor of medicine and epidemiology at the University of Illinois in Chicago, is a co-author and collaborator on this project.